FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Druey, KM Ugur, O Caron, JM Chen, CK Backlund, PS Jones, TLZ AF Druey, KM Ugur, O Caron, JM Chen, CK Backlund, PS Jones, TLZ TI Amino-terminal cysteine residues of RGS16 are required for palmitoylation and modulation of G(i)- and G(q)-mediated signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; PLASMA-MEMBRANE LOCALIZATION; ACTIVITY IN-VITRO; ALPHA-SUBUNITS; CORE DOMAIN; TRANSITION-STATE; GAIP; PHOSPHORYLATION; REGULATOR; RECEPTOR AB RGS proteins (Regulators of G protein Signaling) are a recently discovered family of proteins that accelerate the GTPase activity of heterotrimeric G protein a subunits of the i, q, and 12 classes. The proteins share a homologous core domain but have divergent amino-terminal sequences that are the site of palmitoylation for RGS-GAIP and RGS4. We investigated the function of palmitoylation for RGS16, which shares conserved amino-terminal cysteines with RGS4 and RGS5. Mutation of cysteine residues at residues 2 and 12 blocked the incorporation of [H-3]palmitate into RGS16 in metabolic labeling studies of transfected cells or into purified RGS proteins in a cell-free palmitoylation assay. The purified RGS16 proteins with the cysteine mutations were still able to act as GTPase-activating protein for G(i)alpha. Inhibition or a decrease in palmitoylation did not significantly change the amount of protein that was membrane-associated. However, palmitoylation-defective RGS16 mutants demonstrated impaired ability to inhibit both G(i)-and G(q)-linked signaling pathways when expressed in HEK293T cells. These findings suggest that the aminoterminal region of RGS16 may affect the affinity of these proteins for Ga subunits in vivo or that palmitoylation localizes the RGS protein in close proximity to Ga subunits on cellular membranes. C1 NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Physiol, Farmington, CT 06030 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Jones, TLZ (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bldg 10,Rm 9C101, Bethesda, MD 20892 USA. NR 55 TC 68 Z9 69 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 1999 VL 274 IS 26 BP 18836 EP 18842 DI 10.1074/jbc.274.26.18836 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209PJ UT WOS:000081056700094 PM 10373502 ER PT J AU Plaksin, D Chacko, S Navaza, J Margulies, DH Padlan, EA AF Plaksin, D Chacko, S Navaza, J Margulies, DH Padlan, EA TI The X-ray crystal structure of a V alpha 2.6J alpha 38 mouse T cell receptor domain at 2.5 angstrom resolution: Alternate modes of dimerization and crystal packing SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE T cell receptor; MHC class I; human immunodeficiency virus; X-ray crystallography; molecular recognition ID PEPTIDE-MHC COMPLEXES; PROTEIN DATA-BANK; CLASS-I H-2K(B); V-ALPHA DOMAIN; ANTIGEN RECEPTOR; HISTOCOMPATIBILITY ANTIGEN; MACROMOLECULAR STRUCTURES; 3-DIMENSIONAL STRUCTURE; SIGNAL-TRANSDUCTION; BETA DOMAIN AB We describe here the structure of a murine T cell receptor (TCR) V alpha 2.6J alpha 38 (TCXAV2S6J38) domain, derived from a T cell hybridoma with specificity for the H-2D(d) major histocompatibility complex class I molecule bound to a decamer peptide, P18-I10, from the HIV envelope glycoprotein gp120, determined by X-ray crystallography at 2.5 Angstrom resolution. Unlike other TCR Vet domains that have been studied in isolation, this one does not dimerize in solution at concentrations below 1 mM, and the crystal fails to show dimer contacts that are likely to be physiological. Ln comparison to other Vet domains, this V alpha 2.6 shows great similarity in the packing of its core residues, and exhibits the same immunoglobulin-like fold characteristic of other TCR Va domains. There is good electron density in all three complementarity-determining regions (CDRs), where the differences between this Va domain and others are most pronounced, in particular in CDR3. Examination of crystal contacts reveals an association of Va domains distinct from those previously seen. Comparison with other Vee domain structures reveals variability in all loop regions, as well as in the first beta strand where placement and configuration of a proline residue at position 6, 7, 8, or 9 affects the backbone structure. The great variation in CDR3 conformations among TCR structures is consistent with an evolving view that CDR3 of TCR plays a plastic role in the interaction of the TCR with the MHC/peptide complex as well as with CDR3 of the paired TCR chain. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. CNRS, Phys Lab, Paris, France. RP Margulies, DH (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 53 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 25 PY 1999 VL 289 IS 5 BP 1153 EP 1161 DI 10.1006/jmbi.1999.2855 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212NM UT WOS:000081223100001 PM 10373358 ER PT J AU Kosikov, KM Gorin, AA Zhurkin, VB Olson, WK AF Kosikov, KM Gorin, AA Zhurkin, VB Olson, WK TI DNA stretching and compression: Large-scale simulations of double helical structures SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Review DE DNA stretching; conformational transitions; molecular simulation; RecA-DNA assembly; TBP-DNA complex ID DOUBLE-STRANDED DNA; ANGLE NEUTRON-SCATTERING; RECA PROTEIN; CRYSTAL-STRUCTURE; NUCLEIC-ACID; MINOR-GROOVE; MOLECULAR-DYNAMICS; ESCHERICHIA-COLI; TATA-BOX; B-DNA AB Computer-simulated elongation and compression of A- and B-DNA structures beyond the range of thermal fluctuations provide new insights into high energy "activated" forms of DNA implicated in biochemical processes, such as recombination and transcription. All-atom potential energy studies of regular poly(dG).poly(dC) and poly(dA).poly(dT) double helices, stretched from compressed states of 2.0 Angstrom per base-pair step to highly extended forms of 7.0 Angstrom per residue, uncover four different hyperfamilies of right-handed structures that differ in mutual base-pair orientation and sugar-phosphate backbone conformation. The optimized structures embrace all currently known right-handed forms of doublehelical DNA identified in single crystals as well as non-canonical forms, such as the original "Watson-Crick" duplex with trans conformations about the P-O5' and C5'-C4' backbone bonds. The lowest energy minima correspond to canonical A and B-form duplexes. The calculations further reveal a number of unusual helical conformations that are energetically disfavored under equilibrium conditions but become favored when DNA is highly stretched or compressed. The variation of potential energy versus stretching provides a detailed picture of dramatic conformational changes that accompany the transitions between various families of double-helical forms. Ln particular, the interchanges between extended canonical and non-canonical states are reminiscent of the cooperative transitions identified by direct stretching experiments. The large-scale, concerted changes in base-pair inclination, brought about by changes in backbone and glycosyl torsion angles, could easily give rise to the observed sharp increase in force required to stretch single DNA molecules more than 1.6-1.65 times their canonical extension. Our extended duplexes also help to tie together a number of previously known structural features of the RecA-DNA complex and offer a self-consistent stereochemical model for the single-stranded/duplex DNA recognition brought in register by recombination proteins. The compression of model duplexes, by contrast, yields non-canonical structures resembling the deformed steps in crystal complexes of DNA with the TATA-box binding protein (TBP). The crystalline TBP-bound DNA steps follow the calculated compression-elongation pattern of an unusual "vertical" duplex with base planes highly inclined with respect to the helical axis, exposed into the minor groove, and accordingly accessible for recognition. Significantly, the double helix can be stretched by a factor of two and compressed roughly in half before its computed internal energy rises sharply. The energy profiles show that DNA extension-compression is related not only to the variation of base-pair Rise but also to concerted changes of Twist, Roll, and Slide. We suggest that the high energy "activated" forms calculated here are critical for DNA processing, e.g. nucleoprotein recognition, DNA/RNA synthesis, and strand exchange. (C) 1999 Academic Press. C1 Rutgers State Univ, Dept Chem, Wright Rieman Labs, Piscataway, NJ 08854 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zhurkin, VB (reprint author), Rutgers State Univ, Dept Chem, Wright Rieman Labs, 610 Taylor Rd, Piscataway, NJ 08854 USA. EM zhurkin@structure.nci.nih.gov; olson@rutchem.rutgers.edu RI Gorin, Andrey/B-1545-2014 FU NCI NIH HHS [N10-CO-74102]; NIGMS NIH HHS [GM20861] NR 117 TC 99 Z9 103 U1 2 U2 15 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 25 PY 1999 VL 289 IS 5 BP 1301 EP 1326 DI 10.1006/jmbi.1999.2798 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212NM UT WOS:000081223100012 PM 10373369 ER PT J AU Moon, HR Kim, HO Chun, MW Jeong, LS Marquez, VE AF Moon, HR Kim, HO Chun, MW Jeong, LS Marquez, VE TI Synthesis of cyclopropyl-fused carbocyclic nucleosides via the regioselective opening of cyclic sulfites SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CYCLOBUT-A; OXETANOCIN ANALOGS; NEPLANOCIN-C; SULFATES; DERIVATIVES; INHIBITORS; ALCOHOLS; REAGENT; INVITRO; AIDS AB The syntheses of some carbocyclic nucleosides that are conformationally locked as "northern" mimics of antiviral active, ring-expanded oxetanocin analogues are reported. The target compounds derived their rigid conformation from a common bicyclo[3.1.0]hexane template. The uracil (3a), cytosine (3b), and adenine (3c) analogues were synthesized from an intermediate cyclic sulfite (12a) that underwent selective ring opening with nucleophiles. Reaction of 12a with sodium azide provided access to the uracil and cytosine analogues (3a and 3b) after construction of the pyrimidine rings, and reaction with the sodium salt of adenine provided an efficient convergent, approach to 3c. The preponderance of the undesired N-7 regioisomer obtained from the coupling of 12a with 2-amino-6-chloropurine was unanticipated. Hence, the diol derivative 11 was selectively protected and coupled under Mitsunobu conditions to give, after deprotection, the desired guanine analogue 3d. With the exception of the guanine analogue, the cyclic sulfite chemistry described here represents a useful alternative as a general approach to carbocyclic nucleosides. None of the target nucleosides 3a-d demonstrated significant antiviral activity against HIV-1, HSV-1, HSV-2, and HCMV. Relative to other conformationally rigid, northern carbocyclic analogues that have shown good anti-HSV and anti-HCMV activities, it is concluded that the hydroxymethyl group is a poor substitute for the hydroxyl group in these rigid bicyclic nucleoside templates. C1 Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. Kyungin Womens Coll, Dept Ind Safety & Hyg, Inchon 407050, South Korea. Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jeong, LS (reprint author), Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. NR 43 TC 49 Z9 49 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 25 PY 1999 VL 64 IS 13 BP 4733 EP 4741 DI 10.1021/jo990010m PG 9 WC Chemistry, Organic SC Chemistry GA 210ZV UT WOS:000081136200027 ER PT J AU Trejo, F Vergara, P Brenner, M Segovia, J AF Trejo, F Vergara, P Brenner, M Segovia, J TI Gene therapy in a rodent model of Parkinson's disease using differentiated C6 cells expressing a GFAP-tyrosine hydroxylase transgene SO LIFE SCIENCES LA English DT Article DE GFAP promoter; tyrosine hydroxylase; transplants; C6 cells; Parkinson's disease ID ASTROCYTE-SPECIFIC EXPRESSION; IN-VITRO CHARACTERIZATION; DOPAMINERGIC DENERVATION; RAT; RECOVERY; MARKER; LINES; MICE AB Cells expressing a tyrosine hydroxylase (TH) cDNA under control of the promoter of the human glial fibrillary acidic protein (GFAP) gene were tested far therapeutic efficacy in a rat model of Parkinson's disease. The GFAP gene encodes an intermediate filament protein found almost exclusively in astrocytes. Its promoter is of interest for gene therapy as it is expressed in astrocytes throughout postnatal life and is upregulated in response to almost any damage to the central nervous system, including Parkinson's disease. We previously showed that a line of C6 rat glioma cells that expresses a GFAP-TH transgene, C6-THA, displays increased transgene activity when differentiated by forskolin treatment. Accordingly, the effects were investigated of implantation of both undifferentiated and differentiated C6-THA cells into the striatum of rats that had been lesioned with 6-hydroxydopamine. Implantation of either cell type produced significant behavioral recovery one week after transplantation, as judged by the turning response to apomorphine. At two and three weeks after transplantation, the behavioral effect of the undifferentiated cells was no longer statistically significant, whereas that for the forskolin-differentiated cells remained robust. Transgenic TH mRNA and protein could be detected in implants of both cell types, and in agreement with the behavioral results, levels were higher for the differentiated C6-THA cells than for the undifferentiated cells. These results indicate that the GFAP promoter is sufficiently active to enable production of therapeutic levels of dopamine from a GFAP-TH transgene, and suggest the use of astrocytes for gene therapy for Parkinson's disease. They also show that beneficial modifications of cells produced by treatment while in culture may be maintained following implantation. C1 IPN, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & Neurociencias, Mexico City 07300, DF, Mexico. IPN, Programa Multidisciplinario Biomed Mol, Mexico City, DF, Mexico. NINDS, NIH, Stroke Branch, Bethesda, MD USA. RP Segovia, J (reprint author), IPN, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & Neurociencias, Av Inst Politecn Nacl 2508, Mexico City 07300, DF, Mexico. RI Segovia, Jose/C-9277-2011 OI Segovia, Jose/0000-0001-8215-4772 NR 22 TC 13 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 25 PY 1999 VL 65 IS 5 BP 483 EP 491 DI 10.1016/S0024-3205(99)00269-6 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 213UB UT WOS:000081290700002 PM 10462075 ER PT J AU Deitsch, KW del Pinal, A Wellems, TE AF Deitsch, KW del Pinal, A Wellems, TE TI Intra-cluster recombination and var transcription switches in the antigenic variation of Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE var genes; antigenic variation; PfEMP1; cytoadherence; recombination; chromatin ID GENE-EXPRESSION SITE; MUTUALLY EXCLUSIVE TRANSCRIPTION; HUMAN MALARIA PARASITES; TRYPANOSOMA-BRUCEI; PHASE VARIATION; INFLUENZAE LIPOPOLYSACCHARIDE; ERYTHROCYTES; PROMOTER; SURFACE; SEQUENCES AB Antigenic variation and immune evasion by Plasmdium falciparum parasitized erythrocytes are mediated by expression switches among members of the multicopy var gene family. Here we describe a cluster of var genes on chromosome 12 that showed spontaneous recombination and switches in the transcription of individual genes. The transcription switches were not associated with sequence changes in promoter regions. Transfected episomes containing a luciferase reporter under control of a var promoter were expressed regardless of the transcriptional status of the endogenous promoter. The results suggest epigenetic regulation of P. falciparum var gene transcription that depends upon the local structure of chromatin and its associated proteins. (C) 1999 Published by Elsevier Science B.V. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 39 TC 85 Z9 86 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN 25 PY 1999 VL 101 IS 1-2 BP 107 EP 116 DI 10.1016/S0166-6851(99)00062-6 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 210TB UT WOS:000081119800010 PM 10413047 ER PT J AU Soubes, SC Liu, X Miller, LH AF Soubes, SC Liu, X Miller, LH TI Representational difference analysis of cDNA between two Dd2 clones of Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; sialic acid-independent invasion; RDA ID PROTEIN; ERYTHROCYTES; MALARIA; GENE; IDENTIFICATION; EXPRESSION; PHENOTYPES; PARASITES; FAMILY C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Blaise Pascal, CNRS, URA 1944, Lab Protistol Mol & Cellulaire Parasites, Aubiere, France. RP Miller, LH (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN 25 PY 1999 VL 101 IS 1-2 BP 217 EP 221 DI 10.1016/S0166-6851(99)00034-1 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 210TB UT WOS:000081119800019 PM 10413056 ER PT J AU Templeton, TJ Kaslow, DC AF Templeton, TJ Kaslow, DC TI Identification of additional members define a Plasmodium falciparum gene superfamily which includes Pfs48/45 and Pfs230 SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; malaria; Pfs48/45; Pfs230; six-cys domain ID TRANSMISSION-BLOCKING IMMUNITY; TARGET ANTIGENS; SEXUAL STAGE; VACCINE CANDIDATE; HUMAN MALARIA; EXPRESSION; BIOSYNTHESIS; ANTIBODIES; SEQUENCE; CLONING C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Templeton, TJ (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 17 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN 25 PY 1999 VL 101 IS 1-2 BP 223 EP 227 DI 10.1016/S0166-6851(99)00066-3 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 210TB UT WOS:000081119800020 PM 10413057 ER PT J AU Tarttelin, EE Kirschner, LS Bellingham, J Baffi, J Taymans, SE Gregory-Evans, K Csaky, K Stratakis, CA Gregory-Evans, CY AF Tarttelin, EE Kirschner, LS Bellingham, J Baffi, J Taymans, SE Gregory-Evans, K Csaky, K Stratakis, CA Gregory-Evans, CY TI Cloning and characterization of a novel orphan G-protein-coupled receptor localized to human chromosome 2p16 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HONEYCOMB RETINAL DYSTROPHY; RHODOPSIN AB We report the identification and characterisation of a novel human orphan G-protein-coupled receptor (GPR) which maps to chromosome 2p16. We have determined the full-length coding sequence and genomic structure of a gene corresponding to the anonymous expressed sequenced tag, WI-31133. This gene encodes a novel protein that is 540 amino acids in length. Protein sequence analysis predicts the presence of seven transmembrane domains, a characteristic feature of GPRs. In situ, hybridisation to human retina and Northern blot analysis of human retinal pigment epithelium (RPE) showed localisation of this transcript to the RPE and cells surrounding retinal arterioles; In contrast, the transcript was localised to the photoreceptor inner segments and the outer plexiform layer in mouse sections. Northern blot analysis demonstrated a 7 kb transcript highly expressed in the brain. No mutations were identified during a screen of patients suffering from Doyne's honeycomb retinal dystrophy (DHRD), an inherited retinal degeneration which maps to chromosome 2p16. (C) 1999 Academic Press. C1 Univ London Imperial Coll Sci Technol & Med, Sch Med, Div Biomed Sci, Mol Genet Sect, London SW7 2AZ, England. Univ London Imperial Coll Sci Technol & Med, Sch Med, Western Eye Hosp, Acad Unit Ophthalmol, London SW7 2AZ, England. NICHHD, Unit Genet & Endocrinol, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, Sect Gene Therapy, NIH, Bethesda, MD 20892 USA. RP Gregory-Evans, CY (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Med, Div Biomed Sci, Mol Genet Sect, Sir Alexander Fleming Bldg, London SW7 2AZ, England. RI Gregory-Evans, Kevin/G-9551-2011; Gregory-Evans, Cheryl/G-9550-2011 FU Wellcome Trust NR 16 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 24 PY 1999 VL 260 IS 1 BP 174 EP 180 DI 10.1006/bbrc.1999.0753 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 211AX UT WOS:000081138700029 PM 10381362 ER PT J AU Ciotti, M Basu, N Brangi, M Owens, IS AF Ciotti, M Basu, N Brangi, M Owens, IS TI Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COS-1 CELLS; CPT-11; CAMPTOTHECIN; METABOLITE; IRINOTECAN; EXPRESSION; IDENTIFICATION; BILIRUBIN; CLONING; PLASMA AB 7-Ethyl-10-hydroxycamptothecin (SN-38) is a very promising anticancer drug used for the treatment of metastatic colonrectal cancer, SN-38 is the active metabolite of irinotecan, a semisynthetic anticancer drug derived from 20(S)camptothecin. In this study, we examined the potential for each of the UGT1-encoded isoforms (UGT1A1 and UGT1A3 through UGT1A10) to glucuronidate SN-38, The amount of specific protein for each isoform was determined by Western blot analysis, Although UGT1A1 was previously shown to metabolize this drug, the results of this study show that UGT1A7 glucuronidates this chemical at a 9- to 21-fold higher level at pH 6.4 and pH 7.6, respectively, than that by UGT1A1, The activity of UGT1A7 is from 8.4- to 19-fold higher at pH 6.4 and 12- to 40-fold higher at pH 7.6 than that by the other 7 UGT1 encoded isoforms, UGT1A7 glucuronidates SN-38 with an apparent Km of 5 mu M. Hence, the distribution of this isoform in the gastrointestinal tract has the potential to impact the effectiveness of this chemotherapeutic agent. (C) 1999 Academic Press. C1 NICHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Owens, IS (reprint author), NIH, Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 17 TC 103 Z9 107 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 24 PY 1999 VL 260 IS 1 BP 199 EP 202 DI 10.1006/bbrc.1999.0453 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 211AX UT WOS:000081138700033 PM 10381366 ER PT J AU Roden, MM Lee, KH Panelli, MC Marincola, FM AF Roden, MM Lee, KH Panelli, MC Marincola, FM TI A novel cytolysis assay using fluorescent labeling and quantitative fluorescent scanning technology SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cytotoxicity; calcein; killer T-cells; immunotherapy; fluorescent assays ID MELANOMA ANTIGEN GP100; T-LYMPHOCYTES; RELEASE-ASSAY; CYTO-TOXICITY; IN-VIVO; TUMOR; CELLS; CYTOTOXICITY; RECOGNITION AB A novel cellular cytotoxicity assay using Calcein acetoxymethyl (Calcein-AM), a cytoplasmic fluorescent label, has been developed as an alternative to the standard (51)Chromium (Cr)-release. Target cells were loaded with Calcein-AM and then co-incubated with effector cells. An additional reagent, FluoroQuench, is added to extinguish fluorescence of dying target cells and of the culture media. Assay plates are read on a quantitative fluorescent scanner for determination of viable target cells. percent lysis is calculated as one minus the percent viable cells as compared to fluorescent-labeled targets-only wells. The assay was tested to demonstrate the lytic activity of cytotoxic T lymphocyte (CTL) cultures, lymphokine-activated killer (LAK), and natural killer (NK) cell line effecters against peptide-pulsed and melanoma targets. In addition to the acquisition of results comparable to the Cr-51-release assay, the Calcein assay reliably measures cell-mediated cytotoxicity with little variance among replicates. The fluorescent assay represents a simple and useful alternative to the use of radioactive materials and adds the additional benefit of digital images and analysis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, NIH, Bldg 10-2B42, Bethesda, MD 20892 USA. NR 16 TC 57 Z9 58 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 24 PY 1999 VL 226 IS 1-2 BP 29 EP 41 DI 10.1016/S0022-1759(99)00039-3 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 211LD UT WOS:000081161800004 PM 10410969 ER PT J AU Tyson, JE Wright, LL Oh, WOM Kennedy, KA Mele, L Ehrenkranz, RA Stoll, BJ Lemons, JA Stevenson, DK Bauer, CR Korones, SB Fanaroff, AA AF Tyson, JE Wright, LL Oh, WOM Kennedy, KA Mele, L Ehrenkranz, RA Stoll, BJ Lemons, JA Stevenson, DK Bauer, CR Korones, SB Fanaroff, AA CA Natl Inst Child Hlth Human Dev Neonatal Res Net TI Vitamin A supplementation for extremely-low-birth-weight infants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BINDING PROTEIN RESPONSE; BRONCHOPULMONARY DYSPLASIA; A SUPPLEMENTATION; PREMATURE-INFANTS; SERUM RETINOL; TRIAL; CAROTENOIDS; LIVER; PREVENTION; MORTALITY AB Background Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants. The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials. Methods We performed a multicenter, blinded, randomized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth. The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks. Results By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died. The primary outcome - death or chronic lung disease at 36 weeks' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group (55 percent vs. 62 percent; relative risk, 0.89; 95 percent confidence interval, 0.80 to 0.99). Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements. The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar. The proportion of infants with serum retinol values below 20 mu g per deciliter (0.70 mu mol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001). Conclusions Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants. (N Engl J Med 1999;340:1962-8.) (C) 1999, Massachusetts Medical Society. C1 Univ Texas, SW Med Ctr, Houston, TX 77030 USA. NICHHD, Bethesda, MD 20892 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Yale Univ, New Haven, CT USA. Emory Univ, Atlanta, GA 30322 USA. Indiana Univ, Indianapolis, IN 46204 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Tyson, JE (reprint author), Univ Texas, SW Med Ctr, 6431 Fannin,Suite 3-228, Houston, TX 77030 USA. FU NICHD NIH HHS [U10 HD19897, U10 HD21373, U10 HD27904] NR 37 TC 250 Z9 266 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 24 PY 1999 VL 340 IS 25 BP 1962 EP 1968 DI 10.1056/NEJM199906243402505 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 210CX UT WOS:000081088500005 PM 10379020 ER PT J AU Alexander, GE Mentis, MJ Van Horn, JD Grady, CL Berman, KF Furey, ML Pietrini, P Rapoport, SI Schapiro, MB Moeller, JR AF Alexander, GE Mentis, MJ Van Horn, JD Grady, CL Berman, KF Furey, ML Pietrini, P Rapoport, SI Schapiro, MB Moeller, JR TI Individual differences in PET activation of object perception and attention systems predict face matching accuracy SO NEUROREPORT LA English DT Article DE cognition; face matching; mental effort; object perception; PET; principal component analysis; rCBF; Scaled Subprofile Model; task performance; visual attention ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; CEREBRAL BLOOD-FLOW; ALZHEIMERS-DISEASE; SPATIAL VISION; PATHWAYS; ASSOCIATION; BRAIN AB WE sought to investigate how individual differences in the regional patterns of cerebral blood flow (rCBF) relate to task performance during the perceptual matching of faces. We analyzed rCBF data obtained by PET and (H2O)-O-15 from nine young healthy, right-handed, adult males (mean age 29 +/- 3 years) using a statistical model of regional covariance, the Scaled Subprofile Model (SSM). SSM analysis performed on a voxel-basis for scan subtractions comparing face-matching and control tasks extracted two patterns whose subject expression in a multiple regression analysis was highly predictive of task accuracy (R-2 = 0.87, p < 0.002). The pattern reflecting this linear combination was principally characterized by higher rCBF in regions of bilateral occipital and occipitotemporal cortex, right orbitofrontal cortex, left thalamus, basal ganglia, midbrain, and cerebellum with relatively lower rCBF in anterior cingulate, regions in bilateral prefrontal and temporal cortex, right thalamus, and right inferior parietal cortex. The results indicate that individual subject differences in face matching performance are specifically associated with the functional interaction of cortical and subcortical brain regions previously implicated in aspects of object perception and visual attentional processing. NeuroReport 10:1965-1971 (C) 1999 Lippincott Williams & Wilkins. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Alexander, GE (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C414, Bethesda, MD 20892 USA. RI Furey, Maura/H-5273-2013 NR 26 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 23 PY 1999 VL 10 IS 9 BP 1965 EP 1971 DI 10.1097/00001756-199906230-00032 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 212PM UT WOS:000081225500035 PM 10501542 ER PT J AU Takebayashi, Y Pourquier, P Yoshida, A Kohlhagen, G Pommier, Y AF Takebayashi, Y Pourquier, P Yoshida, A Kohlhagen, G Pommier, Y TI Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor groove SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE minor groove ligand; DNA-protein crosslink; DNA damage; DNA alkylation ID CARIBBEAN TUNICATE; CAMPTOTHECIN DERIVATIVES; CLEAVABLE COMPLEXES; CRYSTAL-STRUCTURES; ANTITUMOR-ACTIVITY; SEQUENCE; CYTOTOXICITY; DOXORUBICIN; TURBINATA; AGENT AB Ecteinascidin 743 (Et743, National Service Center 648766) is a potent antitumor agent from the Caribbean tunicate Ecteinascidia turbinata, Although Et743 is presently in clinical trials for human cancers, the mechanisms of antitumor activity of Et743 hale not been elucidated. Et743 can alkylate selectively guanine NZ from the DNA minor groove, and this alkylation is reversed by DNA denaturation, Thus, Et743 differs from other DNA alkylating agents presently in the clinic (by both its biochemical activities and its profile of antitumor activity in preclinical models), In this study, we investigated cellular proteins that can bind to DNA. alkylated by Et743. By using an oligonucleotide containing high-affinity Et743 binding sites and nuclear extracts from human leukemia CEM cells, we purified a 100-kDa protein as a cellular target of Et743 and identified it as topoisomerase I (top 1), Purified top1 was then tested and found to produce cleavage complexes in the presence of Et743, whereas topoisomerase Il had no effect. DNA alkylation was essential for the formation of top1-mediated cleavage complexes by Et743. and the distribution of the drug-induced top1 sites was different for Et743 and camptothecin. top1-DNA complexes were also detected in Et743-treated CEM cells by using cesium chloride gradient centrifugation followed by top1 immunoblotting. These data indicate that DNA minor groove alkylation by Et743 induces top1-mediated protein-linked DNA breaks and that top1 is a target for Et743 in vitro and in vivo. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Room 5D02, Bethesda, MD 20892 USA. NR 34 TC 74 Z9 78 U1 0 U2 4 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 JUN 22 PY 1999 VL 96 IS 13 BP 7196 EP 7201 DI 10.1073/pnas.96.13.7196 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000017 PM 10377391 ER PT J AU Adachi, M Iwasa, KH AF Adachi, M Iwasa, KH TI Electrically driven motor in the outer hair cell: Effect of a mechanical constraint SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COCHLEAR AMPLIFIER; FORCE GENERATION; MOTILITY; CAPACITANCE; RESPONSES AB The outer hair cell has a unique voltage-dependent motility associated with charge transfer across the plasma membrane. To examine mechanical changes in the membrane that are coupled with such charge movements, we digested the undercoating of the membrane with trypsin. We inflated the cell into a sphere and constrained the surface area by not allowing volume changes. We found that this constraint on the membrane area sharply reduced motor-associated charge movement across the membrane, demonstrating that charge transfer is directly coupled with membrane area change, This electromechanical coupling in the plasma membrane must be the key element for the motile mechanism of the outer hair cell. C1 Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, 9 Ctr Dr, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 27 TC 44 Z9 45 U1 0 U2 0 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 JUN 22 PY 1999 VL 96 IS 13 BP 7244 EP 7249 DI 10.1073/pnas.96.13.7244 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000025 PM 10377399 ER PT J AU Yakar, S Liu, JL Stannard, B Butler, A Accili, D Sauer, B LeRoith, D AF Yakar, S Liu, JL Stannard, B Butler, A Accili, D Sauer, B LeRoith, D TI Normal growth and development in the absence of hepatic insulin-like growth factor I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONGITUDINAL BONE-GROWTH; IGF-I; TISSUE CONCENTRATIONS; HEPATOCYTE GROWTH; BINDING-PROTEINS; TRANSGENIC MICE; GENE-EXPRESSION; CRE RECOMBINASE; ADIPOSE-TISSUE; MESSENGER-RNA AB The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) uas a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we hale used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver, igf1 gene deletion in the li, er abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However er, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates, Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I. C1 NIDDK, Sect Cellular & Mol Physiol, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Sect Cellular & Mol Physiol, Mol & Cellular Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 34 TC 887 Z9 908 U1 1 U2 22 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 JUN 22 PY 1999 VL 96 IS 13 BP 7324 EP 7329 DI 10.1073/pnas.96.13.7324 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000039 PM 10377413 ER PT J AU Nussenblatt, RB Fortin, E Schiffman, R Rizzo, L Smith, J Van Veldhisen, P Sran, P Yaffe, A Goldman, CK Waldmann, TA Whitcup, SM AF Nussenblatt, RB Fortin, E Schiffman, R Rizzo, L Smith, J Van Veldhisen, P Sran, P Yaffe, A Goldman, CK Waldmann, TA Whitcup, SM TI Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: A phase I/II clinical trial SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; INTERLEUKIN-2 RECEPTOR; BLOCKADE AB To evaluate the safety and potential therapeutic activity of humanized anti-IL-2 receptor mAb (Daclizumab) therapy in the treatment of patients with se cere, sight-threatening, intermediate and posterior noninfectious uveitis, a nonrandomized, open-label, pilot study was performed, Patients with uveitis were treated with a minimum of 20 mg of prednisone, cyclosporine, antimetabolites, or any combination of these agents were eligible. Patients were weaned off their systemic immunosuppressive agents according to a standardized schedule, while ultimately receiving Daclizumab infusions every 4 weeks. Anti-IL-2 receptor antibody therapy, given intravenously with intervals of up to 4 weeks in lieu of standard immunosuppressive therapy, appeared to prevent the expression of severe sight-threatening intraocular inflammatory disease in 8 of 10 patients treated over a 12-month period, with noted improvements in visual acuity. One patient met a primary endpoint with a loss of vision of 10 letters or more from baseline in one eye and another patient discontinued therapy because of evidence of increased ocular inflammation. hll patients were able to tolerate the study medications,without the need for dose reduction. We report effective long-term use of anti-IL-2 therapy for an autoimmune indication. These initial findings would suggest that anti-IL-2? receptor therapy ma be an effective therapeutic approach for uveitis and, by implication, other disorders with a predominant Th1 profile. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Clin Branch, NIH, Bethesda, MD 20892 USA. NEI, Ocular Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. EMMES Corp, Potomac, MD 20854 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N202,10 Ctr Dr,MSC 1858, Bethesda, MD 20892 USA. NR 14 TC 177 Z9 184 U1 1 U2 2 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 JUN 22 PY 1999 VL 96 IS 13 BP 7462 EP 7466 DI 10.1073/pnas.96.13.7462 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000063 PM 10377437 ER PT J AU Laghi, L Randolph, AE Chauhan, DP Marra, G Major, EO Neel, JV Boland, CR AF Laghi, L Randolph, AE Chauhan, DP Marra, G Major, EO Neel, JV Boland, CR TI JC virus DNA is present in the mucosa of the human colon and in colorectal cancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LARGE-T-ANTIGEN; HUMAN-BRAIN-TUMORS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN PLEURAL MESOTHELIOMA; BK VIRUS; CHROMOSOMAL DAMAGE; POLYOMAVIRUS-JC; HUMAN PAPOVAVIRUSES; SIMIAN VIRUS-40; CHOROID-PLEXUS AB JC virus (JCV) is a polyoma virus that commonly infects humans. We have found T antigen DNA sequences of JCV in the mucosa of normal human colons, colorectal cancers, colorectal cancer xenografts raised in nude mice, and in the human colon cancer cell line SW480. A larger number of viral copies is present in cancer cells than in non-neoplastic colon cells, and sequence microheterogeneity occurs within individual colonic mucosal specimens. The improved yield of detection after treatment with topoisomerase I suggests that the viral DNA is negatively supercoiled in the human tissues. These results indicate that JCV DNA can be found in colonic tissues, which raises the possibility that this virus may play a role in the chromosomal instability observed in colorectal carcinogenesis. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Boland, CR (reprint author), Univ Calif San Diego, Dept Med, 4028 Basic Sci Bldg,9500 Gilman Dr, La Jolla, CA 92093 USA. FU NCI NIH HHS [R01 CA72851, CA46592, P30 CA046592, R01 CA072851, R01 CA26803] NR 48 TC 153 Z9 160 U1 0 U2 2 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 JUN 22 PY 1999 VL 96 IS 13 BP 7484 EP 7489 DI 10.1073/pnas.96.13.7484 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000067 PM 10377441 ER PT J AU Xiao, XD Wu, LJ Stantchev, TS Feng, YR Ugolini, S Chen, H Shen, ZM Riley, JL Broder, CC Sattentau, QJ Dimitrov, DS AF Xiao, XD Wu, LJ Stantchev, TS Feng, YR Ugolini, S Chen, H Shen, ZM Riley, JL Broder, CC Sattentau, QJ Dimitrov, DS TI Constitutive cell surface association between CD4 and CCR5 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV; AIDS; receptors ID ENVELOPE GLYCOPROTEIN; MAJOR DETERMINANT; HIV-1 ENTRY; RECEPTOR; GP120; FUSION; INFECTION; ANTIBODY; COMPLEX; BINDING AB HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any other receptor-specific ligand. The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4-CCR5 coimmunoprecipitation Was not significantly increased by gp120. The CD4-CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4 It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry, These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on EnvCD4-CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross talk between cell surface receptors. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. LeukoSite Inc, Cambridge, MA 02142 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Ctr Immunol Marseille Luminy, F-13288 Marseille 9, France. Walter Reed Army Inst Res, Dept Retroviral, Rockville, MD 20850 USA. RP Dimitrov, DS (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, NIH, Bldg 469,Room 216,POB B,Miller Dr, Frederick, MD 21702 USA. OI Riley, James/0000-0002-1057-576X FU NIAID NIH HHS [R01 AI043885, R01AI43885] NR 42 TC 150 Z9 152 U1 0 U2 0 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 JUN 22 PY 1999 VL 96 IS 13 BP 7496 EP 7501 DI 10.1073/pnas.96.13.7496 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000069 PM 10377443 ER PT J AU Sheikh, KA Sun, J Liu, YJ Kawai, H Crawford, TO Proia, RL Griffin, JW Schnaar, RL AF Sheikh, KA Sun, J Liu, YJ Kawai, H Crawford, TO Proia, RL Griffin, JW Schnaar, RL TI Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SAMPLING SCHEMES; FIBER SIZE; GLYCOPROTEIN; DEFICIENT; NEUROFILAMENTS; SPECIFICITY; EXPRESSION; DIAMETER; NUMBER AB Gangliosides are a family of sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system, Although they are the major sialoglycoconjugates in the brain, their neurobiological Functions remain poorly defined. By disrupting the gene for a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase; EC 2.4.1.92) we generated mice that express only simple gangliosides (GM3/GD3) and examined their central and peripheral nervous systems. The complex ganglioside knockout mice display decreased central myelination, axonal degeneration in both the central and peripheral nervous systems, and demyelination in peripheral nerves. The pathological features of their nervous system closely resemble those reported in mice with a disrupted gene for myelin-associated glycoprotein (MAG)! a myelin receptor that binds to complex brain gangliosides in vitro. Furthermore, GM2/GD2 synthase knockout mice have reduced MAG expression in the central nervous system. These results indicate that complex gangliosides function in central myelination and maintaining the integrity of axons and myelin. They also support the theory that complex gangliosides are endogenous ligands for MAG. The data extend and clarify prior observations on a similar mouse model, which reported only subtle conduction defects in their nervous system. C1 Johns Hopkins Univ, Dept Pharmacol, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Schnaar, RL (reprint author), Johns Hopkins Univ, Dept Pharmacol, Sch Med, 725 N Wolfe St, Baltimore, MD 21205 USA. RI Proia, Richard/A-7908-2012; Crawford, Thomas/E-6307-2012; Schnaar, Ronald/S-8967-2016 OI Schnaar, Ronald/0000-0002-7701-5484 FU NINDS NIH HHS [NS37096, R01 NS037096, R37 NS037096] NR 40 TC 242 Z9 247 U1 0 U2 4 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 JUN 22 PY 1999 VL 96 IS 13 BP 7532 EP 7537 DI 10.1073/pnas.96.13.7532 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 209PB UT WOS:000081056000075 PM 10377449 ER PT J AU Zaman, V Zaki, M Howe, J Ng, M Leipe, DD Sogin, ML Silberman, JD AF Zaman, V Zaki, M Howe, J Ng, M Leipe, DD Sogin, ML Silberman, JD TI Hyperamoeba isolated from human feces: Description and phylogenetic affinity SO EUROPEAN JOURNAL OF PROTISTOLOGY LA English DT Article DE feces; amoeboflagellate; ultrastructure; Eumycetozoa; Hyperamoeba; 16S-like rRNA; phylogeny ID FREE-LIVING AMEBA; FLAGELLAR APPARATUS; N-SP; PHREATAMOEBA-BALAMUTHI; PHYSARUM-POLYCEPHALUM; RIBOSOMAL-RNA; EVOLUTION; EUKARYOTES; HETEROLOBOSEA; PROTOSTELIDS AB The morphology and phylogenetic affinity of Hyperamoeba isolated from human feces is described. During its life cycle, it switches reversibly from flagellate to aflagellated amoebae and is capable of forming cysts. It grows aerobically. Under anaerobic conditions it persists but does not replicate. The amoeboflagellate has a single nucleus with a distinct nucleolus. Its mitochondria possess tubular cristae and a central electron dense body, similar to that of plasmodial slime molds. A single contractile vacuole is evident. The flagellate has one detectable anterior flagellum but two basal bodies are visible at the ultrastructure level. The flagellar apparatus is very similar to that found in some Eumycetozoa, especially the myxogastrids. The uninucleate cyst has a bi-layered endocyst and a membranous, irregular shaped, faintly laminated ectocyst that harbors bacterial inclusions. Phylogenetic reconstructions based on nuclear small subunit ribosomal gene sequence comparisons show that Hyperamoeba is closely related to the plasmodial slime mold Physarum polycephalum. These protists share a most recent common ancestry that excludes all other taxa in the database. This phylogenetic relationship is supported by detailed similarities in both mitochondrial and flagellar apparatus ultrastructure. C1 Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, Woods Hole, MA 02543 USA. NIH, NCBI, Natl Lib Med, Bethesda, MD 20984 USA. Natl Univ Singapore, Fac Med, Dept Microbiol, Singapore 117548, Singapore. Aga Khan Univ, Coll Med, Fac Hlth Sci, Dept Microbiol, Karachi 74800, Pakistan. RP Silberman, JD (reprint author), Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Marine Biol Lab, Woods Hole, MA 02543 USA. EM Silberman@Evol5.mbl.edu NR 41 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0932-4739 EI 1618-0429 J9 EUR J PROTISTOL JI Eur. J. Protistol. PD JUN 21 PY 1999 VL 35 IS 2 BP 197 EP 207 PG 11 WC Microbiology SC Microbiology GA 220HN UT WOS:000081659300010 ER PT J AU Srikantan, V Sesterhenn, IA Davis, L Hankins, FR Avallone, FA Livezey, JR Connelly, R Mostofi, FK McLeod, DG Moul, JW Chandrasekharappa, SC Srivastava, S AF Srikantan, V Sesterhenn, IA Davis, L Hankins, FR Avallone, FA Livezey, JR Connelly, R Mostofi, FK McLeod, DG Moul, JW Chandrasekharappa, SC Srivastava, S TI Allelic loss on chromosome 6q in primary prostate cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; BREAST-CANCER; PROXIMAL 6Q; IMBALANCE; DELETION; REGIONS; ARM AB Molecular genetic analyses of human prostate cancer (CaP) has revealed frequent loss of specific chromosome regions suggesting the presence of putative tumor suppressor gene(s) (TSG) on these chromosome loci whose inactivation may play a role in prostate tumorigenesis. To understand the role of 6q alterations in CaP, we have undertaken a comprehensive analysis of proximal 6q. Genomic DNA from tumor and normal prostate tissues from radical prostatectomy specimens of 38 patients were analyzed by polymerase chain reaction (PCR) for 13 polymorphic microsatellite loci on 6q. Allelic losses of 1 or more polymorphic loci were detected in 11 of 38 patients (29%). Six of 11 tumors showing any 6q deletion were found to have allelic losses at D6S1056 and D6S300 loci. Our results revealed a 1.5 megabase interval between D6S1056 and D6S300 at 6q16.3-21 as the minimal region of deletion, which may contain the putative TSG involved in prostate tumorigenesis. One of the tumor samples demonstrated homozygous deletion at a distal location D6S314 (6q23-24), suggesting another locus potentially associated with Cap. Although the relationship of 6q loss of heterozygosity (LOH) with various clinico-pathologic variables, i.e., cancer recurrence or pathologic stage, did not reveal a statistically significant association, the risk for 6q LOH to non-organ confined (pT3) disease was 5-fold higher than for organ confined disease. Int. J. Cancer (Pred. Oncol) 84:331-335, 1999. (C) 1999 Wiley-Liss, Inc. C1 Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20306 USA. Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. Walter Reed Army Med Ctr, Dept Surg, Serv Urol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. NIH, Natl human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 23 TC 42 Z9 45 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 21 PY 1999 VL 84 IS 3 BP 331 EP 335 DI 10.1002/(SICI)1097-0215(19990621)84:3<331::AID-IJC23>3.0.CO;2-J PG 5 WC Oncology SC Oncology GA 202MZ UT WOS:000080657600023 PM 10371356 ER PT J AU Broxmeyer, HE Cooper, S Hangoc, G Gao, JL Murphy, PM AF Broxmeyer, HE Cooper, S Hangoc, G Gao, JL Murphy, PM TI Dominant myelopoietic effector functions mediated by chemokine receptor CCR1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE CC chemokine receptor 1; macrophage inflammatory protein 1 alpha; progenitor cells; proliferation; mobilization ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MYELOID PROGENITOR CELLS; COLONY FORMATION INVITRO; HUMAN-BONE-MARROW; HEMATOPOIETIC PROGENITORS; BETA-CHEMOKINE; MURINE; PROLIFERATION; INVIVO; MOBILIZATION C1 Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Immunol Microbiol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN 46208 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Broxmeyer, HE (reprint author), Indiana Univ, Sch Med, Walther Oncol Ctr, 1044 W Walnut St, Indianapolis, IN 46202 USA. FU NHLBI NIH HHS [R01 HL56416, R01 HL056416]; NIDDK NIH HHS [R01 DK053674, R01 DK53674] NR 27 TC 68 Z9 71 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 21 PY 1999 VL 189 IS 12 BP 1987 EP 1992 DI 10.1084/jem.189.12.1987 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 211JG UT WOS:000081157000015 PM 10377195 ER PT J AU Collins, FS Chandrasekharappa, SC Spiegel, AM Marx, SJ AF Collins, FS Chandrasekharappa, SC Spiegel, AM Marx, SJ TI Hot papers - Genetics - Positional cloning of the gene for multiple endocrine neoplasia-type I by S.C. Chandrasekharappa, S.C. Guru, P. Manickam, S. Olufemi, F.S. Collins, M.R. Emmert-Buck, L.V. Deblenko, Z. Zhuang, I.A. Lubensky, L.A. Liotta, J.S. Crabtree, Y. Wang, B.A. Roe, J. Weisemann, M. Boguski, S.K. Agarwal, M.B. Kester, Y.S. Kim, C. Heppener, Q. Dong, A.M. Spiegel, A.L. Burns, S.J. Marx - Comments SO SCIENTIST LA English DT Editorial Material ID MEN1 GENE; PARATHYROID TUMORS; CHROMOSOME-11 AB Francis S. Collins and Settara C. Chandrasekharappa of the National Human Genetics Research Institute and Allen M. Spiegel and Stephen J. Marx of the National Institute of Diabetes and Digestive and Kidney Diseases discuss the search for MENI, a tumor suppressor gene. C1 NIDDK, Bethesda, MD 20892 USA. NIDDK, Genet & Endocrinol Sect, Metabol Dis Branch, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JUN 21 PY 1999 VL 13 IS 13 BP 10 EP + PG 0 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 207PX UT WOS:000080946200009 ER PT J AU Dimitrov, DS Norwood, D Stantchev, TS Feng, YR Xiao, XD Broder, CC AF Dimitrov, DS Norwood, D Stantchev, TS Feng, YR Xiao, XD Broder, CC TI A mechanism of resistance to HIV-1 entry: Inefficient interactions of CXCR4 with CD4 and gp120 in macrophages SO VIROLOGY LA English DT Article DE HIV-1; CD4; CXCR4; coreceptors; chemokine receptors; envelope glycoprotein; membrane fusion ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; ENVELOPE GLYCOPROTEIN; FUNCTIONAL CORECEPTOR; MONOCLONAL-ANTIBODY; TYPE-1 TROPISM; CELL FUSION; EXPRESSION; INFECTION; RECEPTOR AB To test the hypothesis that inefficient interactions of CXCR4 with CD4 and gp120 could affect HIV-1 entry, we incubated macrophages, monocytes, and lymphocytes with gp120 and coimmunoprecipitated CD4 by using anti-CXCR4 antibodies. CD4 was efficiently coimmunoprecipitated in lymphocytes and monocytes but not in macrophages. Overexpression of CD4 in macrophages resulted in detection of CD4-CXCR4 and gp120-CD4-CXCR4 complexes in parallel with the restoration of macrophage fusion susceptibility. These results suggest a mechanism of resistance to entry of some X4 HIV-1 strains into macrophages and a method for dissection of the initial stages of HIV entry. C1 NCI, Lab Expt & Computat Biol, DBS, FCRDC,NIH, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Dimitrov, DS (reprint author), NCI, Lab Expt & Computat Biol, DBS, FCRDC,NIH, Bldg 469,Room 216,POB B,Miller Dr, Frederick, MD 21702 USA. FU NIAID NIH HHS [R01AI43885]; PHS HHS [R073FG] NR 38 TC 53 Z9 55 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 1999 VL 259 IS 1 BP 1 EP 6 DI 10.1006/viro.1999.9747 PG 6 WC Virology SC Virology GA 209AT UT WOS:000081025400001 PM 10364484 ER PT J AU Eberling, JL Bankiewicz, KS Pivirotto, P Bringas, J Chen, K Nowotnik, DP Steiner, JP Budinger, TF Jagust, WJ AF Eberling, JL Bankiewicz, KS Pivirotto, P Bringas, J Chen, K Nowotnik, DP Steiner, JP Budinger, TF Jagust, WJ TI Dopamine transporter loss and clinical changes in MPTP-lesioned primates SO BRAIN RESEARCH LA English DT Article DE Parkinson's disease; MPTP; monkey; single photon emission computed tomography; dopamine transporter; beta-CIT ID I-123 BETA-CIT; POSITRON EMISSION TOMOGRAPHY; COCAINE RECOGNITION SITES; MONOAMINE REUPTAKE SITES; H-3 PAROXETINE BINDING; SEROTONIN UPTAKE SITES; PARKINSONS-DISEASE; HUMAN-BRAIN; SPECT; KINETICS AB Single photon emission computed tomography (SPECT) and the dopamine (DA) transporter tracer, 2 beta-carboxymethoxy-3 beta-(4-iodophenyl)tropane ([I-123]beta-CIT), were used to determine DA transporter density in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys with varying degrees of parkinsonism. The clinical stage of parkinsonism corresponded to SPECT measures of striatal DA transporter density suggesting that more severe parkinsonism was associated with a greater degree of dopaminergic terminal degeneration. These findings are similar to those reported earlier using positron emission tomography (PET) and the DA metabolism tracer, 6-[F-18]fluoro-L-m-tyrosine (FMT), indicating that both are good methods for evaluating nigrostriatal degeneration in MPTP primate models. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, Berkeley, CA 94720 USA. NINDS, NIH, Bethesda, MD 20892 USA. CroMed Biosci, Orinda, CA USA. Guilford Pharmaceut, Baltimore, MD USA. Martinez VA Med Ctr, Dept Neurol, Martinez, CA USA. Univ Calif Davis, Davis, CA 95616 USA. RP Eberling, JL (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Ctr Funct Imaging, 1 Cyclotron Rd, Berkeley, CA 94720 USA. NR 25 TC 20 Z9 20 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 JUN 19 PY 1999 VL 832 IS 1-2 BP 184 EP 187 DI 10.1016/S0006-8993(99)01491-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 209UG UT WOS:000081066800024 PM 10375668 ER PT J AU Staprans, S Marlowe, N Glidden, D Novakovic-Agopian, T Grant, RM Heyes, M Aweeka, F Deeks, S Price, RW AF Staprans, S Marlowe, N Glidden, D Novakovic-Agopian, T Grant, RM Heyes, M Aweeka, F Deeks, S Price, RW TI Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection SO AIDS LA English DT Article DE AIDS; AIDS dementia complex; antiviral; cerebrospinal fluid; HIV; meningitis; quinolinic acid; RNA; treatment; viral load ID VIRUS TYPE-1 RNA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HIV-1 RNA; VIRAL LOAD; HIV-1-INFECTED PATIENTS; QUINOLINIC ACID; NEUROLOGICAL DISORDERS; COMBINATION THERAPY; ZIDOVUDINE; DEMENTIA AB Objectives: To compare the kinetics and magnitude of HIV-1 RNA responses to antiretroviral therapy (ART) in the cerebrospinal fluid (CSF) and plasma. Design: Repeated lumbar punctures (LPs) were performed after the initiation or change in ART in 15 HIV-1-infected subjects, with the focus on two phases of response: an acute phase within the first 11 days, for which crude estimates of viral RNA half-lives and decay rates were derived and CSF : plasma relative decay ratios quantitatively analysed; and a longer-term phase beyond 4 weeks that was descriptively assessed. Results: In 13 subjects studied during the acute phase, the crude HIV-1 RNA half-life was longer (median 2.0 compared with 1.9 days), the decay rate slower (median 0.13 compared with 0.16 log(10) copies/day) and, most notably, the variability greater (intraquartile range of half-life 1.8-4.3 compared with 1.7-2.1 days) in the CSF than in the plasma. A slower decay in the CSF correlated with lower initial blood CD4 T lymphocyte counts (P = 0.001). Seven of 11 subjects studied at 4 weeks or later, including some with slower acute-phase CSF responses, showed greater or more durable viral suppression in the CSF. Conclusion: Divergent acute-phase viral kinetics in the CSF and plasma, and proportionally greater long-term decrements in CSF HIV-1 RNA in slow early-responders or poor overall plasma responders indicate variable compartmentalization of CSF infection, consistent with a model of two prototypes of CSF infection: short-lived, transitory infection that predominates in early HIV-1 infection and longer-lived, more autonomous CSF infection predominating in late HIV-1 infection. Additional studies will be needed to define more precisely the acute and longer-term CSF kinetics in different clinical settings and to assess this model. (C) 1999 Lippincott Williams & Wilkins. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Clin Pharmacol, San Francisco, CA 94143 USA. NIMH, Gladstone Inst Virol & Immunol, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Price, RW (reprint author), San Francisco Gen Hosp, Room 4M62,1001 Potrero Ave, San Francisco, CA 94110 USA. EM price@itsa.ucsf.edu FU NCRR NIH HHS [5-MO1-RR-00083-36]; NIAID NIH HHS [P30 AI27763]; NINDS NIH HHS [R01 NS37660] NR 44 TC 101 Z9 103 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 18 PY 1999 VL 13 IS 9 BP 1051 EP 1061 DI 10.1097/00002030-199906180-00008 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 207GL UT WOS:000080927900008 PM 10397535 ER PT J AU Detera-Wadleigh, SD Barden, N Craddock, N Ewald, H Foroud, T Kelsoe, J McQuillin, A AF Detera-Wadleigh, SD Barden, N Craddock, N Ewald, H Foroud, T Kelsoe, J McQuillin, A TI Chromosomes 12 and 16 Workshop SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT VIth World Congress of Psychiatric Genetics CY OCT 07-10, 1998 CL BONN, GERMANY ID INITIATIVE BIPOLAR PEDIGREES; MANIC-DEPRESSIVE ILLNESS; GENOME-WIDE SEARCH; DARIERS-DISEASE; AFFECTIVE-DISORDER; GENE; LINKAGE; 12Q23-Q24.1; REGION; SCREEN AB Recent linkage results independently derived from a large French Canadian pedigree and Danish kindreds coupled with supportive data from other studies provide compelling evidence for a bipolar disorder susceptibility locus on chromosome 12q23-q24, The idea is further strengthened by the finding that Darier's disease, which maps to this region, has been shown to cosegregate with affective disorder in a family. This linkage finding, however, was not supported in other independent genome scans. On chromosome 16, bipolar families from Denmark exhibited suggestive linkage with D16S510, on 16p13, Multipoint nonparametric analysis on the NIMH Genetics Initiative bipolar pedigrees yielded increased allele sharing that maximized similar to 18 cM proximal to the latter locus. In contrast, evidence of linkage was not detected in other panels of bipolar families that were presented. At 16p13, a maximum multipoint lod score of 4 for a latent class-derived phenotype that has aspects of alcohol dependence was found in a genome scan of 105 families from the Collaborative Study of the Genetics of Alcoholism, identifying a potential vulnerability locus. Am. J. Med, Genet, (Neuropsychiatr. Genet,) 88: 255-259, 1999, Published 1999 Wiley-Liss, Inc.dagger. C1 NIMH, Intramural Program, NIH, Bethesda, MD 20892 USA. RP Detera-Wadleigh, SD (reprint author), NIMH, Intramural Program, NIH, Bldg 10,Rm 3N218, Bethesda, MD 20892 USA. RI McQuillin, Andrew/C-1623-2008 OI McQuillin, Andrew/0000-0003-1567-2240 NR 20 TC 31 Z9 32 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 18 PY 1999 VL 88 IS 3 BP 255 EP 259 DI 10.1002/(SICI)1096-8628(19990618)88:3<255::AID-AJMG8>3.0.CO;2-V PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 200TE UT WOS:000080555500008 PM 10374740 ER PT J AU Jin, DY Giordano, V Kibler, KV Nakano, H Jeang, KT AF Jin, DY Giordano, V Kibler, KV Nakano, H Jeang, KT TI Role of adapter function in oncoprotein-mediated activation of NF-kappa B - Human T-cell leukemia virus type i tax interacts directly with I kappa B kinase gamma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HTLV-I; IKK-ALPHA; PROTEIN; BETA; ASSOCIATION; LYMPHOCYTES; COMPLEX; P16(INK4A); REPRESSOR; INDUCTION AB Mechanisms by which the human T-cell leukemia virus tyre I Tax oncoprotein activates NF-kappa B remain incompletely understood. Although others have described an interaction between Tax and a holo-I kappa B kinase (IKK) complex, the exact details of protein-protein contact are not fully defined. Here we show that Tax binds to neither IKK-alpha nor IKH-beta but instead complexes directly with IKK-gamma, a newly characterized component of the IKK complex. This direct interaction with IKK-gamma correlates with Tax-induced I kappa B-alpha phosphorylation and NF-kappa B activation, Thus, our findings establish IKK-gamma as a key molecule for adapting an oncoprotein-specific signaling to IKK-alpha and IKK-beta. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Tokyo 1010062, Japan. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 40 TC 183 Z9 185 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17402 EP 17405 DI 10.1074/jbc.274.25.17402 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300003 PM 10364167 ER PT J AU Morinaga, N Adamik, R Moss, J Vaughan, M AF Morinaga, N Adamik, R Moss, J Vaughan, M TI Brefeldin A inhibited activity of the Sec7 domain of p200, a mammalian guanine nucleotide-exchange protein for ADP-ribosylation factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST GOLGI-APPARATUS; PHOSPHOLIPASE-D; HOMOLOGY DOMAINS; CHOLERA-TOXIN; ARF; COMPARTMENTS; CYTOHESIN-1; PLECKSTRIN; ACTIVATION; TRANSPORT AB A brefeldin A (BFA)-inhibited guanine nucleotide-exchange protein (GEP) for ADP-ribosylation factors (ARF) was purified earlier from bovine brain cytosol. Cloning and expression of the cDNA confirmed that the recombinant protein (p200) is a PEA-sensitive ARF GEP. p200 contains a domain that is 50% identical in amino acid sequence to a region in yeast Sec7, termed the Sec7 domain. Sec7 domains have been identified also in other proteins with ARF GEP activity, some of which are not inhibited by BFA. To identify structural elements that influence GEP activity and its BFA sensitivity, several truncated mutants of p200 were made. Deletion of sequence C-terminal to the Sec7 domain did not affect GEP activity. A protein lacking 594 amino acids at the N terminus, as well as sequence following the Sec7 domain, also had high activity, The mutant lacking 630 N-terminal amino acids was, however, only 1% as active, as was the Sec7 domain itself (mutant lacking 697 N-terminal residues). It appears that the Sec7 domain of p200 contains the catalytic site but additional sequence (perhaps especially that between positions 595 and 630) modifies activity dramatically. Myristoylated recombinant ARFs were better than non-myristoylated as substrates; ARFs 1 and 3 were better than ARF5, and no activity was detected with ARF6. Physical interaction of the Sec7 domain with an ARF1 mutant was demonstrated, but it was much weaker than that of the cytohesin-1 Sec7 domain with the same ARF protein. Effects of BFA on p200 and all mutants with high activity were similar with similar to 50% inhibition at less than or equal to 50 mu M. The inactive BFA analogue B36 did not inhibit the Sec7 domain or p200. Thus, the Sec7 domain of p200, like that of Sec7 itself (Sata, M., Donaldson, J. G., Moss, J., and Vaughan, M. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 4204-4208), plays a role in BFA inhibition as well as in GEP activity, although the latter is markedly modified by other structural elements. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Morinaga, N (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Rm 5N-307,Bldg 10,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. NR 30 TC 36 Z9 37 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17417 EP 17423 DI 10.1074/jbc.274.25.17417 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300006 PM 10364170 ER PT J AU Van Ryk, DI Venkatesan, S AF Van Ryk, DI Venkatesan, S TI Real-time kinetics of HIV-1 Rev-Rev response element interactions - Definition of minimal, binding sites on RNA and protein and stoichiometric analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SURFACE-PLASMON RESONANCE; STRUCTURAL GENE-EXPRESSION; NUCLEAR EXPORT SIGNAL; VIRAL MESSENGER-RNA; TYPE-1 REV; TRANS-ACTIVATOR; TARGET SEQUENCE; REGULATORY PROTEINS; FUNCTIONAL-ANALYSIS AB The kinetics of interaction between the human immunodeficiency virus-1 Rev protein and its RNA target, Rev response element (RRE) RNA was determined in vitro using a biosensor technique. Our results showed that the primary Rev binding site is a core stem-loop RNA molecule of 30 nucleotides that bound Rev at a 1:1 ratio, whereas the 244-nucleotide full-length RRE bound four Rev monomers. At high Rev concentrations, additional binding of Rev to RRE was observed with ratios of more than 10:1. Because RRE mutants that lacked the core binding site and were inactive in vivo bound Rev nonspecifically at these concentrations, the real stoichiometric ratio of Rev-RRE is probably closer to 4:1. Binding affinity of Rev for RRE was approximately 10(-10) M, whereas the affinity for the core RNA was about 10(-11) M, the difference being due to the contribution of low affinity binding sites on the RRE. Mathematical analysis suggested cooperativity of Rev binding, probably mediated by the Rev oligomerization domains. C-terminal deletions of Rev had no effect on RRE binding, but truncation of the N terminus by as few as 11 residues significantly reduced binding specificity. This method was also useful to rapidly evaluate the potential of aminoglycoside antibiotics, to inhibit the Rev-RRE interaction. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Venkatesan, S (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 10,Rm 6A05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 82 TC 59 Z9 60 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17452 EP 17463 DI 10.1074/jbc.274.25.17452 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300011 PM 10364175 ER PT J AU Hou, ZL Cashel, M Fromm, HJ Honzatko, RB AF Hou, ZL Cashel, M Fromm, HJ Honzatko, RB TI Effecters of the stringent response target the active site of Escherichia coli adenylosuccinate synthetase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURES; IDENTIFICATION; 5'-PHOSPHATE; HYDANTOCIDIN; HADACIDIN; BINDING; MG2+; GDP AB Guanosine 5'-diphosphate 3'-diphosphate (ppGpp), a pleiotropic effector of the stringent response, potently inhibits adenylosuccinate synthetase from Escherichia coli as an allosteric effector and/or as a competitive inhibitor with respect to GTP. Crystals of the synthetase grown in the presence of IMP, hadacidin, NO3- and Mg2+, then soaked with ppGpp, reveal electron density at the GTP pocket which is consistent with guanosine 5'-diphosphate 2':3'-cyclic monophosphate. Unlike ligand complexes of the synthetase involving IMP and GDP, the coordination of Mg2+ in this complex is octahedral with the side chain of Asp(13) in the inner sphere of the cation. The cyclic phosphoryl group interacts directly with the side chain of Lys(49) and indirectly through bridging water molecules with the side chains of Asn(295) and Arg(305). Th, synthetase either directly facilitates the formation of the cyclic nucleotide or scavenges trace amounts of the cyclic nucleotide from solution. Regardless of its mode of generation, the cyclic nucleotide binds far more tightly to the active site than does ppGpp. Conceivably, synthetase activity in vivo during the stringent response may be sensitive to the relative concentrations of several effecters, which together exercise precise control over the de novo synthesis of AMP. C1 Iowa State Univ Sci & Technol, Dept Biochem & Biophys, Ames, IA 50011 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Honzatko, RB (reprint author), Iowa State Univ Sci & Technol, Dept Biochem & Biophys, Ames, IA 50011 USA. EM honzatko@iastate.edu FU NINDS NIH HHS [NS 10546] NR 31 TC 26 Z9 29 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17505 EP 17510 DI 10.1074/jbc.274.25.17505 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300018 PM 10364182 ER PT J AU Quinto, I Mallardo, M Baldassarre, F Scala, G Englund, G Jeang, KT AF Quinto, I Mallardo, M Baldassarre, F Scala, G Englund, G Jeang, KT TI Potent and stable attenuation of live-HIV-1 by gain of a proteolysis-resistant inhibitor of NF-kappa B (I kappa B-alpha S32/36A) and the implications for vaccine development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; DYNAMICS IN-VIVO; EFFICIENT REPLICATION; CHEMOKINE RECEPTORS; INDUCED APOPTOSIS; SIV VACCINE; T-CELLS; ALPHA; TYPE-1; LIVE AB Live-attenuated human immunodeficiency viruses (HIVs) are candidates for Acquired Immunodeficiency Syndrome (AIDS) vaccine. Based on the simian immunodeficiency virus (SIV) model for AIDS, loss-of-function (e.g. deletion of accessory genes such as nef) has been forwarded as a primary approach for creating enfeebled, but replication-competent, HIV-1/SIV. Regrettably, recent evidence suggests that loss-of-function alone is not always sufficient to prevent the emergence off virulent mutants. New strategies that attenuate via mechanisms distinct from loss-of-function are needed for enhancing the safety phenotype of viral genome. Here, we propose gain-of-function to be used simultaneously with loss-of-function as a novel approach for attenuating HIV-1, We have constructed an HIV-1 genome carrying the cDNA of a proteolysis-resistant nuclear factor-kappa B inhibitor (I kappa B-alpha S32/36A) in the nef region. HIV-1 expressing 1 kappa B-alpha S32/36A down-regulates viral expression and is highly attenuated in both Jurkat and peripheral blood mononuclear cells. We provide formal proof that the phenotypic and attenuating characteristics of I kappa B-alpha S32/36A permit its stable maintenance in a live, replicating HIV-1 despite 180 days of forced ex vivo passaging in tissue culture. As compared with other open-reading frames embedded into HIV/SIV genome, this degree of stability is unprecedented. Thus, I kappa B-alpha S32/36A offers proof-of-principle that artifactually gained functions, when used to attenuate the replication of live HIV-1, can be stable. These findings illustrate gain-of-function as a feasible strategy for developing safer live-attenuated HIVs to be tested as candidates for AIDS vaccine. C1 Univ Naples, Dipartimento Biochim & Biotecnol Med, I-80131 Naples, Italy. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Univ Catanzaro, Dipartimento Med Sperimentale & Clin, I-88100 Cantanzaro, Italy. RP Quinto, I (reprint author), Univ Naples, Dipartimento Biochim & Biotecnol Med, Via Sergio Pansini 5, I-80131 Naples, Italy. RI SCALA, GIUSEPPE/A-3280-2009; Jeang, Kuan-Teh/A-2424-2008 NR 45 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17567 EP 17572 DI 10.1074/jbc.274.25.17567 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300027 PM 10364191 ER PT J AU Santalucia, T Boheler, KR Brand, NJ Sahye, U Fandos, C Vinals, F Ferre, J Testar, X Palacin, M Zorzano, A AF Santalucia, T Boheler, KR Brand, NJ Sahye, U Fandos, C Vinals, F Ferre, J Testar, X Palacin, M Zorzano, A TI Factors involved in GLUT-1 glucose transporter gene transcription in cardiac muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEOXYRIBONUCLEIC-ACID SYNTHESIS; BROWN ADIPOSE-TISSUE; SKELETAL-MUSCLE; POSTNATAL-DEVELOPMENT; CELL-DIFFERENTIATION; SP1-MEDIATED TRANSCRIPTION; REGULATE EXPRESSION; VESICLE POPULATIONS; BIOCHEMICAL ASPECTS; THYROID-HORMONE AB Glucose constitutes a major fuel for the heart, and high glucose uptake during fetal development is coincident with the highest level of expression of the glucose transporter GLUT-1 during life. We have previously reported that GLUT-1 is repressed perinatally in rat heart, and GLUT-1, which shows a low level of expression in the fetal stage, becomes the main glucose transporter in the adult. Here, we show that the perinatal expression of GLUT-1 and GLUT-1 glucose transporters in heart is controlled directly at the level of gene transcription. Transient transfection assays show that the -99/-33 fragment of the GLUT-1 gene is sufficient to drive transcriptional activity in rat neonatal cardiomyocytes. Electrophoretic mobility shift assays demonstrate that the transcription factor Sp1, a trans-activator of GLUT-1 promoter, binds to the -102/-82 region of GLUT-2 promoter during the fetal state but not during adulthood. Mutation of the Sp1 site in this region demonstrates that Sp1 is essential for maintaining a high transcriptional activity in cardiac myocytes. Sp1 is markedly down-regulated both in heart and in skeletal muscle during neonatal life, suggesting an active role for Sp1 in the regulation of GLUT-1 transcription. In all, these results indicate that the expression of GLUT-1 and GLUT-I in heart during perinatal development is largely controlled at a transcriptional level by mechanisms that might be related to hyperplasia and that are independent from the signals that trigger cell hypertrophy in the developing heart. Furthermore, our results provide the first functional insight into the mechanisms regulating muscle GLUT-1 gene expression in a live animal. C1 Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. NIA, Gerontol Res Ctr, Mol Cardiol Unit, Cardiovasc Sci Lab,NIH, Baltimore, MD 21224 USA. Imperial Coll, Sch Med, Natl Heart & Lung Inst, London SW3 6LY, England. RP Zorzano, A (reprint author), Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, Diagonal 645, E-08028 Barcelona, Spain. RI Santalucia, Tomas/B-6140-2012 OI Santalucia, Tomas/0000-0003-4604-9195 NR 67 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17626 EP 17634 DI 10.1074/jbc.274.25.17626 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300036 PM 10364200 ER PT J AU Ma, JX Qu, W Scarborough, PE Tomer, KB Moomaw, CR Maronpot, R Davis, LS Breyer, MD Zeldin, DC AF Ma, JX Qu, W Scarborough, PE Tomer, KB Moomaw, CR Maronpot, R Davis, LS Breyer, MD Zeldin, DC TI Molecular cloning, enzymatic characterization, developmental expression, and cellular localization of a mouse cytochrome p450 highly expressed in Kidney SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARACHIDONIC-ACID EPOXYGENASE; SPONTANEOUSLY HYPERTENSIVE RATS; EPOXYEICOSATRIENOIC ACIDS; HUMAN LIVER; MICROSOMAL CYTOCHROME-P450; ENANTIOFACIAL SELECTIVITY; FUNCTIONAL-SIGNIFICANCE; OMEGA-HYDROXYLATION; EPITHELIAL-CELLS; PROXIMAL TUBULE AB A cDNA encoding a new cytochrome P450 was isolated from a mouse liver library. Sequence analysis reveals that this 1,886-base pair cDNA encodes a 501-amino acid polypeptide that is 69-74% identical to CYP2J subfamily P450s and is designated CYP2J5. Recombinant CYP2J5 was co-expressed with NADPH-cytochrome P450 oxidoreductase in Sf9 cells using a baculovirus system. Microsomal fractions of CYP2J5/NADPH-cytochrome P450 oxidoreductase-transfected cells metabolize arachidonic acid to 14,15-, 11,12-, and 8,9-epoxyeicosatrienoic acids and 11- and 15-hydroxyeicosatetraenoic acids (catalytic turnover, 4.5 nmol of product/nmol of cytochrome P450/min at 37 degrees C); thus CYP2J5 is enzymologically distinct. Northern analysis reveals that CYP2J5 transcripts are most abundant in mouse kidney and present at lower levels in liver. Immunoblotting using a polyclonal antibody against a CYP2J5-specific peptide detects a protein with the same electrophoretic mobility sis recombinant CYP2J5 most abundantly in mouse kidney microsomes. CYP2J5 is regulated during development in a tissue-specific fashion. In the kidney, CYP2J5 is present before birth and reaches maximal levels at 2-4 weeks of age. In the liver, CYP2J5 is absent prenatally and during the early postnatal period, first appears at 1 week, and then remains relatively constant. Immunohistochemical staining of kidney sections with anti-human CYP2J2 IBG reveals that CYP2J protein(s) are present primarily in the proximal tubules and collecting ducts, sites where the epoxyeicosatrienoic acids are known to modulate fluid/electrolyte transport and mediate hormonal action. In situ hybridization confirms abundant CYP2J5 mRNA within tubules of the renal cortex and outer medulla. Epoxyeicosatrienoic acids are endogenous constituents of mouse kidney thus providing direct evidence for the in vivo metabolism of arachidonic acid by the mouse renal epoxygenase(s). Based on these data, we conclude that CYP2J5 is an enzymologically distinct, developmentally regulated, protein that is localized to specific nephron segments and contributes to the oxidation of endogenous renal arachidonic acid pools. In light of the well documented effects of epoxyeicosatrienoic acids in modulating renal tubular transport processes, we postulate that CYP2J5 products play important functional roles in the kidney. C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. RP NIEHS, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU NIDDK NIH HHS [P01-DK38226] NR 82 TC 71 Z9 73 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 18 PY 1999 VL 274 IS 25 BP 17777 EP 17788 DI 10.1074/jbc.274.25.17777 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208DE UT WOS:000080974300057 PM 10364221 ER PT J AU Ponting, CP Aravind, L Schultz, J Bork, P Koonin, EV AF Ponting, CP Aravind, L Schultz, J Bork, P Koonin, EV TI Eukaryotic signalling domain homologues in archaea and bacteria. Ancient ancestry and horizontal gene transfer SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE horizontal gene transfer; signalling domains; homology; genome comparison; sequence profiles ID SYNECHOCYSTIS PCC6803; PHOSPHOLIPID SYNTHASES; CONSERVED DOMAINS; SIGNALING DOMAINS; PROTEIN SEQUENCES; CRYSTAL-STRUCTURE; PROFILE SEARCHES; INORGANIC CARBON; BINDING PROTEINS; ESCHERICHIA-COLI AB Phyletic distributions of eukaryotic signalling domains were studied using recently developed sensitive methods for protein sequence analysis, with an emphasis on the detection and accurate enumeration of homologues in bacteria and archaea. A major difference was found between the distributions of enzyme families that are typically found in all three divisions of cellular life and non-enzymatic domain families that are usually eukaryote-specific. Previously undetected bacterial homologues were identified for# plant pathogenesis-related proteins, Pad1, von Willebrand factor type A, src homology 3 and YWTD repeat-containing domains. Comparisons of the domain distributions in eukaryotes and prokaryotes enabled distinctions to be made between the domains originating prior to the last common ancestor of all known life forms and those apparently originating as consequences of horizontal gene transfer events. A number of transfers of signalling domains from eukaryotes to bacteria were confidently identified, in contrast to only a single case of apparent transfer from eukaryotes to archaea. (C) 1999 Academic Press. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. European Mol Biol Lab, D-69012 Heidelberg, Germany. RP Ponting, CP (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A, Bethesda, MD 20894 USA. EM ponting@ncbi.nlm.nih.gov RI Schultz, Joerg/B-9346-2008; Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 99 TC 216 Z9 225 U1 2 U2 14 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 18 PY 1999 VL 289 IS 4 BP 729 EP 745 DI 10.1006/jmbi.1999.2827 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212BH UT WOS:000081196100006 PM 10369758 ER PT J AU Baber, JL Libutti, D Levens, D Tjandra, N AF Baber, JL Libutti, D Levens, D Tjandra, N TI High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE hnRNP K; KH domain; dipolar coupling; nucleic acid-binding; c-myc ID FRAGILE-X-SYNDROME; ROTATIONAL DIFFUSION ANISOTROPY; QUANTITATIVE J-CORRELATION; 2-DIMENSIONAL NMR-SPECTRA; MAGNETIC-FIELD DEPENDENCE; RNA-BINDING PROTEINS; CRYSTAL-STRUCTURE; RIBOSOMAL-RNA; DIPOLAR COUPLINGS; HNRNP-K AB Among it's many reported functions, heterogeneous nuclear ribonucleoprotein (hnRNP) K is a transcription factor for the c-myc gene, a proto-oncogene critical for the regulation of cell growth and differentiation. We have determined the solution structure of the Gly26 --> Arg mutant of the C-terminal K-homology (KH) domain of hnRNP K by NMR spectroscopy. This is the first structure investigation of hnRNP K. Backbone residual dipolar couplings, which provide information that is fundamentally different from the standard NOE-derived distance restraints, were employed to improve structure quality. An independent assessment of structure quality was achieved by comparing the backbone N-15 T-1/T-2 ratios to the calculated structures. The C-terminal KH module of hnRNP K (KH3) is revealed to be a three-stranded beta-sheet stacked against three alpha-helices, two of which are nearly parallel to the strands of the beta-sheet. The Gly26 --> Arg mutation abolishes single-stranded DNA binding without altering the overall fold of the protein. This provides a clue to possible nucleotide binding sites of KH3. It appears unlikely that the solvent-exposed side of the beta-sheet will be the site of protein-nucleic acid complex formation. This is in contrast to the earlier theme for protein-RNA complexes incorporating proteins structurally similar to KH3. We propose that the surface of KH3 that interacts with nucleic acid is comparable to the region of DNA interaction for the double-stranded DNA-binding domain of bovine papillomavirus-1 E2 that has a three-dimensional fold similar to that of KH3. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 82 TC 73 Z9 75 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 18 PY 1999 VL 289 IS 4 BP 949 EP 962 DI 10.1006/jmbi.1999.2818 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212BH UT WOS:000081196100022 PM 10369774 ER PT J AU Wong, ML Webster, EL Spokes, H Phu, P Ehrhart-Bornstein, M Bornstein, S Park, CS Rice, KC Chrousos, GP Licinio, J Gold, PW AF Wong, ML Webster, EL Spokes, H Phu, P Ehrhart-Bornstein, M Bornstein, S Park, CS Rice, KC Chrousos, GP Licinio, J Gold, PW TI Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress SO LIFE SCIENCES LA English DT Article DE stress; antalarmin; cortisol; adrenocorticotropic hormone; immobilization; corticotropin releasing hormone receptors ID CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA; RAT-BRAIN; THERAPEUTIC IMPLICATIONS; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; DEPRESSION; CLONING; WEIGHT AB Antalarmin is a pyrrolopyrimidine compound that antagonizes corticotropin-releasing hormone (CRH) type 1 receptors (CRHR1). In order to assess the effects of antalarmin treatment on hypothalamic-pituitary-adrenal (HPA) function we measured the plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in animals treated with either antalarmin or vehicle for 1 week or for 8 weeks. We found that antalarmin treatment for 1 week did not affect basal concentrations of ACTH or corticosterone. In contrast, treatment for 8 weeks significantly lowered basal ACTH and corticosterone concentrations and also significantly decreased the basal corticosterone to ACTH ratio, indicating decreased basal adrenocortical responsiveness to ACTH. However, immobilization stress resulted in ACTH and corticosterone concentrations that were the same in animals treated with vehicle or antalarmin for either 1 or 8 weeks. We conclude that even though g-week antagonism of CRHR1 by the non-peptide antalarmin blunts basal concentrations of ACTH and corticosterone, and affects the adrenal responsiveness to ACTH, it does not blunt the HPA response to acute stress, and it does not appear to cause stress-induced adrenal insufficiency. Published by Elsevier Science Inc. C1 NIMH, NIH, Clin Neuroendocrinol Branch, Intramural Res Program, Bethesda, MD 20892 USA. NICHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Licinio, J (reprint author), NIMH, NIH, Clin Neuroendocrinol Branch, Intramural Res Program, Bldg 10-2D46, Bethesda, MD 20892 USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 22 TC 22 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 18 PY 1999 VL 65 IS 4 BP PL53 EP PL58 DI 10.1016/S0024-3205(99)00268-4 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 210RA UT WOS:000081117400013 PM 10421433 ER PT J AU Li, BS Veeranna Grant, P Pant, HC AF Li, BS Veeranna Grant, P Pant, HC TI Calcium influx and membrane depolarization induce phosphorylation of neurofilament (NF-M) KSP repeats in PC12 cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE neurofilament; phosphorylation; calcium channel; depolarization; MAPK; PC12 cell ID AMYOTROPHIC-LATERAL-SCLEROSIS; EPIDERMAL GROWTH-FACTOR; RAT SPINAL-CORD; MAP KINASE; STIMULATED PROTEIN; IN-VIVO; ACTIVATION; IDENTIFICATION; CHANNELS; NEURONS AB Signals activating the kinases that phosphorylate neurofilament proteins in the axon remain unknown. In a previous study, we have demonstrated that a constitutively active form of MEK1 activates Erk1 and Erk2 kinases, which phosphorylate co-transfected NF-M in NM 3T3 cells. In this study,we report the activation of endogenous Erk1 and Erk2 by membrane depolarization and calcium influx through L-type calcium channels, which resulted in phosphorylation of the NF-M tail domain in PC12 cells. This phosphorylation was inhibited in the presence of nifedipine, an L-type calcium channel inhibitor, and PD98059, a specific MEK1 inhibitor. Our data suggest a mechanism linking calcium influx through voltage-gated calcium channels with the MAP kinase pathway and NF-M tail domain phosphorylation in cell body and neurite. These findings may provide significant new insights into mechanisms involved in some neurological diseases. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Li, BS (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D04,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN 18 PY 1999 VL 70 IS 1 BP 84 EP 91 DI 10.1016/S0169-328X(99)00142-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 209NK UT WOS:000081054500010 ER PT J AU Lenfant, C AF Lenfant, C TI June 17, 1999 - A symposium: From increased energy metabolism to cardiac hypertrophy and failure: Mediators and molecular mechanisms - Foreword SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), NHLBI, NIH, 3100 Ctr Dr,Bldg 31,MSC2486, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 17 PY 1999 VL 83 IS 12A SI SI BP 3H EP 3H PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 214BN UT WOS:000081307900002 ER PT J AU Izraeli, S Lowe, LA Bertness, VL Good, DJ Dorward, DW Kirsch, IR Kuehn, MR AF Izraeli, S Lowe, LA Bertness, VL Good, DJ Dorward, DW Kirsch, IR Kuehn, MR TI The SIL gene is required for mouse embryonic axial development and left-right specification SO NATURE LA English DT Article ID LEFT-RIGHT ASYMMETRY; SIGNALING PATHWAY; SONIC HEDGEHOG; TRANSCRIPTION FACTOR; NODAL EXPRESSION; NOTOCHORD; ZEBRAFISH; INDUCTION; PATTERN; PITX2 AB The establishment of the main body axis and the determination of left-right asymmetry are fundamental aspects of vertebrate embryonic development. A link between these processes has been revealed by the frequent finding of midline defects in humans with left-right anomalies(1). This association is also seen in a number of mutations in mouse(2-4) and zebrafish(1,5), and in experimentally manipulated Xenopus embryos(5). However, the severity of laterality defects accompanying abnormal midline development varies(6), and the molecular basis for this variation is unknown. Here we show that mouse embryos lacking the early-response gene SIL have axial midline defects, a block in midline Sonic hedgehog (Shh) signalling and randomized cardiac looping. Comparison with Shh mutant embryos(7), which have axial defects but normal cardiac looping, indicates that the consequences of abnormal midline development for left-right patterning depend on the time of onset, duration and severity of disruption of the normal asymmetric patterns of expression of nodal, lefty-2 and Pitx2. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Genet, Med Branch, NIH, Bethesda, MD 20889 USA. Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Kuehn, MR (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 30 TC 142 Z9 143 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 17 PY 1999 VL 399 IS 6737 BP 691 EP 694 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 207JB UT WOS:000080932800061 PM 10385121 ER PT J AU Eisenhofer, G Lenders, JWM Linehan, WM Walther, MM Goldstein, DS Keiser, HR AF Eisenhofer, G Lenders, JWM Linehan, WM Walther, MM Goldstein, DS Keiser, HR TI Plasma normetanephrine and metanephrine for detecting pheochromocytoma in Von Hippel-Lindau disease and multiple endocrine neoplasia type 2 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LIQUID-CHROMATOGRAPHY; DIAGNOSIS; URINARY; CATECHOLAMINES; METABOLISM AB Background. The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel-Lindau disease or multiple endocrine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measurements of plasma normetanephrine and metanephrine for detecting pheochromocytomas in patients with von Hippel-Lindau disease or MEN-2. Methods. We studied 26 patients with von Hippel-Lindau disease and 9 patients with MEN-2 who had histologically verified pheochromocytomas and 50 patients with von Hippel-Lindau disease or MEN-2 who had no radiologic evidence of pheochromocytoma. Von Hippel-Lindau disease and MEN-2 were diagnosed on the basis of germ-line mutations of the appropriate genes. The plasma concentrations of normetanephrine and metanephrine were compared with the plasma concentrations of catecholamines (norepinephrine and epinephrine) and urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid. Results. The sensitivity of measurements of plasma normetanephrine and metanephrine for the detection of tumors was 97 percent, whereas the other biochemical tests had a sensitivity of only 47 to 74 percent. All patients with MEN-2 had high plasma concentrations of metanephrine, whereas the patients with von Hippel-Lindau disease had almost exclusively high plasma concentrations of only normetanephrine. One patient with von Hippel-Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (< 1 cm). The high sensitivity of measurements of plasma normetanephrine and metanephrine was accompanied by a high level of specificity (96 percent). Conclusions. Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familiar predisposition to these tumors. (N Engl J Med 1999; 340:1872-9.) (C) 1999, Massachusetts Medical Society. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. Univ Nijmegen St Radboud Hosp, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. RP Eisenhofer, G (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Rm 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. RI Lenders, J.W.M./L-4487-2015 NR 29 TC 198 Z9 205 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 17 PY 1999 VL 340 IS 24 BP 1872 EP 1879 DI 10.1056/NEJM199906173402404 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 206EC UT WOS:000080863500004 PM 10369850 ER PT J AU Varmus, H AF Varmus, H TI Evaluating the burden of disease and spending the research dollars of the National Institutes of Health SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Varmus, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 32 Z9 32 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 17 PY 1999 VL 340 IS 24 BP 1914 EP 1915 DI 10.1056/NEJM199906173402411 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 206EC UT WOS:000080863500011 PM 10369857 ER PT J AU Amundson, SA Bittner, M Chen, YD Trent, J Meltzer, P Fornace, AJ AF Amundson, SA Bittner, M Chen, YD Trent, J Meltzer, P Fornace, AJ TI Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses SO ONCOGENE LA English DT Article DE cDNA microarray; ionizing radiation; leukemia; p53; genotoxic stress ID GENE-EXPRESSION PATTERNS; GAMMA-RAY RESPONSE; TUMOR-SUPPRESSOR; DNA-DAMAGE; GROWTH ARREST; P53; INDUCTION; APOPTOSIS; ATF3; PROTEINS AB The fate of cells exposed to ionizing radiation (IR) may depend greatly on changes in gene expression, so that an improved, view of gene induction profiles is important for understanding mechanisms of checkpoint control, repair and cell death following such exposures. We have used a quantitative fluorescent cDNA microarray hybridization approach to identify genes regulated in response gamma- irradiation in the p53 wild-type ML-1 human myeloid cell line. Hybridization of the array to fluorescently-labeled RNA from treated and untreated cells Has followed by computer analysis to derive relative changes in expression levels of the genes present in the array which agreed well with actual quantitative changes in expression. Forty-eight sequences, 30 not previously identified as IR-responsive, were significantly regulated by IR. Induction by IR and other stresses of a subset of these genes, including the previously characterized CIP1/WAF1, MDM and BAX genes, as well as nine genes not previously reported to be IR-responsive, was examined in a panel of 12 human cell lines. Responses varied widely in cell lines with different tissues of origin and different genetic backgrounds, highlighting the importance of cellular contest to genotoxic stress responses. Two of the newly identified IR-responsive genes, FRA-1 and ATF3, showed a p53-associated component to their IR-induction, and this was confirmed both in isogenic human cell lines and in mouse thymus. The majority of the IR-responsive genes, however, showed no indication of p53-dependent regulation, representing a potentially important class of stress-responsive genes in leukemic cells. C1 NCI, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Amundson, SA (reprint author), NCI, NIH, 37 Convent Dr,Bldg 37-Rm 5C09, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 45 TC 257 Z9 272 U1 0 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 17 PY 1999 VL 18 IS 24 BP 3666 EP 3672 DI 10.1038/sj.onc.1202676 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 206QZ UT WOS:000080891700014 PM 10380890 ER PT J AU Yoshida, A Hattori, K Hisatome, I Taniguchi, S Ueta, Y Hukui, H Santo, Y Igawa, O Shigemasa, C Kosugi, S Grollman, EF AF Yoshida, A Hattori, K Hisatome, I Taniguchi, S Ueta, Y Hukui, H Santo, Y Igawa, O Shigemasa, C Kosugi, S Grollman, EF TI A TSH dibutyryl cAMP activated Cl-/I- channel in FRTL-5 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CHLORIDE CHANNELS; APICAL MEMBRANE; THYROID-CELLS; CYCLIC-AMP; CONDUCTANCE; TRANSPORT; LINE; SCN AB An iodide (I) and chloride (Cl) channel has been identified in the continuously cultured FRTL-5 thyroid cell line using a cell attached patch clamp technique. The channel is activated by TSH and dibutyryladenosine cyclic monophosphate (Bt(2)-cAMP) but not by phorbol 12-myristate 13-acetate (TPA). Gluconate can not replace chloride or iodide and the channel is impermeable to Na+,K+ and tetraethylammonium ions. The current-voltage relationship demonstrates that the single channel current is a Linear function of the clamp voltage. Single channel currents reversed at a pipette potential close to 0 mV. The mean single channel conductance was 60 pS for Cl- and 50 pS for I-. From the I-V relationship there was a strong outward rectification with Cl-, and a complete block with I-, in the single channel current above +40 mV. The feature of the channel is manifested in the single channel records by four distinct, equally spaced conductance levels. We suggest the channel is important for the transport of I and Cl ions across the apical membrane into the colloid space and is important for hormone synthesis and follicle formation. (C) 1999 Academic Press. C1 Tottori Univ, Sch Med, Dept Internal Med 1, Yonago, Tottori 683, Japan. Kyoto Univ, Sch Med, Dept Lab Med, Kyoto 60601, Japan. NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Yoshida, A (reprint author), Tottori Univ, Sch Med, Dept Internal Med 1, Nishimachi 36-1, Yonago, Tottori 683, Japan. NR 26 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 16 PY 1999 VL 259 IS 3 BP 631 EP 635 DI 10.1006/bbrc.1999.0836 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 208XC UT WOS:000081016300022 PM 10364469 ER PT J AU Cohen, SG AF Cohen, SG TI Max Samter, MD - Obituary SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Biographical-Item C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 16 PY 1999 VL 281 IS 23 BP 2255 EP 2256 DI 10.1001/jama.281.23.2255 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 204RB UT WOS:000080777000045 ER PT J AU Fraumeni, JF Rimer, BK AF Fraumeni, JF Rimer, BK TI Cancer surveillance series: Inauguration SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Rimer, BK (reprint author), NIH, Execut Plaza N,Rm 242, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1004 EP 1004 DI 10.1093/jnci/91.12.1004 PG 1 WC Oncology SC Oncology GA 206AC UT WOS:000080853000009 ER PT J AU Graubard, BL Korn, EL AF Graubard, BL Korn, EL TI Analyzing health surveys for cancer-related objectives SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID EPIDEMIOLOGIC FOLLOW-UP; NUTRITION EXAMINATION SURVEY; 1ST NATIONAL-HEALTH; UNITED-STATES; BREAST-CANCER; CIGARETTE-SMOKING; NHANES-I; INTERVIEW SURVEY; RISK-FACTORS; ORAL-CONTRACEPTIVES AB Large-scale health surveys conducted by government agencies record information on a large number of health-related variables, We review the use of these data for performing analyses that address cancer-related objectives. After describing the conduct of a large-scale health survey (the third National Health and Nutrition Examination Survey [NHANES III]), we discuss some of the issues involved in analyzing data collected in such a survey. In particular, the use of sample weights in the analysis and the importance of accounting for the complex survey design when estimating standard errors are discussed. Six applications are then presented that involve the following: I) estimating demographic factors associated with snuff use, 2) estimating the association of type of health insurance with the probability of receiving a digital rectal examination, 3) estimating the association of body iron stores with the probability of later developing cancer, 3) estimating the changing rates of mammography screening in the United States between 1987 and 1992, 5) evaluating smoking and alcohol consumption as risk factors for digestive cancer by use of a population-based, case-control study, and 6) evaluating a randomized community-intervention experiment to encourage smoking cessation. These applications use data from the National Health Interview Survey, the NHANES I Epidemiologic Followup Study, the 1986 National Mortality Followback Survey, and the Community Intervention Trial for Smoking Cessation. The availability of public-use data files is discussed for surveys sponsored by the U.S. government that collect health-related information. We demonstrate that statistical methods and computer software are available for analyzing public-use data files of surveys to address different types of cancer-related objectives. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Graubard, BL (reprint author), NIH, Execut Plaza S,Rm 8024, Bethesda, MD 20892 USA. NR 90 TC 49 Z9 49 U1 1 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1005 EP 1016 DI 10.1093/jnci/91.12.1005 PG 12 WC Oncology SC Oncology GA 206AC UT WOS:000080853000010 PM 10379963 ER PT J AU Hankey, BF Feuer, EJ Clegg, LX Hayes, RB Legler, JM Prorok, PC Ries, LA Merrill, RM Kaplan, RS AF Hankey, BF Feuer, EJ Clegg, LX Hayes, RB Legler, JM Prorok, PC Ries, LA Merrill, RM Kaplan, RS TI Cancer surveillance series: Interpreting trends in prostate cancer - Part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEW-MEXICO; CARCINOMA; EPIDEMIOLOGY; US AB Background: The prostate-specific antigen test was approved by the U.S. Food and Drug Administration in 1986 to monitor the disease status in patients with prostate cancer and, in 1994, to aid in prostate cancer detection. However, after 1986, the test was performed on many men who had not been previously diagnosed with prostate cancer, apparently resulting in the diagnosis of a substantial number of early tumors. Our purpose is to provide insight into the effect of screening on prostate cancer rates, Detailed data are presented for whites because the size of the population allows for calculating statistically reliable rates; however, similar overall trends are seen for African-Americans and other races. Methods: Prostate cancer incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and mortality data from the National Center for Health Statistics were analyzed, Results/Conclusions: The following findings are consistent with a screening effect: 1) the recent decrease since 1991 in the incidence of distant stage disease, after not having been perturbed by screening; 2) the decline in the incidence of earlier stage disease beginning the following year (i.e,, 1992); 3) the recent increases and decreases in prostate cancer incidence and mortality by age that appear to indicate a calendar period effect; and 4) trends in the incidence of distant stage disease by tumor grade and trends in the survival of patients,vith distant stage disease by calendar year that provide suggestive evidence of the tendency of screening to detect slower growing tumors, Implications: The decline in the incidence of distant stage disease holds the promise that testing for prostate-specific antigen may lead to a sustained decline in prostate cancer mortality. However, population data are complex, and it is difficult to confidently attribute relatively small changes in mortality to any one cause. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Treatment, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. RP Hankey, BF (reprint author), NIH, Execut Plaza N,Rm 343J, Bethesda, MD 20892 USA. NR 30 TC 393 Z9 403 U1 1 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1017 EP 1024 DI 10.1093/jnci/91.12.1017 PG 8 WC Oncology SC Oncology GA 206AC UT WOS:000080853000011 PM 10379964 ER PT J AU Feuer, EJ Merrill, RM Hankey, BF AF Feuer, EJ Merrill, RM Hankey, BF TI Cancer surveillance series: Interpreting trends in prostate cancer - Part II: Cause of death misclassification and the recent rise and fall in prostate cancer mortality SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RADICAL PROSTATECTOMY; UNITED-STATES; ON-CANCER; CARCINOMA; RADIOTHERAPY; OUTCOMES AB Background. The rise and fall of prostate cancer mortality correspond closely to the rise and fall of newly diagnosed cases. To understand this phenomenon, we explored the role that screening, treatment, iatrogenic (i.e., treatment-induced) deaths, and attribution bias (incorrect labeling of death from other causes as death from prostate cancer) have played in recent mortality trends. Methods. Join point regression is utilized to assess the recent rise and fall in mortality and the relationship of total U.S. trends to those areas served by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Cancer Registry Program. Incidence-based mortality (IBM) is estimated with the use of prostate cancer data from the SEER Program to partition (from overall prostate cancer mortality trends) the contribution of cases diagnosed since the widespread use of prostate-specific antigen (PSA) testing starting in 1987, IBM is also used to examine the contribution of stage at diagnosis to the recent prostate cancer mortality trends. Results, LBR I for cases diagnosed since 1987 rose above the pre-1987 secular (i.e., background) trend, peaked in the early 1990s, and almost returned to the secular trend by 1994. This rise and fall of IBM track with the pool of prevalent cases diagnosed within the prior 2 years. IBM for cases diagnosed with metastatic disease fell starting in 1991, while IBM for those diagnosed with localized/regional disease was relatively flat, Conclusions. The rise and fall in prostate cancer mortality observed since the introduction of PSA testing in the general population are consistent with a hypothesis that a fixed percent of the rising and falling pool of recently diagnosed patients who die of other causes may be mislabeled as dying of prostate cancer. The decline in IBM for distant stage disease and flat IBM trends for localized/regional disease provide some evidence of improved prognosis for screen-detected cases, although alternative interpretations are possible. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. Brigham Young Univ, Provo, UT 84602 USA. RP Feuer, EJ (reprint author), NIH, Execut Plaza N,Rm 313, Bethesda, MD 20892 USA. NR 31 TC 155 Z9 156 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1025 EP 1032 DI 10.1093/jnci/91.12.1025 PG 8 WC Oncology SC Oncology GA 206AC UT WOS:000080853000012 PM 10379965 ER PT J AU Etzioni, R Legler, JM Feuer, EJ Merrill, RM Cronin, KA Hankey, BF AF Etzioni, R Legler, JM Feuer, EJ Merrill, RM Cronin, KA Hankey, BF TI Cancer surveillance series: Interpreting trends in prostate cancer - Part III: Quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MEN AB Background: The objective of this study was to investigate the circumstances under which dissemination of prostate-specific antigen (PSA) testing, beginning in 1988, could plausibly explain the declines in prostate cancer mortality observed from 1992 through 1994. Methods: We developed a computer simulation model by use of information on population-based PSA testing patterns, cancer detection rates, average lead time (the time by which diagnosis is advanced by screening), and projected decreased risk of death associated with early diagnosis of prostate cancer through PSA testing. The model provides estimates of the number of deaths prevented by PSA testing for the 7-year period from 1988 through 1994 and projects what prostate cancer mortality for these years would have been in the absence of PSA testing, Results: Results were generated by assuming a level of screening efficacy similar to that hypothesized for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Under this assumption, the projected mortality in the absence of PSA testing continued the increasing trend observed before 1991 only when it was assumed that the mean lead time was 3 years or less. Projected mortality trends in the absence of PSA screening were not consistent with pre-1991 increasing trends for lead times of 5 gears and 7 years, Conclusions: When screening is assumed to be at least as efficacious as hypothesized in the PLCO trial, it is unlikely that the entire decline in prostate cancer mortality can be explained by PSA testing based on current beliefs concerning lead time. Only very short lead times would produce a decline in mortality of the magnitude that has been observed. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. RP Etzioni, R (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP-665,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [N01CN67009, R29CA70227] NR 15 TC 146 Z9 149 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1033 EP 1039 DI 10.1093/jnci/91.12.1033 PG 7 WC Oncology SC Oncology GA 206AC UT WOS:000080853000013 PM 10379966 ER PT J AU Devesa, SS Grauman, DJ Blot, WJ Fraumeni, JF AF Devesa, SS Grauman, DJ Blot, WJ Fraumeni, JF TI Cancer surveillance series: Changing geographic patterns of lung cancer mortality in the United States, 1950 through 1994 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COASTAL VIRGINIA; MESOTHELIOMA; EMPLOYMENT AB Background: Geographic surveys revealing variations in lung cancer mortality rates across the United States have prompted epidemiologic studies in high-risk communities. We have updated these maps to track the changing patterns and to provide further clues to the determinants of lung cancer. Methods: Age-adjusted race- and ses-specific lung cancer mortality rates from 1950 through 1994 were calculated for nine Census Divisions and 508 State Economic Areas of the United States. Results: Pronounced geographic variation in lung cancer rates was evident, with the patterns changing substantially over time. Among white males in the 1950s and 1960s, high rates were observed in urban areas of the northeast and north central states and in areas along the southeast and Gulf coasts. By the 1970s, the northern excess began to fade, with high rates starting to cover wider areas of the south. By the 1980s to the mid-1990s, clustering of elevated rates was prominent across the southeast and south central areas, with relatively low rates throughout much of the northeast. Among white females, little geographic variation was evident in the 1950s, but thereafter relatively high rates began to appear in clusters along the Atlantic and Pacific coasts. For both sexes, consistently low rates were seen in the mountain and the plains states, Rates among blacks were consistently elevated in northern areas and lon across the south, Conclusions: The changing mortality patterns for lung cancer generally coincide with regional trends in cigarette smoking, indicating that public health measures aimed at smoking prevention and cessation should have a dramatic effect in reducing lung cancer rates. C1 NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Epidemiol Inst Ltd, Rockville, MD USA. RP Devesa, SS (reprint author), NIH, Div Canc Epidemiol & Genet, Execut Plaza S,Rm 8048, Bethesda, MD 20892 USA. NR 36 TC 47 Z9 49 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1040 EP 1050 DI 10.1093/jnci/91.12.1040 PG 11 WC Oncology SC Oncology GA 206AC UT WOS:000080853000014 PM 10379967 ER PT J AU Linet, MS Ries, LAG Smith, MA Tarone, RE Devesa, SS AF Linet, MS Ries, LAG Smith, MA Tarone, RE Devesa, SS TI Cancer surveillance series: Recent trends in childhood cancer incidence and mortality in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BRITISH COOPERATIVE GROUP; ACUTE MYELOID-LEUKEMIA; DERMATOFIBROSARCOMA-PROTUBERANS; BRAIN-TUMORS; CLASSIFICATION; NEUROBLASTOMA; CHILDREN; EPIDEMIOLOGY; DIAGNOSIS; CRITERIA AB Background: Public concern about possible increases in childhood cancer incidence in the United States led us to examine recent incidence and mortality patterns. Methods: Cancers diagnosed in 14540 children under age 15 years from 1975 through 1995 and reported to nine population-based registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program mere investigated. Age-adjusted incidence was analyzed according to anatomic site and histologic categories of the International Classification of Childhood Cancer. Age-adjusted U.S, mortality rates were calculated. Trends in rates were evaluated by use of standard regression methods. Results: A modest rise in the incidence of leukemia, the most common childhood cancer, was largely due to an abrupt increase from 1983 to 1984; rates have decreased slightly since 1989, For brain and other central nervous system (CNS) cancers, incidence rose modestly, although statistically significantly (two-sided P = .020), largely from 1983 through 1986, A few rare childhood cancers demonstrated upward trends (e.g., the 40% of skin cancers designated as dermatofibrosarcomas, adrenal neuroblastomas, and retinoblastomas, the latter two in infants only), In contrast, incidence decreased modestly but statistically significantly for Hodgkin's disease (two-sided P = .037). Mortality rates declined steadily for all major childhood cancer categories, although less rapidly for brain/CNS cancers. Conclusions: There was no substantial change in incidence for the major pediatric cancers, and rates have remained relatively stable since the mid-1980s, The modest increases that were observed for brain/CNS cancers, leukemia, and infant neuroblastoma were confined to the mid-1980s, The patterns suggest that the increases likely reflected diagnostic improvements or reporting changes. Dramatic declines in childhood cancer mortality represent treatment-related improvements in survival. C1 NIH, Div Canc Control & Genet, Bethesda, MD 20892 USA. NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NIH, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Linet, MS (reprint author), NIH, Div Canc Control & Genet, Execut Plaza S,Rm 7054,MSC 7238, Bethesda, MD 20892 USA. NR 46 TC 226 Z9 237 U1 1 U2 10 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1051 EP 1058 DI 10.1093/jnci/91.12.1051 PG 8 WC Oncology SC Oncology GA 206AC UT WOS:000080853000015 PM 10379968 ER PT J AU Ursin, G London, S Stanczyk, FZ Gentzschein, E Paganini-Hill, A Ross, RK Pike, MC AF Ursin, G London, S Stanczyk, FZ Gentzschein, E Paganini-Hill, A Ross, RK Pike, MC TI Urinary 2-hydroxyestrone/16 alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ESTROGEN METABOLISM; OXIDATIVE-METABOLISM; LOS-ANGELES; ESTRADIOL; CELLS; EXCRETION; ESTRIOL; DIET; 16-ALPHA-HYDROXYLATION; PROLIFERATION AB Background: It has been suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16 alpha-hydroxylation pathway may be at elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxylation pathway. However, the supporting epidemiologic data are scant. Consequently, we compared the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16 alpha-hydroxyestrone (16 alpha-OHE1) in postmenopausal women with breast cancer and in healthy control subjects. Methods: Estrogen metabolites were measured in urine samples obtained from white women who had participated in a previous population-based, breast cancer case-control study at our institution. All P values are from two-sided tests. Results: All of the urinary estrogens measured, with the exception of estriol, were higher in the 66 case patients than in the 76 control subjects, The mean value of urinary 2-OHE1 in case patients was 13.8% (P = .20) higher than that in control subjects, 16 alpha-OHE1, was 12.1% (P = .23) higher, estrone was 20.9% higher (P = .14), and 17 beta-estradiol was 12.0% higher (P = .36), The ratio of 2-OHE1 to 16 alpha-OHE1 was 1.1% higher in the patients (P = .84), contrary to the hypothesis. Compared with women in the lowest third of the values for the ratio of urinary 2-OHE1 to 16 alpha-OHE1, women in the highest third were at a nonstatistically significantly increased risk of breast cancer (odds ratio = 1.13; 95% confidence interval = 0.46-2.78), again contrary to the hypothesis. Conclusion: This study does not support the hypothesis that the ratio of the two hydroxylated metabolites (2-OHE1/16 alpha-OHE1) is an important risk factor for breast cancer. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ So Calif, Los Angeles Cty Womens Hosp, Dept Gynecol & Obstet, Los Angeles, CA 90089 USA. RP Ursin, G (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,MS 44,Suite 4407, Los Angeles, CA 90033 USA. FU NCI NIH HHS [P01CA17054] NR 53 TC 94 Z9 96 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1067 EP 1072 DI 10.1093/jnci/91.12.1067 PG 6 WC Oncology SC Oncology GA 206AC UT WOS:000080853000017 PM 10379970 ER PT J AU Penninx, BWJH Guralnik, JM AF Penninx, BWJH Guralnik, JM TI Chronically depressed mood and cancer risk in older persons - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Free Univ Amsterdam, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Penninx, BWJH (reprint author), Free Univ Amsterdam, Inst Res Extramural Med, Boechorstststr 7, NL-1081 BT Amsterdam, Netherlands. NR 1 TC 0 Z9 0 U1 1 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 16 PY 1999 VL 91 IS 12 BP 1080 EP 1081 PG 2 WC Oncology SC Oncology GA 206AC UT WOS:000080853000026 ER PT J AU Coates, RJ Bowen, DJ Kristal, AR Feng, ZD Oberman, A Hall, WD George, V Lewis, CE Kestin, M Davis, M Evans, M Grizzle, JE Clifford, CK AF Coates, RJ Bowen, DJ Kristal, AR Feng, ZD Oberman, A Hall, WD George, V Lewis, CE Kestin, M Davis, M Evans, M Grizzle, JE Clifford, CK TI The Women's Health Trial Feasibility Study in Minority Populations: Changes in dietary intakes SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE blacks; clinical trials; diet; dietary fats; health education; Hispanic Americans; nutrition ID LOW-FAT DIET; FACTOR-INTERVENTION-TRIAL; BREAST-CANCER; RANDOMIZED TRIAL; PREVENTION; RISK; NUTRIENT; PROGRAM; THERAPY; DESIGN AB This randomized clinical trial examined the feasibility of low-fat dietary interventions among postmenopausal women of diverse backgrounds. During 1992-1994, 2,208 women aged 50-79 years, 28% of whom were black and 16% Hispanic, enrolled at clinics in Atlanta, Georgia, Birmingham, Alabama, and Miami, Florida. Intervention/support groups met periodically with a nutritionist to reduce fat intake to 20% of energy and to make other diet modifications. At 6 months postrandomization, the intervention group reduced fat intake from 39.7% of energy at baseline to 26.4%, a reduction of 13.3% of energy, compared with 2.3% among controls. Saturated fatty acid and cholesterol intakes were reduced, but intakes of fruits and vegetables, but not grain products, increased. Similar effects were observed at 12 and 18 months. Black and non-Hispanic white women had similar levels of reduction in fat, but the decrease in Hispanic women was less. Changes did not vary significantly by education. While bias in self-reported intakes may have resulted in somewhat overestimated changes in fat intake, the reported reduction was similar to the approximately 10% of energy decrease found in most trials and suggests that large changes in fat consumption can be attained in diverse study populations and in many subgroups. C1 Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Dept Publ Hlth Sci, Seattle, WA 98104 USA. Univ Alabama, Med Sch Birmingham, Div Prevent Med, Birmingham, AL USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Univ Miami, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. Emory Univ, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. NHLBI, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. RP Coates, RJ (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, MS K-55,4770 Buford Highway,NE, Atlanta, GA 30341 USA. RI Kristal, Alan/A-8779-2008; OI Kristal, Alan/0000-0002-7329-1617 FU NCI NIH HHS [N01-CN-25425, N01-CN-25426, N01-CN-25427] NR 36 TC 52 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 1999 VL 149 IS 12 BP 1104 EP 1112 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 205HA UT WOS:000080814200004 PM 10369504 ER PT J AU Roy, S AF Roy, S TI An exact solution of abortive initiation rate equation SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID REPRESSION; ACTIVATION C1 Bose Inst, Dept Biophys, Calcutta 700054, W Bengal, India. RP Roy, S (reprint author), NCI, Mol Biol Lab, Dev Genet Sect, NIH, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 15 PY 1999 VL 271 IS 1 BP 86 EP 89 DI 10.1006/abio.1999.4103 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 208VA UT WOS:000081011500011 PM 10361008 ER PT J AU Ciolino, HP Daschner, PJ Yeh, GC AF Ciolino, HP Daschner, PJ Yeh, GC TI Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially SO BIOCHEMICAL JOURNAL LA English DT Article DE chemoprevention; flavonoid; MCF-7 cells; 2,3,7,8-tetrachlorodibenzo-p-dioxin; xenobiotic-responsive element ID BREAST-CANCER CELLS; AH-RECEPTOR; DIOXIN RECEPTOR; REGULATORY ELEMENTS; INDUCTION; GENE; ACTIVATION; PROTEIN; COMPLEX; MCF-7 AB Transcriptional activation of the human CYP1A1 gene (coding for cytochrome P450 1A1) is mediated by the aryl hydrocarbon receptor (AhR). In the present study we have examined the effect of the common dietary polyphenolic compounds quercetin and kaempferol on the transcription of CYP1A1 and the function of the AhR in MCF-7 human breast cancer cells. Quercetin caused a time- and concentration-dependent increase in the amount of CYP1A1 mRNA and CYP1A1 enzyme activity in MCF-7 cells. The increase in CYP1A1 mRNA caused by quercetin was prevented by the transcription inhibitor actinomycin D. Quercetin also caused an increase in the transcription of a chloramphenicol reporter vector containing the CYP1A1 promoter. Quercetin failed to induce CYP1A1 enzyme activity in AhR-deficient MCF-7 cells. Gel retardation studies demonstrated that quercetin activated the ability of the AhR to bind to an oligonucleotide containing the xenobiotic-responsive element (XRE) of the CYP1A1 promoter. These results indicate that quercetin's effect is mediated by the AhR. Kaempferol did not affect CYP1A1 expression by itself but it inhibited the transcription of CYP1A1 induced by the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as measured by a decrease in TCDD-induced CYP1A1 promoter-driven reporter Vector activity, and CYP1A1 mRNA in cells. Kaempferol also abolished TCDD-induced XRE binding in a gel-shift assay. Both compounds were able to compete with TCDD for binding to a cytosolic extract of MCF-7 cells. Known ligands of the AhR are, for the most part, man-made compounds such as halogenated and polycyclic aromatic hydrocarbons. These results demonstrate that the dietary flavonols quercetin and kaempferol are natural dietary ligands of the AhR that exert different effects on CYP1A1 transcription. C1 NCI, Cellular Def & Carcinogenesis Sect, Basic Res Lab,Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP NCI, Cellular Def & Carcinogenesis Sect, Basic Res Lab,Frederick Canc Res & Dev Ctr, NIH, Bldg 560,Room 12-05,POB B, Frederick, MD 21702 USA. EM hciolino@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 46 TC 229 Z9 240 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1999 VL 340 BP 715 EP 722 DI 10.1042/0264-6021:3400715 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209UB UT WOS:000081066300018 PM 10359656 ER PT J AU Kotsonis, P Frey, A Frohlich, LG Hofmann, H Reif, A Wink, DA Feelisch, M Schmidt, HHHW AF Kotsonis, P Frey, A Frohlich, LG Hofmann, H Reif, A Wink, DA Feelisch, M Schmidt, HHHW TI Autoinhibition of neuronal nitric oxide synthase: distinct effects of reactive nitrogen and oxygen species on enzyme activity SO BIOCHEMICAL JOURNAL LA English DT Article DE autoregulation; hydrogen peroxide; NOS catalysis ID L-ARGININE; HYDROGEN-PEROXIDE; NO SYNTHASE; TETRAHYDROBIOPTERIN; SUPEROXIDE; PHOSPHORYLATION; PEROXYNITRITE; ACTIVATION; GENERATION; COFACTOR AB Nitric oxide (NO) synthases (NOSs), which catalyse the oxidation of L-arginine to L-citrulline and an oxide of nitrogen, possibly NO or nitroxyl (NO(-)), are subject to autoinhibition by a mechanism that has yet to be fully elucidated. In the present study we investigated the actions of NO and other NOS-derived products as possible autoregulators of enzyme activity. With the use of purified NOS-I, L-arginine turnover was found to operate initially at V(max) (0-15 min, phase I) although, despite the presence of excess substrate and cofactors, prolonged catalysis (15-90 min, phase II) was associated with a rapid decline in L-arginine turnover. Taken together, these observations suggested that one or more NOS products inactivate NOS. Indeed, exogenously applied reactive nitrogen oxide species (RNSs) decreased V(max) during phase I, although with different potencies (NO- > NO > ONOO(-)); and efficacies (NO > NO(-) = ONOO(-)). The NO scavengers oxyhaemoglobin (HbO(2); 100 mu M) and 1H-imidazol-1-yloxy-2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-3-oxide (CPTIO; 10 mu M) and the ONOO(-) scavenger GSH (7 mM) had no effect on NOS activity during phase I, except for an endogenous autoinhibitory influence of NO and ONOO(-). However, superoxide dismutase (SOD; 300 units/ml), which is thought either to increase the half-life of NO or to convert NO(-) to NO, lowered V(max) in an NO-dependent manner because this effect was selectively antagonized by HbO(2) (100 mu M). This latter observation demonstrated the requirement of SOD to reveal endogenous NO-mediated autoinhibition. Importantly, during phase II of catalysis, NOS became uncoupled and began to form H(2)O(2) because catalase, which metabolizes H(2)O(2), increased enzyme activity. Consistent with this, exogenous H(2)O(2) also inhibited NOS activity during phase I. Thus during catalysis NOS is subject to complex autoinhibition by both enzyme-derived RNS and H(2)O(2), differentially affecting enzyme activity. C1 Univ Wurzburg, Dept Pharmacol & Toxicol, D-97078 Wurzburg, Germany. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. UCL, Wolfson Inst Biomed Res, London W1P 9LN, England. RP Kotsonis, P (reprint author), Univ Wurzburg, Dept Pharmacol & Toxicol, Versbacher Str 9, D-97078 Wurzburg, Germany. EM kotsonis@toxi.uni-wuerzburg.de RI Schmidt, Harald H. H. W./B-1549-2008; Feelisch, Martin/C-3042-2008 OI Schmidt, Harald H. H. W./0000-0003-0419-5549; Feelisch, Martin/0000-0003-2320-1158 NR 49 TC 32 Z9 33 U1 0 U2 0 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 JUN 15 PY 1999 VL 340 BP 745 EP 752 DI 10.1042/0264-6021:3400745 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209UB UT WOS:000081066300022 PM 10359660 ER PT J AU Shou, MG Mei, Q Ettore, MW Dai, RK Baillie, TA Rushmore, TH AF Shou, MG Mei, Q Ettore, MW Dai, RK Baillie, TA Rushmore, TH TI Sigmoidal kinetic model for two co-operative substrate-binding sites in a cytochrome P450 3A4 active site: an example of the metabolism of diazepam and its derivatives SO BIOCHEMICAL JOURNAL LA English DT Article DE cDNA expression; drug interaction; drug metabolism; enzyme kinetics; monoclonal antibody ID HUMAN-LIVER-MICROSOMES; HEPATIC MICROSOMES; CDNA EXPRESSION; ENZYMES; RAT; COOPERATIVITY; LOCALIZATION; ACTIVATION; SEQUENCE; CYP3A4 AB Cytochrome P450 3A4 (CYP3A4) plays a prominent role in the metabolism of a vast array of drugs and xenobiotics and exhibits broad substrate specificities. Most cytochrome P450-mediated reactions follow simple Michaelis-Menten kinetics. These parameters are widely accepted to predict pharmacokinetic and pharmacodynamic consequences in vivo caused by exposure to one or multiple drugs. However, CYP3A4 in many cases exhibits allosteric (sigmoidal) characteristics that make the Michaelis constants difficult to estimate. In the present study, diazepam, temazepam and nordiazepam were employed as substrates of CYP3A4 to propose a kinetic model. The model hypothesized that CYP3A4 contains two substrate-binding sites in a single active site that are both distinct and co-operative, and the resulting velocity equation had a good fit with the sigmoidal kinetic observations. Therefore, four pairs of the kinetic estimates (K-S1, K-alpha, K-S2, k(beta), K-S3, k(delta), K-S4, and k(gamma)) were resolved to interpret the features of binding affinity and catalytic ability of CYP3A4. Dissociation constants K-S1 and K-S2 for two single-substrate-bound enzyme molecules (SE and ES) were 3-50-fold greater than K-S3 and K-S4 for a two-substrate-bound enzyme (SES), while respective rate constants k(delta) and k(gamma) were 3-218-fold greater than k(alpha) and k(beta), implying that access and binding of the first molecule to either site in an active pocket of CYP3A4 can enhance the binding affinity and reaction rate of the vacant site for the second substrate. Thus our results provide some new insights into the co-operative binding of two substrates in the inner portions of an allosteric CYP3A4 active site. C1 Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Shou, MG (reprint author), Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. NR 34 TC 118 Z9 119 U1 0 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 15 PY 1999 VL 340 BP 845 EP 853 DI 10.1042/0264-6021:3400845 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 209UB UT WOS:000081066300034 PM 10359672 ER PT J AU Koskela, S Hakkola, J Hukkanen, J Pelkonen, O Sorri, M Saranen, A Anttila, S Fernandez-Salguero, P Gonzalez, F Raunio, H AF Koskela, S Hakkola, J Hukkanen, J Pelkonen, O Sorri, M Saranen, A Anttila, S Fernandez-Salguero, P Gonzalez, F Raunio, H TI Expression of CYP2A genes in human liver and extrahepatic tissues SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cytochrome P450 gene expression; CYP2A; nasal mucosa; liver; extrahepatic tissues; xenobiotic metabolism ID CYTOCHROMES P450 2A6; HUMAN NASAL-MUCOSA; COUMARIN 7-HYDROXYLATION; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE NNK; METABOLIC-ACTIVATION; RAT LUNG; MICROSOMES; IDENTIFICATION; CARCINOGEN; OXIDATION AB Members of the human cytochrome P450 ZA (CYP2A) subfamily are known to metabolize several promutagens, procarcinogens, and pharmaceuticals. In this study, the expression of the three genes found in the human CYP2A gene cluster was investigated in the liver and several extrahepatic tissues by gene-specific reverse transcriptase polymerase chain reaction (RT-PCR). All three transcripts (CYP2A6, CYP2A7, and CYP2A13) were found to be present in liver, Quantitative RT-PCR analysis showed that CYP2A6 and CYP2A7 mRNAs were present at roughly equal levels in the liver, while CYP2A13 was expressed at very low levels. Two putative splicing variants of CYP2A7 were found in the liver. Nasal mucosa contained a low level of CYP2A6 and a relatively high level of CYP2A13 transcripts. Kidney, duodenum, lung, alveolar macrophages, peripheral lymphocytes, placenta, and uterine endometrium were negative for all transcripts. This survey gives a comprehensive picture of the expression pattern of CYP2A genes in liver and extrahepatic tissues and constitutes a basis for a search for functional CYP2A forms and their roles in chemical toxicity in liver and nasal mucosa. (C) 1999 Elsevier Science Inc. C1 Univ Oulu, Dept Pharmacol & Toxicol, FIN-90220 Oulu, Finland. Univ Oulu, Dept Otolaryngol, FIN-90220 Oulu, Finland. Finnish Inst Occupat Hlth, Helsinki, Finland. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Raunio, H (reprint author), Univ Oulu, Dept Pharmacol & Toxicol, FIN-90220 Oulu, Finland. RI Hukkanen, Janne/C-7292-2013; OI Hukkanen, Janne/0000-0003-4981-0525; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 41 TC 119 Z9 121 U1 0 U2 2 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 JUN 15 PY 1999 VL 57 IS 12 BP 1407 EP 1413 DI 10.1016/S0006-2952(99)00015-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 198YG UT WOS:000080451600010 PM 10353262 ER PT J AU Mitchell, DC Litman, BJ AF Mitchell, DC Litman, BJ TI Effect of protein hydration on receptor conformation: Decreased levels of bound water promote metarhodopsin II formation SO BIOCHEMISTRY LA English DT Article ID TRANSFORM INFRARED-SPECTROSCOPY; RECOMBINANT MEMBRANES; BOVINE RHODOPSIN; EQUILIBRIUM; PRESSURE; PHOSPHOLIPIDS; CHOLESTEROL; HEMOGLOBIN; SOLVATION; VESICLES AB Neutral solutes were used to investigate the effects of osmotic stress both on the ability of rhodopsin to undergo its activating conformation change and on acyl chain packing in the rod outer segment (ROS) disk membrane. The equilibrium concentration of metarhodopsin II (MII), the conformation of photoactivated rhodopsin, which binds and activates transducin, was increased by glycerol, sucrose, and stachyose in a manner which was linear with osmolality. Analysis of this shift in equilibrium in terms of the dependence of In(K-eq) on osmolality revealed that 20 +/- 1 water molecules are released during the MI-to-MII transition at 20 degrees C, and at 35 degrees C 13 +/- 1 waters are released. At 35 OC the average time constant for MII formation was increased from 1.20 +/- 0.09 ms to 1.63 rt 0.09 ms by addition of 1 osmolal sucrose or glycerol. The effect of the neutral solutes on acyl chain packing in the ROS disk membrane was assessed via measurements of the fluorescence lifetime and anisotropy decay of 1,6diphenyl-1,3,5-hexatriene (DPH), Analysis of the anisotropy decay of DPH in terms of the rotational diffusion model showed that the angular width of the equilibrium orientational distribution of DPH about the membrane normal was progressively narrowed by increased osmolality. The parameter f(v), which is proportional to the overlap between the DPH orientational probability distribution and a random orientational distribution, was reduced by the osmolytes in a manner which was linear with osmolality. This study highlights the potentially opposing interplay between the effect of membrane surface hydration on both the lipid bilayer and integral membrane protein structure. Our results further demonstrate that the binding and release of water molecules play an important role in modulating functional conformational changes for integral membrane proteins, as well as for soluble globular proteins. C1 NIAAA, Lab Membrane Biophys & Biochem, Sect Fluorescene Studies, NIH, Rockville, MD 20852 USA. RP Litman, BJ (reprint author), Pk Bldg,Room 158,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 44 TC 37 Z9 38 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 15 PY 1999 VL 38 IS 24 BP 7617 EP 7623 DI 10.1021/bi990634m PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208XB UT WOS:000081016200002 PM 10387000 ER PT J AU Fan, YX McPhie, P Miles, EW AF Fan, YX McPhie, P Miles, EW TI Guanidine hydrochloride exerts dual effects on the tryptophan synthase alpha(2)beta(2) complex as a cation activator and as a modulator of the active site conformation SO BIOCHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; MONOVALENT CATIONS; INTERSUBUNIT COMMUNICATION; ELECTROSTATIC REPULSIONS; 3-DIMENSIONAL STRUCTURE; BIENZYME COMPLEX; ENZYME CATALYSIS; ALPHA-SUBUNIT AB To characterize the conformational transitions that regulate the activity and specificity of the tryptophan synthase alpha(2)beta(2) complex, we have determined some effects of low concentrations of guanidine hydrochloride (GuHCl) and of urea on functional properties. We report the novel finding that GuHCl at low concentrations (0.02-0.08 M) is a cation activator of the tryptophan synthase alpha(2)beta(2) complex. Molecular modeling studies show that GuH(+) could bind at a previously identified cation binding site in the tryptophan synthase beta subunit. Addition of increasing concentrations of GuHCl has strikingly different effects on the rates of different reactions with L-serine or beta-chloro-L-alanine in the presence or absence of indole. Spectroscopic studies demonstrate that GuHCl alters the equilibrium distribution of pyridoxal 5'-phosphate intermediates formed in reactions at the active site of the beta subunit. Data analysis shows that GuHCl binds preferentially with the conformer of the enzyme that predominates when the aldimine of L-serine is formed and shifts the equilibrium in favor of this conformer. These results provide evidence that GuHCl. exerts dual effects on tryptophan synthase as a cation, stimulating activity, and as a chaotropic agent, altering the distribution of conformational states that exhibit different reaction specificities. Our finding that the nonionic urea stabilizes the aldimine of L-serine in the presence, but not in the absence, of NaCl shows that cation binding plays an important role in the conformational transitions that regulate activity and the transmission of allosteric signals between the alpha and beta sites. C1 NIDDKD, Sect Enzyme Struct & Funct, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDKD, Sect Enzyme Struct & Funct, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM EdithM@intra.niddk.nih.gov NR 48 TC 20 Z9 24 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 15 PY 1999 VL 38 IS 24 BP 7881 EP 7890 DI 10.1021/bi990307e PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208XB UT WOS:000081016200031 PM 10387029 ER PT J AU Bloch, M Schmidt, PJ Danaceau, MA Adams, LF Rubinow, DR AF Bloch, M Schmidt, PJ Danaceau, MA Adams, LF Rubinow, DR TI Dehydroepiandrosterone treatment of midlife dysthymia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dehydroepiandrosterone; dysthymia; midlife; adrenal androgens; mood ID GABA-A RECEPTOR; POSTMENOPAUSAL WOMEN; MAJOR DEPRESSION; ANDROGENIC STEROIDS; AFFECTIVE-DISORDERS; SEX-DIFFERENCES; SULFATE; DHEA; MEN; NEUROSTEROIDS AB Background: This study evaluated the efficacy of the adrenal androgen, dehydroepiandrosterone, in the treatment of midlife-onset dysthymia. Methods: A double-blind, randomized crossover treatment study was performed as follows: 3 weeks on 90 mg dehydroepiandrosterone, 3 weeks on 450 mg dehydroepiandrosterone, and 6 weeks on placebo. Outcome measures consisted of the following. Cross-sectional self-ratings included the Beck Depression Inventory, and visual analogue symptom scales. Cross-sectional objective ratings included the Hamilton Depression Rating Scale, the Cornell Dysthymia Scale and a cognitive test battery. Seventeen men and women aged 45 to 63 years with midlife-onset dysthymia participated in this study. Response to dehydroepiandrosterone or placebo was defined as a 50% reduction from baseline in either the Hamilton Depression Rating Scale or the Beck Depression Inventory. Results: In 15 patients who completed the study, a robust effect of dehydroepiandrosterone on mood was observed compared with placebo. Sixty percent of the patients responded to dehydroepiandrosterone at the end of the 6-week treatment period compared with 20% on placebo. A significant response was seen after 3 weeks of treatment on 90 mg per day, The symptoms that improved most significantly were anhedonia, loss of energy, lack of motivation, emotional "numbness," sadness, inability to cope, and worry. Dehydroepiandrosterone showed no specific effects on cognitive function or sleep disturbance, although a type II error could not be ruled out. Conclusions: This pilot study suggests that dehydroepiandrosterone is an effective treatment for midlife-onset dysthymia. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Rambam Med Ctr, Div Psychiat, Haifa, Israel. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. NR 58 TC 143 Z9 148 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1999 VL 45 IS 12 BP 1533 EP 1541 DI 10.1016/S0006-3223(99)00066-9 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 205XC UT WOS:000080845000002 PM 10376113 ER PT J AU Garvey, MA Perlmutter, SJ Allen, AJ Hamburger, S Lougee, L Leonard, HL Witowski, ME Dubbert, B Swedo, SE AF Garvey, MA Perlmutter, SJ Allen, AJ Hamburger, S Lougee, L Leonard, HL Witowski, ME Dubbert, B Swedo, SE TI A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections SO BIOLOGICAL PSYCHIATRY LA English DT Article DE penicillin prophylaxis; streptococcal; obsessive compulsive disorder; tic disorders; clinical trials ID OBSESSIVE COMPULSIVE SCALE; RHEUMATIC-FEVER; TIC SEVERITY; DISORDERS; VALIDITY; CHOREA; RELIABILITY; CHILDHOOD; OCD AB Background: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant Sydenham's chorea. Because;penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent srreptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and srreptococcal-triggered symptom exacerbations. Methods: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study. Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V, Tie, OCD, and other psychiatric symptoms were monitored monthly. Throat cultures and streptococcal antibody titers were also obtained. Results: There were an equal number of infections in both the active and placebo phases of the study. There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases. Conclusions: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations. Future studies should employ a more effective prophylactic agent, and include a larger sample size. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA. Brown Univ, Providence, RI 02912 USA. RP Garvey, MA (reprint author), 10 Ctr Dr,Room 4N208,MSC 1255, Bethesda, MD 20892 USA. NR 44 TC 140 Z9 145 U1 4 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 1999 VL 45 IS 12 BP 1564 EP 1571 DI 10.1016/S0006-3223(99)00020-7 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 205XC UT WOS:000080845000005 PM 10376116 ER PT J AU Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G AF Aoki, Y Jaffe, ES Chang, Y Jones, K Teruya-Feldstein, J Moore, PS Tosato, G TI Angiogenesis and hematopoiesis induced by Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 SO BLOOD LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Hematology CY DEC 05, 1998 CL MIAMI BEACH, FLORIDA SP Amer Soc Hematol ID ENDOTHELIAL GROWTH-FACTOR; MULTICENTRIC CASTLEMANS DISEASE; PRIMARY EFFUSION LYMPHOMA; B-CELL GROWTH; DNA-SEQUENCES; MYELOMA CELLS; EXPRESSION; MICE; CYTOKINE; VIRUS AB Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is a herpesvirus linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma, and a proportion of Castleman's disease. KSHV encodes viral interleukin-6 (vIL-6), which is structurally homologous to human and murine IL-6, The biological activities of vIL-6 are largely unknown. To gain insight into the biology of vIL-6, we expressed vIL-6 in murine fibroblasts NIH3T3 cells and inoculated stable vIL-6-producing clones into athymic mice. vIL-6 was detected selectively in the blood of mice injected with vIL-6-expressing clones. Compared with controls, vIL-6-positive mice displayed increased hematopoiesis in the myeloid, erythroid, and megakaryocytic lineages; plasmacytosis in spleen and lymph nodes; hepatosplenomegaly; and polyclonal hypergammaglobulinemia, vIL-6-expressing NIH3T3 cells gave rise to tumors more rapidly than did control cells, and vIL-6-positive tumors were more vascularized than controls. Vascular endothelial growth factor (VEGF) was detected at higher levels in the culture supernatant of vIL-6-expressing cells compared with controls, and immunohistochemical staining detected VEGF in spleen, lymph nodes, and tumor tissues from mice bearing vIL-6-producing tumors but not control tumors. Thus, vIL-6 is a multifunctional cytokine that promotes hematopoiesis, plasmacytosis, and angiogenesis, Through these functions, vIL-6 may play an important role in the pathogenesis of certain KSHV-associated disorders. (C) 1999 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, NIH, Bethesda, MD USA. Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY USA. RP Aoki, Y (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29A,Room 2DO6 HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Chang, Yuan/F-4146-2011; Moore, Patrick/F-3960-2011 OI Moore, Patrick/0000-0002-8132-858X NR 50 TC 287 Z9 304 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4034 EP 4043 PG 10 WC Hematology SC Hematology GA 204TK UT WOS:000080780200002 PM 10361100 ER PT J AU Monini, P Colombini, S Sturzl, M Goletti, D Cafaro, A Sgadari, C Butto, S Franco, M Leone, P Fais, S Leone, P Melucci-Vigo, G Chiozzini, C Carlini, F Ascherl, G Cornali, E Zietz, C Ramazzotti, E Ensoli, F Andreoni, W Pezzotti, P Rezza, G Yarchoan, R Gallo, RC Ensoli, B AF Monini, P Colombini, S Sturzl, M Goletti, D Cafaro, A Sgadari, C Butto, S Franco, M Leone, P Fais, S Leone, P Melucci-Vigo, G Chiozzini, C Carlini, F Ascherl, G Cornali, E Zietz, C Ramazzotti, E Ensoli, F Andreoni, W Pezzotti, P Rezza, G Yarchoan, R Gallo, RC Ensoli, B TI Reactivation and persistence of human herpesvirus-8 infection in B cells and monocytes by Th-1 cytokines increased in Kaposi's sarcoma SO BLOOD LA English DT Article ID FIBROBLAST GROWTH-FACTOR; BLOOD MONONUCLEAR-CELLS; SPINDLE CELLS; ENDOTHELIAL-CELLS; PERIPHERAL-BLOOD; TAT PROTEIN; T-CELLS; INFLAMMATORY CYTOKINES; VASCULAR-PERMEABILITY; INTERFERON-GAMMA AB Patients with Kaposi's sarcoma (KS) have a human herpesvirus-8 (HHV-8) load higher than patients without KS and present a CD8(+) T-cell activation with production of Th1-type cytokines both in tissues and peripheral blood mononuclear cells (PBMC). Because in tissues of KS patients detection of inflammatory cytokines (IC) can precede detection of HHV-8 DNA and because signs of immunoactivation and/or dysregulation can precede KS development, we investigated the effect of IC on HHV-8 infection. To achieve this goal, PBMC and purified cell populations from 45 patients with KS and 45 patients at risk of KS were analyzed for HHV-8 DNA and/or gene expression and for cell survival, growth, and phenotype before or after culture with or without the IC increased in KS. The results indicate that PBMC that are polymerase chain reaction (PCR)-positive at day 0 generally loose the virus upon culture. However, the presence of IC maintains HHV-8 DNA load in cultured cells. In addition, IC increase viral load to detectable levels in PBMC from serologically positive patients that were PCR-negative before culture. gamma Interferon is sufficient for these effects, whereas tumor necrosis factor and interleukin-6 have little or no activity. The increase of HHV-8 DNA by IC is observed after short-term (7 days) or long-term (28 days) culture of the cells and occurs in one or both of the two circulating cell types that are infected in vivo: B cells and monocytes. In both cases it is associated with lytic gene expression, suggesting that virus reactivation is one of the most likely mechanisms for the effect of IC on virus load. However, IC have also effects on the cells target of HHV-8 infection, because they increase B-cell survival and induce the growth and differentiation of monocytes into KS-like spindle cells with markers of endothelial macrophages. Because cells with markers of endothelial macrophages are present in blood and lesions from KS patients and are infected by HHV-8, these data may explain the high HHV-8 load associated with KS development and suggest that infected monocytes may carry the virus to tissues, transmit the infection, or differentiate in loco in spindle cells with endothelial macrophage markers. (C) 1999 by The American Society of Hematology. C1 Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. Univ Maryland, Inst Human Virol, Baltimore, MD USA. GSF, Natl Res Ctr Environm & Hlth, Inst Mol Virol, Neuherberg, Germany. Max Planck Inst Biochem, Abt Virusforsch, Martinsried, Germany. Univ Munich, Inst Pathol, Munich, Germany. Univ Rome La Sapienza, Dept Allergy & Clin Immunol, I-00185 Rome, Italy. Univ Roma Tor Vergata, Chair Infect Dis, Rome, Italy. Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD USA. RP Ensoli, B (reprint author), Ist Super Sanita, Virol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. RI Sturzl, Michael/B-3019-2015; REZZA, GIOVANNI/D-4393-2016; CARLINI, FRANCESCA/D-7945-2016; Sgadari, Cecilia/H-4302-2016; Fais, Stefano/J-8638-2016; Ensoli, Barbara/J-9169-2016; Monini, Paolo/K-1429-2016; Cafaro, Aurelio/K-5314-2016; OI Sturzl, Michael/0000-0002-9276-2824; Goletti, Delia/0000-0001-8360-4376; REZZA, GIOVANNI/0000-0003-0268-6790; Sgadari, Cecilia/0000-0003-0364-4912; Fais, Stefano/0000-0001-9060-2766; Ensoli, Barbara/0000-0002-0545-8737; Monini, Paolo/0000-0002-4941-6854; Andreoni, Massimo/0000-0002-3205-9758 NR 55 TC 148 Z9 152 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4044 EP 4058 PG 15 WC Hematology SC Hematology GA 204TK UT WOS:000080780200003 PM 10361101 ER PT J AU Cohen, A Rovelli, A Bakker, B Uderzo, C van Lint, MT Esperou, H Gaiero, A Leiper, AD Dopfer, R Cahn, JY Merlo, F Kolb, HJ Socie, G AF Cohen, A Rovelli, A Bakker, B Uderzo, C van Lint, MT Esperou, H Gaiero, A Leiper, AD Dopfer, R Cahn, JY Merlo, F Kolb, HJ Socie, G CA EBMT Late Effects Working Party TI Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: A study by the working party for late effects-EBMT SO BLOOD LA English DT Article ID TOTAL-BODY IRRADIATION; GROWTH-HORMONE DEFICIENCY; ACUTE-LEUKEMIA; CHILDREN; BUSULFAN; CYCLOPHOSPHAMIDE; FAILURE; TUMORS AB Few data are available on the long-term effect of bone marrow transplantation (BMT) on growth. This study examines those factors that play a role in the final height outcome of patients who underwent BMT during childhood. Data on 181 of 230 patients with aplastic anemia, leukemias, and lymphomas who had BMT before puberty (mean age, 9.8 +/- 2.6 years) and who had reached their final height were analyzed. An overall decrease in final height standard deviation score (SDS) value was found compared with the height at BMT (P < 10(7)) and with the genetic height (P < 10(7)). Girls did better than boys, and the younger in age the person was at time of BMT, the greater the loss in height. Previous cranial irradiation + single-dose total body irradiation (TBI) caused the greatest negative effect on final height achievement (P < 10(4)). Fractionation of TBI reduces this effect significantly and conditioning with busulfan and cyclophosphamide seems to eliminate it. The type of transplantation, graft-versus-host disease, growth hormone, or steroid treatment did not influence final height. Irradiation, male gender and young age at BMT were found to be major factors for long-term height loss. Nevertheless, the majority of patients (140/181) have reached adult height within the normal range of the general population. (C) 1999 by The American Society of Hematology. C1 Univ Genoa, Childrens Hosp, Dept Pediat, Gaslini Inst, I-16147 Genoa, Italy. San Gerardo Hosp, Pediat Clin, Monza, Italy. Leiden Univ, Med Ctr, Dept Pediat, Leiden, Netherlands. Osped San Martino Genova, Ctr Trapianti Midollo, Genoa, Italy. Hop St Louis, Serv Hematol Greffe de Moelle, Paris, France. Great Ormond St Hosp Children, NHS Trust, Dept Haematol & Oncol, London WC1N 3JH, England. Univ Tubingen Hosp, Dept Pediat, Tubingen, Germany. Hosp Jean Minjoz, Serv Hematol, Besancon, France. Natl Canc Inst, Dept Environm Epidemiol & Biostat, Genoa, Italy. Klinikum Grosshadern, Med Klin 3, Munich, Germany. RP Cohen, A (reprint author), Univ Genoa, Childrens Hosp, Dept Pediat, Gaslini Inst, Largo Gaslini 5, I-16147 Genoa, Italy. NR 26 TC 79 Z9 79 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4109 EP 4115 PG 7 WC Hematology SC Hematology GA 204TK UT WOS:000080780200009 PM 10361107 ER PT J AU O'Brien, S Kantarjian, H Koller, C Feldman, E Beran, M Andreeff, M Giralt, S Cheson, B Keating, M Freireich, E Rios, MB Talpaz, M AF O'Brien, S Kantarjian, H Koller, C Feldman, E Beran, M Andreeff, M Giralt, S Cheson, B Keating, M Freireich, E Rios, MB Talpaz, M TI Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia SO BLOOD LA English DT Article ID THERAPY; SURVIVAL; TRIAL AB Homoharringtonine (HHT) is a novel plant alkaloid that produced a complete hematologic remission (CHR) in 72% of patients with late chronic phase chronic myelogenous leukemia (CML). Cytogenetic (CG) remissions were noted in 31%. In this study, six courses of HHT were administered to 90 patients with early chronic phase CML (< 1 year from diagnosis). Patients then received interferon-alpha (IFN-alpha) with a target dose of 5 MU/m(2) daily. Results were compared with those in a prior group of patients treated with IFN-alpha-based therapy between 1982 and 1990, Ninety-two percent of patients achieved CHR with HHT; CG responses were observed in 60% and were major in 27%. Both CHR and CG response rates were significantly higher than those seen in historical control patients after 6 months of IFN-alpha therapy. After receiving HHT, patients required lower doses of IFN-alpha to maintain a CHR. The median dose delivered was 2.4 MU/m(2). This reduction in IFN-alpha dose was associated with a lower incidence of myalgia and gastrointestinal (GI) disturbances than that seen in patients treated at the 5 MU/m2 dose. Overall, CG responses were seen in 66% of the patients who received HHT and IFN-alpha compared with 61% of the historical control patients. HHT is a very effective treatment of early chronic phase CML, and ongoing trials are investigating the simultaneous administration of HHT and IFN-alpha, as well as that of HHT and low-dose cytosine arabinoside in patients failing IFN-alpha therapy. (C) 1999 by The American Society of Hematology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Div Med, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. RP O'Brien, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 14 TC 78 Z9 78 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4149 EP 4153 PG 5 WC Hematology SC Hematology GA 204TK UT WOS:000080780200014 PM 10361112 ER PT J AU Coleman, AE Kovalchuk, AL Janz, S Palini, A Ried, T AF Coleman, AE Kovalchuk, AL Janz, S Palini, A Ried, T TI Jumping translocation breakpoint regions lead to amplification of rearranged Myc SO BLOOD LA English DT Letter ID CHROMOSOMAL TRANSLOCATIONS; MULTIPLE-MYELOMA; MOUSE; PLASMACYTOMAS; CELLS; 1Q21 C1 NCI, Genet Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. FAST Syst, Gaithersburg, MD USA. NIH, Natl Ctr Human Genome Res, Genome Technol Branch, Bethesda, MD 20892 USA. RP Coleman, AE (reprint author), NCI, Genet Lab, Div Basic Sci, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 1999 VL 93 IS 12 BP 4442 EP 4444 PG 3 WC Hematology SC Hematology GA 204TK UT WOS:000080780200046 PM 10391697 ER PT J AU Rugge, M Busatto, G Cassaro, M Shiao, YH Russo, V Leandro, G Avellini, C Fabiano, A Sidoni, A Covacci, A AF Rugge, M Busatto, G Cassaro, M Shiao, YH Russo, V Leandro, G Avellini, C Fabiano, A Sidoni, A Covacci, A TI Patients younger than 40 years with gastric carcinoma - Helicobacter pylori genotype and associated gastritis phenotype SO CANCER LA English DT Article; Proceedings Paper CT 89th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-APR 01, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res DE gastric carcinoma; Helicobacter pylori; cagA gene; cagA pathogenicity island; environmental gastric carcinoma; cancer in youth; multifocal atrophic gastritis; intestinal-type gastric carcinoma; diffuse-type gastric carcinoma ID DUODENAL-ULCER; ATROPHIC GASTRITIS; CANCER MORTALITY; CAGA STATUS; INFECTION; RISK; ADENOCARCINOMAS; CARCINOGENESIS; STRAINS; STOMACH AB BACKGROUND. In the general population, Helicobacter pylori (H. pylori, particularly the cagA positive strain, has been associated with intestinal-type gastric carcinoma. Gastric carcinomas are rarely observed in patients age less than or equal to 40 years. Host-related factors have been thought to be more important than environmental agents in these early-onset cancers. The aim of this study was to ascertain the possible role of H. pylori infection and that of cagA positive strains in the development of gastric carcinoma in these young patients. METHODS. In this case-control study, 105 gastric carcinoma patients (male-to-female ratio = 1.1; mean age, 34.4 years; range, 16-40 years) and an equal number of controls (matched for gender and age) were retrospectively selected from the same geographic area. The phenotypes of gastritis and H. pylori were histologically assessed, and the presence of the ureC gene, which is indicative of H. pylori infection, and the cagA genotype were determined by polymerase chain reaction. Gastric carcinoma risk was calculated by both univariate and multivariate statistical methods, taking into account the cancer phenotype, the gastritis phenotype detected in both patients and controls, and the H. pylori genotype. RESULTS. For 74 diffuse and 31 intestinal gastric carcinomas, multivariate logistic regression analysis produced results consistent with those of univariate statistical tests, showing a significant association between gastric carcinoma and both H. pylori infection (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.52-5.11) and cagA positive status (OR = 2.94; 95% CI = 1.56-5.52). CONCLUSIONS. In young Italian patients with gastric carcinoma, the significant association with cagA positive H. pylori infection suggests that the bacterium has an etiologic role in both diffuse-type and intestinal-type gastric carcinoma. Cancer 1999;85:2506-11. (C) 1999 American Cancer Society. C1 Univ Padua, Dept Oncol & Surg Sci, I-35121 Padua, Italy. ULSS, Padua, Italy. NCI, Comparat Carcinogenesis Lab, FCRDC, NIH, Frederick, MD 21701 USA. Univ Catania, Dept Pathol, Catania, Italy. Hosp Saverio Bellis, Dept Med, Castellana Grotte, Italy. Univ Udine, Dept Pathol, I-33100 Udine, Italy. Fatebenefratelli Hosp, Dept Pathol, Rome, Italy. Univ Perugia, Dept Pathol, I-06100 Perugia, Italy. IRIS, CHIRON, Siena, Italy. RP Rugge, M (reprint author), Univ Padua, Dept Oncol & Surg Sci, Via Aristide Gabelli 61, I-35121 Padua, Italy. RI Rugge, Massimo/K-7525-2016 NR 44 TC 90 Z9 96 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1999 VL 85 IS 12 BP 2506 EP 2511 DI 10.1002/(SICI)1097-0142(19990615)85:12<2506::AID-CNCR3>3.0.CO;2-I PG 6 WC Oncology SC Oncology GA 204RL UT WOS:000080777900003 PM 10375095 ER PT J AU Vortmeyer, AO Stavrou, T Selby, D Li, G Weil, RJ Park, WS Moon, YW Chandra, R Goldstein, AM Zhuang, ZP AF Vortmeyer, AO Stavrou, T Selby, D Li, G Weil, RJ Park, WS Moon, YW Chandra, R Goldstein, AM Zhuang, ZP TI Deletion analysis of the adenomatous polyposis coli and PTCH gene loci in patients with sporadic and nevoid basal cell carcinoma syndrome-associated medulloblastoma SO CANCER LA English DT Article DE medulloblastoma; nevoid basal cell carcinoma syndrome; adenomatous polyposis coil; PTCH; allelic deletion ID PRIMITIVE NEUROECTODERMAL TUMORS; HUMAN HOMOLOG; TURCOTS-SYNDROME; SOMATIC MUTATIONS; BRAIN-TUMORS; APC GENE; HETEROZYGOSITY; 9Q AB BACKGROUND, Medulloblastomas can occur sporadically or may be associated with hereditary tumor syndromes including familial adenomatous polyposis (FAP) and nevoid basal cell carcinoma syndrome (NBCCS). METHODS. The authors performed a retrospective analysis for allelic deletion of the adenomatous polyposis coli (APC) and PTCH gene loci using paraffin embedded medulloblastoma specimens from patients who were admitted to Children's National Medical Center in Washington, DC, between 1982 and 1997. Thirty-five cases from which tumor and normal tissue could be procured were analyzed. Two of the analyzed cases had a positive family and personal history for NBCCS; in both cases the histology of the medulloblastoma revealed a desmoplastic phenotype. Thirty-three cases were not known to be associated with hereditary disease; 2 of those cases revealed desmoplastic and 31 cases revealed nondesmoplastic "classic" medulloblastoma histology. RESULTS. Although medulloblastoma tumorigenesis has been associated strongly with FAP associated with APC germline mutation, none of the 22 informative sporadic cases revealed loss of heterozygosity of the APC gene locus. PTCH gene deletion was detected in the tumors of both patients with NBCCS. In contrast, only 1 of 33 sporadic medulloblastomas revealed PTCH gene deletion. The sporadic case with PTCH gene deletion did not demonstrate the desmoplastic phenotype. CONCLUSIONS. In conjunction with previous studies, the data from the current study confirm that allelic deletion occurs in NBCCS-associated medulloblastomas, consistent with the role of PTCH as a tumor suppressor gene. However, in sporadic medulloblastomas, allelic deletion of PTCH is an infrequent event. Morphologic examination in conjunction with genetic analysis of PTCH gene deletion in medulloblastoma tissue may prove to be a quick and efficient test with which to screen for NBCCS in patients with medulloblastomas. Although medulloblastoma is a component of Turcot syndrome with demonstrated APC mutations, APC gene deletions appear to be absent or very uncommon in patients with sporadic and NBCCS-associated medulloblastomas. Cancer 1999;85:2662-7. (C) 1999 American Cancer Society. C1 Natl Canc Inst, Pathol Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. Natl Canc Inst, Genet Epidemiol Branch, Bethesda, MD USA. RP Vortmeyer, AO (reprint author), Natl Canc Inst, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 31 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1999 VL 85 IS 12 BP 2662 EP 2667 DI 10.1002/(SICI)1097-0142(19990615)85:12<2662::AID-CNCR24>3.0.CO;2-0 PG 6 WC Oncology SC Oncology GA 204RL UT WOS:000080777900024 PM 10375116 ER PT J AU Wang, JX Saunthararajah, Y Redner, RL Liu, JM AF Wang, JX Saunthararajah, Y Redner, RL Liu, JM TI Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; TRANSCRIPTIONAL ACTIVATION; CHROMOSOME-TRANSLOCATION; FUSION TRANSCRIPT; ARSENIC TRIOXIDE; GENE; PROTEIN; ALPHA; HEMATOPOIESIS AB The (8;21) translocation, found in 12% of acute myeloid leukemia (AML), creates the chimeric fusion product, AML1-ETO. Previously, we demonstrated that the ETO moiety recruits a transcription repression complex that includes the histone deacetylase (HDAC1) enzyme, Here, we used inhibitors of HDAC1 to study the pathophysiology of AML1-ETO. Both the potent inhibitor, trichostatin (TSA), and the Hell-known but less specific inhibitor, phenylbutyrate (PB), could partially reverse ETO-mediated transcriptional repression. PB was also able to induce partial differentiation of the AML1-ETO cell line, Kasumi-1. With the intention of developing a clinically useful protocol, we combined PB with a number of other agents that induced differentiation and apoptosis of Kasumi-1 cells, In summary, transcriptional repression mediated by AML1-ETO appears to play a mechanistic role in the t(8;21) AML, and relief of repression using agents such as PB (alone or in combination) may prove to be therapeutically useful. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, 10-ACRF-7C103, Bethesda, MD 20892 USA. NR 21 TC 145 Z9 153 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1999 VL 59 IS 12 BP 2766 EP 2769 PG 4 WC Oncology SC Oncology GA 207NE UT WOS:000080942300003 PM 10383127 ER PT J AU Soga, S Neckers, LM Schulte, TW Shiotsu, Y Akasaka, K Narumi, H Agatsuma, T Ikuina, Y Murakata, C Tamaoki, T Akinaga, S AF Soga, S Neckers, LM Schulte, TW Shiotsu, Y Akasaka, K Narumi, H Agatsuma, T Ikuina, Y Murakata, C Tamaoki, T Akinaga, S TI KF25706, a novel oxime derivative of radicicol, exhibits in vivo antitumor activity via selective depletion of Hsp90 binding signaling molecules SO CANCER RESEARCH LA English DT Article ID HEAT-SHOCK PROTEINS; TYROSINE-KINASE INHIBITOR; MICROCULTURE TETRAZOLIUM ASSAY; IMPORTANT BIOLOGIC ACTIVITIES; HUMAN BREAST-CANCER; TUMOR CELL-LINES; IN-VIVO; CARCINOMA-CELLS; INDUCIBLE CYCLOOXYGENASE; HSP90-BINDING AGENT AB Radicicol, a macrocyclic antifungal antibiotic, has been shown to bind to the heat shock protein 90 (Hsp90) chaperone, interfering with its function. Hsp90 family chaperones have been shown to associate with several signaling molecules and play. an essential role in signal transduction, which is important for tumor cell growth, Because radicicol lacks antitumor activity in vivo in experimental animal models, we examined the antitumor activity of a novel radicicol oxime derivative, radicicol 6-oxime (KF25706), on human tumor cell growth both in vitro and in vivo. KF25706 showed potent antiproliferative activities against various human tumor cell lines in vitro and inhibited v-src- and g-ras-activated signaling as well as radicicol. In addition, Hsp90 family chaperone-associated proteins, such as p185(erbB2), Raf-1, cyclin-dependent kinase?, and mutant p53, were depleted by KF25706 at a dose comparable to that required for antiproliferative activity. KF25706 was also shown to compete with geldanamycin for binding to Hsp90, KF29163, which is an inactive derivative of radicicol, was less potent both in p185(erbB2) depletion and Hsp90 binding. More importantly, KF25706 showed significant growth-inhibitory activity against human breast carcinoma MX-1 cells transplanted into nude mice at a dose of 100 mg/kg twice daily for five consecutive i.v. injections, KF15706 was also shown to possess antitumor activity against human breast carcinoma MCF-7, colon carcinoma DLD-1, and vulval carcinoma A431 cell lines in vivo in an animal model. Finally, we confirmed the depletion of Hsp90-associated signaling molecules (Raf-1 and cyclin-dependent kinase 4) with ex vivo Western blotting analysis using MX-1 xenografts, In agreement with in vivo antitumor activity, KF25706 depleted Hsp90-associated molecules in vivo, whereas KF29163 and radicicol did not show this activity bl vivo. Taken together, these results suggest that antitumor activity of KF25706 may be mediated, at least in part, by binding to Hsp90 family proteins and destabilization of Hsp90-associated signaling molecules. C1 Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Labs, Nagaizumi, Shizuoka 4118731, Japan. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Akinaga, S (reprint author), Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Labs, Shimotogari 1188, Nagaizumi, Shizuoka 4118731, Japan. NR 58 TC 124 Z9 131 U1 3 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 1999 VL 59 IS 12 BP 2931 EP 2938 PG 8 WC Oncology SC Oncology GA 207NE UT WOS:000080942300033 PM 10383157 ER PT J AU Stickle, DF Reynolds, MA Morris, MD Quon, MJ AF Stickle, DF Reynolds, MA Morris, MD Quon, MJ TI Dynamic changes in plasma proinsulin/insulin ratio during insulin secretion influence correlation between radioimmunoassay (RIA) and IMX measurements of insulin SO CLINICA CHIMICA ACTA LA English DT Article DE insulin; proinsulin; RIA; IMX ID IMPAIRED GLUCOSE-TOLERANCE; NIDDM; SENSITIVITY; RESISTANCE; IMMUNOASSAY; NONOBESE; OBESE AB Because proinsulin and insulin have different circulatory half-lives, the ratio of proinsulin to insulin in plasma depends on the dynamics of insulin secretion. This variation can potentially influence comparison of IMX assays and radioimmunoassays (RIAs) for [insulin], given that the antibody used in the IMX assay has negligible cross-reactivity with proinsulin compared to the 40% cross-reactivity with proinsulin of the antibody used in the RIA. Simulation of a simple mass balance model for insulin and proinsulin concentrations during an oral glucose tolerance test predicts that the ratio (R) of RIA to IMX insulin measurements of [insulin] should transiently decrease, pass through a minimum, increase past the initial value, pass through a maximum and eventually return to the initial value. Using time course specimens from patients, this pattern of variation in R was observed in the majority (12/16) of cases studied. The variation in R for time course specimens (CV = 26%) was significantly greater than for other specimens (fasting, random or undesignated; P < 0.05). Thus, when comparing IMX and RIA measurements of [insulin], variation in R for samples from differing states of dynamic insulin secretion contains a component that is attributable to dynamic changes in the ratio of [proinsulin]/[insulin] in plasma. Published by Elsevier Science B.V. C1 Brooke Army Med Ctr, Dept Pathol, Ft Sam Houston, TX 78234 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Stickle, DF (reprint author), Brooke Army Med Ctr, Dept Pathol, Ft Sam Houston, TX 78234 USA. RI Quon, Michael/B-1970-2008; Stickle, Douglas/A-9682-2009; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 28 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JUN 15 PY 1999 VL 284 IS 1 BP 1 EP 13 DI 10.1016/S0009-8981(99)00072-8 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 218DP UT WOS:000081538200001 PM 10437638 ER PT J AU Francis, N Farinas, I Brennan, C Rivas-Plata, K Backus, C Reichardt, L Landis, S AF Francis, N Farinas, I Brennan, C Rivas-Plata, K Backus, C Reichardt, L Landis, S TI NT-3, like NGF, is required for survival of sympathetic neurons, but not their precursors SO DEVELOPMENTAL BIOLOGY LA English DT Article DE neurotrophin; sympathetic neuron; survival; cell death ID NERVE GROWTH-FACTOR; SUPERIOR CERVICAL-GANGLION; SENSORY NEURONS; DIFFERENT NEUROTROPHINS; RECEPTOR GENE; IN-VIVO; RAT; EXPRESSION; NEUROBLASTS; TRKA AB Superior cervical ganglia of postnatal mice with a targeted disruption of the gene for neurotrophin-3 have 50% fewer neurons than those of wild-type mice. In culture, neurotrophin-3 increases the survival of proliferating sympathetic precursors. Both precursor death (W. ElShamy et al., 1996, Development 122, 491-500) and, more recently, neuronal death (S. Wyatt et al., 1997, EMBO J. 16, 3115-3123) have been described in mice lacking NT-3. Consistent with the second report, we found that, in vivo, neurogenesis and precursor survival were unaffected by the absence of neurotrophin-3 but neuronal survival was compromised so that only 50% of the normal number of neurons survived to birth. At the time of neuron loss, neurotrophin-3 expression, assayed with a lacZ reporter, was detected in sympathetic target tissues and blood vessels, including those along which sympathetic axons grow, suggesting it may act as a retrograde neurotrophic factor, similar to nerve growth factor. To explore this possibility, we compared neuron loss in neurotrophin-3-deficient mice with that in nerve growth factor-deficient mice and found that neuronal losses occurred at approximately the same time in both mutants, but were less severe in mice lacking neurotrophin-3. Eliminating one or both neurotrophin-3 alleles in mice that lack nerve growth factor does not further reduce sympathetic neuron number in the superior cervical ganglion at E17.5 but does alter axon outgrowth and decrease salivary gland innervation. Taken together these results suggest that neurotrophin-3 is required for survival of some sympathetic neurons that also require nerve growth factor. (C) 1999 Academic Press. C1 Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. NINDS, Neural Dev Sect, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, Program Neurosci, San Francisco, CA 94143 USA. RP Francis, N (reprint author), Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. RI Farinas, Isabel/L-7118-2014 OI Farinas, Isabel/0000-0003-2903-4960 FU NICHD NIH HHS [HD 25681]; NIMH NIH HHS [MH48200] NR 51 TC 91 Z9 93 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1999 VL 210 IS 2 BP 411 EP 427 DI 10.1006/dbio.1999.9269 PG 17 WC Developmental Biology SC Developmental Biology GA 213AG UT WOS:000081249400012 PM 10357900 ER PT J AU Horiuchi, M Caughey, B AF Horiuchi, M Caughey, B TI Specific binding of normal prion protein to the scrapie form via a localized domain initiates its conversion to the protease-resistant state SO EMBO JOURNAL LA English DT Article DE cell-free conversion; prion protein; scrapie ID CELL-FREE CONVERSION; SYNTHETIC PEPTIDES; NEUROBLASTOMA-CELLS; MASS-SPECTROMETRY; MOLECULAR-BIOLOGY; TRANSGENIC MICE; AMYLOID PLAQUES; CULTURED-CELLS; NMR STRUCTURE; NORMAL BRAIN AB In the transmissible spongiform encephalopathies, normal prion protein (PrP-sen) is converted to a protease-resistant isoform, PrP-res, by an apparent self-propagating activity of the latter. Here we describe new, more physiological cell-free systems for analyzing the initial binding and subsequent conversion reactions between PrP-sen and PrP-res, These systems allowed the use of antibodies to map the sites of interaction between PrP-sen and PrP-res. Binding of antibodies (alpha 219-232) to hamster PrP-sen residues 219-232 inhibited the binding of PrP-sen to PrP-res and the subsequent generation of PK-resistant PrP, However, antibodies to several other parts of PrP-sen did not inhibit. The alpha 219-232 epitope itself was not required for PrP-res binding; thus, inhibition by alpha 219-232 was likely due to steric blocking of a binding site that is close to, but does not include the epitope in the folded PrP-sen structure. The selectivity of the binding reaction was tested by incubating PrP-res with cell lysates or culture supernatants. Only PrP-sen was observed to bind PrP-res, This highly selective binding to PrP-res and the localized nature of the binding site on PrP-sen support the idea that PrP-sen serves as a critical ligand and/or receptor for PrP-res in the course of PrP-res propagation and pathogenesis in vivo. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 54 TC 179 Z9 187 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 1999 VL 18 IS 12 BP 3193 EP 3203 DI 10.1093/emboj/18.12.3193 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 210BQ UT WOS:000081085600002 PM 10369660 ER PT J AU Kuratomi, Y Nomizu, M Nielsen, PK Tanaka, K Song, SY Kleinman, HK Yamada, Y AF Kuratomi, Y Nomizu, M Nielsen, PK Tanaka, K Song, SY Kleinman, HK Yamada, Y TI Identification of metastasis-promoting sequences in the mouse laminin alpha 1 chain SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE laminin; peptide; metastasis; migration; adhesion ID INHIBITS EXPERIMENTAL METASTASIS; TERMINAL GLOBULAR DOMAIN; MEDIATES CELL-ADHESION; AMINO-ACID-SEQUENCE; A-CHAIN; MELANOMA-CELLS; SYNTHETIC PEPTIDE; TUMOR-GROWTH; EXTRACELLULAR-MATRIX; BINDING SEQUENCES AB Laminin-1, a major basement membrane matrix glycoprotein, enhances adhesion, migration, and metastasis of tumor cells. We have screened 208 overlapping synthetic peptides covering the short and long arms of mouse laminin alpha 1 chain for their adhesion activity with B16-F10 mouse melanoma cells. Cell adhesion activity was determined using various amounts of peptides coated on plastic dishes and by measuring cell adhesion on peptide-conjugated Sepharose beads. Nineteen peptides showed B16-F10 cell adhesion activity. Three peptides, designated A-13, -24, and -208, showed the strongest attachment activity in the plate assay, whereas 4 peptides, ALS, -51, -99, and -112, demonstrated the strongest cell adhesion when conjugated to beads. The 19 peptides were tested in vivo for their effect on experimental pulmonary metastasis by B16-F10 cells. Four peptides, A-13, -51, -64, and -119, significantly enhanced metastasis, with A-13 showing the strongest dramatic enhancement. The four metastasis-promoting peptides also stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro with A-13 being the most potent stimulator. In addition, the 4 peptides inhibited laminin-induced cell attachment and migration, which indicates that these four sequences are possible functional B16-F10 cell binding sites in laminin-l. All the four sequences are located on the globular domains of the short arm. Other peptides, including strong adhesion-active peptides, A-24, -99, -112, and a scrambled A-13 peptide, did not stimulate either migration or metastasis. Thus, laminin-l has multiple active sites in the globular domains of the short arm which promote migration and metastasis of B16-F10 cells. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 405, Bethesda, MD 20892 USA. NR 46 TC 36 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 15 PY 1999 VL 249 IS 2 BP 386 EP 395 DI 10.1006/excr.1999.4497 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 207CL UT WOS:000080917800021 PM 10366438 ER PT J AU Chadwick, BP Mull, J Helbling, LA Gill, S Leyne, M Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, N Gusella, JF Slaugenhaupt, SA AF Chadwick, BP Mull, J Helbling, LA Gill, S Leyne, M Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, N Gusella, JF Slaugenhaupt, SA TI Cloning, mapping, and expression of two novel actin genes, actin-like-7A (ACTL7A) and actin-like-7B (ACTL7B), from the familiar dysautonomia candidate region on 9q31 SO GENOMICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; HUMAN-CHROMOSOME; PROTEIN; SWI/SNF; COMPLEX; CHROMATIN; SEQUENCE AB Two novel human actin-like genes, ACTL7A and ACTL7B, were identified by cDNA selection and direct genomic sequencing from the familial dysautonomia candidate region on 9q31. ACTL7A encodes a 435-amino-acid protein (predicted molecular mass 48.6 kDa) and ACTL7B encodes a 415-amino-acid protein (predicted molecular mass 45.2 kDa) that show greater than 65% amino acid identity to each other. Genomic analysis revealed ACTL7A and ACTL7B to be intronless genes contained on a common 8-kb HindIII fragment in a "head-to-head" orientation. The murine homologues were cloned and mapped by linkage analysis to mouse chromosome 4 in a region of gene order conserved with human chromosome 9q31. No recombinants were observed between the two genes, indicating a close physical proximity in mouse. ACTL7A is expressed in a wide variety of adult tissues, while the ACTL7B message was detected only in the testis and, to a lesser extent, in the prostate. No coding sequence mutations, genomic rearrangements, or differences in expression were detected for either gene in familial dysautonomia patients. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA. NIMH, Canc Genet Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NIMH, Genome Technol Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. RP Slaugenhaupt, SA (reprint author), HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Brownstein, Michael/B-8609-2009; Pinkett, Heather/M-9235-2014 FU NINDS NIH HHS [NS36326] NR 35 TC 19 Z9 24 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1999 VL 58 IS 3 BP 302 EP 309 DI 10.1006/geno.1999.5848 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 211FH UT WOS:000081149500010 PM 10373328 ER PT J AU Su, SB Gong, WH Grimm, M Utsunomiya, I Sargeant, R Oppenheim, JJ Wang, JM AF Su, SB Gong, WH Grimm, M Utsunomiya, I Sargeant, R Oppenheim, JJ Wang, JM TI Inhibition of tyrosine kinase activation blocks the down-regulation of CXC chemokine receptor 4 by HIV-1 gp120 in CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; PROTEIN; TYPE-1; EXPRESSION; INFECTION; CLONING; CCR5; NEUTRALIZATION; INTERLEUKIN-16; REPLICATION AB Because the binding of HIV-1 envelope to CD4 initiates a cofigurational change in glycoprotein 120 (gp120), enabling it to interact with fusion coreceptors, we investigated how this process interferes with the expression and function of CXC chemokine receptor 4 (CXCR4) in CD4(+) T lymphocytes, A recombinant gp120 (MN), after preincubation with CD4(+) T lymphocytes, significantly inhibited the binding and chemotaxis of the cells in response to the CXCR4 ligand stromal cell-derived factor-1 alpha (SDF-1 alpha), accompanied by a markedly reduced surface expression of CXCR4, gp120, but not SDF-1 alpha, induced rapid tyrosine phosphorylation of src-like kinase p56(lck) in CD4(+) T cells, whereas both gp120 and SDF-1 alpha caused phosphorylation of the CXCR4, The tyrosine kinase inhibitor herbimycin A abolished the phosphorylation of p56(lck) and CXCR4 induced by gp120 in association with maintenance of normal expression of cell surface CXCR4 and a migratory response to SDF-1 alpha, Thus, a CD4-associated signaling molecule(s) including p56(lck) is activated by gp120 and is required for the down-regulation of CXCR4. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Immunogenet Mol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. Millenium Biotechnol, Ramona, CA 92065 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Immunogenet Mol Lab, Bldg 560,Room 31-19, Frederick, MD 21702 USA. NR 30 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7128 EP 7132 PG 5 WC Immunology SC Immunology GA 205BT UT WOS:000080802000026 PM 10358157 ER PT J AU Marth, T Zeitz, M Ludviksson, BR Strober, W Kelsall, BL AF Marth, T Zeitz, M Ludviksson, BR Strober, W Kelsall, BL TI Extinction of IL-12 signaling promotes Fas-mediated apoptosis of antigen-specific T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; ORAL TOLERANCE; AUTOIMMUNE-DISEASES; DEATH; MICE; INTERLEUKIN-12; INDUCTION; PATHOGENESIS; ACTIVATION; MUTATIONS AB In previous studies rye have shown that peripheral tolerance achieved by high dose feeding of OVA to intact OVA-TCR transgenic mice was enhanced when endogenous IL-12 was neutralized simultaneously, To generalize this phenomenon, in the present study we investigated the tolerogenic mechanisms underlying the blockade of IL-12 signaling following oral and systemic Ag delivery. We found that the numbers of Ag-specific T cells in several lymphoid organs were significantly reduced due to T cell apoptosis following oral OVA or systemic OVA administration when combined with anti-IL-12 injection, but there was no decrease in T cell numbers for OVA-fed, OVA-injected, or anti-IL-12 alone-treated mice compared with those in untreated control mice, In addition, mostly Fas(+) T cells were subject to apoptotic deletion in the OVA- plus anti-IL-12-treated groups, and an enhanced cell death of T cells upon OVA restimulation in vitro could be partially reversed by blockade of the Fas/Fas ligand interaction. Finally, in a murine model of superantigen-driven T cell expansion and deletion, we observed no deletional effects of anti-IL-12 treatment on CD4(+) cells in Fas-deficient (MRL/lpr) mice, but did find these effects in MRL wild-type mice. In summary, our data suggest that in the course of Ag-induced cell proliferation of Th1 cells, signaling through IL-12 is-required to prevent an induction of Fas-mediated apoptosis, Thus, the use of anti-Ii-it may be potentially useful in modulating peripheral immune responses by promotion of Fas-mediated cell death. C1 Univ Saarlandes, D-66421 Homburg, Germany. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Marth, T (reprint author), Univ Saarlandes, D-66421 Homburg, Germany. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 37 TC 49 Z9 52 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7233 EP 7240 PG 8 WC Immunology SC Immunology GA 205BT UT WOS:000080802000039 PM 10358170 ER PT J AU Galon, J Sudarshan, C Ito, S Finbloom, D O'Shea, JJ AF Galon, J Sudarshan, C Ito, S Finbloom, D O'Shea, JJ TI IL-12 induces IFN regulating factor-1 (IRF-1) gene expression in human NK and T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR IRF-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NATURAL-KILLER-CELLS; INTERFERON-ALPHA; TYROSINE PHOSPHORYLATION; GAMMA PRODUCTION; IMMUNE-RESPONSE; TH2 CELLS; INDUCTION; ACTIVATION AB IL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses and the differentiation of naive CD4(+) cells to: Th1 cells; however, relatively few IL-12 target genes have been identified, To better clarify the molecular basis of IL-12 action, we set out to characterize genes up-regulated by IL-12, first by contrasting IL-12 and IFN-alpha-inducible genes. We identified several genes up-regulated by IL-12, namely, MIP-1 alpha, MIP-1 beta, IL-1RA, and IFN regulatory factor-1 (IRF-1), IRF-1 is a transcription factor regulated by IFNs that is also essential for Th1 responses, We demonstrated that IL-12 directly up-regulates IRF-1 to the same extent as IFN-alpha in normal human T cells and in NK cells. We showed that IL-12 had a direct effect on IRF-1, an effect not mediated indirectly by the induction of IFN-gamma production, Furthermore,: IL-2 and IL-12 synergistically induced IRF-1, whereas IFN-alpha and IL-12 did not. The participation of STAT4 in-the regulation of IRF-1 was demonstrated in two ways, First, STAT4 was required for the IL-12-dependent transactivation of an IRF-1 reporter construct, and second, STAT4 binding to the IRF-1 promoter was shown using EMSA. In contrast to IL-12, no up-regulation of IRF-1 was found in IL-4-stimulated cells, and IL-4 did not block IL-12-dependent up-regulation of IRF-1, Therefore, IRF-1 may be an important contributor to IL-12 signaling, and we speculate that the defective IL-12 responses seen in IRF-1(-/-) mice might be attributable, in part, to the absence of this transcription factor. C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Cytokine Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Galon, J (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N 252,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. NR 39 TC 75 Z9 76 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7256 EP 7262 PG 7 WC Immunology SC Immunology GA 205BT UT WOS:000080802000042 PM 10358173 ER PT J AU Hirunpetcharat, C Vukovic, P Xue, QL Kaslow, DC Miller, LH Good, MF AF Hirunpetcharat, C Vukovic, P Xue, QL Kaslow, DC Miller, LH Good, MF TI Absolute requirement for an active immune response involving B cells and Th cells in immunity to Plasmodium yoelii passively acquired with antibodies to the 19-kDa carboxyl-terminal fragment of merozoite surface protein-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MALARIA; MICE; VACCINE; IMMUNIZATION; ANTIGEN; GENE AB Vaccination of mice with the leading malaria vaccine candidate homologue, the 19-kDa carboxyl terminus of merozoite surface protein-1 (MSP1(19)), results in sterile immunity to Plasmodium yoelii, with no parasites detected in blood. Although such immunity depends upon high titer Abs at challenge, high doses of immune sera transferred into naive mice reduce parasitemia (and protect from death) but do not result in a similar degree of protection (with most mice experiencing high peak parasitemias); this finding suggests that ongoing parasite-specific immune responses postchallenge are essential. We analyzed this postchallenge response by transferring Abs into manipulated but malaria-naive mice and observed that Abs cannot protect SCID, nude, CD4(+) T cell-depleted, or B cell knockout mice, with all mice dying. Thus, in addition to the Abs that develop following MSP1(19) vaccination, a continuing active immune response postchallenge is required for protection. MSP1(19)-specific Abs can adoptively transfer protection to strains of mice that are not protected following vaccination with MSP1(19), suggesting that the Ags targeted by the immune response postchallenge include Ags apart from MSP1(19). These data have important implications for the development of a human malaria vaccine. C1 PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Good, MF (reprint author), PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. NR 16 TC 59 Z9 60 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7309 EP 7314 PG 6 WC Immunology SC Immunology GA 205BT UT WOS:000080802000049 PM 10358180 ER PT J AU Miller, JS Cervenka, T Lund, J Okazaki, IJ Moss, J AF Miller, JS Cervenka, T Lund, J Okazaki, IJ Moss, J TI Purine metabolites suppress proliferation of human NK cells through a lineage-specific purine receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; EXTRACELLULAR ATP; ADENOSINE; INTERLEUKIN-2; NUCLEOTIDES; CYTOTOXICITY; NUCLEOSIDES; ACTIVATION AB NK cell proliferation is suppressed in some patients with cancer by unknown mechanisms. Because purine metabolites released into the extracellular space during cell lysis may affect cell function, we hypothesized that:these metabolites could serve as feedback regulators of NK cell proliferation. Sorted NK (CD56(+)/CD3(-)) cells were incubated with IL-2 (1000 U/ml) in a 4-day thymidine uptake assay with or without 10-10,000 mu M of nucleotides; Adenine nucleotides inhibited NK cell proliferation, with ATP = ADP > 5'-adenylylimidodiphosphate > AMP = adenosine; ADP-ribose and nicotinamide: adenine dinucleotide, but not nicotinamide or UTP, caused a dose-dependent suppression of thymidine uptake. A total of 100 mu M ATP, a concentration that induced a maximal (80%) inhibition of thymidine uptake, did not inhibit cytotoxic activity against K562 targets. Because NK cells retained the ability to lyse K562 targets 4 days after exposure to 500 mu M ATP or 1000 mu M adenosine, inhibition of thymidine uptake was not due to cell death. Incubation of NK cells with dibutyryl cAMP and forskolin also suppressed thymidine,uptake. Cholera toxin and pertussis toxin suppressed NR cell proliferation. Pertussis toxin did not block the adenine nucleotide effects. Further, ATP, but not adenosine or other nucleotides, markedly increased intracellular cAMP in a dose-dependent manner. The ATP-induced increase in cAMP was specific to, cytolytic cells, because CD19(+) B cells and CD4(+) T cells did not increase the intracellular cAMP, These studies demonstrate that NK proliferation is regulated through purine receptors by adenine nucleotides, which may play a, role in decreased NK cell activity. The response to adenine nucleotides is lineage-specific. C1 Univ Minnesota, Ctr Canc, Div Hematol Oncol & Transplantat, Dept Med, Minneapolis, MN 55455 USA. NHLBI, Pulmonary Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Miller, JS (reprint author), Univ Minnesota, Ctr Canc, Div Hematol Oncol & Transplantat, Dept Med, Box 806,Harvard St & E River Rd, Minneapolis, MN 55455 USA. OI Miller, Jeffrey S/0000-0002-0339-4944 FU NCI NIH HHS [P01-CA-65493]; NHLBI NIH HHS [R29-HL-55417] NR 37 TC 25 Z9 27 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7376 EP 7382 PG 7 WC Immunology SC Immunology GA 205BT UT WOS:000080802000058 PM 10358189 ER PT J AU Kantakamalakul, W Politis, AD Marecki, S Sullivan, T Ozato, K Fenton, MJ Vogel, SN AF Kantakamalakul, W Politis, AD Marecki, S Sullivan, T Ozato, K Fenton, MJ Vogel, SN TI Regulation of IFN consensus sequence binding protein expression in murine macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; TRANSCRIPTION FACTOR; INTERFERON-ALPHA; FACTOR FAMILY; INDUCIBLE GENES; PERITONEAL-MACROPHAGES; MOUSE MACROPHAGES; GAMMA-INTERFERON; NUCLEAR FACTOR; ICSBP GENE AB Recent work has demonstrated that the transcription fatter, IFN consensus sequence binding protein (ICSBP), plays a critical role in the capacity of mice to control infection with Toxoplasma gondii and Leishmania major, agents that require highly activated macrophages for, their elimination, In this report the regulation of ICSBP mRNA and protein were analyzed in murine macrophages stimulated with LPS and/or IFN-gamma. Like induction of leishmaniacidal activity, LPS and IFN-gamma, synergize to induce ICSBP mRNA and protein. Deletion analysis of the ICSBP promoter identified regions that were IFN-gamma responsive, regions that mediate the ability of LPS and IFN-gamma to activate this promoter synergistically, as well as regions that normally repress ICSBP transcription. Finally, exogenous expression of ICSBP, found in previous studies to down-regulate MHC I gene expression, failed to repress basal or IFN-gamma-induced ICSBP transcription, This demonstrates that ICSBP can selectively suppress the expression of IFN-responsive genes. These findings extend in a significant way our understanding of the regulation of ICSBP by LPS and IFN-gamma and provide important clues as to its role in macrophage activation. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Vogel, SN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [AI18797]; NIGMS NIH HHS [GM57053] NR 50 TC 42 Z9 43 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7417 EP 7425 PG 9 WC Immunology SC Immunology GA 205BT UT WOS:000080802000064 PM 10358195 ER PT J AU Hong, K Chu, A Ludviksson, BR Berg, EL Ehrhardt, RO AF Hong, K Chu, A Ludviksson, BR Berg, EL Ehrhardt, RO TI IL-12, independently of IFN-gamma, plays a crucial role in the pathogenesis of a murine psoriasis-like skin disorder SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; INFLAMMATORY BOWEL-DISEASE; LEUKOCYTE ADHESION MOLECULE-1; HLA-B27 TRANSGENIC RATS; T-HELPER TYPE-1; INTERFERON-GAMMA; L-SELECTIN; BACTERIAL SUPERANTIGENS; EXPERIMENTAL COLITIS; MONOCLONAL-ANTIBODY AB The onset of acute psoriasis and the; exacerbation of chronic psoriasis are often associated with a history of bacterial infection. We demonstrate that while only few scid/scid mice develop disease when CD4(+)CD45Rb(high) T cells are transferred alone, coadministration of LPS plus IL-12 or staphylococcal enterotoxin B into scid/scid mice 1 day after CD4(+)CD45Rb(high) T cell transfer greatly enhances disease penetrance and severity. Most importantly, the skin lesions induced by this method exhibit many of the histologic hallmarks observed inhuman psoriasis, Skin infiltrating CD4(+) T cells were predominantly memory/effector cells (CD45Rb(low)) and,exhibited a highly polarized Th1 phenotype,: To test whether the development of pathogenic T cells was dependent on their production of IFN-gamma, we transferred IFN-gamma(-/-) CD4(+)CD45Rb(high) T cells into scid/scid or into T, B and NK cell-deficient scid/beige mice. Surprisingly, the incidence of psoriasis was similar to scid/scid:animals that received IFN-gamma(+/+) T cells, although acanthosis of the skin was attenuated. In contrast, the development of psoriasis was abolished if anti-II-12 mAb was administered on day 7 and 35 after T cell transfer. Skin-derived IFN-gamma(-/-) inflammatory cells, but not cells from anti-IL-treated animals, secreted substantial amounts of TNF-alpha, suggesting that the inflammatory effect of IFN-gamma(-/-) T cells may be,partly exerted by TNF-alpha and that the therapeutic effect of anti-IL-12 may depend on its ability to down-regulate both TNF-alpha and IFN-gamma,Overall, these results suggest that IL-12, independently of IFN-gamma, is able to induce pathogenic, inflammatory T cells that are able to induce psoriasiform lesions in mice. C1 Protein Design Labs Inc, Fremont, CA 94555 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Ehrhardt, RO (reprint author), Protein Design Labs Inc, 34801 Campus Dr, Fremont, CA 94555 USA. RI Berg, Ellen/D-9076-2014; OI Berg, Ellen/0000-0001-5149-6665; Ludviksson, Bjorn/0000-0002-6445-148X NR 95 TC 88 Z9 99 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7480 EP 7491 PG 12 WC Immunology SC Immunology GA 205BT UT WOS:000080802000072 PM 10358203 ER PT J AU Moriuchi, H Moriuchi, M Fauci, AS AF Moriuchi, H Moriuchi, M Fauci, AS TI Induction of HIV-1 replication by allogeneic stimulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1-INFECTED INDIVIDUALS; PERIPHERAL-BLOOD; BETA-CHEMOKINES; CORD BLOOD; T-CELLS; INFECTION; IMMUNIZATION; MACAQUES; DISEASE AB Allogeneic stimulation presents an immunologic challenge during pregnancy, blood transfusions, and transplantations, and has been associated with reactivation of latently infected virus such as CMV, Since HIV-1 is transmitted vertically, sexually, or via contaminated blood, we have tested the effects of allostimulation on HIV-1 infection. 1) We show that allostimulated lymphocytes are highly susceptible to acute infection with T cell-tropic or dual-tropic HIV-1. 2) We show that allostimulation has dichotomous effects on replication of macrophage-tropic HIV-1 it activates HIV expression in already infected cells but inhibits HN entry by secreting HIV-suppressive CC chemokines. 3) We show that allogeneic stimulation of latently infected, resting CD4(+) T cells induced replication of HIV-1 in these cells. These observations suggest that allogeneic stimulation may play a role in the transmission, replication, and phenotypic transition of HIV-1. C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Moriuchi, H (reprint author), Nagasaki Univ, Sch Med, Dept Pediat, 1-7-1 Sakamoto, Nagasaki 8528501, Japan. NR 38 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 1999 VL 162 IS 12 BP 7543 EP 7548 PG 6 WC Immunology SC Immunology GA 205BT UT WOS:000080802000079 PM 10358210 ER PT J AU Maric, D Maric, I Wen, XL Fritschy, JM Sieghart, W Barker, JL Serafini, R AF Maric, D Maric, I Wen, XL Fritschy, JM Sieghart, W Barker, JL Serafini, R TI GABA(A) receptor subunit composition and functional properties of Cl- channels with differential sensitivity to zolpidem in embryonic rat hippocampal cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA(A) receptors; zolpidem; oxonol; FACS; development; rat; hippocampus ID A-BENZODIAZEPINE RECEPTOR; DRUG-BINDING PROFILE; MESSENGER-RNAS; NERVOUS-SYSTEM; SPINAL-CORD; PATCH RECORDINGS; ION CHANNELS; BRAIN; NEURONS; EXPRESSION AB Using flow cytometry in conjunction with a voltage-sensitive fluorescent indicator dye (oxonol), we have identified and separated embryonic hippocampal cells according to the sensitivity of their functionally expressed GABA, receptors to zolpidem. Immunocytochemical and RT-PCR analysis of sorted zolpidem-sensitive (ZS) and zolpidem-insensitive (ZI) subpopulations identified ZS cells as postmitotic, differentiating neurons expressing alpha 2, alpha 4, alpha 5, beta 1, beta 2, beta 3, gamma 1, gamma 2, and gamma 3 GABA(A) receptor subunits, whereas the ZI cells were neuroepithelial cells or newly postmitotic neurons, expressing predominantly alpha 4, alpha 5, beta 1, and gamma 2 subunits. Fluctuation analyses of macroscopic Cl- currents evoked by GABA revealed three kinetic components of GABA(A) receptor/Cl- channel activity in both subpopulations. We focused our study on ZI cells, which exhibited a limited number of subunits and functional channels, to directly correlate subunit composition with channel properties. Biophysical analyses of GABA-activated Cl- currents in ZI cells revealed two types of receptor-coupled channel properties: one comprising short-lasting openings, high affinity for GABA, and low sensitivity to diazepam, and the other with long-lasting openings, low affinity for GABA, and high sensitivity to diazepam. Both types of channel activity were found in the same cell. Channel kinetics were well modeled by fitting dwell time distributions to biliganded activation and included two open and five closed states. We propose that short- and long-lasting openings correspond to GABA(A) receptor/Cl- channels containing alpha 4 beta 1 gamma 2 and alpha 5 beta 1 gamma 2 subunits, respectively. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Pharmacol, CH-8057 Zurich, Switzerland. Univ Vienna, Psychiat Clin, Dept Biochem Psychiat, A-1090 Vienna, Austria. RP Maric, D (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Rm 2C-02, Bethesda, MD 20892 USA. RI Sieghart, Werner/A-4877-2013 OI Sieghart, Werner/0000-0002-0443-0302 NR 54 TC 25 Z9 25 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1999 VL 19 IS 12 BP 4921 EP 4937 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 204FQ UT WOS:000080753800024 PM 10366626 ER PT J AU Wang, H Copeland, NG Gilbert, DJ Jenkins, NA Tessier-Lavigne, M AF Wang, H Copeland, NG Gilbert, DJ Jenkins, NA Tessier-Lavigne, M TI Netrin-3, a mouse homolog of human NTN2L, is highly expressed in sensory ganglia and shows differential binding to netrin receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE netrin-3; axon guidance; sensory neurons; mouse chromosome 17; peripheral nervous system; DCC ID PIONEER AXON MIGRATIONS; C-ELEGANS; COLORECTAL-CANCER; COMMISSURAL AXONS; ZEBRAFISH EMBRYO; GENETIC-ANALYSIS; MOTOR AXONS; GUIDES CELL; DCC; GUIDANCE AB The netrins comprise a small phylogenetically conserved family of guidance cues important for guiding particular axonal growth cones to their targets. Two netrin genes, netrin-1 and netrin-2, have been described in chicken, but in mouse so far a single netrin gene, an ortholog of chick netrin-1, has been reported. We report the identification of a second mouse netrin gene, which we name netrin-3. Netrin-3 does not appear to be the ortholog of chick netrin-2 but is the ortholog of a recently identified human netrin gene termed NTN2L ("netrin-2-like"), as evidenced by a high degree of sequence conservation and by chromosomal localization. Netrin-3 is expressed in sensory ganglia, mesenchymal cells, and muscles during the time of peripheral nerve development but is largely excluded from the CNS at early stages of its development. The murine netrin-3 protein binds to netrin receptors of the DCC (deleted in colorectal cancer) family [DCC and neogenin] and the UNC5 family (UNC5H1, UNC5H2 and UNC5H3). Unlike chick netrin-1, however, murine netrin-3 binds to DCC with lower affinity than to the other four receptors. Consistent with this finding, although murine netrin-3 can mimic the outgrowth-promoting activity of netrin-1 on commissural axons, it has lower specific activity than netrin-1. Thus, like netrin-1, netrin-3 may also function in axon guidance during development but may function predominantly in the development of the peripheral nervous system and may act primarily through netrin receptors other than DCC. C1 Univ Calif San Francisco, Dept Anat, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Howard Hughes Med Inst, San Francisco, CA 94143 USA. NCI, Mammalian Genet Lab, Adv Biosci Labs Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Tessier-Lavigne, M (reprint author), Univ Calif San Francisco, Dept Anat, Howard Hughes Med Inst, 513 Parnassus Ave,Room S-1479, San Francisco, CA 94143 USA. NR 33 TC 95 Z9 98 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1999 VL 19 IS 12 BP 4938 EP 4947 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 204FQ UT WOS:000080753800025 PM 10366627 ER PT J AU Pozzo-Miller, LD Gottschalk, W Zhang, L McDermott, K Du, J Gopalakrishnan, R Oho, C Sheng, ZH Lu, B AF Pozzo-Miller, LD Gottschalk, W Zhang, L McDermott, K Du, J Gopalakrishnan, R Oho, C Sheng, ZH Lu, B TI Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; knockout mice; hippocampus; synaptic fatigue; vesicle docking; synaptobrevin; synaptophysin ID LONG-TERM POTENTIATION; NEUROTROPHIC FACTOR; RAT HIPPOCAMPUS; MESSENGER-RNA; CLOSTRIDIAL NEUROTOXINS; NEURONAL PLASTICITY; TRANSMITTER RELEASE; CENTRAL SYNAPSES; NERVOUS-SYSTEM; VISUAL-CORTEX AB Brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) at hippocampal CA1 synapses by a presynaptic enhancement of synaptic transmission during high-frequency stimulation (HFS). Here we have investigated the mechanisms of BDNF action using two lines of BDNF knockout mice. Among other presynaptic impairments, the mutant mice exhibited more pronounced synaptic fatigue at CA1 synapses during high-frequency stimulation, compared with wild-type animals. Quantitative analysis of CA1 synapses revealed a significant reduction in the number of vesicles docked at presynaptic active zones in the mutant mice. Synaptosomes prepared from the mutant hippocampus exhibited a marked decrease in the levels of synaptophysin as well as synaptobrevin [vesicle-associated membrane protein (VAMP-2)], a protein known to be involved in vesicle docking and fusion. Treatment of the mutant slices with BDNF reversed the electrophysiological and biochemical deficits in the hippocampal synapses. Taken together, these results suggest a novel role for BDNF in the mobilization and/or docking of synaptic vesicles to presynaptic active zones. C1 NICHHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Unit Synapt Funct, NIH, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHHD, Unit Synapse Dev & Plast, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38,49 Convent Dr,MSC4480, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; Du, Jing/A-9023-2012; yu, yan/C-2322-2012 NR 58 TC 321 Z9 324 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1999 VL 19 IS 12 BP 4972 EP 4983 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 204FQ UT WOS:000080753800028 PM 10366630 ER PT J AU Hatzidimitriou, G McCann, UD Ricaurte, GA AF Hatzidimitriou, G McCann, UD Ricaurte, GA TI Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/--)3,4-methylenedioxymethamphetamine seven years previously: Factors influencing abnormal recovery SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amphetamines; methylenedioxymethamphetamine; serotonin; neurotoxicity; regeneration; 5-HT axon ID EXHIBIT DIFFERENTIAL VULNERABILITY; RAT-BRAIN; AXON TERMINALS; MDMA ECSTASY; (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; RADIOLIGAND BINDING; NONHUMAN-PRIMATES; CEREBRAL-CORTEX; RHESUS-MONKEYS AB The recreational drug (+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a potent and selective brain serotonin (5-HT) neurotoxin in animals and, possibly, in humans. The purpose of the present study was to determine whether brain 5-HT deficits persist in squirrel monkeys beyond the 18-month period studied previously and to identify factors that influence recovery of injured 5-HT axons. Seven years after treatment, abnormal brain 5-HT innervation patterns were still evident in MDMA-treated monkeys, although 5-HT deficits in some regions were less severe than those observed at 18 months. No loss of 5-HT nerve cell bodies in the rostral raphe nuclei was found, indicating that abnormal innervation patterns in MDMA-treated monkeys are not the result of loss of a particular 5-HT nerve cell group. Factors that influence recovery of 5-HT axons after MDMA injury are (1) the distance of the affected axon terminal field from the rostral raphe nuclei, (2) the degree of initial 5-HT axonal injury, and possibly (3) the proximity of damaged 5-HT axons to myelinated fiber tracts. Additional studies are needed to better understand these and other factors that influence the response of primate 5-HT neurons to MDMA injury and to determine whether the present findings generalize to humans who use MDMA for recreational purposes. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. NIMH, Unit Anxiety Disorders, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Ricaurte, GA (reprint author), Johns Hopkins Med Inst, Dept Neurol, 5501 Hopkins Bayview Circle,Room 5B71E, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA00206, DA05707, DA06275] NR 49 TC 221 Z9 223 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 15 PY 1999 VL 19 IS 12 BP 5096 EP 5107 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 204FQ UT WOS:000080753800040 PM 10366642 ER PT J AU Yang, ZN Mueser, TC Kaufman, J Stahl, SJ Wingfield, PT Hyde, CC AF Yang, ZN Mueser, TC Kaufman, J Stahl, SJ Wingfield, PT Hyde, CC TI The crystal structure of the SIV gp41 ectodomain at 1.47 angstrom resolution SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE SIV; HIV; gp41; X-ray crystallography; protein structure; coiled coil; membrane fusion; peptide inhibitors ID SIMIAN IMMUNODEFICIENCY VIRUS; GP120 ENVELOPE GLYCOPROTEIN; 44 KDA ECTODOMAIN; COILED-COIL; TRANSMEMBRANE GLYCOPROTEIN; HIV-1 GP41; EXTRACELLULAR DOMAIN; DIFFRACTION DATA; ATOMIC-STRUCTURE; HEPTAD REPEAT AB Cell membrane fusion by human (HIV) and simian (SIV) immunodeficiency viruses is mediated by the envelope glycoproteins gp120 and gp41. Although the precise mechanism of the fusion process is unknown, the ectodomain of gp41 is thought to undergo dramatic rearrangement from its prefusogenic state. To elucidate this process further, the crystal structure of the SN gp41 ectodomain (residues 27-149) was determined at 1.47 Angstrom resolution and is reported herein. It is the most accurate and complete structure of a retroviral gp41 ectodomain determined to date. The rod-like trimeric structure of SIV gp41 comprises three parallel N-terminal alpha-helices assembled as a coiled coil in the center with three antiparallel C-terminal alpha-helices packed on the outside connected by highly flexible loops. Portions of the loops in all three monomers are crystallographically disordered and could not be accurately modeled. The core of the structure is similar (but not identical) to those of smaller HIV/SIV gp41 segments previously determined by X-ray crystallography with root mean square deviations in main chain atoms of less than 1.0 Angstrom The crystal structure differs more substantially from the reported NMR solution structure of the identical SIV construct. The mechanisms of viral fusion and the inhibition by peptides are discussed in the context of the three-dimensional structure. C1 NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Protein Express Lab, NIH, Bethesda, MD 20892 USA. RP Hyde, CC (reprint author), NIAMS, Struct Biol Res Lab, Bldg 6,Rm B2-34,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 93 Z9 94 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUN 15 PY 1999 VL 126 IS 2 BP 131 EP 144 DI 10.1006/jsbi.1999.4116 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 216ZZ UT WOS:000081475500005 PM 10388624 ER PT J AU Gehrke, BC Vogel, LP Wolff, AV AF Gehrke, BC Vogel, LP Wolff, AV TI Veterinary human capital-knowledge, skills, and abilities that enhance employment opportunities outside private practice SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 AVMA, Sci Activities Div, Schaumburg, IL 60173 USA. AVMA, Ctr Informat Management, Schaumburg, IL 60173 USA. NIH, Off Res Serv, Div Intramural REs Serv, Vet Resources Program, Bethesda, MD 20892 USA. RP Gehrke, BC (reprint author), USDA, Rural Business Cooperat Serv, 1400 Independence Ave SW, Washington, DC 20250 USA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUN 15 PY 1999 VL 214 IS 12 BP 1781 EP 1784 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 207JN UT WOS:000080933900017 PM 10382018 ER PT J AU Haque, MSR Arora, JK Dikdan, G Lysz, TW Zelenka, PS AF Haque, MSR Arora, JK Dikdan, G Lysz, TW Zelenka, PS TI The rabbit lens epithelial cell line N/N1003A requires 12-lipoxygenase activity for DNA synthesis in response to EGF SO MOLECULAR VISION LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ARACHIDONIC-ACID; ALPHA-CRYSTALLIN; LIPOXYGENASE; EXPRESSION; INSULIN; 12(S)-HETE; INHIBITION; PROTEINS AB PURPOSE: Cultured rat lenses and primary human lens epithelial cells (HLECs) express12-lipoxygenase (12-LOX) and require a 12-LOX metabolite of arachidonic acid for growth in response to EGF and insulin. This study seeks to identify an established cell line with these characteristics. METHODS: Immunoblotting was used to screen eight lens epithelial cell lines for 12-LOX expression: the human line, HLE-B3; mouse lines alpha TN4, 17EM15, 21EM15, and MLE6, and rabbit lines N/N1003A, LEP2 and B3. DNA synthesis was measured as incorporation of 3H-thymidine into DNA. Expression of c-fos mRNA was detected by RT-PCR. The involvement of 12-lipoxygenase metabolites was determined using the lipoxygenase inhibitors baicalein, cinnamyl 3,4-dihydroxy-alpha-cyanocinnamate (CDC), or nordihydroguiairetic acid (NDGA). RESULTS: 12-LOX was detected only in the rabbit lines N/N1003A, LEP2 and B3. N/N1003A cells were chosen for further study. 12-LOX inhibitors blocked DNA synthesis in response to EGF with or without insulin. Inhibition of EGF-stimulated DNA synthesis was reversed by 0.3 mu M to 3 mu M 12(S)hydroxyeicosatetraenoic acid (HETE), but not by equivalent concentrations of 5(S)HETE, 8(S)HETE, 15(S)HETE, or 12(R)HETE. Baicalein prevented EGF induction of c-fos mRNA. The transformed HLEC line, HLE-B3, showed little stimulation of DNA synthesis in response to EGF and was unaffected by the presence of 12-LOX inhibitors. CONCLUSIONS: N/N1003A cells, like primary cultured human lens epithelial cells or neonatal rat lenses, require 12-LOX activity for EGF dependent growth. This line will be useful for studies of the mechanism of action of 12(S)HETE. C1 NEI, NIH, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg Anat & Cell Biol, Newark, NJ 07103 USA. RP Zelenka, PS (reprint author), NEI, NIH, Mol & Dev Biol Lab, Bldg 6,Rm 214,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 15 PY 1999 VL 5 IS 8 BP U1 EP U6 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 240JV UT WOS:000082823600001 ER PT J AU Osaki, E Nishina, Y Inazawa, J Copeland, NG Gilbert, DJ Jenkins, NA Ohsugi, M Tezuka, T Yoshida, M Semba, K AF Osaki, E Nishina, Y Inazawa, J Copeland, NG Gilbert, DJ Jenkins, NA Ohsugi, M Tezuka, T Yoshida, M Semba, K TI Identification of a novel Sry-related gene and its germ cell-specific expression SO NUCLEIC ACIDS RESEARCH LA English DT Article ID AUTOSOMAL SEX REVERSAL; DROSOPHILA FISH-HOOK; DNA-BINDING MOTIF; CAMPOMELIC DYSPLASIA; HIRSCHSPRUNG-DISEASE; TRANSCRIPTION FACTOR; DETERMINING REGION; SOX10 MUTATIONS; COLLAGEN GENE; MOUSE MODEL AB Sox family proteins are characterized by a unique DNA-binding domain, a HMG box which shows at least 50% sequence similarity with mouse Sry, the sex-determining factor. At present almost 30 Sox genes have been identified, Members of this family have been shown to be conserved during evolution and to play key roles during animal development. Some are involved in human diseases, including sex reversal. Here we report the isolation of a novel member of the Sox gene family, Sox30, which may constitute a distinct subgroup of this family, Using a bacterially expressed DNA-binding domain of Sox30, we show that it is able to specifically recognize the ACAAT motif. Furthermore, Sox30 is capable of activating transcription from a synthetic promoter containing the ACAAT motif. The specific expression of Sox30 in normal testes, but not in maturing germ cell-deficient testes, suggests the involvement of Sox30 in differentiation of male germ cells. Mapping analyses revealed that the Sox30 gene is located on human chromosome 5 (5q33) and on mouse chromosome 11. C1 Univ Tokyo, Inst Med Sci, Dept Cell & Mol Biol, Minato Ku, Tokyo 1088639, Japan. Univ Tokyo, Inst Med Sci, Dept Oncol, Minato Ku, Tokyo 1088639, Japan. Yokohama City Univ, Grad Sch Integrated Sci, Dept Biol, Kanazawa Ku, Yokohama, Kanagawa 2360027, Japan. Yokohama City Univ, Fac Sci, Kanazawa Ku, Yokohama, Kanagawa 2360027, Japan. Tokyo Med & Dent Univ, Inst Med Res, Div Genet, Dept Mol Cytogenet,Bunkyo Ku, Tokyo 1138519, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Semba, K (reprint author), Univ Tokyo, Inst Med Sci, Dept Cell & Mol Biol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM ksemba@ims.u-tokyo.ac.jp NR 51 TC 44 Z9 52 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1999 VL 27 IS 12 BP 2503 EP 2510 DI 10.1093/nar/27.12.2503 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208BC UT WOS:000080969500009 PM 10359848 ER PT J AU Balajee, AS May, A Bohr, VA AF Balajee, AS May, A Bohr, VA TI DNA repair of pyrimidine dimers and 6-4 photoproducts in the ribosomal DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-POLYMERASE-I; CHINESE-HAMSTER CELLS; ULTRAVIOLET-LIGHT; ALKYLATING-AGENTS; HUMAN NUCLEI; GENES; TRANSCRIPTION; DAMAGE; SITES; VISUALIZATION AB The nucleolus is a unique structural component of interphase nuclei where the ribosomal genes, transcribed by RNA polymerase I (RNA pol I), are organized. In the present study, the repair of UV-induced photolesions was investigated in the ribosomal DNA (rDNA) in relation to RNA pol I transcription. We used hamster cells because their repair phenotype permits the separate analysis of the major photoproducts induced by UV light, Immunofluorescent labeling of UV-induced DNA repair and transcription sites showed that the nucleolar regions were deficient in DNA repair despite the presence of abundant RNA pol I transcription foci, Immunological staining indicated that various NER proteins, including TFIIH (subunits p62 and p89), p53, Gadd 45 and proliferating cell nuclear antigen are all enriched in the nuclei but distinctly absent in nucleoli, This lack of enrichment of NER factors in the nucleolus may be responsible for the inefficient repair of photoproducts in the rDNA, UV irradiation generates two major photoproducts, the cyclobutane pyrimidine dimers (CPDs) and the 6-4 photoproducts (6-4 PPs), The repair kinetics of these two lesions were assessed simultaneously by the immunological isolation of bromodeoxyuridine (BudR) containing excision repair patches using an antibody to BudR, We found that the repair of the photolesions was less efficient in the rDNA compared to that of the endogenous housekeeping gene, dihydrofolate reductase (DHFR). Gene specific repair of each of these two photoproducts was then measured separately in the rDNA and in the DHFR gene, which is transcribed by RNA poi II, The removal of CPDs was deficient in the rDNA as compared to the DHFR gene, On the contrary, 6-4 PPs were removed efficiently from the rDNA although somewhat slower than from the DHFR gene. The relatively efficient repair of 6-4 PPs in the rDNA is consistent with the notion that the 6-4 PPs are repaired efficiently in different genomic regions by the global genome repair pathway. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Genet Mol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 15 Z9 15 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1999 VL 27 IS 12 BP 2511 EP 2520 DI 10.1093/nar/27.12.2511 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208BC UT WOS:000080969500010 PM 10352180 ER PT J AU Choi, SC Lee, YJ AF Choi, SC Lee, YJ TI Interim analyses with delayed observations in clinical trials SO STATISTICS IN MEDICINE LA English DT Article AB The interim analyses based on group sequential procedures are not convenient if the response time relative to the patient accrual rate is long. Since in most trials patients are accrued and randomized continuously, the response data from those already randomized will continue to accumulate when a trial terminates at an interim test. One should analyse all observations received after the trial terminates along with the data that led to the decision to terminate the trial. Although the most likely case is that the combined results are significant, it could happen that the combined results are not significant. We examined the likelihood of such an event, Our study indicated that the O'Brien-Fleming type of group sequential tests with conservative boundaries in the early stages protects from such an unsettling event. (C) 1999 John Wiley & Sons, Ltd. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Biostat, Richmond, VA 23298 USA. NICHHD, Biometry & Math Stat Branch, Div Prevent Res, Bethesda, MD 20892 USA. RP Choi, SC (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Biostat, Box 980032, Richmond, VA 23298 USA. NR 15 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1999 VL 18 IS 11 BP 1297 EP 1306 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 204LA UT WOS:000080764700001 PM 10399197 ER PT J AU Lubkowski, J Hennecke, F Pluckthun, A Wlodawer, A AF Lubkowski, J Hennecke, F Pluckthun, A Wlodawer, A TI Filamentous phage infection: crystal structure of g3p in complex with its coreceptor, the C-terminal domain of TolA SO STRUCTURE LA English DT Article DE phage display; phage infection; protein fusion; protein structure; structure refinement ID TONB-EXBB-EXBD; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; PERIPLASMIC PROTEINS; ADSORPTION PROTEIN; OUTER-MEMBRANE; GENE-PRODUCTS; COAT PROTEIN; FD; BACTERIOPHAGES AB Background: Infection of male Escherichia coli cells by filamentous Ff bacteriophages (M13, fd, and f1) involves interaction of the phage minor coat gene 3 protein (g3p) with the bacterial F pilus (primary receptor), and subsequently with the integral membrane protein TolA (coreceptor). G3p consists of three domains (N1, N2, and CT). The N2 domain interacts with the F pilus, whereas the N1 domain - connected to N2 by a flexible glycine-rich linker and tightly interacting with it on the phage - farms a complex with the C-terminal domain of TolA at later stages of the infection process. Results: The crystal structure of the complex between g3p N1 and TolA D3 was obtained by fusing these domains with a long flexible linker, which was not visible in the structure, indicating its very high disorder and presumably a lack of interference with the formation of the complex. The interface between both domains, corresponding to similar to 1768 Angstrom(2) of buried molecular surface, is clearly defined. Despite the lack of topological similarity between TolA D3 and g3p N2, both domains interact with the same region of the g3p N1 domain. The fold of TolA D3 is not similar to any previously known protein motifs. Conclusions: The structure of the fusion protein presented here clearly shows that, during the infection process, the g3p N2 domain is displaced by the TolA D3 domain. The folds of g3p N2 and TolA D3 are entirely different, leading to distinctive interdomain contacts observed in their complexes with g3p N1. We can now also explain how the interactions between the g3p N2 domain and the F pilus enable the g3p N1 domain to form a complex with TolA. C1 NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. RP Lubkowski, J (reprint author), NCI, Macromol Struct Lab, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI Pluckthun, Andreas/C-2746-2009 OI Pluckthun, Andreas/0000-0003-4191-5306 NR 64 TC 107 Z9 110 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD JUN 15 PY 1999 VL 7 IS 6 BP 711 EP 722 DI 10.1016/S0969-2126(99)80092-6 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 208AB UT WOS:000080967100014 PM 10404600 ER PT J AU Yeh, SY AF Yeh, SY TI Effects of antihistamines on fenfluramine-induced depletion of indoles in the brain of rats SO SYNAPSE LA English DT Article DE fenfluramine; neurotoxicity; chlorpheniramine; diphenhydramine; tripelennamine; pyrilamine; antihistamine ID SEROTONIN NEUROTOXICITY; D-NORFENFLURAMINE; UPTAKE INHIBITORS; DOSE-RESPONSE; DEXFENFLURAMINE; HYPERTHERMIA; MICRODIALYSIS; TEMPERATURES; HYPOTHERMIA; MECHANISMS AB Various effects of chlorpheniramine (CPA), diphenhydramine (DIPH), tripelennamine (TRIP), and pyrilamine (PYRI) on fenfluramine (FEN)-induced depletion of serotonin in the brain of rats were observed to be dependent on body temperature. Levels of 5-HT and 5-HIAA in the frontal cortex, hippocampus, and striatum of rats treated with FEN (10 mg/kg, once or twice daily x 4 days) decreased to approximately 30% (P < 0.01) that of controls with no significant changes after CPA, DIPH, TRIP, and PYRI. Treatment with FEN plus CPA (5, 10, 20 mg/kg) and FEN plus DIPH (20 mg/kg), but not FEN plus TRIP (20 mg/kg) and FEN plus PYRI (20 mg/kg), increased brain serotonin levels 2- to S-fold more than those treated with FEN plus saline. Treatment with FEN plus CPA and FEN plus DIPH, but not FEN plus TRIP and FEN plus PYRI, decreased rectal temperature with no significant change after FEN. The antihistamines alone decreased temperature at a 1-hour period and enhanced FEN-induced reduction in body weight. Possible mechanisms of the different effects of antihistamines on FEN-induced depletion of serotonin are discussed. C1 NIDA, Addict Res Ctr, Mol Neuropsychiat Sect,Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Yeh, SY (reprint author), NIDA, Addict Res Ctr, Mol Neuropsychiat Sect,Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 51 TC 4 Z9 4 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN 15 PY 1999 VL 32 IS 4 BP 301 EP 311 DI 10.1002/(SICI)1098-2396(19990615)32:4<301::AID-SYN6>3.0.CO;2-G PG 11 WC Neurosciences SC Neurosciences & Neurology GA 193JH UT WOS:000080131800006 PM 10332805 ER PT J AU Kannell, WB D'Agostino, RB Silbershatz, H Belanger, AJ Wilson, PWF Levy, D AF Kannell, WB D'Agostino, RB Silbershatz, H Belanger, AJ Wilson, PWF Levy, D TI Profile for estimating risk of heart failure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; FRAMINGHAM; CAPTOPRIL; SURVIVAL AB Context: We devised a risk appraisal function to assess the hazard of heart failure in persons who are predisposed by coronary disease, hypertension, or valvular heart disease. Objective: To provide general practitioners and internists with a cost-effective method to select people at high risk who are likely to have impaired left ventricular systolic function and may therefore require further evaluation and aggressive preventive measures. Methods: The routinely measured risk factors used in constructing the heart failure profile include age, electrocardiographic left ventricular hypertrophy, cardiomegaly on chest x-ray film, heart rate, systolic blood pressure, vital capacity, diabetes mellitus, evidence of myocardial infarction, and valvular disease or hypertension. Based on 486 heart failure cases during 38 years of follow-up, 4-year probabilities of failure were computed using the pooled logistic regression model for each sex; a simple point score system was employed. A multivariate profile was also produced without the vital capacity or chest x-ray film because these may not be readily available in some clinical settings. Results: Using the risk factors that make up the multivariate risk formulation-derived from ordinary office procedures-the probability of developing heart failure can be estimated and compared with the average risk for persons of the same age and sex. Using this risk profile, 60% of events in men and 73% in women occurred in subjects in the top quintile of multivariate risk. Conclusions: Using this multivariate risk formulation, it is possible to identify high-risk candidates for heart failure who are likely to have a substantial yield of positive findings when tested for objective evidence of presymptomatic left ventricular dysfunction. The risk profile may also identify candidates who are at high risk for heart failure because of multiple, marginal risk factor abnormalities that might otherwise be overlooked. C1 Boston Univ, Sch Med, Evans Dept Clin Res, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Kannell, WB (reprint author), Boston Univ, Sch Med, 5 Thurber St, Framingham, MA 01701 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 14 TC 193 Z9 196 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 14 PY 1999 VL 159 IS 11 BP 1197 EP 1204 DI 10.1001/archinte.159.11.1197 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 205LX UT WOS:000080823800007 PM 10371227 ER PT J AU Kokate, TG Juhng, KN Kirkby, RD Llamas, J Yamaguchi, S Rogawski, MA AF Kokate, TG Juhng, KN Kirkby, RD Llamas, J Yamaguchi, S Rogawski, MA TI Convulsant actions of the neurosteroid pregnenolone sulfate in mice SO BRAIN RESEARCH LA English DT Article DE neurosteroid; pregnenolone sulfate; NMDA receptor; GABA(A) receptor; seizure ID D-ASPARTATE RECEPTOR; PROGESTERONE METABOLITE 5-ALPHA-PREGNAN-3-ALPHA-OL-20-ONE; GABA-A RECEPTOR; NEUROACTIVE STEROIDS; HIPPOCAMPAL-NEURONS; NMDA-ANTAGONIST; POTENTIATION; MODULATION; SEIZURES; COMPLEX AB Pregnenolone sulfate (PS) is an endogenous neurosteroid known to antagonize GABA(A) receptor-mediated inhibitory responses and potentiate NMDA receptor-mediated excitatory responses in vitro. To assess the actions of the steroid as a modulator of seizure susceptibility in vivo, PS (30-300 nmol) was administered intracerebroventricularly in mice. At doses of 50 to 150 nmol, PS elicited seizures characterized by head jerks, rearing and falling, severe forelimb and hindlimb clonus, opisthotonos and explosive running. The seizures increased in severity and frequency with time and eventually progressed to status epilepticus, tonic hindlimb extension and death. The doses producing convulsions in 50% (CD50) and 97% (CD97) of animals were 92 and 205 nmol, respectively. A subconvulsant dose of PS (50 nmol) significantly increased the convulsant potencies of systemically administered pentylenetetrazol (30-50 mg/kg) and NMDA (50-100 mg/kg). Systemically administered PS at doses as high as 100 mg/kg failed to induce seizures or alter the convulsant potencies of pentylenetetrazol and NMDA. Protection against PS (205 nmol)-induced seizures and lethality was conferred by the GABA(A) receptor positive allosteric modulators clonazepam and allopregnanolone, and by the NMDA receptor antagonists dizocilpine and (R)-CPP. The overall pharmacological profile suggests that the convulsant actions of PS are mediated predominantly via its effects on GABA(A) receptors, and also possibly by effects on NMDA receptors. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 38 TC 36 Z9 37 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 JUN 12 PY 1999 VL 831 IS 1-2 BP 119 EP 124 DI 10.1016/S0006-8993(99)01287-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 207MB UT WOS:000080939700013 PM 10411990 ER PT J AU Fisher, B Dignam, J Wolmark, N Wickerham, DL Fisher, ER Mamounas, E Smith, R Begovic, M Dimitrov, NV Margolese, RG Kardinal, CG Kavanah, MT Fehrenbacher, L Oishi, RH AF Fisher, B Dignam, J Wolmark, N Wickerham, DL Fisher, ER Mamounas, E Smith, R Begovic, M Dimitrov, NV Margolese, RG Kardinal, CG Kavanah, MT Fehrenbacher, L Oishi, RH TI Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial SO LANCET LA English DT Article ID CARCINOMA IN-SITU; RADIATION-THERAPY; RECEPTORS; ESTROGEN; LUMPECTOMY; INSITU; PROGESTERONE; FAILURE; DMBA; P53 AB Background: We have shown previously that lumpectomy with radiation therapy was more effective than lumpectomy alone for the treatment of ductal carcinoma in situ (DCIS). We did a double-blind randomised controlled trial to find out whether lumpectomy, radiation therapy, and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS. Methods: 1804 women with DCIS, including those whose resected sample margins were involved with tumour, were randomly assigned lumpectomy, radiation therapy (50 Gy), and placebo (n = 902), or lumpectomy, radiation therapy, and tamoxifen (20 mg daily for 5 years, n = 902). Median follow-up was 74 months (range 57-93), We compared annual event rates and cumulative probability of invasive or non-invasive ipsilateral and contralateral tumours over 5 years. Findings: Women in the tamoxifen group had fewer breast-cancer events at 5 years than did those on placebo (8.2 vs 13.4%, p = 0 0009). The cumulative incidence of all invasive breast-cancer events in the tamoxifen group was 4.1% at 5 years: 2.1% in the ipsilateral breast, 1.8% in the contralateral breast, and 0.2% at regional or distant sites. The risk of ipsilateral-breast cancer was lower in the tamoxifen group even when sample margins contained tumour and when DCIS was associated with comedonecrosis. Interpretation: The combination of lumpectomy, radiation therapy, and tamoxifen was effective in the prevention of invasive cancer. C1 Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, NSABP Biostat Ctr, Pittsburgh, PA 15260 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Shadyside Hosp, Inst Pathol, Pittsburgh, PA 15232 USA. Mt Sinai Ctr Breast Hlth, Cleveland, OH USA. Michigan State Univ, E Lansing, MI 48824 USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Boston Med Ctr, Boston, MA USA. Kaiser Permanente, No Calif Reg, Oakland, CA USA. Univ Hawaii, Honolulu, HI USA. RP Fisher, B (reprint author), Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Suite 602, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-37377, U10-CA-12027, U10-CA-69651] NR 26 TC 601 Z9 634 U1 0 U2 7 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 12 PY 1999 VL 353 IS 9169 BP 1993 EP 2000 DI 10.1016/S0140-6736(99)05036-9 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 205GD UT WOS:000080812200008 PM 10376613 ER PT J AU Biesecker, LG Happle, R Mulliken, JB Weksberg, R Graham, JM Viljoen, DL Cohen, MM AF Biesecker, LG Happle, R Mulliken, JB Weksberg, R Graham, JM Viljoen, DL Cohen, MM TI Proteus syndrome: Diagnostic criteria, differential diagnosis, and patient evaluation SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE connective tissue nevus; epidermal nevus; hyperostosis; megaspondylodysplasia; disproportionate overgrowth; Klippel-Trenaunay syndrome; hemihyperplasia multiple lipomatosis syndrome ID ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; SOMATIC MOSAICISM; CLASSIFICATION; TRANSMISSION; PHENOTYPE; NEOPLASMS; SKIN; NEVI; SON AB Proteus syndrome is a complex disorder comprising malformations and overgrowth of multiple tissues. The disorder is highly variable and appears to affect patients in a mosaic manner. This intrinsic variability has led to diagnostic confusion associated with a dearth of longitudinal data on the natural history of Proteus syndrome, To clarify some of these issues, a workshop on Proteus syndrome was held in March 1998 at the National Institutes of Health, and participants developed recommendations for diagnostic criteria, differential diagnosis, and guidelines for the evaluation of patients, This is a review of those recommendations. Am, J, Med, Genet. 84:389-395, 1999, (C) 1999 Wiley-Liss, Inc. C1 Dalhousie Univ, Dept Oral & Maxillofacial Sci, Halifax, NS B3H 3J5, Canada. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Marburg, Dept Dermatol, Marburg, Germany. Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA. Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med,Ahmanson Dept Pediat, Med Genet Birth Defects Ctr, Los Angeles, CA 90048 USA. Univ Cape Town, Sch Med, Dept Human Genet, ZA-7925 Cape Town, South Africa. Dalhousie Univ, Dept Pediat, Halifax, NS B3H 3J5, Canada. Dalhousie Univ, Dept Epidemiol & Community Hlth, Halifax, NS B3H 3J5, Canada. Dalhousie Univ, Dept Hlth Serv Adm, Halifax, NS B3H 3J5, Canada. Dalhousie Univ, Dept Sociol & Social Anthropol, Halifax, NS B3H 3J5, Canada. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Steven Spielberg Pediat Res Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med,Int Skeletal Dysplasia Registry, SHARES Child Disabil Ctr,Univ Affiliated Program, Los Angeles, CA 90048 USA. RP Cohen, MM (reprint author), Dalhousie Univ, Dept Oral & Maxillofacial Sci, Halifax, NS B3H 3J5, Canada. EM remaclea@is.dal.ca FU NICHD NIH HHS [P01 HD22657-06]; NIGMS NIH HHS [GM08243] NR 35 TC 239 Z9 248 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 11 PY 1999 VL 84 IS 5 BP 389 EP 395 DI 10.1002/(SICI)1096-8628(19990611)84:5<389::AID-AJMG1>3.0.CO;2-O PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 198WT UT WOS:000080447800001 PM 10360391 ER PT J AU Khachigian, LM Santiago, FS Rafty, LA Chan, OLW Delbridge, GJ Bobik, A Collins, T Johnson, AC AF Khachigian, LM Santiago, FS Rafty, LA Chan, OLW Delbridge, GJ Bobik, A Collins, T Johnson, AC TI GC factor 2 represses platelet-derived growth factor A-chain gene transcription and is itself induced by arterial injury SO CIRCULATION RESEARCH LA English DT Article DE GC factor 2; platelet-derived growth factor-A; DNA binding protein; transcription; injury ID SMOOTH-MUSCLE CELLS; TUMOR-SUPPRESSOR WT1; VASCULAR ENDOTHELIAL-CELLS; RAT CAROTID-ARTERY; TRANSFORMING GROWTH-FACTOR-BETA-1; BALLOON INJURY; FACTOR-I; MOLECULAR-CLONING; PROMOTER ACTIVITY; BINDING FACTOR AB Platelet-derived growth factor (PDGF) is a mitogen and chemoattractant for a wide variety of cell types. The genes encoding PDGF A chain (PDGF-A) and PDGF B chain(PDGF-B) reside on separate chromosomes and are independently regulated at the level of transcription. Regulatory events underlying inducible PDCF-A expression have been the focus of much investigation However, mechanisms that inhibit transcription of this gene are not well understood. In this study, we report the capacity of a newly cloned DNA binding factor, GC factor:! (GCF2), to repress expression driven by the human PDGF-A promoter. 5' Deletion and transient cotransfection analysis in vascular endothelial cells revealed that GCF2 repression is mediated by a nucleotide region located in the proximal region of the PDCF-A promoter. Electrophoretic mobility shift assays demonstrate that GCF2 binds to this region in a specific and dose-dependent manner. Interestingly, the site bound by GCF2 overlaps those for specificity protein-1 (Spl) and early growth response factor-1 (Egr-1), zinc finger transcription factors that direct basal and inducible expression of the PDGF-A gene. Gel shift experiments revealed that GCF2. competes with these factors for interaction with the PDGF-A promoter. Overexpression of GCF2 suppressed endogenous PDGF-A expression in vascular endothelial cells and smooth muscle cells. GCF2 was induced on mechanical injury of cells in culture as well as after balloon injury of the rat carotid artery wall. Time course studies revealed the sustained induction of GCF2 after injury while PDGF-A levels sharply returned to baseline. Smooth muscle cell proliferation was inhibited by GCF2, an effect reversed by the addition of exogenous PDGF-AA. These findings demonstrate negative regulation of PDGF-A expression by GCF2. This is the first report of the induction of an endogenous transcriptional repressor in the rat vessel wall. C1 Univ New S Wales, Sch Pathol, Ctr Thrombosis & Vasc Res, Sydney, NSW 2052, Australia. Prince Wales Hosp, Dept Haematol, Sydney, NSW, Australia. Baker Med Res Inst, Prahran, Vic, Australia. Brigham & Womens Hosp, Div Vasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Khachigian, LM (reprint author), Univ New S Wales, Sch Pathol, Ctr Thrombosis & Vasc Res, Sydney, NSW 2052, Australia. FU NHLBI NIH HHS [HL35716] NR 62 TC 40 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 11 PY 1999 VL 84 IS 11 BP 1258 EP 1267 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 207BR UT WOS:000080915900004 PM 10364563 ER PT J AU Martin, C Hartley, R Mauguen, Y AF Martin, C Hartley, R Mauguen, Y TI X-ray structural analysis of compensating mutations at the barnase-barstar interface SO FEBS LETTERS LA English DT Article DE protein-protein recognition; compensating mutation; RNase-inhibitor complex; X-ray crystallography ID 3-DIMENSIONAL SOLUTION STRUCTURE; MAGNETIC-RESONANCE SPECTROSCOPY; INTRACELLULAR INHIBITOR; MOLECULAR REPLACEMENT; CRYSTALLIZATION; RECOGNITION; CRYSTALS; PROTEINS AB The crystal structure of the barstar mutants (Y29P) and (Y29D, Y30W) as well as that of the complexes of barstar(Y29P) with mild-type barnase and barnase(H102K) have been determined, These barstar mutants compensate for the dramatic loss of barnase-barstar interaction energy caused by a single mutation of the barnase active site His-102 to a lysine. The latter introduces an uncompensated charge in the pocket at the surface of barstar where Lys-102 is located. The analysis of the structures suggests a mechanism for this compensation based on the solvation of the charge of Lys-102. Additional compensation occurs through the formation of a hydrogen bond. (C) 1999 Federation of European Biochemical Societies. C1 Ctr Etud Pharmaceut, Phys Lab, F-92296 Chatenay Malabry, France. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mauguen, Y (reprint author), Ctr Etud Pharmaceut, Phys Lab, Rue JB Clement, F-92296 Chatenay Malabry, France. NR 35 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 11 PY 1999 VL 452 IS 3 BP 128 EP 132 DI 10.1016/S0014-5793(99)00621-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 207UK UT WOS:000080954000003 PM 10386576 ER PT J AU Ma, JX Zhang, DC Laser, M Brownlee, NA Re, GG Hazen-Martin, DJ Redmond, TM Crouch, RK AF Ma, JX Zhang, DC Laser, M Brownlee, NA Re, GG Hazen-Martin, DJ Redmond, TM Crouch, RK TI Identification of RPE65 in transformed kidney cells SO FEBS LETTERS LA English DT Article DE COS cell; kidney; retinal pigment epithelium; retinoid; RPE65; tumor ID RETINAL-PIGMENT EPITHELIUM; ACID RECEPTOR-BETA; BINDING PROTEIN; MEMBRANE-RECEPTOR; CONGENITAL AMAUROSIS; MICROSOMAL PROTEIN; MOLECULAR-CLONING; RETINOIDS; EXPRESSION; EMBRYOGENESIS AB The protein RPE65 has an important role in retinoid processing and/or retinoid transport in the eye, Retinoids are involved in cell differentiation, embryogenesis and carcinogenesis. Since the kidney is known as an important site for retinoid metabolism, the expression of RPE65 in normal kidney and transformed kidney cells has been examined, The RPE65 mRNA was detected in transformed kidney cell lines including the human embryonic kidney cell line HEK293 and the African green monkey kidney cell lines COS-1 and COS-7 by reverse transcription PCR, In contrast, it was not detected in human primary kidney cells or monkey kidney tissues under the same PCR conditions. The RPE65 protein was also identified in COS-7 and HEK293 cells by Western blot analysis using a monoclonal antibody to RPE65, but not in the primary kidney cells or kidney tissues. The RPE65 cDNA containing the full-length encoding region was amplified from HEK293 and COS-7 cells. DNA sequencing showed that the RPE65 cDNA from HEK293 cells is identical to the RPE65 cDNA from the human retinal pigment epithelium. The RPE65 from COS-7 cells shares 98 and 99% sequence identity with human RPE65 at the nucleotide and amino acid levels, respectively. Moreover, the RPE65 mRNA was detected in three out of four renal tumor cultures analyzed including congenital mesoblastic nephroma and clear cell sarcoma of the kidney. These results demonstrated that transformed kidney cells express this retinoid processing protein, suggesting that these transformed tells may have an alternative retinoid metabolism not present in normal kidney cells. (C) 1999 Federation of European Biochemical Societies. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ma, JX (reprint author), Med Univ S Carolina, Dept Ophthalmol, 7th Floor,167 Ashley Ave, Charleston, SC 29425 USA. OI Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [EY04939, EY122301] NR 46 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 11 PY 1999 VL 452 IS 3 BP 199 EP 204 DI 10.1016/S0014-5793(99)00606-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 207UK UT WOS:000080954000017 PM 10386590 ER PT J AU Gong, MK Cowan, KH Gudas, J Moscow, JA AF Gong, MK Cowan, KH Gudas, J Moscow, JA TI Isolation and characterization of genomic sequences involved in the regulation of the human reduced folate carrier gene (RFC1) SO GENE LA English DT Article DE cell cycle regulation; leucovorin; methotrexate; trimetrexate ID BREAST-CANCER CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; METHOTREXATE RESISTANCE; TRANSPORT-DEFICIENT; MULTIPLE PROMOTERS; MESSENGER-RNA; L1210 CELLS; EXPRESSION; LINE; CDNA AB Decreased reduced folate carrier (RFC) activity has been associated with MTX resistance in experimental models of transport-mediated MTX resistance, and has been attributed to changes in the expression of RFC1, the gene that encodes a protein with this activity. RNA transcripts of RFC1 may contain any one of four distinct 5' untranslated regions (UTRs). We cloned a human genomic DNA fragment upstream from the RFC1 translation start site and determined the nucleotide sequence of a 4.8 kb region that contained the exons corresponding to each of the reported UTRs. To identify regulatory elements that may be involved in RFC1 transcription, we first developed a semi-quantitative RT-PCR assay using primers specific for each of the 5' UTRs to amplify RNA transcripts containing each of the RFC1 5' exons, and found evidence for differential transcription of RFC1 noncoding exons in tissues, during development, and in MTX-resistant, transport-deficient cells. We also found that RFC1 RNA levels are cell cycle regulated and peak at the G1 to S transition. Then, using a series of RFC1 promoter-reporter fusion constructs, we identified genomic sequences that may be involved in the regulation of expression of exons Ib and Ic of the RFC1 gene. These studies therefore identify regulatory regions of RFC1 promoters and potential models of regulation in which these regions may exert control. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Med Breast Canc Sect, Med Branch, Bethesda, MD 20892 USA. RP Moscow, JA (reprint author), Univ Kentucky, Albert B Chandler Med Ctr, Dept Pediat, Div Pediat Hematol Oncol, Kentucky Clin Room J457,740 S Limestone, Lexington, KY 40536 USA. NR 36 TC 24 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 JUN 11 PY 1999 VL 233 IS 1-2 BP 21 EP 31 DI 10.1016/S0378-1119(99)00166-3 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 211NY UT WOS:000081168100003 PM 10375617 ER PT J AU Darwiche, N Freeman, LA Strunnikov, A AF Darwiche, N Freeman, LA Strunnikov, A TI Characterization of the components of the putative mammalian sister chromatid cohesion complex SO GENE LA English DT Article DE cell cycle; chromosome; PW29; SMC proteins ID SMC PROTEIN COMPLEXES; CHROMOSOME DYNAMICS; DNA-REPLICATION; IDENTIFICATION AB Establishing and maintaining proper sister chromatid cohesion throughout the cell cycle are essential for maintaining genome integrity. To understand how sister chromatid cohesion occurs in mammals, we have cloned and characterized mouse orthologs of proteins known to be involved in sister chromatid cohesion in other organisms. The cDNAs for the mouse orthologs of SMC1(S.c.) and SMC3(S.c.), mSMCB and mSMCD respectively, were cloned and the corresponding transcripts and proteins were characterized, mSMCB and mSMCD are transcribed at similar levels in adult mouse tissues except in testis, which has an excess of mSMCD transcripts. The mSMCB and mSMCD proteins, as well as the PW29 protein, a mouse homolog of Mcd1p(S.c.)/Rad21(S.p.), form a complex similar to cohesin in X. laevis. mSMCB, mSMCD and PW29 protein levels show no significant cell-cycle dependence. The bulk of the mSMCB, mSMCD and PW29 proteins undergo redistribution from the chromosome vicinity to the cytoplasm during prometaphase and back to the chromatin in telophase. This pattern of intracellular localization suggests a complex role for this group of SMC proteins in chromosome dynamics. The PW29 protein and PCNA, which have both been implicated in sister chromatid cohesion, do not colocalize, indicating that these proteins may not function in the same cohesion pathway. Overexpression of a PW29-GFP fusion protein in mouse fibroblasts leads to inhibition of proliferation, implicating this protein and its complex with SMC proteins in the control of mitotic cycle progression. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NICHD, Unit Chromosome Struct & Funct, NIH, Mol Embryol Lab, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHD, Unit Chromosome Struct & Funct, NIH, Mol Embryol Lab, 18T Lib Dr,Room 106, Bethesda, MD 20892 USA. OI Strunnikov, Alexander/0000-0002-9058-2256; Darwiche, Nadine/0000-0002-1862-5426 FU Intramural NIH HHS [Z01 HD001903-11, Z99 AI999999] NR 19 TC 83 Z9 87 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 11 PY 1999 VL 233 IS 1-2 BP 39 EP 47 DI 10.1016/S0378-1119(99)00160-2 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 211NY UT WOS:000081168100005 PM 10375619 ER PT J AU Miyazaki, S Rasmussen, S Imatani, A Diella, F Sullivan, DT Callahan, R AF Miyazaki, S Rasmussen, S Imatani, A Diella, F Sullivan, DT Callahan, R TI Characterization of the Drosophila ortholog of mouse eIF-3p48/INT-6 SO GENE LA English DT Article DE eucaryotic translation initiation factor 3; mammary tumor gene INT6 ID MAMMARY-TUMOR VIRUS; HTLV-I TAX; GENE; INT-6; MELANOGASTER; EXPRESSION; PROTEINS; BINDING AB The mouse mammary tumor virus (MMTV) has been shown to integrate frequently into INT-6 in MMTV-induced mouse mammary tumors. The INT6 gene has been highly conserved through evolution and has recently been shown to encode the p48 component of the eucaryotic translation initiation factor 3 (eIF-3) complex. We report here the isolation of the Drosophila eIF-3p48/INT-6. The gene comprises three exons within 1.8 kb of genomic DNA located at cytogenetic position 73C2 in the Diosophila genome. The 1.5 kb eIF-3p48/INT-6 RNA species encodes a protein composed of 364 amino-acid residues whose sequence is 71% similar to that of the mouse/human eIF-3/INT-6 amino-acid sequence. eIF-3p48/INT-6 RNA is expressed throughout development in Drosophila and the encoded protein is associated with the microsomal subcellular fraction. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA. RP Callahan, R (reprint author), NCI, Tumor Immunol & Biol Lab, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 10 Z9 11 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 JUN 11 PY 1999 VL 233 IS 1-2 BP 241 EP 247 DI 10.1016/S0378-1119(99)00130-4 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 211NY UT WOS:000081168100027 PM 10375641 ER PT J AU Chow, WH Swanson, CA Lissowska, J Groves, FD Sobin, LH Nasierowska-Guttmejer, A Radziszewski, J Regula, J Hsing, AW Jagannatha, S Zatonski, W Blot, WJ AF Chow, WH Swanson, CA Lissowska, J Groves, FD Sobin, LH Nasierowska-Guttmejer, A Radziszewski, J Regula, J Hsing, AW Jagannatha, S Zatonski, W Blot, WJ TI Risk of stomach cancer in relation to consumption of cigarettes, alcohol, tea and coffee in Warsaw, Poland SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID N-NITROSO COMPOUNDS; GASTRIC-CANCER; PROSPECTIVE COHORT; FOLLOW-UP; SMOKING; TOBACCO; POPULATION; CARDIA; ADENOCARCINOMAS; ESOPHAGUS AB To identify reasons for the high incidence rates of stomach cancer in Poland, we conducted a population-based case-control study in Warsaw, Cases were residents aged 21 to 79 years who were newly diagnosed with stomach cancer between March 1, 1994, and April 30, 1997, Controls were randomly selected from Warsaw residents registered at the nationwide Polish Electronic System of Residence Evidency, frequency-matched to cases by age and sex, Information on demographic characteristics; consumption of cigarettes, alcohol, tea and coffee; diet; medical history; family history of cancer; occupational history; and living conditions during adolescence was elicited by trained interviewers using a structured questionnaire. Included were 464 cases (90% of eligible) and 480 controls (87% of eligible). Among men, the risk of stomach cancer was significantly elevated among current smokers (OR = 1.7, 95% CI = 1.1-2.7) but not among former smokers. The excess risk was largely confined to long-term and heavy smokers, with significant 2-fold excess risk among men who smoked 40 or more pack-years. Among women, an 80% increase in risk was observed in both current and former smokers but dose-response trends were less consistent than among men, Alcohol consumption was not clearly related to risk, and no association was found for drinking regular coffee or herbal tea or using milk/cream in coffee or tea. A significant reduction in risk was linked to daily tea drinking among women, but not among men. Our findings confirm an association with cigarette smoking, which is estimated to account for approximately 20% of stomach cancers diagnosed among Warsaw residents during the study period. Published 1999 Wiley-Liss, Inc.(dagger). C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curi Inst Oncol, Warsaw, Poland. Armed Forces Inst Pathol, Div Gastrointestinal Pathol, Washington, DC 20306 USA. Ctr Canc, Div Histopathol, Warsaw, Poland. Ctr Canc, Div Upper Digest Tract Canc, Warsaw, Poland. Ctr Canc, Med Ctr Postgrad Educ, Dept Gastroenterol, Warsaw, Poland. Westat Inc, Rockville, MD USA. Int Epidemiol Inst, Rockville, MD USA. RP Chow, WH (reprint author), NCI, Div Canc Epidemiol & Genet, MSC 7240,6120 Execut Blvd,EPS 8100, Bethesda, MD 20892 USA. OI Lissowska, Jolanta/0000-0003-2695-5799 FU NCI NIH HHS [N01-CP-05626, N02-CP-40501, N02-CP-71103] NR 29 TC 86 Z9 89 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 11 PY 1999 VL 81 IS 6 BP 871 EP 876 DI 10.1002/(SICI)1097-0215(19990611)81:6<871::AID-IJC6>3.0.CO;2-# PG 6 WC Oncology SC Oncology GA 201EC UT WOS:000080581200006 PM 10362132 ER PT J AU Konczalik, P Moss, J AF Konczalik, P Moss, J TI Identification of critical, conserved vicinal aspartate residues in mammalian and bacterial ADP-ribosylarginine hydrolases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE CELLS; RHODOSPIRILLUM-RUBRUM; NITROGENASE ACTIVITY; RIBOSYLATION; RIBOSYLTRANSFERASE; INTEGRIN; PROTEIN; BINDING; SUBSTRATE; LAMININ AB NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyze opposing arms of a putative ADP-ribosylation cycle. ADP-ribosylarsnine hydrolases from mammalian tissues and Rhodospirillum rubrum exhibit three regions of similarity in deduced amino acid sequence. We postulated that amino acids in these consensus regions could be critical for hydrolase function. To test this hypothesis, hydrolase, cloned from rat brain, was expressed as a glutathione S-transferase fusion protein in Escherichia coli and purified by glutathione-Sepharose affinity chromatography. Conserved amino acids in each of these regions were altered by site-directed mutagenesis. Replacement of Asp-60 or Asp-61 with Ala, Gin, or Asn, but not Glu, significantly reduced enzyme activity. The double Asp-60 --> Glu/Asp-61 --> Glu mutant was inactive, as were Asp-60 --> Gln/Asp-61 --> Gln or Asp-60 --> Asn/Asp-61 --> Asn. The catalytically inactive single and double mutants appeared to retain conformation, since they bound ADP-ribose, a substrate analogue and an inhibitor of enzyme activity, with affinity similar to that of the wild-type hydrolase and with the expected stoichiometry of one. Replacing His-65, Arg-139, Asp-285, which are also located in the conserved regions, with alanine did not change specific activity. These data clearly show that the conserved vicinal aspartates 60 and 61 in rat ADP-ribosylarginine hydrolase are critical for catalytic activity, but not for high affinity binding of the substrate analogue, ADP-ribose. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Konczalik, P (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Rm 5N307,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. NR 26 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 1999 VL 274 IS 24 BP 16736 EP 16740 DI 10.1074/jbc.274.24.16736 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204TL UT WOS:000080780400012 PM 10358013 ER PT J AU Nath, A Conant, K Chen, PQ Scott, C Major, EO AF Nath, A Conant, K Chen, PQ Scott, C Major, EO TI Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes - A hit and run phenomenon SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; GENE-EXPRESSION; GLIAL-CELLS; T-CELLS; INDUCTION; DISEASE; INTERLEUKIN-6; DEMENTIA AB The pathological correlates of dementia due to human immunodeficiency virus (HIV) infection are glial cell activation and cytokine dysregulation, These findings occur in the setting of small numbers of productively infected cells within the brain. We determined whether exposure of susceptible cells to Tat protein of HIV could result in the production of select proinflammatory cytokines. In a dose-responsive manner, Tat induced interleukin (IL)-1 beta production in monocytic cells, while astrocytic cells showed an increase in mRNA for IL-1 beta, but had a translation block for IL-1 beta protein production. Conversely, IL-6 protein and mRNA productions were strongly induced in astrocytic cells and minimally in monocytic cells. IL-IP and IL-6 production were independent of tumor necrosis factor-alpha production. An exposure to Tat for a few minutes was sufficient for sustained releases of cytokines for several hours. This prolonged cytokine production is likely maintained by a positive feed back loop of Tat-induced nuclear factor kappa B activation and cytokine production that is independent of extracellular calcium. Thus a transient exposure may be sufficient to initiate a cascade of events resulting in cerebral dysfunction and a "hit and run" approach may be in effect. Hence cross-sectional measurement of viral load in the brain may not be a useful indicator of the role of viral products in the neuropathogenesis of HIV dementia. C1 Univ Kentucky, Dept Neurol, Kentucky Clin, Lexington, KY 40536 USA. Univ Kentucky, Dept Microbiol, Lexington, KY 40536 USA. Univ Kentucky, Dept Immunol, Lexington, KY 40536 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E OW3, Canada. RP Nath, A (reprint author), Univ Kentucky, Dept Neurol, Kentucky Clin, Rm L-445, Lexington, KY 40536 USA. NR 40 TC 243 Z9 250 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 1999 VL 274 IS 24 BP 17098 EP 17102 DI 10.1074/jbc.274.24.17098 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204TL UT WOS:000080780400062 PM 10358063 ER PT J AU Yao, XL Cowan, MJ Gladwin, MT Lawrence, MM Angus, CW Shelhamer, JH AF Yao, XL Cowan, MJ Gladwin, MT Lawrence, MM Angus, CW Shelhamer, JH TI Dexamethasone alters arachidonate release from human epithelial cells by induction of p11 protein synthesis and inhibition of phospholipase A(2) activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROUP-II PHOSPHOLIPASE-A2; CA2+-SENSITIVE CYTOSOLIC PHOSPHOLIPASE-A2; LIPID 2ND MESSENGERS; RAT MESANGIAL CELLS; BINDING PROTEINS; GENE-EXPRESSION; SUBSTRATE; CLONING; FAMILY; RNA AB The effect of the glucocorticosteroid, dexamethasone, on arachidonic acid (AA) release and on protein levels of p11 and cytosolic phospholipase A(2) (cPLA(2)) was studied in two epithelial cell lines, HeLa cells and BEAS-2B cells. Dexamethasone treatment of HeLa cells and BEAS-2B cells increased cellular pll protein and mRNA levels in a time- and dose-dependent manner. It had little effect on levels of cPLA(2) protein. In order to determine if increased pll protein expression resulted in increased interaction between p11 and cPLA(2), anti-cPLA(2) antibodies were used to immunoprecipitate p11.cPLA(2) complexes and Western blots of the immunoprecipitate were used to detect p11, In cells treated with dexamethasone, more p11 was detected in the anti-cPLA(2) immunoprecipitate compared with control cells. Dexamethasone treatment of HeLa cells prelabeled with [H-3]AA decreased the release of [H-3]AA under basal conditions and after stimulation with the calcium ionophore A23187 (10(-6) M). In order to determine if altering the p11 protein levels in HeLa cells independent of glucocorticosteroid treatment could also produce an effect on [H-3]AA release, cells were stably transfected with plasmids expressing either p11 antisense mRNA or p11 mRNA Cloned HeLa cells expressing p11 antisense mRNA exhibited less cellular p11 protein compared with control cells and greater [H-3]AA release compared with cells transfected with a control vector. Cloned HeLa cells stably transfected with a p11 expression vector exhibited increased p11 cellular protein and diminished [H-3]AA release under basal conditions and in response to A23187, Therefore, dexamethasone alteration of epithelial cell AA release may be due in part to induction of p11 protein expression. C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Shelhamer, JH (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10,Rm 7-D-43, Bethesda, MD 20892 USA. NR 44 TC 61 Z9 61 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 1999 VL 274 IS 24 BP 17202 EP 17208 DI 10.1074/jbc.274.24.17202 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204TL UT WOS:000080780400077 PM 10358078 ER PT J AU Jayaraman, G Srinivas, R Duggan, C Ferreira, E Swaminathan, S Somasundaram, K Williams, J Hauser, C Kurkinen, M Dhar, R Weitzman, S Buttice, G Thimmapaya, B AF Jayaraman, G Srinivas, R Duggan, C Ferreira, E Swaminathan, S Somasundaram, K Williams, J Hauser, C Kurkinen, M Dhar, R Weitzman, S Buttice, G Thimmapaya, B TI p300/cAMP-responsive element-binding protein interactions with Ets-1 and Ets-2 in the transcriptional activation of the human stromelysin promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; GENE-EXPRESSION; ONCOGENIC ACTIVITY; ADENOVIRUS E1A; FAMILY MEMBER; C-JUN; P300; CBP; CREB; COACTIVATOR AB In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a.a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP. C1 Northwestern Univ, Sch Med, Lurie Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Microbiol & Immunol, Chicago, IL 60611 USA. CNRS, Inst Biol Lille, F-59021 Lille, France. Burnham Inst, La Jolla, CA 92037 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Thimmapaya, B (reprint author), Northwestern Univ, Sch Med, Lurie Canc Ctr, Div Hematol Oncol, 303 E Chicago Ave, Chicago, IL 60611 USA. RI Duggan, Catherine/F-9414-2015; OI Duggan, Catherine/0000-0001-7369-4021; Swaminathan, Sathyamangalam/0000-0002-4388-2248 FU NCI NIH HHS [CA74403, NCI 1P20CA65764]; NIA NIH HHS [AG11536] NR 76 TC 107 Z9 107 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 1999 VL 274 IS 24 BP 17342 EP 17352 DI 10.1074/jbc.274.24.17342 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204TL UT WOS:000080780400094 PM 10358095 ER PT J AU Chen, HM Wei, SQ Engelman, A AF Chen, HM Wei, SQ Engelman, A TI Multiple integrase functions are required to form the native structure of the human immunodeficiency virus type I intasome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETROVIRAL DNA INTEGRATION; PHOTO-CROSS-LINKING; HIV-1 INTEGRASE; CONCERTED INTEGRATION; PREINTEGRATION COMPLEXES; INVITRO; VITRO; PROTEIN; BINDING; MUTAGENESIS AB Mu-mediated polymerase chain reaction footprinting was used to investigate the protein-DNA structure of human immunodeficiency virus type I (HIV-I) preintegration complexes. Preintegration complexes were partially purified from cells after using an established coculture infection technique as well as a novel technique using cell-free supernatant from transfected cells as the source of virus. Footprinting revealed that bound proteins protected the terminal 200-250 base pairs of each viral end from nuclease attack. Bound proteins also caused strong transpositional enhancements near each end of HIV-I. In contrast, regions of viral DNA internal to the ends did not show evidence of strong protein binding. The end regions of preintegrative HIV-I apparently form a unique nucleoprotein structure, which we term the intasome to distinguish it from the greater preintegration complex. Our novel system also allowed us to analyze the structure and function of preintegration complexes isolated from cells infected with integrase mutant viruses. Complexes were derived from viruses defective for either integrase catalysis, integrase binding to the viral DNA substrate, or an unknown function in the carboxyl-terminal domain of the integrase protein. None of these mutant complexes supported detectable integration activity. Despite the presence of the mutant integrase proteins in purified samples, none of these nucleoprotein complexes displayed the native intasome structure detected in wildtype preintegration complexes. We conclude that multiple integrase functions are required to form the native structure of the HIV-I intasome in infected cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Aids, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394] NR 40 TC 59 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 1999 VL 274 IS 24 BP 17358 EP 17364 DI 10.1074/jbc.274.24.17358 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204TL UT WOS:000080780400096 PM 10358097 ER PT J AU Ellingson, T Duddempudi, S Greenberg, BD Hooper, D Eisenhofer, G AF Ellingson, T Duddempudi, S Greenberg, BD Hooper, D Eisenhofer, G TI Determination of differential activities of soluble and membrane-bound catechol-O-methyltransferase in tissues and erythrocytes SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE catechol-O-methyltransferase; enzymes; catecholamines ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ELECTROCHEMICAL DETECTION; METABOLISM; ALLELE; ASSAY; SCHIZOPHRENIA; ASSOCIATION; GENOTYPE; DIHYDROXYPHENYLALANINE; IDENTIFICATION AB Catechol-O-methyltransferase (COMT) exists as two isoenzymes, a membrane-bound form (MB-COMT) and a soluble form (S-COMT), with different roles in the metabolism of catecholamines and other catechol compounds. This report documents an HPLC assay for separate estimation of S-COMT and MB-COMT activity and examines activities of the two isoezymes among different rat tissues and in human and rat erythrocytes. Activities of MB-COMT and S-COMT varied widely among tissues. There were higher activities of S-COMT than MB-COMT in all tissues except the adrenal medulla where MB-COMT was the predominant isoenzyme, consistent with the importance of this tissue and MB-COMT for the O-methylation of catecholamines. MB-COMT and S-COMT in rat and human erythrocytes showed divergent levels acid patterns of activity. The assay represents a rapid and accurate method for quantifying MB-COMT and S-COMT in various tissues and examining the relative roles of COMT isoenzymes in the metabolism of catechol compounds in health and disease. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Room 6N252, Bethesda, MD 20892 USA. NR 34 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUN 11 PY 1999 VL 729 IS 1-2 BP 347 EP 353 DI 10.1016/S0378-4347(99)00125-5 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 207JC UT WOS:000080932900040 PM 10410961 ER PT J AU Gruschus, JM Tsao, DHH Wang, LH Nirenberg, M Ferretti, JA AF Gruschus, JM Tsao, DHH Wang, LH Nirenberg, M Ferretti, JA TI The three-dimensional structure of the vnd/NK-2 Homeodomain-DNA complex by NMR spectroscopy SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE nuclear magnetic resonance; X-ray crystallography; mutation; DNA-binding specificity; protein-DNA interaction ID MAGNETIC-RESONANCE SPECTROSCOPY; 3-DIMENSIONAL NOESY-HMQC; CENTRAL-NERVOUS-SYSTEM; NK-2 HOMEOBOX GENE; CRYSTAL-STRUCTURE; TRANSCRIPTION FACTOR; ANTENNAPEDIA HOMEODOMAIN; PROTEIN; DROSOPHILA; SPECIFICITY AB The three-dimensional solution structure obtained by NMR of the complex formed between the uniformly singly N-15 and doubly C-13/N-15-labeled vnd/NK-2 homeodomain and its consensus 16 base-pair DNA binding sequence was determined. This work was carried out using the accepted repertoire of experiments augmented with a novel implementation of the water flipback technique to enhance signals from exchangeable amide protons. The results using this new technique confirm the existence of hydrogen bonding between the invariant Asn51 and the second adenine of the DNA binding sequence, as seen in crystal structures of other homeodomain-DNA complexes, but never before detected by NMR. Hydrogen bonding by Arg5 and Lys3 in the minor groove of the DNA appears to be responsible for two unusually upfield-shifted ribose H1' resonances. The DNA duplex is nearly straight and its structure is primarily that of B-DNA. A detailed comparison is presented for all available homeodomain-DNA structures including the vnd/NK-2 DNA complex, which demonstrates that homology is maintained in the protein structure, whereas for the orientation of the homeodomain relative to DNA, small but significant variations are observed. Interactions are described involving certain residues in specific positions of the homeodomain, namely Leu7, Thr41, and Gln50 of vnd/NK-2, where single amino acid residue mutations lead to dramatic developmental alterations. The availability of our previously determined three-dimensional structure of the vnd/NK-2 homeodomain in the absence of DNA allows us to assess structual changes in the homeodomain induced by DNA binding. (C) 1999 Academic Press. C1 NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. Genet Inst, Cambridge, MA 02140 USA. RP Ferretti, JA (reprint author), NHLBI, Biophys Chem Lab, Bldg 10, Bethesda, MD 20892 USA. NR 77 TC 42 Z9 42 U1 1 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 11 PY 1999 VL 289 IS 3 BP 529 EP 545 DI 10.1006/jmbi.1999.2774 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210MT UT WOS:000081109800009 PM 10356327 ER PT J AU Godfrey, VB Chen, LJ Griffin, RJ Lebetkin, EH Burka, LT AF Godfrey, VB Chen, LJ Griffin, RJ Lebetkin, EH Burka, LT TI Distribution and metabolism of (5-hydroxymethyl)furfural in male F344 rats and B6C3F1 mice after oral administration SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID DISPOSITION; 5-HYDROXYMETHYL-2-FURALDEHYDE; EXCRETION AB (5-Hydroxymethyl)furfural (HMF), a heat-induced decomposition product of hexoses, is present in food and drink. Recent reports have shown HMF to be an in vitro mutagen after sulfate conjugation and to be a promoter as well as a weak initiator of colonic aberrant foci in rats, in order to investigate the metabolic activation further and to provide information for HMF toxicology studies, the disposition of [C-14]-HMF has been investigated in male F344 rats and B6C3F1 mice following po administration of either 5, 10, 100, or 500 mg/kg. Tissue distribution results indicated that absorption of HMF was rapid in male rats and mice and that tissue concentrations in male mice at the earliest time point are not linearly proportional to dose. Excretion was primarily via the urine in both, with 60-80% of the administered dose excreted by this route in 48 h. Tissue/blood ratios of HMF-derived radioactivity were greater than I for liver and kidney. Three metabolites were identified and quantitated in urine. Formation of one of the metabolites, N-(5-hydroxymethyl-2-furoyl)glycine, was inversely proportional to dose in rats but not mice. None of the metabolites were sulfate conjugates nor likely to be formed from sulfate conjugates. There were relatively low levels of nonextractable radioactivity in liver, kidney, and intestines, indicating that some reactive intermediate(s) may be formed. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Burka, LT (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 30 Z9 30 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0098-4108 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD JUN 11 PY 1999 VL 57 IS 3 BP 199 EP 210 DI 10.1080/009841099157764 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 200VG UT WOS:000080560300005 PM 10376886 ER PT J AU Shi, SH Hayashi, Y Petralia, RS Zaman, SH Wenthold, RJ Svoboda, K Malinow, R AF Shi, SH Hayashi, Y Petralia, RS Zaman, SH Wenthold, RJ Svoboda, K Malinow, R TI Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation SO SCIENCE LA English DT Article ID LONG-TERM POTENTIATION; CULTURED HIPPOCAMPAL-NEURONS; EVOKED DENDRITIC EXOCYTOSIS; GLUTAMATE RECEPTORS; SILENT SYNAPSES; PHOSPHORYLATION; CA1; LTP; TRANSMISSION; EXPRESSION AB To monitor changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP), This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons, in dendrites visualized with two-photon Laser scanning microscopy or electron microscopy, most of the GluR1-GFP was intracellular, mimicking endogenous GluR1 distribution. Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites. These postsynaptic trafficking events required synaptic N-methyl-D-aspartate (NMDA) receptor activation and may contribute to the enhanced AMPA receptor-mediated transmission observed during long-term potentiation and activity-dependent synaptic maturation. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NIDODS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Malinow, R (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. RI Hayashi, Yasunori/C-2249-2008 OI Hayashi, Yasunori/0000-0002-7560-3004 NR 42 TC 853 Z9 875 U1 4 U2 58 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 11 PY 1999 VL 284 IS 5421 BP 1811 EP 1816 DI 10.1126/science.284.5421.1811 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205EU UT WOS:000080809000042 PM 10364548 ER PT J AU Moriuchi, M Moriuchi, H Fauci, AS AF Moriuchi, M Moriuchi, H Fauci, AS TI HTLV type I tax activation of the CXCR4 promoter by association with nuclear respiratory factor I SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-I; CHEMOKINE RECEPTOR CXCR4; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; DNA-BINDING; HIV-1 ENTRY; TRANSCRIPTION FACTORS; GENOMIC ORGANIZATION; DISEASE PROGRESSION; PROTEIN; INFECTION AB Human T lymphotropic virus type I trans-activator Tax protein regulates expression of several cellular genes that are involved in cellular activation, proliferation, and transformation. Tax mediates its regulatory activity through interaction with cellular transcription factors such as members of the cAMP-responsive element-binding factors/ATF family or the NF-kappa B/Rel family, In this study we have demonstrated that Tax trans-activates the promoter for CXCR4, a coreceptor for T cell-tropic HIV-1 through its association with nuclear respiratory factor 1 (NRF1), The promoter region for CXCR4 contains an NRF1-binding site, which is crucial for basal and Tax-induced activity, Glutathione S-transferase (GST) pull-down experiments showed association of GST-Tax fusion protein,vith NRF1 in vitro. Expression of Tax, in addition to stimulation with phorbol myristate acetate and ionomycin, increased formation of the NRF1 complex in a gel-mobility shift assay, indicating that Tax association with NRF1 in vivo facilitates its DNA binding. HTLV-1 Tax activation of CXCR4 may contribute to the rapid progression of HIV disease observed in certain coinfected individuals. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Moriuchi, H (reprint author), Nagasaki Univ, Sch Med, Dept Pediat, 1-7-1 Sakamoto, Nagasaki 8528501, Japan. NR 43 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN 10 PY 1999 VL 15 IS 9 BP 821 EP 827 DI 10.1089/088922299310728 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 204UZ UT WOS:000080784100005 PM 10381170 ER PT J AU Bedell, BL Goldfarb, L Mysak, ER Samet, C Maynard, A AF Bedell, BL Goldfarb, L Mysak, ER Samet, C Maynard, A TI Matrix isolation infrared and ab initio study of the 1 : 1 complexes of bromocyclopropane with NH3 and (CH3)(3)N: Evidence for a novel C-H center dot center dot center dot N hydrogen bond SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID VIBRATIONAL SPECTROSCOPY; MOLECULAR-COMPLEXES; ROTATIONAL SPECTRUM; SMALL RINGS; CYCLOPROPANE; BASES; AMMONIA; ALKYNES; GEOMETRY; HALIDES AB Hydrogen-bonded complexes of bromocyclopropane with the strong bases ammonia and trimethylamine have been isolated and characterized for the first time in argon matrices at 16 K. Coordination of the proton adjacent to the Br substituent on the cyclopropane ring to the nitrogen of the base was evidenced by distinct blue shifts of the C-H(Br) bending modes in the infrared spectrum. These shifts (similar to 12 cm(-1) for the in-plane bend and similar to 6 cm(-1) for the out-of-plane bend) are much smaller than those observed for alkenes and alkynes, suggesting a distinct but extremely weak interaction. Ab initio calculations yield an essentially linear BrC-H ... NH3 hydrogen bond with a C-H ... N distance of 2.301 Angstrom and a hydrogen bond energy of 2.35 kcal/mol, thus supporting that this hydrogen bond is one of the weakest observed thus far in a matrix. This study represents the first example of a (substituted) cyclopropane acting as a proton donor and only the second example of an alkane taking part in a C-H ... N hydrogen bond. C1 Dickinson Coll, Dept Chem, Carlisle, PA 17013 USA. NCI, Lab Expt & Computat Biol, IRSP, SAIC Frederick,FCRDC, Frederick, MD 21702 USA. RP Samet, C (reprint author), Dickinson Coll, Dept Chem, Carlisle, PA 17013 USA. NR 47 TC 19 Z9 19 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JUN 10 PY 1999 VL 103 IS 23 BP 4572 EP 4579 DI 10.1021/jp990493y PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 206YH UT WOS:000080907800019 ER PT J AU Beldarrain, MG Grafman, J Pascual-Leone, A Garcia-Monco, JC AF Beldarrain, MG Grafman, J Pascual-Leone, A Garcia-Monco, JC TI Procedural learning is impaired in patients with prefrontal lesions SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CARD-SORTING-TEST; FUNCTIONAL-ANATOMY; PARKINSONS-DISEASE; MEMORY; SEQUENCE; IMPLICIT; PET; CEREBELLAR; KNOWLEDGE AB Objectives: To 1) determine the effect of prefrontal cortex lesions on procedural learning (PL), measured by a serial reaction-time task (SRTT); 2) confirm whether visuomotor PL is lateralized to one hemisphere; and 3) clarify the relation between visuomotor sequence learning and verbal sequence learning, working memory, and executive functions. Background: Previous cognitive neuroscience research has implicated the prefrontal cortex in visuomotor PL but there is a lack. of studies examining patients with prefrontal cortex lesions. Methods: We studied 22 patients with strictly unilateral prefrontal cortex lesions (traumatic, ischemic, hemorrhagic, or tumors) and 52 cognitively intact controls matched for age, sex, and educational level. We administered to subjects long (10-item sequence) and short (4-item sequence) versions of the SRTT. With the long version, each hand was evaluated separately. Learning was indicated by the shortening of response times (RT) and decrease in errors across the sequential blocks and, most importantly, the rebound increase in RTs and errors when comparing the last sequence block with the next random block. Frontal lobe functions and verbal sequence learning were also assessed. Results: Patients with unilateral prefrontal cortex lesions show PL impairment that involves both hands, although more errors were observed when the hand contralateral to the lesion was performing. Only those patients whose lesions were >2 cm in diameter were impaired. Neuropsychologic evaluation indicated impaired verbal sequence learning and executive function deficits. Patients with poorer working memory and verbal sequence learning were also more impaired in visuomotor sequence learning. Conclusions: The prefrontal cortex has a role in PL and is part of the neural circuit that mediates this type of learning. C1 Hosp Galdacano, Serv Neurol, Vizcaya 48960, Spain. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Boston, MA 02115 USA. RP Beldarrain, MG (reprint author), Hosp Galdacano, Serv Neurol, Vizcaya 48960, Spain. RI Pascual-Leone, Alvaro/G-6566-2011; OI Grafman, Jordan H./0000-0001-8645-4457 NR 39 TC 34 Z9 35 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 10 PY 1999 VL 52 IS 9 BP 1853 EP 1860 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 204HP UT WOS:000080758500023 ER PT J AU Kwatkowski, TG Libman, RB Frankel, M Tilley, BC Morgenstern, LB Lu, M Broderick, JP Lewandowski, CA Marler, JR Levine, SR Brott, T AF Kwatkowski, TG Libman, RB Frankel, M Tilley, BC Morgenstern, LB Lu, M Broderick, JP Lewandowski, CA Marler, JR Levine, SR Brott, T CA Natl Inst Neurological Disorders Stroke R TI Effects of tissue plasminogen activator for acute ischemic stroke at one year SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID THROMBOLYTIC THERAPY; TELEPHONE INTERVIEW; RELIABILITY; INFARCTION; RECURRENCE; TRIALS; ECASS; SCALE AB Background In 1995, the two-part National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator Stroke Study found that patients who were treated with tissue plasminogen activator (t-PA) within three hours after the onset of symptoms of acute ischemic stroke were at least 30 percent more likely than patients given placebo to have minimal or no disability three months after the stroke. It was unknown, however, whether the benefit would be sustained for longer periods. Methods In the NINDS trial, a total of 624 patients with stroke were randomly assigned to receive either t-PA or placebo. We collected outcome data over a period of 12 months after the occurrence of stroke. The primary outcome measure was a "favorable outcome," defined as minimal or no disability as measured by the Barthel index, the modified Rankin Scale, and the Glasgow Outcome Scale. We assessed the treatment effect using a global statistic. Results Using an intention-to-treat analysis for the combined results of the two parts of the trial at 6 months and 12 months, we found that the global statistic favored the t-PA group (odds ratio for a favorable outcome at 6 months, 1.7; 95 percent confidence interval, 1.3 to 2.3; odds ratio at12 months, 1.7; 95 percent confidence interval, 1.2 to 2.3). The patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at 12 months than were the placebo-treated patients (absolute increase in the proportion with a favorable outcome, 11 to 13 percentage points). There was no significant difference in mortality at 12 months between the t-PA group and the placebo group (24 percent vs. 28 percent, P = 0.29). There was no interaction between the type of stroke identified at base line and treatment with respect to the long-term response. The rate of recurrent stroke at 12 months was similar in the two groups. Conclusions During 12 months of follow-up, the patients with acute ischemic stroke who were treated with t-PA within three hours after the onset of symptoms were more likely to have minimal or no disability than the patients given placebo. These results indicate a sustained benefit of t-PA for such patients. (N Engl J Med 1999;340:1781-7) (C) 1999, Massachusetts Medical Society. C1 Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Park, NY 11040 USA. Long Isl Jewish Med Ctr, Dept Neurol, New Hyde Park, NY 11040 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Univ Texas, Sch Med, Dept Neurol, Houston, TX USA. Henry Ford Hlth Sci Ctr, Dept Biostat & Res Epidemiol, Detroit, MI USA. Henry Ford Hlth Sci Ctr, Dept Emergency Med, Detroit, MI USA. Univ Cincinnati, Med Ctr, Dept Neurol, Cincinnati, OH 45267 USA. NINDS, Div Stroke & Trauma, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Kwatkowski, TG (reprint author), Long Isl Jewish Med Ctr, Dept Emergency Med, 270-05 76th Ave, New Hyde Park, NY 11040 USA. NR 27 TC 22 Z9 23 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 1999 VL 340 IS 23 BP 1781 EP 1787 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 203UU UT WOS:000080726800002 ER PT J AU Wilcox, AJ Baird, DD Wenberg, CR AF Wilcox, AJ Baird, DD Wenberg, CR TI Time of implantation of the conceptus and loss of pregnancy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; URINARY ESTROGEN; PROGESTERONE METABOLITES; INVITRO FERTILIZATION; RADIOIMMUNOASSAY; BLASTOCYST; OVULATION; SECRETION; WINDOW; WOMEN AB Background Implantation of the conceptus is a key step in pregnancy, but little is known about the time of implantation or the relation between the time of implantation and the outcome of pregnancy. Methods We collected daily urine samples for up to six months from 221 women attempting to conceive after ceasing to use contraception. Ovulation was identified on the basis of the ratio of urinary estrogen metabolites to progesterone metabolites, which changes rapidly with luteinization of the ovarian follicle, The time of implantation was defined by the appearance of chorionic gonadotropin in maternal urine. Results There were 199 conceptions, for 95 percent of which (189) we had sufficient data for analysis. Of these 189 pregnancies, 141 (75 percent) lasted at least six weeks past the last menstrual period, and the remaining 48 pregnancies (25 percent) ended in early loss. Among the pregnancies that lasted 6 weeks or more, the first appearance of chorionic gonadotropin occurred 6 to 12 days after ovulation; 118 women (84 percent) had implantation on day 8, 9, or 10, The risk of early pregnancy loss increased with later implantation (P < 0.001), Among the 102 conceptuses that implanted by the ninth day, 13 percent ended in early loss. This proportion rose to 26 percent with implantation on day 10, to 52 percent on day 11, and to 82 percent after day 11. Conclusions In most successful human pregnancies, the conceptus implants 8 to 10 days after ovulation, The risk of early pregnancy loss increases with later implantation. (N Engl J Med 1999;340:1796-9,) (C) 1999, Massachusetts Medical Society. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, MD A3-05, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 34 TC 418 Z9 430 U1 1 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 1999 VL 340 IS 23 BP 1796 EP 1799 DI 10.1056/NEJM199906103402304 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 203UU UT WOS:000080726800004 PM 10362823 ER PT J AU Huang, Y Sheikh, MS Fornace, AJ Holbrook, NJ AF Huang, Y Sheikh, MS Fornace, AJ Holbrook, NJ TI Serine protease inhibitor TPCK prevents Taxol-induced cell death and blocks c-Raf-1 and Bcl-2 phosphorylation in human breast carcinoma cells SO ONCOGENE LA English DT Article DE MAP kinases; TPCK; apoptosis; c-Raf-1; Bcl-2 ID INDUCED APOPTOSIS; POLY(ADP-RIBOSE) POLYMERASE; CYSTEINE PROTEASE; DNA FRAGMENTATION; KINASE ACTIVATION; LEUKEMIA-CELLS; T-LYMPHOCYTES; CANCER CELLS; RAF-1; INVOLVEMENT AB The mechanism of Taxol-induced apoptosis was investigated in MCF-7 human breast carcinoma cells, Taxol-induced apoptosis was associated with phosphorylation of both c-Raf-1 and Bcl-2 and activation of ERK and JNK MAP kinases, The serine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) effectively blocked apoptosis, but N-p-tosyl-L-lysine chloromethyl ketone (TLCK), another serine protease inhibitor, was without effect. TPCK treatment also prevented phosphorylation of c-Raf-1 and Bcl-2 in response to Taxol treatment. The serine protease inhibitor did not alter JNK activity, but it enhanced Taxol-induced activation of ERK1/2 Treatment of cells with the inhibitor of MEK activation, PD98059, prevented Taxol-induced ERK activation both in the presence and absence of TPCK, but did not influence survival of either Taxol- or Taxol plus TPCK-treated cells. In addition, PD98059 had no effect on c-Raf-1 or Bcl-2 phosphorylation, Thus, while the Taxol-induced phosphorylations of c-Raf-1 and Bcl-2 proteins appear to be coupled, these events can be disassociated from ERK1/2 activation, In summary, these findings suggest that phosphorylation of c-Raf-1 and Bcl-2, but not ERK1/2, are important signaling events in Taxol-induced apoptosis of MCF-7 breast cancer cells and that a TPCK inhibitable protease(s) is required for these processes. C1 NIA, Gene Express & Aging Sect, Biol Chem Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Holbrook, NJ (reprint author), NIA, Gene Express & Aging Sect, Biol Chem Lab, Gerontol Res Ctr, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 61 TC 72 Z9 73 U1 0 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 10 PY 1999 VL 18 IS 23 BP 3431 EP 3439 DI 10.1038/sj.onc.1202685 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 205ZF UT WOS:000080850600001 PM 10376521 ER PT J AU Kawai, T Nomura, F Hoshino, K Copeland, NG Gilbert, DJ Jenkins, NA Akira, S AF Kawai, T Nomura, F Hoshino, K Copeland, NG Gilbert, DJ Jenkins, NA Akira, S TI Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity SO ONCOGENE LA English DT Article DE DAP kinase family; calcium/calmodulin-dependent kinase; apoptosis ID SERINE THREONINE KINASE; JUN ACTIVATION DOMAIN; INDUCED CELL-DEATH; C-JUN; DAP-KINASE; IDENTIFICATION; INDUCTION; CASPASES; PHOSPHORYLATES; REQUIREMENT AB We have identified and characterized a new calcium/calmodulin (Ca2+/CaM) dependent protein kinase termed death-associated protein kinase 2 (DAPK2) that contains an N-terminal protein kinase domain followed by a conserved CaM-binding domain with significant homologies to those of DAP kinase, a protein kinase involved in apoptosis, DAPK2 mRNA is expressed abundantly in heart, lung and skeletal muscle. The mapping results indicated that DAPK2 is located in the central region of mouse chromosome 9, bl vitro kinase assay revealed that DAPK2 is autophosphorylated and phosphorylates myosin light chain (MLC) as an exogenous substrate. DAPK2 binds directly to CaM and is activated in a Ca2+/CaM-dependent manner. A constitutively active DAPK2 mutant is generated by removal of the CaM-binding domain (Delta CaM). Treatment of agonists that elevate intracellular Ca2+-concentration led to the activation of DAPK2 and transfection studies revealed that DAPK2 is localized in the cytoplasm. Overexpression of DAPK2, but not the kinase negative mutant, significantly induced the morphological changes characteristic of apoptosis, These results indicate that DAPK2 is an additional member of DAP kinase family involved in apoptotic signaling. C1 Hyogo Coll Med, Dept Biochem, Nishinomiya, Hyogo 6638501, Japan. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Japan Sci & Technol Corp, CREST, Tokyo, Japan. RP Akira, S (reprint author), Hyogo Coll Med, Dept Biochem, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan. RI Akira, Shizuo/C-3134-2009; Hoshino, Katsuaki/L-9162-2014 OI Hoshino, Katsuaki/0000-0003-0493-4815 NR 45 TC 80 Z9 86 U1 0 U2 20 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 10 PY 1999 VL 18 IS 23 BP 3471 EP 3480 DI 10.1038/sj.onc.1202701 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 205ZF UT WOS:000080850600005 PM 10376525 ER PT J AU Park, BC Kido, Y Accili, D AF Park, BC Kido, Y Accili, D TI Differential signaling of insulin and IGF-1 receptors to glycogen synthesis in murine hepatocytes SO BIOCHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; PROTEIN-KINASE-B; GLUCOSE-TOLERANCE; HYBRID RECEPTORS; SKELETAL-MUSCLE; MICE; SYNTHASE; ACTIVATION; SPECIFICITY; STIMULATION AB We have used SV40-transformed hepatocytes from insulin receptor-deficient mice (-/-) and normal mice (WT) to investigate the different abilities of insulin and IGF-1 receptors to stimulate glycogen synthesis. We report that insulin receptors are more potent than IGF-1 receptors in stimulating glycogen synthesis. Both receptors stimulate glycogen synthesis in a PI 3-kinase-dependent manner, but only the effect of insulin receptors is partially rapamycin-dependent. Insulin and IGF-I receptors activate Akt to a similar extent, whereas GSK-3 inactivation in response to IGF-1 is considerably lower in both -/- and WT cells, compared to the effect of insulin in WT cells. The findings indicate that (i) the potency of insulin and IGF-1 receptors in stimulating glycogen synthesis correlates with their ability to inactivate GSK-3, (ii) the extent of GSK-3 inactivation does not correlate with the extent of Akt activation mediated by insulin or IGF-1 receptors, indicating that the effect of insulin on GSK-3 requires additional kinases, and (iii) the pathways required for insulin stimulation of glycogen synthesis in mouse hepatocytes are PI 3-kinase-dependent and rapamycin-sensitive. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Accili, D (reprint author), Room 10D18,Bldg 10, Bethesda, MD 20892 USA. NR 31 TC 35 Z9 35 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 8 PY 1999 VL 38 IS 23 BP 7517 EP 7523 DI 10.1021/bi9830718 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 206ZV UT WOS:000080911600013 PM 10360949 ER PT J AU Lammers, CH D'Souza, UH Qin, ZH Lee, SH Yajima, S Mouradian, MM AF Lammers, CH D'Souza, UH Qin, ZH Lee, SH Yajima, S Mouradian, MM TI Regulation of striatal dopamine receptors by corticosterone: an in vivo and in vitro study SO MOLECULAR BRAIN RESEARCH LA English DT Article DE dopamine receptor; corticosterone; caudate-putamen; nucleus accumbens; promoter; transcription ID RAT-BRAIN; GLUCOCORTICOIDS; GENE; EXPRESSION; STRESS; SUPERSENSITIVITY; AMPHETAMINE; SECRETION; MORPHINE; ESTROGEN AB The effects of chronic corticosterone administration and adrenalectomy on the expression of brain dopamine receptors were studied in rats. in situ hybridization and receptor binding autoradiography were carried our to determine D-1, D-2 and D-3 receptor expression in dorsal and ventral striata. Except for down-regulation of D-2 mRNA in dorsal striatum after 2 week corticosterone treatment, no other significant changes were detected. in addition, the transcriptional regulation of D-1 and D-2 gene promoters by glucocorticoids was studied in neuroblastoma cell lines using transient transfections. While a small segment of the D-2-promoter could be activated three-fold by dexamethasone, large fragments of neither D-1 or D-2 promoters were regulated by this treatment. Glucocorticoids do not appear to have direct overall effects on striatal dopamine receptor expression, The observed down-regulation of D-2 receptor mRNA in the dorsal striatum in vivo is likely secondary to increased striatal dopamine release induced by corticosterone. (C) 1999 Elsevier Science B.V, All rights reserved. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Pharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, 10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 27 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN 8 PY 1999 VL 69 IS 2 BP 281 EP 285 DI 10.1016/S0169-328X(99)00105-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 205TL UT WOS:000080836600013 ER PT J AU Wallace, AM Dass, B Ravnik, SE Tonk, V Jenkins, NA Gilbert, DJ Copeland, NG MacDonald, CC AF Wallace, AM Dass, B Ravnik, SE Tonk, V Jenkins, NA Gilbert, DJ Copeland, NG MacDonald, CC TI Two distinct forms of the 64,000 M-r protein of the cleavage stimulation factor are expressed in mouse male germ cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-POLYMERASE-II; PRE-MESSENGER-RNA; POLYADENYLATION SPECIFICITY FACTOR; ZINC FINGER GENE; 3' END FORMATION; BINDING PROTEIN; POLY(A) SITE; MOLECULAR-CLONING; INVITRO TRANSCRIPTION; FUNCTIONAL-ANALYSIS AB Polyadenylation in male germ cells differs from that in somatic cells, Many germ cell mRNAs do not contain the canonical AAUAAA in their 3' ends but are efficiently polyadenylated. To determine whether the 64,000 M-r protein of the cleavage stimulation factor (CstF-64) is altered in male germ cells, we examined its expression in mouse testis, In addition to the 64,000 M-r form, we found a related approximate to 70,000 M-r protein that is abundant in testis, at low levels in brain, and undetectable in all other tissues examined. Expression of the approximate to 70,000 M-r CstF-64 was limited to meiotic spermatocytes and postmeiotic spermatids in testis, In contrast, the 64,000 M-r form was absent from spermatocytes, suggesting that the testis-specific CstF-64 might control expression of meiosis-specific genes. To determine why the 64,000 M-r CstF-64 is not expressed in spermatocytes, we mapped its chromosomal location to the X chromosome in both mouse and human. CstF-64 may, therefore, be absent in spermatocytes because the X chromosome is inactivated during male meiosis, By extension, the testis-specific CstF-64 may be expressed from an autosomal homolog of the X chromosomal gene. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Ctr Med, Lubbock, TX 79430 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Pediat & Pathol, Ctr Med, Lubbock, TX 79430 USA. Texas Tech Univ, Hlth Sci Ctr, SW Canc Ctr, Ctr Med, Lubbock, TX 79430 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Adv Biosci Labs,Basic Res Program, Frederick, MD 21702 USA. RP MacDonald, CC (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Ctr Med, 3601 4th St, Lubbock, TX 79430 USA. NR 92 TC 84 Z9 85 U1 0 U2 1 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 JUN 8 PY 1999 VL 96 IS 12 BP 6763 EP 6768 DI 10.1073/pnas.96.12.6763 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200035 PM 10359786 ER PT J AU Brocke, S Piercy, C Steinman, L Weissman, IL Veromaa, T AF Brocke, S Piercy, C Steinman, L Weissman, IL Veromaa, T TI Antibodies to CD44 and integrin alpha(4), but not L-selectin, prevent central nervous system inflammation and experimental encephalomyelitis by blocking secondary leukocyte recruitment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ANTIGEN-SPECIFIC LYMPHOCYTES; T-CELL; MULTIPLE-SCLEROSIS; PRIMARY ADHESION; PHYSIOLOGICAL FLOW; HOMING RECEPTOR; TRAFFIC SIGNALS; IMMUNE-SYSTEM AB The role of various adhesion molecules in lymphocyte homing to the brain and in inflammatory autoimmune disease of the central nervous system (CNS) was examined in mice, Activated T cell lines and clones expressed CD44 and integrin alpha(4), but not L-selectin, and entered the CNS independent of their antigen specificity. mAbs directed against CD44 and integrin alpha(4) prevented the transfer of experimental autoimmune encephalomyelitis (EAE) by myelin basic protein-specific T cells. T cells preincubated with anti-CD44 or antiintegrin alpha(4) were blocked only partially from entering the brain parenchyma, However, both antibodies efficiently prevented CNS inflammation and clinical expression of EAE when injected in vivo. This effect lasted as long as antibodies were administered. Antibodies specific for L-selectin had no effect on homing of encephalitogenic T cells to the brain or development of EAE, Antiintegrin alpha(4) and anti-CD44 did not impair the activation and function of encephalitogenic T cells in vitro and did not deplete integrin alpha(4)- or CD44-positive cells in vivo. These data suggest that, in the absence of leukocyte recruitment, the entry of a reduced number of activated myelin basic protein-reactive T cells in the CNS is not sufficient for the development and expression of EAE. We propose that antibodies to integrin alpha(4) and CD44 prevent clinical disease by partially targeting the primary influx of encephalitogenic T cells and by preventing the secondary influx of leukocytes to lesions initiated by the transferred T cells. C1 Hebrew Univ Jerusalem, Dept Pathol, Hadassah Med Sch, IL-91120 Jerusalem, Israel. Natl Inst Neurol Disorders & Stroke, NIH, Neurol Dis Sect, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Pathol & Dev Biol, Stanford, CA 94305 USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. RP Brocke, S (reprint author), Hebrew Univ Jerusalem, Dept Pathol, Hadassah Med Sch, POB 12272, IL-91120 Jerusalem, Israel. NR 70 TC 213 Z9 217 U1 0 U2 2 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 JUN 8 PY 1999 VL 96 IS 12 BP 6896 EP 6901 DI 10.1073/pnas.96.12.6896 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200059 PM 10359810 ER PT J AU Walker, PS Scharton-Kersten, T Krieg, AM Love-Homan, L Rowton, ED Udey, MC Vogel, JC AF Walker, PS Scharton-Kersten, T Krieg, AM Love-Homan, L Rowton, ED Udey, MC Vogel, JC TI Immunostimulatory oligodeoxynucleotides promote protective immunity and provide systemic therapy for leishmaniasis via IL-12-and IFN-gamma-dependent mechanisms SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTRADERMAL GENE IMMUNIZATION; T-CELL; DENDRITIC CELLS; BACTERIAL-DNA; CPG MOTIFS; IN-VIVO; INTERFERON-GAMMA; MAJOR INFECTION; INTERLEUKIN-12; ANTIGEN AB Resistance to murine leishmaniasis correlates with development of a CD4(+) T helper 1 (Th1)-predominant immune response, To determine whether immunostimulatory CpG-containing oligodeoxynucleotides (CpG-ODN), known to promote a Th1 immune response, could provide protection from Leishmania infection, CpG-ODN and freeze-thawed (F/T) Leishmania major were coinjected intradermally into susceptible BALE/c mice. A Leishmania-specific Th1-predominant immune response was induced, and 40% of animals were protected from subsequent challenge with infectious organisms, with 0% protection of animals injected with F/T Leishmania organisms and PBS, F/T organisms and control ODN, or F/T organisms alone. More striking protection (65-95%) was seen in mice first infected with intact Leishmania organisms and then injected with CpG-ODN, either at the site of infection or at a remote site. To determine whether the therapeutic protection provided by CpG-ODN depended on IL-12 and IFN-gamma production, both IFN-gamma-deficient BALB/c mice and BALB/c mice treated with neutralizing anti-IL-12 mAb were first inoculated with Leishmania and then treated with either CpG-ODN, ODN, or PBS, None of these IFN-gamma-deficient mice survived (0/20, 0/20, and 0/20 respectively). Furthermore, neutralization of IL-12 completely abolished the therapeutic protection provided by CpG-ODN (0/20 mice surviving). We conclude that immunostimulatory DNA sequences likely exert systemic effects via IL-12 and IFN-gamma-dependent mechanisms and hold considerable promise as both vaccine adjuvants and potential therapeutic agents in the prevention and treatment of leishmaniasis. C1 Natl Canc Inst, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Vogel, JC (reprint author), Natl Canc Inst, Dermatol Branch, NIH, Bldg 10 Room 12N260,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-1975-2011; Rowton, Edgar/A-4474-2012 OI Rowton, Edgar/0000-0002-1979-1485; NR 33 TC 180 Z9 189 U1 0 U2 2 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 JUN 8 PY 1999 VL 96 IS 12 BP 6970 EP 6975 DI 10.1073/pnas.96.12.6970 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200072 PM 10359823 ER PT J AU Spouge, JL Layne, SP AF Spouge, JL Layne, SP TI A practical method for simultaneously determining the effective burst sizes and cycle times of viruses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE reproductive statistics; age-specific fertility; inverse problem; therapeutics; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIVITY; CHEMOKINES AB We describe combined analytic and experimental methods for determining reproductive statistics from time-series data. Our computational methods derive four fundamental measures from laboratory experiments: (i) average number of viral daughters; (ii) mean viral cycle time; (iii) standard deviation of the viral cycling time; and (iv) viral doubling time. Taken together, these four reproductive statistics characterize "age-specific fertility," a quantity that provides complete information on the reproduction of the average viral particle. In this paper, we emphasize applications relating to HIV and experiments for assessing cellular tropism, viral phenotypes, antiviral drugs, humoral immunity, and cytotoxic cellular immunity, Nevertheless, our method is quite flexible and applicable to the evaluation of drugs against bacterial, fungal, and parasitic infections, antineoplastic agents against cancer cells, and perturbations involving pest and wildlife releases in ecosystems. C1 Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. NR 21 TC 4 Z9 4 U1 0 U2 2 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 JUN 8 PY 1999 VL 96 IS 12 BP 7017 EP 7022 DI 10.1073/pnas.96.12.7017 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200080 PM 10359831 ER PT J AU Sun, MK Nelson, TJ Xu, H Alkon, DL AF Sun, MK Nelson, TJ Xu, H Alkon, DL TI Calexcitin transformation of GABAergic synapses: From excitation filter to amplifier SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIPPOCAMPAL PYRAMIDAL CELLS; SYNAPTIC PLASTICITY; GABA(A) RECEPTORS; RAT HIPPOCAMPUS; INTERNEURONS; NEURONS; MEMORY; SELECTIVITY; PERMEATION; CHANNEL AB Encoding an experience into a lasting memory is thought to involve an altered operation of relevant synapses and a variety of other subcellular processes, including changed activity of specific proteins. Here, we report direct evidence that co-applying (associating) membrane depolarization of rat hippocampal CAI pyramidal cells with intracellular microinjections of calexcitin (CE), a memory-related signaling protein, induces a long-term transformation of inhibitory postsynaptic potentials from basket interneurons (BAS) into excitatory postsynaptic potentials, This synaptic transformation changes the function of the synaptic inputs from excitation filter to amplifier, is accompanied by a shift of the reversal potential of BAS-CA1 postsynaptic potentials, and is blocked by inhibiting carbonic anhydrase or antagonizing ryanodine receptors. Effects in the opposite direction are produced when anti-CE antibody is introduced into the cells, whereas heat-inactivated CE and antibodies are ineffective. These data suggest that CE is actively involved in shaping BAS-CA1 synaptic plasticity and controlling information processing through the hippocampal networks. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Sun, MK (reprint author), NINDS, Lab Adapt Syst, NIH, Bldg 36,Room 4A24,36 Convent Dr, Bethesda, MD 20892 USA. NR 30 TC 19 Z9 19 U1 0 U2 0 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 JUN 8 PY 1999 VL 96 IS 12 BP 7023 EP 7028 DI 10.1073/pnas.96.12.7023 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200081 PM 10359832 ER PT J AU Sjogren, K Liu, JL Blad, K Skrtic, S Vidal, O Wallenius, V LeRoith, D Tornell, J Isaksson, OGP Jansson, JO Ohlsson, C AF Sjogren, K Liu, JL Blad, K Skrtic, S Vidal, O Wallenius, V LeRoith, D Tornell, J Isaksson, OGP Jansson, JO Ohlsson, C TI Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HORMONE INSENSITIVITY SYNDROME; LONGITUDINAL BONE-GROWTH; TRANSGENIC MICE; TISSUE CONCENTRATIONS; BINDING-PROTEINS; GENE; SOMATOMEDIN; EXPRESSION; DELETION; DWARFISM AB The body growth of animals is regulated by growth hormone and IGF-I, The classical theory of this regulation is that most IGF-I in the blood originates in the liver and that body growth is controlled by the concentration of IGF-I in the blood, We have abolished IGF-I production in the livers of mice by using the Cre/loxP recombination system. These mice demonstrated complete inactivation of the IGF-I gene in the hepatocytes, Although the liver accounts for less than 5% of body mass, the concentration of IGF-I in the serum was reduced by 75%, This finding confirms that the liver is the principal source of IGF-I in the blood. However, the reduction in serum IGF-I concentration had no discernible effect on postnatal body growth. We conclude that postnatal body growth is preserved despite complete absence of IGF-I production by the hepatocytes. C1 Sahlgrens Univ Hosp, Dept Internal Med, Div Endocrinol, S-41345 Gothenburg, Sweden. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Physiol, S-40530 Gothenburg, Sweden. RP Isaksson, OGP (reprint author), Sahlgrens Univ Hosp, Dept Internal Med, Div Endocrinol, S-41345 Gothenburg, Sweden. NR 33 TC 582 Z9 592 U1 0 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 JUN 8 PY 1999 VL 96 IS 12 BP 7088 EP 7092 DI 10.1073/pnas.96.12.7088 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 205VX UT WOS:000080842200092 PM 10359843 ER PT J AU Gladyshev, VN Krause, M Xu, XM Korotkov, KV Kryukov, GV Sun, QA Lee, BJ Wootton, JC Hatfield, DL AF Gladyshev, VN Krause, M Xu, XM Korotkov, KV Kryukov, GV Sun, QA Lee, BJ Wootton, JC Hatfield, DL TI Selenocysteine-containing thioredoxin reductase in C-elegans SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GLUTATHIONE-PEROXIDASE; ESCHERICHIA-COLI; HUMAN PLACENTA; SELENIUM; DEHYDROGENASE; NADPH; SELENOENZYME; ALKYLATION; INHIBITION; ASCORBATE AB Mammalian thioredoxin reductases contain a TGA-encoded C-terminal penultimate selenocysteine (Sec) residue, and show little homology to bacterial, yeast, and plant thioredoxin reductases. Here we show that the nematode, Caenorhabditis elegans, contains two homologs related to the mammalian thioredoxin reductase family. The gene. for one of these homologs contains a cysteine codon in place of TGA, and its product, designated TR-S, was previously suggested to function as thioredoxin reductase. The other gene contains TGA and its product is designated TR-Se. This Sec-containing thioredoxin reductase lacks a canonical Sec insertion sequence element in the 3'-untranslated area of the gene. TR-Se shows greater sequence similarity to mammalian thioredoxin reductase isozymes TR1 and TR2, whereas TR-S is more similar to TR3. TR-Se was identified as a thioredoxin reductase selenoprotein by labeling C. elegans with Se-75 and characterizing the resulting Se-75-labeled protein by affinity and other column chromatography and gel-eleetrophoresis. TR-Se was expressed in Escherichia coli as a selenoprotein when a bacterial SECIS element was introduced downstream of the Sec TGA codon. The data show that TR-Se is the major naturally occurring selenoprotein in C. elegans, and suggest an important role for selenium and the thioredoxin system in this organism. (C) 1999 Academic Press. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NIDDKD, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Bethesda, MD 20892 USA. Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Genet Mol Lab, Inst Mol Biol & Genet, Seoul 151742, South Korea. RP Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vng@unlinfo2.unl.edu RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013; OI Krause, Michael/0000-0001-6127-3940 NR 32 TC 63 Z9 64 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 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 7 PY 1999 VL 259 IS 2 BP 244 EP 249 DI 10.1006/bbrc.1999.0765 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 207AB UT WOS:000080912200003 PM 10362494 ER PT J AU Zhong, SB Nguyen, NY Eggerman, TL AF Zhong, SB Nguyen, NY Eggerman, TL TI Detection of apolipoprotein B mRNA editing by peptide nucleic acid mediated PCR clamping SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apolipoprotein B; peptide nucleic acid; PCR; primer extension; mutant; mRNA editing ID MESSENGER-RNA; PNA; RAT AB Apolipoprotein B (apoB) mRNA editing leads to a single base change in its mRNA and the production of apoB-48. Currently, the degree of apoB mRNA editing is analyzed by the RT-PCR primer extension method. While this method is quantitative, it is labor intensive, utilizes radioactivity for labeling and may not be sensitive enough to discriminate between low levels of editing and inherent assay background levels. Peptide nucleic acid (PNA) oligonucletides have been used in single point mutation detection through PCR. clamping. In the present work, we developed a PCR based assay which can detect the single base change responsible for the apoB-48 production. We found that as low as 0.5% of the edited form can be clearly detected by PNA mediated PCR clamping. When combined with the primer extension assay, an approximately 180-fold enrichment of the edited percentage is observed, reflecting selected PCR amplification of templates containing the edited base. (C) 1999 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. RP Eggerman, TL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN12, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 7 PY 1999 VL 259 IS 2 BP 311 EP 313 DI 10.1006/bbrc.1999.0687 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 207AB UT WOS:000080912200013 PM 10362504 ER PT J AU Muller, S Maas, A Islam, TC Sideras, P Suske, G Philipsen, S Xanthopoulos, KG Hendriks, RW Smith, CIE AF Muller, S Maas, A Islam, TC Sideras, P Suske, G Philipsen, S Xanthopoulos, KG Hendriks, RW Smith, CIE TI Synergistic activation of the human Btk promoter by transcription factors Sp1/3 and PU.1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TYROSINE KINASE GENE; EXPRESSION; SP3; AGAMMAGLOBULINEMIA; DOMAINS; BINDING; DROSOPHILA; PROTEINS; CLONING; DIFFERENTIATION AB Analysis of the human Bruton's agammaglobulinemia tyrosine kinase (Btk) gene promoter revealed that 280 bp upstream of the transcriptional start site is sufficient for a cell restricted expression pattern. Here, the interplay of the transcription factors Sp1, Sp3, and PU.1 binding to this promoter area was analysed. All three proteins are able to independently activate the promoter in Drosophila Schneider (SL2) cells lacking endogenous Sp- or PU.1-like activities. Furthermore, PU.1 is able to act synergistically with Sp1 as well as Sp3 to transactivate the promoter. This transactivation is mediated through adjacent binding sites rather than through the more distant Sp binding site, suggesting a possible direct interaction between PU.1 and Sp1/3. Expression of Etk was found in ES cells and levels of expression were the same as in ES cells with a targeted deletion of the Sp1 gene, suggesting that Sp3 acts as a positive regulator of Btk in vivo in the absence of Sp1. (C) 1999 Academic Press. C1 Karolinska Inst, Novum, Ctr Biotechnol, Dept Biosci, S-14157 Huddinge, Sweden. Umea Univ, Dept Cell & Mol Biol, S-90187 Umea, Sweden. Univ Marburg, Inst Mol Biol & Tumorforsch, D-35037 Marburg, Germany. Natl Ctr Human Genome Res, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Fac Med, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Fac Med, Dept Immunol, NL-3000 DR Rotterdam, Netherlands. Huddinge Hosp, Dept Immunol, Div Clin Immunol Microbiol Pathol & Infect Dis, S-14186 Huddinge, Sweden. RP Muller, S (reprint author), Karolinska Inst, Ctr Genom Res, S-17177 Stockholm, Sweden. NR 31 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 7 PY 1999 VL 259 IS 2 BP 364 EP 369 DI 10.1006/bbrc.1999.0677 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 207AB UT WOS:000080912200024 PM 10362515 ER PT J AU Gulati, S Brody, LC Banerjee, R AF Gulati, S Brody, LC Banerjee, R TI Posttranscriptional regulation of mammalian methionine synthase by B-12 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN THYMIDYLATE SYNTHASE; NEURAL-TUBE DEFECTS; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; VITAMIN-B-12 REPRESSION; TRANSLATIONAL CONTROL; CDNA CLONING; COB OPERON; PIG-LIVER; BTUB GENE AB Methionine synthase is one of two key enzymes involved in the removal of the metabolite, homocysteine. Elevated homocysteine levels constitute a risk factor for cardiovascular diseases and for neural tube defects. In cell culture, the activity of methionine synthase is enhanced several-fold by supplementation with its cofactor, B-12 The mechanism of this regulation is unknown, although it has been ascribed to a shift from apoenzyme to holoenzyme. Using sensitive assay techniques as well asa combination of Northern and Western analyses, we demonstrate that the effect of B-12 on induction of methionine synthase activity is paralleled by an increase in the level of the enzyme. These studies exclude conversion of apoenzyme to holoenzyme as a basis for activation that had been described previously. Since the mRNA levels do not change during the same period that the methionine synthase levels increase, regulation of this protein by its cofactor must be exerted posttranscriptionally. (C) 1999 Academic Press. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Natl Human Genome Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Banerjee, R (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. FU NIDDK NIH HHS [DK45776] NR 31 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 7 PY 1999 VL 259 IS 2 BP 436 EP 442 DI 10.1006/bbrc.1999.0696 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 207AB UT WOS:000080912200035 PM 10362526 ER PT J AU Chen, WS Yewdell, JW Levine, RL Bennink, JR AF Chen, WS Yewdell, JW Levine, RL Bennink, JR TI Modification of cysteine residues in vitro and in vivo affects the immunogenicity and antigenicity of major histocompatibility complex class I-restricted viral determinants SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE antigen processing; cysteine immunology; major histocompatibility complex immunology; viral vaccines immunology; peptides immunology ID PEPTIDE; AFFINITY; MOLECULES AB In studying the subdominant status of two cysteine-containing influenza virus nuclear protein (NP) determinants (NP39-47 and NP218-226) restricted by H-2K(d), we found that the antigenicity of synthetic peptides was enhanced 10-100-fold by treatment with reducing agents, despite the fact that the affinity for Kd was not enhanced. Reducing agents also markedly enhanced the immunogenicity of cysteine-containing peptides, as measured by propagation of long-term T cell lines in vitro. Similar enhancing effects were obtained by substituting cysteine with alanine or serine in the synthetic peptides, demonstrating that sulfhydryl modification of cysteine is responsible for the impaired antigenicity and immunogenicity of NP39-47 and NP218-226. We found similar effects for two widely studied, cysteine-containing peptides from lymphocytic choriomeningitis virus. The major modifications of cysteine-containing synthetic peptides are cysteinylation and dimerization occurring through cysteine residues. We demonstrate that both of these modifications occur in cells synthesizing a cytosolic NP218-226 minigene product and, further, that T cells specific for cysteinylated NP218-226 are induced by influenza virus infection in mice, demonstrating that this modification occurs in vivo. These findings demonstrate that posttranslational modifications affect the immunogenicity and antigenicity of cysteine-containing viral peptides and that this must be considered in studying the status of such peptides in immunodominance hierarchies. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Rm 213,Bldg 4,4 Ctr Dr,MSC 0440, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012; Levine, Rodney/D-9885-2011 NR 14 TC 77 Z9 77 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 7 PY 1999 VL 189 IS 11 BP 1757 EP 1764 DI 10.1084/jem.189.11.1757 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 206BB UT WOS:000080855200009 PM 10359579 ER PT J AU Bertini, R Howard, OMZ Dong, HF Oppenheim, JJ Bizzarri, C Sergi, R Caselli, G Pagliei, S Romines, B Wilshire, JA Mengozzi, M Nakamura, H Yodoi, J Pekkari, K Gurunath, R Holmgren, A Herzenberg, LA Herzenberg, LA Ghezzi, P AF Bertini, R Howard, OMZ Dong, HF Oppenheim, JJ Bizzarri, C Sergi, R Caselli, G Pagliei, S Romines, B Wilshire, JA Mengozzi, M Nakamura, H Yodoi, J Pekkari, K Gurunath, R Holmgren, A Herzenberg, LA Herzenberg, LA Ghezzi, P TI Thioredoxin, a redox enzyme released in infection and inflammation, is a unique chemoattractant for neutrophils, monocytes, and T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemotaxis; thioredoxin; HTLV-1; migration ID LEUKEMIA-DERIVED FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; HTLV-I; LYMPHADENOPATHY SYNDROME; EXPRESSION; PROTEIN; MIGRATION; LINES; IDENTIFICATION; GLUTAREDOXIN AB Thioredoxin (Trx) is a ubiquitous intracellular protein disulfide oxidoreductase with a CXXC active site that can be released by various cell types upon activation. We show here that Trx is chemotactic for monocytes, polymorphonuclear leukocytes, and T lymphocytes, both in vitro in the standard micro Boyden chamber migration assay and in vivo in the mouse air pouch model. The potency of the chemotactic action of Tn: for all leukocyte populations is in the nanomolar range, comparable with that of known chemokines. However, Trx does not increase intracellular Ca2+ and its activity is not inhibited by pertussis toxin. Thus, the chemotactic action of Trx differs from that of known chemokines in that it is G protein independent. Mutation of the active site cysteines resulted in loss of chemotactic activity, suggesting that the latter is mediated by the enzyme activity of Trx. Trx also accounted for part of the chemotactic activity released by human T lymphotropic virus (HTLV)-1-infected cells, which was inhibited by incubation with anti-Trx antibody. Since Trx production is induced by oxidants, it represents a link between oxidative stress and inflammation that is of particular interest because circulating Tn: levels are elevated in inflammatory diseases and HIV infection. C1 Stanford Univ, Dept Genet, Sch Med, Sch Med, Stanford, CA 94305 USA. Dompe Res Ctr, I-67100 Laquila, Italy. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Consorzio Biolaq, I-67100 Laquila, Italy. Kyoto Univ, Inst Virus Res, Dept Biol Responses, Kyoto 606, Japan. Karolinska Inst, Med Nobel Inst Biochem, S-17177 Stockholm, Sweden. RP Ghezzi, P (reprint author), Stanford Univ, Dept Genet, Sch Med, Sch Med, B-007,300 Pasteur Dr, Stanford, CA 94305 USA. RI Howard, O M Zack/B-6117-2012; Ramanathan, Gurunath/B-4757-2011 OI Howard, O M Zack/0000-0002-0505-7052; Ramanathan, Gurunath/0000-0003-4627-1677 FU NCI NIH HHS [CA42509, N01-CO-56000] NR 54 TC 227 Z9 233 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 7 PY 1999 VL 189 IS 11 BP 1783 EP 1789 DI 10.1084/jem.189.11.1783 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 206BB UT WOS:000080855200012 PM 10359582 ER PT J AU Lekstrom-Himes, JA Dorman, SE Kopar, P Holland, SM Gallin, JI AF Lekstrom-Himes, JA Dorman, SE Kopar, P Holland, SM Gallin, JI TI Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT enhancer binding protein epsilon SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE myelopoiesis; lactoferrin; granulocyte; immunodeficiency; neutrophil ID LACTOFERRIN DEFICIENCY; MESSENGER-RNA; C/EBP-EPSILON; PATIENT; ABSENCE; GENE; RECEPTOR; CELLS; ALPHA; DIFFERENTIATION AB Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)epsilon, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBP epsilon locus. The predicted frame shift results in a truncation of the 32-kD major C/EBP epsilon isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBP epsilon deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBP epsilon for the promyelocyte-myelocyte transition in myeloid differentiation. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Gallin, JI (reprint author), Bldg 10,Rm 2C146,10 Ctr Dr,MSC 1504, Bethesda, MD 20892 USA. NR 37 TC 112 Z9 117 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 7 PY 1999 VL 189 IS 11 BP 1847 EP 1852 DI 10.1084/jem.189.11.1847 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 206BB UT WOS:000080855200018 PM 10359588 ER PT J AU Oren, M Vousden, KH AF Oren, M Vousden, KH TI Hot papers - Cancer research - Mdm2 promotes the rapid degradation of p53 by Y. Haupt, R. Maya, A. Kazaz, M. Oren and Regulation of p53 stability by Mdm2 by M.H.G. Kubbutat, S.N. Jones, K.H. Vousden - Comments SO SCIENTIST LA English DT Editorial Material AB Moshe Oren of the Weizmann Institute of Science and Karen H. Vousden of The Frederick Cancer Research and Development Center discuss the Mdm2-p53 relationship. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD USA. RP Oren, M (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NR 5 TC 1 Z9 1 U1 0 U2 3 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JUN 7 PY 1999 VL 13 IS 12 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 203RX UT WOS:000080721600008 ER PT J AU Teomim, D Nyska, A Domb, AJ AF Teomim, D Nyska, A Domb, AJ TI Ricinoleic acid-based biopolymers SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE biodegradable polymers; polyanhydride; fatty acid ester; ricinoleic acid; biocompatibility ID BIODEGRADABLE POLYMERS; CONTROLLED-RELEASE; FATTY-ACIDS; POLYANHYDRIDES; BIOCOMPATIBILITY; IMPLANTATION; INVIVO; DIMER; DELIVERY; RATS AB Polyanhydrides synthesized from pure ricinoleic acid half-esters with maleic and succinic anhydrides possess desired physicochemical and mechanical properties for use as drug carriers. Ricinoleic acid maleate or succinate diacid half-esters were prepared from the reaction of crude ricinoleic acid (85% content) with succinic or maleic anhydride. The pure diacid monomers were obtained by chromatography purification through silica gel using petroleum ether/ethyl acetate/acetic acid (80/30/1 v/v/v) mixture as eluent. The pure diacid monomers (>99%) were polymerized by melt condensation to yield film-forming polymers with molecular weights exceeding 40,000 with a polydispersity of 2. Extensive biocompatibility study demonstrated their toxicological inertness and biodegradability. Their rate of elimination from rats in the course of about 4-6 weeks was faster than that found for similar fatty acid-based polyanhydrides previously tested. In vitro studies showed that these polymers underwent rapid hydrolytic degradation in 10 days. Methotrexate release from the polymers was not affected by the initial polymer molecular weight in the range of 10,000-35,000. The in vitro drug release correlated with the degradation of the polymers. The fatty acid ester monomers were further degraded to its counterparts, ricinoleic acid and succinic or maleic acid. (C) 1999 John Wiley & Sons, Inc. C1 Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Dept Med Chem,David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Domb, AJ (reprint author), Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Dept Med Chem,David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. NR 28 TC 82 Z9 83 U1 0 U2 15 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUN 5 PY 1999 VL 45 IS 3 BP 258 EP 267 DI 10.1002/(SICI)1097-4636(19990605)45:3<258::AID-JBM14>3.0.CO;2-W PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 183QX UT WOS:000079565900014 PM 10397984 ER PT J AU Manns, A Hisada, M La Grenade, L AF Manns, A Hisada, M La Grenade, L TI Human T-lymphotropic virus type I infection SO LANCET LA English DT Review ID TROPICAL SPASTIC PARAPARESIS; CELL LEUKEMIA-VIRUS; POLYMERASE CHAIN-REACTION; TRINIDAD-AND-TOBAGO; HTLV-I; C RETROVIRUS; RISK-FACTORS; MOLECULAR MECHANISMS; CHILD TRANSMISSION; BLOOD-TRANSFUSION AB Human T-cell lymphotropic virus type I (HTLV-I) is the first human retrovirus to be associated with malignant disease-namely, adult T-cell leukaemia/lymphoma. HTLV-I has also been associated with several non-malignant conditions, notably the chronic neurodegenerative disorder, HTLV-I associated myelopathy (also known as tropical spastic paraparesis), infective dermatitis of children and uveitis. More recent evidence points to disease associations not previously linked to HTLV-I. Thus, the disease spectrum of HTLV-I is not fully known. HTLV-I has a worldwide distribution with major endemic foci in the Caribbean and southern Japan. The public health importance is confirmed by the major routes of transmission, which are mother-to-child, blood transfusion, and sexual activity. Unfortunately, no vaccine is available yet and there is no proven treatment for advanced HTLV-I disease. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ W Indies, Dept Med, Kingston 7, Jamaica. RP Manns, A (reprint author), 6120 Execut Blvd,Room 8008,MSC 7248, Rockville, MD 20852 USA. EM mannsa@epndce.nci.nih.gov NR 115 TC 212 Z9 228 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN 5 PY 1999 VL 353 IS 9168 BP 1951 EP 1958 DI 10.1016/S0140-6736(98)09460-4 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 202TP UT WOS:000080668500045 PM 10371587 ER PT J AU Xia, DX Straus, SE AF Xia, DX Straus, SE TI Transcript mapping and transregulatory behavior of varicella-zoster virus gene 21, a latency-associated gene SO VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; OPEN READING FRAME-62; DNA-BINDING PROTEIN; VZV TRANSCRIPTION; INFECTED-CELLS; CDNA LIBRARY; UL37 PROTEIN; PROMOTER; TYPE-1; LOCALIZATION AB Gene 21 is one of at least four genes transcribed during latent infection of varicella-zoster virus (VZV) in human ganglia. It may encode a nucleocapsid protein, but its function in lytic and latent infection is not clear. To characterize further the structure and the function of the gene 21 open reading frame (ORF 21), precise localization of its transcripts and their termini was determined by using Northern analysis, S1 nuclease or RNase protection, and primer extension assays. One abundant 3.5-kb transcript that spans ORF 21 was identified, A predominant transcription start site was defined at -78 nucleotide (nt) relative to the ORF 21 translation start codon ATG, and two potential TATA elements were identified at 26 and 83 nt upstream of the 5' end of gene 21 transcripts. Transcription was found to terminate 210 nt beyond the ORF 21 translation stop codon and immediately before the start codon of ORF 22. In transient expression assays. the ORF 21 showed no significant transregulatory activity on promoters of diverse kinetic classes. The ORF 21 promoter, however, was transactivated strongly by VN infection or by ORF 62. C1 NIAID, Med Virol Sect, LCI, NIH, Bethesda, MD 20892 USA. RP Xia, DX (reprint author), NIAID, Med Virol Sect, LCI, NIH, Bldg 10,Rm 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 1999 VL 258 IS 2 BP 304 EP 313 DI 10.1006/viro.1999.9746 PG 10 WC Virology SC Virology GA 206YN UT WOS:000080908300011 PM 10366567 ER PT J AU Katsafanas, GC Moss, B AF Katsafanas, GC Moss, B TI Histidine codons appended to the gene encoding the RP022 subunit of vaccinia virus RNA polymerase facilitate the isolation and purification of functional enzyme and associated proteins from virus-infected cells SO VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTATIONS; EARLY TRANSCRIPTION FACTOR; 147-KILODALTON SUBUNITS; 2ND-LARGEST SUBUNIT; IDENTIFICATION; EXPRESSION; PROMOTER; SEQUENCE; 22-KILODALTON; SPECIFICITY AB Vaccinia virus encodes a eukaryotic-like RNA polymerase composed of two large and six small subunit protein species. A replication-competent virus with 10 histidine codons added to the single endogenous J4R open reading frame was constructed. The altered migration of the 22-kDa subunit of RNA polymerase on SDS-polyacrylamide gel electrophoresis confirmed that J4R encoded the RPO22 subunit and that the mutant virus was genetically stable. The histidine-tagged RNA polymerase bound quantitatively to metal-affinity resins and was eluted in an active form upon addition of imidazole. Glycerol gradient sedimentation of the eluted fraction indicated that most of the RPO22 in infected cells is associated with RNA polymerase. Using stringent washing conditions, metal-affinity chromatography resulted in a several hundred-fold increase in RNA-polymerase-specific activity, and substantially pure enzyme was obtained with an additional conventional chromatography step. When mild conditions were used for washing the metal-affinity resin, the vaccinia virus-encoded capping enzyme, early transcription factor, and nucleoside triphosphate phosphohydrolase I specifically co-eluted with the tagged RNA polymerase, consistent with their physical association. The ability to selectively bind RNA polymerase to an affinity column provided a simple and rapid method of concentrating and purifying active enzyme and protein complexes. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 1999 VL 258 IS 2 BP 469 EP 479 DI 10.1006/viro.1999.9744 PG 11 WC Virology SC Virology GA 206YN UT WOS:000080908300029 PM 10366585 ER PT J AU Licht, T Hafkemeyer, P AF Licht, T Hafkemeyer, P TI Topical aspects of somatic gene therapy SO DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT LA German DT Review ID HEMATOPOIETIC STEM-CELLS; HIV-INFECTED INDIVIDUALS; HUMAN MDR1 GENE; RETROVIRAL VECTOR; BONE-MARROW; PHASE-I; VIRUS-REPLICATION; NASAL EPITHELIUM; CYSTIC-FIBROSIS; DENDRITIC CELLS C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Licht, T (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,MSC 4255,Bldg 37,Room 1B28, Bethesda, MD 20892 USA. NR 44 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0012-0472 J9 DEUT MED WOCHENSCHR JI Dtsch. Med. Wochenschr. PD JUN 4 PY 1999 VL 124 IS 22 BP 700 EP 706 DI 10.1055/s-2007-1024401 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 204PV UT WOS:000080774100006 PM 10394351 ER PT J AU Izenwasser, S Coy, AE Ladenheim, B Loeloff, RJ Cadet, JL French, D AF Izenwasser, S Coy, AE Ladenheim, B Loeloff, RJ Cadet, JL French, D TI Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; dopamine; transporter; methylphenidate ID NUCLEUS-ACCUMBENS; RAT; STRIATUM; ANALOGS; BRAIN; ACID; MICE AB Continuous infusion of cocaine produces partial behavioral tolerance to its locomotor activating effects, while daily injections produce sensitization. Methylphenidate binds with a similar affinity to cocaine at the dopamine transporter, but has a much lower affinity for the serotonin transporter than does cocaine. This study was done to compare the effects of chronic methylphenidate with chronic cocaine. The pattern of locomotor activity over a 7 day treatment period was significantly different from cocaine. Methylphenidate elevated activity on each day, compared to saline, yet neither tolerance to a continuous infusion of the drug, nor sensitization to repeated daily injections was produced. We have previously shown that neither of these treatments with cocaine produces significant alterations in dopamine transporter density 1 day after the end of treatment. In contrast, methylphenidate injections significantly decreased dopamine transporters in rostral caudate putamen, with no change in nucleus accumbens. Continuous infusion of methylphenidate had no effect on dopamine transporters in either brain region. These findings provide further evidence that different classes of dopamine uptake inhibitors may interact with the dopamine transporter in qualitatively different manners. Furthermore, it is possible that the inhibition of serotonin uptake by cocaine may contribute to the adaptations in behavioral activity that are seen during chronic treatment. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIDA, Psychobiol Sect, Div Intramural Res, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Sect, Div Intramural Res, Baltimore, MD 21224 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. RP Izenwasser, S (reprint author), NIDA, Psychobiol Sect, Div Intramural Res, POB 5180, Baltimore, MD 21224 USA. RI Izenwasser, Sari/G-9193-2012 NR 22 TC 54 Z9 54 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUN 4 PY 1999 VL 373 IS 2-3 BP 187 EP 193 DI 10.1016/S0014-2999(99)00274-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 207ZR UT WOS:000080966100009 PM 10414438 ER PT J AU Nakae, J Park, BC Accili, D AF Nakae, J Park, BC Accili, D TI Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through wortmannin-sensitive pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; INDUCED GLUCOSE-TRANSPORT; CAENORHABDITIS-ELEGANS; PHOSPHATIDYLINOSITOL 3-KINASE; 3T3-L1 ADIPOCYTES; SER/THR KINASE; RAT ADIPOCYTES; POTENTIAL ROLE; FAMILY MEMBER; LONGEVITY AB In the nematode Caenorhabditis elegans, mutations of the insulin/insulin-like growth factor-1 receptor homologue Daf-a gene cause developmental arrest at the dauer stage. The effect of Daf-2 mutations is counteracted by mutations in the Daf-16 gene, suggesting that Daf-16 is required for signaling by Daf-2. Daf-16 encodes a forkhead transcription factor. Based on sequence similarity, the FKHR genes are the likeliest mammalian Daf-16 homologues, FKHR proteins contain potential sites for phosphorylation by the serine/threonine kinase Akt. Because Akt is phosphorylated in response to insulin and has been implicated in a variety of insulin effects, we investigated whether insulin affects phosphorylation of FKHR. Insulin stimulated phosphorylation of endogenous FKHR and of a recombinant c-Myc/FKHR fusion protein transiently expressed in murine SV40-transformed hepatocytes. The effect of insulin was inhibited by wortmannin treatment, suggesting that PI S-kinase activity is required for FKHR phosphorylation. Mutation of serine 253, located in a consensus Akt phosphorylation site at the carboxyl-terminal end of the forkhead domain, abolished the effect of insulin on FKHR phosphorylation. In contrast, mutation of two additional Akt phosphorylation sites, at amino acids threonine 24 or serine 316, did not abolish insulin-induced phosphorylation. These data indicate that FKHR may represent a distal effector of insulin action. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Accili, D (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10D18, Bethesda, MD 20892 USA. NR 28 TC 324 Z9 330 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 1999 VL 274 IS 23 BP 15982 EP 15985 DI 10.1074/jbc.274.23.15982 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600005 PM 10347145 ER PT J AU Howard, OMZ Shirakawa, AK Turpin, JA Maynard, A Tobin, GJ Carrington, M Oppenheim, JJ Dean, M AF Howard, OMZ Shirakawa, AK Turpin, JA Maynard, A Tobin, GJ Carrington, M Oppenheim, JJ Dean, M TI Naturally occurring CCR5 extracellular and transmembrane domain variants affect HIV-1 co-receptor and ligand binding function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE-RECEPTOR; ENVELOPE GLYCOPROTEINS; DISEASE PROGRESSION; ENTRY; INFECTION; CORECEPTOR; ASSOCIATION; INHIBITION; MACROPHAGE AB Analysis of CCR5 variants in human immunodeficiency virus, type 1 (HIV-1), high risk cohorts led to the identification of multiple single amino acid substitutions in the amino-terminal third of the HIV-1 co-receptor CCR5 suggesting the possibility of protective and permissive genotypes; unfortunately, the low frequency of these mutations did not led to correlation with function. Therefore, we used analytical methods to assess the functional and structural significance of six of these variant receptors in vitro. These studies showed three categories of effects on CCR5 function. 1) Mutations in the first extracellular domain of CCR5 severely reduce specific ligand binding and chemokine-induced chemotaxis. 2) An extracellular domain variant, A29S, when co-expressed with CD4, supported HIV-1 infection whereas the others do not. 3) The transmembrane region variants of CCR5 support monotropic HIV-1 infection that is blocked by addition of some receptor agonists, Mutations in the first and second transmembrane domains increase RANTES (regulated on activation normal T-cell expressed) binding affinity but did not affect MIP1 beta binding affinity presumably based on differences in ligand-receptor interaction sites. Furthermore, the CCR5 transmembrane mutants do not respond to RANTES with the classical bell-shaped chemotactic response curve, suggesting that they are resistant to RANTES-induced desensitization. These data demonstrate that single amino acid changes in the extracellular domains of CCR5 can have profound effects on both HIV-1 coreceptor and specific ligand-induced functions, whereas mutations in the transmembrane domain only affect the response to chemokine ligands. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. SW Res Inst, Frederick, MD 21701 USA. RP Howard, OMZ (reprint author), POB B, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012; Howard, O M Zack/B-6117-2012 OI Dean, Michael/0000-0003-2234-0631; Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000] NR 47 TC 59 Z9 61 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 1999 VL 274 IS 23 BP 16228 EP 16234 DI 10.1074/jbc.274.23.16228 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600038 PM 10347178 ER PT J AU Ried, S Jager, C Jeffers, M Vande Woude, GF Graeff, H Schmitt, M Lengyel, E AF Ried, S Jager, C Jeffers, M Vande Woude, GF Graeff, H Schmitt, M Lengyel, E TI Activation mechanisms of the urokinase-type plasminogen activator promoter by hepatocyte growth factor scatter factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASE; RHO-FAMILY PROTEINS; GRB2 BINDING-SITE; RAS TRANSFORMATION; MET PROTOONCOGENE; SIGNALING PATHWAY; EPITHELIAL-CELLS; OVARIAN-CANCER; ONCOGENIC RAS; PHORBOL-ESTER AB Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic effector inducing invasion and metastasis of tumor cells that express the Met tyrosine kinase receptor, One of the effecters of HGF/SF is the urokinase-type plasminogen activator, a serine protease that facilitates tumor progression and metastasis by controlling the synthesis of the extracellular matrix degrading plasmin, Stimulation of NIH 3T3 cells that were stably trans fected with the human Met receptor (NIH 3T3-Met(hum)) with HGF/SF induced a trans-activation of the urokinase promoter and urokinase secretion. Induction of the urokinase promoter by HGF/SF via the Met receptor was blocked by co-expression of a dominant-negative Grb2 and Sos1 expression construct. Further, the expression of the catalytically inactive mutants of Ha-Ras, RhoA, c-Raf, and Erk2 or addition of the Mek1-specific inhibitor PD 098059 abrogated the stimulation of the urokinase promoter by HGF/SF. A sequence residing between -2109 and -1870 base pairs (bp) was critical for stimulation of the urokinase gene by HGF/SF. Mobility shift assays with oligonucleotides spanning an AP-1 site at -1880 bp or a combined PEA3/AP-1 site at -1967 bp showed binding of nuclear factors from NIH 3T3-Met(hum) cells. Expression of an expression plasmid that inhibits DNA binding of AP-1 proteins (A-Fos) abrogated inducible and basal activation of the urokinase promoter. Nuclear extract from unstimulated NIH 3T3-Met(hum) cells contained more JunD and showed a stronger JunD supershift with the AP-I oligonucleotides, compared with HGF/SF-stimulated cells. Consistent with the levels of JunD expression being functionally important for basal expression of the urokinase promoter, we found that overexpression of wild type JunD inhibited the induction of the urokinase promoter by HGF/SF. These data suggest that the induction of urokinase by HGF/SF is regulated by a Grb2/Sos1/Ha-Ras/c-Raf/RhoA/Mek1/ Erk2/c-Jun-dependent mitogen-activated protein kinase pathway. C1 Tech Univ Munich, Dept Obstet & Gynecol, D-81675 Munich, Germany. NCI, ABL Basic Res Program, NIH, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Lengyel, E (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Dept Obstet & Gynecol, Ismaninger Str 22, D-81675 Munich, Germany. RI Lengyel, Ernst/D-9220-2014 OI Lengyel, Ernst/0000-0001-8624-1507 NR 61 TC 76 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 1999 VL 274 IS 23 BP 16377 EP 16386 DI 10.1074/jbc.274.23.16377 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600057 PM 10347197 ER PT J AU Sathyanarayana, UG Freeman, LA Lee, MS Garrard, WT AF Sathyanarayana, UG Freeman, LA Lee, MS Garrard, WT TI RNA polymerase-specific nucleosome disruption by transcription in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRE-MESSENGER-RNA; C-TERMINAL DOMAIN; YEAST HSP82 GENE; SACCHAROMYCES-CEREVISIAE; CHROMATIN STRUCTURE; HISTONE OCTAMER; DNA-TEMPLATE; IN-VITRO; ELONGATION; EXPRESSION AB The nucleosomal chromatin structure within genes is disrupted upon transcription by RNA polymerase II. To determine whether this disruption is caused by transcription per se as opposed to the RNA polymerase source, we engineered the yeast chromosomal HSP82 gene to be exclusively transcribed by bacteriophage T7 RNA polymerase in vivo. Interestingly, we found that a fraction of the T7-generated transcripts were 3' end processed and polyadenylated at or near the 3' ends of the hsp82 and the immediately downstream CIN2 genes. Surprisingly, the nucleosomal structure of the T7-transcribed hsp82 gene remained intact, in marked contrast to the disrupted structure generated by much weaker, basal level transcription of the wild type gene by RNA polymerase II under non-heat shock conditions. Therefore, disruption of chromatin structure by transcription is dependent on the RNA polymerase source. We propose that the observed RNA polymerase dependence for transcription-induced nucleosome disruption may be related either to the differential recruitment of chromatin remodeling complexes, the rates of histone octamer translocation and nucleosome reformation during polymerase traversal, and/or the degree of transient torsional stress generated by the elongating polymerase. C1 Univ Texas, SW Med Ctr, Dept Mol Biol & Oncol, Dallas, TX 75235 USA. NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Sookmyung Womens Univ, Dept Biol, Seoul 140742, South Korea. RP Univ Texas, SW Med Ctr, Dept Mol Biol & Oncol, Hammon Biomed Res Bldg,5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM garrard@utsw.swmed.edu FU NIGMS NIH HHS [GM22201, GM29935] NR 61 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 1999 VL 274 IS 23 BP 16431 EP 16436 DI 10.1074/jbc.274.23.16431 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600064 PM 10347204 ER PT J AU Sheikh, MS Fernandez-Salas, E Yu, MH Hussain, A Dinman, JD Peltz, SW Huang, Y Fornace, AJ AF Sheikh, MS Fernandez-Salas, E Yu, MH Hussain, A Dinman, JD Peltz, SW Huang, Y Fornace, AJ TI Cloning and characterization of a human genotoxic and endoplasmic reticulum stress-inducible cDNA that encodes translation initiation factor 1 (eIF(1A121/SUI1)) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CA2+ TRANSPORT ATPASE; SACCHAROMYCES-CEREVISIAE; GENE; DNA; PROTEIN; GROWTH; YEAST; SUI1; THAPSIGARGIN; TRANSCRIPTS AB We report the cloning and characterization of a DNA damage-inducible (DDI) transcript DDI A121. The full-length human DDI A121 cDNA contains an open reading frame of 113 amino acids, corresponding to a protein of 12.7 kDa. The deduced amino acid sequence of A121 shows high homology to the yeast translation initiation factor (eIF) sui1 and also exhibits perfect identity to the partial sequence of recently purified human eIF1. Expression of human A121 corrected the mutant suil phenotype in yeast, demonstrating that human A121 encodes a bona fide translation initiation factor that is equivalent to yeast sui1p. The mammalian A121/SUI1 gene exhibits two transcripts (1.35 kilobases and 0.65 kilobases) containing a common coding region but differing in their 3'-untranslated region. The long and short A121/SUI1 mRNAs are differentially regulated by genotoxic and endoplasmic reticulum stress. The genotoxic stress induction of A121/SUI1 mRNA is conserved in both humans and rodents and occurs in a p53-independent manner. Our identification of a stress-inducible cDNA that encodes eIF1 suggests that modulation of translation initiation appears to occur during cellular stress and may represent an important adaptive response to genotoxic as well as endoplasmic reticulum stress. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Grad Programs Mol Biosci Rutgers, Piscataway, NJ 08854 USA. NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Sheikh, MS (reprint author), NCI, Div Basic Sci, NIH, Bldg 37,Rm 5C09, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; Dinman, Jonathan/0000-0002-2402-9698 NR 26 TC 24 Z9 27 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 1999 VL 274 IS 23 BP 16487 EP 16493 DI 10.1074/jbc.274.23.16487 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600071 PM 10347211 ER PT J AU Zeng, FY Hopp, A Soldner, A Wess, J AF Zeng, FY Hopp, A Soldner, A Wess, J TI Use of a disulfide cross-linking strategy to study muscarinic receptor structure and mechanisms of activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; 3RD CYTOPLASMIC LOOP; SITE-DIRECTED MUTAGENESIS; ACETYLCHOLINE-RECEPTOR; LIGAND-BINDING; HORMONE RECEPTOR; BOVINE RHODOPSIN; CONFORMATIONAL-CHANGES; TRANSMEMBRANE HELICES; CHOLINERGIC RECEPTOR AB To gain insight into the molecular architecture of the cytoplasmic surface of G protein-coupled receptors, we have developed a disulfide cross-linking strategy using the m3 muscarinic receptor as a model system. To facilitate the interpretation of disulfide cross-linking data, we initially generated a mutant m3 muscarinic receptor (referred to as m3'(3C)-Xa) in which most native Cys residues had been deleted or substituted with Ala or Ser (remaining Cys residues Cys-140, Cys-220, and Cys-532) and in which the central portion of the third intracellular loop had been replaced with a factor Xa cleavage site. Radioligand binding and second messenger assays showed that the m3'(3C)-Xa mutant receptor was fully functional. In the next step, pairs of Cys residues were reintroduced into the m3'(3C)-Xa construct, thus generating 10 double Cys mutant receptors, All 10 mutant receptors contained a Cys residue at position 169 at the beginning of the second intracellular loop and a second Cys within the C-terminal portion of the third intracellular loop, at positions 484-493, Radioligand binding studies and phosphatidylinositol assays indicated that all double Cys mutant receptors were properly folded. Membrane lysates prepared from COS-7 cells transfected with the different mutant receptor constructs were incubated with factor Xa protease and the oxidizing agent Cu(II)-(1,10-phenanthroline)(3), and the formation of intramolecular disulfide bonds between juxtaposed Cys residues was monitored by using a combined immunoprecipitation/immunoblotting strategy. To our surprise, efficient disulfide cross-linking was observed with 8 of the 10 double Cys mutant receptors studied (Cys-169/Cys-484 to Cys-491), suggesting that the intracellular m3 receptor surface is characterized by pronounced backbone fluctuations. Moreover, [S-35]guanosine 5'-3-O-(thio)triphosphate binding assays indicated that the formation of intramolecular disulfide cross-links prevented or strongly inhibited receptor-mediated G protein activation, suggesting that the highly dynamic character of the cytoplasmic receptor surface is a prerequisite for efficient receptor-G protein interactions. This is the first study using a disulfide mapping strategy to examine the three-dimensional structure of a hormone-activated G protein-coupled receptor. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. NR 68 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 1999 VL 274 IS 23 BP 16629 EP 16640 DI 10.1074/jbc.274.23.16629 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202TQ UT WOS:000080668600090 PM 10347230 ER PT J AU Li, JG Chen, CG Yin, JL Rice, K Zhang, Y Matecka, D de Riel, JK DesJarlais, RL Liu-Chen, LY AF Li, JG Chen, CG Yin, JL Rice, K Zhang, Y Matecka, D de Riel, JK DesJarlais, RL Liu-Chen, LY TI Asp147 in the third transmembrane helix of the rat mu opioid receptor forms ion-pairing with morphine and naltrexone SO LIFE SCIENCES LA English DT Article DE mu opioid receptor; structure-function relationship; site-directed mutagenesis ID SITE-DIRECTED MUTAGENESIS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; OPIATE-RECEPTOR; LIGAND-BINDING; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; TRH RECEPTOR; HORMONE TRH; AMINO-ACIDS AB We tested the hypotheses that the carboxylate side chain of Asp147 of the mu opioid receptor interacts with the protonated nitrogen of naltrexone and morphine and that this interaction is important for pharmacological properties of the two compounds. Mutation of Asp147 to Ala or Asn substantially reduced the affinity of naltrexone and the affinity, potency and efficacy of morphine, while the Glu mutant had similar properties as the wildtype, indicating the significant role of the carboxylate group of Asp147 in receptor binding and activation. This role could be due to its direct interaction with ligands or involvement in interhelical interactions. The unprotonated analogs of naltrexone and morphine, cyclopropylcarbonyl noroxymorphone (CPCNOM) and N-formylnormorphine (NFNM), respectively, were used to discriminate between these mechanisms. CPCNOM was much less potent as an antagonist and had substantially lower affinity for the mu receptor than naltrexone. Similarly, NFNM was unable to activate the mu receptor and had much lower affinity than morphine. These results indicate the importance of the protonated nitrogen. Notably, the D147A and D147N mutations did not appreciably affect the binding affinities of CPCNOM and NFNM. In addition, the D147E mutant had similar affinities for CPCNOM and NFNM as the D147A and D147N mu receptors. Thus, the carboxylate group of Asp147 is not important for binding of the two unprotonated compounds. These results indicate that the carboxylate group of Asp147 of the mu receptor interacts directly with the protonated nitrogen of naltrexone and morphine and this interaction is important for binding and receptor activation. C1 Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Fels Inst Mol Biol & Canc Res, Philadelphia, PA 19140 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. SmithKline Beecham Pharmaceut, Dept Phys & Struct Chem, King Of Prussia, PA 19406 USA. RP Liu-Chen, LY (reprint author), Temple Univ, Sch Med, Dept Pharmacol, 3420 N Broad St, Philadelphia, PA 19140 USA. FU NIDA NIH HHS [DA 04745, DA06650, DA10702] NR 39 TC 46 Z9 47 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUN 4 PY 1999 VL 65 IS 2 BP 175 EP 185 DI 10.1016/S0024-3205(99)00234-9 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 206BH UT WOS:000080855800007 PM 10416823 ER PT J AU Borlongan, CV Kwanbara, Y Fujisaki, T Watanabe, S AF Borlongan, CV Kwanbara, Y Fujisaki, T Watanabe, S TI Cyclosporine-A reduces spontaneous place preference in adult rats SO NEUROSCIENCE LETTERS LA English DT Article DE immunosuppressant; conditioning; place preference; reinforcing effect; aversive stimulus; drug abuse ID DOPAMINERGIC-NEURONS; NEUROTROPHIC ACTIONS; 6-HYDROXYDOPAMINE; SURVIVAL; DECREASE; BRAIN; MICE AB Cyclosporine-A (CsA) and its analogues have been shown to directly alter locomotor activity. The present study examined CsA effects on spontaneous preferential behavior in adult rats, using a two-shuttle compartment box. The initial preference (>450 s staying time) of the animal for one compartment was measured at pre-conditioning session (900 s). During conditioning session tone 60-min session per day for 6 consecutive days), the animal was alternately injected with CsA (5, 10, 20 and 30 mg/kg per day, i.p.) and vehicle, and its movement restricted to the preferred compartment and the other compartment, respectively. At post-conditioning session (900 s), animals were allowed to freely explore the box. Animals that were treated with 10 mg/kg CsA significantly spent less staying time in the preferred compartment, while those that received other CsA doses displayed a trend of decreased staying time in the preferred compartment. The present data demonstrate that CsA antagonized the spontaneous preferential behavior of animals, and warrant investigations on the drug's utility in altering other preferential behaviors (e.g. drug addiction, alcohol abuse). (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Keio Univ, Dept Psychol, Minato Ku, Tokyo 108, Japan. NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Watanabe, S (reprint author), Keio Univ, Dept Psychol, Minato Ku, 2-15-45 Mita, Tokyo 108, Japan. OI Borlongan, Cesar/0000-0002-2966-9782 NR 20 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 4 PY 1999 VL 267 IS 3 BP 169 EP 172 DI 10.1016/S0304-3940(99)00357-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 202LK UT WOS:000080653600006 PM 10381003 ER PT J AU Nathanson, N Auerbach, JD AF Nathanson, N Auerbach, JD TI Confronting the HIV pandemic SO SCIENCE LA English DT Editorial Material C1 NIH, Off AIDS Res, US Dept HHS, Bethesda, MD 20892 USA. RP Nathanson, N (reprint author), NIH, Off AIDS Res, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 4 PY 1999 VL 284 IS 5420 BP 1619 EP 1619 DI 10.1126/science.284.5420.1619 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 202TM UT WOS:000080668300017 PM 10383335 ER PT J AU Clemens, J Hoffman, S Ivanoff, B Klugman, K Levine, MM Neira, M Pang, T AF Clemens, J Hoffman, S Ivanoff, B Klugman, K Levine, MM Neira, M Pang, T TI Typhoid fever vaccines SO VACCINE LA English DT Letter C1 NICHD, Bethesda, MD USA. NMRC, Rockville, MD USA. WHO, HTD, CH-1211 Geneva, Switzerland. Univ Witwatersrand, Johannesburg, South Africa. S African Inst Med Res, ZA-2000 Johannesburg, South Africa. CVD, Baltimore, MD USA. Univ Malaya, Kuala Lumpur, Malaysia. RP Clemens, J (reprint author), NICHD, Bethesda, MD USA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 4 PY 1999 VL 17 IS 20-21 BP 2476 EP 2478 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 210JH UT WOS:000081101000001 PM 10418892 ER PT J AU Clements-Mann, ML Makhene, MK Mrukowicz, J Wright, PF Hoshino, Y Midthun, K Sperber, E Karron, R Kapikian, AZ AF Clements-Mann, ML Makhene, MK Mrukowicz, J Wright, PF Hoshino, Y Midthun, K Sperber, E Karron, R Kapikian, AZ TI Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants SO VACCINE LA English DT Article DE rotavirus vaccines; human-bovine reassortant rotavirus vaccines; pediatric vaccines; live attenuated virus vaccines; diarrheal vaccines ID RHESUS-ROTAVIRUS; QUADRIVALENT VACCINE; VENEZUELAN INFANTS; ANTIBODY-RESPONSE; EFFICACY; WC3; CANDIDATES; TRIAL; VP7; GASTROENTERITIS AB Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 3 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-I, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or Ige ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected mast infants. 10/20 (50%) by D x UK 9/11 (82%) by DS-l x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK, All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Internal Med, Ctr Immunizat Res, Baltimore, MD 21205 USA. RP Kapikian, AZ (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Room 100,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. FU NIAID NIH HHS [1-AI-05050, 1-AI-15095] NR 37 TC 48 Z9 50 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 4 PY 1999 VL 17 IS 20-21 BP 2715 EP 2725 DI 10.1016/S0264-410X(98)00497-6 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 210JH UT WOS:000081101000032 PM 10418923 ER PT J AU Gnadisch, D London, ED Terry, P Hill, GR Mukhin, AG AF Gnadisch, D London, ED Terry, P Hill, GR Mukhin, AG TI High affinity binding of [H-3]epibatidine to rat brain membranes SO NEUROREPORT LA English DT Article DE affinity; cytisine; epibatidine; nicotine; nicotinic acetylcholine receptor; receptor binding ID NICOTINIC ACETYLCHOLINE-RECEPTORS; CHOLINERGIC RECEPTORS; IN-VITRO; EPIBATIDINE; AGONIST; SUBTYPE; POTENT; ANALOG; SITES AB SEVERAL compounds, such as epibatidine, A-85380, and their analogs, have been identified recently as nAChR ligands whose affinities lie in the low picomolar range. Accurate measurement of such high affinities is fraught with certain technical difficulties, which may account for the inconsistency of previously reported affinities of epibatidine, ranging from 4 to 60 pM. Here, we demonstrate that (+/-)-[H-3]epibatidine (1-500 pM) binds to a single population of sites in rat brain with K-D of 8+/-2 pM. This affinity was confirmed in both kinetic experiments and competition assays with (+/-)[H-3]epibatidine and (-)-[H-3]cytisine, which were performed under experimental conditions developed specifically for ligands with subnanomolar affinities. Variations from these conditions decreased the observed affinities. NeuroReport 10:1631-1636 (C) 1999 Lippincott Williams & Wilkins. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Mukhin, AG (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 26 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 3 PY 1999 VL 10 IS 8 BP 1631 EP 1636 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 212PJ UT WOS:000081225200004 PM 10501548 ER PT J AU Cavallaro, S Gibbs, CJ Pergami, P AF Cavallaro, S Gibbs, CJ Pergami, P TI Early induction of protein nexin-I in scrapie SO NEUROREPORT LA English DT Article DE differential display; prion disease; protein nexin-I ID MESSENGER-RNA; DIFFERENTIAL DISPLAY; PRION PROTEIN; EXPRESSION; DISEASE; IDENTIFICATION; LOCALIZATION; BRAIN; DEATH; GENES AB WE used RNA fingerprinting by arbitrary primed PCR to identify genes whose expression is up-regulated in the brain of hamsters affected by prion disease. One gene implicated by RNA fingerprinting encoded the hamster homologue of protein nexin-I (PN-I), a serine proteinase inhibitor, and was further investigated by Northern blot analysis. PN-I mRNA levels were increased at pre-clinical stages (19 days after inoculation) and remained elevated when the spongiform encephalopathy was anatomopathologically and clinically evident (at 50 and 80 days). Future RNA screening conducted as illustrated may help to reveal a spectrum of genes relevant for the etiopathogenesis and/or diagnosis of prion disease. NeuroReport 10:1677-1681 (C) 1999 Lippincott Williams & Wilkins. C1 CNR, Ist Bioimmagini & Fisiopatol Sistema Nervoso Cent, I-95123 Catania, Italy. IRCCS, Oasi Inst Res Mental Retardat & Brain Aging, Troina, EN, Italy. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20814 USA. IRCCS C Mondino, Ist Neurol, I-27100 Pavia, Italy. RP Cavallaro, S (reprint author), CNR, Ist Bioimmagini & Fisiopatol Sistema Nervoso Cent, Piazza Roma 2, I-95123 Catania, Italy. RI Cavallaro, Sebastiano/F-3104-2010 OI Cavallaro, Sebastiano/0000-0001-7590-1792 NR 26 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 3 PY 1999 VL 10 IS 8 BP 1677 EP 1681 DI 10.1097/00001756-199906030-00010 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 212PJ UT WOS:000081225200012 PM 10501556 ER PT J AU Collins, KL Nabel, GJ AF Collins, KL Nabel, GJ TI Naturally attenuated HIV lessons for AIDS vaccines and treatment SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY VIRUS TYPE-1; NEF PROTEIN; INFECTION; GENE; RECIPIENTS; DONOR; LIVE; SIV C1 Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. RP Collins, KL (reprint author), Univ Michigan, Med Ctr, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1999 VL 340 IS 22 BP 1756 EP 1757 DI 10.1056/NEJM199906033402210 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 201WQ UT WOS:000080620200010 PM 10352170 ER PT J AU Zametkin, AJ Ernst, M AF Zametkin, AJ Ernst, M TI Attention-deficit-hyperactivity disorder - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. Natl Inst Drug Abuse, Baltimore, MD 21334 USA. RP Zametkin, AJ (reprint author), NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 1999 VL 340 IS 22 BP 1767 EP 1767 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 201WQ UT WOS:000080620200026 ER PT J AU Keane, MM Ettenberg, SA Nau, MM Banerjee, P Cuello, M Penninger, J Lipkowitz, S AF Keane, MM Ettenberg, SA Nau, MM Banerjee, P Cuello, M Penninger, J Lipkowitz, S TI cbl-3: a new mammalian cbl family protein SO ONCOGENE LA English DT Article DE cbl proteins; EGF receptor; signal transduction ID PROTOONCOGENE C-CBL; PHOSPHOTYROSINE-BINDING DOMAIN; SIGNAL-TRANSDUCTION; V-CBL; NEGATIVE REGULATOR; POINT MUTATIONS; TYROSINE KINASE; ONCOGENE; MOTIF; ACTIVATION AB We have cloned a new human gene, cbl-3, which encodes a protein with marked homology to the cbl family of proteins. The predicted protein encoded by this gene retains the conserved phosphotyrosine binding domain (PTB) in the N-terminal and the zinc finger but is significantly shorter (MW 52.5 kDa) than the other mammalian cbl proteins. The protein lacks the extensive proline rich domain and leucine zipper seen in c-cbl and cbl-b and structurally most resembles the C. elegans and Drosophila cbl proteins. The gene is ubiquitously expressed with highest expression in the aerodigestive tract, prostate, adrenal gland, and salivary gland. The protein is phosphorylated and recruited to the EGFR upon EGF stimulation and inhibits EGF stimulated MAP kinase activation. In comparison to the other mammalian cbl proteins (e.g. cbl-b), cbl-3 interacts with a restricted range of proteins containing Src Homology 3 regions, An alternatively spliced form of the cbl-3 protein was also identified which deletes a critical region of the PTB domain and which does not interact with the EGFR nor inhibit EGF stimulated MAP kinase activation. These data demonstrate that cbl-3, a novel mammalian cbl protein, is a regulator of EGFR mediated signal transduction. C1 Bethesda Naval Hosp, Dept Genet, Med Branch, NCI, Bethesda, MD 20889 USA. Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Amgen Inst, Toronto, ON, Canada. Univ Toronto, Dept Immunol, Ontario Canc Inst, Amgen Inst, Toronto, ON, Canada. RP Lipkowitz, S (reprint author), NCI, Dept Genet, Med Branch, Natl Naval Med Ctr, Bldg 8,Room 5101, Bethesda, MD 20889 USA. RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 NR 43 TC 84 Z9 88 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 3 PY 1999 VL 18 IS 22 BP 3365 EP 3375 DI 10.1038/sj.onc.1202753 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 201HL UT WOS:000080589300007 PM 10362357 ER PT J AU Day, RM Cioce, V Breckenridge, D Castagnino, P Bottaro, DP AF Day, RM Cioce, V Breckenridge, D Castagnino, P Bottaro, DP TI Differential signaling by alternative HGF isoforms through c-Met: activation of both MAP kinase and PI 3-kinase pathways is insufficient for mitogenesis SO ONCOGENE LA English DT Article DE HGF; c-met; MAPK; PI 3-kinase; motogenesis; mitogenesis ID HEPATOCYTE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; FACTOR SCATTER FACTOR; KIDNEY-CELLS REQUIRES; GRB2 BINDING-SITE; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; TRANSFORMATION; TRANSDUCTION; MOTILITY AB HGF/NK2, a naturally occurring truncated HGF isoform, antagonizes the mitogenic and morphogenic activities of full length HGF, but stimulates cell scatter, or the motogenic response to HGF. We studied postreceptor signaling by these HGF isoforms in the human breast epithelial cell line 184B5, and in murine myeloid progenitor 32D cells transfected with c-Met, the human HGF receptor (32D/c-Met). HGF stimulated DNA synthesis in 184B5 and 32D/c-Met cells, while HGF/NK2 was mitogenically inactive, despite the ability of HGF/NK2 to stimulate c-Met autophosphorylation, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) in both cell systems. In 184B5 cells, HGF stimulated sustained MAPK activation, while activation by HGF/NK2 declined rapidly. In contrast, both isoforms activated MAPK with rapidly attenuated kinetics in 32D/c-Met cells. In both cell systems the increased motility observed in response to either HGF or HGF/NK2 treatment was more potently blocked by the PI3 kinase inhibitor wortmannin, than by PD98059, an inhibitor of MAPK kinase (MEK1). These data suggest that (1) alternative HGF isoforms signaling through c-Met generate both common and distinct biological responses, (2) the extent and duration of ligand-stimulated c-Met and MAPK activities are dependent on the cellular context and are not predictive of mitogenic signaling, and (3) in at least some HGF target cells, the activation of both MAPK and PI3K signaling pathways is insufficient for mitogenesis elicited through c-Met. C1 NCI, Cellular & Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), NCI, Cellular & Mol Biol Lab, Div Basic Sci, Bldg 37,Room 1E24,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 45 TC 65 Z9 66 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 3 PY 1999 VL 18 IS 22 BP 3399 EP 3406 DI 10.1038/sj.onc.1202683 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 201HL UT WOS:000080589300011 PM 10362361 ER PT J AU Yoshikawa, H Nagashima, M Khan, MA McMenamin, MG Hagiwara, K Harris, CC AF Yoshikawa, H Nagashima, M Khan, MA McMenamin, MG Hagiwara, K Harris, CC TI Mutational analysis of p73 and p53 in human cancer cell lines SO ONCOGENE LA English DT Article DE p73; mutation; deletion ID TUMOR-SUPPRESSOR GENE; RAS MUTATIONS; LUNG-CANCER; COLORECTAL-CANCER; CARCINOMAS; FREQUENT; PROTEIN; EXPRESSION; INHIBITOR; KINASES AB p73 is a candidate tumor suppressor gene with substantial DNA and protein homology to the p53 tumor suppressor gene. We have investigated two hypotheses: (a) p73 is mutated in diverse types of human cancer, and (b) p73 is functionally redundant with p53 in carcinogenesis so that mutations would be exclusive in these two genes. The entire coding region and intronic splice junctions of p73 were examined in 54 cancer cell lines. Three lung cancer cell lines contained mutations that affected the amino acid sequence. One amino acid substitution was in a region with homology to the specific DNA binding region of p53 and two microdeletions were outside the region of homology. Two of the cell lines with p73 mutations also carried p53 mutations. Although our results are inconsistent with the two hypotheses tested, p73 mutations may contribute infrequently to the molecular pathogenesis of human lung cancer. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2CD5, Bethesda, MD 20892 USA. NR 28 TC 50 Z9 54 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 3 PY 1999 VL 18 IS 22 BP 3415 EP 3421 DI 10.1038/sj.onc.1202677 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 201HL UT WOS:000080589300013 PM 10362363 ER PT J AU Kibler, KV Jeang, KT AF Kibler, KV Jeang, KT TI Taxing the cellular capacity for repair: Human T-Cell leukemia virus type 1, DNA damage, and adult T-Cell leukemia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID HTLV-I; PROTEIN; GROWTH; TRANSFORMATION; MICRONUCLEI; P16(INK4A); ACTIVATION; INDUCTION; GENES C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 306, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 18 TC 11 Z9 11 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 2 PY 1999 VL 91 IS 11 BP 903 EP 904 DI 10.1093/jnci/91.11.903 PG 2 WC Oncology SC Oncology GA 202YV UT WOS:000080680600001 PM 10359537 ER PT J AU Liaw, KL Glass, AG Manos, MM Greer, CE Scott, DR Sherman, M Burk, RD Kurman, RJ Wacholder, S Rush, BB Cadell, DM Lawler, P Tabor, D Schiffman, M AF Liaw, KL Glass, AG Manos, MM Greer, CE Scott, DR Sherman, M Burk, RD Kurman, RJ Wacholder, S Rush, BB Cadell, DM Lawler, P Tabor, D Schiffman, M TI Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INFECTION; RISK; NEOPLASIA; DETERMINANTS; PREVALENCE; GENOTYPES; CANCER AB Background: Human papillomavirus (HPV) infection has been strongly associated with cervical carcinoma and its cytologic precursors, squamous intraepithelial lesions (SIL). We investigated the risk of SIL prospectively following polymerase chain reaction (PCR)based DNA testing for a wide range of genital HPV types in a cohort of initially cytologically normal women, to clarify the role of HPV in the etiology of SIL. Methods: Starting in April 1989, 17 654 women who were receiving routine cytologic screening at Kaiser Permanente (Portland, OR) were followed for the development of incident SIL. During follow-up, 380 incident case patients and 1037 matched control subjects were eligible for this nested case-control study. Cervical lavages collected at enrollment and, later, at the time of case diagnosis (or the corresponding time for selection of central subjects) were tested for HPV DNA using a PCR-based method. The data were analyzed as contingency tables with two-sided P values or, for multivariable analyses, using odds ratios (ORs) with 95% confidence intervals (CLs). Results: In comparison with initially HPV-negative women, women who tested positive for HPV DNA at enrollment were 3.8 times (95% CI = 2.6-5.5) more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely (95% CI = 6.2-25.9) to develop high-grade SIL. At the time of diagnosis, the cross-sectional association of HPV DNA and SIL was extremely strong (OR = 44.4 and 95% CI = 24.2-81.5 for low-grade SIL and OR = 67.1 and 95% CI = 19.3-233.7 for high-grade SIL). HPV16 was the virus type most predictive of SIL, even low-grade SIL. Conclusions: These findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia, Furthermore, they support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Kaiser Permanente, Portland, OR USA. Cetus Corp, Emeryville, CA 94608 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Westal Inc, Rockville, MD USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Rm 7066, Bethesda, MD 20892 USA. NR 24 TC 182 Z9 192 U1 2 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 2 PY 1999 VL 91 IS 11 BP 954 EP 960 DI 10.1093/jnci/91.11.954 PG 7 WC Oncology SC Oncology GA 202YV UT WOS:000080680600012 PM 10359548 ER PT J AU Medina, D Smith, GH AF Medina, D Smith, GH TI Chemical carcinogen-induced tumorigenesis in parous, involuted mouse mammary glands SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER; REFRACTORINESS; RATS; DIFFERENTIATION; PROGESTERONE; EXPRESSION; PREVENTION; PREGNANCY; TISSUES; BRCA1 C1 Baylor Coll Med, Texas Med Ctr, Dept Cell Biol, Houston, TX 77030 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Medina, D (reprint author), Baylor Coll Med, Texas Med Ctr, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 23 TC 61 Z9 63 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 2 PY 1999 VL 91 IS 11 BP 967 EP 969 DI 10.1093/jnci/91.11.967 PG 3 WC Oncology SC Oncology GA 202YV UT WOS:000080680600014 PM 10359550 ER PT J AU Smith, MA Freidlin, B Ries, LAG Simon, R AF Smith, MA Freidlin, B Ries, LAG Simon, R TI Trends in reported incidence of primary malignant brain tumors in children in the United States - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID RHEUMATOID-ARTHRITIS; ASPIRIN; CANCER C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Canc Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Execut Plaza N,Rm 741, Bethesda, MD 20892 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 2 PY 1999 VL 91 IS 11 BP 973 EP 974 PG 2 WC Oncology SC Oncology GA 202YV UT WOS:000080680600018 ER PT J AU Ackerman, MJ AF Ackerman, MJ TI The Visible Human Project (R): A resource for education SO ACADEMIC MEDICINE LA English DT Article AB Throughout recorded history, the relationship between biological structure and function have been central to the understanding of health and disease. For many centuries, the anatomy illustrations originally created during the medieval period formed the basis for the study of medicine. But learning and understanding anatomic structures is limited by the fundamentally two-dimensional images traditionally used to teach them. The digital computer now allows scientists to acquire, store, manipulate, and display complex images. In 1989, the National Library of Medicine (NLM) began a project to use computer technologies to build a prototype digital image human male and female, the Visible Human Project (VHP), the digital images currently available in the VHP database, ongoing research and development, and plans for the future of the VHP. C1 Natl Lib Med, Off High Performance Comp & Commun, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Ackerman, MJ (reprint author), Natl Lib Med, Off High Performance Comp & Commun, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike,Bldg 38A,Room B1-N30, Bethesda, MD 20894 USA. NR 8 TC 86 Z9 127 U1 0 U2 5 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1999 VL 74 IS 6 BP 667 EP 670 DI 10.1097/00001888-199906000-00012 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 207TE UT WOS:000080951200016 PM 10386094 ER PT J AU Varrot, A Yamamoto, H Sekiguchi, J Thompson, J Davies, GJ AF Varrot, A Yamamoto, H Sekiguchi, J Thompson, J Davies, GJ TI Crystallization and preliminary X-ray analysis of the 6-phospho-alpha-glucosidase from Bacillus subtilis SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI K12; FUSOBACTERIUM-MORTIFERUM; FAMILY 4; PHOSPHOENOLPYRUVATE; PROTEINS; SEQUENCE; CLASSIFICATION; EXPRESSION AB 6-Phospho-alpha-glucosidase (GIvA) is the protein involved in the dissimilation of a-glycosides accumulated viaaphosphoenolpyruvate-dependent maltose phosphotransferase system (PEP-PTS) in Bacillus subtilis. The purified enzyme has been crystallized in a form suitable for X-ray diffraction analysis. Thin rod-like crystals have been grown by the hanging-drop method in the presence of manganese and NAD. They diffract beyond 22 Angstrom using synchrotron radiation and belong to the space group I222 (or its enantiomorph) with unit-cell dimensions a = 83.26, b = 102.56, c = 145.31 Angstrom and contain a single molecule of GIvA in the asymmetric unit. C1 Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England. Shinshu Univ, Fac Text Sci & Technol, Dept Appl Biol, Ueda, Nagano 386, Japan. NIDR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Davies, GJ (reprint author), Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England. RI Sekiguchi, Junichi/F-9963-2010; Davies, Gideon/A-9042-2011 OI Davies, Gideon/0000-0002-7343-776X NR 24 TC 9 Z9 10 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUN PY 1999 VL 55 BP 1212 EP 1214 DI 10.1107/S0907444999003790 PN 6 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 208NG UT WOS:000080997500018 PM 10329789 ER PT J AU Nelson, CB Rehm, J Ustun, TB Grant, B Chatterji, S AF Nelson, CB Rehm, J Ustun, TB Grant, B Chatterji, S TI Factor structures for DSM-IV substance disorder criteria endorsed by alcohol, cannabis, cocaine and opiate users: results from the WHO reliability and validity study SO ADDICTION LA English DT Article ID HEALTH INTERVIEW SURVEY; DEPENDENCE SYNDROME; III-R; SYMPTOM; DIMENSIONALITY; PROGRESSION; POPULATION; ABUSE AB Aims. The factor structure of DSM-IV substance disorder criteria is examined among alcohol, cannabis, cocaine and opiate users to determine the dimensionality of abuse and dependence criteria within each of these drug classes and whether a common construct can be generalized across drug classes. Design. 12-month criterion prevalence was assessed as part of the World Health Organization's Study on the Reliability and Validity of the Alcohol and Drug Use Disorder Instruments in various settings at eight sites around the world wing the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). A majority of respondents were recruited from non-treatment settings, in addition to exploratory factor analysis, confirmatory factor analysis was used to analyse factor structures using weighted least square methods and tetrachoric correlation matrices. Multi-sample analysis techniques were used to model differences between drug-classes. Findings. In the full data analyses identified a single factor solution for each user population and across user populations. However, analyses of data from users reporting low to moderate symptomatology identified a two-dimensional construct among alcohol, cannabis and opiate users consisting of a major "dependence" factor and a lesser "abuse" factor. In addition, results showed that neither the abuse criterion "(A2) use in physical hazardous situations" or the dependence criterion "(D7) use despite knowledge of psychological/physical problems" were central to the latent construct in ally of the user populations, except for D7 among alcohol users. Conclusions. The multi-dimensional results found among users with low to moderate symptomatology indicate that: (1) previous results from relatively homogeneous populations may have been biased towards lesser order solutions, and that (2) the DSM-IV substance disorder criteria describe at least two distinct phenomena, supporting the current DSM-IV organization of substance disorder criteria. Further work need to evaluate whether prevalent symptoms are present in random or predictable combinations, whether combinations reflecting a specific hierarchy of severity call be identified, and whether incident symptoms are accumulated in a predictable pattern, within specific user populations and across user populations. C1 WHO, Hlth & Social Change Cluster, Assessment Classificat & Epidemiol Grp, CH-1211 Geneva, Switzerland. NIAAA, Div Biometry & Epidemiol, Bethesda, MD USA. Fachhsch Hamburg, Hamburg, Germany. RP Nelson, CB (reprint author), WHO, Hlth & Social Change Cluster, Assessment Classificat & Epidemiol Grp, Ave Appia 20, CH-1211 Geneva, Switzerland. RI Rem, Jurgen/H-1309-2011 NR 30 TC 177 Z9 178 U1 2 U2 11 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 1999 VL 94 IS 6 BP 843 EP 855 DI 10.1046/j.1360-0443.1999.9468438.x PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 207FB UT WOS:000080924500007 PM 10665074 ER PT J AU Lands, WEM AF Lands, WEM TI Alcohol, slow wave sleep, and the somatotropic axis SO ALCOHOL LA English DT Review DE cholecystokinin; cytokines; leptin; low-dose alcohol; rapid eye movement (REM) sleep; slow wave sleep (SWS); somatotropin; somatostatin; thalamus; withdrawal ID GROWTH-HORMONE SECRETION; FATAL FAMILIAL INSOMNIA; OBSESSIVE-COMPULSIVE DISORDER; CAT THALAMOCORTICAL NEURONS; REM-SLEEP; DOPAMINERGIC SENSITIVITY; GAMMA-HYDROXYBUTYRATE; LEPTIN CONCENTRATIONS; DEPENDENT PATIENTS; P300 AMPLITUDE AB When alcohol is a large proportion of daily nutrient energy, the network of signals for energy homeostasis appears to adapt with abnormal patterns of sleep and growth hormone (GH) release along with gradual acquisition of an addictive physical dependency on alcohol. Early relapse during treatment of alcoholism is associated with a lower GH response to challenge, perhaps reflecting an altered balance of somatostatin (SS) to somatotropin releasing hormone (GHRH) that also affects slow wave sleep (SWS) in dependent patients. Normal patterns of sleep have progressively shorter SWS episodes and longer rapid eye movement (REM) episodes during the overall sleep period, but the early sleep cycles of alcoholics have truncated or non-existent SWS episodes, and the longer REM episodes occur in early cycles. During SWS delta wave activity, the hypothalamus releases GHRH, which causes the pituitary to release GH. Alcohol-dependent patients have lower levels of SWS power and GH release than normal subjects, and efforts to understand the molecular basis for this maladaptation and its relation to continued alcohol dependence merit encouragement. More needs to be learned about the possibility of decreasing alcohol dependency by increasing SWS or enhancing GHRH action. Published by Elsevier Science Inc. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Lands, WEM (reprint author), NIAAA, NIH, Willco Bldg,Suite 400,6000 Execut Blvd, Bethesda, MD 20892 USA. NR 101 TC 12 Z9 12 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN-JUL PY 1999 VL 18 IS 2-3 BP 109 EP 122 DI 10.1016/S0741-8329(98)00073-1 PG 14 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 222LU UT WOS:000081787700003 PM 10456561 ER PT J AU Zakhari, S AF Zakhari, S TI Molecular mechanisms underlying alcohol-induced cardioprotection: Contribution of hemostatic components - Introduction to the symposium SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID LOW-DENSITY LIPOPROTEINS; CORONARY HEART-DISEASE; EXPRESSION; ATHEROSCLEROSIS; INDUCTION; PROTEIN; CELLS; RISK C1 NIAAA, Bethesda, MD 20892 USA. RP Zakhari, S (reprint author), NIAAA, 600 Execut Blvd, Bethesda, MD 20892 USA. NR 19 TC 15 Z9 15 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 1999 VL 23 IS 6 BP 1108 EP 1110 DI 10.1111/j.1530-0277.1999.tb04232.x PG 3 WC Substance Abuse SC Substance Abuse GA 208KB UT WOS:000080989000022 PM 10397298 ER PT J AU Walsh, JK Benca, RM Bonnet, M Buysse, DJ Hauri, PJ Kiley, J Monjan, A Morin, CM Ricca, JG Rogus, S Roth, T Simon, RD AF Walsh, JK Benca, RM Bonnet, M Buysse, DJ Hauri, PJ Kiley, J Monjan, A Morin, CM Ricca, JG Rogus, S Roth, T Simon, RD CA Natl Heart Lung Blood Inst Working Grp Insomnia TI Insomnia: Assessment and management in primary care SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID PSYCHIATRIC-DISORDERS; DAYTIME SLEEPINESS; TREATMENT EFFICACY; PREVALENCE; COMPLAINTS; METAANALYSIS; POPULATION; TRIAZOLAM; TRAZODONE; ZOLPIDEM AB Patients with insomnia may experience one or more of the following problems: difficulty falling asleep, difficulty maintaining sleep. waking up too early in the morning and nonrefreshing sleep. In addition, daytime consequences such as fatigue, lack of energy, difficulty concentrating and irritability are often present. Approximately 10 percent of adults experience persistent insomnia, although most patients do not mention it during routine office visits. Asking sleep-related questions during the general review of systems and asking patients with sleep complaints to keep a sleep diary are helpful approaches in detecting insomnia. Behavior and pharmacologic therapies are used in treating insomnia. Behavior approaches take a few weeks to improve sleep but continue to provide relief even after training sessions have ended. Hypnotic medications are safe and effective in inducing, maintaining and consolidating sleep. Effective treatment of insomnia may improve the quality of life for many patients. C1 St Louis Univ, Hlth Sci Ctr, Dept Psychiat, St Louis, MO 63103 USA. RP Rogus, S (reprint author), NHLBI, Natl Ctr Sleep Disorders Res, NIH, Bldg 31,Room 4A-16,31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA. RI Morin, Charles/G-1021-2011 NR 36 TC 49 Z9 49 U1 0 U2 4 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUN PY 1999 VL 59 IS 11 BP 3029 EP 3038 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 205XG UT WOS:000080845700009 ER PT J AU Picciano, MF AF Picciano, MF TI Iron and folate supplementation: an effective intervention in adolescent females SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Picciano, MF (reprint author), Penn State Univ, Dept Nutr, 126 Henderson Bldg S, University Pk, PA 16802 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1999 VL 69 IS 6 BP 1069 EP 1070 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 199UT UT WOS:000080503000005 PM 10357724 ER PT J AU Potischman, N Weed, DL AF Potischman, N Weed, DL TI Causal criteria in nutritional epidemiology SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Workshop on the Role of Epidemiology in Determining When Evidence is Sufficient to Support Nutrition Recommendations CY OCT 07-08, 1997 CL WASHINGTON, D.C. SP ILSI N Amer DE causation; diet; epidemiology; nutrition recommendations; disease prevention; cancer prevention; disease etiology; causal criteria; causal inference; dose response; temporality; plausibility; study design; bias; confounding ID DIET HISTORY QUESTIONNAIRE; INVASIVE CERVICAL-CANCER; FOOD-FREQUENCY; UNDERDETERMINATION; INDICATORS; INFERENCE; RECORDS; WOMEN AB Making nutrition recommendations involves complex judgments about the balance between benefits and risks associated with a nutrient or food. Causal criteria are central features of such judgments but are not sufficient. Other scientific considerations include study designs, statistical tests, bias, confounding, and measurement issues. At a minimum, the set of criteria includes consistency, strength of association, dose response, plausibility, and temporality. The current practice, methods, and theory of causal inference permit flexibility in the choice of criteria, their relative priority, and the rules of inference assigned to them. Our approach is as follows. Consistency across study designs is compelling when the studies are of high quality and are not subject to biases. A statistically significant risk estimate with a >20% increase or decrease in risk is considered a positive finding. A statistically significant linear or otherwise regularly increasing trend reinforces the judgment in favor of a recommendation. A plausible hypothesis likewise reinforces a recommendation, although the rules of inference for biological evidence are highly variable and depend on the situation. Temporality is, for nutrition recommendations, more a consideration of the extent to which a dietary factor affects disease onset or progression. Evidence supporting these criteria provides a strong basis for making a nutrition recommendation, given due consideration of the balance between presumed benefits and presumed harms. Recommendations should make clear their breadth of application; a narrow recommendation involves a single disease or condition whereas a broad recommendation involves all relevant diseases or conditions. C1 NCI, Bethesda, MD 20892 USA. RP Potischman, N (reprint author), Univ Massachusetts, Dept Biostat & Epidemiol, Arnold House, Amherst, MA 01003 USA. NR 34 TC 35 Z9 35 U1 1 U2 12 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1999 VL 69 IS 6 BP 1309S EP 1314S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 199UT UT WOS:000080503000047 PM 10359231 ER PT J AU Sempos, CT Liu, K Ernst, ND AF Sempos, CT Liu, K Ernst, ND TI Food and nutrient exposures: what to consider when evaluating epidemiologic evidence SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Workshop on the Role of Epidemiology in Determining When Evidence is Sufficient to Support Nutrition Recommendations CY OCT 07-08, 1997 CL WASHINGTON, D.C. SP ILSI N Amer DE nutrition; epidemiology; cancer; coronary heart disease; coronary artery disease; diet; dietary survey methods; study design ID CORONARY HEART-DISEASE; DOUBLY LABELED WATER; SERUM-CHOLESTEROL; DIET-HEART; FREQUENCY QUESTIONNAIRES; INTERVENTION TRIAL; LIMITATIONS; NUTRITION; ENERGY; DEATH AB Nutritional epidemiology is the science concerned with conducting research into the relation between diet and disease risk. The public has a great deal of interest in this issue. Much of that interest, however, is fueled by the publication of sensationalized, startling, and often contradictory health messages. Unfortunately there is a great deal of confusion in both the scientific press and the public or lay press about the nature of nutritional epidemiology, its strengths, and its limitations. The purpose of this article is to discuss these strengths and limitations. It is hoped that clarification of these issues can help lead to a resolution of the research community's and lay public's misunderstandings about nutritional epidemiology research. C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD USA. Northwestern Univ, Sch Med, Dept Community Hlth & Prevent Med, Chicago, IL 60611 USA. RP Sempos, CT (reprint author), NIH, Off Res Minor Hlth, Bldg 1,Room 255,MSC 0164, Bethesda, MD 20817 USA. NR 60 TC 30 Z9 34 U1 1 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1999 VL 69 IS 6 BP 1330S EP 1338S PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 199UT UT WOS:000080503000050 PM 10357757 ER PT J AU Albanes, D AF Albanes, D TI beta-carotene and lung cancer: a case study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Workshop on the Role of Epidemiology in Determining When Evidence is Sufficient to Support Nutrition Recommendations CY OCT 07-08, 1997 CL WASHINGTON, D.C. SP ILSI N Amer DE beta-carotene; carotenoids; antioxidants; lung cancer; clinical trials; epidemiology; prevention ID VITAMIN-A; CARDIOVASCULAR-DISEASE; EPIDEMIOLOGIC EVIDENCE; HEART-DISEASE; RISK; PREVENTION; SUPPLEMENTATION; MORTALITY; VEGETABLES; POPULATION AB The conflicting evidence of the relation between beta-carotene and lung cancer in humans serves as a poignant case study with respect to what types of evidence are sufficient to support or change a nutrition recommendation. This article is a review of the available evidence of the relation between beta-carotene and lung cancer, including data regarding beta-carotene intake (from diet and supplements), beta-carotene biochemical status, and vegetable and fruit consumption, and a discussion of the role of this evidence in making nutrition recommendations. More than 30 case-control and cohort studies were conducted over many years in various populations and indicated that people who eat more vegetables and fruit, foods rich in carotenoids, and carotenoids (beta-carotene in particular), as well as those with higher blood beta-carotene concentrations, have a lower risk of lung cancer than those who eat fewer such foods or have lower beta-catotene concentrations. In contrast, the intervention results from large, controlled trials of beta-carotene supplementation do not support the observed beneficial associations or a role for supplemental beta-carotene in lung cancer prevention; instead, they provide striking evidence for adverse effects tie, excess lung cancer incidence and overall mortality) in smokers. The findings require that caution be exercised in recommending supplemental beta-carotene, particularly for smokers, and argue against changing the vegetable-fruit recommendations in the direction of greater nutrient specificity. This case study of beta-carotene and lung cancer stresses the importance of having results from at least one, and preferably more, large, randomized intervention trial before public health recommendations concerning micronutrient supplementation are considered. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Albanes, D (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 37 TC 51 Z9 51 U1 0 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1999 VL 69 IS 6 BP 1345S EP 1350S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 199UT UT WOS:000080503000052 PM 10359235 ER PT J AU Sander, CA Flaig, MJ Kaudewitz, P Jaffe, ES AF Sander, CA Flaig, MJ Kaudewitz, P Jaffe, ES TI The Revised European-American Classification of Lymphoid Neoplasms (REAL): A preferred approach for the classification of cutaneous lymphomas SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE cutaneous lymphoma; T cell; B cell; non-Hodgkin lymphoma ID B-CELL LYMPHOMA; SUBCUTANEOUS TISSUE; TRANSLOCATION; PROPOSAL AB The Revised European-American Classification of Lymphoid Neoplasms (REAL) classification is based on the principle that each type of lymphoma is a distinct disease defined by morphology, immunophenotypic and genetic features, clinical presentation, and course. If either primary or secondary involvement of the skin is a constant factor, this aspect is considered integral to disease definition. Organ-specific classification schemes, such as that proposed by the European Organization for Research and Treatment of Cancer (EORTC) for cutaneous lymphomas, are not required, and indeed may impede the recognition of common features of diseases involving multiple anatomic sites. The use of multiple classification systems is a step backward, and may lead to confusion among hematologists/oncologists and dermatologists. Nevertheless, cutaneous lymphomas in many instances are distinct. Their natural history is often more indolent than nodal lymphomas, and for that reason they often require different therapeutic approaches. We agree with the efforts of the EORTC classification to emphasize the unique clinical aspects of many cutaneous lymphomas, as this recognition is essential for appropriate clinical management. As has been learned for nodal lymphomas, clinical features play an important role in prognosis and should be used in guiding therapy. For cutaneous lymphomas, the presence or absence of systemic spread is particularly important. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. Univ Munich, Dept Dermatol, D-8000 Munich, Germany. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Bldg 10,Room 2N202,10 Ctr Dr MSC-1500, Bethesda, MD 20892 USA. NR 24 TC 25 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD JUN PY 1999 VL 21 IS 3 BP 274 EP 278 DI 10.1097/00000372-199906000-00012 PG 5 WC Dermatology SC Dermatology GA 202KN UT WOS:000080651600012 PM 10380051 ER PT J AU Linet, MS Gridley, G Nyren, O Mellemkjaer, L Olsen, JH Keehn, S Adami, HO Fraumeni, JF AF Linet, MS Gridley, G Nyren, O Mellemkjaer, L Olsen, JH Keehn, S Adami, HO Fraumeni, JF TI Primary liver cancer, other malignancies, and mortality risks following porphyria: A cohort study in Denmark and Sweden SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE incidence; liver cirrhosis; liver neoplasms; lung diseases, neoplasms; mortality; porphyria, acute intermittent; porphyria cutanea tarda ID ACUTE INTERMITTENT PORPHYRIA; POPULATION-BASED COHORT; CUTANEA-TARDA; HEPATOCELLULAR-CARCINOMA; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; FREQUENCY; HEMOCHROMATOSIS; SPLENECTOMY; MUTATIONS AB Cancer incidence and mortality risks were evaluated in a combined cohort of patients who were hospitalized for porphyria in Denmark (1977-1989) and Sweden (1965-1983). Patients were identified by using population-based hospitalization registries. The unique individual identification numbers of 530 patients with porphyria cutanea tarda (PCT) and 296 with acute intermittent porphyria (AIP) were linked to the nationwide cancer and death registries. Among patients with both types of porphyria, the authors found small but significantly elevated risks of all cancers combined (PCT, standardized incidence ratio (SIR) = 1.7, 95% confidence interval (CI) 1.3-2.2; AIP: SIR = 1.8, 95% CI 1.1-2.8) due to pronounced excesses of primary liver cancer (PCT: SIR = 21.2, 95% CI 8.5-43.7; AIP: SIR = 70.4, 95% CI 22.7-164.3) and moderate increases in lung cancer (PCT: SIR = 2.9, 95% CI 1.5-5.2; AIP: SIR = 2.8, 95% CI 0.3-10.2). PCT patients had a significantly increased risk of mortality from liver cirrhosis (standardized mortality ratio (SMR) = 8.4, 95% CI 3.1-18.4) or chronic obstructive pulmonary disease (SMR = 3.1, 95% CI 1.1-6.7). The increased risk of primary liver cancer and the increased risk of mortality from cirrhosis of the liver are consistent with findings from previous clinical surveys, but the new observations of excess lung cancer and chronic obstructive pulmonary disease require confirmation. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Danish Canc Soc, Div Canc Epidemiol, Copenhagen, Denmark. Informat Management Serv Inc, Silver Spring, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Linet, MS (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 7054,6120 Execut Blvd MSC7238, Bethesda, MD 20892 USA. NR 45 TC 44 Z9 46 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 BP 1010 EP 1015 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200DJ UT WOS:000080524100005 PM 10355376 ER PT J AU Tseng, M Morgenstern, H AF Tseng, M Morgenstern, H TI "Eating patterns and risk of colon cancer" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID DIETARY PATTERNS; CLUSTER-ANALYSIS; HEALTH C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. RP Tseng, M (reprint author), NIEHS, Epidemiol Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 NR 11 TC 0 Z9 0 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 BP 1074 EP 1075 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200DJ UT WOS:000080524100016 PM 10355386 ER PT J AU Buekens, P Notzon, F Kotelchuck, M Wilcox, A AF Buekens, P Notzon, F Kotelchuck, M Wilcox, A TI Why do Mexican-Americans have few low birthweight infants? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NIEHS, Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 109 BP S28 EP S28 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500109 ER PT J AU Cooper, GS Ephross, SA Sandler, DP AF Cooper, GS Ephross, SA Sandler, DP TI Menstrual periods and risk of adult-onset diabetes mellitus. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 5 BP S2 EP S2 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500006 ER PT J AU Devesa, S Grauman, D Blot, W Pennello, G Hoover, R Fraumeni, J AF Devesa, S Grauman, D Blot, W Pennello, G Hoover, R Fraumeni, J TI Atlas of cancer mortality in the United States, 1950-94. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 269 BP S68 EP S68 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500268 ER PT J AU Dorgan, J McMahon, R Hunsberger, S Friedman, L AF Dorgan, J McMahon, R Hunsberger, S Friedman, L CA DISC Callaborative Res Grp TI Diet and serum hormones in adolescence: Findings from the dietary intervention study in children. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 124 BP S31 EP S31 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500124 ER PT J AU Fillmore, CM Woodward, WE Dosemeci, M Hall, T AF Fillmore, CM Woodward, WE Dosemeci, M Hall, T TI Mortality of mariners on land and at sea. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20962 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 132 BP S33 EP S33 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500132 ER PT J AU Goldstein, AM Martinez, M Tucker, MA Demenais, F AF Goldstein, AM Martinez, M Tucker, MA Demenais, F TI Gene-covariate interaction between dysplastic nevi and the CDKN2A gene in American melanoma-prone families. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RI Demenais, Florence/G-3298-2013; Tucker, Margaret/B-4297-2015 OI Demenais, Florence/0000-0001-8361-0936; NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 206 BP S52 EP S52 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500207 ER PT J AU Hartman, T Dorgan, J Woodson, K Virtamo, J Tangrea, J Heinonen, OP Taylor, P Albanes, D AF Hartman, T Dorgan, J Woodson, K Virtamo, J Tangrea, J Heinonen, OP Taylor, P Albanes, D TI Effects of alpha-tocopherol supplementation on serum hormones in older men. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 85 BP S22 EP S22 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500085 ER PT J AU Lacey, J Brinton, L Abbas, F Barnes, W Gravitt, P Greenberg, M Hadjimichael, O Silverberg, S McGowan, L Mortel, R Schwartz, P Hildesheim, A AF Lacey, J Brinton, L Abbas, F Barnes, W Gravitt, P Greenberg, M Hadjimichael, O Silverberg, S McGowan, L Mortel, R Schwartz, P Hildesheim, A TI Oral contraceptive use in adenocarcinomas and squamous cell cancers of the cervix. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 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 JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 23 BP S6 EP S6 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500023 ER PT J AU Lacy, J Deng, J Gao, YT Mostofi, KF Sesterhenn, I Xie, T Hsing, A AF Lacy, J Deng, J Gao, YT Mostofi, KF Sesterhenn, I Xie, T Hsing, A TI Prostate cancer, benign prostatic hyperplasia, and physical activity in Shanghai, China. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 112 BP S28 EP S28 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500112 ER PT J AU Leveille, SG Gray, S LaCroix, AZ Ferrucci, L Black, DJ Guralnik, JM AF Leveille, SG Gray, S LaCroix, AZ Ferrucci, L Black, DJ Guralnik, JM TI Risk factors for infections involving hospitalization in older women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 246 BP S62 EP S62 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500246 ER PT J AU Marcus, PM Vineis, P Rothman, N AF Marcus, PM Vineis, P Rothman, N TI NAT2 slow acetylation and bladder cancer risk: A meta-analysis of 24 case-control studies. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 189 BP S48 EP S48 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500189 ER PT J AU Marcus, PM Newman, B Millikan, RC Baird, DD Moorman, PG Qaqish, B AF Marcus, PM Newman, B Millikan, RC Baird, DD Moorman, PG Qaqish, B TI Breast cancer epidemiology: The case for adolescent exposures. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 106 BP S27 EP S27 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500107 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Glucose regulation and gallstone disease. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 10 BP S3 EP S3 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500012 ER PT J AU Schairer, C Lubin, J Troisi, R Sturgeon, S Brinton, L Hoover, R AF Schairer, C Lubin, J Troisi, R Sturgeon, S Brinton, L Hoover, R TI Estrogen and estrogen-progestin replacement therapy and breast cancer risk. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 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 JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 225 BP S57 EP S57 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500225 ER PT J AU Sussman, JB Seeman, TE Albert, MS Berkman, LF Blazer, DG Rowe, JW Reuben, DB Harris, TB AF Sussman, JB Seeman, TE Albert, MS Berkman, LF Blazer, DG Rowe, JW Reuben, DB Harris, TB TI Inflammation mortality association is explained by cardiovascular risk factors. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1999 VL 149 IS 11 SU S MA 245 BP S62 EP S62 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200EK UT WOS:000080526500244 ER PT J AU Reid, AE Koziel, MJ Aiza, I Jeffers, L Reddy, R Schiff, E Lau, JYN Dienstag, JL Liang, TJ AF Reid, AE Koziel, MJ Aiza, I Jeffers, L Reddy, R Schiff, E Lau, JYN Dienstag, JL Liang, TJ TI Hepatitis C virus genotypes and viremia and hepatocellular carcinoma in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; POLYMERASE CHAIN-REACTION; VIRAL GENOTYPES; INFECTION; RNA; CIRRHOSIS; RISK; VARIABILITY; MORTALITY; SEVERITY AB OBJECTIVE: Hepatitis C virus (HCV) is a well recognized cause of hepatocellular carcinoma (HCC). The pathogenic significance of HCV genotypes in hepatocarcinogenesis is undefined. The aim of this study was to investigate the genotypic distribution and viremic level of HCV in patients with HCV-associated cirrhosis with or without HCC. METHODS: A total of 28 HCV-infected patients with HCC (HCC+) and 38 patients with HCV-associated cirrhosis without HCC (HCC-) were studied. HCV genotype was assessed by the genotype-specific polymerase chain reaction (PCR) method of Okamoto and restriction fragment length polymorphism (RFLP) of the 5' untranslated region (5' UTR). Hepatitis C viremia was quantitated with the branched-chain DNA (bDNA) assay. RESULTS: Using the Okamoto method, we found genotype Ib in 63% of the HCC+ group and 74% of the HCC- group, 36% of the HCC+ group and 16% of the HCC- group were coinfected with a combination of genotype Ib and another genotype. Using the RFLP method, we found genotype Ib in 41% of the HCC+ group and in 24% of the HCC- group. Other genotypes accounted for 18% of the HCC+ group and 55% of the HCC- group; no combination genotypes were identified. Poor concordance occurred between the two genotyping methods. Mean bDNA levels were not significantly different between the two groups. CONCLUSIONS: Our study demonstrates that no particular HCV genotypes were associated with HCC and genotype did not appear to influence the development of HCV-associated HCC. (Am J Gastroenterol 1999;94:1619-1626. (C) 1999 by Am. Cell. of Gastroenterology). C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Ctr Liver Dis, Miami, FL USA. Univ Florida, Div Gastroenterol Hepatol & Nutr, Gainesville, FL USA. RP Reid, AE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GI Unit GJ724,Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [K08AI01210]; NIDDK NIH HHS [P30DK43351-08, T32DK07191-23] NR 37 TC 29 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 1999 VL 94 IS 6 BP 1619 EP 1626 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 203NQ UT WOS:000080714100033 PM 10364034 ER PT J AU Pearson, JL Caine, ED Lindesay, J Conwell, Y Clark, DC AF Pearson, JL Caine, ED Lindesay, J Conwell, Y Clark, DC TI Studies of suicide in later life - Methodologic considerations and research directions SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID DELIBERATE SELF-HARM; PSYCHOLOGICAL AUTOPSY; RATIONAL SUICIDE; FOLLOW-UP; OLD-AGE; DEPRESSION; SEX; HOPELESSNESS; PEOPLE; STATES AB Later-life suicide is a tragedy that occurs worldwide. Often it is preventable. Here, the authors summarize an international workshop where they review four research approaches to studying putative risk factors: epidemiologic studies of suicidal behaviours, clinic-based follow-up studies, studies of suicide attempters, and psychological autopsy studies. They provide brief descriptions of the approaches, examples of questions best addressed by each approach, and their weakness and limitations; they also recommend promising areas for the future research and propose opportunities for research that could be conducted cross-nationally. C1 NIMH, Bethesda, MD 20892 USA. RP Pearson, JL (reprint author), NIMH, Room 7160,6001 Execut Blvd,MSC 9635, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH51201] NR 72 TC 8 Z9 8 U1 2 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SUM PY 1999 VL 7 IS 3 BP 203 EP 210 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 211XX UT WOS:000081188100003 PM 10438690 ER PT J AU Seppala, R Lehto, VP Gahl, WA AF Seppala, R Lehto, VP Gahl, WA TI Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ACID STORAGE DISEASE; FREE SIALIC-ACID; FIRST 2 STEPS; ACETYLNEURAMINIC ACID; SALLA DISEASE; RAT-LIVER; 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; FIBROBLASTS; METABOLISM; DISORDER AB Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free N-acetylneuraminic acid (NeuAc, sialic acid). Overproduction of NeuAc is believed to result from loss of feedback inhibition of uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac). We report the cloning and characterization of human UDP-GlcNAc 2-epimerase cDNA, with mutation analysis of three patients with sialuria. Their heterozygote mutations, R266W; R266Q, and R263L, indicate that the allosteric site of the epimerase resides in the region of codons 263-266. The heterozygous nature of the mutant allele in all three patients reveals a dominant mechanism of inheritance for sialuria. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Oulu Univ, Dept Pathol, SF-90220 Oulu, Finland. RP Gahl, WA (reprint author), NICHD, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK48796]; PHS HHS [M01-00064] NR 27 TC 90 Z9 93 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1999 VL 64 IS 6 BP 1563 EP 1569 DI 10.1086/302411 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 203FA UT WOS:000080696200008 PM 10330343 ER PT J AU Kovach, MJ Lin, JP Boyadjiev, S Campbell, K Mazzeo, L Herman, K Rimer, LA Frank, W Llewellyn, B Jabs, EW Gelber, D Kimonis, VE AF Kovach, MJ Lin, JP Boyadjiev, S Campbell, K Mazzeo, L Herman, K Rimer, LA Frank, W Llewellyn, B Jabs, EW Gelber, D Kimonis, VE TI A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PERIPHERAL MYELIN PROTEIN-22; DEJERINE-SOTTAS NEUROPATHY; SENSORINEURAL HEARING-LOSS; MOTOR-SENSORY NEUROPATHY; TREMBLER-J MOUSE; HEREDITARY NEUROPATHY; AUTOSOMAL-DOMINANT; PRESSURE PALSIES; DEMYELINATING NEUROPATHY; TRINUCLEOTIDE REPEATS AB Charcot-Marie-Tooth disease (CMT) with deafness is clinically distinct among:the genetically heterogeneous group of CMT disorders. Molecular studies in a large family with-autosomal dominant CMT and deafness have not been reported. The present molecular study involves a family with progressive features of CMT and deafness, originally reported by Kousseff et al. Genetic analysis of 70 individuals (31 affected, 28 unaffected, and 11 spouses):revealed linkage to markers on chromosome 17p11.2-p12, with a maximum LOD score of 9.01 for marker D17S1357 at a recombination fraction of .03. Haplotype-analysis placed:the CMT-deafness locus between markers D17S839 and D17S122, a similar to 0.6-Mb interval. This critical region lies: within the CMT type 1A duplication region and excludes MYO15, a gene coding an unconventional myosin that causes a form of autosomal recessive deafness called DFNB3. Affected individuals from this family do not have the common 1.5- Mb duplication of CMT type 1A. Direct sequencing of the candidate peripheral myelin protein 22 (PMP22) gene detected a unique G-->C transversion in the heterozygous state in all affected individuals, at position 248 in coding exon, predicted to result in an Ala67Pro substitution in the second transmembrane domain of PMP22. C1 So Illinois Univ, Sch Med, Dept Pediat, Div Genet & Metab, Springfield, IL 62794 USA. So Illinois Univ, Sch Med, Dept Surg, Springfield, IL 62794 USA. So Illinois Univ, Sch Med, Dept Neurol, Springfield, IL 62794 USA. Illinois State Police Lab, Springfield, IL USA. NIAMSD, Genet Study Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Dept Pediat Med & Surg, Baltimore, MD USA. RP Kimonis, VE (reprint author), So Illinois Univ, Sch Med, Dept Pediat, Div Genet & Metab, POB 19230, Springfield, IL 62794 USA. OI Jabs, Ethylin/0000-0001-8983-5466 FU NCRR NIH HHS [RR00722] NR 66 TC 42 Z9 45 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1999 VL 64 IS 6 BP 1580 EP 1593 DI 10.1086/302420 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 203FA UT WOS:000080696200010 PM 10330345 ER PT J AU Balemans, W Van Den Ende, J Paes-Alves, AF Dikkers, FG Willems, PJ Vanhoenacker, F de Almeida-Melo, N Alves, CF Stratakis, CA Hill, SC Van Hul, W AF Balemans, W Van Den Ende, J Paes-Alves, AF Dikkers, FG Willems, PJ Vanhoenacker, F de Almeida-Melo, N Alves, CF Stratakis, CA Hill, SC Van Hul, W TI Localization of the gene for sclerosteosis to the van Buchem Disease-gene region on chromosome 17q12-q21 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HYPEROSTOSIS CORTICALIS GENERALISATA; AUTOSOMAL DOMINANT OSTEOSCLEROSIS; FEATURES AB Sclerosteosis is an uncommon, autosomal recessive, progressive, sclerosing, bone dysplasia characterized by generalized osteosclerosis and hyperostosis of the skeleton, affecting mainly the skull and mandible. In most patients this causes facial paralysis and hearing loss. Other features are gigantism and hand abnormalities. In the present study, linkage analysis in two consanguineous families with sclerosteosis resulted in the assignment of the sclerosteosis gene to chromosome 17q12-q21. This region was analyzed because of the recent assignment to this chromosomal region of the gene causing van Buchem disease, a fare autosomal recessive condition with a hyperostosis similar to sclerosteosis. Because of the clinical similarities between sclerosteosis and van Buchem disease, it has previously been suggested that both conditions might be caused by mutations in the same gene. Our study now provides genetic evidence for this hypothesis. C1 Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium. Univ Antwerp, Dept Biochem Physiol & Genet, B-2020 Antwerp, Belgium. Univ Antwerp, Dept Radiol, B-2020 Antwerp, Belgium. Univ Fed Bahia, Dept Ginecol Obstet & Reprod, Salvador, BA, Brazil. Univ Groningen Hosp, Dept Otorhinolaryngol, Groningen, Netherlands. Escola Bahiana Med, Salvador, BA, Brazil. NICHHD, Unit Genet Endocrinol, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Van Hul, W (reprint author), Univ Antwerp, Dept Med Genet, Univ Plein 1, B-2610 Antwerp, Belgium. RI Dikkers, Frederik/M-1212-2013 NR 40 TC 57 Z9 63 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1999 VL 64 IS 6 BP 1661 EP 1669 DI 10.1086/302416 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 203FA UT WOS:000080696200018 PM 10330353 ER PT J AU Foster, MW Sharp, RR Freeman, WL Chino, M Bernsten, D Carter, TH AF Foster, MW Sharp, RR Freeman, WL Chino, M Bernsten, D Carter, TH TI The role of community review in evaluating the risks of human genetic variation research SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DISCRIMINATION; POPULATIONS; DISEASE; HEALTH; FUTURE; GENOME AB The practicality and moral value of community review of human genetic research has become a focus of debate. Examples from two Native American communities are used to address four aspects of that debate: (1) the value of community review in larger, geographically dispersed populations; (2) the identification of culturally specific risks; (3) the potential conflict between individual and group assessments of research-related risks; and (4) the confusion of social categories with biological categories. Our experiences working with these two communities suggest that: (1) successful community review may require the involvement of private social units (e.g., families); (2) culturally specific implications of genetic research may be identifiable only by community members and are of valid concern in their moral universes; (3) community concerns can be incorporated into existing review mechanisms without necessarily giving communities the power to veto research proposals; and (4) the conflation of social and biological categories presents recruitment problems for genetic studies. These conclusions argue for the use of community review to identify and minimize research-related risks posed by genetic studies. Community review also can assist in facilitating participant recruitment and retention, as well as in developing partnerships between researchers and communities. C1 Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Indian Hlth Serv, Albuquerque, NM USA. Albuquerque Indian Hlth Board, Albuquerque, NM USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. RP Foster, MW (reprint author), Univ Oklahoma, Dept Anthropol, 455 W Lindsey Ave,Room 515, Norman, OK 73019 USA. FU NHGRI NIH HHS [HG010302] NR 43 TC 61 Z9 61 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1999 VL 64 IS 6 BP 1719 EP 1727 DI 10.1086/302415 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 203FA UT WOS:000080696200025 PM 10330360 ER PT J AU Allison, DB Heo, M Kaplan, N Martin, ER AF Allison, DB Heo, M Kaplan, N Martin, ER TI Sibling-based tests of linkage and association for quantitative traits SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRANSMISSION DISEQUILIBRIUM TEST; DISCORDANT SIB PAIRS; TRANSMISSION/DISEQUILIBRIUM TEST; LOCI; SELECTION; POWER; EFFICIENCY; PEDIGREES; DISEASES; OBESITY AB The transmission/disequilibrium test (TDT) developed by Spielman et al. can be a powerful family-based test of linkage and, in some cases, a test of association as well as linkage. It has recently been extended in several ways; these include allowance for implementation with quantitative traits, allowance for multiple alleles, and, in the case of dichotomous traits, allowance for testing in the absence of parental data. In this article, these three extensions are combined, and two procedures are developed that offer valid joint tests of linkage and (in the case of certain sibling configurations) association with quantitative traits, with use of data from siblings only, and that can accommodate biallelic or multiallelic loci. The first procedure uses a mixed-effects (i.e., random and fixed effects) analysis of variance in which sibship is. the random factor, marker genotype is the red factor, and the continuous phenotype is the dependent variable. Covariates can easily be accommodated, and the procedure can be implemented in commonly available statistical software. The second procedure is a permutation-based procedure. Selected power studies are conducted to illustrate the relative power of each test under a variety of circumstances. C1 Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, New York, NY 10025 USA. NIEHS, Biostat Branch, Dept Hlth & Human Resources, NIH, Bethesda, MD USA. Duke Univ, Med Ctr, Dept Med, Med Genet Sect, Durham, NC 27710 USA. RP Allison, DB (reprint author), Columbia Univ, Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, 1090 Amsterdam Ave,14th Floor, New York, NY 10025 USA. OI Allison, David/0000-0003-3566-9399 FU NIDDK NIH HHS [R01DK51716, R29DK47256, P30DK26687] NR 47 TC 96 Z9 97 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 1999 VL 64 IS 6 BP 1754 EP 1764 DI 10.1086/302404 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 203FA UT WOS:000080696200028 PM 10330363 ER PT J AU Jordan, EK McFarland, HI Lewis, BK Tresser, N Gates, MA Johnson, M Lenardo, M Matis, LA McFarland, HF Frank, JA AF Jordan, EK McFarland, HI Lewis, BK Tresser, N Gates, MA Johnson, M Lenardo, M Matis, LA McFarland, HF Frank, JA TI Serial MR imaging of experimental autoimmune encephalomyelitis induced by human white matter or by chimeric myelin-basic and proteolipid protein in the common marmoset SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; REMITTING MULTIPLE-SCLEROSIS; BRAIN-BARRIER BREAKDOWN; CONTRAST-ENHANCED MRI; IN-VIVO MRI; DISEASE-ACTIVITY; ADOPTIVE TRANSFER; GUINEA-PIG; GADOLINIUM ENHANCEMENT; DEMYELINATING DISEASE AB BACKGROUND AND PURPOSE: Experimental autoimmune encephalomyelitis (EAE) in the marmoset was monitored by serial MR imaging to determine correlates to the natural-history MR studies in multiple sclerosis (MS), The relationships of MR-revealed lesions to clinical status and histopathologic findings were also explored. METHODS: We induced EAE by subcutaneous inoculation in two marmosets by human white matter (HWM) and in seven marmosets by MP4 (a Chimeric recombinant fusion protein of myelin-basic and proteolipid protein) in adjuvant along with intravenous inactivated pertussis vaccine to facilitate the disease process, The HWM-inoculated animals were induced with Freund's adjuvant as the established model of marmoset EAE, The MP4-inoculated animals were induced with either Freund's incomplete adjuvant or TiterMax as part of a preclinical treatment trial. MR imaging was performed at 1.5 T at baseline, and repeated at 1- to 2-week intervals for a period of up to 16 weeks in six EAE-induced marmosets, and intermittently for up to 70 weeks in three EAE-induced and two control marmosets, Proton density- (PD) and T2-weighted, pre- and postgadopentetate dimeglumine enhancement, T1-weighted, and magnetization transfer (MT) images were obtained. The brains were prepared for histologic evaluation of lesion distribution and counts, characterization of lesions as demyelinating or inflammatory, and histopathologic scoring, The clinical, MR, and pathologic scoring were done on grading systems, and correlated for evaluation. RESULTS: White matter (WM) changes after EAE induction were observed first at 9 days in the HWM-induced animals and at 2.5 weeks in the MP4-induced animals, with subsequent week-to-week fluctuations on PD- and T2-weighted images. Contrast-enhancing lesions were not observed in all animals. MR-revealed WM lesions correlated to histopathologic analysis of EAE lesions, measuring from 0.5 mm to 1.5 mm, The lesion count and extent of demyelination was greater in the HWM-induced animals than in the MP4-induced animals, Some MR-revealed lesions correlated directly to clinical symptoms, but the majority of lesions were clinically silent. CONCLUSION: On MR images, lesions in the EAE marmoset model were confined to the WM, and their development, resolution, distribution, and enhancing characteristics fluctuated over the duration of the study. The dynamic presentation of MR-revealed lesions confirms the parallels between EAE in the marmoset and relapsing-remitting MS, Clinical symptoms alone were not representative of ongoing pathologic brain lesions, Therefore, serial MR imaging serves as a very important adjunct to clinical and histologic surveillance of the development of new and the persistence of existing brain lesions in this animal model of MS. C1 NIH, Lab Diagnost Radiol Res, CC, OIR, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Alexion Pharmaceut, New Haven, CT USA. RP Frank, JA (reprint author), NIH, Lab Diagnost Radiol Res, CC, OIR, Bldg 10,Rm B1N256,Ctr Dr MSC 1074, Bethesda, MD 20892 USA. RI McFarland, Hugh/K-1503-2016 OI McFarland, Hugh/0000-0002-3322-038X NR 77 TC 36 Z9 38 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 1999 VL 20 IS 6 BP 965 EP 976 PG 12 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 224WC UT WOS:000081922100006 PM 10445431 ER PT J AU Bryan, N Mathis, J Rigamonti, D AF Bryan, N Mathis, J Rigamonti, D TI Long-term outcomes of Guglielmi detachable coil packing for acutely ruptured cerebral aneurysms - Reply SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Bryan, N (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 1999 VL 20 IS 6 BP 1184 EP 1184 PG 1 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 224WC UT WOS:000081922100046 ER PT J AU Geradts, J Maynard, R Birrer, MJ Hendricks, D Abbondanzo, SL Fong, KM Barrett, JC Lombardi, DP AF Geradts, J Maynard, R Birrer, MJ Hendricks, D Abbondanzo, SL Fong, KM Barrett, JC Lombardi, DP TI Frequent loss of KAI1 expression in squamous and lymphoid neoplasms - An immunohistochemical study of archival tissues SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID METASTASIS-SUPPRESSOR GENE; PROSTATE-CANCER; KAI1/CD82 EXPRESSION; SYNCYTIUM FORMATION; PANCREATIC-CANCER; DOWN-REGULATION; BREAST-CANCER; ALLELIC LOSS; CELL-LINES; HIGH-GRADE AB The metastasis suppressor gene KAI1 was identified by its ability to inhibit the formation of pulmonary metastases in experimental models for prostatic carcinoma. Down-regulation of this gene may be correlated with the invasive phenotype in melanomas and colon and bladder carcinomas and with the metastatic phenotype in carcinomas of the lung, breast, prostate, and pancreas. The goal of our study was to establish an immunohistochemical method to detect KAI1 expression in archival tissues. Using cell lines with known KAI1 levels and paraffin-embedded KAI1 positive tissues as controls,we observed strong membrane staining in lymphoid follicular centers and squamous epithelia. We then demonstrated the utility of our assay by studying KAI1 expression in 34 lymphoid and 57 squamous lesions. All eight reactive lymph nodes were KAI1 positive. In contrast, three of 13 follicular small cleaved and five of 13 diffuse large cell lymphomas were KAI1 negative. Seventy-nine percent (37 of 47) of invasive squamous cell carcinomas from the lung (n = 15), head and neck (n = 18), and cervix (n = 14) showed extensive KAI1 down-regulation. Loss of KAI1 expression was also found in a subset of 10 high-grade cervical dysplasias. Our data show that (i) immunohistochemistry is a suitable technique for evaluating KAI1 expression in archival tissues; (ii) KAI1 was not expressed in a subset of both low-grade and high-grade lymphomas; and (iii) there was extensive down-regulation of KAI1 in squamous cell carcinomas, suggestive of an important role of the gene in the suppression of invasion in these malignancies. C1 Univ Oxford, Nuffield Dept Pathol & Bacteriol, Oxford, England. Univ N Carolina Hosp, Dept Hosp Labs, Chapel Hill, NC 27514 USA. NCI, Biomarkers & Prevent Res Branch, Rockville, MD USA. Armed Forces Inst Pathol, Dept Hematol & Lymphat Pathol, Washington, DC 20306 USA. Prince Charles Hosp, Dept Thorac Med, Chermside, Qld, Australia. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA. RP Geradts, J (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Pathol & Bacteriol, Oxford OX3 9DU, England. RI Fong, Kwun/G-6369-2010 FU NCRR NIH HHS [M01 RR000046, MO1 RR00046-38S2] NR 31 TC 35 Z9 44 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1999 VL 154 IS 6 BP 1665 EP 1671 DI 10.1016/S0002-9440(10)65422-3 PG 7 WC Pathology SC Pathology GA 202YB UT WOS:000080678800008 PM 10362791 ER PT J AU Santoni-Rugiu, E Jensen, MR Factor, VM Thorgeirsson, SS AF Santoni-Rugiu, E Jensen, MR Factor, VM Thorgeirsson, SS TI Acceleration of c-myc-induced hepatocarcinogenesis by co-expression of transforming growth factor (TGF)-alpha in transgenic mice is associated with TGF-beta 1 signaling disruption SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITOR; TGF-BETA RECEPTOR; CELL-CYCLE ARREST; FACTOR-ALPHA; II RECEPTOR; NEOPLASTIC DEVELOPMENT; LIVER CARCINOGENESIS; EPITHELIAL-CELLS; CANCER CELLS; CDK ACTIVITY AB We have previously shown in transgenic mice that transforming growth factor (TGF)-alpha dramatically enhances c-myc-induced hepatocarcinogenesis by promoting proliferation and survival of hepatocellular carcinoma (HCC) cells. As transgenic livers display increased levels of mature TGF-beta 1 from the early stages of hepatocarcinogenesis, we have now assessed whether impairment of TGF-beta 1 signaling contributes to the deregulation of cell cycle progression and apoptosis observed during this process. Focal preneoplastic lesions lacking expression of TGF-P receptor type II (T beta RII) were detected in c-myc/TGF-alpha but not in c-myc Livers, in c-myc/TGF-alpha mice, 40% (2/5) of adenomas and 90% (27/30) of HCCs showed down-regulation of T beta RII expression in comparison with 11% (2/18) of adenomas and 47% (14/30) of HCCs in c-myc mice. Down-regulation of the TGF-beta 1-inducible p15(INK4B) mRNA and reduced apoptotic rates in T beta RII-negative HCCs further indicated the disruption of TGF-beta 1 signaling. Furthermore, both T beta RII negative and -positive c-myc TGF-alpha HCCs, but not c-myc HCCs, were characterized by decreased levels of the cell cycle inhibitor p27, These results suggest 1) an inverse correlation of decreased p27 expression with the particularly strong expression of TGF-alpha in these lesions, consistent with the capacity of TGF-alpha signaling to post-transcriptionally regulate p27, and 2) the presence of alternative, downstream defects of TGF-beta 1 signaling in c-myc/TGF-alpha HCCs that may impair the growth-inhibitory response to TGF-beta 1, Thus, the accelerated neoplastic development in c-myc/ TGF-alpha mice is associated with an early and frequent occurrence of T beta RII-negative lesions and with reduced levels of p27 in HCC cells, indicating that disruption of TGF-beta 1 responsiveness may play a crucial role in the enhancement of c-myc-induced hepatocarcinogenesis by TGF-alpha. C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. Univ Pisa, Dept Expt Pathol, Pisa, Italy. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Bldg 37,Room 3C28,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Jensen, Michael/E-9677-2011 NR 51 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1999 VL 154 IS 6 BP 1693 EP 1700 DI 10.1016/S0002-9440(10)65425-9 PG 8 WC Pathology SC Pathology GA 202YB UT WOS:000080678800011 PM 10362794 ER PT J AU Fend, F Quintanilla-Martinez, L Kumar, S Beaty, MW Blum, L Sorbara, L Jaffe, ES Raffeld, M AF Fend, F Quintanilla-Martinez, L Kumar, S Beaty, MW Blum, L Sorbara, L Jaffe, ES Raffeld, M TI Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas - A molecular analysis using laser capture microdissection SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IMMUNOGLOBULIN LIGHT-CHAINS; DEPENDENT KINASE INHIBITOR; SINGLE CLONAL ORIGIN; RICHTERS-SYNDROME; FOLLICULAR LYMPHOMAS; MULTIPLE-MYELOMA; GENE REARRANGEMENT; EXPRESSION; NEOPLASMS AB Low grade B-cell lymphomas comprise several well defined, clinically and immunophenotypically distinct disease entities. Composite lymphomas showing phenotypic characteristics of more than one of these tumor subtypes in the same site are rare, and both common and separate clonal origins of the two tumor parts have been reported for cases studied by molecular methods. We describe the detailed immunohistochemical and molecular findings in three cases with features of composite low grade B-cell non-Hodgkin's lymphoma (B-NHL). All three neoplasms contained morphologically distinct but interwoven compartments of different cell, types, which exhibited discordant expression of several markers, including CD5, CD10, CD43, and cyclin D1, According to their morphology and phenotypes, they were classified as mantle cell lymphoma and follicular lymphoma (Case 1), follicular lymphoma and small lymphocytic lymphoma (Case 2), and mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (Case 3). PCR analysis of DNA obtained from whole tissue sections failed to reveal evidence for biclonality in any of the cases. We therefore isolated cell populations with different antigen expression patterns by laser capture microdissection and analyzed them by polymerase chain reaction amplification and sequencing of clonal immunoglobulin heavy chain gene rearrangements and oncogene rearrangements. Sequence analysis revealed unrelated clonal rearrangements in each of the two tumor parts in all three cases, suggesting distinct clonal origins. In addition, Case 1 showed a bcl-2 rearrangement present only in the follicular lymphoma part. Our findings suggest that low grade B-NHL with two distinct morphological and immunophenotypic patterns in the same anatomical site are frequently biclonal. This is in keeping with current classification schemes, which recognize subtypes of low grade B-NHL as separate disease entities. Furthermore, our analysis demonstrates the power of laser capture microdissection in revealing molecular microheterogeneity in complex neoplasms. C1 NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Raffeld, M (reprint author), NCI, Pathol Lab, Hematopathol Sect, NIH, Bldg 10,Room 2N110,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 102 Z9 107 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1999 VL 154 IS 6 BP 1857 EP 1866 DI 10.1016/S0002-9440(10)65443-0 PG 10 WC Pathology SC Pathology GA 202YB UT WOS:000080678800029 PM 10362812 ER PT J AU Xiao, ZL Chen, Q Amaral, J Biancani, P Jensen, RT Behar, J AF Xiao, ZL Chen, Q Amaral, J Biancani, P Jensen, RT Behar, J TI CCK receptor dysfunction in muscle membranes from human gallbladders with cholesterol stones SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association / Digestive Disease Week CY MAY 16-20, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Gastroenterol Assoc DE smooth muscle; cholecystokinin receptors; liposomes ID CHOLECYSTOKININ RECEPTORS; SMOOTH-MUSCLE; BINDING; CELLS; AFFINITY; FLUIDITY; GASTRIN; STOMACH AB Human gallbladders with cholesterol stones exhibit impaired muscle contraction induced by agonists that act on transmembrane receptors, increased membrane cholesterol content, and abnormal cholesterol-to-phospholipid ratio compared with those with pigment stones. The present study was designed to investigate the functions of the CCK receptor of gallbladder muscle membranes by radioreceptor assay and cross-linking. I-125-labeled CCK-8 binding was time-dependent, competitive, and specific. Scatchard analysis showed that the maximum specific binding (B-max) was significantly decreased in cholesterol compared with pigment stone gallbladders (0.18 +/- 0.07 vs. 0.38 +/- 0.05 pmol/mg protein, P < 0.05). In contrast, the affinity for CCK was higher in cholesterol than pigment stone gallbladders (0.18 +/- 0.06 vs. 1.2 +/- 0.23 nM). Similar results were observed in binding studies with the CCK-A receptor antagonist [H-3]L-364,718. Cross-linking and saturation binding studies also showed significantly less CCK binding in gallbladders with cholesterol stones. These abnormalities were reversible after incubation with cholesterol-free liposomes. The B-max increased (P < 0.01) and the dissociation constant decreased (P < 0.001) after incubation with cholesterol-free liposomes. In conclusion, human gallbladders with cholesterol stones have impaired CCK receptor binding compared with those with pigment stones. These changes are reversed by removal of the excess membrane cholesterol. These receptor alterations may contribute to the defective contractility of the gallbladder muscle in patients with cholesterol stones. C1 Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Surg, Providence, RI 02903 USA. Brown Univ, Sch Med, Providence, RI 02903 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Behar, J (reprint author), Div Gastroenterol, APC 421,593 Eddy St, Providence, RI 02903 USA. EM Jose_Behar@brown.edu FU NIDDK NIH HHS [R01-DK-27389] NR 28 TC 54 Z9 56 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 1999 VL 276 IS 6 BP G1401 EP G1407 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 204VR UT WOS:000080785800011 PM 10362643 ER PT J AU Chen, W Glasgow, W Murphy, E Steenbergen, C AF Chen, W Glasgow, W Murphy, E Steenbergen, C TI Lipoxygenase metabolism of arachidonic acid in ischemic preconditioning and PKC-induced protection in heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE 12-lipoxygenase; 12(S)-hydroperoxyeicosatetraenoic acid; eicosanoids ID PROTEIN-KINASE-C; CANINE MYOCARDIAL-INFARCTION; RAT-HEART; CHANNEL ANTAGONIST; POTASSIUM CHANNELS; K+ CHANNELS; ACTIVATION; EXPRESSION; 5-HYDROXYDECANOATE; CARDIOPROTECTION AB Lipoxygenase metabolism of arachidonic acid in ischemic preconditioning and PKC-induced protection in heart. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H2094-H2101, 1999.-We tested the hypothesis that activation of the 12-lipoxygenase (12-LO) pathway of arachidonic acid metabolism contributes to the protective effect of protein kinase C (PKC) activation and ischemic preconditioning (PC), and we report, in perfused rat heart, that both PC and the PKC activator 1,2-dioctanoyl-sn-glycerol (DOG;) confer a similar protective effect and stimulate a comparable accumulation of 12-LO metabolites. The 12-LO product, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], was increased in DOG-treated (22.8 +/- 4.4 ng/g wet wt) and PC hearts (26.8 +/- 5.5 ng/g wet wt) compared with control (13.8 +/- 2.1 ng/g wet wt, P < 0.05), and this increase was blocked by 12-LO or PKC inhibitors. Both DOG pretreatment and PC improved recovery of left ventricular developed pressure (LVDP) nearly twofold after 20 min of ischemia; this improvement was blocked by 12-LO inhibitors and was mimicked by infusion of 12-hydroperoxyeicosatetraenoic acid [12(S)-HpETE; 67 +/- 6% recovery of LVDP vs. 35 +/- 3% for untreated hearts]. Also, the protection afforded by 12(S)-HpETE, as well as by PC, was attenuated by the K+-channel blocker 5-hydroxydecanoate, suggesting that the downstream mechanisms of 12(S)-HpETE-mediated protection are similar to PC. Furthermore, PC stimulates 12-LO metabolism in perfused rabbit heart, and 12-LO inhibition blocks PC-induced cardioprotection. Thus the data suggest that 12-LO metabolism plays an important role in cardioprotection. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Steenbergen, C (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3712, Durham, NC 27710 USA. EM steen001@mc.duke.edu FU NHLBI NIH HHS [R01 HL039752, R01-HL-39752] NR 35 TC 41 Z9 42 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 1999 VL 276 IS 6 BP H2094 EP H2101 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 205LU UT WOS:000080823500036 PM 10362692 ER PT J AU Sweet, DH Miller, DS Pritchard, JB AF Sweet, DH Miller, DS Pritchard, JB TI Localization of an organic anion transporter-GFP fusion construct (rROAT1-GFP) in intact proximal tubules SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney; killifish; Xenopus; transfection; Madin-Darby canine kidney cells; LLC-PK(1) cells; green flourescent protein ID CATION TRANSPORTER; FUNCTIONAL EXPRESSION; RAT-KIDNEY; CLONING; AMINOHIPPURATE; MECHANISMS; SECRETION; MEMBRANE; PROTEIN; CELLS AB The organic anion transporter, rROAT1, is a dicarboxylate/ organic anion exchanger, a function associated with the basolateral membrane in rat proximal tubule. To directly establish the subcellular localization of rROAT1 in renal epithelia, we made a rROAT1-green fluorescent protein (GFP) fusion construct (rROAT1-GFP). Plasma membrane-associated fluorescence was observed in rROAT1-GFP-expressing Xenopus oocytes examined by confocal microscopy. Uptake of (3)H-labeled p-aminohippurate (PAH) increased 2.5-fold in rROAT1-GFP-expressing Xenopus oocytes, and this increase was abolished by 1 mM probenecid. Thus the construct was capable of specific organic anion transport. Cultured renal epithelial cell lines (MDCK and LLC-PK1) transfected with the vector pEGFP-C3 showed a diffuse, evenly distributed cytoplasmic signal. However, when transfected with pEGFPC3/rROAT1 (vector coding for rROAT1-GFP), both cell lines showed predominantly plasma membrane fluorescence. The expression and distribution of rROAT1-GFP in intact renal proximal tubules was also investigated. Isolated killifish (Fundulus heteroclitus) renal tubules transfected with pEGFPC3/rROAT1 showed marked basal and lateral membrane-associated fluorescence, but no detectable signal in the nucleus or the apical pole of tubule cells. Tubules transfected with pEGFP-C3 showed diffuse cytoplasmic fluorescence. Function of the rROAT1-GFP construct was demonstrated in transfected killifish tubules by fluorescein transport assay. These results demonstrate the basolateral subcellular localization of rROAT1 in polarized renal epithelia and validate a new technique for localizing cloned transporters within intact renal tubules. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Pritchard, JB (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, Mail Drop F1-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM pritchard@niehs.nih.gov RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 NR 27 TC 36 Z9 37 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 1999 VL 276 IS 6 BP F864 EP F873 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 205LQ UT WOS:000080823200007 PM 10362775 ER PT J AU Leadbetter, RA Shutty, MS Elkashef, AM Kirch, DG Spraggins, T Cail, WS Wu, HW Bilder, RM Lieberman, JA Wyatt, RJ AF Leadbetter, RA Shutty, MS Elkashef, AM Kirch, DG Spraggins, T Cail, WS Wu, HW Bilder, RM Lieberman, JA Wyatt, RJ TI MRI changes during water loading in patients with polydipsia and intermittent hyponatremia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the Society-for-Biological-Psychiatry CY MAY 18-22, 1994 CL PHILADELPHIA, PENNSYLVANIA SP Soc Biol Psychiat ID SCHIZOPHRENIC-PATIENTS; HOMEOSTASIS AB Objective: Patients with polydipsia and intermittent hyponatremia have greater ventricle-brain ratios (VBRs) than matched patients without polydipsia and intermittent hyponatremia and normal subjects. Unlike previous studies, this study controlled for the impact of water loading when examining the volume of intracranial structures. Method: Under controlled conditions, eight male schizophrenic patients with polydipsia and intermittent hyponatremia were first assigned to either normal fluid intake or oral water loading and then the alternative condition the following day. Magnetic resonance imaging (MRI) volumetric measurements were made with the use of a standardized protocol. Results: During water loading, total VER and lateral ventricle volume significantly decreased by 13.1% and 12.6%, respectively. A strong association between change in serum sodium concentration and change in VER was noted across conditions. Conclusions: These findings indicate that 1) water loading does not account for the diminished brain volume observed in patients with polydipsia and intermittent hyponatremia in previous studies, and 2) hyponatremia can significantly alter brain morphology on MRI. C1 Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. NIMH, St Elizabeths Hosp, Ctr Neurosci, Washington, DC 20032 USA. Med Coll Georgia, Off Dean, Augusta, GA 30912 USA. Univ Virginia, Hlth Sci Ctr, Dept Radiol, Charlottesville, VA 22908 USA. Hillside Hosp, Long Isl Jewish Med Ctr, Dept Psychiat, Glen Oaks, NY 11004 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Western State Hosp, Clin Studies Unit, Staunton, VA USA. RP Leadbetter, RA (reprint author), Parke Davis Pharmaceut Res, 2800 Plymouth Rd, Ann Arbor, MI 48105 USA. RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 NR 9 TC 13 Z9 14 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1999 VL 156 IS 6 BP 958 EP 960 PG 3 WC Psychiatry SC Psychiatry GA 203FW UT WOS:000080698500027 PM 10360142 ER PT J AU Malcoe, LH Shaw, GM Lammer, EJ Herman, AA AF Malcoe, LH Shaw, GM Lammer, EJ Herman, AA TI The effect of congenital anomalies on mortality risk in White and Black infants SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BIRTH-WEIGHT; RACIAL-DIFFERENCES; DEATH; MALFORMATIONS; POPULATION; DEFECTS; AGE AB Objectives. This population-based study examined the effect of all major congenital anomalies on the mortality of White and Black infants by infant sex, birthweight, gestational age, and lethality of the anomaly. The study also determined the total contribution of anomalies to infant mortality. Methods. California Birth Defects Monitoring Program data were merged with linked birth-death files for 278 646 singleton non-Hispanic White and Black infants born in 1983 through 1986. Malformed infants were compared with nonmalformed infants to determine the effect of anomalies on mortality Results. The presence of any congenital anomaly increased mortality 9.0-fold (95% CI = 7.3, 11.1) for Black infants and 17.8-fold (95% CI = 16.2, 19.6) for White infants. Even "non-lethal" anomalies increased mortality up to 8.9-fold. Overall, anomalies contributed to 33% of White infant deaths, to 19% of Black infant deaths, and to over 60% of deaths among Black and White neonates weighing over 1499 g. Conclusions. The contribution of congenital anomalies to mortality of both low- (<2500 g) and normal-birthweight infants is substantially higher than previously estimated representing a large public health problem for both Black and White infants. C1 Calif Birth Defects Monitoring Program, Emeryville, CA USA. Childrens Hosp, Div Med Genet, Oakland, CA 94609 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Malcoe, LH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Biostat & Epidemiol, POB 26901,CHB-309, Oklahoma City, OK 73190 USA. NR 23 TC 24 Z9 24 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1999 VL 89 IS 6 BP 887 EP 892 DI 10.2105/AJPH.89.6.887 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200PC UT WOS:000080548000015 PM 10358680 ER PT J AU Schwartz, MD Rimer, BK Daly, M Sands, C Lerman, C AF Schwartz, MD Rimer, BK Daly, M Sands, C Lerman, C TI A randomized trial of breast cancer risk counseling: The impact on self-reported mammography use SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PSYCHOLOGICAL DISTRESS; WOMEN; BEHAVIORS; ADHERENCE AB Objectives. We evaluated the impact of individualized breast cancer risk counseling on mammography use among women at risk for breast cancer. Methods. Participants (n = 508) were randomized to the breast cancer risk counseling intervention or a general health education control intervention, and 85% completed follow-up. Results. in multivariate modeling, a significant group-by-education interaction demonstrated that among less-educated participants, breast cancer risk counseling led to reduced mammography use. There was no intervention effect among the more-educated participants. Conclusions. These results suggest that standard breast cancer risk counseling could have an adverse impact on the health behaviors of less-educated women. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. RP Schwartz, MD (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave NW,Suite 317, Washington, DC 20007 USA. FU NCI NIH HHS [R01 CA57767, KO7 CA65597] NR 14 TC 47 Z9 47 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1999 VL 89 IS 6 BP 924 EP 926 DI 10.2105/AJPH.89.6.924 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200PC UT WOS:000080548000024 PM 10358689 ER PT J AU Pahor, M Guralnik, JM Wan, JY Ferrucci, L Penninx, BWJH Lyles, A Ling, S Fried, LP AF Pahor, M Guralnik, JM Wan, JY Ferrucci, L Penninx, BWJH Lyles, A Ling, S Fried, LP TI Lower body osteoarticular pain and dose of analgesic medications in older disabled women: The Women's Health and Aging Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GENERAL-POPULATION; RISK; PREVALENCE; OSTEOARTHRITIS; ACETAMINOPHEN; GUIDELINES; MANAGEMENT; FAILURE; ASPIRIN C1 Univ Tennessee, Dept Prevent Med, Memphis, TN 38105 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Ist Nazl Ric & Cura Anziani, Dept Geriatr, Florence, Italy. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. RP Pahor, M (reprint author), Univ Tennessee, Dept Prevent Med, 66 N Pauline,Suite 633, Memphis, TN 38105 USA. FU NIA NIH HHS [N01-AG-1-2112] NR 33 TC 43 Z9 46 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 1999 VL 89 IS 6 BP 930 EP 934 DI 10.2105/AJPH.89.6.930 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200PC UT WOS:000080548000026 PM 10358691 ER PT J AU Harrison, AM Bonville, CA Rosenberg, HF Domachowske, JB AF Harrison, AM Bonville, CA Rosenberg, HF Domachowske, JB TI Respiratory syncytical virus-induced chemokine expression in the lower airways - Eosinophil recruitment and degranulation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; EPITHELIAL-CELLS; CATIONIC PROTEIN; GENE-EXPRESSION; T-CELLS; INFECTION; MIP-1-ALPHA; RANTES; MIP-1-BETA; INTERLEUKIN-8 AB Characterization of chemokine expression patterns in virus-infected epithelial cells provides important clues to the pathophysiology of such infections. The aim of this study was to determine the chemokine response pattern of respiratory epithelium when infected with respiratory syncytial virus (RSV). Macrophage inflammatory protein-1-alpha (MIP-1-alpha), interleukin-8 (IL-8), and RANTES concentrations were measured from RSV-infected HEp-2, MRC-5, and WI-38 cell culture supernatants daily following infection. Additionally, MIP-l-cu, IL-8, and RANTES concentrations were measured from lower respiratory secretions obtained from 10 intubated infants (0-24 mo) with RSV bronchiolitis, and from 10 control subjects. Our results indicate that respiratory epithelial cells respond to RSV infection by producing MIP-1-alpha, IL-8, and RANTES. Production of MIP-1-alpha required ongoing viral replication, whereas RANTES and IL-8 could be elicited by inactivated forms of the virus. MIP-1-alpha, RANTES, and IL-8 were also present in lower airway secretions obtained from patients with RSV bronchiolitis. Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), the eosinophil secretory ribonucleases, were detected in lower airway secretions from RSV-infected patients; ECP concentrations correlated with MIP-1-alpha concentrations (r = 0.93). We conclude that MIP-1-alpha is present in the lower airways during severe RSV disease. The correlation between MIP-1-alpha and ECP concentrations suggests a role for eosinophil degranulation products in the pathogenesis of RSV bronchiolitis. C1 SUNY Hlth Sci Ctr, Dept Pediat, Div Crit Care, Syracuse, NY 13210 USA. SUNY Hlth Sci Ctr, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Hlth Sci Ctr, Dept Pediat, Div Crit Care, 750 E Adams St, Syracuse, NY 13210 USA. NR 35 TC 159 Z9 159 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1999 VL 159 IS 6 BP 1918 EP 1924 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 204TH UT WOS:000080780000036 PM 10351940 ER PT J AU Kumon, Y Suehiro, T Nishiya, K Hashimoto, K Nakatani, K Sipe, JD AF Kumon, Y Suehiro, T Nishiya, K Hashimoto, K Nakatani, K Sipe, JD TI Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Article DE rheumatoid arthritis; osteoarthritis; synovial fluid; serum amyloid A; C-reactive protein; ferritin ID HIGH-DENSITY-LIPOPROTEIN; RHEUMATOID-ARTHRITIS; A PROTEIN; IRON; DISEASE; INFLAMMATION; PATHOPHYSIOLOGY; OSTEOARTHRITIS; REDUCTION AB Objective: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). Methods: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. Results: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p<0.0001, p<0.0001), and correlated with ESR in all arthritis (r = 0.658, p<0.0001, r = 0.404, p<0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727 p<0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p<0.01, p<0.0001, p<0.001) that those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. Conclusion: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA. C1 Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 7838505, Japan. Bay Side Misato Med Ctr, Kochi 7810112, Japan. NIH, Biochem Sci IRG, Ctr Sci Rev, Bethesda, MD 20892 USA. RP Kumon, Y (reprint author), Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 7838505, Japan. NR 32 TC 20 Z9 20 U1 0 U2 2 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD JUN PY 1999 VL 6 IS 2 BP 130 EP 135 DI 10.3109/13506129909007314 PG 6 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 221AG UT WOS:000081701600008 PM 10439120 ER PT J AU Virador, VM Kobayashi, N Matsunaga, J Hearing, VJ AF Virador, VM Kobayashi, N Matsunaga, J Hearing, VJ TI A standardized protocol for assessing regulators of pigmentation SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE melanin; pigmentation; assay; tyrosinase ID HUMAN-MELANOMA CELLS; HUMAN MELANOCYTES; ULTRAVIOLET-RADIATION; MAMMALIAN TYROSINASE; INHIBITION; MELANOGENESIS; ARBUTIN; STIMULATION; MURINE; HYPERPIGMENTATION AB Varied effects of chemical or biological compounds on mammalian pigmentation have been reported by many groups, but to date, no standardized method has established necessary and/or optimal parameters for testing such agents. A standardized method has been developed to screen compounds with potential effects on pigmentation. The protocol comprises basic parameters to analyze melanogenic effects and allows for further characterization of candidate compounds, providing important insights into their mechanism of action. In this protocol (termed STOPR, for standardized testing of pigmentation regulators), compounds are initially screened using purified tyrosinase and are then tested on melanocytes in culture, After treatment of melanocytes with potentially bioactive compounds, cell proliferation and viability, total melanin accumulated, and melanogenic potential are measured. This protocol is an important first step in characterizing chemical regulation of effects on melanogenesis. When bioactive candidate compounds are identified, testing may proceed for pharmacological or otherwise commercial applications in coculture and/or organ culture models followed by in vivo testing. As an application of this method, results for compounds known to stimulate and/or inhibit melanogenesis (including arbutin, hydroquinone, kojic acid, melanocyte-stimulating hormone, and thymidine dimers) as well as some commercial skin whiteners are reported. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. NR 57 TC 90 Z9 98 U1 1 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 1 PY 1999 VL 270 IS 2 BP 207 EP 219 DI 10.1006/abio.1999.4090 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 202KQ UT WOS:000080651800004 PM 10334838 ER PT J AU Le, YZ Miller, JL Sauer, B AF Le, YZ Miller, JL Sauer, B TI GFPcre fusion vectors with enhanced expression SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID MAMMALIAN-CELLS; GENE; RECOMBINATION; ACTIVATION; SYSTEM; MICE C1 Oklahoma Med Res Fdn, Dev Biol Program, Oklahoma City, OK 73104 USA. NIDDKD, Biol Chem Lab, Bethesda, MD 20892 USA. RP Sauer, B (reprint author), Oklahoma Med Res Fdn, Dev Biol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. NR 14 TC 32 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 1 PY 1999 VL 270 IS 2 BP 334 EP 336 DI 10.1006/abio.1999.4110 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 202KQ UT WOS:000080651800019 PM 10334853 ER PT J AU Cohen, JI Brunell, PA Straus, SE Krause, PR AF Cohen, JI Brunell, PA Straus, SE Krause, PR TI Recent advances in varicella-zoster virus infection SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; ACUTE HERPES-ZOSTER; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HUMAN TRIGEMINAL GANGLIA; POSTHERPETIC NEURALGIA; ORAL ACYCLOVIR; IMMUNOCOMPROMISED PATIENTS; PHARMACOKINETIC PROPERTIES; IMMUNOSUPPRESSED PATIENTS; VIDARABINE THERAPY C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11N-228, Bethesda, MD 20892 USA. NR 104 TC 100 Z9 104 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1999 VL 130 IS 11 BP 922 EP 932 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 200PB UT WOS:000080547900007 PM 10375341 ER PT J AU Yiannoutsos, CT Major, EO Curfman, B Jensen, PN Gravell, M Hou, J Clifford, DB Hall, CD AF Yiannoutsos, CT Major, EO Curfman, B Jensen, PN Gravell, M Hou, J Clifford, DB Hall, CD TI Relation of JC virus DNA in the cerebrospinal fluid to survival in acquired immunodeficiency syndrome patients with biopsy-proven progressive multifocal leukoencephalopathy SO ANNALS OF NEUROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; STEREOTAXIC BRAIN BIOPSY; PROLONGED SURVIVAL; INFECTED PATIENTS; HIV-INFECTION; DIAGNOSIS; AIDS AB The detection and semiquantitation of JC virus (JCV) DNA in cerebrospinal fluid (CSF) is prognostic of survival and is a marker of the course of progressive multifocal leukoencephalopathy (PML). CSF samples from 15 acquired immunodeficiency syndrome (AIDS) patients with biopsy-proven PML were analyzed by semiquantitative polymerase chain reaction (PCR). A low JCV burden was predictive of longer survival compared with a high JCV burden (median survival from entry, 24 [2-63] vs 7.6 [4-17] weeks). Further analyses indicated a possible threshold of 50 to 100 copies/mu l separating high- and moderate-risk cases. Patients with a JCV load below this level survived longer than those with a JCV load above it. C1 Harvard Univ, Sch Publ Hlth, Ctr Biostat & AIDS Res, Boston, MA 02115 USA. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. RP Yiannoutsos, CT (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat & AIDS Res, 651 Huntington Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [RR00036-37, RR00046]; NINDS NIH HHS [P01 NS3228] NR 21 TC 57 Z9 59 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1999 VL 45 IS 6 BP 816 EP 820 DI 10.1002/1531-8249(199906)45:6<816::AID-ANA21>3.0.CO;2-W PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 203PC UT WOS:000080715200021 PM 10360779 ER PT J AU DeAngelis, LM Burger, PC Green, SB Cairncross, JG AF DeAngelis, LM Burger, PC Green, SB Cairncross, JG TI Malignant glioma: Who benefits from adjuvant chemotherapy? Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Johns Hopkins Med Ctr, Dept Pathol, Baltimore, MD USA. NCI, Clin & Diagnost Trials Sect, Bethesda, MD 20892 USA. London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. RP DeAngelis, LM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1999 VL 45 IS 6 BP 824 EP 824 DI 10.1002/1531-8249(199906)45:6<824::AID-ANA24>3.0.CO;2-M PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 203PC UT WOS:000080715200025 ER PT J AU Deleyiannis, FWB Gillespie, M Bielamowicz, S Yamashita, T Ludlow, CL AF Deleyiannis, FWB Gillespie, M Bielamowicz, S Yamashita, T Ludlow, CL TI Laryngeal long latency response conditioning in abductor spasmodic dysphonia SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE abductor spasmodic dysphonia; electromyography; laryngeal long latency response ID BOTULINUM TOXIN INJECTION; NERVE-STIMULATION; MUSCLE-ACTIVITY; BLINK REFLEX; ADDUCTOR; DYSTONIA; EXCITABILITY; SPEECH; SERIES AB previously we demonstrated that patients with adductor spasmodic dysphonia (ADSD) have a disinhibition of laryngeal responses to sensory input. In this study, sensorimotor responses to stimulation of the superior laryngeal nerve were compared between 10 subjects with abductor spasmodic dysphonia (ABSD) and 15 normal volunteers. The groups had similar latency and frequency characteristics of their unconditioned adductor responses (p >.05). The conditioned R1 (early) responses of the subjects with ABSD were greater and more variable in amplitude than those of the normal volunteers (p less than or equal to.008). Similar R2 (late) conditioning effects were found in both groups, with a nonsignificant trend toward reduced inhibition of contralateral R2 responses at lower interstimulus intervals (p =.01) in the patient group. Thus, inhibitory mechanisms that modulate the R1 laryngeal sensorimotor pathway in the brain stem may be abnormal in subjects with ABSD. Abnormal modulation of laryngeal sensorimotor responses seems present in both types of spasmodic dysphonia. C1 Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, Div Intramural Res, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, Div Intramural Res, Bldg 10,Room 5D38,10 Ctr Dr MSC 1416, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 30 TC 14 Z9 14 U1 0 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JUN PY 1999 VL 108 IS 6 BP 612 EP 619 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 205DZ UT WOS:000080807200015 PM 10378532 ER PT J AU Para, MF Meehan, P Holden-Wiltse, J Fischl, M Morse, G Shafer, R Demeter, LM Wood, K Nevin, T Virani-Ketter, N Freimuth, WW AF Para, MF Meehan, P Holden-Wiltse, J Fischl, M Morse, G Shafer, R Demeter, LM Wood, K Nevin, T Virani-Ketter, N Freimuth, WW CA AIDS Clin Trials Grp Protocol 260 Team TI ACTG 260: a randomized, phase I-II, dose-ranging trial of the anti-human immunodeficiency virus activity of delavirdine monotherapy SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REVERSE-TRANSCRIPTASE; TYPE-1; NEVIRAPINE; ASSAY; INFECTION; PLASMA AB ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 mu M). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV 1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log(10) for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log(10) reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log(10), respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance. C1 Ohio State Univ, ACTU, Div Infect Dis, Columbus, OH 43210 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. SUNY Buffalo, Dept Pharm Practice, Buffalo, NY 14260 USA. Frontier Sci & Technol Res Fdn, Amherst, NY USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. Univ Rochester, Infect Dis Unit, Rochester, NY USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. RP Para, MF (reprint author), Ohio State Univ, ACTU, Div Infect Dis, Room 4725,456 W 10th Ave, Columbus, OH 43210 USA. FU NIAID NIH HHS [U01-AI-38858, U01 AI025924, AI-25924, U01 AI038858] NR 17 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1999 VL 43 IS 6 BP 1373 EP 1378 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 201NK UT WOS:000080601500011 PM 10348755 ER PT J AU Uchida, H Kodama, EN Yoshimura, K Maeda, Y Kosalaraksa, P Maroun, V Qiu, YL Zemlicka, J Mitsuya, H AF Uchida, H Kodama, EN Yoshimura, K Maeda, Y Kosalaraksa, P Maroun, V Qiu, YL Zemlicka, J Mitsuya, H TI In vitro anti-human immunodeficiency virus activities of Z- and E-methylenecyclopropane nucleoside analogues and their phosphoro-L-alaninate diesters SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIHERPETIC ACTIVITY; ANTIVIRAL AGENTS; TYPE-1 VARIANTS; HIV; THERAPY; DIDEOXYNUCLEOSIDES; RESISTANCE; INVITRO AB Nucleoside analogues with a Z- or an E-methylenecyclopropane moiety were synthesized and examined for activity against human immunodeficiency virus type 1 (HIV-1) in vitro. The addition of a methyl phenyl phosphoro-L-alaninate moiety to modestly active analogues resulted in potentiation of their anti-HIV-1 activity. Two such compounds, designated QYL-685 (with 2,6-diaminopurine) and QYL-609 (with adenine), were most potent against HIV-1 in vitro, with 50% inhibitory concentrations of 0.034 and 0.0026 mu M, respectively, in MT-2 cell-based assays. Both compounds were active against zidovudine-resistant, didanosine-resistant, and multi-dideoxynucleoside-resistant infectious clones in vitro. Further development of these analogues as potential therapies for HIV-1 infection is warranted. C1 NCI, Expt Retrovirol Sect, Dept Dev Therapeut, Med Branch,NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Dept Chem,Barbara Ann Karmanos Canc Inst, Expt & Clin Chemotherapy Program, Detroit, MI 48201 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, Dept Dev Therapeut, Med Branch,NIH, Bldg 10,Room 5A11,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Kodama, Eiichi /C-4032-2009 OI Kodama, Eiichi /0000-0002-6622-2752 FU NCI NIH HHS [CA32779, R01 CA032779] NR 27 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1999 VL 43 IS 6 BP 1487 EP 1490 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 201NK UT WOS:000080601500033 PM 10348777 ER PT J AU Jacobson, KA Hoffmann, C Cattabeni, F Abbracchio, MP AF Jacobson, KA Hoffmann, C Cattabeni, F Abbracchio, MP TI Adenosine-induced cell death: evidence for receptor-mediated signalling SO APOPTOSIS LA English DT Article DE adenosine; apoptosis; necrosis; physiopathological implications ID C2C12 MYOBLASTIC CELLS; PURINERGIC RECEPTOR; ACTIN CYTOSKELETON; PHYSIOLOGICAL-ROLE; DNA FRAGMENTATION; INDUCED APOPTOSIS; ASTROGLIAL CELLS; PRIMARY CULTURES; HUMAN THYMOCYTES; HL-60 CELLS AB Adenosine modulates the proliferation, survival and apoptosis of many different cell types, ranging from epithelial, endothelial and smooth muscle cells, to cells of the immune and neural lineages. In this review, we critically discuss the available in vitro and in vivo data which support a role for adenosine in both development-associated apoptosis, and in diseases characterized by either pathologically increased cell death (e.g., ischemia, trauma and aging-associated neurodegeneration) or abnormally reduced spontaneous apoptosis (e.g., cancer). Particular emphasis is given to the possible role of extracellular adenosine receptors, since these may represent novel and attractive molecular targets for the pharmacological modulation of apoptosis. In some instances, adenosine-induced cell death has been demonstrated to require entry of the nucleoside inside cells; however, in many other cases, activation of specific adenosine extracellular receptors has been demonstrated. Of the four G protein-coupled adenosine receptors so far identified, the A(2A) and the A(3) receptors have been specifically implicated in modulation of cell death. For the A(3) receptor, results obtained by exposing both cardiomyocytes and brain astrocytes to graded concentrations of selective agonists suggest induction of both cell protection and cell death. Such opposite effects, which likely depend on the degree of receptor activation, may have important therapeutic implications in the pharmacological modulation of cardiac and brain ischemia. For the A(2A) receptor, recent intriguing data suggest a specific role in immune cell death and immunosuppression, which may be relevant to both adenosine-deaminase-immunodeficiency syndrome (a pathology characterized by accumulation of adenosine to toxic levels) and in tumors where induction of apoptosis via activation of specific extracellular receptors may be desirable. Finally, preliminary data suggest that, in a similar way to the adenosine-deaminase-immunodeficiency syndrome, the abnormal accumulation of adenosine in degenerative muscular diseases may contribute to muscle cell death. Although the role of adenosine receptors in this effect still remains to be determined, these data suggest that adenosine-induced apoptosis may also represent a novel pathogenic pathway in muscular dystrophies. C1 Univ Milan, Inst Pharmacol Sci, I-20133 Milan, Italy. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Milan, Sch Pharm, Inst Pharmacol Sci, I-20133 Milan, Italy. RP Abbracchio, MP (reprint author), Univ Milan, Inst Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy. RI Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388 NR 72 TC 83 Z9 83 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JUN PY 1999 VL 4 IS 3 BP 197 EP 211 DI 10.1023/A:1009666707307 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 215XN UT WOS:000081408900006 PM 14634282 ER PT J AU Nanda, N Iismaa, SE Copeland, NG Gilbert, DJ Jenkins, N Graham, RM Sutrave, P AF Nanda, N Iismaa, SE Copeland, NG Gilbert, DJ Jenkins, N Graham, RM Sutrave, P TI Organization and chromosomal mapping of mouse G(h)/T tissue transglutaminase gene (Tgm2) SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE G(h); tissue transglutaminase; gene; mapping; organization; sequence ID PROSTATE-SPECIFIC TRANSGLUTAMINASE; CROSS-LINKING ENZYMES; BINDING PROTEIN; FACTOR-XIII; ALPHA-1-ADRENERGIC RECEPTOR; COAGULATION FACTOR; LEUKEMIA-VIRUS; CDNA CLONES; LOCALIZATION; EXPRESSION AB The mouse G(h)/tissue transglutaminase gene (Tgm2), coding a dual-function protein that both binds guanosine triphosphate (GTP) and catalyzes the posttranslational modification of proteins by transamidation of glutamine residues, has been cloned. Sequence analysis of Tgm2 and comparison with the TGase sequences of other species allowed correction of several apparent sequencing artifacts in the Tgm2 cDNA. Tgm2 spans approximately 34 kb and has 13 exons and 12 introns. Although the structure of Tgm2 shows similarity to that of other transglutaminase genes, with introns ranging from 921 bp to >5 kb, several introns differ considerably in size from those of the human G(h) gene, TGM2. Tgm2 maps to the distal region of mouse chromosome 2, a region syntenic to human chromo some 20q containing TGM2. Tgm2 is in the vicinity of two uncloned mouse mutations, diminutive (dm) and blind-sterile (bs). Genomic DNA from dm mice was unavailable; however. Southern blot analysis of bs DNA showed no gross rearrangements of Tgm2. (C) 1999 Academic Press. C1 Victor Chang Cardiac Res Inst, Mol Cardiol Unit, Darlinghurst, NSW 2010, Australia. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Graham, RM (reprint author), Victor Chang Cardiac Res Inst, Mol Cardiol Unit, 384 Victoria St, Darlinghurst, NSW 2010, Australia. RI Iismaa, Siiri/A-9924-2008; Iismaa, Siiri/C-9300-2013 OI Iismaa, Siiri/0000-0003-2409-7356 NR 30 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 1999 VL 366 IS 1 BP 151 EP 156 DI 10.1006/abbi.1999.1189 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 202JK UT WOS:000080648400020 PM 10334875 ER PT J AU Crits-Christoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, LR Thase, ME Weiss, RD Gastfriend, DR Woody, GE Barber, JP Butler, SF Daley, D Salloum, I Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT AF Crits-Christoph, P Siqueland, L Blaine, J Frank, A Luborsky, L Onken, LS Muenz, LR Thase, ME Weiss, RD Gastfriend, DR Woody, GE Barber, JP Butler, SF Daley, D Salloum, I Bishop, S Najavits, LM Lis, J Mercer, D Griffin, ML Moras, K Beck, AT TI Psychosocial treatments for cocaine dependence - National Institute on Drug Abuse Collaborative Cocaine Treatment Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID INTERPERSONAL PSYCHOTHERAPY; OPIATE ADDICTS; RATING-SCALE; THERAPIES; SEVERITY; PHARMACOTHERAPY; ABSTINENCE AB Background: This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients. Methods: Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month. Results: Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed. Conclusion: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence. C1 Univ Penn, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. NIDA, Treatment Res Branch, Div Clin & Res Serv, Rockville, MD USA. Harvard Univ, Sch Med, Brookside Hosp, Nashua, NH USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Grp Drug Counseling Unit, Pittsburgh, PA 15213 USA. Univ Penn, Cognit Therapy Training Unit, Sch Med, Philadelphia, PA 19104 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Penn, Vet Affairs, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Treatment Res Unit, Philadelphia, PA 19104 USA. Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Brown Univ, Butler Hosp, Providence, RI 02912 USA. Univ Penn, Express Therapy Training Unit, Sch Med, Philadelphia, PA 19104 USA. RP Crits-Christoph, P (reprint author), Univ Penn, Dept Psychiat, Sch Med, 3600 Market St,Room 700, Philadelphia, PA 19104 USA. OI Butler, Stephen/0000-0002-6132-5883 FU NIDA NIH HHS [U01-DA07090, K02-DA00326, R01 DA012249, K05-DA00168, U18 DA007090] NR 43 TC 296 Z9 298 U1 2 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1999 VL 56 IS 6 BP 493 EP 502 DI 10.1001/archpsyc.56.6.493 PG 10 WC Psychiatry SC Psychiatry GA 201NL UT WOS:000080601600001 PM 10359461 ER PT J AU Simpson, DD Joe, GW Fletcher, BW Hubbard, RL Anglin, MD AF Simpson, DD Joe, GW Fletcher, BW Hubbard, RL Anglin, MD TI A national evaluation of treatment outcomes for cocaine dependence SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DRUG-ABUSE TREATMENT; FOLLOW-UP OUTCOMES; TREATMENT RETENTION; TIME SPENT; DATOS; HISTORY AB Background: This national study focused on post-treatment outcomes of community treatments of cocaine dependence. Relapse to weekly (or more frequent) cocaine use in the first year after discharge from 3 major treatment modalities was examined in relation to patient problem severity at admission to the treatment program and length of stay. Methods: We studied 1605 cocaine-dependent patients from 11 cities located throughout the United Stares using a naturalistic, nonexperimental evaluation design. They were sequentially admitted from November 1991 to December 1993 to 55 community-based treatment programs in the national Drug Abuse Treatment Outcome Studies. Included were 542 patients admitted to 19 long-term residential programs, 458 patients admitted to 24 outpatient drug-free programs, and 605 patients admitted to 12 short-term inpatient programs. Results: Of 1605 patients, 377 (23.5%) reported weekly cocaine use in the year following treatment (dropping from 73.1% in the year before admission). An additional 18.0% had returned to another drug treatment program. Higher severity of patient problems at program intake and shorter stays in treatment (<90 days) were related to higher cocaine relapse rates. Conclusions: Patients with the most severe problems were more likely to enter long-term residential programs, and better outcomes were reported by those treated 90 days or longer. Dimensions of psychosocial problem severity and length of stay are, therefore, important considerations in the treatment of cocaine dependence. Cocaine relapse rates for patients with few problems at program intake were most favorable across all treatment conditions, but better outcomes for patients with medium- to high-level problems were dependent on longer treatment stays. C1 Texas Christian Univ, Inst Behav Res, Ft Worth, TX 76129 USA. NIDA, Serv Res Branch, Rockville, MD USA. Natl Dev & Res Inst Inc, Raleigh, NC USA. Univ Calif Los Angeles, Drug Abuse Res Ctr, Los Angeles, CA USA. RP Simpson, DD (reprint author), Texas Christian Univ, Inst Behav Res, TCU Box 298740, Ft Worth, TX 76129 USA. FU NIDA NIH HHS [U01-DA10374] NR 37 TC 224 Z9 225 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1999 VL 56 IS 6 BP 507 EP 514 DI 10.1001/archpsyc.56.6.507 PG 8 WC Psychiatry SC Psychiatry GA 201NL UT WOS:000080601600004 PM 10359464 ER PT J AU Alving, B Alcorn, K AF Alving, B Alcorn, K TI How to improve transfusion medicine - A treating physician's perspective SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT College-of-American-Pathologists Conference XXXIII on Transfusion Medicine Performance Improvement CY AUG 20-22, 1998 CL SAN FRANCISCO, CALIFORNIA SP Coll Amer Pathologists, Amer Assoc Blood Banks ID FRESH-FROZEN PLASMA; PLATELET TRANSFUSIONS; BLOOD COMPONENTS; FIBRIN SEALANT; EDUCATION; LEUKEMIA; SAFETY; TRIAL AB As transfusion medicine becomes more complex, cooperative strategies are gaining increasing importance in relaying information to the treating physician and in incorporating the treating physician into the education and quality control processes. The broad domain of transfusion medicine is illustrated by the variety of disciplines involved in defining the use of products such as fresh frozen plasma and the newly released solvent-detergent-treated plasma, fibrin glue and highly purified fibrin sealant, and leukoreduced and irradiated blood products. Cooperative efforts among physicians and other personnel of multiple disciplines are essential to ensure appropriate use and continuous evaluation of blood products. C1 Washington Hosp Ctr, Sect Hematol Med Oncol, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Pathol, Washington, DC 20010 USA. RP Alving, B (reprint author), NHLBI, NIH, 6701 Rockledge Dr,MSC 7950, Bethesda, MD 20892 USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUN PY 1999 VL 123 IS 6 BP 492 EP 495 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 201YB UT WOS:000080623900012 PM 10383800 ER PT J AU McCartney-Francis, NL Song, XY Mizel, DE Wahl, CL Wahl, SM AF McCartney-Francis, NL Song, XY Mizel, DE Wahl, CL Wahl, SM TI Hemoglobin protects from streptococcal cell wall-induced arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NITRIC-OXIDE SYNTHASE; ADJUVANT ARTHRITIS; RHEUMATOID-ARTHRITIS; PEROXYNITRITE FORMATION; INFLAMMATORY ARTHRITIS; KAPPA-B; EXPRESSION; CYTOKINE; SUPPRESSION; INHIBITOR AB Objective, To investigate the ability of hemoglobin (Hgb), a nitric oxide (NO) scavenger, to deplete excess NO and reduce inflammation and injury in synovial tissue from joints with inflammatory arthritis. Methods. The severity of streptococcal cell wall-induced arthritis was monitored following administration of Hgb. Plasma nitrite and nitrate levels were measured, and inducible NO synthase (iNOS) and cytokine messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) and joint tissue were evaluated. Results. Following systemic administration of Hgb to arthritic rats, plasma levels of nitrite and nitrate as well as iNOS mRNA expression in the joints and PBMC were significantly reduced. Moreover, inflammatory cell accumulation and disease pathology in the joint tissue were dramatically attenuated without obvious side effects, Consistent with this reduction in the inflammatory response, cytokine gene expression was decreased in the synovium of Hgb-treated rats. Conclusion. Modulation of NO levels through the use of a NO scavenger, Hgb, influences the development and severity of arthritis. These findings suggest that depletion of excess NO by NO scavengers provides a prototype for further exploration of potential treatments for chronic arthritis. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP McCartney-Francis, NL (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, 30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 54 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1999 VL 42 IS 6 BP 1119 EP 1127 DI 10.1002/1529-0131(199906)42:6<1119::AID-ANR8>3.0.CO;2-3 PG 9 WC Rheumatology SC Rheumatology GA 204VU UT WOS:000080786000008 PM 10366104 ER PT J AU Schumacher, HR Arayssi, T Crane, M Lee, J Gerard, H Hudson, AP Klippel, J AF Schumacher, HR Arayssi, T Crane, M Lee, J Gerard, H Hudson, AP Klippel, J TI Chlamydia trachomatis nucleic acids can be found in the synovium of some asymptomatic subjects SO ARTHRITIS AND RHEUMATISM LA English DT Article ID POLYMERASE-CHAIN-REACTION; BORRELIA-BURGDORFERI; REITERS-SYNDROME; BACTERIAL-DNA; LYME-DISEASE; ARTHRITIS; FLUID; IDENTIFICATION; AMPLIFICATION; PNEUMONIAE AB Objective. The recent identification of antigens or nucleic acids of infectious agents in the joints of patients with reactive arthritis has raised questions about whether chlamydial or other infectious agent nucleic acids are also present in normal joints, We had the opportunity to study synovium from 30 asymptomatic volunteer subjects by use of polymerase chain reaction (PCR) for attempted identification of Chlamydia and other infectious agents, Methods, All subjects had blind needle synovial biopsies with the Parker-Pearson needle. DNA was extracted and PCR performed using primers for Chlamydia trachomatis, Chlamydia pneumoniae, Borrelia burgdorferi, and pan bacterial 16S ribosomal RNA (rRNA), Results. Two subjects were identified with nucleic acid for the 16S rRNA gene of C trachomatis. All other PCR reactions were negative except for the pan bacterial 16S rRNA in the C trachomatis-positive subjects. Both subjects, although symptom free, had some evidence of synovial reaction. Conclusion. C trachomatis appears to occasionally be disseminated to joints without producing overt disease. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Schumacher, HR (reprint author), Dept Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. OI Arayssi, Thurayya/0000-0003-2469-0272 FU NIAMS NIH HHS [AR-42541] NR 27 TC 73 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1999 VL 42 IS 6 BP 1281 EP 1284 DI 10.1002/1529-0131(199906)42:6<1281::AID-ANR27>3.0.CO;2-8 PG 4 WC Rheumatology SC Rheumatology GA 204VU UT WOS:000080786000027 PM 10366123 ER PT J AU Tully, JG AF Tully, JG TI Mycoplasma - NOT Mycobacterium-genitalium SO ASM NEWS LA English DT Letter C1 NIAID, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD JUN PY 1999 VL 65 IS 6 BP 389 EP 389 PG 1 WC Microbiology SC Microbiology GA 206EU UT WOS:000080865000007 ER PT J AU Schmeelk, KH Granger, DA Susman, EJ Chrousos, GP AF Schmeelk, KH Granger, DA Susman, EJ Chrousos, GP TI Maternal depression and risk for postpartum complications: Role of prenatal corticotropin-releasing hormone and interleukin-1 receptor antagonist SO BEHAVIORAL MEDICINE LA English DT Article DE corticotropin-releasing hormone (CRH) depression; interleukin-1ra; neuroendocrine immune interactions; pregnancy ID PITUITARY-ADRENAL AXIS; ENDOTOXIN EXPOSURE ALTERS; BEHAVIORAL HOMEOSTASIS; CORTISOL REACTIVITY; HUMAN PARTURITION; PREGNANT-WOMEN; STRESS; PROSTAGLANDINS; LABOR; ADOLESCENTS AB The pregnancies of 58 healthy adolescents (ages 13 to 19 years) were followed to examine links between symptoms of depression, corticotropin-releasing hormone (CRH), interleukin-1 beta, (IL-1 beta), and IL-1 receptor antagonist (IL-Ira) as possible predictors of maternal and infant outcomes. Maternal psychological adjustment and medical complications during gestation, labor delivery, and the postpartum period were monitored. Plasma samples collected during gestation were assayed for CRH, IL-1 beta, and IL-1ra. During gestation, symptoms of maternal depression were found to be associated with lower levels of CRH; lower levels of CRH were associated with lower levels of IL-1ra. In addition, lower revels of IL-1ra predicted higher rates of maternal complications after childbirth. IL-IP, detected in only 4 mothers, was not associated with any predictor or outcome measures. During gestation, CRH may induce circulating cytokine inhibitors without significantly affecting cytokine production or synthesis. Maternal symptoms of depression during gestation may attenuate the association between CRH and IL-1ra. C1 Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. NICHD, Sect Pediat Endocrinol, Bethesda, MD USA. RP Schmeelk, KH (reprint author), Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. FU NICHD NIH HHS [R01 HD26004] NR 42 TC 17 Z9 17 U1 1 U2 6 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0896-4289 J9 BEHAV MED JI Behav. Med. PD SUM PY 1999 VL 25 IS 2 BP 88 EP 94 PG 7 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 214GM UT WOS:000081320300005 PM 10401538 ER PT J AU Macdonald, JM LeBlanc, DA Haas, AL London, RE AF Macdonald, JM LeBlanc, DA Haas, AL London, RE TI An NMR analysis of the reaction of ubiquitin with [acetyl-1-C-13]aspirin SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE NMR; aspirin; ubiquitin; protein adducts; protein modification; acetylation; histidine acetylation ID HUMAN-SERUM ALBUMIN; PARA-NITROPHENYL ACETATE; SICKLE-CELL HEMOGLOBIN; ACETYLSALICYLIC-ACID; ACTIVATING ENZYME; ACETYLATION; ASPIRIN; PROTEIN; PROSTAGLANDIN; DEGRADATION AB The acetylation of ubiquitin by [acetyl-1-C-13]aspirin has been studied using 2D NMR methods. Studies performed in a 50:50 H2O:D2O medium show doubling of the acetyl carbonyl resonances, indicating that all of the stable adducts formed involved amide linkages. Assignment of the heteronuclear multiple quantum coherence (HMQC) resonances was accomplished based on comparison of resonance intensities with the results of an Edman degradation analysis, pH titration studies of acetylated ubiquitin, and analysis of two ubiquitin mutants, K33R and K63R. The presence of a single tyrosine residue in close proximity to lysine-48 suggested another assignment strategy. Nitration of tyrosine-59 resulted in a small, pH-dependent shift of the resonance assigned to lysine-48, with a pK of 7.0, close to that expected for the nitrotyrosyl hydroxyl group. An additional adduct resonance with very low intensity also was observed and tentatively assigned to the acetylated N-terminal methionine residue. The relative rates of acetylation of the various lysine residues were obtained from time-dependent HMQC studies. Since no sample preparation artifacts were introduced, the levels of modification of the various residues could be determined with relatively high accuracy. Based on the time-dependent intensity data, the relative rate constants for modification of K6, K48, K63, K11, K33, and M1 were 1.0, 0.59, 0.43, 0.26, 0.23, and 0.03, respectively. These results were in much better agreement with amino accessibility predictions based on the crystal structure of the ubiquitin monomer than with predictions based on the ubiquitin structure in the crystallized dimeric and tetrameric forms. This approach provides a useful basis for understanding how local environmental factors can influence protein adduct formation, as well as for comparing the extent and specificity of various acetylation reagents. BIOCHEM PHARMACOL 57;1 1:1233-1244, 1999. (C) 1999 Elsevier Science Inc. C1 NIEHS, Lab Struct Biol, Res Triangle Pk, NC 27709 USA. Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA. RP London, RE (reprint author), NIEHS, Lab Struct Biol, MR-01,POB 12233, Res Triangle Pk, NC 27709 USA. FU NIGMS NIH HHS [GM 34009] NR 47 TC 14 Z9 14 U1 2 U2 6 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 JUN 1 PY 1999 VL 57 IS 11 BP 1233 EP 1244 DI 10.1016/S0006-2952(99)00039-8 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 189UQ UT WOS:000079924900005 PM 10230767 ER PT J AU Rivera, MI Stinson, SF Vistica, DT Jorden, JL Kenney, S Sausville, EA AF Rivera, MI Stinson, SF Vistica, DT Jorden, JL Kenney, S Sausville, EA TI Selective toxicity of the tricyclic thiophene NSC652287 in renal carcinoma cell lines - Differential accumulation and metabolism SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE thiophene; renal carcinoma; antineoplastic agent; drug metabolism ID ANTICANCER DRUG SCREEN; REACTIVE METABOLITES; IN-VITRO; CANCER; ASSAY; NUCLEOPHILES; FEASIBILITY; INHIBITORS; OXIDATION; PATTERNS AB The tricyclic compound 2,5-bis(5-hydroxymethyl-2-thienyl)fura (NSC 652287) has shown a highly selective pattern of differential cytotoxic activity in the tumor cell lines comprising the National Cancer Institute (NCI) Anticancer Drug Screen. The mechanism underlying the selective cytotoxicity is unknown. We hypothesized that differential sensitivity to the compound observed in several renal tumor cell lines could be the result of selective accumulation or differential metabolism of this agent. We demonstrated here that the capacity of certain renal cell lines to accumulate and retain the compound, determined by accumulation of [(14)C]NSC 652287-derived radioactivity and by flow cytometric determination of unlabeled compound, paralleled the sensitivity of the renal cell lines re, growth inhibition by NSC 652287: A-498 > TK-10 >> ACHN similar to UO-31. The ability of the cell lines to metabolize [(14)C]NSC 652287 to a reactive species capable of binding covalently to cellular macromolecules also directly correlated with sensitivity to the compound. Different patterns of metabolites were generated by relatively more drug-sensitive cell lines in comparison with drug-resistant cell lines. The metabolizing capacity for NSC 652287 was localized primarily to the cytosolic (S100) fraction. The rate of metabolism in the cytosolic fraction from the most sensitive renal cell line, A-498, was faster than that observed in the cytosolic fractions from the other, less sensitive cell lines. The data support the hypothesis that both selective cellular accumulation and the capacity to metabolize NSC 652287 to a reactive species by certain renal carcinoma cell types are the basis fur the differential cytotoxicity of this compound class. BIOCHEM PHARMACOL 57;11:1283-1295, 1999. (C) 15)99 Elsevier Science Inc. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,FCRDC, Frederick, MD 21701 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Rivera, MI (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,FCRDC, Bldg 560,32-60 Frederick, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CM-47008, N01-CO-56000] NR 31 TC 32 Z9 32 U1 0 U2 2 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 JUN 1 PY 1999 VL 57 IS 11 BP 1283 EP 1295 DI 10.1016/S0006-2952(99)00046-5 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 189UQ UT WOS:000079924900010 PM 10230772 ER PT J AU Yasumori, T Chen, LS Li, QH Ueda, M Tsuzuki, T Goldstein, JA Kato, R Yamazoe, Y AF Yasumori, T Chen, LS Li, QH Ueda, M Tsuzuki, T Goldstein, JA Kato, R Yamazoe, Y TI Human CYP2C-mediated stereoselective phenytoin hydroxylation in Japanese: Difference in chiral preference of CYP2C9 and CYP2C19 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE phenytoin; cytochrome P450; human liver; drug metabolism; expression in yeast; polymorphism; pharmacogenetics ID S-MEPHENYTOIN 4'-HYDROXYLATION; HUMAN LIVER-MICROSOMES; GENETIC-POLYMORPHISM; POOR METABOLIZERS; TOLBUTAMIDE; CAUCASIANS; INVIVO; DOG; RAT; PHARMACOGENETICS AB Regio- and stereoselective hydroxylation of phenytoin was determined in liver microsomes of nine extensive (EM) and three poor metabolizers (PM) of mephenytoin. Hydroxyphenytoins (HPPH) were isolated and quantified after separation into four regio- and stereoisomers. The total rates of microsomal phenytoin 4'- hydroxylation were approximately 3-fold higher than those of 3'-hydroxylation, and not significantly different in EM and PM. Formation of 4'-(R)-HPPH was 4.4-fold higher in EM than in PM, whereas no clear differences between EM and PM were detected in the formation of 4'-(S)-, 3'- (R)-, and 3'- (S)-HPPH. Cytochrome P450 (CYP)2C9, expressed in a fission yeast, Schizosaccharomyces pombe, catalyzed the formation of 4'-(R)- and 4'-(S)-HPPH stereoselectively, as observed with EM, in which predominantly 4'- (S)-HPPH was formed. Recombinant CYP2C19 was more stereoselective for 4'-(R)-HPPH formation. These results, in addition to inhibition experiments with anti-human CYP2C antibody, indicate that phenytoin hydroxylation is mainly catalyzed by CYP2C9. Furthermore, CYP2C19 showed limited contribution to phenytoin 4'-hydroxylation with a different chiral preference from CYP2C9. BIOCHEM PHARMACOL 57;11:1297-1303, 1999. (C) 1999 Elsevier Science Inc. C1 Keio Univ, Sch Med, Dept Pharmacol, Shinjuku Ku, Tokyo 160, Japan. Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 160, Japan. NIEHS, Res Triangle Pk, NC 27709 USA. Tohoku Univ, Fac Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Sendai, Miyagi 98077, Japan. RP Yasumori, T (reprint author), Banyu Pharmaceut Co Ltd, Dev Res Labs, Drug Metab, 810 Nishijo, Menuma, Saitama 3600214, Japan. NR 35 TC 37 Z9 41 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 JUN 1 PY 1999 VL 57 IS 11 BP 1297 EP 1303 DI 10.1016/S0006-2952(99)00034-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 189UQ UT WOS:000079924900011 PM 10230773 ER PT J AU Chandler, SP Guschin, D Landsberger, N Wolffe, AP AF Chandler, SP Guschin, D Landsberger, N Wolffe, AP TI The methyl-CpG binding transcriptional repressor MeCP2 stably associates with nucleosomal DNA SO BIOCHEMISTRY LA English DT Article ID HISTONE H1; CHROMATIN STRUCTURE; LINKER HISTONES; CHROMOSOMAL PROTEIN; GLOBULAR DOMAIN; RNA GENE; RESPONSE ELEMENT; IN-VITRO; XENOPUS; TEMPLATES AB We have investigated the interactions of the methyl-CpG binding transcriptional repressor MeCP2 with nucleosomal DNA. We find that MeCP2 forms discrete complexes with nucleosomal DNA associating with methyl-CpGs exposed in the major groove via the methyl-CDG-binding domain (MBD). In addition to the MBD, the carboxyl-terminal segment of MeCP2 facilitates binding both to naked DNA and to the nucleosome core. These observations provide a molecular mechanism by which MeCP2 can gain access to chromatin in order to target corepressor complexes that further modify chromatin structure. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. OI Landsberger, Nicoletta/0000-0003-0820-3155 NR 82 TC 127 Z9 130 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 1 PY 1999 VL 38 IS 22 BP 7008 EP 7018 DI 10.1021/bi990224y PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 203CZ UT WOS:000080691200004 PM 10353812 ER PT J AU Redowicz, MJ Hammer, JA Bowers, B Zolkiewski, M Ginsburg, A Korn, ED Rau, DC AF Redowicz, MJ Hammer, JA Bowers, B Zolkiewski, M Ginsburg, A Korn, ED Rau, DC TI Flexibility of Acanthamoeba myosin rod minifilaments SO BIOCHEMISTRY LA English DT Article ID ACTIN-ACTIVATED ATPASE; AMINO-ACID-SEQUENCE; 3 PHOSPHORYLATION SITES; HEAVY-CHAIN; ELECTRIC BIREFRINGENCE; MG2+-ATPASE ACTIVITY; COILED COILS; II FILAMENTS; TAIL; POLYMERIZATION AB Previous electric birefringence experiments have shown that the actin-activated Mg2+-ATPase activity of Acanthamoeba myosin II correlates with the ability of minifilaments to cycle between flexible and stiff conformations. The cooperative transition between conformations was shown to depend on Mg2+ concentration, on ATP binding, and on the state of phosphorylation of three serines in the C-terminal end of the heavy chains. Since the junction between the heavy meromyosin (HMM) and light meromyosin (LMM) regions is expected to disrupt the alpha-helical coiled-coil structure of the rod, this region was anticipated to be the flexible site. We have now cloned and expressed the wild-type rod (residues 849-1509 of the full-length heavy chain) and rods mutated within the junction in order to test this. The sedimentation and electric birefringence properties of minifilaments formed by rods and by native myosin II are strikingly similar. In particular, the Mg2+-dependent flexible-to-stiff transitions of native myosin II and wild-type rod minifilaments are virtually superimposable. Mutations within the junction between the HMM and LMM regions of the rod modulate the ability of Mg2+ to stabilize the stiff conformation. Less Mg2+ is required to induce minifilament stiffening if proline-1244 is replaced with alanine. Deleting the entire junction region (25 amino acids) results in a even greater decrease in the Mg2+ concentration necessary for the transition. The HMM-LMM junction does indeed seem to act as a Mg2+-dependent flexible hinge. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Rau, DC (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RI Korn, Edward/F-9929-2012; Redowicz, Maria Jolanta/R-4083-2016 NR 41 TC 7 Z9 7 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 1 PY 1999 VL 38 IS 22 BP 7243 EP 7252 DI 10.1021/bi982679d PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 203CZ UT WOS:000080691200028 PM 10353836 ER PT J AU Katsuno, T Pradhan, TK Ryan, RR Mantey, SA Hou, W Donohue, PJ Akeson, MA Spindel, ER Battey, JF Coy, DH Jensen, RT AF Katsuno, T Pradhan, TK Ryan, RR Mantey, SA Hou, W Donohue, PJ Akeson, MA Spindel, ER Battey, JF Coy, DH Jensen, RT TI Pharmacology and cell biology of the bombesin receptor subtype 4 (BB4-R) SO BIOCHEMISTRY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; HUMAN ORPHAN RECEPTOR; MAMMALIAN BOMBESIN; MOLECULAR-CLONING; HIGH-AFFINITY; BOMBINA-ORIENTALIS; PHOSPHOLIPASE-D; 3T3 CELLS; RAT-BRAIN; ANTAGONISTS AB Recently, a fourth member of the bombesin (Bn) receptor family (fBB(4)-R) was isolated from a cDNA library from the brain of the frog, Bombina orientalis. Its pharmacology and cell biology are largely unknown, and no known natural cell lines or tissues possess sufficient numbers of fBB(4)-R's to allow either of these to be determined. To address these issues, we have used three different strategies. fBB(4)-R expression in cells widely used for other Bn receptor subtypes was unsuccessful as was expression in two frog cell lines. However, stable fBB(4)-R cell lines were obtained in CHO-K1 cells which were shown to faithfully demonstrate the correct pharmacology of the related Bn receptor, the GRP receptor, when expressed in these cells. [DPhe(6),beta Ala(11),Phe(13),Nle1(4)]Bn(6-14) was found to have high affinity (K-i = 0.4 nM) for the fBB(4)-R receptor and I-125-[DTyr(6),beta ala(11),Phe(13),Nle(14)]Bn(6-14) to be an excellent ligand for this receptor. The fBB(4)-R had a unique pharmacology for naturally occurring Bn-related agonists, with the presence of a penultimate phenylalanine being critical for high-affinity interaction. It also had a unique profile for six classes of Bn antagonists. The fBB(4)-R was coupled to phospholipase C with activation increasing [H-3]inositol phosphates and mobilizing Ca2+ almost entirely from cellular sources. There was a close correlation between agonist the receptor occupation and the receptor activation. Three of the five classes of Bn receptor antagonists that interacted with higher affinity with the fBB(4)-R functioned as fBB(4)-R antagonists and two as partial agonists, fBB(4)-R activation stimulated increases in phospholipase D (PLD) over the same range of concentrations at which it activated phospholipase C. These results demonstrate that the fBB(4) receptor has a unique pharmacology for agonists and antagonists and is coupled to phospholipase C and D. The availability of these cell lines, this novel ligand, and the identification of three classes of antagonists that can be used as lead compounds should facilitate the further investigation of the pharmacology and cell biology of the BB4 receptor. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. Tulane Univ, Peptide Res Labs, New Orleans, LA 70112 USA. Oregon Reg Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS35580] NR 40 TC 36 Z9 36 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 1 PY 1999 VL 38 IS 22 BP 7307 EP 7320 DI 10.1021/bi990204w PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 203CZ UT WOS:000080691200034 PM 10353842 ER PT J AU Bak, CI Huh, JW Hong, S Song, BJ AF Bak, CI Huh, JW Hong, S Song, BJ TI Noncompetitive, Ca2+-independent inhibition of pyruvate dehydrogenase phosphatase by fluphenazine SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE mitochondria; pyruvate dehydrogenase; PDH complex; PDH phosphatase; calmodulin antagonist; antipsychotics; kinetics; non-competitive inhibition; fluphenazine ID BOVINE KIDNEY; COMPLEX; CALMODULIN; BINDING; HEART; PHOSPHORYLATION; PURIFICATION; CYCLE; IONS AB The effects of two different classes of calmodulin antagonists on the catalytic activities of purified pyruvate dehydrogenase (PDH) phosphatase and PDH complex (PDC) were studied. In general, PDH phosphatase was more strongly inhibited than PDC by the calmodulin antagonists with the following potency order: fluphenazine > chlorpromazine > thioridazine > triflupromazine. Promazine and two sulfonamides (W-5 and W-7) did not suppress PDH phosphatase activity at 1 mM concentrations, while about 20% of PDC activity was inhibited by these antagonists. Fluphenazine-mediated inhibition of PDH phosphatase was observed with the purified PDC as well as intact mitochondria, Although Ca2+ stimulates PDH phosphatase activity, the addition of exogenous Ca2+ did not overcome the inhibition by calmodulin antagonists. These results suggest that the suppression of PDH phosphatase activity is dependent upon the structure of the individual calmodulin antagonist and appears to be Ca2+-independent, Kinetic analysis showed a noncompetitive inhibition of PDH phosphatase by fluphenazine, indicating that it binds to different site(s) from the catalytic site of the enzyme. C1 Sungkyunkwan Univ, Dept Genet Engn, Suwon, South Korea. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Sungkyunkwan Univ, Korea Green Cross Corp, Suwon, South Korea. RP Song, BJ (reprint author), Sungkyunkwan Univ, Dept Genet Engn, Suwon, South Korea. EM bs7t@nih.gov NR 30 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD JUN PY 1999 VL 47 IS 6 BP 1029 EP 1037 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210KQ UT WOS:000081104700014 PM 10410249 ER PT J AU Ibba, M Curnow, AW Bono, J Rosa, PA Woese, CR Soll, D AF Ibba, M Curnow, AW Bono, J Rosa, PA Woese, CR Soll, D TI Archaeal aminoacyl-tRNA synthesis: Unique determinants of a universal genetic code? SO BIOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT Workshop on Evolution - A Molecular Point of View CY 1997 CL MARINE BIOL LAB, WOODS HOLE, MASSACHUSETTS SP NASA, Ctr Adv Studies Space Life Sci, MBL HO MARINE BIOL LAB ID TRANSFER-RNA SYNTHETASE; TRANSLATION C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. NIAID, Rocky Mt Lab, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. Univ Illinois, Dept Microbiol, Champaign, IL 61801 USA. RP Ibba, M (reprint author), Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 J9 BIOL BULL JI Biol. Bull. PD JUN PY 1999 VL 196 IS 3 BP 335 EP 336 DI 10.2307/1542964 PG 2 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 210KR UT WOS:000081104800026 PM 10390832 ER PT J AU Taranger, J Trollfors, B Lagergard, T Robbins, JB AF Taranger, J Trollfors, B Lagergard, T Robbins, JB TI Protection against pertussis with a monocomponent pertussis toxoid vaccine SO BIOLOGICALS LA English DT Article C1 Univ Gothenburg, Dept Paediat, Gothenburg, Sweden. Univ Gothenburg, Dept Med Microbiol, Gothenburg, Sweden. Univ Gothenburg, Dept Immunol, Gothenburg, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. RP Taranger, J (reprint author), Univ Gothenburg, Dept Paediat, Gothenburg, Sweden. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 1999 VL 27 IS 2 BP 89 EP 89 DI 10.1006/biol.1999.0186 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 257DK UT WOS:000083766900007 PM 10600190 ER PT J AU Wang, SL Cukierman, E Swaim, WD Yamada, KM Baum, BJ AF Wang, SL Cukierman, E Swaim, WD Yamada, KM Baum, BJ TI Extracellular matrix protein-induced changes in human salivary epithelial cell organization and proliferation on a model biological substratum SO BIOMATERIALS LA English DT Article DE salivary epithelia; cell attachment; extracellular matrix; cell organization; biological substratum; artificial device; salivary hypofunction ID LINE; DIFFERENTIATION; REPOPULATION; STIMULATION; GLAND AB We have used a denuded rat tracheal preparation as a biological substratum on which to examine the growth and morphology of a salivary epithelial cell line (HSG) in vitro. In the absence of an additional coating of matrix proteins, HSG cells grew at low density on tracheae. Coating the tracheae with Vitrogen (a commercial collagen I preparation) or fibronectin promoted HSG cell growth and monolayer formation. Conversely, if a coating of Matrigel was applied, cells grew in a more organized fashion, but at low density. Generally similar results were obtained with cells grown on laminin and collagen IV but with less organization. These studies demonstrate the utility of a natural, tubular substratum for testing the influence of different matrix proteins on salivary epithelial cell behavior. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Cellular Imaging Core Facil, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Gene Therapy & Therapeut Branch, Bldg 10,Room 1N113,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 22 TC 24 Z9 28 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUN PY 1999 VL 20 IS 11 BP 1043 EP 1049 DI 10.1016/S0142-9612(98)00255-5 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 197KE UT WOS:000080363300006 PM 10378804 ER PT J AU Lee, JK Lascoux, M Newton, MA Nordheim, EV AF Lee, JK Lascoux, M Newton, MA Nordheim, EV TI A study of deleterious gene structure in plants using Markov chain Monte Carlo SO BIOMETRICS LA English DT Article DE deleterious genes; hierarchical modeling; lethal equivalents; Markov chain Monte Carlo; Metropolis-Hastings algorithm; peeling ID INBREEDING DEPRESSION; BAYESIAN COMPUTATION; POPULATIONS; PROBABILITY AB The characteristics of deleterious genes have been of great interest in both theory and practice in genetics. Because of the complex genetic mechanism of these deleterious genes, most current studies try to estimate the overall magnitude of mortality effects on a population, which is characterized classically by the number of lethal equivalents. This number is a combination of several parameters, each of which has a distinct biological effect on genetic mortality. In conservation and breeding programs, it is important to be able to distinguish among different combinations of these parameters that lead to the same number of lethal equivalents, such as a large number of mildly deleterious genes or a few lethal genes. The ability to distinguish such parameter combinations requires more than one generation of mating. We propose a model for survival data from a two-generation mating experiment on the plant species Brassica rapa, and we enable inference with Markov chain Monte Carlo. This computational strategy is effective because a vast amount of missing genotype information must be accounted for. In addition to the lethal equivalents, the two-generation data provide separate information on the average intensity of mortality and the average number of deleterious genes carried by an individual. In our Markov chain Monte Carlo algorithm, we use a vector proposal distribution to overcome inefficiency of a single-site Gibbs sampler. Information about environmental effects is obtained from an outcrossing experiment conducted in parallel with the two-generation mating experiments. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Swedish Univ Agr Sci, Uppsala Genet Ctr, Dept Forest Genet, S-75007 Uppsala, Sweden. Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. Univ Wisconsin, Dept Biostat, Madison, WI 53706 USA. Univ Wisconsin, Dept Forestry, Madison, WI 53706 USA. RP Lee, JK (reprint author), NCI, Div Basic Sci, NIH, Bldg 37,Room 5D02,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Ruezinsky, Diane/E-6208-2011 NR 28 TC 0 Z9 0 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 376 EP 386 DI 10.1111/j.0006-341X.1999.00376.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800007 PM 11318190 ER PT J AU Follmann, DA Hunsberger, SA Albert, PS AF Follmann, DA Hunsberger, SA Albert, PS TI Repeated probit regression when covariates are measured with error SO BIOMETRICS LA English DT Article DE errors-in-variables; measurement error; probit regression; random effects models ID LONGITUDINAL DATA; IN-VARIABLES; MODELS AB This paper develops a model for repeated binary regression when a covariate is measured with error. The model allows for estimating the effect of the true value of the covariate on a repeated binary response. The choice of a probit link for the effect of the error-free covariate, coupled with normal measurement error for the error-free covariate, results in a probit model after integrating over the measurement error distribution. We propose a two-stage estimation procedure where, in the first stage, a linear mixed model is used to fit the repeated covariate. In the second stage, a model for the correlated binary responses conditional on the linear mixed model estimates is fit to the repeated binary data using generalized estimating equations. The approach is demonstrated using nutrient safety data from the Diet Intervention of School Age Children (DISC) study. C1 NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Follmann, DA (reprint author), NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. NR 16 TC 3 Z9 3 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 403 EP 409 DI 10.1111/j.0006-341X.1999.00403.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800010 PM 11318193 ER PT J AU Simon, R AF Simon, R TI Bayesian design and analysis of active control clinical trials SO BIOMETRICS LA English DT Article DE active control trials; Bayesian; clinical trials; equivalence trials AB We consider the design and analysis of active control clinical trials, i.e., clinical trials comparing an experimental treatment E to a control treatment C considered to be effective. Direct comparison of E to placebo P, or no treatment, is sometimes ethically unacceptable. Much discussion of the design and analysis of such clinical trials has focused on whether the comparison of E to C should be based on a test of the null hypothesis of equivalence, on a test of a nonnull hypothesis that the difference is of some minimally medically important size delta, or on one or two-sided confidence intervals. These approaches are essentially the same for study planning. They all suffer from arbitrariness in specifying the size of the difference delta that must be excluded. We propose an alternative Bayesian approach to the design and analysis of active control trials. We derive the posterior probability that E is superior to P or that E is at least k% as good as C and that C is more effective than P. Wie also derive approximations for use with logistic and proportional hazard models. Selection of prior distributions is discussed, and results are illustrated using data from an active control trial of a drug for the treatment of unstable angina. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NR 7 TC 71 Z9 73 U1 1 U2 9 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 484 EP 487 DI 10.1111/j.0006-341X.1999.00484.x PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800021 PM 11318204 ER PT J AU Dunson, DB Weinberg, CR Perreault, SD Chapin, RE AF Dunson, DB Weinberg, CR Perreault, SD Chapin, RE TI Summarizing the motion of self-propelled cells: Applications to sperm motility SO BIOMETRICS LA English DT Article DE CASA; complexity theory; fractal random walk ID UTEROTUBAL JUNCTION; ALPHA-CHLOROHYDRIN; IN-VIVO; FERTILITY; PARAMETERS AB Proper characterization of the motion of spermatozoa is an important prerequisite for interpreting differences in sperm motility that might arise from exposure to toxicants. Patterns of sperm movement can be extremely complex. On the basis of an exponential model that relates the discretely approximated curvilinear velocity to the tracking rate, we develop a statistic that indexes the predictability of the path for individual sperm. We summarize the path of each sperm using this and two other statistics: (1) the path displacement velocity and (2) linearity of movement. We apply the method to a set of rat sperm tracks representative of both normal and abnormal motion characteristics. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. US EPA, NHEERL, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. NIEHS, Environm Toxicol Program, Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 23 TC 6 Z9 6 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 537 EP 543 DI 10.1111/j.0006-341X.1999.00537.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800028 PM 11318211 ER PT J AU Kulldorff, M Hjalmars, U AF Kulldorff, M Hjalmars, U TI The Knox method and other tests for space-time interaction SO BIOMETRICS LA English DT Article DE bias; epidemiology; Jacquez's test; Knox test; Mantel's test; population shifts; power; space-time clustering; spatial statistics ID LEUKEMIA AB The Knox method, as well as other tests for space-time interaction, are biased when there are geographical population shifts, i.e., when there are different percent population growths in different regions. In this paper, the size of the population shift bias is investigated for the Knox test, and it is shown that it can be a considerable problem. A Monte Carlo method for constructing unbiased space-time interaction tests is then presented and illustrated on the Knox test as well as for a combined Knox test. Practical implications are discussed in terms of the interpretation of past results and the design of future studies. C1 NCI, Biometry Branch, DCP, Bethesda, MD 20892 USA. RP Kulldorff, M (reprint author), Univ Connecticut, Sch Med, Div Biostat, Farmington, CT 06030 USA. RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 NR 18 TC 79 Z9 84 U1 0 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 544 EP 552 DI 10.1111/j.0006-341X.1999.00544.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800029 PM 11318212 ER PT J AU Follmann, DA Albert, PS AF Follmann, DA Albert, PS TI Bayesian monitoring of event rates with censored data SO BIOMETRICS LA English DT Article DE beta prior; data augmentation; Dirichlet prior; group sequential monitoring; mixtures ID CLINICAL-TRIALS AB A Bayesian approach to monitoring event rates with censored data is proposed. A Dirichlet prior for discrete time event probabilities is blended with discrete survival times to provide a posterior distribution that is a mixture of Dirichlets. Approximation of the posterior distribution via data augmentation is discussed. Practical issues involved in implementing the procedure are discussed and illustrated with a simulation of the single arm Cord Blood Transplantation Study where B-month survival is monitored. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Follmann, DA (reprint author), NHLBI, Off Biostat Res, 2 Rockledge Ctr, Bethesda, MD 20892 USA. NR 11 TC 10 Z9 10 U1 1 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 603 EP 607 DI 10.1111/j.0006-341X.1999.00603.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800038 PM 11318221 ER PT J AU Graubard, BI Korn, EL AF Graubard, BI Korn, EL TI Predictive margins with survey data SO BIOMETRICS LA English DT Article DE adjusted mean; adjusted treatment mean; analysis of covariance; logistic regression; prediction; sample weights; survey methods; survival analysis ID COVARIANCE AB In the analysis of covariance, the display of adjusted treatment means allows one to compare mean (treatment) group outcomes controlling for different covariate distributions in the groups. Predictive margins are a generalization of adjusted treatment means to nonlinear models. The predictive margin for group represents the average predicted response if everyone in the sample had been in group r. This paper discusses the use of predictive margins with complex survey data, where an important consideration is the choice of covariate distribution used to standardize the predictive margin. It is suggested that the textbook formula for the standard error of an adjusted treatment mean from the analysis of covariance may be inappropriate for applications involving survey data, Applications are given using data from the 1992 National Health Interview Survey (NHIS) and the Epidemiologic Followup Study to the first National Health and Nutrition Examination Survey (NHANES I). C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, EPS-8024, Bethesda, MD 20892 USA. NR 17 TC 420 Z9 421 U1 1 U2 14 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 1999 VL 55 IS 2 BP 652 EP 659 DI 10.1111/j.0006-341X.1999.00652.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214GT UT WOS:000081320800046 PM 11318229 ER PT J AU Proschan, MA AF Proschan, MA TI Properties of spending function boundaries SO BIOMETRIKA LA English DT Article DE clinical trial monitoring; repeated significance testing ID CLINICAL-TRIALS; DESIGN AB Clinical trials are monitored periodically for safety and efficacy, resulting in several 'looks' at interim data. If no account is taken of this, the type I error rate may be substantially higher than planned. One of the most popular methods of generating interim boundaries that result in an overall type I error rate of a is the spending function approach. This paper proves several properties of these boundaries, including a continuity-like property for looks occurring close to each other and a monotonicity property when additional looks are taken. How past monitoring affects future boundaries is also studied. C1 NHLBI, Rockledge Ctr, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NHLBI, Rockledge Ctr, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 1999 VL 86 IS 2 BP 466 EP 473 DI 10.1093/biomet/86.2.466 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 214XK UT WOS:000081352700020 ER PT J AU Chao, YH Kuo, SC Ku, K Chiu, IP Wu, CH Mauger, A Wang, HK Lee, KH AF Chao, YH Kuo, SC Ku, K Chiu, IP Wu, CH Mauger, A Wang, HK Lee, KH TI Synthesis and cytotoxicity of methyl-4,8-dihydrobenzo[1,2-b : 5,4-b ']dithiophene-4,8-dione derivatives SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 4,8-dihydrobenzo[1,2-b : 4,5-b ']dithiophene-4,8-diones; 4,8-dihydrobenzo[1,2-b : 5,4-b ']dithiophene-4,8-diones; antineoplastic activity; cytotoxicity; structural modification ID TUMOR-CELL-LINES AB 2- and 3-Methyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione and related derivatives were synthesized and evaluated in vitro by NCI against eight cancer types. Compounds 12-15 showed significant activity against melanoma, NCl-H23 non-small cell lung cancer, and MDA-MB-435 and MDA-N breast cancer cell lines; 2-hydroxymethyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene4,8-dione (13) showed the highest activity against melanoma (mean log GI(50) = -7.74) and the highest overall potency (mean log GI50 = -6.99). (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 China Med Coll, Grad Inst Pharmaceut Chem, Taichung 400, Taiwan. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Natl Prod Lab, Chapel Hill, NC 27599 USA. NCI, Drug Synth & Chem Branch, NIH, Bethesda, MD 20892 USA. RP Kuo, SC (reprint author), China Med Coll, Grad Inst Pharmaceut Chem, Taichung 400, Taiwan. FU NCI NIH HHS [CA 17625] NR 6 TC 11 Z9 11 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN PY 1999 VL 7 IS 6 BP 1025 EP 1031 DI 10.1016/S0968-0896(98)00241-7 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 210AY UT WOS:000081084000004 PM 10428370 ER PT J AU Li, LP Darden, TA Bartolotti, L Kominos, D Pedersen, LG AF Li, LP Darden, TA Bartolotti, L Kominos, D Pedersen, LG TI An atomic model for the pleated beta-sheet structure of A beta amyloid protofilaments SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; SYNCHROTRON X-RAY; ALZHEIMERS-DISEASE; CONGO-RED; FIBRIL FORMATION; SECONDARY STRUCTURE; IN-VITRO; PROTEIN; PEPTIDE; AGGREGATION AB Synchrotron x-ray studies on amyloid fibrils have suggested that the stacked pleated beta-sheets are twisted so that a repeating unit of 24 beta-strands forms a helical turn around the fibril axis (Sunde et al,, 1997. J. Mol. Biol. 273:729-739). Based on this morphological study, we have constructed an atomic model for the twisted pleated beta-sheet of human A beta amyloid protofilament. In the model, A beta monomers of A beta 12-42 stack (four per layer) to form a helical turn of beta-sheet, Each monomer is in an antiparallel beta-sheet conformation with a turn located at residues 25-28. Residues 17-21 and 31-36 form a hydrophobic core along the fibril axis. The hydrophobic core should play a critical role in initializing A beta aggregation and in stabilizing the aggregates. The model was tested using molecular dynamics simulations in explicit aqueous solution, with the particle mesh Ewald (PME) method employed to accommodate long-range electrostatic forces. Based on the molecular dynamics simulations, we hypothesize that an isolated protofilament, if it exists, may not be twisted, as it appears to be when in the fibril environment. The twisted nature of the protofilaments in amyloid fibrils is likely the result of stabilizing packing interactions of the protofilaments, The model also provides a binding mode for Congo red on A beta amyloid fibrils. The model may be useful for the design of A beta aggregation inhibitors. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. NIOSH, Hlth Effects Lab Div, Morgantown, WV 26505 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. N Carolina Supercomp Ctr, Res Triangle Pk, NC 27709 USA. Hoechst Marion Roussel, Somerville, NJ 08876 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06350] NR 52 TC 101 Z9 105 U1 1 U2 19 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1999 VL 76 IS 6 BP 2871 EP 2878 DI 10.1016/S0006-3495(99)77442-4 PG 8 WC Biophysics SC Biophysics GA 200TT UT WOS:000080556700001 PM 10354415 ER PT J AU Chizmadzhev, YA Kumenko, DA Kuzmin, PI Chernomordik, LV Zimmerberg, J Cohen, FS AF Chizmadzhev, YA Kumenko, DA Kuzmin, PI Chernomordik, LV Zimmerberg, J Cohen, FS TI Lipid flow through fusion pores connecting membranes of different tensions SO BIOPHYSICAL JOURNAL LA English DT Article ID PLANAR BILAYER-MEMBRANES; CELL-CELL FUSION; INFLUENZA HEMAGGLUTININ; EXOCYTOTIC FUSION; TETHER FORMATION; VIRUS-CELL; PROTEIN; HEMIFUSION; MOLECULES; SHAPE AB When two membranes fuse, their components mix; this is usually described as a purely diffusional process. However, if the membranes are under different tensions, the material will spread predominantly by convection. We use standard fluid mechanics to rigorously calculate the steady-state convective flux of lipids. A fusion pore is modeled as a toroid shape, connecting two planar membranes, Each of the membrane monolayers is considered separately as incompressible viscous media with the same shear viscosity, eta(s) The two monolayers interact by sliding past each other, described by an intermonolayer viscosity, eta(r), Combining a continuity equation with an equation that balances the work provided by the tension difference, Delta sigma, against the energy dissipated by flow in the viscous membrane, yields expressions for lipid velocity, upsilon, and area of lipid flux, Phi. These expressions for upsilon and Phi depend on Delta sigma, eta(s), eta(r), and geometrical aspects of a toroidal pore, but the general features of the theory hold for any fusion pore that has a roughly hourglass shape. These expressions are readily applicable to data from any experiments that monitor movement of lipid dye between fused membranes under different tensions. Lipid velocity increases nonlinearly from a small value for small pore radii, r(p), to a saturating value at large r(p), As a result of velocity saturation, the fur increases linearly with pore radius for large pores. The calculated lipid flux is in agreement with available experimental data for both large and transient fusion pores. C1 Rush Med Coll, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. AN Frumkin Electrochem Inst, Moscow 117071, Russia. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Cohen, FS (reprint author), Rush Med Coll, Dept Mol Biophys & Physiol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. RI Chizmadzhev, Yuri/L-1984-2013 FU FIC NIH HHS [R03 TW00715]; NIGMS NIH HHS [GM27367] NR 56 TC 36 Z9 36 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1999 VL 76 IS 6 BP 2951 EP 2965 DI 10.1016/S0006-3495(99)77450-3 PG 15 WC Biophysics SC Biophysics GA 200TT UT WOS:000080556700009 PM 10354423 ER PT J AU Nagao, E Dvorak, JA AF Nagao, E Dvorak, JA TI Phase imaging by atomic force microscopy: Analysis of living homoiothermic vertebrate cells SO BIOPHYSICAL JOURNAL LA English DT Article AB Atomic force microscope-based phase imaging in air is capable of elucidating variations in material properties such as adhesion, friction, and viscoelasticity. However, the interpretation of phase images of specimens in a fluid environment requires clarification. In this report, we systematically analyzed atomic force microscope-derived phase images of mica, glass, and collagen under the same conditions as used for living cells at various tapping forces; the resulting data provide critical information for the interpretation of phase images of living cells. The peripheral regions of COS-1 cells consistently show a more negative phase shift than the glass substrate in phase images at set-point amplitude: free amplitude (A(sp)/A(o)) = 0.6-0.8. In addition, at all A(sp)/A(o) values suitable for phase imaging, tapping frequency appears to be high enough to ensure that phase shifts are governed primarily by stiffness. Consequently, phase imaging is capable of high resolution studies of the cellular surface by detecting localized variations in stiffness. We demonstrate that phase imaging of a bifurcating fiber in COS-1 cell cytoplasm is readily capable of a lateral resolution of similar to 30 nm. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Dvorak, JA (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. NR 14 TC 42 Z9 42 U1 1 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1999 VL 76 IS 6 BP 3289 EP 3297 DI 10.1016/S0006-3495(99)77481-3 PG 9 WC Biophysics SC Biophysics GA 200TT UT WOS:000080556700040 PM 10354454 ER PT J AU Su, SB Gong, WH Gao, JL Shen, WP Grimm, MC Deng, XY Murphy, PM Oppenheim, JJ Wang, JM AF Su, SB Gong, WH Gao, JL Shen, WP Grimm, MC Deng, XY Murphy, PM Oppenheim, JJ Wang, JM TI T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor SO BLOOD LA English DT Article ID FMET-LEU-PHE; ENVELOPE GLYCOPROTEIN; CHEMOATTRACTANT RECEPTORS; SYNTHETIC PEPTIDE; CHEMOTACTIC RECEPTOR; CHEMOKINE RECEPTOR; POTENT INHIBITOR; HIV-1; PROTEIN; NEUTROPHILS AB Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. The peptide segment T20/DP178, located in the C-terminus of the ectodomain of gp41, interacts with the N-terminal leucine zipper-like domain on 9941 to establish the fusogenic conformation of the virus. Synthetic T20/DP178 peptide is highly efficacious in inhibiting HIV-1 infection in vitro by disrupting the transformation of fusogenic status of viral gp41; thus, it has been proposed for clinical trial. We report that synthetic T20/DP178 is a chemoattractant and activator of human peripheral blood phagocytes but not of T lymphocytes. We further demonstrate that T20/DP178 specifically activates a seven-transmembrane, G-protein-coupled phagocyte receptor for N-formylated chemotactic peptides, formyl peptide receptor (FPR), Moreover, synthetic T20/DP178 analogs lacking N-terminal amino acids acted as FPR antagonists. Our results suggest that gp41 peptides regulate phagocyte function via FPR and identify a novel mechanism by which HIV-1 may modulate innate immunity. (C) 1999 by The American Society of Hematology. C1 NCI, Lab Mol Immunoregulat, Div Basic Sci, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Lab Mol Immunoregulat, Div Basic Sci, SAIC Frederick,Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-40, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 47 TC 62 Z9 65 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1999 VL 93 IS 11 BP 3885 EP 3892 PG 8 WC Hematology SC Hematology GA 200UM UT WOS:000080558500038 PM 10339497 ER PT J AU Okunieff, P Barrett, AJ Phang, SE Li, A Constine, LS Williams, JP Rubin, P Wang, X Wu, T Chen, Y Ding, I AF Okunieff, P Barrett, AJ Phang, SE Li, A Constine, LS Williams, JP Rubin, P Wang, X Wu, T Chen, Y Ding, I TI Circulating basic fibroblast growth factor declines during Cy TBI bone marrow transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE FGF; cytokine; angiogenesis; apoptosis ID FACTOR FGF RECEPTORS; IN-VIVO; BREAST-CARCINOMA; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; CANCER; MOUSE; MICE; RADIOPROTECTION; EXPRESSION AB Basic fibroblast growth factor (bFGF) inhibits radiation-induced apoptosis, and radioprotects haematopoietic, cartilage growth plate, pulmonary and gastrointestinal tissues. Conversely, chronic overexpression of bFGF may promote fibrosis, We measured the endogenous circulating bFGF in blood of patients undergoing conditioning TBI, Twenty-six patients with haematopoietic malignancies were conditioned with cyclophosphamide/TBI for allogeneic BMT, Daily blood samples were collected each morning prior to, during, and for several days after TBI, bFGF levels in plasma of normal volunteers are 0.8-26 pg/ml, bFGF was below detectability in 22%, 30% and 45% of patients pre-TBI, during TBI or post-TBI respectively, Mean circulating plasma levels of bFGF decreased from a median of 52 pg/ml pre-TBI to 26 pg/ml during TBI, and to 5 pg/ml post-TBI, Among the 26 patients, 13 had more than one non-detectable plasma bFGF level, an additional five had at least one non-detectable level, and only eight patients had detectable levels in all daily samples, Naturally high levels of bFGF were observed in some patients undergoing fractionated TBI, In contrast, as many as 79% of patients had low bFGF levels in one or more samples. The impact of endogenous bFGF on the tolerance of normal tissues to irradiation is unknown, and warrants further study. C1 Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. NHLBI, NCI, Bethesda, MD 20892 USA. RP Okunieff, P (reprint author), Univ Rochester, Strong Mem Hosp, Dept Radiat Oncol, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. NR 45 TC 10 Z9 10 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUN PY 1999 VL 23 IS 11 BP 1117 EP 1121 DI 10.1038/sj.bmt.1701778 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 201XA UT WOS:000080621100004 PM 10382950 ER PT J AU Laudenslager, ML Rasmussen, KL Berman, CM Lilly, AA Shelton, SE Kalin, NH Suomi, SJ AF Laudenslager, ML Rasmussen, KL Berman, CM Lilly, AA Shelton, SE Kalin, NH Suomi, SJ TI A preliminary description of responses of free-ranging rhesus monkeys to brief capture experiences: Behavior, endocrine, immune, and health relationships SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE cortisol; prolactin; growth hormone; insulin; natural cytotoxicity; phenotypes; CMV; parasitism; Macaca mulatta; behavioral trait; Cayo Santiago ID MACACA-FASCICULARIS; PERSONALITY-TRAITS; NONHUMAN-PRIMATES; HEART-RATE; MACAQUES; CELLS; SEPARATION; STRESS; REACTIVITY; ANTIBODIES AB A cohort of free-ranging rhesus monkeys has been followed since birth in 1993 on the island of Cayo Santiago, Puerto Rico. At 3 years of age, subjects were trapped and blood samples were collected after capture and prior to release the following day. Blood samples were processed for natural cytotoxicity toward xenogeneic tumors, phenotyping, and plasma hormones. Intestinal parasites were determined from fresh stool samples collected during trapping. Data were also available from the previous year for antibody titers to latent viruses prevalent in this population. Behavioral traits of each monkey were characterized using a previously developed trait scale for rhesus monkeys. Natural cytotoxicity toward both K563 and Raji targets declined from capture until release the following day. Plasma cortisol rose and plasma prolactin and growth hormone fell during the period of captivity; a rise in insulin was significant. It was expected that individual differences in behavioral traits might predict immune and hormone levels at the time of capture or changes in these parameters during the capture period. Although behavioral adjectives tended to cluster along three orthogonal dimensions (Insecurity, Irritability, and Sociability), they bore no relationship to the physiological parameters collected acutely (in vitro immune and endocrine parameters). The individual difference markers of Sender and maternal rank were not related to the magnitude of the observed changes in these in vitro parameters, either. However, an in vivo measure (CMV titer) was related to individual differences in Irritability. It was concluded that the magnitude of the stress associated with capture overwhelmed the individual difference effects. (C) 1999 Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80220 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. SUNY Buffalo, Dept Anthropol, Buffalo, NY 14214 USA. Med Coll S Carolina, Charleston, SC 29401 USA. Univ Wisconsin, Sch Med, Dept Psychiat & Psychol, Hlth & Emot Res Inst, Madison, WI 53706 USA. RP Laudenslager, ML (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4455 E 12th Ave, Denver, CO 80220 USA. OI Laudenslager, Mark/0000-0002-9815-3026 FU NIMH NIH HHS [MH37373] NR 29 TC 29 Z9 29 U1 0 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JUN PY 1999 VL 13 IS 2 BP 124 EP 137 DI 10.1006/brbi.1998.0548 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 204GX UT WOS:000080756800006 PM 10373277 ER PT J AU Carrossino, D Zappi, I Villani, L Mignone, L Nicosia, F AF Carrossino, D Zappi, I Villani, L Mignone, L Nicosia, F TI Pre- and post-incisional blpivacaine for axillary post-dissection pain treatment SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract ID WOUND INFILTRATION; POSTOPERATIVE PAIN C1 Natl Canc Inst, Genoa, Italy. NR 2 TC 0 Z9 0 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 1999 VL 82 SU 1 MA A664 BP 198 EP 199 PG 2 WC Anesthesiology SC Anesthesiology GA 211KG UT WOS:000081159400654 ER PT J AU Aneman, A Eisenhofer, G Fandriks, L Olbe, L Dalenback, J Nitescu, P Friberg, P AF Aneman, A Eisenhofer, G Fandriks, L Olbe, L Dalenback, J Nitescu, P Friberg, P TI Splanchnic circulation and regional sympathetic outflow, during peroperative PEEP ventilation in humans SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE ventilation, positive end-expiratory pressure; sympathetic nervous system, norepinephrine; cardiovascular system, effects; liver, blood flow ID END-EXPIRATORY PRESSURE; PORTAL BLOOD-FLOW; CARDIAC-OUTPUT; NERVE ACTIVITY; HEMODYNAMICS; ANESTHESIA; ISOFLURANE; VOLUME AB The splanchnic organs represent a major target for sympathetic outflow and an important region for haemodynamic effects on cardiovascular homeostasis, We have studied regional haemodynamic and sympathetic changes in the splanchnic bed during standardized circulatory stress from positive end-expiratory pressure ventilation (PEEP). We investigated eight patients undergoing major upper abdominal surgery using a radiotracer method to measure plasma spillover of norepinephrine as an index of sympathetic nerve activity using arterial, portal and hepatic venous blood sampling. Mesenteric and hepatic perfusion were measured by ultrasound transit time flowmetry and blood-gas analyses. Steady state measurements were performed before and during PEEP ventilation at 10 cm H2O. Plasma spillover of norepinephrine in the mesenteric and hepatic organs represented mean 49 (SEM 8)% and 7 (2)% respectively, of systemic norepinephrine spillover at baseline, and PEEP ventilation did not cause any significant changes. However, PEEP ventilation significantly decreased portal venous blood flow while hepatic blood flow was preserved by a compensatory increase in hepatic arterial blood flaw. Mesenteric and hepatic oxygen delivery changed according to blood flow, and there were no changes in regional oxygen consumption. Thus PEEP ventilation altered mesenteric and hepatic perfusion, independent of any change in corresponding sympathetic nerve activity. Regulation of hepatic blood supply, not related to sympathetic activity, maintained liver oxygenation during PEEP ventilation despite a simultaneous decrease in mesenteric perfusion. C1 Sahlgrens Univ Hosp, Dept Anaesthesiol & Intens Care, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Surg, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Physiol, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Ctr Gastroenterol Res, S-41345 Gothenburg, Sweden. Natl Inst Neurol Disorders & Stroke, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Aneman, A (reprint author), Sahlgrens Univ Hosp, Dept Anaesthesiol & Intens Care, S-41345 Gothenburg, Sweden. NR 23 TC 14 Z9 14 U1 0 U2 2 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 1999 VL 82 IS 6 BP 838 EP 842 PG 5 WC Anesthesiology SC Anesthesiology GA 211KE UT WOS:000081159100006 PM 10562775 ER PT J AU Bertelli, G Venturini, M Bergaglio, M Gustavino, C Rosso, R Valenzano, M AF Bertelli, G Venturini, M Bergaglio, M Gustavino, C Rosso, R Valenzano, M TI Progestins and the endometrium in patients receiving tamoxifen SO BRITISH JOURNAL OF CANCER LA English DT Letter C1 Natl Canc Inst, Genoa, Italy. Univ Genoa, Dept Obstet & Gynecol, Genoa, Italy. RP Bertelli, G (reprint author), Natl Canc Inst, Genoa, Italy. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1999 VL 80 IS 7 BP 1114 EP 1114 PG 1 WC Oncology SC Oncology GA 197VK UT WOS:000080386300030 PM 10362126 ER PT J AU Kang, SH Bang, YJ Jong, HS Seo, JY Kim, NK Kim, SJ AF Kang, SH Bang, YJ Jong, HS Seo, JY Kim, NK Kim, SJ TI Rapid induction of p21(WAF1) but delayed down-regulation of Cdc25A in the TGF-beta-induced cell cycle arrest of gastric carcinoma cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE TGF-beta; cell cycle arrest; cdk inhibitors; p21(WAF1); Cdc25A; gastric cancer cells ID GROWTH-FACTOR-BETA; DEPENDENT KINASE INHIBITOR; CDK INHIBITOR; LINES; P15(INK4B); MECHANISM; ACTIVATOR; P27(KIP1); PROTEINS; MEDIATOR AB Transforming growth factor-beta (TGF-beta) is a multifunctional polypeptide that inhibits cellular proliferation in most epithelial cells. cdk4 and several cyclin-dependent kinase (cdk) inhibitors (p15(INK4B), p21(WAFI/Cip1) and p27(Kip1)) have been implicated in the TGF-beta-induced cell cycle arrest. More recently, down-regulation of Cdc25A, a cdk activator, was additionally suggested as a mechanism underlying growth inhibition by TGF-beta. The existence of diverse cellular mediators, of TGF-beta, however, raises the question of whether their involvement might occur in a redundant manner or coordinately in a certain cell type. Using two TGF-beta-sensitive gastric carcinoma cell lines (SNU-16 and -620), we addressed the contributory roles of several cdk inhibitors, and of cdk4 and Cdc25A, in TGF-beta-induced cell cycle arrest by comparing their temporal expression pattern in response to TGF-beta. Among the cdk inhibitors examined, p21 mRNA was most rapidly (in less than 1 h) and prominently induced by TGF-beta. In contrast, p15 mRNA was more slowly induced than p21 in SNU-620: cells, and not expressed in SNU-16 cells harbouring homozygous deletion of p15. Western blotting results confirmed the rapid increase of p21 while opposite patterns of p27 expression were observed in the two cell lines. The down-regulation of Cdc25A mRNA occurred, but was more delayed than that of p15 or p21. Until G1 arrest was established, changes in the protein levels of both Cdc25A and cdk4 were marginal. Co-immunoprecipitation with anti-cdk4 antibody showed that induced p21 associates with cdk4, and that its kinase activity is reduced by TGF-beta, which kinetically correlates closely with G1 arrest following TGF-beta treatment of both cell lines. These results suggest that in certain human epithelial cells, p21 may play an early role in TGF-beta-induced cell cycle arrest, and its cooperation with other cdk inhibitors is different depending on cell type. Delayed down-regulation of Cdc25A and cdk4 may contribute to cell adaptation to the quiescent state in the two gastric carcinoma cell lines studied. C1 Seoul Natl Univ, Coll Med, Canc Res Ctr, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110799, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Bang, YJ (reprint author), Seoul Natl Univ Hosp, Dept Internal Med, 28 Yongon Dong Chongno Ku, Seoul 110799, South Korea. RI Bang, Yung Jue/J-2759-2012 NR 26 TC 21 Z9 23 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1999 VL 80 IS 8 BP 1144 EP 1149 DI 10.1038/sj.bjc.6690478 PG 6 WC Oncology SC Oncology GA 204XP UT WOS:000080790900005 PM 10376964 ER PT J AU van Rhee, F Jiang, YZ Vigue, F Kirby, M Mavroudis, D Hensel, NF Agarwala, V Clave, E Childs, R Raptis, A Sloand, E Carter, C Read, EJ Barrett, J AF van Rhee, F Jiang, YZ Vigue, F Kirby, M Mavroudis, D Hensel, NF Agarwala, V Clave, E Childs, R Raptis, A Sloand, E Carter, C Read, EJ Barrett, J TI Human G-CSF-mobilized CD34-positive peripheral blood progenitor cells call stimulate allogeneic T-cell responses: implications for graft rejection in mismatched transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD34(+) cells; bone marrow transplantation; graft rejection; G-CSF-mobilized peripheral blood progenitor cells; T-cell responses ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; DENDRITIC CELLS; HEMATOPOIETIC-CELLS; STEM-CELLS; CD34(+); ENGRAFTMENT; LIGAND; DONOR; PROLIFERATION AB To investigate mechanisms of stem cell graft rejection we studied the allo-stimulatory potential of G-CSF mobilized peripheral blood progenitor cells (PBPC). CD34(+) cells were purified (>95%) in a two-step procedure using immunoaffinity columns for CD34 selection and T-depletion. The capacity of CD34(+) cells to stimulate allogeneic T-cell responses was compared with Other cells from the same individual. CD34(+) cells induced potent proliferative responses at stimulator:responder ratios of 1:20, but were approximately 50-fold less efficient compared to dendritic cells. Furthermore, CD34(+) cells primed responses from partially matched allogeneic T cells in bulk cultures. Dual-colour flow cytometry showed that the co-stimulatory molecules B7.1. CD40 and ICAM-1 were absent on resting CD34-positive progenitor cells, but were induced during incubation with allogeneic lymphocytes due to a cytokine-mediated effect. Up-regulation of accessory molecules on CD34(+) cells was reproduced by incubation with interferon-gamma or GM-CSF which enhanced the allo-stimulatory activity of CD34(+) cells. Blocking studies with inhibitory antibodies suggested cu-stimulatory functions for B7.2, ICAM-3, CD40 and LFA-3. CD34(+) cells were more efficient in inducing allogeneic T-cell responses when compared to the unprocessed leukapheresis products, The reduced allo-stimulatory ability of G-CSF mobilized PBPC could be explained by the presence of CD3(+)4(+) and CD3(+)8(+) lymphocytes with suppressor activity, We conclude that current methods of stem cell selection for transplantation do not avoid allosensitization of the recipient and that further graft manipulation with add-back of lymphocytes or selection of subsets of CD34(+) cells with reduced allo-stimulatory ability may reduce graft rejection. C1 NHLBI, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP van Rhee, F (reprint author), Palmetto Richard Mem Hosp, 7 Richland Med Pk Dr,Suite 600, Columbia, SC 29203 USA. NR 26 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1999 VL 105 IS 4 BP 1014 EP 1024 DI 10.1046/j.1365-2141.1999.01470.x PG 11 WC Hematology SC Hematology GA 213FV UT WOS:000081262800024 PM 10554815 ER PT J AU Brown, LM Linet, MS Greenberg, RS Silverman, DT Hayes, RB Swanson, GM Schwartz, AG Schoenberg, JB Pottern, LM Fraumeni, JF AF Brown, LM Linet, MS Greenberg, RS Silverman, DT Hayes, RB Swanson, GM Schwartz, AG Schoenberg, JB Pottern, LM Fraumeni, JF TI Multiple myeloma and family history of cancer among blacks and whites in the US SO CANCER LA English DT Article DE case-control studies; familial cancer; multiple myeloma; race ID UNITED-STATES; DELETION; GENE; RISK AB BACKGROUND. In the U.S., the incidence rate of multiple myeloma is more than twice as high for blacks as for whites, but the etiology of this malignancy is not well understood. METHODS. A population-based case-control interview study of 565 subjects (361 white, 204 black) with multiple myeloma and 2104 controls (1150 white, 954 black) living in 3 areas of the U.S. offered the opportunity to explore whether family history of cancer contributes to the risk of multiple myeloma and explains the racial disparity in risk. RESULTS. For both races combined, the risk of multiple myeloma was significantly elevated for subjects who reported that a first-degree relative had multiple myeloma (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.2-12.0). Increased risk was also associated with a family history of any hematolymphoproliferative (HLP) cancer (OR = 1.7, 95% CI = 1.0-2.8), especially in a sibling (OR = 2.3, 95% CI = 1.1-4.5). The risk associated with familial occurrence of HLP cancer was higher for blacks than for whites, but the difference between the ORs was not statistically significant. CONCLUSIONS, These data are consistent with previous studies that indicate a familial risk of multiple myeloma, but they explain little of the race-related difference in incidence rates. Cancer 1999;85:2385-90. (C) 1999 American Cancer Society. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Michigan State Univ, Ctr Canc, Lansing, MI USA. Inst Canc, Detroit, MI USA. New Jersey State Dept Hlth, Chron Dis Epidemiol Program, Trenton, NJ 08625 USA. NHLBI, Womens Hlth Initiat, NIH, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 8026,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. NR 19 TC 59 Z9 63 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 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1999 VL 85 IS 11 BP 2385 EP 2390 PG 6 WC Oncology SC Oncology GA 199WR UT WOS:000080507500013 PM 10357409 ER PT J AU Roselli, M Milenic, DE Brechbiel, MW Mirzadeh, S Pippin, CG Gansow, OA Colcher, D Schlom, J AF Roselli, M Milenic, DE Brechbiel, MW Mirzadeh, S Pippin, CG Gansow, OA Colcher, D Schlom, J TI In vivo comparison of CHX-DTPA ligand isomers in athymic mice bearing carcinoma xenografts SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE monoclonal antibody; radioimmunotherapy; yttrium; indium; chelates ID MONOCLONAL-ANTIBODY B72.3; SINGLE-CHAIN-FV; CHELATING AGENT; OVARIAN-CANCER; BREAST-CANCER; RADIOIMMUNOTHERAPY; BIODISTRIBUTION; THERAPY; IN-111; PHARMACOKINETICS AB Monoclonal antibodies (MAbs) labeled with radiometallonuclides via metal chelators are being investigated in the laboratory for use in clinical trials. The biodistribution of In-111- and Y-88-labeled antibody (MAb B72.3) using two isomeric forms (CHX-A and CHX-B) of the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA was compared in athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. CHX-(A or B)-I-125- DTPA-B72.3 was co-injected in all athymic mice to assess if the chelate conjugation altered the properties of MAb B72.3. In vitro studies demonstrated maintenance of integrity and immunoreactivity for both radioimmunoconjugates. The in vivo analysis, however, indicated major differences between the two isomer forms. In fact, the Y-88-CHX-A-DTPA radioimmunoconjugate demonstrated over the 7-day study period, a more efficient and stable tumor localization as well as a slower blood clearance rate than the CHX-B-DTPA chelate conjugate, suggesting a greater in vivo stability. Differences were also evident in critical normal organ uptake: no significant increase in liver- and spleen- or bone-to-blood ratios was observed when the CHX-A-DTPA chelate was labeled with indium or yttrium. The results described here demonstrate that the CHX-A-DTPA chelate conjugate can be considered move suitable than the CHX-B-DTPA isomer form when radiometallonuclides are coupled to an MAb. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 9000 Rockville Pike,Bld 10,Room 8B07, Bethesda, MD 20892 USA. NR 49 TC 15 Z9 15 U1 2 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD JUN PY 1999 VL 14 IS 3 BP 209 EP 220 DI 10.1089/cbr.1999.14.209 PG 12 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 208HE UT WOS:000080984300007 PM 10850305 ER PT J AU Cheng, YJ Hildesheim, A Hsu, MM Chen, IH Brinton, LA Levine, PH Chen, CJ Yang, CS AF Cheng, YJ Hildesheim, A Hsu, MM Chen, IH Brinton, LA Levine, PH Chen, CJ Yang, CS TI Cigarette smoking, alcohol consumption and risk of nasopharyngeal carcinoma in Taiwan SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol consumption; cigarette smoking; nasopharyngeal carcinoma ID EPSTEIN-BARR-VIRUS; SALTED FISH; PRESERVED FOODS; HONG-KONG; CHINA; TOBACCO AB Objectives: Nasopharyngeal carcinoma (NPC) is rare in most countries but occurs with relatively high frequency among southern Chinese populations throughout the world. A case-control study of NPC was conducted in Taiwan to investigate the importance of active and passive cigarette exposure and alcohol consumption as risk factors for this disease. Methods: 375 histologically confirmed incident NPC cases (99% response rate) were prospectively identified from two hospitals in Taipei between July 1991 and December 1994 and administered a detailed questionnaire. 327 healthy community controls individually matched to cases on sex, age and residence were selected (88% response rate). Results: After multivariate adjustment, the odds ratio (OR) and 95% confidence interval (CI) was 1.7 (1.1-2.9 with p = 0.03 for increasing dose-response) for those who smoked for 25 years compared with non-smokers. Passive smoking during childhood or adult life was not associated with an increased risk of disease. Alcohol consumption was not associated with NPC risk. The OR for subjects with 15 grams of ethanol per day compared to non-drinkers was 1.1 (95% CI = 0.7-1.7). Conclusions: Our results suggest that long term cigarette smoking is associated with NPC but that low level exposure to cigarette smoke via passive exposure and alcohol consumption are not associated with disease risk. C1 Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10018, Taiwan. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. MacKay Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei, Taiwan. RP Chen, CJ (reprint author), Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, 1 Jen-Ai Rd Sect 1, Taipei 10018, Taiwan. RI Chen, Chien-Jen/C-6976-2008; Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 27 TC 70 Z9 81 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 1999 VL 10 IS 3 BP 201 EP 207 DI 10.1023/A:1008893109257 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 208RA UT WOS:000081004100004 PM 10454065 ER PT J AU Woodson, K Albanes, D Tangrea, JA Rautalahti, M Virtamo, J Taylor, PR AF Woodson, K Albanes, D Tangrea, JA Rautalahti, M Virtamo, J Taylor, PR TI Association between alcohol and lung cancer in the alpha-tocopherol, beta-carotene cancer prevention study in Finland SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; ATBC study; cohort studies; ethanol; lung cancer ID N-NITROSODIMETHYLAMINE; CONSUMPTION; COHORT; MORTALITY; ETHANOL; RISK; QUESTIONNAIRE; DRINKING; TOBACCO; DIETARY AB Objectives: We evaluated the association between alcohol intake and lung cancer in a trial-based cohort in Finland, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study). Methods: During an average of 7.7 years of follow-up, 1059 lung cancer cases were diagnosed among the 27,111 male smokers with complete alcohol and dietary information. The relationship between alcohol and lung cancer was assessed in multivariate Cox regression models that adjusted for age, smoking, body mass index and intervention group. Results: Nondrinkers, 11% of the study population, were at increased lung cancer risk compared to drinkers (RR = 1.2, 95% CI: 1.0-1.4), possibly due to the inclusion of ex-drinkers who had stopped drinking for health reasons. Among drinkers only, we observed no association between lung cancer and total ethanol or specific beverage (beer, wine, spirits) intake. We found no significant effect modification by level of smoking, dietary micronutrients or trial intervention group; however, for men in the highest quartile of alcohol intake, we observed a slight increase in risk for lighter smokers (< 1 pack/day) and reduced risk among the heaviest smokers (> 30 cigarettes/day). Conclusions: We concluded that alcohol consumption was not a risk factor for lung cancer among male cigarette smokers, and its effect was not significantly modified by other factors, notably smoking history. C1 NCI, Div Clin Sci, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. RP Woodson, K (reprint author), NCI, Div Clin Sci, Canc Prevent Studies Branch, 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN45165] NR 39 TC 30 Z9 31 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 1999 VL 10 IS 3 BP 219 EP 226 DI 10.1023/A:1008911624785 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 208RA UT WOS:000081004100006 PM 10454067 ER PT J AU Brown, AP Morrissey, RL Crowell, JA Levine, BS AF Brown, AP Morrissey, RL Crowell, JA Levine, BS TI Thirteen-week oral toxicity study of difluoromethylornithine in combination with tamoxifen citrate in female dogs SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE tamoxifen; difluoromethylornithine; dogs; reproductive system toxicity; GI toxicity ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ORNITHINE DECARBOXYLASE INHIBITOR; BREAST-CANCER PREVENTION; PHASE-I TRIAL; ALPHA-DIFLUOROMETHYLORNITHINE; CHEMOPREVENTION; CARCINOGENESIS; POLYAMINES; DRUG AB Purpose: Cancer chemoprevention is the use of pharmacologic or natural agents to inhibit the development of cancer. Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in the biosynthesis of polyamines. DFMO has demonstrated chemopreventive efficacy in animal models of tumorigenesis. Tamoxifen (TAM), a nonsteroidal antiestrogen, is approved for use in the treatment of estrogen receptor-positive breast carcinoma and has demonstrated efficacy in chemoprevention of breast cancer in women at high risk for the disease. The administration of TAM with DFMO is being considered for development by the National Cancer Institute as a potential drug regimen for the chemoprevention of breast carcinoma. Methods: The toxicity of DFMO in combination with TAM was evaluated in female Beagle dogs following 13 weeks of daily oral administration by capsule. Dose levels in milligrams per kilogram body weight per day were: 0 (vehicle control), 100 DFMO, 0.1 TAM, 1.0 TAM, 0.1 TAM + 100 DFMO and 1.0 TAM + 100 DFMO. Results: No mortalities occurred. Diarrhea was produced by TAM and vaginal discharge, due to reproductive tract lesions, was produced by both DFMO and TAM, either alone or in combination. DFMO decreased reticulocyte counts and TAM increased counts of mature neutrophils. DFMO alone resulted in lesions to the intestines and ovaries, and cornified epithelium of vagina and cervix. TAM produced cornified epithelium of vagina and cervix, and numerous lesions in the ovaries, fallopian tube, uterus, cervix and vagina which were likely due to an estrogen agonist effect. Coadministration of DFMO increased the incidence and/or severity of these reproductive tract lesions. Each compound alone produced ovarian atrophy, and antral follicles and corpora lutea were completely absent in the 1.0 TAM + 100 DFMO group. Conclusions: Coadministration of DFMO and TAM resulted in additive toxicity involving the female reproductive system. C1 Univ Illinois, Dept Pharmacol, Toxicol Res Lab, Chicago, IL 60612 USA. Pathol Assoc Int, Chicago, IL USA. NCI, Div Canc Prevent & Control, NIH, Rockville, MD USA. RP Levine, BS (reprint author), Univ Illinois, Dept Pharmacol, Toxicol Res Lab, 1940 W Taylor St, Chicago, IL 60612 USA. FU NCI NIH HHS [N01-CN-55144-MAO] NR 27 TC 3 Z9 3 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1999 VL 43 IS 6 BP 479 EP 488 DI 10.1007/s002800050927 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 188UP UT WOS:000079867300007 PM 10321508 ER PT J AU Malila, N Virtamo, J Virtanen, M Albanes, D Tangrea, JA Huttunen, JK AF Malila, N Virtamo, J Virtanen, M Albanes, D Tangrea, JA Huttunen, JK TI The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-E; RANDOMIZED TRIAL; ANTIOXIDANT VITAMINS; CANCER PREVENTION; LUNG-CANCER; LARGE-BOWEL; POLYPS; INTERVENTION; RECURRENCE; RETINOL AB Epidemiological and experimental studies have indicated that dietary factors such as vitamin C, vitamin E, and beta-carotene are associated with the risk of colorectal cancer. This study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study), whose participants were randomly assigned to four supplementation groups: (a) alpha-tocopherol (AT), 50 mg/day; (b) beta-carotene (BC), 20 mg/ day; (c) both AT and BC; and (d) placebo. We included the 15,538 ATBC Study participants who had been randomized within the areas of three major cities in southern Finland, Cases of colorectal adenoma (n = 146) were identified by the pathology laboratories in the study areas, and these participants' medical records were collected and reviewed. alpha-tocopherol supplementation increased the risk for adenomas (relative risk, 1.66; 95% confidence interval, 1.19-2.32), whereas beta-carotene supplementation had no effect on the risk (relative risk, 0.98; 95% confidence interval, 0.71-1.35). Slightly more prediagnosis rectal bleeding and intestinal pain occurred in those adenoma cases who received alpha-tocopherol supplements than in those who did not. Thus, some bias may have resulted, with alpha-tocopherol supplementation leading to more colonoscopies and, thus, to an increased detection of incident polyps in this group. This is further supported by the trial finding that alpha-tocopherol supplementation did not increase the risk of colorectal cancer. C1 Natl Publ Hlth Inst, Dept Nutr, FIN-00300 Helsinki, Finland. NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Malila, N (reprint author), Natl Publ Hlth Inst, Dept Nutr, Mannerheimintie 166, FIN-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 27 TC 41 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1999 VL 8 IS 6 BP 489 EP 493 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 204TJ UT WOS:000080780100001 PM 10385137 ER PT J AU McKelvey, W Greenland, S Chen, MJ Longnecker, MP Frankl, HD Lee, ER Haile, RW AF McKelvey, W Greenland, S Chen, MJ Longnecker, MP Frankl, HD Lee, ER Haile, RW TI A case-control study of colorectal adenomatous polyps and consumption of foods containing partially hydrogenated oils SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLON-CANCER; UNITED-STATES; DIETARY-FAT; RISK; EPIDEMIOLOGY; SUGAR; QUESTIONNAIRE; SIGMOIDOSCOPY; PREVENTION; TRANS AB The trans fatty acids produced by partially hydrogenating vegetable oils may cause colorectal neoplasia by interfering with cell membrane function or eicosanoid synthesis. This possibility provides a rationale for looking at the relation between colorectal adenomatous polyps and consumption of foods containing partially hydrogenated vegetable oils (PHVOs), A total of 516 cases and 551 controls who underwent screening sigmoidoscopy from 1991-1993 were recruited from a prepaid Los Angeles health plan. Subjects were interviewed and given a self-administered food frequency questionnaire. Food items containing PHVOs were divided into four groups characterized by principal ingredients and preparation methods: sweetened baked goods, candy bars, oils and condiments, and french fries and chips. After adjusting for age, sex, physical activity, body mass index, smoking, total energy, and red meat and vegetable intake, there was a positive association between polyps and sweetened baked goods [350+ versus <50 kcal/day (odds ratio, 2.1; 95% confidence interval, 1.3-3.5)]. No association was found with the other food groups after adjustment for dietary and nondietary covariates, Neither was total dietary trans fatty acid associated with adenomas after adjustment for sweetened baked goods and other covariates, These results do not support the hypothesis that eating foods containing PHVOs increases the risk of colorectal adenomas, but they are consistent with the hypothesis that foods high in fat and sugar and low in fiber and correlated micronutrients increase the risk of adenomas. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Kaiser Permanente Med Ctr, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP McKelvey, W (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, CB 7400,Rosenau Hall, Chapel Hill, NC 27599 USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [2RO1CA51923] NR 35 TC 21 Z9 22 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1999 VL 8 IS 6 BP 519 EP 524 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 204TJ UT WOS:000080780100006 PM 10385142 ER PT J AU Helzlsouer, KJ Alberg, AJ Huang, HY Hoffman, SC Strickland, PT Brock, JW Burse, VW Needham, LL Bell, DA Lavigne, JA Yager, JD Comstock, GW AF Helzlsouer, KJ Alberg, AJ Huang, HY Hoffman, SC Strickland, PT Brock, JW Burse, VW Needham, LL Bell, DA Lavigne, JA Yager, JD Comstock, GW TI Serum concentrations of organochlorine compounds and the subsequent development of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; ADIPOSE-TISSUE; BLOOD-LEVELS; RISK; PESTICIDES; GLUTATHIONE; EXPOSURE; WOMEN; DDT; POLYMORPHISMS AB A nested case-control study was conducted to examine the association between serum concentrations of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), the primary metabolite of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), and polychlorinated biphenyls (PCBs) and the development of breast cancer up to 20 years later. Cases (n = 346) and controls (n = 346) were selected from cohorts of women who donated blood in 1974, 1989, or both, and were matched on age, race, menopausal status, and month and year of blood donation. Analyses were stratified by cohort participation because median DDE and PCB concentrations among the controls were 59 and 147% higher in 1974 than 1989, respectively. Median concentrations of DDE were lower among cases than controls in both time periods [11.7% lower in 1974 (P = 0.06) and 8.6% lower in 1989 (P = 0.41)]. Median concentrations of PCBs were similar among cases and controls [P = 0.21 for 1974 and P = 0.37 for 1989 (Wilcoxon signed rank test)]. The risk of developing breast cancer among women with the highest concentrations of DDE was roughly half that among women with the lowest concentrations, whether based on concentrations in 1974 [odds ratio (OR), 0.50; 95% confidence interval (CI), 0.27-0.89; P-trend = 0.02] or in 1989 (OR, 0.53; 95% CI, 0.24-1.17; P-trend = 0.08). The associations between circulating concentrations of PCBs and breast cancer were less pronounced but still in the same direction (1974: OR, 0.68; 95% CI, 0.36-12.9; P-trend = 0.2; and 1989: OR, 0.73; 95% CI, 0.37-1.46; P-trend = 0.6). Adjustment for family history of breast cancer, body mass index, age at menarche or first birth, and months of lactation did not materially alter these associations. These associations remained consistent regardless of lactation history and length of the follow-up interval, with the strongest inverse association observed among women diagnosed 16-20 years after blood drawing. Results from this prospective, community-based nested case-control study are reassuring. Even after 20 years of follow-up, exposure to relatively high concentrations of DDE or PCBs showed no evidence of contributing to an increased risk of breast cancer. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Ctr Dis Control, Div Environm Hlth Lab Sci, Atlanta, GA 30341 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Helzlsouer, KJ (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Room E-6132,615 N Wolfe St, Baltimore, MD 21205 USA. RI Needham, Larry/E-4930-2011 FU NCI NIH HHS [CA62988]; NHLBI NIH HHS [HL21670]; NIEHS NIH HHS [ES03819] NR 41 TC 128 Z9 129 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1999 VL 8 IS 6 BP 525 EP 532 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 204TJ UT WOS:000080780100007 PM 10385143 ER PT J AU Falk, RT Gail, MH Fears, TR Rossi, SC Stanczyk, F Adlercreutz, H Kiura, P Wahala, K Donaldson, JL Vaught, JB Fillmore, CM Hoover, RN Ziegler, RG AF Falk, RT Gail, MH Fears, TR Rossi, SC Stanczyk, F Adlercreutz, H Kiura, P Wahala, K Donaldson, JL Vaught, JB Fillmore, CM Hoover, RN Ziegler, RG TI Reproducibility and validity of radioimmunoassays for urinary hormones and metabolites in pre- and postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTRADIOL; SERUM; ASSAYS; PROGESTERONE; RELIABILITY; ESTROGENS AB The reproducibility of RIAs of circulating sex hormones has been evaluated as part of recent epidemiological investigations, but none seem to have addressed the reproducibility or validity of RIAs for urinary hormones or their metabolites. As part of a case-control study of breast cancer in Asian-American women, 12-h overnight urine samples were obtained, and a methodological study was conducted to identify laboratories capable of assaying urinary hormones. For the reproducibility component of this study, two laboratories with extensive experience in hormone assays measured urinary estrone, estradiol, estriol, pregnanediol glucuronide, and estrone glucuronide using samples from 15 women (5 midfollicular, 5 midluteal, and 5 postmenopausal). Variance estimates from these measurements were used to calculate the laboratory variability (coefficient of variation) and to assess the magnitude of the biological variability among the women in relation to the total variability (intraclass correlation coefficient). For the validity component, urinary estrone, estradiol, and estriol levels were measured in the same samples by gas chromatography-mass spectroscopy in the laboratory of Dr. Herman Adlercreutz (University of Helsinki, Helsinki, Finland). We found that the degree of assay reproducibility differed between the laboratories, but that laboratory variability was usually low compared with the range of hormone values among women, particularly for the estrogens. Values for estrone and estradiol were well correlated among all of the laboratories. For estriol, the RIAs tended to overestimate levels compared with gas chromatography-mass spectroscopy. In one laboratory, assays for pregnanediol glucuronide and estrone glucuronide were consistently reproduced; in the other, the reproducibility of the RIA for pregnanediol glucuronide was problematic, and estrone glucuronide was not measured. Despite some limitations, urinary hormones and their metabolites can be reliably measured by current RIAs in large investigations attempting to link hormone level to disease risk and may be particularly advantageous for studies of postmenopausal women, where serum concentrations of estrone and estradiol are low and assay measurements are not as dependable. C1 NCI, Environm Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. Univ So Calif, Womens & Childrens Hosp, Infertil & Endocrinol Dept, Los Angeles, CA 90033 USA. Univ Helsinki, Dept Chem, SF-00290 Helsinki, Finland. Microbiol Associates, Rockville, MD 20850 USA. RP Falk, RT (reprint author), NCI, Environm Epidemiol Branch, NIH, 6130 Execut Blvd,MSC 7234,Suite 7070, Bethesda, MD 20892 USA. NR 18 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 1999 VL 8 IS 6 BP 567 EP 577 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 204TJ UT WOS:000080780100013 PM 10385149 ER PT J AU Zhang, J Glatfelter, AA Taetle, R Trent, JM AF Zhang, J Glatfelter, AA Taetle, R Trent, JM TI Frequent alterations of evolutionarily conserved regions of chromosome 1 in human malignant melanoma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HETEROZYGOSITY; TRANSLOCATIONS; TUMORIGENICITY; DELETIONS; CLONING; CANCER; GENE; SITE; DNA AB Recurring alterations of chromosome 1 represent the most frequent site of structural chromosome abnormalities across all human solid tumors, including human cutaneous malignant melanoma. In melanoma, breakpoints involving chromosome 1 appear to accumulate most frequently at the paracentromeric regions, and secondly, to cluster within 1p36. Of interest, these three band regions (1p11-12, 1q21, and 1p36) were simultaneously recognized by a single YAC clone which was isolated from sequences mapping to 1q21. This observation indicates the common and highly conserved nature of sequences residing within these three bands. Because of this finding, we have examined the possible association of these recurring sites of rearrangements of chromosome 1 in malignant melanoma. To elucidate genomic alterations in these regions, we have analyzed melanoma samples simultaneously by fluorescence in situ hybridization (FISH) using both the YAC clone encoding 1p11, 1q21, and 1p36 homologous sequences, and an alpha-satellite probe for the chromosome 1 centromere. Twelve of 20 (60%) randomly selected melanoma cell lines showed detectable rearrangements in one or more of the chromosome 1 band regions. These results provide support for the notion that the homology between these regions is associated with chromosomal instability, and possibly, is of biologic relevance in malignant melanoma. (C) Elsevier Science Inc., 1999. All rights reserved. C1 NIH, Canc Genet Branch, NHGRI, Bethesda, MD 20892 USA. Arizona Comprehensive Canc Ctr, Hematol Oncol Sect, Dept Internal Med, Tucson, AZ USA. RP Trent, JM (reprint author), NIH, Canc Genet Branch, NHGRI, 49 Convent Dr MSC 4470, Bethesda, MD 20892 USA. NR 22 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1999 VL 111 IS 2 BP 119 EP 123 DI 10.1016/S0165-4608(98)00196-4 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 197AH UT WOS:000080342100003 PM 10347547 ER PT J AU Munro, J Stott, FJ Vousden, KH Peters, G Parkinson, EK AF Munro, J Stott, FJ Vousden, KH Peters, G Parkinson, EK TI Role of the alternative INK4A proteins in human keratinocyte senescence: Evidence for the specific inactivation of p16(INK4A) upon immortalization SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; TUMOR SUPPRESSION; HUMAN HEAD; LIFE-SPAN; LOCUS; P19(ARF); P53; FIBROBLASTS; MUTATIONS; PRODUCT AB The INK4A locus on human chromosome 9p21 encodes two genes that have been implicated in replicative senescence and tumor suppression, p16(INK4A) and p14(ARF). In contrast to p16(INK4A), Which is up-regulated to high levels, we were unable to detect p(14ARF) protein in senescent human keratinocytes. Also, p53, an established target of p14(ARF), did not increase, suggesting that p14(ARF) is not instrumental in human keratinocyte senescence,In neoplastic keratinocyte cultures, p16(INK4A) inactivation was invariably associated With the immortal phenotype, and there,vas evidence for the inactivation of p(16INK4A), independent of p14(ARF) in 6 of 10 lines that lacked large homozygous deletions. In contrast, we failed to detect exon Ip mutations or p16(INK4A)-independent deletions. These results emphasize the previously proposed role for p16(INK4A) in human keratinocyte senescence but do not rule out a supporting role for p14(ARF) inactivation. C1 Beatson Inst Canc Res, Canc Res Campaign, Beatson Labs, Glasgow G61 1BD, Lanark, Scotland. Imperial Canc Res Fund Labs, London WC2A 3PX, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Parkinson, EK (reprint author), Beatson Inst Canc Res, Canc Res Campaign, Beatson Labs, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland. NR 20 TC 71 Z9 74 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2516 EP 2521 PG 6 WC Oncology SC Oncology GA 203NA UT WOS:000080712700003 PM 10363964 ER PT J AU Irvine, KR Parkhurst, MR Shulman, EP Tupesis, JP Custer, M Touloukian, CE Robbins, PF Yafal, AG Greenhalgh, P Sutmuller, RPM Offringa, R Rosenberg, SA Restifo, NP AF Irvine, KR Parkhurst, MR Shulman, EP Tupesis, JP Custer, M Touloukian, CE Robbins, PF Yafal, AG Greenhalgh, P Sutmuller, RPM Offringa, R Rosenberg, SA Restifo, NP TI Recombinant virus vaccination against "self" antigens using anchor-fixed immunogens SO CANCER RESEARCH LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; IN-VIVO; PEPTIDES; GP100; VACCINES; AFFINITY; CTL; RECOGNITION AB To study the induction of anti-"self" CD8(+) T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 K-b molecule (A2/K-b). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8(+) T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/K-b-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Therion Biol Corp, Cambridge, MA 02142 USA. Leiden Univ, Med Ctr, NL-2333 ZA Leiden, Netherlands. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 23 TC 34 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2536 EP 2540 PG 5 WC Oncology SC Oncology GA 203NA UT WOS:000080712700007 PM 10363968 ER PT J AU Lunn, RM Langlois, RG Hsieh, LL Thompson, CL Bell, DA AF Lunn, RM Langlois, RG Hsieh, LL Thompson, CL Bell, DA TI XRCC1 polymorphisms: Effects on aflatoxin B-1-DNA adducts and glycophorin A variant frequency SO CANCER RESEARCH LA English DT Article ID STRAND-BREAK REPAIR; SISTER-CHROMATID EXCHANGE; DNA-REPAIR; POLY(ADP-RIBOSE) POLYMERASE; GENOMIC STABILITY; CELL-LINES; A LOCUS; GENE; EXPRESSION; MUTATIONS AB Hereditary genetic defects in DNA repair lead to increased risk of cancer. Polymorphisms in several DNA repair genes have been identified; however, the impact on repair phenotype has not been elucidated. We explored the relationship between polymorphisms in the DNA repair enzyme, XRCC1 (codons 194, 280, and 399), and genotoxic end points measured in two populations: (a) placental aflatoxin B-1 DNA (AFB(1)-DNA) adducts in a group of Taiwanese maternity subjects (rr = 120); and (b) somatic glycophorin A (GPA) variants in erythrocytes from a group of North Carolina smokers and nonsmokers (11 = 59), AFB(1),-DNA adducts were measured by ELISA, and erythrocyte GPA variant frequency (NN and N phi was assessed in MN heterozygotes with a flow cytometric assay. XRCC1 genotypes were identified by PCR-RFLPs. The XRCC1 399Gln allele was significantly associated with higher levels of both AFB(1)-DNA adducts and GPA NN mutations. Individuals with the 399Gln allele were at risk for detectable adducts (odds ratio, 2.4; 95% confidence interval, 1.1-5.4; P = 0.03), GPA NN variant frequency was significantly higher in 399Gln homozygotes (19.6 x 10(-6)) than in Gln/Arg heterozygotes (11.4 x 10(-6); P < 0.05) or Arg/Arg homozygotes (10.1 x 10(-6); P = 0.01), No significant effects were observed for other XRCC1 polymorphisms. These results suggest that the Arg399Gln amino acid change may alter the phenotype of the XRCC1 protein, resulting in deficient DNA repair. C1 NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. Univ Calif Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. Chang Gung Med Coll, Dept Publ Hlth, Tao Yuan 10018, Taiwan. RP Bell, DA (reprint author), NIEHS, LCBRA, POB 12233,MD C3-03, Res Triangle Pk, NC 27709 USA. NR 28 TC 455 Z9 486 U1 3 U2 13 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2557 EP 2561 PG 5 WC Oncology SC Oncology GA 203NA UT WOS:000080712700011 PM 10363972 ER PT J AU Zaharevitz, DW Gussio, R Leost, M Senderowicz, AM Lahusen, T Kunick, C Meijer, L Sausville, EA AF Zaharevitz, DW Gussio, R Leost, M Senderowicz, AM Lahusen, T Kunick, C Meijer, L Sausville, EA TI Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases SO CANCER RESEARCH LA English DT Article ID FLAVOPIRIDOL; IDENTIFICATION; DEHYDROGENASE; CYTOTOXICITY; ROSCOVITINE; POTENT; CDK2; CDC2 AB Analysis of the National Cancer Institute Human Tumor Cell Line Anti-Cancer Drug Screen data using the COMPARE algorithm to detect similarities in the pattern of compound action to flavopiridol, a known inhibitor of cyclin-dependent kinases (CDKs), has suggested several possible,novel CDK inhibitors, 9-Bromo-7,12-dihydro-indolo[3,2-d][1]benzazepin-6(5H)-one, NSC-664704 (kenpaullone), is reported here to be a potent inhibitor of CDK1/cyclin B (IC50 0.4 mu M). This compound also inhibited CDK2/cyclin A (IC50 0.68 mu M), CDK2/cyclin E (IC50 7.5 mu M), and CDK5/p25 (IC50 0.85 mu M) but had much less effect on other kinases; only c-src (IC50 15 mu M), casein-kinase 2 (IC50 20 mu M), erk 1 (IC50 20 mu M), and erk 2 (IC50 9 mu M) were inhibited with IC(50)s less than 35 mu M. Kenpaullone acts by competitive inhibition of ATP binding, Molecular modeling indicates that kenpaullone can bind in the ATP binding site of CDK2 with residue contacts similar to those observed in the crystal structures of other CDK2-bound inhibitors, Analogues of kenpaullone, in particular 10-bromopaullone (NSC-672234), also inhibited various protein kinases including CDKs, Cells exposed to kenpaullone and 10-bromopaullone display delayed cell cycle progression. Kenpaullone represents a novel chemotype:for compounds that preferentially inhibit CDKs. C1 NCI, Dev Therapeut Program, EPN, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. CNRS, Cell Cycle Grp, F-29680 Roscoff, Bretagne, France. Univ Hamburg, Inst Pharm, D-20146 Hamburg, Germany. RP Zaharevitz, DW (reprint author), NCI, Dev Therapeut Program, EPN, Div Canc Treatment & Diagnosis, Suite 811,6130 Execut Blvd,MSC 7444, Bethesda, MD 20892 USA. NR 20 TC 193 Z9 198 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2566 EP 2569 PG 4 WC Oncology SC Oncology GA 203NA UT WOS:000080712700013 PM 10363974 ER PT J AU Ryu, DY Pratt, VSW Davis, CD Schut, HAJ Snyderwine, EG AF Ryu, DY Pratt, VSW Davis, CD Schut, HAJ Snyderwine, EG TI In vivo mutagenicity and hepatocarcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in bitransgenic c-myc/lambda lacZ mice SO CANCER RESEARCH LA English DT Article ID TRANSGENIC MOUSE MODEL; DNA ADDUCT LEVELS; HETEROCYCLIC AMINES; IN-VIVO; LIVER CARCINOGENESIS; CHEMICAL CARCINOGENS; GENE AMPLIFICATION; GROWTH-FACTOR; COOKED FOODS; CANCER RISK AB 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a mutagenic and carcinogenic heterocyclic amine found in cooked meat, Hepatic DNA adduct formation, in vivo mutagenicity, and hepatocarcinogenicity of MeIQx were examined in mice harboring the lacZ mutation reporter gene (Muta mice) and bitransgenic mice overexpressing the c-myc oncogene. C57Bl/lambda lacZ and bitransgenic c-myc (albumin promoter)/lambda lacZ mice were bred and weaned onto an American Institute of Nutrition-76-based diet containing 0.06% (w/w) MeIQx or onto control diet. After 30 weeks on diet, only male bitransgenic mice on MeIQx developed hepatocellular carcinoma (100% incidence). By 40 weeks, hepatic tumor incidence was 100%/75% (17%/0%) and 44%/17% (0%/0%) in male c-myc/lambda lacZ and C57Bl/lambda lacZ mice who were given MeIQx (or control) diet, respectively, supporting a synergism between MeIQx and c-myc overexpression in hepatocarcinogenesis. At either time point, mutant frequency in the lacZ gene was at least 40-fold higher in MeIQx-treated mice than in control mice of either strain. These findings suggest that MeIQx-induced hepatocarcinogenesis is associated with MeIQx-induced mutations, Elevated mutant frequency in MeIQx-treated mice also occurred concomitant with the formation of MeIQx-guanine adducts, as detected by the P-32-postlabeling assay. Irrespective of strain or diet, sequence analysis of the lacZ mutants from male mouse liver showed that the principal sequence alterations were base substitutions at guanine bases. Adenine mutations, however, were detected only in animals on control diet. MeIQx-fed mice harboring the c-myc oncogene showed, a 1.4-2.6-fold higher mutant frequency in the lacZ gene than mice not carrying the transgene, Although there was a trend toward higher adduct levels in c-myc mice, MeIQx-DNA adduct levels were not significantly different between c-myc/lambda lacZ and C57Bl/lambda lacZ mice after 30 weeks on diet. Thus, it seemed that factors in addition to MeIQx-DNA adduct levels, such as the enhanced rate of proliferation associated with c-myc overexpression, may have accounted for a higher mutant frequency in c-myc mice. In the control diet groups, the lacZ mutant frequency was significantly higher in c-myc/lambda lacZ mice than in C57Bl/lambda lacZ mice. The findings are consistent with the notion that c-myc overexpression is associated with an increase in mutagenesis. The mechanism for the synergistic effects of c-myc overexpression on MeIQx hepatocarcinogenicity seems to involve an enhanced expression of MeIQx-induced mutations. C1 NCI, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Snyderwine, EG (reprint author), NCI, Expt Carcinogenesis Lab, Chem Carcinogenesis Sect, Bldg 37,Room 3C28,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 34 TC 16 Z9 17 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2587 EP 2592 PG 6 WC Oncology SC Oncology GA 203NA UT WOS:000080712700017 PM 10363978 ER PT J AU Adams, J Palombella, VJ Sausville, EA Johnson, J Destree, A Lazarus, DD Maas, J Pien, CS Prakash, S Elliott, PJ AF Adams, J Palombella, VJ Sausville, EA Johnson, J Destree, A Lazarus, DD Maas, J Pien, CS Prakash, S Elliott, PJ TI Proteasome inhibitors: A novel class of potent and effective antitumor agents SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; INDUCED CELL-DEATH; INDUCED APOPTOSIS; CANCER; PROLIFERATION; ACTIVATION; SUPPRESSION; PROTEIN; PATHWAY; GROWTH AB The ubiquitin-proteasome pathway plays a critical role in the regulated degradation of proteins involved in cell cycle control and tumor growth. Dysregulating the degradation of such proteins should have profound effects on tumor growth and cause cells to undergo apoptosis. To test this hypothesis, we developed a novel series of proteasome inhibitors, exemplified by PS-341, which we describe here. As determined by the National Cancer Institute bl vitro screen, PS-341 has substantial cytotoxicity against a broad range of human tumor cells, including prostate cancer cell lines, The PC-3 prostate cell line was, therefore, chosen to further examine the antitumor activity of PS-341. In vitro, PS-341 elicits proteasome inhibition, leading to an increase in the intracellular levels of specific proteins, including the cyclin-dependent kinase inhibitor, p21, Moreover, exposure of such cells to PS-341 caused them to accumulate in the G(2)-M phase of the cell cycle and subsequently undergo apoptosis, as indicated by nuclear condensation and poly(ADP-ribose) polymerase cleavage. Following weekly i.v. treatment of PS-341 to mice bearing the PC-3 tumor, a significant decrease (60%) in tumor burden was observed in vivo. Direct injection of PS-341 into the tumor also caused a substantial (70%) decrease in tumor volume with 40% of the drug-treated mice having no detectable tumors at the end of the study, Studies also revealed that i.v, administration of PS-341 resulted in a rapid and widespread distribution of PS-341, with highest levels identified in the liver and gastrointestinal tract and lowest levels in the skin and muscle, Modest levels were found in the prostate, whereas there was no apparent penetration of the central nervous system. An assay to follow the biological activity of the PS-341 was established and used to determine temporal drug activity as well as its ability to penetrate tissues. As such, PS-341 was shown to penetrate PC-3 tumors and inhibit intracellular proteasome activity 1.0 h after i.v. dosing, These data illustrate that PS-341 not only reaches its biological target but has a direct effect on its biochemical target, the proteasome. Importantly, the data show that inhibition of this target site by PS-341 results in reduced tumor growth in murine tumor models, Together, the results highlight that the proteasome is a novel biochemical target and that inhibitors such as PS-341 represent a unique class of antitumor agents. PS-341 is currently under clinical evaluation for advanced cancers. C1 ProScript Inc, Cambridge, MA 02139 USA. Hoechst Marion Roussel, D-60486 Frankfurt, Germany. Hoechst Marion Roussel, Bridgewater, NJ 08807 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Adams, J (reprint author), ProScript Inc, 38 Sidney St, Cambridge, MA 02139 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 32 TC 1029 Z9 1076 U1 10 U2 61 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2615 EP 2622 PG 8 WC Oncology SC Oncology GA 203NA UT WOS:000080712700022 PM 10363983 ER PT J AU Giacomini, P Giorda, E Fraioli, R Nicotra, MR Vitale, N Setini, A Delfino, L Morabito, A Benevolo, M Venturo, I Mottolese, M Ferrara, GB Natali, PG AF Giacomini, P Giorda, E Fraioli, R Nicotra, MR Vitale, N Setini, A Delfino, L Morabito, A Benevolo, M Venturo, I Mottolese, M Ferrara, GB Natali, PG TI Low prevalence of selective human leukocyte antigen (HLA)-A and HLA-B epitope losses in early-passage tumor cell lines SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT XII International Histocompatibility Workshop CY JUN 09-12, 1996 CL ST MALO, FRANCE ID CLASS-I PHENOTYPES; HUMAN SOLID TUMORS; MHC CLASS-I; MONOCLONAL-ANTIBODIES; MELANOMA-CELLS; HEAVY-CHAINS; INTRALOCUS DETERMINANT; LOCUS PRODUCTS; MESSENGER-RNA; C-MYC AB The down-regulation of human leukocyte antigen (HLA) class I molecules, especially the selective down-regulation of certain allelic products, is believed to represent a major mechanism of tumor escape from immune surveillance. In the present report, an original approach is described to precisely evaluate and classify HLA class I epitope losses in 30 cancer patients with malignant melanoma and lung, breast, endometrium, ovary, and colon carcinoma tumors. Early-passage tumor cell lines were established in culture from the corresponding metastatic tumor lesions obtained in each patient. Both the cell lines and the tumor Lesions were compared, in their HLA-A and -B expression, to the peripheral blood mononuclear cells (PBMCs) obtained from the same patient (autologous PBMCs). On the basis of HLA-genotyping data, the appropriate monoclonal antibodies identifying mono- and poly-morphic HLA-A and HLA-B epitopes were selected from a panel of 34 antibodies for a total of 24 testable alleles. The selected antibodies were used not only in immunohistochemical assays on cryostatic tumor sections and cytospins of PBMCs but also in quantitative, sensitive flow cytometry assays on early-passage tumor cells and PBMC suspensions. With this latter method, a low overall HLA expression was detected in 26 tumor cell explants and a complete, generalized HLA-A, HLA-B, HLA-C loss in the remaining 4 cases. However, no complete, selective loss of any of the 45 tested HLA-A and HLA-B allomorphs was observed. Sequences from all of the HLA class I alleles could be detected at the genomic DNA level in tumor cells and tissues. At variance from the literature and the results of immunohistochemical experiments performed in parallel on the corresponding tumor lesions, the relative proportions of the various HLA epitopes were relatively preserved in each early-passage cell line/PBMC pair, and selective increases, rather than decreases, in the expression of polymorphic HLA epitopes had the highest prevalence and greatest magnitude. Our data suggest an alternative tumor stealth strategy in which up- and down-regulation are equally important. This alternative model of tumor-host interaction better fits the available models of tumor cell recognition by CTLs and natural killer cells bearing activatory and inhibitory receptors for HLA-A, HLA-B, HLA-C molecules. C1 Ist Regina Elena CRS, Immunol Lab, I-00158 Rome, Italy. Natl Res Council, Inst Biomed Technol, I-00162 Rome, Italy. Natl Canc Inst, Immunogenet Lab, Ctr Adv Biotechnol, I-16132 Genoa, Italy. Regina Elena Canc Inst, Pathol Lab, I-00162 Rome, Italy. RP Giacomini, P (reprint author), Ist Regina Elena CRS, Immunol Lab, Via Messi Oro 156, I-00158 Rome, Italy. RI Giacomini, Patrizio/K-5217-2016 OI Giacomini, Patrizio/0000-0001-6109-1709 NR 43 TC 20 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2657 EP 2667 PG 11 WC Oncology SC Oncology GA 203NA UT WOS:000080712700028 PM 10363989 ER PT J AU Ingvarsson, S Agnarsson, BA Sigbjornsdottir, BI Kononen, J Kallioniemi, OP Barkardottir, RB Kovatich, AJ Schwarting, R Hauck, WW Huebner, K McCue, PA AF Ingvarsson, S Agnarsson, BA Sigbjornsdottir, BI Kononen, J Kallioniemi, OP Barkardottir, RB Kovatich, AJ Schwarting, R Hauck, WW Huebner, K McCue, PA TI Reduced Fhit expression in sporadic and BRCA2-linked breast carcinomas SO CANCER RESEARCH LA English DT Article ID SINGLE BRCA2 MUTATION; CANCER FAMILIES; ICELANDIC BREAST; 999DEL5 MUTATION; DNA-REPAIR; SHORT ARM; GENE; TUMORS; CHROMOSOME-3; CARRIERS AB Evidence for alteration of the FHIT gene in a significant fraction of breast carcinomas has been reported, in apparent concordance with loss of heterozygosity (LOH) at chromosome region 3p14.2 in breast cancer and benign proliferative breast disease, A significantly higher frequency of LOH at the FHIT locus was reported for BRCA2(-/-) tumors, possibly due to misrepaired double-strand breaks at this common fragile region, To determine whether such genomic alterations lead to Fhit inactivation, we have assessed the level of Fhit expression by immunohistochemical detection in sporadic tumors and cancers occurring in BRCA2 999del5 carriers. To determine whether Fhit inactivation may have prognostic significance, we have also assessed expression of breast cancer markers and clinical features in sporadic tumors relative to Fhit expression. Of 40 consecutive sporadic breast carcinomas studied for tumor markers, 50% showed reduced Fhit expression; In these sporadic cancers, loss of Fhit expression was not correlated significantly with the presence or absence of other tumor markers. In a study of 58 sporadic and 34 BRCA2 999del5 Icelandic invasive cancers, there was a significant association of LOH at 3p14.2 with reduced expression of Fhit (P = 0.001); also the lower expression of Fhit and higher LOB at 3p14.2 in BRCA2 999del5 tumors relative to sporadic cancers was significant (P = 0.002), Thus, genetic alteration at the fragile site within the FHIT gene leads to loss of Fhit protein in a significant fraction of sporadic breast cancers and a much larger fraction of familial breast cancers with an inherited BRCA2 mutation, consistent with the Idea that loss of BRCA2 function affects stability of the FHIT/FRA3B locus. C1 Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Univ Hosp Iceland, Dept Pathol, IS-121 Reykjavik, Iceland. Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD 20892 USA. RP Huebner, K (reprint author), Kimmel Canc Ctr, Bluemle Life Sci Bldg,Room 1008,233 S 10th St, Philadelphia, PA 19107 USA. RI Ingvarsson, Sigurdur/E-7448-2011; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NCI NIH HHS [CA21124, CA56336] NR 33 TC 53 Z9 55 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1999 VL 59 IS 11 BP 2682 EP 2689 PG 8 WC Oncology SC Oncology GA 203NA UT WOS:000080712700031 PM 10363992 ER PT J AU Chhabra, SK Reed, CD Anderson, LM Shiao, YH AF Chhabra, SK Reed, CD Anderson, LM Shiao, YH TI Comparison of the polymorphic regions of the cytochrome P450CYP2E1 gene of humans and patas and cynomolgus monkeys SO CARCINOGENESIS LA English DT Article ID FRAGMENT-LENGTH-POLYMORPHISM; ALCOHOLIC LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; LUNG-CANCER; 5'-FLANKING REGION; RSAI POLYMORPHISM; P4502E1 LOCUS; SUSCEPTIBILITY; RISK; 2E1 AB Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight toxicants. CYP2EI gene polymorphisms have been linked to risk of various cancers and liver disease in humans. Since the patas monkey is a promising model for study of cancer-related alcohol/nitrosamine interactions, we examined CYP2EI in this monkey for characteristics of two regions that are polymorphic in humans, an RsaI site in the 5' promoter region and a DraI site in intron 6, Another monkey species often used in biomedical research, the cynomolgus monkey, was also examined. Human DNA primers used to amplify a 413 bp segment around the RsaI site also amplified a segment of similar size (409 bp) from DNA of 25 patas monkeys, whereas a product of similar to 800 bp was amplified from DNA of eight cynomolgus monkeys. RsaI did not cut the amplified DNA product from either monkey species. Sequencing revealed that the patas RsaI site was identical to that in humans with the c2c2 CYP2E1 genotype, GTAT, The equivalent cynomolgus sequence, CTAC, has not been observed in humans. Thus, the patas monkey appears to be a useful model for CYP2E1 c2c2 humans, and this genotype, present in 2-25% of humans, may be more primitive than c1c1, For the DraI site, the human primers amplified DNA products similar in size to those from humans, from all patas and cynomolgus monkey DNA samples; none mere cut by DraI, Thus, both monkey species appeared to be generally similar to humans of CYP2E1 CC DraI genotype, which is the rarer form of the gene. C1 NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Shiao, YH (reprint author), NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1999 VL 20 IS 6 BP 1031 EP 1034 DI 10.1093/carcin/20.6.1031 PG 4 WC Oncology SC Oncology GA 205AF UT WOS:000080798500017 PM 10357784 ER PT J AU Srivastava, DK Husain, I Arteaga, CL Wilson, SH AF Srivastava, DK Husain, I Arteaga, CL Wilson, SH TI DNA polymerase beta expression differences in selected human tumors and cell lines SO CARCINOGENESIS LA English DT Article ID BASE-EXCISION-REPAIR; HAMSTER OVARY CELLS; MESSENGER-RNA; ABASIC SITE; COLORECTAL-CANCER; GENE-EXPRESSION; NUCLEAR EXTRACT; BOVINE TESTIS; UP-REGULATION; CDNA CLONING AB A long-standing question in cancer biology has been the extent to which DNA repair may be altered during the process of carcinogenesis. We have shown recently that DNA polymerase beta (P-pol) provides a rate-determining function during in vitro repair of abasic sites by one of the mammalian DNA base excision repair pathways. Therefore, altered expression of beta-pol during carcinogenesis could alter base excision repair and, consequently, be critical to the integrity of the mammalian genome. We examined the expression of beta-pol in several cell lines and human adenocarcinomas using a quantitative immunoblotting method. In cell lines from normal breast or colon, the level of beta-pol was similar to 1 ng/mg cell extract, whereas in all of the breast and colon adenocarcinoma cell lines tested, a higher level of beta-pol was observed, In tissue samples, colon adenocarcinomas had a higher level of beta-pol than adjacent normal mucosa. Breast adenocarcinomas exhibited a wide range of beta-pol expression: one tumor had a much higher level of beta-pol (286 ng/mg cell extract) than adjacent normal breast tissue, whereas another tumor had the same level of beta-pol as adjacent normal tissue. Differences in beta-pol expression level, from normal to elevated, were also observed with prostate adenocarcinomas. All kidney adenocarcinomas tested had a slightly lower beta-pol level than adjacent normal tissue. This study reveals that the base excision repair enzyme DNA polymerase beta is upregulated in some types of adenocarcinomas and cell lines, but not in others. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Inc, Dept Funct Genet, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Sch Med, Dept Med & Cell Biol, Nashville, TN 37232 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 46 TC 105 Z9 119 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1999 VL 20 IS 6 BP 1049 EP 1054 DI 10.1093/carcin/20.6.1049 PG 6 WC Oncology SC Oncology GA 205AF UT WOS:000080798500020 PM 10357787 ER PT J AU Giandomenico, V Andreola, F de la Concepcion, MLR Collins, SJ De Luca, LM AF Giandomenico, V Andreola, F de la Concepcion, MLR Collins, SJ De Luca, LM TI Retinoic acid and 4-hydroxyphenylretinamide induce growth inhibition and tissue transglutaminase through different signal transduction pathways in mouse fibroblasts (NIH 3T3 cells) SO CARCINOGENESIS LA English DT Article ID APOPTOSIS; EXPRESSION; TRANSFORMATION; INVOLVEMENT; METABOLISM; LINES AB 4-Hydroxyphenylretinamide (4-HPR) is a synthetic retinoid with minimal toxicity and favorable pharmacokinetics during long-term administration to patients in clinical trials, Since 4-HPR binds poorly to the retinoic acid receptors, the issue of whether 4-HPR exerts its biological actions via classical retinoid receptor pathways remains to be resolved. We have previously reported that stable expression of a truncated retinoic acid receptor alpha, RAR alpha 403, transduced in NIH 3T3 cells by a retroviral vector, rendered the cells resistant to retinoic acid for growth inhibition and induction of tissue transglutaminase (TGase II). sere, we report that stable expression of the dominant negative construct RAR alpha 403 fails to blunt growth inhibition and TGase II induction by 4-HPR, a potent chemopreventive retinoid, in the same cells. These data show that retinoic acid receptors do not mediate either growth inhibition or induction of TGase II activity by 4-HPR in mouse fibroblast cells. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Room 3A-17,37 Convent Dr, Bethesda, MD 20892 USA. EM luigi_de_luca@nih.gov NR 18 TC 16 Z9 16 U1 0 U2 1 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 JUN PY 1999 VL 20 IS 6 BP 1133 EP 1135 DI 10.1093/carcin/20.6.1133 PG 3 WC Oncology SC Oncology GA 205AF UT WOS:000080798500033 PM 10357800 ER PT J AU Yagodin, S Pivovarova, NB Andrews, SB Sattelle, DB AF Yagodin, S Pivovarova, NB Andrews, SB Sattelle, DB TI Functional characterization of thapsigargin and agonist-insensitive acidic Ca2+ stores in Drosophila melanogaster S2 cell lines SO CELL CALCIUM LA English DT Article ID CULTURED RAT ASTROCYTES; ENDOPLASMIC-RETICULUM; INOSITOL 1,4,5-TRISPHOSPHATE; SECRETORY GRANULES; CA-2+ MOBILIZATION; SENSITIVE POOLS; GOLGI-APPARATUS; ELECTRON-PROBE; CALCIUM; LOCALIZATION AB The role of acidic intracellular calcium stores in calcium homeostasis was investigated in the Drosophila Schneider cell line 2 (S2) by means of free cytosolic calcium ([Ca2+](i)) and intracellular pH (pH(i)) imaging together with measurements of total calcium concentrations within intracellular compartments. Both a weak base (NH4Cl, 15 mM) and a Na+/H+ ionophore (monensin, 10 mu M) evoked cytosolic alkalinization followed by Ca2+ release from acidic intracellular Ca2+ stores. Pretreatment of S2 cells with either thapsigargin (1 mu M), an inhibitor of endoplasmic reticulum Ca2+-ATPases, or with the Ca2+ ionophore ionomycin (10 mu M) was without effect on the amplitude of Ca2+ release evoked by alkalinization. Application of the cholinergic agonist carbamylcholine (100 mu M) to transfected S2-DM1 cells expressing a Drosophila muscarinic acetylcholine receptor (DM1) emptied the InsP(3)-sensitive Ca2+ store but failed to affect the amplitude of alkalinization-evoked Ca2+ release. Glycyl-L-phenylalanine-beta-naphthylamide (200 mu M), a weak hydrophobic base known to permeabilize lysosomes by osmotic swelling, triggered Ca2+ release from internal stores, while application of brefeldin A (10 mu M), an antibiotic which disperses the Golgi complex, resulted in a smaller increase in [Ca2+](i). These results suggest that the alkali-evoked calcium release is largely attributable to lysosomes, a conclusion that was confirmed by direct measurements of total calcium content of S2 organelles. Lysosomes and endoplasmic reticulum were the only organelles found to have concentrations of total calcium significantly higher than the cytosol. However, NH4Cl (15 mM) reduced the level of total calcium only in lysosomes, Depletion of acidic Ca2+ stores did not elicit depletion-operated Ca2+ entry. They were refilled upon re-exposure of cells to normal saline ([Ca2+](o) = 2 mM), but not by thapsigargin-induced [Ca2+](i) elevation in Ca2+-free saline. C1 Univ Cambridge, Dept Zool, Babraham Inst, Mol Signalling Lab, Cambridge CB2 3EJ, England. NINDS, NIH, Neurobiol Lab, Bethesda, MD USA. RP Sattelle, DB (reprint author), Univ Cambridge, Dept Zool, Babraham Inst, Mol Signalling Lab, Downing St, Cambridge CB2 3EJ, England. NR 52 TC 33 Z9 33 U1 4 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JUN PY 1999 VL 25 IS 6 BP 429 EP 438 DI 10.1054/ceca.1999.0043 PG 10 WC Cell Biology SC Cell Biology GA 243ZR UT WOS:000083027800005 PM 10579054 ER PT J AU Damjanovski, S Ishizuya-Oka, A Shi, YB AF Damjanovski, S Ishizuya-Oka, A Shi, YB TI Spatial and temporal regulation of collagenases-3,-4, and stromelysin-3 implicates distinct functions in apoptosis and tissue remodeling during frog metamorphosis SO CELL RESEARCH LA English DT Article DE apoptosis; thyroid hormone; matrix metalloproteinase; extracellular matrix (ECM); amphibian ID ANURAN LARVAL SKIN; EXTRACELLULAR-MATRIX; THYROID-HORMONE; XENOPUS-LAEVIS; TADPOLE TAIL; METALLOPROTEINASE ACTIVITY; ULTRASTRUCTURAL-CHANGES; GENE-EXPRESSION; TRANSGENIC MICE; SMALL-INTESTINE AB are present in regions where extensive connective tissue remodeling take place. These results indicate that ST3 is likely to play a role in ECM-remodeling that facilitate apoptotic tissue remodeling or resorption while Col3 and Col4 appear to participate in connective tissue degradation during development. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 32102, Japan. RP Shi, YB (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov RI Damjanovski, Sashko/N-8728-2015 NR 46 TC 56 Z9 56 U1 0 U2 0 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JUN PY 1999 VL 9 IS 2 BP 91 EP 105 DI 10.1038/sj.cr.7290009 PG 15 WC Cell Biology SC Cell Biology GA 277JQ UT WOS:000084930800002 PM 10418731 ER PT J AU Fritsch, N Wu, C AF Fritsch, N Wu, C TI Phosphorylation of Drosophila heat shock transcription factor SO CELL STRESS & CHAPERONES LA English DT Article ID PROTEIN-KINASE-C; DNA-BINDING ACTIVITY; ACTIVATION DOMAIN; FACTOR-I; OKADAIC ACID; FACTOR HSF1; HSP70 GENE; TRANSACTIVATION DOMAIN; MOLECULAR-CLONING; STRESS-RESPONSE AB The role that phosphorylation plays in regulating heat shock factor (HSF) function and activity has been the subject of several studies. Here, we demonstrate that Drosophila melanogaster HSF (DmHSF) is a phosphoprotein that is multiply phosphorylated at some sites and is dephosphorylated at others upon heat shock. However, the steady-state level of phosphorylation of Drosophila HSF remains unchanged after heat shock. Phosphoamino-acid analysis reveals that predominantly serine residues are phosphorylated for both the non-shocked and heat shocked molecules. Gel mobility shift assays using extracts from SL2 cells treated with a variety of phosphatase and kinase inhibitors show little or no effect on the heat shock induced DNA binding activity of HSF or on its recovery. We conclude that phosphorylation plays no significant role in regulating the heat induced DNA binding activity of Drosophila HSF. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 5E26, Bethesda, MD 20892 USA. EM carlwu@helix.nih.gov NR 90 TC 7 Z9 7 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1355-8145 EI 1466-1268 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD JUN PY 1999 VL 4 IS 2 BP 102 EP 117 PG 16 WC Cell Biology SC Cell Biology GA 245WZ UT WOS:000083132200004 ER PT J AU Rudorfer, MV Potter, WZ AF Rudorfer, MV Potter, WZ TI Metabolism of tricyclic antidepressants SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE antidepressants; tricyclic; metabolism; hydroxy metabolites; pharmacokinetics; pharmacogenetics; drug-drug interactions; toxicity; plasma concentrations ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; JAPANESE PSYCHIATRIC POPULATION; STATE PLASMA-CONCENTRATIONS; ELDERLY DEPRESSED-PATIENTS; GRAPEFRUIT JUICE; DRUG-METABOLISM; BREAST-MILK; DEBRISOQUINE HYDROXYLATION; THERAPEUTIC RESPONSE; ACTIVE METABOLITES AB 1. Despite the considerable advances in the treatments available for mood disorders over the past generation, tricyclic antidepressants TCAs remain an important option for the pharmacotherapy of depression. 2. The pharmacokinetics of TCAs are characterized by substantial presystemic firstpass metabolism, a large volume of distribution, extensive protein binding, and an elimination half-life averaging about 1 day (up to 3 days for protriptyline). 3. Clearance of tricyclics is dependent primarily on hepatic cytochrome P450 (CYP) oxidative enzymes. Although the activities of some P450 isoenzymes are largely under genetic control, they may be influenced by external factors, such as the concomitant use of other medications or substances. Patient variables, such as ethnicity and age, also affect TCA metabolism. The impact of gender and related reproductive issues is coming under increased scrutiny. 4. Metabolism of TCAs, especially their hydroxylation, results in the formation of active metabolites, which contribute to both the therapeutic and the adverse effects of these compounds. 5. Renal clearance of the polar metabolites of TGAs is reduced by normal aging, accounting for much of the increased risk of toxicity in older patients. 6. Knowledge of factors affecting the metabolism of TCAs can further the development and understanding of newer antidepressant medications. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Lilly Res Labs, Indianapolis, IN USA. RP Rudorfer, MV (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7163,MSC 9635, Bethesda, MD 20892 USA. NR 203 TC 39 Z9 39 U1 2 U2 15 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 1999 VL 19 IS 3 BP 373 EP 409 DI 10.1023/A:1006949816036 PG 37 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 191PH UT WOS:000080030400005 PM 10319193 ER PT J AU Drozdova, Y Steudel, R Koch, W Miaskiewicz, K Topol, IA AF Drozdova, Y Steudel, R Koch, W Miaskiewicz, K Topol, IA TI The formation of the sulfur halides SX4 from SX2 and X-2: Reaction enthalpies, transition states, and activation energies for X = F and Cl SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE ab initio calculations; reaction mechanisms; sulfuranes; sulfur halides; transition states ID SET MODEL CHEMISTRY; D-ORBITAL PARTICIPATION; ROTATIONAL SPECTROSCOPY; MICROWAVE-SPECTRUM; POTENTIAL FUNCTION; RAMAN-SPECTRA; ATOMS; MOLECULES; ABINITIO; SCL2 AB High-level ab initio MO calculations by different methods demonstrate that the reaction of SF2 with F-2 to form SF4 is strongly exothermic and exergonic [CCSD(T)/6-311+G(2df)//MP2/6-311+G*: Delta H(298)degrees = -445 kJ mol(-1), Delta G(298)degrees = -398 kJ mol(-1)] and proceeds via a very weakly bonded intermediate 2 with C-s symmetry. The structure of 2 corresponds to a donor-acceptor complex F2S-->F-2 with a considerable transfer of charge (0.69 e). The transition state (TS1) between 2 and SF4 has a similar structure to 2 but with C-1 symmetry. The energy of the adduct and of TS1 is almost the same as the combined energy of the separate molecules SF2 and F-2. Therefore, the overall activation energy for the reaction of SF2 with F-2 to form SF4 is practically negligible (6 kJ mol(-1) at 298 K). The analogous reaction of SCl2 with Cl-2 to form the hypothetical molecule SCl4 is endothermic and endergonic (Delta H(298)degrees = +32 kJ mol(-1), Delta G(298)degrees = +74 kJ mol(-1)). The ground-state geometry of SCl2 has C-2v symmetry at the MP2/6-311+G* level and the coordination geometry at sulfur is pseudo-trigonal-bipyramidal. The transition state (TS2) of this reaction is ionic ([SCl3+]Cl-) and has C-1 symmetry. The activation energy at 0 K for the chlorination of SCl2 amounts to 203 kJ mol(-1) at the CCSD(T)/6-311+G(2df) level; it is 43 kJ mol(-1) lower than the experimental bond dissociation energy of Cl-2. The proposed formation of the analogous tetrathiasulfuranes S(SR)(4) from (RS)(2)S and RSSR is discussed in connection with the various interconversion reactions of polysulfur compounds. C1 Tech Univ Berlin, Inst Anorgan & Analyt Chem, Sekr C2, D-10623 Berlin, Germany. Gesell Deutsch Chem, D-60444 Frankfurt, Germany. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. RP Steudel, R (reprint author), Tech Univ Berlin, Inst Anorgan & Analyt Chem, Sekr C2, Str 17 Juni 135, D-10623 Berlin, Germany. NR 56 TC 13 Z9 13 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PD JUN PY 1999 VL 5 IS 6 BP 1936 EP 1943 DI 10.1002/(SICI)1521-3765(19990604)5:6<1936::AID-CHEM1936>3.0.CO;2-T PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 205ND UT WOS:000080826700033 ER PT J AU Johnston, M AF Johnston, M TI Preventing the plague SO CHEMISTRY IN BRITAIN LA English DT Article C1 NIAID, Div Aids, Bethesda, MD 20892 USA. RP Johnston, M (reprint author), NIAID, Div Aids, 60003 Execut Blvd,Room 2A07, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0009-3106 J9 CHEM BRIT JI Chem. Br. PD JUN PY 1999 VL 35 IS 6 BP 36 EP 40 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 204ZZ UT WOS:000080797700048 ER PT J AU Schatz, J Craft, S Koby, M Siegel, MJ Resar, L Lee, RR Chu, JY Launius, G Dadash-Zadehm, M DeBaun, MR AF Schatz, J Craft, S Koby, M Siegel, MJ Resar, L Lee, RR Chu, JY Launius, G Dadash-Zadehm, M DeBaun, MR TI Neuropsychologic deficits in children with sickle cell disease and cerebral infarction: Role of lesion site and volume SO CHILD NEUROPSYCHOLOGY LA English DT Article ID FRONTAL-LOBE INJURY; HYPERACTIVITY DISORDER; ABNORMALITIES; CHILDHOOD AB Little is known about the correlation between the location and size of cerebral infarction in children and neuropsychologic deficits. We related lesion location and volume on magnetic resonance exams to neuropsychologic performance in 28 children with cerebral infarcts due to sickle cell disease. Seventeen healthy siblings served as a comparison group. Children with anterior cerebral infarcts (n = 7) showed deficits in attention and executive skills, whereas children with more widespread cerebral infarcts (n = 18) showed additional deficits in spatial skills. The volume of cerebral infarction was associated with spatial and language performance, but minimally related to performance in other cognitive domains. The location and volume of cerebral infarction are both important for defining the type and magnitude of cognitive sequelae in childhood stroke. C1 Washington Univ, St Louis, MO USA. Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. Johns Hopkins Univ, Med Ctr, Dept Pediat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. St Louis Univ, Med Ctr, Dept Radiol, St Louis, MO 63110 USA. Sinai Hosp, Dept Pediat, Baltimore, MD 21215 USA. Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA. RP DeBaun, MR (reprint author), St Louis Childrens Hosp, Campus Box 8116,1 Childrens Pl, St Louis, MO 63110 USA. NR 32 TC 31 Z9 31 U1 1 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD JUN PY 1999 VL 5 IS 2 BP 92 EP 103 DI 10.1076/chin.5.2.92.3170 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 237ME UT WOS:000082659500002 ER PT J AU Riekert, KA Wiener, L Battles, H AF Riekert, KA Wiener, L Battles, H TI Prediction of psychological distress in school-age children with HIV SO CHILDRENS HEALTH CARE LA English DT Article ID RESISTANCE FACTORS; DEPRESSION INVENTORY; MATERNAL DEPRESSION; BEHAVIOR CHECKLIST; CHRONICALLY ILL; CHRONIC ILLNESS; HEMOPHILIA; SYMPTOMS; CANCER; PSYCHOPATHOLOGY AB This study examined the level of psychological distress in 61 children with HIV ages 6 to 11. Three domains of child psychological distress were measured by both caregiver and child report: separation anxiety, generalized anxiety, and depression. Information about caregiver's psychological distress was also collected. Hierarchical multiple regression analyses were conducted to test the hypothesis that caregiver psychological distress would account for significant variance in child psychological distress beyond that accounted for by demographic and disease variables. This hypothesis was confirmed only for the caregiver's report of the child's psychological distress. The child's knowledge of his or her diagnosis affected both parent and child reports of the child's psychological distress. C1 Case Western Reserve Univ, Dept Psychol, Cleveland, OH 44106 USA. NCI, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Riekert, KA (reprint author), Case Western Reserve Univ, Dept Psychol, 10900 Euclid Ave, Cleveland, OH 44106 USA. NR 50 TC 19 Z9 19 U1 2 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0273-9615 J9 CHILD HEALTH CARE JI Child. Health Care PD SUM PY 1999 VL 28 IS 3 BP 201 EP 220 DI 10.1207/s15326888chc2803_1 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 231BL UT WOS:000082286100001 ER PT J AU Matikainen, MP Schleutker, J Morsky, P Kallioniemi, OP Tammela, TLJ AF Matikainen, MP Schleutker, J Morsky, P Kallioniemi, OP Tammela, TLJ TI Detection of subclinical cancers by prostate-specific antigen screening in asymptomatic men from high-risk prostate cancer families SO CLINICAL CANCER RESEARCH LA English DT Article ID SUSCEPTIBILITY LOCUS; CHROMOSOME 1Q; RECEPTOR GENE; HISTORY; INHERITANCE; DIAGNOSIS AB Positive family history is a significant risk factor for prostate cancer. Improved knowledge of the epidemiology and molecular basis of hereditary prostate cancer has led to a need for counseling and clinical follow-up for men with a positive family history of prostate cancer. However, very little information is available on the efficacy of early screening procedures, such as serum prostate-specific antigen (PSA) measurements, in the management of genetically predisposed, high-risk individuals. In a nationwide study, we obtained family histories from 2099 Finnish prostate cancer patients and identified 302 families with two or more affected cases. Here, 209 asymptomatic 45-75-year-old males from these families were included in a study to determine the frequency of serum PSA positivity and the prevalence of subclinical prostate cancers. Serum PSA was elevated in 21 (10.0%) of these high-risk individuals. Seven prostate cancers (3.3%) and two high-grade prostatic intraepithelial neoplasia lesions were diagnosed, with three cancers occurring in men ages less than or equal to 59 years. Men from prostate cancer families,vith an average age of onset of <60 years had a significantly higher frequency of PSA positivity (28.6%, P = 0.01) as well as cancers (14,3%, P = 0.02) than those with a later age of onset. The results suggest that prostate cancer development in genetically predisposed individuals is preceded by a subclinical period when PSA detection is possible. Serum PSA screening may be particularly useful in men with a family history of early-onset prostate cancer. C1 Tampere Univ, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Chem, Div Urol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Surg, Div Urol, FIN-33101 Tampere, Finland. NIH, Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD 20892 USA. RP Matikainen, MP (reprint author), Tampere Univ, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NHGRI NIH HHS [N01-HG-55389] NR 34 TC 24 Z9 24 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1275 EP 1279 PG 5 WC Oncology SC Oncology GA 206MR UT WOS:000080883800004 PM 10389909 ER PT J AU Chikamatsu, K Nakano, K Storkus, WJ Appella, E Lotze, MT Whiteside, TL DeLeo, AB AF Chikamatsu, K Nakano, K Storkus, WJ Appella, E Lotze, MT Whiteside, TL DeLeo, AB TI Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells SO CLINICAL CANCER RESEARCH LA English DT Article ID RESPONSES IN-VITRO; WILD-TYPE P53; ANTITUMOR IMMUNITY; HEALTHY DONORS; TUMOR-ANTIGENS; PEPTIDE; CANCER; PROTEIN; THERAPY; MUTANT AB CTLs recognizing the HLA-A2.1-restricted, wild-type sequence p53 epitopes p53(149-157) and p53(264-272) were generated from CDS-enriched populations of nonadherent peripheral blood lymphocytes (PBLs) obtained from healthy donors. The PBLs were restimulated in vitro with peptide-pulsed granulocyte macrophage colony-stimulating factor- and interleukin (TL) il-induced autologous dendritic cells in the presence of IL-6 and IL-12 and subsequently cultivated with IL-1 alpha, IL-2, IL-4, IL-6, and IL-7. Bulk anti-p53(264-272) CTL populations were generated from PBLs obtained from two of five donors. Both CTL populations were cytotoxic against peptide-pulsed HLA-A2(+) target cells, but not against untreated target cells. A CD8(+) anti-p53 CTL clone designated p264#2 was isolated from one of the bulk populations. It was found to have an intermediate affinity of approximately 10(-9) M for the epitope and to mediate cytotoxicity against several human tumor cell lines, including the squamous cell carcinoma of the head and neck cell line SCC-9, which is known to present the wild-type sequence p53(264-272) epitope, In addition, CTLs reactive against p53(149-157)-pulsed targets as well as a HLA-A2(+) tumor cell line were cloned from a bulk population of antitumor CTLs obtained from one of the five normal PBLs restimulated with this epitope, The results indicate that CTLs recognizing wild-type sequence epitopes can be generated from precursors present in PBLs obtained from some normal individuals using autologous dendritic cells as antigen-presenting cells and suggest that vaccine strategies targeting these epitopes can lead to antitumor CTL generation, thereby emphasizing the therapeutic potential of p53-based cancer vaccines. C1 Univ Pittsburgh, Inst Canc, Div Basic Res, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Div Biol Therapeut, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. NCI, Bethesda, MD 20892 USA. RP DeLeo, AB (reprint author), Univ Pittsburgh, Inst Canc, Div Basic Res, Biomed Tower Room W956, Pittsburgh, PA 15213 USA. OI Storkus, Walter/0000-0001-8961-4444 FU NCI NIH HHS [CA72914]; NIDCR NIH HHS [1P01-DE12321] NR 42 TC 68 Z9 69 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1281 EP 1288 PG 8 WC Oncology SC Oncology GA 206MR UT WOS:000080883800005 PM 10389910 ER PT J AU Morse, MA Deng, YP Coleman, D Hull, S Kitrell-Fisher, E Nair, S Schlom, J Ryback, ME Lyerly, HK AF Morse, MA Deng, YP Coleman, D Hull, S Kitrell-Fisher, E Nair, S Schlom, J Ryback, ME Lyerly, HK TI A phase I study of active immunotherapy with carcinoembryonic antigen peptide (CAP-1)-pulsed, autologous human cultured dendritic cells in patients with metastatic malignancies expressing carcinoembryonic antigen SO CLINICAL CANCER RESEARCH LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; RECOMBINANT VACCINIA VIRUS; CYTOTOXIC T-LYMPHOCYTES; BONE-MARROW; PERIPHERAL-BLOOD; HUMAN-MELANOMA; TUMOR; GENERATION; CANCER; GENE AB Dendritic cells (DCs), antigen-presenting cells capable of priming naive T cells to specific antigens in an HLA-restricted fashion, have been demonstrated to induce protective T cell-mediated immunity in tumor-bearing animals. We performed this study to test the safety, feasibility, and clinical response of immunizations with in vitro-generated DCs, loaded with an HLA-A2-restricted peptide fragment of the tumor antigen carcinoembryonic antigen (CEA), for the treatment of patients with advanced CPA-expressing malignancies. Cell preparations enriched for autologous DCs were generated from the patients' plastic adherent peripheral blood mononuclear cells in serum-free media supplemented with granulocyte macrophage colony-stimulating factor and interleukin-4, Within the cell preparation, 66% of the cells expressed the phenotype typical for DCs (CD86(high), HLA-DRhigh, and CD14(low)). The DCs were loaded with the CEA peptide CAP-1 and cryopreserved. Groups of three to six patients received four weekly or biweekly i,v, infusions of the CAP-1-loaded DC in escalating dose levels of 1 x 10(7), 3 x 10(7), and 1 x 10(8) cells/dose. A subset of the patients in the last group also received intradermal injections of 1 x 10(6) DCs, There were no toxicities directly referable to the treatments. One patient had a minor response, and one had stable disease. Skin punch biopsy at DC injection sites demonstrated pleomorphic infiltrates in the three patients evaluated. We conclude that it is feasible and safe to generate and administer large numbers of previously cryopreserved DCs loaded with CAP-1 peptide to patients with advanced malignancies. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIH, Rockville, MD 20852 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. RP Morse, MA (reprint author), Duke Univ, Med Ctr, Dept Med, Box 2606, Durham, NC 27710 USA. RI Lyerly, Herbert/B-6528-2014 OI Lyerly, Herbert/0000-0002-0063-4770 FU NCI NIH HHS [U01CA72162-01]; NCRR NIH HHS [M01RR00030] NR 33 TC 224 Z9 231 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1331 EP 1338 PG 8 WC Oncology SC Oncology GA 206MR UT WOS:000080883800011 PM 10389916 ER PT J AU Takimoto, CH Yee, LK Venzon, DJ Schuler, B Grollman, F Chabuk, C Hamilton, JM Chen, AP Allegra, CJ Green, JL AF Takimoto, CH Yee, LK Venzon, DJ Schuler, B Grollman, F Chabuk, C Hamilton, JM Chen, AP Allegra, CJ Green, JL TI High inter- and intrapatient variation in 5-fluorouracil plasma concentrations during a prolonged drug infusion SO CLINICAL CANCER RESEARCH LA English DT Article ID DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY; BLOOD MONONUCLEAR-CELLS; ADVANCED COLORECTAL-CANCER; CIRCADIAN-RHYTHM; FLUOROPYRIMIDINE CHEMOTHERAPY; POSSIBLE RELEVANCE; PHASE-I; FLUOROURACIL; LEUCOVORIN; BOLUS AB The purpose of the study was to examine inter- and intrapatient variation in 5-fluorouracil (5-FU) plasma concentrations in adult cancer patients receiving a 3-day drug infusion. Fourteen patients received 1266 mg/m(2) N-(phosphonacetyl)-L-aspartate (PALA) infused i,v, over 15 min on day 1, followed immediately by a loading dose of 500 mg/m(2) calcium leucovorin over 30 min. Then a prolonged infusion of leucovorin at 500 mg/m(2)/day and 5-FU at 1750 mg/m(2)/day was administered as either a constant rate or as a circadian infusion over 72 h, During constant rate infusions, 5-FU concentrations within individuals varied by 1.7-fold, but no uniform time of peak or trough concentration was observed, Transformation of these data by setting the time of peak to 0 h and by expressing concentrations as the percentage of the 24-h mean value revealed a nonrandom distribution of the time from peak to trough with a median time of 12 h (P = 0,027), These transformed data were also successfully fit to a circadian cosinor function (P < 0,001), During multiple constant rate 5-FU infusions, the intrapatient variability was high; the times of peak 5-FU concentration occurred at the same approximate sampling time 43% of the time, and troughs coincided 17% of the time. No difference in clinical toxicity was observed when matched constant rate and circadian infusions of 5-FU were compared, High inter- and intrapatient variability exists in 5-FU plasma concentrations in adult cancer patients during constant rate infusions with no evidence of a consistent circadian rhythm in untransformed data. C1 NCI, Div Clin Sci, Med Branch, Dev Therapeut Dept, Bethesda, MD 20899 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Takimoto, CH (reprint author), Natl Naval Med Ctr, Med Branch, Bldg 8,Room 5101, Bethesda, MD 20889 USA. RI Venzon, David/B-3078-2008 NR 27 TC 38 Z9 38 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1347 EP 1352 PG 6 WC Oncology SC Oncology GA 206MR UT WOS:000080883800013 PM 10389918 ER PT J AU Chen, Z Malhotra, PS Thomas, GR Ondrey, PG Duffey, DC Smith, CW Enamorado, N Yeh, NT Kroog, GS Rudy, S McCullagh, L Mousa, S Quezado, M Herscher, LL Van Waes, C AF Chen, Z Malhotra, PS Thomas, GR Ondrey, PG Duffey, DC Smith, CW Enamorado, N Yeh, NT Kroog, GS Rudy, S McCullagh, L Mousa, S Quezado, M Herscher, LL Van Waes, C TI Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; SERUM LEVELS; TUMOR ANGIOGENESIS; OVARIAN-CANCER; FACTOR VEGF; INTERLEUKIN-6; LINES; MACROPHAGE AB Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma (HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. in this study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry. The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses (i.e., fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin OL)-1 alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma (UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1 alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0,05), The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R-2 = 0.2 and 0,4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients but not in patients with papilloma or control subjects (at P < 0,05), We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy. C1 NIDOCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Dupont Merck Pharmaceut Co, Res & Dev, Wilmington, DE 19880 USA. NCI, Surg Pathol Sect, Pathol Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), NIDOCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bldg 10,Room 5D55,MSC-1419, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [DC 95-01, Z01-DC-00016] NR 47 TC 319 Z9 324 U1 2 U2 14 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1369 EP 1379 PG 11 WC Oncology SC Oncology GA 206MR UT WOS:000080883800016 PM 10389921 ER PT J AU Xu, XC Mitchell, MF Silva, E Jetten, A Lotan, R AF Xu, XC Mitchell, MF Silva, E Jetten, A Lotan, R TI Decreased expression of retinoic acid receptors, transforming growth factor beta, involucrin, and cornifin in cervical intraepithelial neoplasia SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN PAPILLOMAVIRUS; GENE-EXPRESSION; UTERINE CERVIX; CANCER; ALPHA; CHEMOPREVENTION; KERATINOCYTES; PROLIFERATION; INTERFERON AB Cervical intraepithelial neoplasia (CIN) I, II, and III represent a spectrum of premalignant epithelial changes and are ideal targets for application of chemoprevention strategies. Intermediate end point biomarkers are increasingly being used as surrogate end points to monitor clinical chemoprevention trials. To identify potential biomarkers in cervical epithelium, we analyzed the expression of nuclear retinoic acid receptor (RAR) mRNA by in situ hybridization, involucrin, cornifin, and transforming growth factors (TGFs) beta 1 and beta 2 by immunohistochemistry in cervical specimens, which contained adjacent normal epithelium and CIN lesions from 52 patients. These biomarkers were expressed in all adjacent normal cervical epithelia, whereas all CIN lesions including CIN I, CIN II, and CIN III exhibited decreased expression of RAR-alpha by 55.8%, RAR-beta by 64.7%, RAR-gamma by 54.9%, involucrin by 80.8%, cornifin by 88.5%, TGF-beta 1 by 89.7%, and TGF-beta 2 by 85.7%. Viewed as a whole, these biomarkers were down-regulated in 100% of the CIN lesions. Because all of these biomarkers can be modulated in vitro by retinoids, they may serve as intermediate biomarkers for retinoid chemoprevention trials in the patients with CIN lesions. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Xu, XC (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, 1515 Holcombe Blvd,Box 236, Houston, TX 77030 USA. OI Jetten, Anton/0000-0003-0954-4445 FU NCI NIH HHS [N01-CN-25433-01] NR 48 TC 29 Z9 31 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1503 EP 1508 PG 6 WC Oncology SC Oncology GA 206MR UT WOS:000080883800034 PM 10389939 ER PT J AU Bar-Ner, M Thibault, A Tsokos, M Magrath, IT Samid, D AF Bar-Ner, M Thibault, A Tsokos, M Magrath, IT Samid, D TI Phenylbutyrate induces cell differentiation and modulates Epstein-Barr virus gene expression in Burkitt's lymphoma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID AROMATIC FATTY-ACIDS; C-MYC; DOWN-REGULATION; MEMBRANE-PROTEIN; PROSTATE-CANCER; SODIUM-BUTYRATE; N-BUTYRATE; VIRAL-DNA; PHENYLACETATE; GROWTH AB Although Burkitt's lymphoma (BL) is a readily treated malignancy, recurrences, as well as disease arising in immunosuppressed patients, are notoriously resistant to conventional therapeutic approaches. The EBV is associated with a significant proportion of these lymphomas that evade immune surveillance through decreased expression of both viral and cellular antigens, Increasing the immunogenicity of BL cells may, therefore, represent a potentially beneficial therapeutic maneuver. Using in vitro models of EBV-transformed lymphoblastoid as well as BL cell lines, we demonstrate increased expression of genes coding for HLA class I and EBV latent proteins by the differentiation inducer phenylbutyrate (BB). The aromatic fatty acid also caused cytostasis associated with sustained declines in c-myc expression, a direct antitumor effect that was independent of the EBV status. We conclude, therefore, that differentiation therapy of BL with PB may lead to growth arrest with increased tumor immunogenicity in vivo. The findings may have clinical relevance because the in vitro activity has been observed with PB concentrations that are well tolerated and nonimmunosuppressive in humans, a desirable feature for the different patient populations afflicted with this disease. C1 Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, Dept Pathol, Ctr Clin, Bethesda, MD 20892 USA. RP Samid, D (reprint author), Univ Virginia, Hlth Sci Ctr, Jordan Annex,Box 513, Charlottesville, VA 22908 USA. NR 52 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1509 EP 1516 PG 8 WC Oncology SC Oncology GA 206MR UT WOS:000080883800035 PM 10389940 ER PT J AU Kuan, CT Reist, CJ Foulon, CF Lorimer, IAJ Archer, G Pegram, CN Pastan, I Zalutsky, MR Bigner, DD AF Kuan, CT Reist, CJ Foulon, CF Lorimer, IAJ Archer, G Pegram, CN Pastan, I Zalutsky, MR Bigner, DD TI I-125-labeled anti-epidermal growth factor receptor-vIII single-chain Fv exhibits specific and high-level targeting of glioma xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; N-SUCCINIMIDYL 5-IODO-3-PYRIDINECARBOXYLATE; DISULFIDE-STABILIZED FV; MONOCLONAL-ANTIBODIES; TUMOR XENOGRAFTS; INTRATUMOR INJECTION; BACTERIAL EXPRESSION; MALIGNANT GLIOMAS; ESCHERICHIA-COLI; LUNG CARCINOMAS AB A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a deletion in its extracellular domain that results in the formation of a new, tumor-specific antigen found in glioblastomas, breast carcinomas, and other tumors. The scFv molecule, designed as V-H-(Gly(4)-Ser)(3)-V-L, was expressed in Escherichia coli in inclusion body form; recovered scFv fragments were properly refolded in redox-shuffling buffer. Size-exclusion chromatography of purified scFv demonstrated a protein monomer of M-r 26,000, Labeling was performed using N-succinimidyl 5-[I-125]iodo-3-pyridinecarboxylate (SIPC) or Iodogen to specific activities of 0.5-2.0 mCi/mg, with yields of 35-50% and 45-70%, respectively. The immunoreactive fraction (IRF) of the labeled MR1(scFv) was 65-80% when SIPC was used and 50-55% when Iodogen was used. The affinity (K-A) of MR1(scFv) for EGPRvIII was 4.3 x 10(7) +/- 0.1 x 10(7) M-1 by BIAcore analysis, and it was 1.0 x 10(8) + 0.1 x 10(8) M-1 and by Scatchard analysis versus EGFRvIII-expressing cells. After incubation at 37 degrees C for 24 h, the binding affinity was maintained, and the IRF was maintained at 60-70%, The specificity of MR1(scFv) for EGFRvIII,vas demonstrated in vitro by incubation of radiolabeled MR1(scFv) with the EGFRvIII-expressing U87MG.Delta EGFR cell line in the presence or absence of competing unlabeled MR1(scFv) or anti-EGFRvIII MAbs L8A4 and H10. In biodistribution studies using athymic mice bearing s.c. U87MG.Delta EGFR tumor xenografts, animals received intratumoral or i.v. infusions of paired-label [I-125]SIPC-MR1(scFv) and [I-131]SIPC-anti-Tac(scFv) as a control. When given by the intratumoral route, MR1(scFv) retained high tumor uptakes of 85% injected dose per gram of tissue at 1 h and 16% injected dose per gram of tissue at 24 h following administration. Specific: control scFv tumor uptake ratios of more than 20:1 at 24 h demonstrated specific localization of MRl(scFv). The excellent tumor retention of MR1(scFv), combined with its rapid clearance from normal tissues, resulted in high tumor:normal organ ratios. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Ottawa Reg Canc Ctr, Canc Res Grp, Ottawa, ON K1H 8L6, Canada. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bigner, DD (reprint author), Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. FU NCI NIH HHS [CA11898, CA42324]; NINDS NIH HHS [NS20023] NR 57 TC 48 Z9 51 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1539 EP 1549 PG 11 WC Oncology SC Oncology GA 206MR UT WOS:000080883800038 PM 10389943 ER PT J AU Csako, G Tran, A Wang, J Chesler, R Costello, R AF Csako, G Tran, A Wang, J Chesler, R Costello, R TI Evaluation of two semi-automated methods for serum protein and immunofixation electrophoresis. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Ctr Clin, Clin Chem Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A46 EP A47 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500266 ER PT J AU Lindsey, HP George, MR Rehak, NN AF Lindsey, HP George, MR Rehak, NN TI Storage of serum in gel separator tubes: effect on common chemistry tests determined with Hitachi 917. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A7 EP A7 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500137 ER PT J AU Remaley, AT Shirali, A Stonik, J Sampson, ML Csako, G Hoeg, JM Brewer, RH AF Remaley, AT Shirali, A Stonik, J Sampson, ML Csako, G Hoeg, JM Brewer, RH TI A gene-reporter bioassay system for measuring the cholesterol efflux and uptake potential of serum. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A15 EP A15 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500164 ER PT J AU Sampson, ML Nicksa, G Csako, G Remaley, AT AF Sampson, ML Nicksa, G Csako, G Remaley, AT TI The development of a direct high-density lipoprotein phospholipid assay. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A15 EP A16 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500166 ER PT J AU Sampson, ML Csako, G Remaley, AT AF Sampson, ML Csako, G Remaley, AT TI Dual HDL total cholesterol test: a new homogenous assay for the sequential measurement of HDL-cholesterol and total cholesterol. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Dept Clin Pathol, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A15 EP A15 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500165 ER PT J AU Woods, JJ Remaley, AT AF Woods, JJ Remaley, AT TI Development of a rapid intraoperative ACTH assay. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A98 EP A98 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500463 ER PT J AU Carrington, M AF Carrington, M TI Chemokine receptor genes in HIV-1 disease SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP S39 EP S39 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500111 ER PT J AU Koch, CA Robyn, JA Pacak, K AF Koch, CA Robyn, JA Pacak, K TI How do levels of (endogenous) glucocorticoids, interleukin-10 and interleukin-12 relate to multiple sclerosis relapse before, during and after pregnancy? SO CLINICAL ENDOCRINOLOGY LA English DT Letter C1 NIH, Dev Endocrinol, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NIH, Dev Endocrinol, Bldg 10, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 6 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUN PY 1999 VL 50 IS 6 BP 818 EP 819 DI 10.1046/j.1365-2265.1999.0787b.x PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 207MY UT WOS:000080941700020 PM 10468957 ER PT J AU Gagne, SE Larson, MG Pimstone, SN Schaefer, EJ Kastelein, JJP Wilson, PWF Ordovas, JM Hayden, MR AF Gagne, SE Larson, MG Pimstone, SN Schaefer, EJ Kastelein, JJP Wilson, PWF Ordovas, JM Hayden, MR TI A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study SO CLINICAL GENETICS LA English DT Article DE coronary heart disease; gene; lipoprotein lipase; polymorphisms ID HDL CHOLESTEROL LEVELS; ARTERY DISEASE; MUTATION; ATHEROSCLEROSIS; SUBSTITUTION; ASN291SER; GENE AB Genetic variation at the lipoprotein lipase (LPL) locus has been shown to influence plasma lipids and to modulate risk of coronary heart disease (CHD). Recently, we found that the most frequent variant at this locus, involving a C-terminal truncation of two amino acids (Ser447X). was associated with both higher LPL. activity and high density lipoprotein cholesterol (HDL-C) in patients with CHD. However, the impact of this S447X variant on lipids and CHD in the general population was hitherto unknown. We, therefore, analyzed a total of 1114 men and 1144 women randomly ascertained from the Framingham Offspring Study (FOS) for the presence of this LPL variant. Carrier frequency of the S447X allele was 17%, and in men carrier status was associated with higher total cholesterol (Delta = 6.2 mg/dl, p = 0.03), higher HDL-C (Delta = 2.3 mg/dl. p = 0.01), and lower triglyceride (TG) levels (Delta = - 19.4 mg/dl, p = 0.02). Moreover, in men, the S447X allele conferred significant protection against CHD (odds ratio. 0.43. p = 0.04). These effects on lipids and CHD were not seen in women. Our study represents the first report on the impact of this mutation on CHD in men from the general population. and we conclude, therefore, that the S447X variant may confer significant protection against high TG levels, low HDL-C. and premature CHD in these subjects. C1 Univ British Columbia, Ctr Mol Med & Therapeut, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada. Boston Univ, Framingham Heart Study, Framingham, MA USA. NHLBI, Framingham Heart Study, Boston, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA. Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands. RP Hayden, MR (reprint author), Univ British Columbia, Ctr Mol Med & Therapeut, Dept Med Genet, 980 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. RI Hayden, Michael/D-8581-2011; OI Hayden, Michael/0000-0001-5159-1419; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL 54776] NR 19 TC 93 Z9 99 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUN PY 1999 VL 55 IS 6 BP 450 EP 454 DI 10.1034/j.1399-0004.1999.550609.x PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 221CK UT WOS:000081706300011 PM 10450862 ER PT J AU Pachner, AR Delaney, E Zhang, WF O'Neill, T Major, E Frey, AB Davidson, E AF Pachner, AR Delaney, E Zhang, WF O'Neill, T Major, E Frey, AB Davidson, E TI Protection from lyme neuroborreliosis in nonhuman primates with a multiantigenic vaccine SO CLINICAL IMMUNOLOGY LA English DT Article DE vaccine; lyme disease; primate; neuroborreliosis ID BORRELIA-BURGDORFERI; DISEASE; PROTEINS AB In an effort to develop an effective and safe vaccine for lyme disease, rhesus macaques were injected with a multiantigenic preparation of Borrelia burgdorferi, strain N40, One month later animals were boosted before intradermal challenge with infectious B. burgdorferi, Challenges were performed at 1 and again at 5 months after the booster vaccination. Vaccinated and control nonvaccinated animals were monitored for development of systemic infection by measurement of serum anti-spirochetal antibodies by ELISA and Western blotting and neurological involvement was monitored by testing of cerebrospinal fluid (CSF) and PCR analysis of central nervous system (CNS) tissue obtained at necropsy, Two control nonhuman primates (NHPs), given saline injections instead of vaccine and then challenged with B. burgdorferi, developed CSF pleocytosis, PCR positivity of the brain, and high levels of specific anti-B. burgdorferi antibody in the serum and CSF. Necropsy studies revealed widespread invasion of the CNS of one of these animals by the spirochete. In contrast, none of the four vaccinated animals developed evidence of invasion of the CNS after either of two challenge inoculations with infectious B. burgdorferi. In addition to resisting infection, no vaccinated animal demonstrated any untoward consequence of vaccination. These data demonstrate that a multiantigenic vaccine is effective in preventing systemic infection and lyme neuroboreliosis in NHPs and suggest that a successful vaccine could be developed in humans which would prevent lyme disease. (C) 1999 Academic Press. C1 Georgetown Univ, Sch Med, Washington, DC USA. NINDS, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY 10016 USA. RP Frey, AB (reprint author), NYU Med Ctr, Dept Cell Biol, MSB 690,550 1st Ave, New York, NY 10016 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 1999 VL 91 IS 3 BP 310 EP 313 DI 10.1006/clim.1999.4703 PG 4 WC Immunology SC Immunology GA 202DA UT WOS:000080635800008 PM 10370376 ER PT J AU Robbins, JB AF Robbins, JB TI Pertussis in adults: Introduction SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID BORDETELLA-PERTUSSIS; WHOOPING-COUGH; INFECTION; VACCINE; DIPHTHERIA C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Robbins, JB (reprint author), NICHD, Dev & Mol Immun Lab, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 48 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1999 VL 28 SU 2 BP S91 EP S93 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 208MK UT WOS:000080995000001 PM 10447024 ER PT J AU Schneerson, R AF Schneerson, R TI Similarities between the pathogenesis of and immunity to diphtheria and pertussis: The complex nature of serum antitoxin-induced immunity to these two diseases SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Pertussis in Adults - Epidemiology, Signs, Symptoms, and Implications for Vaccination CY OCT 28-29, 1997 CL BETHESDA, MARYLAND SP NICHHD, NIAID, Natl Heart Lung & Blood Inst, Ctr Dis Control & Prevent, Ctr Biolog Evaluat & Res, US FDA ID LYMPHOCYTOSIS-PROMOTING FACTOR; WHOOPING-COUGH; BORDETELLA-PERTUSSIS; TOXOID VACCINE; BLOOD-DONORS; PROTECTION; ANTIBODIES; HYPOTHESIS; EFFICACY; TOXIN AB Despite data from animal studies, seroepidemiological surveys, and controlled clinical trials, skepticism persists about immunity to pertussis conferred by serum IgG neutralizing antibodies (antitoxin). This is largely prompted by the absence of a "protective" level of antitoxin. Examination of the similarities between the pathogenesis and immunity to pertussis and diphtheria provides an explanation for this dilemma. As with pertussis, diphtheria toroid vaccination confers only similar to 70% immunity on an individual basis, individuals with protective levels of antitoxin may contract diphtheria, and about 50% of the entire population, especially adults, have less than protective levels of antitoxin. The virtual disappearance of diphtheria followed vaccination of the entire population with diphtheria toroid, which blocked transmission of toxigenic Corynebacterium diphtheriae and thus reduced the pathogen to almost undetectable levels. The individual and community-based immunity induced by diphtheria toroid, we hypothesize, is similar to that of pertussis and pertussis toroid. C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Schneerson, R (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 62 TC 4 Z9 4 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1999 VL 28 SU 2 BP S136 EP S139 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 208MK UT WOS:000080995000009 PM 10447032 ER PT J AU Hyman, SE AF Hyman, SE TI Prevention of children's behavioral and mental health problems: New horizons for psychology - Foreword SO CLINICAL PSYCHOLOGY REVIEW LA English DT Editorial Material ID HOME VISITATION; TRIAL C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, Room 4A052,31 Ctr Dr, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD JUN PY 1999 VL 19 IS 4 BP 387 EP 390 PG 4 WC Psychology, Clinical SC Psychology GA 198NF UT WOS:000080429800001 ER PT J AU Wiggins, JS AF Wiggins, JS TI Studying the clinician: Judgment research and psychological assessment SO CONTEMPORARY PSYCHOLOGY-APA REVIEW OF BOOKS LA English DT Book Review C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Wiggins, JS (reprint author), NIA, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 17 TC 1 Z9 1 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD JUN PY 1999 VL 44 IS 3 BP 195 EP 196 PG 2 WC Psychology, Multidisciplinary SC Psychology GA 201AB UT WOS:000080571500001 ER PT J AU Ioannidis, JPA Dixon, DO McIntosh, M Albert, JM Bozzette, SA Schnittman, SM AF Ioannidis, JPA Dixon, DO McIntosh, M Albert, JM Bozzette, SA Schnittman, SM TI Relationship between event rates and treatment effects in clinical site differences within multicenter trials: An example from primary Pneumocystis carinii prophylaxis SO CONTROLLED CLINICAL TRIALS LA English DT Article DE multicenter clinical trials; heterogeneity; baseline risk; hierarchical models; Pneumocystis carinii; primary prophylaxis; HIV ID RANDOMIZED TRIAL; AIDS PATIENTS; PNEUMONIA; METAANALYSIS; EFFICACY; RISK; PREDICTORS; CLUSTER AB The results of multicenter clinical trials may differ across participating clinical sites. We present a diagnostic approach for evaluating this diversity that emphasizes the relationship between the observed event rates and treatment effects. We use as an example a trial of sequential strategies of Pneumocystis prophylaxis in human immunodeficiency virus infection with 842 patients randomly allocated to start prophylaxis with trimethoprim/sulfamethoxazole, dapsone, or pentamidine. Prophylaxis failure rates varied significantly across the 30 clinical sites (0-30.3%, p = 0.002 by Fisher's exact test) with prominent variability in the pentamidine arm (0-63.6%). Starting with oral regimens was better than starting with pentamidine in sites with high rates of events, whereas the three strategies had more similar efficacy in other sites. Sites enrolling fewer patients had lower event rates and had more patients who withdrew prematurely or were lost to follow-up. In a hierarchical regression model adjusting for random measurement error in the observed event rates, starting with trimethoprim/sulfamethoxazole was predicted to be increasingly better than starting with aerosolized pentamidine as the risk of prophylaxis failure increased (p = 0.01), reducing the risk of failure by 47% when the failure rate of pentamidine was 30%, whereas the two regimens were predicted to be equivalent when the failure rate was 17%. Differences in event rates could reflect a combination of heterogeneity in diagnosis, administration of treatments, and disease risk in patients across sites. The evaluation of clinical site differences with a systematic approach focusing on event rates may give further insight in the interpretation of the results of multicenter trials beyond an average treatment effect. Control Clin Trials 1999;20:253-266 (C) Elsevier Science Inc. 1999. C1 NIAID, HIV Res Branch, Div Aids, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, Div Aids, Bethesda, MD 20892 USA. NIAID, Therapeut Res Program, Div Aids, Bethesda, MD 20892 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. San Diego Vet Affairs Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Dept Med, San Diego, CA USA. Rand Corp, Hlth Sci Program, La Jolla, CA USA. RP Ioannidis, JPA (reprint author), 23A Kalavryton St, Ano Voula 16673, Greece. RI Ioannidis, John/G-9836-2011 NR 34 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD JUN PY 1999 VL 20 IS 3 BP 253 EP 266 DI 10.1016/S0197-2456(98)00053-1 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 198ZR UT WOS:000080455200004 PM 10357498 ER PT J AU van Leeuwen, JEM Samelson, LE AF van Leeuwen, JEM Samelson, LE TI T cell antigen-receptor signal transduction SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID PHOSPHOTYROSINE-BINDING DOMAIN; ADAPTER PROTEIN SLP-76; TYROSINE KINASE ZAP-70; SYK FAMILY KINASES; MOLECULAR-CLONING; DEFICIENT MICE; MEDIATED ACTIVATION; PLASMA-MEMBRANE; C-CBL; PHOSPHORYLATION AB During the past year, major progress has been made in understanding proximal TCR signal-transduction events. Cbl has been identified as a negative regulator of kinases from the ZAP-70/Syk family. Studies on. LAT, SLP-76, Itk and Vav have revealed their role in the activation of Ras and phospholipase-C gamma 1-Ca2+ signalling pathways, TCR-induced cytoskeletal changes involve signalling through SLP-76-Vav-Nck to activate effecters of the Rho-family of GTPases. Finally, glycolipid-enriched microdomains play a crucial role in T cell activation. C1 NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. RP van Leeuwen, JEM (reprint author), NCI, Lab Cellular & Mol Biol, NIH, Bldg 37,Room 1E24,9000 Rockville Pike, Bethesda, MD 20892 USA. RI van Leeuwen, Jeroen/G-3555-2010 NR 81 TC 198 Z9 200 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1999 VL 11 IS 3 BP 242 EP 248 DI 10.1016/S0952-7915(99)80040-5 PG 7 WC Immunology SC Immunology GA 205AE UT WOS:000080798400002 PM 10375551 ER PT J AU Scaffidi, C Kirchhoff, S Krammer, PH Peter, ME AF Scaffidi, C Kirchhoff, S Krammer, PH Peter, ME TI Apoptosis signaling in lymphocytes SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID NF-KAPPA-B; INDUCED CELL-DEATH; CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; RECEPTOR-INDUCED APOPTOSIS; BURKITT-LYMPHOMA CELLS; FAS-MEDIATED APOPTOSIS; HUMAN T-CELLS; IN-VIVO; LIGAND EXPRESSION AB Lymphocyte apoptosis is essential for proper function of the immune system. Among other functions, it is responsible for the homeostasis of immune cells and plays a key role in the elimination of autoreactive lymphocytes. Recently, progress has been made in the identification of genes that regulate apoptosis. Studies characterizing the basic apoptosis signaling machinery have begun to reveal the molecular control of processes that modulate lymphocyte apoptosis. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. German Canc Res Ctr, Tumor Immunol Program, D-69120 Heidelberg, Germany. RP Scaffidi, C (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Watzl, Carsten/B-4911-2013 OI Watzl, Carsten/0000-0001-5195-0995 NR 113 TC 158 Z9 163 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1999 VL 11 IS 3 BP 277 EP 285 DI 10.1016/S0952-7915(99)80045-4 PG 9 WC Immunology SC Immunology GA 205AE UT WOS:000080798400007 PM 10375553 ER PT J AU Torrence, PF AF Torrence, PF TI 2-5A-antisense chimeras: Inhibitors of respiratory syncytial virus infection SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article ID INTERFERON ACTION; VIRAL-INFECTIONS; 2-5A ANTISENSE; MESSENGER-RNA; ENCEPHALOMYOCARDITIS VIRUS; THERAPEUTIC AGENTS; ALPHA-INTERFERON; TARGETING RNA; INTACT-CELLS; REPLICATION AB A new approach to the chemical control of respiratory syncytial virus infection is reviewed in the context of the biology of the virus and previous treatment approaches. Conjugation of the interferon actionmediator, 2',5'-oligoadenylate (2-5A), to antisense agents provides a strategy for the selective ablation of RNA. This application of this technology to respiratory syncytial virus has provided a potent selective inhibitor of virus replication. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Torrence, PF (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. NR 83 TC 13 Z9 13 U1 0 U2 2 PU PHARMAPRESS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 1999 VL 1 IS 3 BP 307 EP 315 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 342HB UT WOS:000088638200003 PM 11713795 ER PT J AU Cho-Chung, YS Park, YG Lee, YN AF Cho-Chung, YS Park, YG Lee, YN TI Oligonucleotides as transcription factor decoys SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article ID NF-KAPPA-B; HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT PROTEIN-KINASE; IN-VIVO; RESPONSE ELEMENT; NUCLEAR FACTOR; GENE-EXPRESSION; DNA-BINDING; INDUCIBLE TRANSCRIPTION; TARGETED DISRUPTION AB Cellular and molecular research has been focused to develop a means to regulate gene expression in an effort to treat and cure a variety of diseases and abnormal physiological conditions. A successful oligonucleotide-based approach has been the use of synthetic oligonucleotides containing an enhancer element that can penetrate cells, bind sequence-specific DNA-binding proteins and interfere with transcription in vivo. This review describes such decoy oligonucleotides that exhibit high affinity for a target transcription factor and successfully interfere with transcription in vivo. Evidence presented here shows that the decoy oligonucleotide technology offers great promise as a tool for defining cellular regulatory processes and for treating cancer, viral diseases and other pathological conditions. C1 NCI, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Bethesda, MD 20892 USA. NR 68 TC 47 Z9 47 U1 0 U2 0 PU PHARMAPRESS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 1999 VL 1 IS 3 BP 386 EP 392 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 342HB UT WOS:000088638200011 PM 11713803 ER PT J AU Copley, RR Schultz, J Ponting, CP Bork, P AF Copley, RR Schultz, J Ponting, CP Bork, P TI Protein families in multicellular organisms SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; CRYSTAL-STRUCTURE; GENOME EVOLUTION; MODEL ORGANISMS; NMR STRUCTURE; C-ELEGANS; DOMAINS; GENES; DROSOPHILA; DEATH AB The complete sequence of the nematode worm Caenorhabditis elegans contains the genetic machinery that is required to undertake the core biological processes of single cells. However, the genome also encodes proteins that are associated with multicellularity, as well as others that are lineage-specific expansions of phylogenetically widespread families and yet more that are absent in non-nematodes. Ongoing analysis is beginning to illuminate the similarities and differences among human proteins and proteins that are encoded by the genomes of the multicellular worm and the unicellular yeast, and will be essential in determining the reliability of transferring experimental data among phylogenetically distant species. C1 European Mol Biol Lab, D-69012 Heidelberg, Germany. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP European Mol Biol Lab, Meyerhofstr 1, D-69012 Heidelberg, Germany. EM bork@embl-heidelberg.de RI Schultz, Joerg/B-9346-2008; Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 61 TC 37 Z9 38 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X EI 1879-033X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 1999 VL 9 IS 3 BP 408 EP 415 DI 10.1016/S0959-440X(99)80055-4 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 282LQ UT WOS:000085219900017 PM 10361098 ER PT J AU Shohami, E Ginis, I Hallenbeck, JM AF Shohami, E Ginis, I Hallenbeck, JM TI Dual role of tumor necrosis factor alpha in brain injury SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE tumor necrosis factor-alpha; traumatic brain injury; cerebral ischemia ID CLOSED-HEAD INJURY; FOCAL CEREBRAL-ISCHEMIA; FACTOR-BINDING-PROTEIN; NF-KAPPA-B; TNF-ALPHA; RAT-BRAIN; NERVOUS-SYSTEM; CYTOKINE EXPRESSION; CEREBROSPINAL-FLUID; INTERFERON-GAMMA AB Brain injury (ischemia, trauma) is among the leading cause of mortality and disability in the western world. It induces increased production of tumor necrosis factor (TNF alpha) by brain resident cells. There is conflicting evidence on the role of this response in the injured brain, showing its potential effect in both processes of repair and of damage. This review presents data from clinical and experimental studies on the stimulation of TNF alpha production in brain injury and on the deleterious consequence of this acute response. Its inhibition by pharmacologic agents, neutralizing antibodies or soluble receptors has protective effects. In contrast, there are reports (from in-vitro studies or knock-out mice) on the beneficial effects of TNF alpha. To reconcile these apparently conflicting reports, the exact timing and extent of TNF alpha activation must be taken into account, as well as the presence of other mediators such as reactive oxygen species. It is suggested that the appropriate context of mediators, at any given time after brain injury may well determine whether the effect of TNF alpha is protective or toxic. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Shohami, E (reprint author), Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. NR 102 TC 293 Z9 299 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD JUN PY 1999 VL 10 IS 2 BP 119 EP 130 DI 10.1016/S1359-6101(99)00008-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243AZ UT WOS:000082976100003 PM 10743503 ER PT J AU Morsli, H Tuorto, F Choo, D Postiglione, MP Simeone, A Wu, DK AF Morsli, H Tuorto, F Choo, D Postiglione, MP Simeone, A Wu, DK TI Otx1 and Otx2 activities are required for the normal development of the mouse inner ear SO DEVELOPMENT LA English DT Article DE inner ear development; gene expression; sensory organ; mouse; Otx1; Otx2 ID ANTERIOR NEUROECTODERM; BRAIN-DEVELOPMENT; HEAD DEVELOPMENT; SENSORY ORGANS; ROSTRAL BRAIN; GENES; SPECIFICATION; DROSOPHILA; GASTRULATION; EXPRESSION AB The Otx1 and Otx2 genes are two murine orthologues of the orthodenticle (Otd) gene in Drosophila, In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear, Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads, In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes, In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle, Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea, Paint-filled membranous labyrinths of Otx1(-/-) mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea, Defects in the shape of the saccule and cochlea were variable in Otx1(-/-) mice and were much more severe in an Otx1(-/-);Otx2(+/-) background, Histological and in situ hybridization experiments of both Otx1(-/-) and Otx1(-/-);Otx2(+/-) mutants revealed that the lateral crista was absent, In addition, the maculae of the utricle and saccule were partially fused, In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA (hOtx2(1)/ hOtx2(1)), most of the defects associated with Otx1(-/-) mutants were rescued, However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed, These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs. C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Ct, Rockville, MD 20850 USA. FU Telethon [D.037] NR 27 TC 142 Z9 147 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1999 VL 126 IS 11 BP 2335 EP 2343 PG 9 WC Developmental Biology SC Developmental Biology GA 208YF UT WOS:000081019500003 PM 10225993 ER PT J AU Andreazzoli, M Gestri, G Angeloni, D Menna, E Barsacchi, G AF Andreazzoli, M Gestri, G Angeloni, D Menna, E Barsacchi, G TI Role of Xrx1 in Xenopus eye and anterior brain development SO DEVELOPMENT LA English DT Article DE Xrx1; Rx1; Otx2; Pax6; Six3; engrailed repressor; Xenopus laevis; anterior neural plate patterning; eye; forebrain ID HOMEOBOX GENE; EXPRESSION; TRANSCRIPTION; SIGNALS; EMBRYOS; HOMOLOG; COMPETENCE; ORGANIZER; REVEALS; RETINA AB The anteriormost part of the neural plate is fated to give rise to the retina and anterior brain regions. In Xenopus, this territory is initially included within the expression domain of the bicoid-class homeobox gene Xotx2 but very soon, at the beginning of neurulation, it becomes devoid of Xotx2 transcripts in spatiotemporal concomitance with the transcriptional activation of the paired-like homeobox gene Xrx1, By use of gain- and loss-of-function approaches, we have studied the role played by Xrx1 in the anterior neural plate and its interactions with other anterior homeobox genes. We find that, at early neurula stage Xrx1 is able to repress Xotx2 expression, thus first defining the retina-diencephalon territory in the anterior neural plate. Overexpression studies indicate that Xrx1 possesses a proliferative activity that is coupled with the specification of anterior fate. Expression of a Xrx1 dominant repressor construct (Xrx1-EnR) results in a severe impairment of eye and anterior brain development. Analysis of several brain markers in early Xrx1-EnR-injected embryos reveals that anterior deletions are preceded by a reduction of anterior gene expression domains in the neural plate, Accordingly, expression of anterior markers is abolished or decreased in animal caps coinjected with the neural inducer chordin and the Xrx1-EnR construct. The lack of expansion of mid-hindbrain markers, and the increase of apoptosis in the anterior neural plate after Xrx1-EnR injection, indicate that anterior deletions result from an early loss of anterior neural prate territories rather than posteriorization of the neuroectoderm. Altogether, these data suggest that Xrx1 plays a role in assigning anterior and proliferative properties to the rostralmost part of the neural plate, thus being required for eye and anterior brain development. C1 Univ Pisa, Lab Biol Cellulare & Sviluppo, I-56010 Pisa, Italy. Univ Milan, Cattedra Chemioterapia, I-20129 Milan, Italy. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Barsacchi, G (reprint author), Univ Pisa, Lab Biol Cellulare & Sviluppo, Via Carducci 13, I-56010 Pisa, Italy. OI Menna, Elisabetta/0000-0003-2062-0154; Andreazzoli, Massimiliano/0000-0001-9633-204X NR 40 TC 110 Z9 112 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1999 VL 126 IS 11 BP 2451 EP 2460 PG 10 WC Developmental Biology SC Developmental Biology GA 208YF UT WOS:000081019500014 PM 10226004 ER PT J AU Fundin, BT Mikaels, A Westphal, H Ernfors, P AF Fundin, BT Mikaels, A Westphal, H Ernfors, P TI A rapid and dynamic regulation of GDNF-family ligands and receptors correlate with the developmental dependency of cutaneous sensory innervation SO DEVELOPMENT LA English DT Article DE GFR alpha; Ret; mechanoreceptor; Schwann cell; trigeminal ganglion; mouse ID NEUROTROPHIC FACTOR GDNF; MICE LACKING GDNF; NEURONAL ADHESION MOLECULE; LECTIN-BINDING ANALYSIS; TYROSINE KINASE; NEURITE OUTGROWTH; MYSTACIAL PAD; COMPREHENSIVE IMMUNOFLUORESCENCE; FUNCTIONAL RECEPTOR; PERIPHERAL NEURONS AB Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are members of the transforming growth factor-P family and have been shown to elicit neurotrophic effects upon several classes of neurons including dopaminergic neurons, motoneurons, parasympathetic, sympathetic as well as primary sensory neurons. However, there is little information available on their roles in cutaneous innervation. Herein, we have studied the regulation of gdnf, ntn and the GDNF family receptors and examined their role in the development of facial cutaneous innervation in GDNF mutant mice. A dynamic spatial and temporal regulation of gdnf, ntn and their ligand binding receptors within the follicle-sinus complex correlate with development of distinct subclasses of sensory nerve endings. Furthermore, development of NGF-dependent myelinated mechanoreceptors, i.e. reticular and transverse lanceolate endings also require GDNF during ending formation and maintenance. In addition, ligand and receptor association seems to be intricately linked to a local Schwann cell-axon interaction essential for sensory terminal formation. Our results suggests that functionally specified nerve endings depend on different GDNF family members and that in contrast to neurotrophins, this family of neurotrophic factors may be acting at local sites of terminal Schwann cell-axon growth cone interactions and that they collaborate with neurotrophins by supporting the same populations of neurons but at different times in development. C1 Karolinska Inst, MBB, Mol Neurobiol Lab, S-17177 Stockholm, Sweden. Lab Mammalial Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Fundin, BT (reprint author), Karolinska Inst, MBB, Mol Neurobiol Lab, S-17177 Stockholm, Sweden. NR 55 TC 52 Z9 52 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1999 VL 126 IS 12 BP 2597 EP 2610 PG 14 WC Developmental Biology SC Developmental Biology GA 215DG UT WOS:000081366200003 PM 10331972 ER PT J AU Doren, S Landsberger, N Dwyer, N Gold, L Blanchette-Mackie, J Dean, J AF Doren, S Landsberger, N Dwyer, N Gold, L Blanchette-Mackie, J Dean, J TI Incorporation of mouse zona pellucida proteins into the envelope of Xenopus laevis oocytes SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE zona pellucida; vitelline envelope; egg coat; mouse; Xenopus ID SPERM RECEPTOR ACTIVITY; EGG VITELLINE ENVELOPE; O-LINKED OLIGOSACCHARIDES; STRUCTURAL-ANALYSIS; GENE-EXPRESSION; MONOCLONAL-ANTIBODIES; GENOMIC ORGANIZATION; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; PRECURSOR PROTEIN AB All vertebrate eggs have extracellular matrices, referred to as the zona pellucida in Mus musculus and the vitelline envelope in Xenopus laevis. The mouse zona, composed of three sulfated glycoproteins (ZP1, ZP2, ZP3), is critical for fertilization and early development, and mice lacking a zona pellucida produce no live offspring. The primary structures of mouse ZP1 (623 amino acids), ZP2 (713 amino acids) and ZP3 (424 amino acids) have been deduced from full-length cDNAs, but posttranslational modifications result in mature zona proteins with molecular masses of 200-180 kDa, 140-120 kDa, and 83 kDa, respectively. The vitelline envelope forms a similar structure around Xenopus eggs and contains three glycoproteins that are structurally related (39-48% amino acid similarity) to the three mouse zona proteins. To investigate whether the structural semblances are sufficient to allow incorporation of the mouse zona proteins into the Xenopus vitelline envelope, capped synthetic mRNAs encoding ZP1, ZP2, and ZP3 proteins were injected into the cytoplasm of stage VI Xenopus oocytes. After 20 h of incubation the oocytes were harvested, and posttranslationally modified zona proteins were detected with monoclonal antibodies specific to mouse ZP1, ZP2, and ZP3. The oocytes were imaged with confocal microscopy to detect individual zona proteins in the extracellular matrix of the oocytes, and this localization was confirmed biochemically, Thus the mouse zona proteins appear to have been sufficiently conserved through 350 million years of evolution to be incorporated into the extracellular envelope surrounding Xenopus eggs. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, 6 Ctr DR MSC 2715, Bethesda, MD 20892 USA. OI Landsberger, Nicoletta/0000-0003-0820-3155 NR 68 TC 16 Z9 17 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD JUN PY 1999 VL 209 IS 6 BP 330 EP 339 DI 10.1007/s004270050261 PG 10 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 203BC UT WOS:000080686400002 PM 10370114 ER PT J AU Li, WM Nagineni, CN Efiok, B Chepelinsky, AB Egwuagu, CE AF Li, WM Nagineni, CN Efiok, B Chepelinsky, AB Egwuagu, CE TI Interferon regulatory transcription factors are constitutively expressed and spatially regulated in the mouse lens SO DEVELOPMENTAL BIOLOGY LA English DT Article DE IFN gamma; ICSBP; LSIRF Pip; IRF-1; IRF-2; STAT1; lens differentiation ID HISTOCOMPATIBILITY CLASS-I; SEQUENCE BINDING-PROTEIN; DEVELOPING RAT LENS; NF-KAPPA-B; GENE-EXPRESSION; GAMMA-INTERFERON; ALPHA-CRYSTALLIN; TRANSGENIC MICE; FACTOR FAMILY; CELLS AB Interferon regulatory factors (IRFs) are a family of transcription factors involved in regulation of cell growth and immunological responses. Nine IRFs have been described and they are expressed in a variety of cells, except for ICSBP and LSIRF/Pip, which are thought to be expressed exclusively in immune cells. Here, we show that IRF-1, IRF-2, ICSBP, and LSIRF/Pip are constitutively expressed in the mouse lens. These IRFs are present in both the cytoplasm and the nuclei of lens cells. However, the nuclear and cytoplasmic proteins exhibit distinct mobilities on SDS/PAGE. We further show that in the developing mouse lens, IRF-1 and IRF-2 are expressed at high levels in differentiated lens fiber cells with very low and barely detectable levels in undifferentiated lens epithelial cells, although the level of ICSBP expression is very low in the normal mouse lens, in transgenic mice with constitutive expression of interferon gamma in the lens, its level is markedly elevated and ICSBP expression is detected exclusively in the nuclei of undifferentiated lens cells. Taken together, our data suggest that expression of IRF transcription factors is spatially regulated in the lens and that distinct IRFs may contribute to differential gene regulation in the epithelial and fiber compartments of the vertebrate lens. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Immunol Lab, NIH, 10-10 N116,10 Ctr Dr MCS 1858, Bethesda, MD 20892 USA. NR 46 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 BP 44 EP 55 DI 10.1006/dbio.1999.9267 PG 12 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000004 PM 10364426 ER PT J AU Supp, DM Brueckner, M Witte, DP Kuehn, MR Lowe, LA McGrath, JM Corrales, JM Potter, SS AF Supp, DM Brueckner, M Witte, DP Kuehn, MR Lowe, LA McGrath, JM Corrales, JM Potter, SS TI The motor domain of left-right dynein is essential for the development of left-right asymmetry in the mouse SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 34 BP 186 EP 186 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000045 ER PT J AU Iqbal, S Monga, SPS Yang, Y Rashid, A Mishra, B Diahl, AM Mishra, L AF Iqbal, S Monga, SPS Yang, Y Rashid, A Mishra, B Diahl, AM Mishra, L TI Ontogeny, function and role in liver regeneration of MH-4, a liver specific serine protease inhibitor SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Temple Univ, Fels Inst, Philadelphia, PA 19122 USA. DVAMC, Baltimore, MD USA. JHU, Baltimore, MD USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 86 BP 195 EP 195 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000095 ER PT J AU Morasso, MI Kupriyanov, S Robinson, G Mahon, K Grinberg, A Sargent, T Barlbault, H AF Morasso, MI Kupriyanov, S Robinson, G Mahon, K Grinberg, A Sargent, T Barlbault, H TI Placental failure in mice lacking the homeobox gene Dix3. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Burnham Inst, La Jolla, CA 92037 USA. NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 94 BP 196 EP 196 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000103 ER PT J AU Plisov, SY Ivanov, SV Yoshino, K Higinbotham, KG Dovel, L Lerman, M Perantoni, AO AF Plisov, SY Ivanov, SV Yoshino, K Higinbotham, KG Dovel, L Lerman, M Perantoni, AO TI Molecular events involved in mesenchymal-epithelial conversion during kidney development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick, MD 21702 USA. SAIC, IRSP, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 99 BP 197 EP 197 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000108 ER PT J AU Damjanovski, S Shi, YB AF Damjanovski, S Shi, YB TI Contrasting expression profiles for collagenase-3,-4, and stromelysin-3 implicates distinct functions during Xenopus development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, LME, NIH, Bethesda, MD USA. RI Damjanovski, Sashko/N-8728-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 111 BP 199 EP 199 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000119 ER PT J AU Artinger, KB Chitnis, AB Driever, W Mercola, M AF Artinger, KB Chitnis, AB Driever, W Mercola, M TI Zebrafish narrowminded is involved in the specification of neural crest and primary sensory neurons SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. NICHD, NIH, Mol Genet Lab, Unit Vertebrate Neural Dev, Bethesda, MD USA. Univ Freiburg, Inst Zool, D-79104 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 120 BP 200 EP 200 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000128 ER PT J AU Jiang, D Kim, CH Kacergis, M Chitnis, AB AF Jiang, D Kim, CH Kacergis, M Chitnis, AB TI Genesis of ectopic neurons in zebrafish "skirt" mutants SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 118 BP 200 EP 200 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000126 ER PT J AU Piotrowski, T Nusslein-Volhard, C Dawid, IB AF Piotrowski, T Nusslein-Volhard, C Dawid, IB TI Genetic analysis of the lateral line sensory system in the zebrafish (Danio rerio) SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, LMG, Bethesda, MD USA. Max Planck Inst Entwicklungsbiol, Genet Abt, D-72076 Tubingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 121 BP 201 EP 201 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000129 ER PT J AU Kim, CH Kodjabachian, L Chitnis, AB AF Kim, CH Kodjabachian, L Chitnis, AB TI Notch activation influences neural plate formation by multiple mechanisms SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 131 BP 202 EP 202 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000139 ER PT J AU Loftus, S Chen, Y Gooden, G Ryan, J Birznieks, G Hilliard, M Baxevanis, A Bittner, M Meltzer, P Trent, J Pavan, W AF Loftus, S Chen, Y Gooden, G Ryan, J Birznieks, G Hilliard, M Baxevanis, A Bittner, M Meltzer, P Trent, J Pavan, W TI Informatic selection of a neural crest-melanocyte cDNA set for microarray analysis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, GDRB, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, CGB, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, GTB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 152 BP 206 EP 206 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000160 ER PT J AU Morsli, H Turoto, F Choo, D Postiglione, M Simeone, A Wu, D AF Morsli, H Turoto, F Choo, D Postiglione, M Simeone, A Wu, D TI Morphogenesis of the vertebrate inner ear. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 175 BP 210 EP 210 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000183 ER PT J AU Isogai, S Subramanian, R Bennett, PE Weinstein, BM AF Isogai, S Subramanian, R Bennett, PE Weinstein, BM TI Vascular anatomy of the developing zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, LMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 183 BP 211 EP 211 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000191 ER PT J AU Pham, VN Hong, SK Huh, TL Lawson, ND Roman, BL Vogel, AM Fouquet, B Serluca, FC Bennett, PN Fishman, MC Weinstein, BM AF Pham, VN Hong, SK Huh, TL Lawson, ND Roman, BL Vogel, AM Fouquet, B Serluca, FC Bennett, PN Fishman, MC Weinstein, BM TI Studying trunk blood vessel formation using the zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Kyungpook Natl Univ, Dept Genet Engn, Taegu 702701, South Korea. MGH, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 181 BP 211 EP 211 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000189 ER PT J AU Vogel, AM Roman, BL Weinstein, BM AF Vogel, AM Roman, BL Weinstein, BM TI Genetic analysis of the development of the vascular system in zebrafish SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 182 BP 211 EP 211 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000190 ER PT J AU Brody, T Odenwald, WF AF Brody, T Odenwald, WF TI Programmed transformations in gene expression during Drosophila neuroblast lineage development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 203 BP 214 EP 214 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000210 ER PT J AU Mishra, B Monga, SPS Danovitch, S Rashid, A Fleury, T Mishra, L AF Mishra, B Monga, SPS Danovitch, S Rashid, A Fleury, T Mishra, L TI ELF-3, a novel beta spectrin is required for the development of intrahepatic bile ducts. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NHGRI, CGTB, NIH, Bethesda, MD USA. Temple Univ, Feis Inst, Philadelphia, PA 19122 USA. DVAMC, Washington, DC USA. JHU, Baltimore, MD USA. Sibley Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 199 BP 214 EP 214 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000206 ER PT J AU Monga, SPS Rashid, A Wildner, O Condotti, F Mishra, B Blaese, RM Mishra, L AF Monga, SPS Rashid, A Wildner, O Condotti, F Mishra, B Blaese, RM Mishra, L TI Hepatic stem cells in mouse embryonic liver explant cultures. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Temple Univ, Feis Inst, Philadelphia, PA 19122 USA. DVAMC, Washington, DC USA. JHU, Baltimore, MD USA. NHGRI, CGTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 200 BP 214 EP 214 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000207 ER PT J AU Tang, Y Monga, SPS Weinstein, M Yang, X Rashid, A Diehi, AM Deng, CX Mishra, L AF Tang, Y Monga, SPS Weinstein, M Yang, X Rashid, A Diehi, AM Deng, CX Mishra, L TI Ontogeny and role in liver regeneration of Smad2 and Smad3; Essential components in liver formation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Feis Inst, Philadelphia, PA 19122 USA. NIDDK, NIH, Bethesda, MD USA. JHU, Baltimore, MD USA. RI deng, chuxia/N-6713-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 201 BP 214 EP 214 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000208 ER PT J AU Dunn, KJ Mok, J Southard-Smith, EM Bodine, D Pavan, B AF Dunn, KJ Mok, J Southard-Smith, EM Bodine, D Pavan, B TI Analysis of SOX10 function using retroviral infection of mammalian nural crest cells SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 205 BP 215 EP 215 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000212 ER PT J AU Tsang, M Kudoh, TH Dawid, IB AF Tsang, M Kudoh, TH Dawid, IB TI Eyebrow: A zebrafish gene implicated in the family of TGF-beta signalling SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, LMG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 248 BP 222 EP 222 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000254 ER PT J AU Andreazzoli, M Gestri, G Angeloni, D Menna, E Barsacchi, G AF Andreazzoli, M Gestri, G Angeloni, D Menna, E Barsacchi, G TI Xrx1 in Xenopus eye and anterior brain development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Univ Pisa, Lab Biol Cell & Sviluppo, I-56010 Pisa, Italy. NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 292 BP 229 EP 229 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000298 ER PT J AU Mishina, Y Crombie, R Bradley, A Behringer, RR AF Mishina, Y Crombie, R Bradley, A Behringer, RR TI Alk2 signaling in extraembryonic tissues is essential for gastrulation during mouse embryogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA. Baylor Coll Med, HHMI, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 318 BP 233 EP 233 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000322 ER PT J AU Hukriede, NA Joly, L Tsang, M Miles, J Tellis, P Epstein, J Barbazuk, WB Li, FN Paw, B Zon, L Postlethwait, J McPherson, JD Hudson, T Chevrette, M Dawid, IB Johnson, SL Ekker, M AF Hukriede, NA Joly, L Tsang, M Miles, J Tellis, P Epstein, J Barbazuk, WB Li, FN Paw, B Zon, L Postlethwait, J McPherson, JD Hudson, T Chevrette, M Dawid, IB Johnson, SL Ekker, M TI Radiation hybrid mapping of the zebrafish genome SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHD, LMG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 348 BP 238 EP 238 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000349 ER PT J AU Ma, GT Pfendler, KC Iannaccone, PM Kuehn, MR Linzer, DIH AF Ma, GT Pfendler, KC Iannaccone, PM Kuehn, MR Linzer, DIH TI Nodal and activin in placental development SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60614 USA. Childrens Mem Inst Educ & Res, Chicago, IL 60614 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 MA 352 BP 239 EP 239 PG 1 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000353 ER PT J AU Hoogwerf, BJ Waness, A Cressman, M Canner, J Campeau, L Domanski, M Geller, N Herd, A Hickey, A Hunninghake, DB Knatterud, GL White, C AF Hoogwerf, BJ Waness, A Cressman, M Canner, J Campeau, L Domanski, M Geller, N Herd, A Hickey, A Hunninghake, DB Knatterud, GL White, C CA Post CABG Study Investigators TI Effects of aggressive cholesterol lowering and low-dose anticoagulation on clinical and angiographic outcomes in patients with diabetes - The post coronary artery bypass graft trial SO DIABETES LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc ID LONGITUDINAL DATA-ANALYSIS; HEART-DISEASE; CARDIOVASCULAR-DISEASE; PRIMARY-PREVENTION; METABOLIC CONTROL; INSULIN THERAPY; MAMMARY ARTERY; RISK-FACTORS; FOLLOW-UP; COMPLICATIONS AB Diabetic patients have greater risk for coronary heart disease (CND) events after coronary artery bypass graft (CABG) surgery than nondiabetic patients. The Post CABG trial studied the effects of aggressive cholesterol lowering and low-dose anticoagulation in diabetic patients compared with nondiabetic patients. A double-blind, randomized clinical trial in 1,351 patients (1-11 years after CABG), the Post CABG trial consisted of two interventions (aggressive cholesterol-lowering versus moderate lowering and low-dose warfarin versus placebo) on angiographic end points. Angiographic changes in saphenous vein graft conduits 4.3 years after entry were compared in 116 diabetic and 1,235 nondiabetic patients. Seven clinical centers participated in the trial, as well as the National Institutes of Health project office (National Heart, Lung, and Blood Institute), the coordinating center (Maryland Medical Research Institute), and the Angiogram Reading Center (University of Minnesota). Baseline characteristics of the diabetic patients differed from the nondiabetic patients in the following ways: percentage of women participants, 15 vs. 7%, P = 0.002; mean baseline weight, 87.4 vs. 82.8 kg, P = 0.006; mean BMI, 29.5 vs. 27.6 kg/m(2), P = 0.0002; mean systolic blood pressure, 141.7 vs. 133.6, P < 0.0001; mean triglyceride concentrations, 2.09 vs. 1.77 mmol/l, P < 0.0001; and mean HDL cholesterol concentrations, 0.93 vs. 1.02 mmol, P = 0.0001. The percentage of clinical events was higher in diabetic than nondiabetic patients (20.6 vs. 13.4, P = 0.033) and angiographic outcomes were not different. The benefits of aggressive cholesterol lowering were comparable in diabetic and nondiabetic patients for the angiographic end points. Warfarin use was not associated with clinical or angiographic benefit. Diabetic patients in the Post CABG trial had more CHD risk factors at study entry and higher clinical event rates during the study than nondiabetic patients. The benefits of aggressive cholesterol lowering in diabetic patients were comparable to those in nondiabetic patients for both angiographic and clinical end points. The small number of diabetic patients provided limited power to detect significant differences between diabetic and nondiabetic patients or between diabetic patients in the aggressive versus moderate cholesterol treatment strategies. C1 Maryland Med Res Inst, Baltimore, MD 21210 USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Montreal Heart Inst, Montreal, PQ, Canada. Univ Quebec, Montreal, PQ H3C 3P8, Canada. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Hoogwerf, BJ (reprint author), Maryland Med Res Inst, 600 Wyndhurst Ave, Baltimore, MD 21210 USA. FU NHLBI NIH HHS [N01-HC-75073, N01-HC-75071, N01-HC-75072] NR 44 TC 43 Z9 45 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1999 VL 48 IS 6 BP 1289 EP 1294 DI 10.2337/diabetes.48.6.1289 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200YM UT WOS:000080567900012 PM 10342818 ER PT J AU Dabelea, D Pettitt, DJ Hanson, RL Imperatore, G Bennett, PH Knowler, WC AF Dabelea, D Pettitt, DJ Hanson, RL Imperatore, G Bennett, PH Knowler, WC TI Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; FETAL GROWTH; THRIFTY PHENOTYPE; MELLITUS; SIZE; ASSOCIATION; POPULATION; PREVALENCE; THINNESS AB OBJECTIVE - To investigate the mechanisms underlying the association between birth weight and type 2 diabetes in a population-based study of 3,061 Pima Indians aged 5-29 years. RESEARCH DESIGN AND METHODS - Glucose and insulin concentrations were measured during a 75-g oral glucose tolerance test, and insulin resistance was estimated according to the homeostatic model (homeostasis model assessment-insulin resistance [HOMA-IR]). Relationships between birth weight, height, weight, fasting and postload concentrations of glucose and insulin, and HOMA-IR were examined with multiple regression analyses. RESULTS - Birth weight was positively related to current weight and height (P < 0.0001, controlled for age and sex, in each age-group). The 2-h glucose concentrations showed a U-shaped relationship with birth weight in subjects >10 years of age, and this relation was independent of current body size. In 2,272 nondiabetic subjects, after adjustment for weight and height, fasting and 2-h insulin concentrations and HOMA-IR were negatively correlated with birth weight. CONCLUSIONS - Low-birth-weight Pimas are thinner at ages 5-29 years, yet they are more insulin resistant relative to their body size than those of normal birth weight. By contrast, those with high birth weight are more obese but less insulin resistant relative to their body size. The insulin resistance of low-birth-weight Pima Indians may explain their increased risk for type 2 diabetes. C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, Phoenix, AZ 85014 USA. RP Knowler, WC (reprint author), NIDDKD, Diabet & Arthrit Epidemiol Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 27 TC 151 Z9 159 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1999 VL 22 IS 6 BP 944 EP 950 DI 10.2337/diacare.22.6.944 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198WN UT WOS:000080447400013 PM 10372247 ER PT J AU Fetsch, PA Marincola, FM Abati, A AF Fetsch, PA Marincola, FM Abati, A TI Cytokeratin positivity in fine-needle aspirates of metastatic malignant melanoma: Fact or fiction? SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter ID DIFFERENTIAL-DIAGNOSIS; MONOCLONAL-ANTIBODIES; IN-VIVO; EXPRESSION; CELLS; CYTOLOGY; KERATINS; COEXPRESSION; MESOTHELIOMA; EFFUSIONS C1 NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Fetsch, PA (reprint author), NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 1999 VL 20 IS 6 BP 393 EP 396 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 198WM UT WOS:000080447300015 PM 10352917 ER PT J AU Franchimont, D Louis, E Dupont, P Vrindts-Gevaert, Y Dewe, W Chrousos, G Geenen, V Belaiche, J AF Franchimont, D Louis, E Dupont, P Vrindts-Gevaert, Y Dewe, W Chrousos, G Geenen, V Belaiche, J TI Decreased corticosensitivity in quiescent Crohn's disease - An ex-vivo study using whole blood cell cultures SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE glucocorticoids; cytokines; corticosensitivity; Crohn's disease ID STEROID-RESISTANT ASTHMA; FACTOR-KAPPA-B; GLUCOCORTICOID RECEPTOR; RHEUMATOID-ARTHRITIS; TRANSCRIPTION FACTOR; LEWIS RATS; TNF-ALPHA; IFN-GAMMA; IMMUNE; MECHANISMS AB Corticosensitivity influences the degree and the duration of an inflammatory reaction by altering target cell responses to endogenous and/or exogenous glucocorticoids. Indeed, different clinical responses to glucocorticoids have been observed among patients with Crohn's disease, suggesting different degrees of corticosensitivity in these subjects. The purpose of this study was to compare the corticosensitivity of patients with quiescent Crohn's disease to that of healthy subjects (HS). Nineteen patients with quiescent Crohn's disease and 14 HS were studied; all patients were steroid-free for at least six months; 7 of the 19 were corticosteroid-dependent (CSD) and treated with nonglucocorticoid immunosuppressants at the time of the study. Corticosensitivity was measured by the inhibition of LPS-induced cytokine secretion in whole blood cell cultures treated with increasing concentrations (10(-9) to 10(-6) M) of dexamethasone. Tumor-necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) were measured using specific immunoassays, Crohn's disease patients had a markedly decreased dexamethasone-mediated inhibition of TNF-alpha (P < 0.01), IL-6 (P < 0.001), and IL-1 beta (P < 0.01) compared to healthy subjects, with a shift of the dexamethasone dose-response curve to the right. No significant differences in the basal and LPS-stimulated secretion of the three cytokines were observed between CSD and non-CSD patients, and both subgroups of patients had similar degrees of dexamethasone-mediated cytokine inhibition. We conclude that patients with Crohn's disease have a significant decrease in the corticosensitivity of their leukocytes, This may be related to a specific genetic/constitutional background and/or could be acquired, due to inflammation-related endocrine and/or immune factors. C1 Univ Hosp Liege, Dept Med, Div Gastroenterol, Lab Radioimmunol & Neuroendocrine Immunol, Liege, Belgium. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Belaiche, J (reprint author), Univ Liege, Sch Med, Inst Pathol CHUB35, B-4000 Liege 1, Belgium. NR 35 TC 25 Z9 25 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 1999 VL 44 IS 6 BP 1208 EP 1215 DI 10.1023/A:1026644711530 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 211LM UT WOS:000081162600024 PM 10389698 ER PT J AU Frattali, CM Sonies, BC Chi-Fishman, G Litvan, I AF Frattali, CM Sonies, BC Chi-Fishman, G Litvan, I TI Effects of physostigmine on swallowing and oral motor functions in patients with progressive supranuclear palsy: A pilot study SO DYSPHAGIA LA English DT Article DE dysphagia; dysarthria; progressive supranuclear palsy; cholinergic stimulation; deglutition; deglutition disorders ID ALZHEIMERS-DISEASE AB The purpose of this pilot study was to investigate whether cholinergic stimulation reduces swallowing and oral motor disturbances in patients with progressive supranuclear palsy (PSP). A controlled, double-blind crossover trial of physostigmine, a centrally active cholinesterase inhibitor, and placebo was conducted. Patients were randomized to a 10-day crossover placebo-controlled double-blind trial of physostigmine at their previously determined best dose administered orally every 2 hr, six times per day. Patients were evaluated with ultrasound imaging of the oropharynx and an oral motor examination at baseline and during the third or fourth days of each study phase (placebo and drug). Under the double-blind placebo-controlled conditions, patients showed no statistically significant improvement in oral motor functions or swallow durations. Because patients with PSP have increased sensitivity to cholinergic blockade compared with control subjects, studies with newer, more potent cholinergic stimulating agents need further exploration. Suggestions for future research include the evaluation of newer direct cholinergic agonists in the treatment of the less-impaired PSP patients who may have a greater number of cholinergic neurons preserved and the evaluation of combined therapies. C1 NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Def & Vet Head Injury Program, Neuropharmacol Unit, Bethesda, MD USA. NIH, Speech Language Pathol Sect, Dept Rehabil Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Litvan, I (reprint author), NINDS, Med Neurol Branch, NIH, Fed Bldg,Room 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 25 TC 15 Z9 15 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD SUM PY 1999 VL 14 IS 3 BP 165 EP 168 DI 10.1007/PL00009600 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 199UV UT WOS:000080503200008 PM 10341115 ER PT J AU Buzas, Z Kolosova, I Chrambach, A AF Buzas, Z Kolosova, I Chrambach, A TI PhastSystem electrophoresis in beta-octylglucoside containing gels with immunodetection of a nondenatured vesicle-associated membrane protein SO ELECTROPHORESIS LA English DT Article DE PhastSystem; western blot; membrane protein; nondenaturing detergent gel ID SEA-URCHIN EGG; CLOSTRIDIAL NEUROTOXINS; COMPLEX; FUSION; PURIFICATION; EXOCYTOSIS AB Recombinant vesicle-associated membrane protein (rVAMP), implicated as a participant in membrane exocytosis and fusion (a "SNARE protein"), was subjected to gel electrophoresis in the miniaturized gels of the PhastSystem (Pharmacia) containing the nondenaturing, nonionic detergent beta-octylglucoside (OG), followed by immunodetection of the protein. Three major components of nondenatured rVAMP are detected by Western blotting both in 0.5% OG and in the absence of detergent. Their separation increases with increasing gel concentration above 7%T. Ferguson plot analysis indicates that the three species of VAMP are size isomers (i.e., they differ in size but share a common surface net charge density), the common point of intersection of the plots (mu-point) being a measure of their common free mobility. By the criteria of size and free mobility (related to surface net charge), VAMP components I, II and III in 0.5% OG-containing buffer are indistinguishable from components II, III and IV, respectively, observed in the absence of the detergent. The feasibility of immunodetection of nondenatured rVAMP on gels containing nondenaturing detergents opens up the possibility of gaining biochemical information regarding nondenatured SNARE protein complexes and SNARE proteins linked to membrane fragments. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Agr Biotechnol Ctr, Inst Biochem, H-2101 Godollo, Hungary. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 21 TC 1 Z9 1 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1999 VL 20 IS 7 BP 1390 EP 1397 DI 10.1002/(SICI)1522-2683(19990601)20:7<1390::AID-ELPS1390>3.0.CO;2-C PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 210PB UT WOS:000081112900010 PM 10424460 ER PT J AU Brining, SK Chen, N Yi, D Chrambach, A AF Brining, SK Chen, N Yi, D Chrambach, A TI Gel electrophoretic distinction between toxic and nontoxic forms of beta-amyloid (1-40) SO ELECTROPHORESIS LA English DT Article DE beta-amyloid; charge and size isomers; Congo red; Alzheimer's disease ID ALZHEIMERS-DISEASE; SENILE PLAQUES AB The in vitro toxicity of synthetic beta-amyloid (1-40) correlates with its binding to Congo red (CR). Potentially, therefore, CR binding to the beta-amyloid containing neuritic plaques in Alzheimer's disease could be used diagnostically. Using polyacrylamide under nondenaturing conditions, the present study shows that both CR binding and nonbinding synthetic beta-amyloid exhibits multiple charge-isomeric and size;isomeric species. The CR binding species exhibit values of free electrophoretic mobility, related to the surface charge density of the protein, which are less than those of the CR nonbinding species within 95% confidence limits. Since surface net: charge and solubility are correlated, the decreased solubility of the CR binding species may be responsible for the relative abundance and CR binding of beta-amyloid in the neuritic plaques of Alzheimer patients. C1 NICHHD, Sect Macromol Anal, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Brining, SK (reprint author), NICHHD, Sect Macromol Anal, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1999 VL 20 IS 7 BP 1398 EP 1402 DI 10.1002/(SICI)1522-2683(19990601)20:7<1398::AID-ELPS1398>3.0.CO;2-1 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 210PB UT WOS:000081112900011 PM 10424461 ER PT J AU Issaq, HJ Chan, KC Janini, GM Muschik, GM AF Issaq, HJ Chan, KC Janini, GM Muschik, GM TI A simple two-dimensional high performance liquid chromatography high performance capillary electrophoresis set-up for the separation of complex mixtures SO ELECTROPHORESIS LA English DT Article DE protein digest; peptide mapping; complex mixture separation; multidimensional separations; high performance liquid chromatography; capillary electrophoresis ID ZONE ELECTROPHORESIS; PEPTIDES AB A two-dimensional high performance liquid chromatography/capillary electrophoresis (HPLC/CE) instrumental set-up was assembled from commercially available equipment. Fractions of the effluent from the HPLC system are collected into microtiter plates with a microfraction collector. The fractions are then dried under vacuum at room temperature, reconstituted, and analyzed by capillary zone electrophoresis (CZE). This method allows the collection of samples by time, drops, or external signal (peaks). Any size or type of HPLC or CE column can be used with no limitation on the amount of sample injected into the HPLC. Any CE detection, laser-induced fluorescence (LIF), mass spectrometry (MS), ultraviolet (UV) or other, can be used. This setup is practical, simple, robust and allows the separation of complex mixtures. Preliminary results show the utility of this system for the analysis of protein digest. C1 SAIC Frederick, NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), SAIC Frederick, NCI, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 13 TC 43 Z9 44 U1 1 U2 5 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 1999 VL 20 IS 7 BP 1533 EP 1537 DI 10.1002/(SICI)1522-2683(19990601)20:7<1533::AID-ELPS1533>3.0.CO;2-V PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 210PB UT WOS:000081112900027 PM 10424477 ER PT J AU Feuillan, P Merke, D Leschek, EW Cutler, GB AF Feuillan, P Merke, D Leschek, EW Cutler, GB TI Use of aromatase inhibitors in precocious puberty SO ENDOCRINE-RELATED CANCER LA English DT Article; Proceedings Paper CT International Symposium on Aromatase and its Inhibitors - New Biology and Clinical Perspectives CY SEP 03-16, 1998 CL PRAGUE, CZECH REPUBLIC ID MCCUNE-ALBRIGHT SYNDROME; CONGENITAL ADRENAL-HYPERPLASIA; TESTOLACTONE; MUTATION; SPIRONOLACTONE; RECEPTOR AB During puberty, estrogen causes breast maturation and growth of the uterine lining in girls, and accelerates linear growth and bone maturation in both boys and girls. Decreasing the biosynthesis of estrogen can attenuate these processes. In 12 girls with the McCune-Albright syndrome (MAS), in which precocious puberty is due to production of estrogen from ovarian cysts, testolactone (40 mg/kg per day) decreased the volume of ovarian cysts, the frequency of menses, and the rates of growth and bone maturation, for periods of 1-4 years. in a 6-month pilot study of 12 children (eight boys; four girls) with congenital adrenal hyperplasia, testolactone, in combination with an antiandrogen (flutamide), a mineralocorticoid (fludrocortisone acetate, Florinef), and a reduced glucocorticoid dose, improved the control of growth and bone maturation compared with conventional therapy. In a 6-year study of 10 boys with familial male precocious puberty, testolactone, in combination with an antiandrogen (spironolactone), decreased rates of growth and bone maturation, and increased predicted adult height. All patients who developed evidence for gonadotropin-dependent puberty were also treated with a GnRH analog, Testolactone had no important adverse effects in any group of patients, although the need for a four-times-daily dosing schedule made compliance difficult for many families. We conclude that suppressing of estrogen with testolactone was effective therapy, and that more potent and specific inhibitors of aromatase could further improve the treatment of these disorders. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Feuillan, P (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 13 TC 42 Z9 42 U1 1 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 1999 VL 6 IS 2 BP 303 EP 306 DI 10.1677/erc.0.0060303 PG 4 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 199DZ UT WOS:000080466300024 PM 10731123 ER PT J AU Couse, JF Korach, KS AF Couse, JF Korach, KS TI Estrogen receptor null mice: What have we learned and where will they lead us? SO ENDOCRINE REVIEWS LA English DT Review ID FOLLICLE-STIMULATING-HORMONE; BETA-MESSENGER-RNA; GONADOTROPIN-RELEASING-HORMONE; EPIDERMAL GROWTH-FACTOR; POLYCYSTIC-OVARY-SYNDROME; POLYMERASE CHAIN-REACTION; RAT GRANULOSA-CELLS; HUMAN BREAST-CANCER; SEXUALLY DIMORPHIC DISTRIBUTION; LIGAND-INDEPENDENT ACTIVATION C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, POB 12233,MD B3-02, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 499 TC 1390 Z9 1438 U1 13 U2 68 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 1999 VL 20 IS 3 BP 358 EP 417 DI 10.1210/er.20.3.358 PG 60 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 203AU UT WOS:000080685500009 PM 10368776 ER PT J AU Korach, KS AF Korach, KS TI So! Why women's health? SO ENDOCRINOLOGY LA English DT Editorial Material C1 NIEHS, NIH, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, NIH, Reprod & Dev Toxicol Lab, Receptor Biol Sect, POB 12233,11 Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 0 TC 0 Z9 0 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 JUN PY 1999 VL 140 IS 6 BP 2438 EP 2438 DI 10.1210/en.140.6.2438 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400001 PM 10342827 ER PT J AU Maruyama, T Yoshimura, Y Yodoi, J Sabe, H AF Maruyama, T Yoshimura, Y Yodoi, J Sabe, H TI Activation of c-Src kinase is associated with in vitro decidualization of human endometrial stromal cells SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; ESTROGEN-RECEPTOR; FAMILY KINASES; GROWTH-FACTORS; PHOSPHORYLATION; PATHWAY; CAMP; DIFFERENTIATION; OVEREXPRESSION; ADHESION AB Tyrosine phosphorylation of cellular proteins, controlled coordinately by tyrosine kinases and phosphatases, is a critical element in signal transduction pathways involved in the regulation of biological responses including cell growth and differentiation. Decidualization is a dramatic progesterone-induced differentiation of the estrogen-primed endometrium, which is crucial for embryo implantation and maintenance of pregnancy. Here we have shown that the kinase activity of c-Src was increased, accompanied by altered tyrosine phosphorylation of several cellular proteins, during in vitro decidualization of human endometrial stromal cells. Withdrawal of both estrogen and progesterone from the cultures of decidualized stromal cells reduced c-Src kinase activity to the basal level and also changed the pattern of tyrosine phosphorylation of the several cellular proteins to the unstimulated stale. The kinase activity of endometrial c-Src appeared to inversely correlate with the level of its tyrosine phosphorylation. Moreover, although the endometrial stromal cells expressed another src-family kinase, Fyn, the activity of the Fyn kinase was almost undetectable during decidualization and thereafter upon steroid withdrawal. Our findings suggest that the activation of c-Src kinase may be a normal physiological event associated with decidualization, being specifically involved in the signaling cascades mediated by ovarian hormone stimulation. C1 Kyoto Univ, Inst Virus Res, Dept Biol Responses, Kyoto 6068397, Japan. Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 1600016, Japan. Osaka Biosci Inst, Dept Biol Mol, Osaka 5650874, Japan. RP Maruyama, T (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A11, Bethesda, MD 20892 USA. RI Sabe, Hisataka/A-4066-2012 NR 27 TC 25 Z9 26 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 JUN PY 1999 VL 140 IS 6 BP 2632 EP 2636 DI 10.1210/en.140.6.2632 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400025 PM 10342851 ER PT J AU Davis, BJ Lennard, DE Lee, CA Tiano, HF Morham, SG Wetsel, WC Langenbach, R AF Davis, BJ Lennard, DE Lee, CA Tiano, HF Morham, SG Wetsel, WC Langenbach, R TI Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E-2 and interleukin-1 beta SO ENDOCRINOLOGY LA English DT Article ID RAT PREOVULATORY FOLLICLES; CELL-OOCYTE COMPLEX; ENDOPEROXIDE SYNTHASE; HYALURONIC-ACID; LUTEINIZING-HORMONE; GENE DISRUPTION; MESSENGER-RNA; G/H SYNTHASE; H SYNTHASE; INDUCTION AB Mice carrying a null mutation for either of the two cyclooxygenase (COX) isoenzymes, necessary for prostanoid production, exhibit several isotype-specific reproductive abnormalities. Mice deficient in COX-1 are fertile but have decreased pup viability, whereas mice deficient in COX-2 fail to ovulate and have abnormal implantation and decidualization responses. The present study identifies the specific contribution of each COX isoenzyme in hypothalamic, pituitary, and ovarian function and establishes the pathology and rescue of the anovulatory syndrome in the COX-3-deficient mouse. In both COX-1-and COX-2-deficient mice, pituitary gonadotropins were selectively increased, whereas hypothalamic LHRH and serum gonadotropin levels were similar to those in wild-type animals (+/+). No significant differences in serum estrogen or progesterone were noted among the three genotypes. Exogenous gonadotropin stimulation with PMSG and hCG produced a comparable 4-fold increase in ovarian PGE(2) levels in wild-type and COX-1(-/-) mice. COX-2(-/-) mice had no increase in PGE(2) over PMSG-stimulated levels. Wild-type and COX1(-/-) mice ovulated in response to PMSG/hCG; very few COX-2(-/-) animals responded to this regimen. The defect in ovulation in COX-2 mutants was attributed to both an abnormal cumulus oophorum expansion and subsequent stigmata formation. Gonadotropin stimulation and concurrent treatment with PGE(2) or interleukin-1 beta resulted in ovulation of COX-2(-/-) mice comparable to that in COX-2(+/+) whereas treatment with PGF(2 alpha) was less effective. Collectively, these data demonstrate that COX-2, but not COX-1, is required for the gonadotropin induction of ovarian PG levels; that COX-2-related prostanoids are required for stabilization of the cumulus oophorum during ovulation; and that ovulation can be restored in the COX-2(-/-) animals by simultaneous treatment with gonadotropins and PGE(2) or interleukin-1 beta. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis Mutagenesis, Res Triangle Pk, NC 27709 USA. Myriad Genet Inc, Salt Lake City, UT 84108 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. RP NIEHS, Lab Expt Pathol, Box 12233, Res Triangle Pk, NC 27709 USA. EM davis1@niehs.nih.gov NR 57 TC 237 Z9 242 U1 0 U2 4 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2685 EP 2695 DI 10.1210/en.140.6.2685 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400033 PM 10342859 ER PT J AU Schomberg, DW Couse, JF Mukherjee, A Lubahn, DB Sar, M Mayo, KE Korach, KS AF Schomberg, DW Couse, JF Mukherjee, A Lubahn, DB Sar, M Mayo, KE Korach, KS TI Targeted disruption of the estrogen receptor-alpha gene in female mice: Characterization of ovarian responses and phenotype in the adult SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; FOLLICLE-STIMULATING-HORMONE; INDUCED UP-REGULATION; RAT GRANULOSA-CELLS; LUTEINIZING-HORMONE; TRANSGENIC MICE; DOWN-REGULATION; ANTIESTROGEN EM-800; PURE ANTIESTROGEN; PITUITARY-GLAND AB Targeted disruption of the mouse estrogen receptor-alpha gene (estrogen receptor-alpha knockout; ERKO) results in a highly novel ovarian phenotype in the adult. The ERKO mouse model was used to characterize ER alpha-dependent processes in the ovary. Visualization of the ovaries of 10-, 20-, and 50-day-old wild-type (WT) and ERKO mice showed that the ERKO phenotype developed between 20 and 50 days of age. Developmental progression through the primordial, primary, and antral follicle stages appeared normal, but functional maturation of preovulatory follicles was arrested resulting in atresia or in anovulatory follicles, which in many cases formed large, hemorrhagic cysts. Corpora lutea were absent, which also indicates that the normal biochemical and mechanical processes that accomplish ovulation were compromised. Northern and ribonuclease protection analyses indicated that ERKO ovary FSH receptor (FSHR) messenger RNA (mRNA) expression was approximately 4-fold greater than in WT controls. Ovarian LH receptor (LHR) mRNA expression was also higher in the ERKO animals. Cellular localization studies by in situ hybridization analysis of ERKO ovaries showed a high level of LHR mRNA expression in the granulosa and thecal layers of virtually all the antral follicles. Ribonuclease protection analyses showed that ovarian progesterone receptor and androgen receptor mRNA expression were similar in the two groups. These results indicated that ER alpha action was not a prerequisite for LHR mRNA expression by thecal or granulosa cells or for ovarian expression of progesterone receptor mRNA. Ovarian estrogen receptor beta (ERP) was detected immunohistochemically, was sharply compartmentalized to the granulosa cells, and was expressed approximately equally in the ERKO animals and the WT controls. In contrast, ER alpha staining was present in the thecal cells but not the granulosa cells of the WT animals. The summary findings indicate that in the adult the major cause of the ERKO phenotype is high circulating LH interacting with functional LHR of the theca and granulosa cells. These features result in a failure of the normal maturational events leading to successful ovulation and luteinization and presumably involve both hypothalamic-pituitary and intraovarian mechanisms dependent upon ER alpha action. The presence of ER beta in the granulosa cells did not rescue the phenotype of the ovary. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. Northwestern Univ, Dept Biochem, Evanston, IL 60208 USA. Northwestern Univ, Dept Mol & Cell Biol, Evanston, IL 60208 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 44 TC 136 Z9 139 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2733 EP 2744 DI 10.1210/en.140.6.2733 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400038 PM 10342864 ER PT J AU Yang, H Egan, JM Rodgers, BD Bernier, M Montrose-Rafizadeh, C AF Yang, H Egan, JM Rodgers, BD Bernier, M Montrose-Rafizadeh, C TI Differential expression of a novel seven transmembrane domain protein in epididymal fat from aged and diabetic mice SO ENDOCRINOLOGY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; OB GENE-EXPRESSION; 3T3-L1 ADIPOCYTES; SIGNAL-TRANSDUCTION; COUPLED RECEPTORS; FUNCTIONAL EXPRESSION; INSULIN-RESISTANCE; LEPTIN RECEPTOR; GLP-1 RECEPTOR; ADIPOSE-TISSUE AB To identify novel seven transmembrane domain proteins from 3T3-L1 adipocytes, we used PCR to amplify 3T3-L1 adipocyte complementary DNA (cDNA) with primers homologous to the N- and C-termini of pancreatic glucagon-like peptide-1 (GLP-1) receptor. We screened a cDNA library prepared from fully differentiated 3T3-L1 adipocytes using a 500-bp cDNA PCR product probe. Herein describes the isolation and characterization of a 1.6-kb cDNA clone that encodes a novel 298-amino acid protein that we termed TPRA40 (transmembrane domain protein of 40 kDa regulated in adipocytes). TPRA40 has seven putative transmembrane domains and shows little homology with the known GLP-1 receptor or with other G protein-coupled receptors. The levels of TPRA40 mRNA and protein were higher in 3T3-L1 adipocytes than in 3T3-L1 fibroblasts. TPRA40 is present in a number of mouse and human tissues. Interestingly, TPRA40 mRNA levels were significantly increased by 2- to 3-fold in epididymal fat of 24-month-old mice us. young controls as well as in db/db and ob/ob mice vs, nondiabetic control littermates. No difference in TPRA40 mRNA levels was observed in brain, heart, skeletal muscle, liver, or kidney. Furthermore, no difference in TPRA40 expression was detected in brown fat of ob/ob mice when compared with age-matched controls. Taken together, these data suggest that TPRA40 represents a novel membrane-associated protein whose expression in white adipose tissue is altered with aging and type 2 diabetes. C1 NIA, NIH, Clin Invest Lab, Diabet Sect, Baltimore, MD 21224 USA. RP Montrose-Rafizadeh, C (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 1543, Indianapolis, IN 46285 USA. EM montrose@lilly.com OI Bernier, Michel/0000-0002-5948-368X NR 55 TC 7 Z9 9 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 JUN PY 1999 VL 140 IS 6 BP 2859 EP 2867 DI 10.1210/en.140.6.2859 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400052 PM 10342878 ER PT J AU Dearry, AD Collman, GW Saint, C Fields, N Redd, S AF Dearry, AD Collman, GW Saint, C Fields, N Redd, S TI Building a network of research in children's environmental health - Introduction SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. US EPA, Natl Ctr Environm Res & Qual Assurance, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Washington, DC USA. RP Dearry, AD (reprint author), NIEHS, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1999 VL 107 SU 3 BP 391 EP 392 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 206JJ UT WOS:000080874400001 PM 10346987 ER PT J AU Landrigan, PJ Suk, WA Amler, RW AF Landrigan, PJ Suk, WA Amler, RW TI Chemical wastes, children's health, and the Superfund basic research program SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE environmental health; pediatric environmental disease; Superfund ID PUBLIC-HEALTH; POLYCHLORINATED-BIPHENYLS; CELLULAR MECHANISMS; CHILDHOOD CANCERS; CHLORPYRIFOS; EXPOSURE; TRENDS; LEAD AB Three to 4 million children and adolescents in the United States live within 1 mile of a federally designated Superfund hazardous waste disposal site and are at risk of exposure to chemical toxicants released from these sites into air, groundwater, surface water, and surrounding communities. Because of their patterns of exposure and their biological vulnerability, children are uniquely susceptible to health injury resulting from exposures to chemical toxicants in the environment. The Superfund Basic Research Program, funded by the U.S. Environmental Protection Agency and directed by the National institute of Environmental Health Sciences, is extremely well positioned to organize multidisciplinary research that will assess patterns of children's exposures to hazardous chemicals from hazardous waste disposal sites; quantify children's vulnerability to environmental toxicants; assess causal associations between environmental exposures and pediatric disease; and eluciudate the mechanisms of environmetal disease in children at the cellular and molecular level. C1 CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Natl Inst Environm Hlth Sci, Div Environm Res & Training, Res Triangle Pk, NC USA. Agcy Tox Substance & Dis Registry, Atlanta, GA USA. RP Landrigan, PJ (reprint author), CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1057, New York, NY 10029 USA. NR 43 TC 31 Z9 31 U1 1 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1999 VL 107 IS 6 BP 423 EP 427 DI 10.2307/3434621 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 205QJ UT WOS:000080831800017 PM 10339440 ER PT J AU Hooper, K Chuvakova, T Kazbekova, G Hayward, D Tulenova, A Petreas, MX Wade, TJ Benedict, K Cheng, YY Grassman, J AF Hooper, K Chuvakova, T Kazbekova, G Hayward, D Tulenova, A Petreas, MX Wade, TJ Benedict, K Cheng, YY Grassman, J TI Analysis of breast milk to assess exposure to chlorinated contaminants in Kazakhstan: Sources of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposures in an agricultural region of southern Kazakhstan SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast milk; coplanar PCBs; dioxins; exposure assessment; furans; Kazakhstan; TCDD ID TOXIC EQUIVALENCY FACTORS; DIOXIN-LIKE COMPOUNDS; POLYCHLORINATED-BIPHENYLS; PHENOXY HERBICIDES; CANCER MORTALITY; ORGANOCHLORINE PESTICIDES; OCCUPATIONAL EXPOSURE; PERINATAL EXPOSURE; BODY BURDEN; PCDF LEVELS AB High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; up to 208 pg/g fat) were measured in samples of breast milk collected in 1997 from 64 donors [41 first-time mothers (primiparae)] living on state farms in southern Kazakhstan. TCDD was the major contributor (70%) to the toxic equivalents, matching the congener patterns found in breast milk and serum samples collected in 1994 and 1996 from donors in nearby villages. The highest TCDD levels were found in state farms adjacent to a reservoir (zone A), which receives agricultural runoff from cotton fields. TCDD levels in zone A were significantly higher than levels in a region more distant (zone B; > 10 miles) from the reservoir (zone A: mean 53 pg/g, n = 17; zone B: mean 21 pg/g, n = 24; p = 0.0017). Levels of TCDD in breast milk and animal-derived foodstuffs were 10 times U.S. levels. Body burden and dietary data suggest that exposures to TCDD are chronic, environmental, and long term and may be related to the use of chemicals in cotton agriculture. The data suggest that the most likely source is the use of cotton defoliants contaminated with TCDD, and the most likely pathway for human exposure is via the consumption of contaminated foodstuffs. C1 Calif Environm Protect Agcy, Hazardous Mat Lab, Berkeley, CA 94704 USA. Kazakhstan Minist Hlth, Phys Inst Postgrad Training, Alma Ata, Kazakhstan. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. United Nations High Commissioner Refugees, Astana, Kazakhstan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Hooper, K (reprint author), Calif Environm Protect Agcy, Hazardous Mat Lab, 2151 Berkeley Way, Berkeley, CA 94704 USA. NR 63 TC 20 Z9 22 U1 2 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1999 VL 107 IS 6 BP 447 EP 457 DI 10.2307/3434626 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 205QJ UT WOS:000080831800022 PM 10515712 ER PT J AU Gladen, BC Monaghan, SC Lukyanova, EM Hulchiy, OP Shkyryak-Nyzhnyk, ZA Sericano, JL Little, RE AF Gladen, BC Monaghan, SC Lukyanova, EM Hulchiy, OP Shkyryak-Nyzhnyk, ZA Sericano, JL Little, RE TI Organochlorines in breast milk from two cities in Ukraine SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE DDE; DDT; dieldrin; endrin; heptachlor epoxide; hexachlorobenzene; hexachlorocyclohexane; milk; oxychlordane; polychlorinated biphenyls; trans-nonachlor ID POLYCHLORINATED-BIPHENYLS; PESTICIDES; PCBS; RESIDUES; MOTHERS; HEXACHLOROBENZENE; CONTAMINANTS; EXPOSURE; SPAIN; WOMEN AB Reports of environmental problems in the former Soviet Union, including excess use of pesticides, have led to concerns about high levels of contamination in humans, but little information is available to assess whether these concerns are warranted. Samples of breast milk from 197 women from two cities in Ukraine were analyzed for p,p'-DDT, p,p'-DDE, endrin, dieldrin, heptachlor epoxide, trans-nonachlor, oxychlordane, hexachlorobenzene, P-hexachlorocyclohexane (HCH), and 18 polychlorinated biphenyl congeners, and results were compared to previous reports from Europe. The median beta-HCH concentration was 731 ng/g milk fat, which is higher than other reports from Europe but lower than reports from other parts of the world. The median DDE concentration was 2,457 ng/g milk fat, which is higher than most but not all other reports from Europe. Concentrations of other chemicals were comparable to or lower than other reports from Europe. Concentrations from the city of Kyiv were generally lower than those from Dniprodzerzhinsk, but the magnitudes of these differences were modest. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Inst Pediat Obstet & Gynecol, Kyiv, Ukraine. Natl Med Univ, Kyiv, Ukraine. Texas A&M Univ, Geochem & Environm Res Grp, College Stn, TX USA. RP Gladen, BC (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 36 TC 55 Z9 58 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1999 VL 107 IS 6 BP 459 EP 462 DI 10.2307/3434627 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 205QJ UT WOS:000080831800023 PM 10339445 ER PT J AU Suk, WA Anderson, BE Thompson, CL Bennett, DA Vandermeer, DC AF Suk, WA Anderson, BE Thompson, CL Bennett, DA Vandermeer, DC TI Creating multidisciplinary research opportunities SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID BENZENE; SEQUESTRATION; SOIL C1 Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Off Program Dev, Res Triangle Pk, NC 27709 USA. US EPA, Off Emergency & Remedial Response, Washington, DC 20460 USA. RP Suk, WA (reprint author), Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Off Program Dev, Res Triangle Pk, NC 27709 USA. NR 10 TC 5 Z9 5 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD JUN 1 PY 1999 VL 33 IS 11 BP 241A EP 244A PG 4 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 202MC UT WOS:000080655400020 PM 21657308 ER PT J AU Gelius, B Wade, P Wolffe, A Wrange, O Farrants, AKO AF Gelius, B Wade, P Wolffe, A Wrange, O Farrants, AKO TI Characterization of a chromatin remodelling activity in Xenopus oocytes SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE BRG1; chromatin; nucleosome remodeling; SWI SNF; Xenopus oocytes; glucocorticoid receptor ID TUMOR VIRUS PROMOTER; SWI-SNF COMPLEX; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; DROSOPHILA-BRAHMA; NUCLEOSOME DISRUPTION; SWI/SNF COMPLEX; IN-VITRO; YEAST; TRANSCRIPTION AB The yeast SWI2/SNF2 protein is a component of a large protein complex which is involved in the remodelling of chromatin during transcriptional activation. Several homologous complexes have been found in Drosophila and mammals. We have examined the expression of the SWI2/SNF2 homologue BRG1 in Xenopus laevis using two antisera originally raised against the C-terminus of the rat and the human BRG1 protein. These two antisera crossreacted with a protein found in both Xenopus liver and Xenopus oocytes. The Xenopus BRG1-like protein is expressed throughout oogenesis (stages I-VI) and embryogenesis. By injecting an expression vector containing the full-length human BRG1 cDNA into Xenopus oocytes, the relative molecular weight (M-r) of the Xenopus BRG1-like protein was shown to be slightly lower than that of the human BRG1, 190 000 and 200 000, respectively. The Xenopus BRG1-like protein elutes at a M-r of approximate to 2 000 000 on Superose HR6(TM) size-exclusion chromatography, indicating that it is part of a larger complex, as are all other known SWI/SNF proteins. Nucleosome remodelling activity was co-eluted with the BRG1 immunogenic activity in both ion-exchange and size-exclusion chromatography. C1 Karolinska Inst, Med Nobel Inst, Dept Cell & Mol Biol, Mol Genet Lab, S-17177 Stockholm, Sweden. Univ Stockholm, Wenner Gren Inst, Dept Cell Biol, S-11345 Stockholm, Sweden. NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. RP Wrange, O (reprint author), Karolinska Inst, Med Nobel Inst, Dept Cell & Mol Biol, Mol Genet Lab, S-17177 Stockholm, Sweden. NR 47 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN PY 1999 VL 262 IS 2 BP 426 EP 434 DI 10.1046/j.1432-1327.1999.00379.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 203AJ UT WOS:000080684600023 PM 10336627 ER PT J AU Klaus, W Grzesiek, S Labhardt, AM Buchwald, P Hunziker, W Gross, MD Kallick, DA AF Klaus, W Grzesiek, S Labhardt, AM Buchwald, P Hunziker, W Gross, MD Kallick, DA TI NMR investigation and secondary structure of domains I and II of rat brain calbindin D-28k (1-93) SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE calbindin D-28k; calcium binding protein; EF hand; NMR spectroscopy; secondary structure ID CALCIUM-BINDING PROTEIN; SPECTROSCOPY; RESOLUTION; SPECTRA; PROGRAM; DETAILS; SYSTEM; S100B; MODE; C-13 AB Calbindin D-28k, a member of the troponin C superfamily of calcium-binding proteins, contains six putative EF hand domains but binds only four calcium-atoms: one at a binding site of very high affinity and three calcium-atoms at binding sites of lower affinity. The high-affinity site could be located within domain I while domains III, IV, and V bind calcium less tightly. The recombinant protein construct calb I-II (residues 1-93) comprising the first tale EF hands affords a unique opportunity to study a pair of EF hands with one site binding calcium tightly and the second site empty. A series of heteronuclear 2D, 3D and 3D high-resolution NMR experiments were applied to calb I-II, and led to the complete assignment of the H-1, C-13 and N-15 resonances. The secondary structure of the protein was deduced from the size of the (3)J(HN-H alpha) coupling constants, the chemical shift indices of H-1(alpha), C-13(alpha), C-13(i) and C-13(beta) nuclei and from an analysis of back;bone NOEs observed in 3D and 3D NOESY spectra. Four major cx-helices are identified: Ala13-Phe23, Gly33-Ala50, Leu54-Asp63, Val76-Leu90, while residues Ala2-Leu6 form a fifth, flexible helical segment. Two short beta-strands (Tyr30-Glu32, Lys72-Gly74) are found preceding helices B and D and are arranged in an anti-parallel interaction. Based on these data a structural model of calb I-II was constructed that shows that the construct adopts a tertiary structure related to other well-described calcium-binding proteins of the EF-hand family. Surprisingly, the protein forms a homodimer in solution, as was shown by its NMR characterization, size-exclusion chromatography and analytical ultra-centrifugation studies. C1 F Hoffman LaRoche AG, Pharmaceut Res, Basel, Switzerland. NIDDK, Chem Phys Lab, NIH, Bethesda, MD USA. F Hoffman LaRoche AG, Humant Nutr & Hlth Res, Basel, Switzerland. Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN USA. Univ Minnesota, Div Med Chem, Minneapolis, MN USA. RP Klaus, W (reprint author), F Hoffman LaRoche AG, Pharma Res, Bldg 65-514, CH-4070 Basel, Switzerland. NR 30 TC 8 Z9 8 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN PY 1999 VL 262 IS 3 BP 933 EP 938 DI 10.1046/j.1432-1327.1999.00471.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210KT UT WOS:000081104900038 PM 10411658 ER PT J AU Stillman, F Hartman, A Graubard, B Gilpin, E Chavis, D Garcia, J Wun, LM Lynn, W Manley, M AF Stillman, F Hartman, A Graubard, B Gilpin, E Chavis, D Garcia, J Wun, LM Lynn, W Manley, M TI The American stop smoking intervention study - Conceptual framework and evaluation design SO EVALUATION REVIEW LA English DT Article ID NATIONAL-CANCER-INSTITUTE; HEALTH; TRIALS; POLICY; MODEL AB Reducing tobacco use, especially cigarette smoking, is a public health priority. The American Stop Smoking Intervention Study (ASSIST) was initiated in 1991 to prevent and reduce tobacco use primarily through policy-based approaches to alter the social-political environment. This article describes the conceptual design, research framework, evaluation components, and analytic strategies that are guiding the evaluation of this demonstration research endeavor. The ASSIST evaluation is a unique analysis of the complex relationships between the social context, public health activity at the stale level, tobacco use, and individual behavior. The measures of tobacco control activity developed for this evaluation may be useful in ongoing national cancer control surveillance efforts, and the lessons learned will enhance the development of tobacco control programs. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP Stillman, F (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 48 TC 36 Z9 36 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD JUN PY 1999 VL 23 IS 3 BP 259 EP 280 PG 22 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 215VK UT WOS:000081404000001 PM 10538783 ER PT J AU White, IM Wise, SP AF White, IM Wise, SP TI Rule-dependent neuronal activity in the prefrontal cortex SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE frontal cortex; executive functions; rules; arbitrary mapping; working memory ID PRIMATE ORBITOFRONTAL CORTEX; GO/NO-GO DISCRIMINATION; DELAY-RELATED ACTIVITY; UNIT-ACTIVITY; FRONTAL-CORTEX; RHESUS-MONKEYS; WORKING-MEMORY; BEHAVIORAL SIGNIFICANCE; STIMULUS ATTRIBUTES; MACAQUE MONKEY AB We studied single-neuron activity in the prefrontal cortex (PF) while a monkey performed a task according to two different rules, termed conditional and spatial. The monkey viewed a Video screen, and its task required a hand movement in response to the dimming of a light spot. There were four light spots on the screen: right, left, up, and down from the center. Only one of the four spots dimmed, and the degree of dimming was slight. Accordingly, the monkey needed to foveate the "correct" light spot to detect the dimming. A visual cue indicated which of the four light spots would be deemed correct and, thus, would dim on each trial. The sequence of events was as follows: a fixation spot appeared at the center of the screen; then, a cue appeared twice at one of the four potential target locations; then, the four target spots appeared; and, finally, one of them dimmed. Except for the color of an initial fixation point, the cues, their locations, and other events were identical for the conditional and spatial rules. The rules differed in one essential way. For the conditional rule, nonspatial attributes of the visual cue indicated which of the four light spots would dim, and the cue's location was irrelevant. For the spatial rule, the cue's location determined the correct target on that trial. The light spot at the location of the cue always dimmed, regardless of which cue appeared there. Our sample included 221 PF neurons showing significant task-related activity modulation, distributed among dorsal, dorsolateral, and ventral PF regions. Between one-third and one-half of the sample in each of those regions showed statistically significant activity differences that could be attributed to the rule. Selectivity for cues and/or their locations was common. However, there was no significant regional segregation of such selectivity. These data support the hypothesis that PF plays a role in the guidance of behavior according to previously learned rules. C1 NIMH, Lab Syst Neurosci, Poolesville, MD 20837 USA. RP Wise, SP (reprint author), NIMH, Lab Syst Neurosci, POB 608, Poolesville, MD 20837 USA. NR 58 TC 286 Z9 287 U1 0 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 1999 VL 126 IS 3 BP 315 EP 335 DI 10.1007/s002210050740 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 201HY UT WOS:000080590400004 PM 10382618 ER PT J AU Zigova, T Willing, AE Tedesco, EM Borlongan, CV Saporta, S Snable, GL Sanberg, PR AF Zigova, T Willing, AE Tedesco, EM Borlongan, CV Saporta, S Snable, GL Sanberg, PR TI Lithium chloride induces the expression of tyrosine hydroxylase in hNT neurons SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hNT neurons; lithium chloride; tyrosine hydroxylase; morphometric analysis ID NERVE GROWTH-FACTOR; HUMAN CELL-LINE; DOPAMINERGIC-NEURONS; RAT-BRAIN; FUNCTIONAL RECOVERY; NEUROTROPHIC FACTOR; PROGENITOR CELLS; GENE-EXPRESSION; SERTOLI CELLS; IN-VITRO AB In the present study, several doses of lithium chloride were tested for their ability to induce the expression of tyrosine hydroxylase (TH) in neurons derived from a human teratocarcinoma cell line (hNT) after 5 and 10 days in vitro (DIV). Following immunocytochemical staining for tyrosine hydroxylase, the percentage of TH-positive neurons was determined and morphometric analysis, including mean soma profile area and neuritic length, was performed. hNT neurons responded to lithium treatment in a dose-dependent manner. In 5 DIV, the most effective dose of lithium chloride (1.0 mM) increased the number of TH-positive neurons approximately sixfold. In addition, both TH-positive hNT neuron mean soma profile area and neurite length were significantly larger than controls by 60 and 70%, respectively. Moreover, even after withdrawal of lithium chloride on day 5, the number of TH-positive neurons in 10 DIV cultures remained significantly increased. These data suggest that hNT cells are indeed responsive to lithium exposure and may serve as a continual source of TH-expressing neurons in new therapeutic approaches to degenerative brain disease. (C) 1999 Academic Press. C1 Univ S Florida, Coll Med, Dept Surg, Dept Neurosurg, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Anat, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Neurosci Program, Tampa, FL 33612 USA. NIDA, NIH, IRP, Cellular Neurobiol Branch, Baltimore, MD 21224 USA. Layton Biosci Ins, Atherton, CA 94027 USA. RP Zigova, T (reprint author), Univ S Florida, Coll Med, Dept Surg, Dept Neurosurg, Tampa, FL 33612 USA. RI Willing, Alison/I-4946-2012; OI Borlongan, Cesar/0000-0002-2966-9782 NR 36 TC 44 Z9 46 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 1999 VL 157 IS 2 BP 251 EP 258 DI 10.1006/exnr.1999.7054 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 202LD UT WOS:000080653000003 PM 10364437 ER PT J AU Barker, LP Porcella, SF Wyatt, RG Small, PLC AF Barker, LP Porcella, SF Wyatt, RG Small, PLC TI The Mycobacterium marinum G13 promoter is a strong sigma 70-like promoter that is expressed in Escherichia coli and mycobacteria species SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE mycobacterium; Mycobacterium marinum; promoter; green fluorescent protein ID GREEN FLUORESCENT PROTEIN; IDENTIFICATION; TRANSCRIPTION; FUSIONS; LEVEL AB A Mycobacterium marinum promoter, designated G13, was isolated from a promoter-trap library as a constitutive producer of the mutant green fluorescent protein. Sequence analysis, primer extension analysis, and computer promoter prediction analysis indicate that the G13 promoter is very similar to Escherichia coli consensus sigma(70) promoters. Expression of the green fluorescent protein from the G13 promoter in M. marinum is, however, up to 40 times higher than that seen from the mycobacterial hsp60 promoter during exponential growth. Further, expression from this promoter does not appear to affect the growth of the organism in culture media or in macrophages. The strong expression of the G13 promoter allows it to be developed as a useful molecular tool for high level expression of markers in vitro. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 NIAID, Rocky Mt Labs, NIH, Microscopy Branch, Hamilton, MT 59840 USA. NIH, Off Intramural Res, Bethesda, MD 20892 USA. RP Barker, LP (reprint author), NIAID, Rocky Mt Labs, NIH, Microscopy Branch, 903 S 4th St, Hamilton, MT 59840 USA. NR 22 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUN 1 PY 1999 VL 175 IS 1 BP 79 EP 85 DI 10.1016/S0378-1097(99)00169-X PG 7 WC Microbiology SC Microbiology GA 203WG UT WOS:000080730700010 PM 10361711 ER PT J AU Quader, MA Nutan, MTH Rashid, MA AF Quader, MA Nutan, MTH Rashid, MA TI Antitumor alkaloid from Glycosmis pentaphylla SO FITOTERAPIA LA English DT Article DE Glycosmis pentaphylla; arborinine; acridone alkaloids; antitumor activity ID CARBAZOLE ALKALOIDS AB Arborinine, an acridone alkaloid obtained from Glycosmis pentaphylla, exhibited significant inhibition of crown gall tumors produced by Agrobacterium tumefaciens in a potato disc bioassay. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Dhaka, Dept Chem, Dhaka 1000, Bangladesh. Univ Dhaka, Fac Pharm, Dhaka 1000, Bangladesh. RP Rashid, MA (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Bldg 560,Rm 32-63B,POB B, Frederick, MD 21702 USA. EM rashid@mail.ncifcrf.gov NR 17 TC 17 Z9 19 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X EI 1873-6971 J9 FITOTERAPIA JI Fitoterapia PD JUN PY 1999 VL 70 IS 3 BP 305 EP 307 DI 10.1016/S0367-326X(99)00028-3 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 228PZ UT WOS:000082146000018 ER PT J AU Gunther, MR Sampath, V Caughey, WS AF Gunther, MR Sampath, V Caughey, WS TI Potential roles of myoglobin autoxidation in myocardial ischemia-reperfusion injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals; myoglobin; hydrogen peroxide; superoxide; ischemia; reperfusion; oxidative stress ID CENTERED FREE-RADICALS; XANTHINE-OXIDASE; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; OXYGEN RADICALS; SKELETAL-MUSCLE; RAT HEARTS; MECHANISM; ARRHYTHMIAS AB The source(s) of reactive partially reduced oxygen species associated with myocardial ischemia/reperfusion injury remain unclear and controversial. Myoglobin has not been viewed as a participant but is present in relatively high concentrations in heart muscle and, even under normal conditions, undergoes reactions that generate met (Fe3+) species and also superoxide, hydrogen peroxide, and other oxidants, albeit slowly. The degree to which the decrease in DW and the freeing of copper ions, as well as the variations in pO(2) associated with ischemia and reperfusion increase the rates of such myoglobin reactions has been investigated. Solutions of extensively purified myoglobin from bovine heart in 50 mM sodium phosphate buffer were examined at 37 degrees C. Sufficiently mart;ed rate increases were observed to indicate that reactions of myoglobin can indeed contribute substantially to the oxidant stress associated with ischemia/reperfusion injury in myocardial tissues. These findings provide additional targets for therapeutic interventions. (C) 1999 Elsevier Science Inc. C1 Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. RP Caughey, WS (reprint author), NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. FU NHLBI NIH HHS [HL-15890] NR 42 TC 50 Z9 52 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN PY 1999 VL 26 IS 11-12 BP 1388 EP 1395 DI 10.1016/S0891-5849(98)00338-4 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 210VY UT WOS:000081126400005 PM 10401602 ER PT J AU Candotti, F Facchetti, F Blanzuoli, L Stewart, DM Nelson, DL Blaese, RM AF Candotti, F Facchetti, F Blanzuoli, L Stewart, DM Nelson, DL Blaese, RM TI Retrovirus-mediated WASP gene transfer corrects defective actin polymerization in B cell lines from Wiskott-Aldrich syndrome patients carrying 'null' mutations SO GENE THERAPY LA English DT Article DE retroviruses; genetic vectors; gene therapy; cytoskeleton; Wiskott-Aldrich syndrome ID SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW TRANSPLANTATION; SYNDROME PROTEIN; T-CELLS; LYMPHOCYTES; EXPRESSION; ANTIGEN; DONORS AB Boys affected with Wiskott-Aldrich syndrome (WAS) present with variable association of thrombocytopenia, eczema and immune deficiency. If untreated, WAS patients may succumb to intracerebral hemorrhages, severe infections or malignancies. Allogeneic bone marrow transplantation (BMT) can cure all aspects of the disease, but HLA-identical donors are not available to all patients and mismatched BMTs are unfortunately associated with high mortality and morbidity. The good success of HLA-matched BMT, however, makes WAS a potential candidate for hematopoietic stem cell gene therapy. WAS patients carry mutations of the Wiskott-Aldrich syndrome protein gene encoding WASP, a 502-amino acid proline-rich protein with demonstrated involvement in the organization of the actin cytoskeleton. To verify the feasibility of genetic correction for this disease, the WASP cDNA was expressed in EBV-immortalized B cell lines obtained from WAS patients using a retroviral vector. Transduced WAS cells showed levels of WASP expression similar to those found in cells from normal donors, without detectable effects on viability or growth characteristics. In addition, retrovirus-mediated expression of WASP led to improvement of cytoplasmic F-actin expression and formation of F-actin-positive microvilli, a process shown to be defective in untransduced WAS cell lines. These preliminary results indicate a potential use for retrovirus-mediated gene transfer as therapy for WAS. C1 NCI, Clin Gene Therapy Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NCI, Immunophysiol Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Brescia, Spedali Civili, Dept Pathol, Brescia, Italy. RP Candotti, F (reprint author), NCI, Clin Gene Therapy Branch, Natl Human Genome Res Inst, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. RI Facchetti, Fabio/E-7190-2010 OI Facchetti, Fabio/0000-0003-4975-2388 NR 26 TC 34 Z9 36 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JUN PY 1999 VL 6 IS 6 BP 1170 EP 1174 DI 10.1038/sj.gt.3300926 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 204JA UT WOS:000080759700027 PM 10455421 ER PT J AU Bussey, KJ Lawce, HJ Olson, SB Arthur, DC Kalousek, DK Krailo, M Giller, R Heifetz, S Womer, R Magenis, RE AF Bussey, KJ Lawce, HJ Olson, SB Arthur, DC Kalousek, DK Krailo, M Giller, R Heifetz, S Womer, R Magenis, RE TI Chromosome abnormalities of eighty-one pediatric germ cell tumors: Sex-, age-, site-, and histopathology-related differences - A Children's Cancer Group study SO GENES CHROMOSOMES & CANCER LA English DT Article ID YOLK-SAC TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; BENIGN OVARIAN TERATOMAS; ENDODERMAL SINUS TUMORS; CYTOGENETIC ANALYSIS; KLINEFELTERS-SYNDROME; INTERPHASE CYTOGENETICS; PARAFFIN SECTIONS; HISTOLOGIC GRADE; DOWNS-SYNDROME AB The chromosomes of 81 pediatric germ cell tumors (GCTs) were analyzed as part of two clinical treatment trials, INT-0098 and INT-0097, conducted by the Children's Cancer Group. The analysis of chromosome results showed differences with respect to sex, age, tumor location, and histology. Sixteen of 17 benign teratomas of infants and children less than 4 years old and from gonadal and extragonadal locations were chromosomally normal. Twenty-three malignant GCTs from gonadal and extragonadal locations of the same age group were endodermal sinus tumors and varied in their karyotypic findings. The most common abnormalities were gains of Iq and chromosome 3. Of eight benign ovarian teratomas from older girls, five with normal G-banded karyotypes were determined to be homozygous for Q-band heteromorphisms, suggesting a meiosis II error. Among the 12 malignant ovarian GCTs from older girls, the common abnormalities were loss of Ip/gain of Iq, +3, +8, +14, and +21. Four of eight extragonadal tumors from older boys demonstrated +21; one had +X. Five of the eight had associated constitutional chromosome abnormalities, including one trisomy 21 and three with Klinefelter syndrome. The testicular GCTs of adolescents had abnormalities resembling those found in adult testicular GCT, including near-triploidy, loss of chromosomes I I, 13, and 18, and gain of chromosomes 7, 8, the X chromosome, and an isochromosome 12p. The gain of an isochromosome 12p was only frequent in the tumors from adolescent boys. Deletion of Ip/gain of Iq and +3 were the most common abnormalities among the malignant tumors from both sexes. (C) 1999 Wiley-Liss, Inc. C1 Oregon Hlth Sci Univ, Cytogenet Res Lab, Dept Mol & Med Genet, Portland, OR 97201 USA. Childrens Canc Grp, Arcadia, CA USA. NCI, Bethesda, MD 20892 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ So Calif, Dept Prevent Med, San Diego, CA USA. Denver Childrens Hosp, Dept Hematol Oncol, Denver, CO USA. Indiana Univ, Med Ctr, Dept Pathol, Indianapolis, IN USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Magenis, RE (reprint author), Oregon Hlth Sci Univ, Cytogenet Res Lab, Dept Mol & Med Genet, 707 SW Gaines Rd,CDRC 2276, Portland, OR 97201 USA. NR 61 TC 77 Z9 79 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 1999 VL 25 IS 2 BP 134 EP 146 DI 10.1002/(SICI)1098-2264(199906)25:2<134::AID-GCC9>3.3.CO;2-P PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 193QH UT WOS:000080147300009 PM 10337997 ER PT J AU Pack, SD Karkera, JD Zhuang, ZP Pak, ED Balan, KV Hwu, P Park, WS Pham, T Ault, DO Glaser, M Liotta, L Detera-Wadleigh, SD Wadleigh, RG AF Pack, SD Karkera, JD Zhuang, ZP Pak, ED Balan, KV Hwu, P Park, WS Pham, T Ault, DO Glaser, M Liotta, L Detera-Wadleigh, SD Wadleigh, RG TI Molecular cytogenetic fingerprinting of esophageal squamous cell carcinoma by comparative genomic hybridization reveals a consistent pattern of chromosomal alterations SO GENES CHROMOSOMES & CANCER LA English DT Article ID ALLELOTYPE ANALYSIS; SOLID TUMORS; GENE; DNA; CANCERS; NEOPLASMS; ADENOCARCINOMAS; HETEROZYGOSITY; IDENTIFICATION; AMPLIFICATION AB Esophageal cancer is the third most prevalent gastrolntestinal malignancy in the world. The tumor responds poorly to various therapeutic regimens and the genetic events underlying esophageal carcinogenesis are not well understood. To identify overall chromosomal aberrations in esophageal squamous cell carcinoma, we performed comparative genomic hybridization (CGH). All 17 tumor samples were found to exhibit multiple gains and losses involving different chromosomal regions. The frequency of chromosomal loss associated with this type of tumor was as follows: in 2q ( 100%), 3p ( 100%), 13q ( 100%), Xq (94%), 4 (82%), 5q (82%), 18q (76%), 9p (76%), 6q (70%), 12q (70%), 14q (65%), 11q (59%), and Ip (53%). Interstitial deletions on Ip, 3p, 5q, 6q, I Iq, and 12q were detected also. Chromosomal gains were displayed by chromosomes and chromosome areas:19 (100%), 20q (94%), 22 (94%), 16p (65%), 17 (59%), 12q (59%), 8q (53%), 9q (53%), and 3q (50%). Two sites showing apparent amplification were I Iq (70%) and 5p15 (47%). To validate the CGH data, we isolated a BAC clone mapping to 18q12.1. This clone was used as a probe in interphase fluorescence in situ hybridization of tumor touch preparations and allelic loss was clearly revealed. This study represents the first whole-genome analysis in esophageal squamous cell carcinoma for associated chromosomal aberrations that may be involved in either the genesis or progression of this malignancy. (C) 1999 Wiley-Liss, Inc. C1 Dept Vet Affairs Med Ctr, Med Oncol Sect, Washington, DC 20422 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Howard Univ, Dept Biol, Washington, DC 20059 USA. Georgetown Univ, Ctr Diagnost, DC Gen Hosp, Washington, DC USA. NIMH, Unit Gene Mapping & Express, NIH, Bethesda, MD 20892 USA. RP Wadleigh, RG (reprint author), Dept Vet Affairs Med Ctr, Med Oncol Sect, 50 Irving St NW, Washington, DC 20422 USA. RI Pack, Svetlana/C-2020-2014 NR 36 TC 125 Z9 127 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 1999 VL 25 IS 2 BP 160 EP 168 DI 10.1002/(SICI)1098-2264(199906)25:2<160::AID-GCC12>3.0.CO;2-U PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 193QH UT WOS:000080147300012 PM 10338000 ER PT J AU Stacey, MW Wang, JX Byrd, RL Liu, JM Kearns, WG AF Stacey, MW Wang, JX Byrd, RL Liu, JM Kearns, WG TI Nuclear receptor co-repressor gene localizes to 17p11.2, a frequently deleted band in malignant disorders SO GENES CHROMOSOMES & CANCER LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; FUSION PROTEIN; N-COR; AML1; BREAKPOINTS; COMPLEX; ETO AB The t(8;21) between the AMLI and ETO genes is a commonly seen genetic alteration in acute myeloid leukemia. Recently, we reported that the fusion partner ETO binds to the human nuclear receptor co-repressor (NCOR), a member of the NCOR/SIN3/histone deacetylase complex. This complex mediates transcriptional repression as a result of chromatin remodeling. Here, we used a combination of fluorescence in situ hybridization and hybrid panels to localize the human NCOR gene (NCOR) to chromosome band 17p11.2. The position of human NCOR on 17p11 raises the possibility of deranged transcriptional regulation in malignant disorders associated with deletions of 17p. Published 1999 Wiley-Liss, Inc.dagger. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Kings Daughters, Ctr Pediat Res, Div Med Genet, Norfolk, VA USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Childrens Hosp Kings Daughters, Div Hematol Oncol, Norfolk, VA USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,10,ACRF,7C103, Bethesda, MD 20892 USA. OI Stacey, Michael/0000-0002-3807-6233 NR 16 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 1999 VL 25 IS 2 BP 191 EP 193 DI 10.1002/(SICI)1098-2264(199906)25:2<191::AID-GCC16>3.0.CO;2-8 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 193QH UT WOS:000080147300016 PM 10338004 ER PT J AU Spillare, EA Robles, AI Wang, XW Shen, JC Yu, CE Schellenberg, GD Harris, CC AF Spillare, EA Robles, AI Wang, XW Shen, JC Yu, CE Schellenberg, GD Harris, CC TI p53-mediated apoptosis is attenuated in Werner syndrome cells SO GENES & DEVELOPMENT LA English DT Article DE DNA helicase; XPB; XPD; p53 carboxy-terminal domain ID SYNDROME PROTEIN; DNA HELICASES; SYNDROME GENES; IN-VIVO; P53; LOCALIZATION; EXONUCLEASE; MODULATION; MUTATIONS; CANCER AB The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53-mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients. C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, Seattle Div, Seattle, WA 98108 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 FU NIA NIH HHS [AG05427, AG12019] NR 29 TC 135 Z9 140 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 1999 VL 13 IS 11 BP 1355 EP 1360 DI 10.1101/gad.13.11.1355 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 205TM UT WOS:000080836700001 PM 10364153 ER PT J AU Slattery, JP Franchini, G Gessain, A AF Slattery, JP Franchini, G Gessain, A TI Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia lymphotropic viruses SO GENOME RESEARCH LA English DT Review ID COMPLETE NUCLEOTIDE-SEQUENCE; II HTLV-II; FELINE IMMUNODEFICIENCY VIRUS; TROPICAL SPASTIC PARAPARESIS; INFECTED BLOOD-DONORS; DRUG-USERS; MOLECULAR CHARACTERIZATION; SUBTYPE-B; RELATIVE EFFICIENCIES; PHYLOGENETIC ANALYSIS AB Using both env and long terminal repeat (LTR) sequences, with maximal representation of genetic diversity within primate strains, we revise and expand the unique evolutionary history of human and simian T-cell leukemia/lymphotropic viruses (HTLV/STLV). Based on the robust application of three different phylogenetic algorithms of minimum evolution-neighbor joining, maximum parsimony, and maximum likelihood, we address overall levels of genetic diversity, specific rates of mutation within and between different regions of the viral genome, relatedness among viral strains from geographically diverse regions, and estimation of the pattern of divergence of the virus into extant lineages. Despite broad genomic similarities, type I and type II viruses do not share concordant evolutionary histories. HTLV-I/STLV-I are united through district phylogeographic patterns, infection of 20 primate species, multiple episodes of interspecies transmission, and exhibition of a range in levels of genetic divergence. In contrast, type II viruses are isolated from only two species (Homo sapiens and Pan paniscus) and are paradoxically endemic to both Amerindian tribes of the New World and human Pygmy villagers in Africa. Furthermore, HTLV-II is spreading rapidly through new host populations of intravenous drug users. Despite such clearly disparate host populations, the resultant HTLV-II/STLV-II phylogeny exhibits little phylogeographic concordance and indicates low levels of transcontinental genetic differentiation. Together, these patterns generate a model of HTLV/STLV emergence marked by an ancient ancestry, differential rates of divergence, and continued global expansion. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Natl Inst Hlth, Bethesda Res Labs, Bethesda, MD 20892 USA. Inst Pasteur, Unite Oncol Virale, F-5724 Paris, France. RP Slattery, JP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NR 113 TC 150 Z9 154 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 1999 VL 9 IS 6 BP 525 EP 540 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 212WV UT WOS:000081241400001 PM 10400920 ER PT J AU Ellsworth, RE Ionasescu, V Searby, C Sheffield, VC Braden, VV Kucaba, TA McPherson, JD Marra, MA Green, ED AF Ellsworth, RE Ionasescu, V Searby, C Sheffield, VC Braden, VV Kucaba, TA McPherson, JD Marra, MA Green, ED TI The CMT2D locus: Refined genetic position and construction of a bacterial clone-based physical map SO GENOME RESEARCH LA English DT Letter ID MARIE-TOOTH DISEASE; LARGE-INSERT CLONES; CHROMOSOME 7P; HETEROGENEITY; NEUROPATHY; PRIMERS; STS AB Charcot-Marie-Tooth (CMT) disease is a progressive neuropathy of the peripheral nervous system, typically characterized by muscle weakness of the distal limbs. CMT is noted for its genetic heterogeneity, with four distinct loci already identified for the axonal form of the disease (CMT2). In 1996, linkage analysis of a single large family revealed the presence of a CMT2 locus on chromosome 7p14 (designated CMT2D). Additional Families have been linked subsequently to the same genomic region, including one with distal spinal muscular atrophy (dSMA) and one with mixed features of dSMA and CMT2; symptoms in both of these latter families closely resemble those seen ill the original CMT2D Family. There is thus a distinct possibility that CMT2 and dSMA encountered in these families reflect allelic heterogeneity at a single chromosome 7 locus. In the study reported here, we have performed more detailed linkage analysis of the original CMT2D family based on new knowledge of the physical locations of various genetic markers. The region containing the CMT2D gene, as defined by the original family, overlaps with those defined by at least two other families with CMT2 and/or dSMA symptoms. Both yeast artificial chromosome (YAC) and bacterial clone-based [bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC)] contig maps spanning similar to 3.4 Mb have been assembled across the combined CMT2D critical region, with the latter providing suitable clones for systematic sequencing of the interval. Preliminary analyses have already revealed at least 28 candidate genes and expressed-sequence tags (ESTs). The mapping information reported here in conjunction with the evolving sequence data should expedite the identification of the CMT2D/dSMA gene or,genes. C1 NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Iowa, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. Washington Univ, Sch Med, Dept Genet, Genome Sequencing Ctr, St Louis, MO 63108 USA. RP Green, ED (reprint author), NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RI Marra, Marco/B-5987-2008 NR 21 TC 11 Z9 11 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 1999 VL 9 IS 6 BP 568 EP 574 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 212WV UT WOS:000081241400005 PM 10400924 ER PT J AU Fyfe, JC Kurzhals, RL Lassaline, ME Henthorn, PS Alur, PRK Wang, P Wolfe, JH Giger, U Haskins, ME Patterson, DF Sun, HC Jain, S Yuhki, N AF Fyfe, JC Kurzhals, RL Lassaline, ME Henthorn, PS Alur, PRK Wang, P Wolfe, JH Giger, U Haskins, ME Patterson, DF Sun, HC Jain, S Yuhki, N TI Molecular basis of feline beta-glucuronidase deficiency: An animal model of mucopolysaccharidosis VII SO GENOMICS LA English DT Article DE mucopolysaccharidosis; beta-glucuronidase; animal model; mucopolysaccharidosis VII; missense mutation; lysosomal storage disease ID MEDIATED GENE-TRANSFER; HYDROPS-FETALIS; MPS-VII; EXPRESSION; VECTOR; CELLS; CDNA; CLONING; MANNOSIDASE; SEQUENCE AB A family of domestic cats was found that exhibited clinical and biochemical abnormalities consistent with mucopolysaccharidosis VII, an autosomal recessive lysosomal storage disorder caused by beta-glucuronidase deficiency. beta-Glucuronidase activity was undetectable in affected cat fibroblasts and restored by retroviral gene transfer of rat beta-glucuronidase cDNA. beta-Glucuronidase mRNA was normal in affected cat testis by Northern blot analysis. Normal feline beta-glucuronidase cDNA was cloned and characterized, and amplified from affected cat fibroblasts by reverse transcription coupled polymerase chain reaction. There was a G-to-A transition in the affected cat cDNA that predicted an E351K substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression studies. Multiple species comparison and the crystal structure of human beta-glucuronidase indicated that E351 is a highly conserved residue most likely essential in maintenance of the enzyme's conformation. BssSI digestion of polymerase chain reaction products amplified from genomic DNA indicated that affected cats were homozygous and cats with half-normal beta-glucuronidase activity were heterozygous for the missense mutation. Carriers identified in this manner produced affected kittens in prospective breedings, and a feline MPS VII breeding colony has been established. (C) 1999 Academic Press. C1 Michigan State Univ, Dept Microbiol, Coll Vet Med, E Lansing, MI 48824 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. St Louis Univ, Sch Med, St Louis, MO USA. NCI, Viral Carcinogenesis Lab, Frederick, MD USA. RP Fyfe, JC (reprint author), Michigan State Univ, Dept Microbiol, Coll Vet Med, 413 Giltner Hall, E Lansing, MI 48824 USA. FU NCRR NIH HHS [RR02512]; NIDDK NIH HHS [DK42707, DK54481] NR 36 TC 56 Z9 58 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1999 VL 58 IS 2 BP 121 EP 128 DI 10.1006/geno.1999.5825 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 206BY UT WOS:000080857200002 PM 10366443 ER PT J AU Srivastava, AK McMillan, S Jermak, C Shomaker, M Copeland-Yates, SA Sossey-Alaoui, K Mumm, S Schlessinger, D Nagaraja, R AF Srivastava, AK McMillan, S Jermak, C Shomaker, M Copeland-Yates, SA Sossey-Alaoui, K Mumm, S Schlessinger, D Nagaraja, R TI Integrated STS YAC physical, genetic, and transcript map of human Xq21.3 to q23/q24 (DXS1203-DXS1059) SO GENOMICS LA English DT Article ID LINKED MENTAL-RETARDATION; ARTIFICIAL CHROMOSOME LIBRARY; SEQUENCE-TAGGED SITES; RADIATION HYBRID MAP; X-CHROMOSOME; HUMAN GENOME; ALPHA-GALACTOSIDASE; PROTEOLIPID PROTEIN; NEURONAL MIGRATION; SIGNALING PROTEIN AB A map has been assembled that extends from the XY homology region in Xq21.3 to proximal Xq24, approximately 20 Mb, formatted with 200 STSs that include 25 dinucleotide repeat polymorphic markers and more than 80 expressed sequences including 30 genes. New genes HTRP5, CAPN6, STPK, 14-3-3PKR, and CALM1 and previously known genes including BTK, DDP, GLA, PLP, COL4A5, COL4A6, PAK3, and DCX are localized; candidate loci for other disorders for which genes have not yet been identified, including DFN-2, POF, megalocornea, and syndromic and nonsyndromic mental retardation, are also mapped in the region. The telomeric end of the contig overlaps a yeast artificial chromosome (YAC) contig from Xq24-q26 and with other previously published contigs provides complete sequence-tagged site (STS)/YAC-based coverage of the long arm of the X chromosome. The order of published landmark loci in genetic and radiation hybrid maps is in general agreement. Combined with high-density STS landmarks, the multiple YAC clone coverage and integrated genetic, radiation hybrid, and transcript map provide resources to further disease gene searches and sequencing. (C) 1999 Academic Press. C1 Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63110 USA. NIA, Gerontol Res Ctr, Genet Lab, Baltimore, MD 21224 USA. RP Srivastava, AK (reprint author), Greenwood Genet Ctr, JC Self Res Inst Human Genet, 1 Gregor Mendel Circle, Greenwood, SC 29646 USA. FU NHGRI NIH HHS [HG00201]; NINDS NIH HHS [R01-NS35515] NR 70 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUN 1 PY 1999 VL 58 IS 2 BP 188 EP 201 DI 10.1006/geno.1999.5820 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 206BY UT WOS:000080857200010 PM 10366451 ER PT J AU Lippert, DN Dwyer, DW Li, FC Olafson, RW AF Lippert, DN Dwyer, DW Li, FC Olafson, RW TI Phosphoglycosylation of a secreted acid phosphatase from Leishmania donovani SO GLYCOBIOLOGY LA English DT Article DE consensus sequence; in vitro glycosylation; phosphodiester; phosphoglycan; structure ID STRUCTURAL CHARACTERIZATION; DEVELOPMENTAL MODIFICATION; MAJOR PROMASTIGOTES; LIPOPHOSPHOGLYCAN; OLIGOSACCHARIDES; GLYCOPROTEINS; BIOSYNTHESIS; EPITOPES; INVITRO AB The secreted acid phosphatase (SAcP) of L.donovani is a heterogeneous glycoprotein that displays a wide array of N- and O-linked glycosylations, The O-linked sugars are of particular interest due to their similarity to the phosphoglycan structures of the major lipophosphoglycan surface antigen and released phosphoglycan (Turco et at, 1987; Greis et al,, 1992), This study describes a structural analysis of the SAcP O-linked glycosylations using mass spectroscopy, amino acid sequencing, and enzymatic carbohydrate sequencing. Analysis of glycan chain lengths and peptide glycosylation site distribution was performed, revealing that the average O-linked structure was similar to 32 repeat units in length. Amino acid sequence analysis of glycosylated peptides showed that phosphoglycosylations did not occur randomly but were localized to specific serine residues within an array of degenerate serine/threonine-rich repeat sequences localized in the C-terminus. No evidence was obtained for modification of threonine residues. The observed pattern suggested that a consensus sequence may exist for localization of phosphoglycan structures. C1 Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 2Y2, Canada. NIAID, Div Intramural Res, Parasit Dis Lab, Cell Biol Sect,NIH, Bethesda, MD USA. RP Olafson, RW (reprint author), Univ Victoria, Dept Biochem & Microbiol, POB 3055, Victoria, BC V8W 2Y2, Canada. OI Lippert, Dustin/0000-0001-5280-1203 NR 24 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD JUN PY 1999 VL 9 IS 6 BP 627 EP 636 DI 10.1093/glycob/9.6.627 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 197WW UT WOS:000080390200013 PM 10336996 ER PT J AU Vortmeyer, AO Chan, CC Chew, EY Matteson, DM Shen, DF Wellmann, A Weil, R Zhuang, ZP AF Vortmeyer, AO Chan, CC Chew, EY Matteson, DM Shen, DF Wellmann, A Weil, R Zhuang, ZP TI Morphologic and genetic analysis of retinal angioma associated with massive gliosis in a patient with von Hippel-Lindau disease SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article AB We report morphologic and genetic analysis of bilateral retinal angiomas in a 35-year-old patient with von Hippel-Lindau (VHL) disease. Enucleation of both eyes revealed extensive intraocular tumor. Whereas the right eye demonstrated large amounts of retinal angioma tissue, the left eye showed small areas of retinal angioma associated with massive diffuse retinal gliosis. Genetic analysis of the angioma showed allelic deletion of the VHL gene locus, suggesting that the origin of the angiomas was directly related to the patient's underlying VHL disease. Genetic analysis of the pleomorphic glial proliferation showed no allelic VHL gene deletion, which is consistent with the assessment that the glial component represents a reactive process. Apoptosis detected by TUNEL revealed lack of DNA fragmentation in the angioma; in contrast, many positive signals were found in the massive gliosis. We confirmed that the abnormal VHL genes were located in the "stromal" cells of the retinal angioma. Massive gliosis in VHL disease is a true reactive retinal gliosis. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NEI, Clin Trials Branch, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 EY999999] NR 21 TC 13 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUN PY 1999 VL 237 IS 6 BP 513 EP 517 DI 10.1007/s004170050271 PG 5 WC Ophthalmology SC Ophthalmology GA 201LV UT WOS:000080597000015 PM 10379614 ER PT J AU Katz, J Nasatzky, E Werner, H Le Roith, D Shemer, J AF Katz, J Nasatzky, E Werner, H Le Roith, D Shemer, J TI Tumor necrosis factor alpha and interferon gamma-induced cell growth arrest is mediated via insulin-like growth factor binding protein-3 SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE cancer cells; IGFBP-3; tumor necrosis factor; interferon ID FACTOR-I RECEPTOR; RETINOIC ACID; IGF-I; LINE; PROLIFERATION; MODULATION; EXPRESSION; INHIBITION; SECRETION AB Retinoic acid (RA), and the combination of TNF alpha and Interferon (IFN-gamma) inhibit human salivary gland tumor (HSG) cell growth with the combination of all three being even more inhibitory (P<0.05). Previous studies have demonstrated that these inhibitory effects of RA, and the combination of TNF alpha and IFN-gamma are associated with increased accumulation of IGFBP-3 in the culture medium of HSG cells. Therefore, we set out to determine if the increase in IGFBP-3 was due to increased production of IGFBP-3 by the cells and whether IGFBP-3 played a causative role in the inhibition of cellular proliferation. TNF alpha and IFN-gamma induced a rise in IGFBP-3 mRNA levels between 4 and 8 h, which returned to control levels after 24 h. IGFBP-3 was shown to inhibit HSG cell growth at concentrations of greater than or equal to 75 U (P<0.05). When antibodies to IGFBP-3 were used with TNF alpha and IFN-gamma, the inhibitory effect of the cytokines on cell growth was diminished. Retinoic acid with TNF alpha and IFN-gamma had a marked inhibitory effect (P<0.05) which was similarly reversed by increasing concentrations of IGFBP-3 antibody. The present data support the hypothesis that the combination of TNF alpha and IFN-gamma with retinoic acid exert their anti-proliferative effect on HSG cells by reducing the mitogenic effect of IGF-I due to a shift in IGF-I from the free to the IGFBP-3-bound form. (C) 1999 Harcourt Publishers Ltd. C1 Chaim Sheba Med Ctr, Heller Inst Med Res, Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. RP Le Roith, D (reprint author), Mol & Cellular Endocrinol Branch, Room 8D12,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 23 Z9 23 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD JUN PY 1999 VL 9 IS 3 BP 174 EP 178 DI 10.1054/ghir.1999.0101 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 241FP UT WOS:000082872300003 PM 10502453 ER PT J AU Linnan, LA Fava, JL Thompson, B Emmons, K Basen-Engquist, K Probart, C Hunt, MK Heimendinger, J AF Linnan, LA Fava, JL Thompson, B Emmons, K Basen-Engquist, K Probart, C Hunt, MK Heimendinger, J TI Measuring participatory strategies: instrument development for worksite populations SO HEALTH EDUCATION RESEARCH LA English DT Article ID WORKING WELL TRIAL; COMMUNITY COALITIONS; HEALTH PROMOTION; PROJECT; PROGRAM; HEART; PREVENTION; DIETARY AB A participatory strategies approach which involves employees in the planning and delivery of worksite health promotion programs was utilized in the 55 experimental worksites included in the national, NCI-funded Working Well Trial. According to study protocol, Employee Advisory Boards (EABs) were organized in each experimental worksite. This paper describes two substudies designed to develop and measure participatory strategies associated with the EABs in the Working Well Trial. Study 1 determined characteristics of the EABs, developed subscales and assessed the internal consistency of the scales. Study 2 used a confirmatory factor analysis to examine the structure of the developed questionnaire. The four subscales include: Autonomy/Independence, Management Involvement, Institutionalization/Commitment and Others Involvement. Results from Study 1 indicate that the four subscales of the 24-item instrument demonstrated strong internal consistency and three were sensitive enough to register differences by Study Center at the baseline. Study 2 results found that the EAB subscales again demonstrated good internal consistency, structural stability and acceptable sensitivity. An initial validity analysis was performed and yielded results which supported some but not all of the hypothesized associations. Implications for further refinement and application of this new instrument in worksite settings are explored. C1 Miriam Hosp, Div Behav Med, Providence, RI 02906 USA. Brown Univ, Providence, RI 02906 USA. Univ Rhode Isl, N Kingston, RI 02852 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. Penn State Univ, University Pk, PA 16802 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20814 USA. RP Linnan, LA (reprint author), Miriam Hosp, Div Behav Med, 164 Summit Ave, Providence, RI 02906 USA. FU NCI NIH HHS [U01 CA51671, U01 CA51686, U01 CA51687] NR 49 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD JUN PY 1999 VL 14 IS 3 BP 371 EP 386 DI 10.1093/her/14.3.371 PG 16 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 205AL UT WOS:000080799000006 PM 10539228 ER PT J AU Potosky, AL Merrill, RM Riley, GF Taplin, SH Barlow, W Fireman, BH Lubitz, JD AF Potosky, AL Merrill, RM Riley, GF Taplin, SH Barlow, W Fireman, BH Lubitz, JD TI Prostate cancer treatment and ten-year survival among group staff HMO and fee-for-service medicare patients SO HEALTH SERVICES RESEARCH LA English DT Article DE outcomes research; healthcare insurance plans; managed care; prostate cancer treatments; prostate cancer survival ID HEALTH-MAINTENANCE-ORGANIZATIONS; MANAGED CARE; RADICAL PROSTATECTOMY; OUTCOMES; QUALITY; MEN; DIAGNOSIS; INSURANCE; ENROLLEES; THERAPY AB Objective. To compare treatment patterns and the ten-year survival of prostate cancer patients in two large, nonprofit, group/staff HMOs to those of patients receiving care in the fee-for-service health setting. Data Sources/Study Design. A cohort of men age 65 and over diagnosed with prostate cancer between 1985 and the end of 1992 and followed through 1994. Subjects (n = 21,741) were ascertained by two population-based tumor registries covering the greater San Francisco-Oakland and Seattle-Puget Sound areas. Linkage of registry data with Medicare claims data and with HMO inpatient utilization data allowed the determination of health plan enrollment and the measurement of comorbid conditions. Multivariate regression models were used to examine HMO versus FFS treatment and survival differences adjusting for sociodemographic and clinical characteristics. Principal Findings. Among cases with non-metastatic prostate cancer, HMO patients were more likely than FFS patients to receive aggressive therapy (either prostatectomy of radiation) in San Francisco-Oakland (odds ratio [OR] = 1.69, 95% CI=1.46-1.96) but not in Seattle (OR = 1.15, 0.9-1.43). Among men receiving aggressive therapy, HMO cases were three to five times more likely to receive radiation therapy than prostatectomy. Overall mortality was equivalent over ten years (HMO versus FFS mortality risk ratio [RR] = 1.01, 0.94-1.08), but prostate cancer mortality was higher for HMO cases than for FFS cases (RR = 1.25, 1.13-1.39). Conclusion. Despite marked treatment differences for clinically localized prostate cancer, overall ten-year survival for patients enrolled in two nonprofit group/staff HMOs was equivalent to survival among patients receiving care in the FFS setting, even after adjustment for sociodemographic and clinical characteristics. Similar overall but better prostate cancer-specific survival among FFS patients is most plausibly explained by differences between the HMO and FFS patients in both tumor characteristics and unmeasured patient selection factors. C1 Natl Canc Inst, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. US Hlth Care Financing Adm, Div Hlth Syst Res, Baltimore, MD 21207 USA. Univ Puget Sound, Grp Hlth Cooperat, Tacoma, WA 98416 USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Kaiser Permanente, Div Res, Oakland, CA USA. RP Potosky, AL (reprint author), Natl Canc Inst, Appl Res Branch, Div Canc Control & Populat Sci, EPN Room 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 56 TC 42 Z9 42 U1 2 U2 3 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 1999 VL 34 IS 2 BP 525 EP 546 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 198ZZ UT WOS:000080455900005 PM 10357289 ER PT J AU Allikmets, R Seddon, JM Bernstein, PS Hutchinson, A Atkinson, A Sharma, S Gerrard, B Li, W Metzker, ML Wadelius, C Caskey, CT Dean, M Petrukhin, K AF Allikmets, R Seddon, JM Bernstein, PS Hutchinson, A Atkinson, A Sharma, S Gerrard, B Li, W Metzker, ML Wadelius, C Caskey, CT Dean, M Petrukhin, K TI Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies SO HUMAN GENETICS LA English DT Article ID BEAVER DAM EYE; STARGARDT-DISEASE; RETINITIS-PIGMENTOSA; DYSTROPHY; ABCR; MUTATIONS AB Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category. C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Utah, Moran Eye Ctr, Dept Ophthalmol, Salt Lake City, UT 84132 USA. Merck Res Labs, Dept Human Genet, W Point, PA 19486 USA. Univ Uppsala Hosp, Clin Genet Unit, Dept Genet & Pathol, S-75185 Uppsala, Sweden. NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, 2nd Floor,630 W 168th St, New York, NY 10032 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-56000]; NEI NIH HHS [EY11309, EY11600] NR 23 TC 95 Z9 99 U1 0 U2 8 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1999 VL 104 IS 6 BP 449 EP 453 DI 10.1007/s004390050986 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 223RL UT WOS:000081854000002 PM 10453731 ER PT J AU Soares, M Buxbaum, J Sirugo, G Coelho, T Sousa, A Kastner, D Saraiva, MJ AF Soares, M Buxbaum, J Sirugo, G Coelho, T Sousa, A Kastner, D Saraiva, MJ TI Genetic anticipation in Portuguese kindreds with familial amyloidotic polyneuropathy is unlikely to be caused by triplet repeat expansions SO HUMAN GENETICS LA English DT Article ID PROGRESSIVE MYOCLONUS EPILEPSY; EXPANDED CAG REPEATS; CYSTATIN-B GENE; TRINUCLEOTIDE REPEATS; PEDIGREE ANALYSIS; HUMAN GENOME; ONSET; SCHIZOPHRENIA; MUTATION; DISORDER AB Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant type of amyloidosis resulting from the deposition of transthyretin (ATTR) variants in the peripheral and autonomic nervous systems. ATTR V30M-associated FAP exhibits marked genetic anticipation in some families, with clinical symptoms developing at an earlier age in successive generations. The genetic basis of this phenomenon in FAP is unknown. Anticipation has been associated with the dynamic expansion of trinucleotide repents in several neurodegenerative disorders, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. We have used the repeat expansion detection (RED) assay to screen affected members of Portuguese FAP kindreds for expansion of any of the ten possible trinucleotide repeats. Nine generational pairs with differences in their age of onset greater than 12 years and a control pair with identical ages of onset were tested. No major differences were found in the lengths of the ten trinucleotide repeats analyzed, The distribution of the maximal repeat sizes was consistent with reported studies in unrelated individuals with no known genetic disease, The present data do not support a role for trinucleotide repeat expansions as the molecular mechanism underlying anticipation in Portuguese FAP. C1 IBMC, Amyloid Unit, P-4150 Porto, Portugal. NIAMSD, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. NY Dept Vet Affairs Med Ctr, Res Serv, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. IBMC, Neuropsychophysiol Unit, Porto, Portugal. Ctr Estudos Paramiloidose, Porto, Portugal. IBMC, UnIGENe, Porto, Portugal. Inst Ciencias Biomed, Porto, Portugal. RP Saraiva, MJ (reprint author), IBMC, Amyloid Unit, R Campo Alegre 823, P-4150 Porto, Portugal. RI Saraiva, Maria Joao/K-3907-2013; Sousa, Alda/K-4372-2013 OI Saraiva, Maria Joao/0000-0002-3360-6899; Sousa, Alda/0000-0001-5441-1815 NR 32 TC 23 Z9 25 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1999 VL 104 IS 6 BP 480 EP 485 DI 10.1007/s004390050991 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 223RL UT WOS:000081854000007 PM 10453736 ER PT J AU Tassiulas, I Duncan, SR Centola, M Theofilopoulos, AN Boumpas, DT AF Tassiulas, I Duncan, SR Centola, M Theofilopoulos, AN Boumpas, DT TI Clonal characteristics of T cell infiltrates in skin and synovium of patients with psoriatic arthritis SO HUMAN IMMUNOLOGY LA English DT Article DE T cell antigen receptor; alpha-beta; auto-immunity; complementary determining region (CDR3) ID CUTANEOUS LYMPHOCYTE ANTIGEN; AUTOIMMUNE-DISEASE; RECEPTOR BIASES; GENE USAGE; LESIONS; VULGARIS; SELECTIN; GUTTATE; PROLIFERATIONS; SUPERANTIGENS AB Psoriasis is a chronic inflammatory skin disease that is often complicated by an inflammatory arthritis. Considerable evidence implicates cellular immune responses in psoriatic skin lesions, but the pathogenesis of the associated arthritis has not been elucidated. We analyzed T cell antigen receptor beta chain variable (TCR beta V) gene repertoires among peripheral blood lymphocytes, skin and synovium of nine patients with psoriatic arthritis. RNase protection assays were used to quantitate the expression levels of 25 TCR beta V genes, and CDR3 region sequencing was used to further Characterize selected expansions. All patients exhibited significant TCR beta V biases in the peripheral blood and moreover, all had expansions common to both skin and synovium. CDR3 sequencing demonstrated these expansions frequently consisted of oligo- or monoclonal populations. Although no ubiquitous CDR3 nucleotide sequences were identified, two patients shared identical sequences and several highly homologous amino acid motifs were present in skin and synovium among and between individual patients. Findings of common TCR beta V expansions in diverse inflammatory sites, among multiple afflicted individuals, suggest that these T cell proliferations are driven by engagements mit-h a limited set of conventional antigens. These findings demonstrate an important role for cognate T cell responses in the pathogenesis of psoriatic arthritis, and further suggest the inciting antigen(s) is identical or homologous between afflicted skin and synovium. Human Immunology 60. 479-491 (1999). published by Elsevier Science Inc. C1 NIAMSD, Artrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Boumpas, DT (reprint author), NIAMS, ARB, NIH, Bldg 10,Room 9S209,10 Ctr Dr MSC, Bethesda, MD 20892 USA. NR 47 TC 56 Z9 56 U1 1 U2 2 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 JUN PY 1999 VL 60 IS 6 BP 479 EP 491 DI 10.1016/S0198-8859(99)00034-8 PG 13 WC Immunology SC Immunology GA 209KX UT WOS:000081047800004 PM 10408797 ER PT J AU Waragai, M Lammers, CH Takeuchi, S Imafuku, I Udagawa, Y Kanazawa, I Kawabata, M Mouradian, MM Okazawa, H AF Waragai, M Lammers, CH Takeuchi, S Imafuku, I Udagawa, Y Kanazawa, I Kawabata, M Mouradian, MM Okazawa, H TI PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival SO HUMAN MOLECULAR GENETICS LA English DT Article ID PALLIDOLUYSIAN ATROPHY DRPLA; SPINOCEREBELLAR ATAXIA TYPE-2; MACHADO-JOSEPH DISEASE; DOPAMINE-RECEPTOR GENE; EXPANDED POLYGLUTAMINE; CAG REPEAT; INTRANUCLEAR INCLUSIONS; HUNTINGTONS-DISEASE; MESSENGER-RNAS; TRIPLET REPEAT AB A novel gene, designated PQBP-1, which encodes a 265 residue protein, that binds to the polyglutamine tract of the brain-specific transcription factor Brn-2, was identified. PQBP-1, which also interacts with the polyglutamine tract of triplet repeat disease gene products, binds with a higher affinity to an expanded polyglutamine tract. PQBP-1 has several functional domains, including hepta- and di-amino acid repeat sequences rich in polar residues essential for its interaction with the polyglutamine tract, a WWP/WW domain which binds to proline-rich motifs in other proteins, a putative nuclear localization signal sequence and a C-2 domain implicated in Ca2+-dependent phospholipid signaling. PQBP-1 is located in the nucleus and inhibits transcriptional activation by Brn-2. Overexpression of PQBP-1 in P19 embryonic carcinoma cells suppresses their growth rate and enhances their susceptibility to various stresses including serum deprivation, retinoic acid treatment and UV irradiation, Northern blot and in situ hybridization analyses revealed that PQBP-1 is a ubiquitous protein and is expressed primarily in neurons throughout the brain, with abundant levels in hippocampus, cerebellar cortex and olfactory bulb. These results suggest that PQBP-1 mediates important cellular functions under physiological and pathological conditions via its interaction with polyglutamine tracts. C1 Univ Tokyo, Grad Sch Med, Dept Neurol, Grp Mol Neurobiol,Bunkyo Ku, Tokyo 113, Japan. NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Toshima Ku, Tokyo 170, Japan. RP Okazawa, H (reprint author), Univ Tokyo, Grad Sch Med, Dept Neurol, Grp Mol Neurobiol,Bunkyo Ku, 7-3-1 Hongo, Tokyo 113, Japan. OI Mouradian, M. Maral/0000-0002-9937-412X NR 45 TC 128 Z9 133 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1999 VL 8 IS 6 BP 977 EP 987 DI 10.1093/hmg/8.6.977 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 202PV UT WOS:000080662100004 PM 10332029 ER PT J AU Ortmann, O Weiss, JM Polack, S Stojilkovic, SS Diedrich, K AF Ortmann, O Weiss, JM Polack, S Stojilkovic, SS Diedrich, K TI Effects of androgens and insulin on LH secretion from gonadotrophs SO HUMAN REPRODUCTION LA English DT Meeting Abstract C1 Univ Lubeck, Dept Obstet & Gynecol, D-2400 Lubeck, Germany. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1999 VL 14 SU 1 MA R212 BP 374 EP 374 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 223EN UT WOS:000081828000727 ER PT J AU Azorsa, DO Meltzer, PS AF Azorsa, DO Meltzer, PS TI Production and characterization of monoclonal antibodies to the steroid receptor coactivator AIB1 SO HYBRIDOMA LA English DT Article ID NUCLEAR-RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; BINDING; TIF2; ACTIVATION; CBP; TRANSACTIVATION; BREAST; CANCER; MOTIFS AB The steroid coactivator AIB1 (Ampified In Breast cancer 1) is a member of the SRC-1 family of transactivation coactivators that is amplified in about 7% of breast tumor samples. Hybridomas were established that secreted monoclonal antibodies (MAbs) to a recombinant glutathione-S-transferase (GST) fusion protein expressing the steroid receptor interacting domain of AIB1 (GST-AIB.T1: a.a. 605-1294). Four MAbs from these hybridomas were characterized and designated AX15.1, AX15.2, AX15.3, and AX15.4. The MAbs were shown to be specific to AIB1 and did not cross-react with two similar coactivators SRC-1 and TIF2 as shown in Western blot analysis and enzyme-linked immunoadsorbent assay (ELISA), Western blot analysis using the four MAbs showed specific recognition of AIB1 protein as a 160 kDa band in lysates from cell lines containing AIB1 gene-amplification. The MAbs immunoprecipitated in vitro-translated AIB1 and cellular AIB1 from metabolically labeled cells. The results show that these newly described MAbs are useful in studies of AIB1 function and expression. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 49,Room 4A10,49 Convent Dr,MSC 4470, Bethesda, MD 20892 USA. NR 20 TC 9 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1999 VL 18 IS 3 BP 281 EP 287 DI 10.1089/027245799315943 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 228ZJ UT WOS:000082167200009 PM 10475243 ER PT J AU Xu, CY Pham, DL Rettmann, ME Yu, DN Prince, JL AF Xu, CY Pham, DL Rettmann, ME Yu, DN Prince, JL TI Reconstruction of the human cerebral cortex from magnetic resonance images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE cortical surface reconstruction; deformable surface models; fuzzy segmentation; isosurface; magnetic resonance imaging ID ACTIVE CONTOUR MODELS; GRADIENT VECTOR FLOW; BRAIN IMAGES; 3-D IMAGES; SEGMENTATION; ATLAS; BALLOONS; SURFACES; ANATOMY; SYSTEM AB Reconstructing the geometry of the human cerebral cortex from MR images is an important step in both brain mapping and surgical path planning applications, Difficulties with imaging noise, partial volume averaging, image intensity inhomogeneities, convoluted cortical structures, and the requirement to preserve anatomical topology make the development of accurate automated algorithms particularly challenging. In this paper ne address each of these problems and describe a systematic method for obtaining a surface representation of the geometric central layer of the human cerebral cortex. Using fuzzy segmentation, an isosurface algorithm, and a deformable surface model, the method reconstructs the entire cortex with the correct topology, including deep convoluted sulci and gyri. The method is largely automated and its results are robust to imaging noise, partial volume averaging, and image intensity inhomogeneities. The performance of this method is demonstrated, both qualitatively and quantitatively and the results of its application to sis subjects and one simulated MR brain volume are presented. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Ctr Imaging Sci, Baltimore, MD 21218 USA. NIA, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Ctr Imaging Sci, Baltimore, MD 21205 USA. RP Prince, JL (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, Ctr Imaging Sci, Baltimore, MD 21218 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 FU NINDS NIH HHS [1RO1NS37747-01] NR 50 TC 149 Z9 153 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 1999 VL 18 IS 6 BP 467 EP 480 DI 10.1109/42.781013 PG 14 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 227LE UT WOS:000082081200002 PM 10463126 ER PT J AU Seidel, J Vaquero, JJ Siegel, S Gandler, WR Green, MV AF Seidel, J Vaquero, JJ Siegel, S Gandler, WR Green, MV TI Depth identification accuracy of a three layer phoswich PET detector module SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1998 Medical Imaging Conference CY NOV 12-14, 1998 CL TORONTO, CANADA ID CRYSTALS AB We describe a PET detector module that provides three levels of depth-of-interaction (DOI) information. The detector is a 9 x 9 array of 2 mm x 2 mm x 12 mm deep phoswich crystal elements, each consisting of 4 mm long LSO (entrance layer), GSO (middle layer) and EGO (exit layer) crystals joined optically together end-to-end. The EGO exit layer is directly coupled to a miniature position-sensitive photomultiplier tube (PSPMT). Delayed charge integration, a method that exploits differences in the light decay times of these scintillators, is used to determine the layer-of-interaction. DOI accuracy, measured by scanning a slit source of 511 keV radiation along the length of the module was 86% for the LSO layer, 80% for the GSO layer and 84% for the EGO layer. Energy resolution at 511 keV was 19% for LSO, 21% for GSO and 40% for EGO. Apparent gain differed between layers in the ratios 2.7:1.9:1.0 (LSO:GSO:BGO). Crystal separation was good between crystals in the LSO layer, acceptable between crystals in the GSO layer and poor between crystals in the EGO layer due, primarily, to the pronounced spatial non-linearity of the PSPMT. The delayed charge integration method, however, does appear suitable for obtaining multi-level depth information when DOI effects are particularly significant, e.g. in very small ring diameter PET scanners for small animal imaging. C1 NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Seidel, J (reprint author), NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X NR 14 TC 147 Z9 149 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1999 VL 46 IS 3 BP 485 EP 490 DI 10.1109/23.775567 PN 2 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 216UA UT WOS:000081461200007 ER PT J AU Siegel, S Vaquero, JJ Aloj, L Seidel, J Jagoda, E Gandler, WR Eckelman, WC Green, MV AF Siegel, S Vaquero, JJ Aloj, L Seidel, J Jagoda, E Gandler, WR Eckelman, WC Green, MV TI Initial results from a PET planar small animal imaging system SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1998 Medical Imaging Conference CY NOV 12-14, 1998 CL TORONTO, CANADA ID DOPED LUTETIUM OXYORTHOSILICATE; TARGETED DISRUPTION; SPATIAL-RESOLUTION; LSO; MICE; ACID; GENE AB A pair of stationary, opposed scintillation detectors in time coincidence is being used to create planar projection or tomographic images of small animals injected with positron-emitting radiotracers. The detectors are comprised of arrays of individual crystals of bismuth germanate coupled to position-sensitive photomultiplier tubes. The system uses FERA (LeCroy Research Systems) charge-sensitive ADCs and a low cost digital I/O board as a FERA bus-to-host bridge. In projection mode, the animal is placed within the 55 mm x 45 mm useful field-of-view of the detectors and images are formed from coincidence lines that fall close to the normals of both detectors. In tomographic mode, the animal is placed on a rotation stage between the detectors and rotated around a vertical axis to acquire all possible lines-of-response. Tomographic images are then reconstructed from those lines falling within a user-specified angle of each detector normal. In mice, the system is capable of high-speed, whole-body dynamic projection imaging, and whole body tomographic imaging of slowly varying tracer distributions. An ECG gating capability is also available for evaluating cardiac function. This system is currently being used to study tracer transport in normal and genetically engineered mice. C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Siegel, S (reprint author), Concorde Microsyst, 10427 Cogdill Rd,Suite 500, Knoxville, TN 37932 USA. RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X NR 19 TC 45 Z9 45 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1999 VL 46 IS 3 BP 571 EP 575 DI 10.1109/23.775581 PN 2 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 216UA UT WOS:000081461200021 ER PT J AU Mansour, PM Smith, MF Barker, WC Dilsizian, V Srinivasan, G Bacharach, SL AF Mansour, PM Smith, MF Barker, WC Dilsizian, V Srinivasan, G Bacharach, SL TI Regional left ventricular function from short-duration SPECT gated blood pool studies SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1998 Medical Imaging Conference CY NOV 12-14, 1998 CL TORONTO, CANADA ID EJECTION FRACTION; RECONSTRUCTION; IMAGES AB SPECT gated blood pool scans can provide accurate 3D assessments of resting regional left-ventricular (LV) function. However, due to limited scan times for stress studies, SPECT GBP images are often too noisy for standard. visual analysis. in this investigation, we examined whether quantitative regional analysis could be performed despite this increased noise. A counts-based scheme for measuring regional ejection fraction (REF) and relative regional phase (RRP) was investigated. Constructing a rest normal database (NLDB) from the 30-min. SPECT GBP's of 10 volunteers, the mean and standard deviation (sigma((rest NLDB))) Of these parameters was calculated for each of twelve 3D regions. Adding statistical noise, the expected normal database variability at stress (sigma((stress NLDB))) from 3-min. scans was estimated for each parameter. The variability due to increased noise (sigma(noise)) resulted in an average: increase from sigma((rest NLDB)) to sigma((stress NLDB)) of 19% in REF, and 45% in RRP. Analyzing rest scans from two patients with regional defects, regions were classified twice; first based on a criterion of +/-2 sigma((rest NLDB)) about the average normal database value for that region, then again using +/-2 sigma((stress NLDB)). Of the 19 abnormal regions identified at rest, 18 were still detected with the +/-2 sigma((stress NLDB)) criterion. This suggests that quantitative regional analysis may be relatively insensitive to the increased noise from a 3-min. scan, making stress SPECT GBP studies potentially feasible. C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. RP Mansour, PM (reprint author), NIH, Dept Nucl Med, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1999 VL 46 IS 3 BP 680 EP 685 DI 10.1109/23.775598 PN 2 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 216UA UT WOS:000081461200038 ER PT J AU Riddell, C Brigger, P Carson, RE Bacharach, SL AF Riddell, C Brigger, P Carson, RE Bacharach, SL TI The watershed algorithm: A method to segment noisy PET transmission images SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1998 Medical Imaging Conference CY NOV 12-14, 1998 CL TORONTO, CANADA ID POSITRON EMISSION TOMOGRAPHY; ATTENUATION CORRECTION; RECONSTRUCTION AB Attenuation correction is essential to PET imaging but often requires impractical acquisition times. Segmentation of short noisier transmission scans has been proposed as a solution. We report that a 3D morphological tool - the watershed algorithm - is well adapted for segmenting even 2-minute PET transmission images. The technique is noniterative, fast, and fully 3-D. It inherently ensures class continuity and eliminates outliers. Pre-filtering the data induced smoother class edges, showing that a multi-resolution approach could be used to deal with partial volume effect and excessive noise in the data. The algorithm was tested on 2-minute scans of a torso phantom and on a human study. C1 NIH, Bethesda, MD 20892 USA. RP Riddell, C (reprint author), NIH, Bldg 10,Room 1C401, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 14 TC 29 Z9 29 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1999 VL 46 IS 3 BP 713 EP 719 DI 10.1109/23.775604 PN 2 PG 7 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 216UA UT WOS:000081461200044 ER PT J AU Smith, MF Brigger, P Ferrand, SK Dilsizian, V Bacharach, SL AF Smith, MF Brigger, P Ferrand, SK Dilsizian, V Bacharach, SL TI Regional cardiac wall motion from gated myocardial perfusion SPECT studies SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1998 Medical Imaging Conference CY NOV 12-14, 1998 CL TORONTO, CANADA ID EMISSION COMPUTED-TOMOGRAPHY; LEFT-VENTRICULAR FUNCTION; EJECTION FRACTION; TL-201; TECHNETIUM-99M-SESTAMIBI; QUANTIFICATION; INFARCTION AB A method for estimating regional epicardial and endocardial wall motion from gated myocardial perfusion SPECT studies has been developed. The method uses epicardial and endocardial boundaries determined from four long axis slices at each gate of the cardiac cycle, Epicardial and endocardial wall position at each time gate is computed with respect to stationary reference ellipsoids and wall motion is measured along lines normal to these ellipsoids. An initial quantitative evaluation of the method was made using the beating heart from the dynamic mathematical cardiac torso (MCAT) phantom, with and without a 1.5 cm FWHM Gaussian blurring filter. Epicardial wall motion was generally well-estimated within a fraction of a 3.56 mm voxel, although apical motion was overestimated with the Gaussian filter. Endocardial wall motion was underestimated by about two voxels with and without the Gaussian filter. The MCAT heart phantom was modified to model hypokinetic and dyskinetic wall motion. The wall motion analysis method enabled this abnormal motion to be differentiated from normal motion. Regional cardiac wall motion also was analyzed for Tl-201 patient studies. Estimated wall motion was consistent with a nuclear medicine physician's visual assessment of motion from gated long axis slices for example male and female studies. Additional research is required for a comprehensive evaluation of the applicability of the method to patient studies with normal and abnormal wall motion. C1 NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Smith, MF (reprint author), NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1999 VL 46 IS 3 BP 727 EP 736 DI 10.1109/23.775606 PN 2 PG 10 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 216UA UT WOS:000081461200046 ER PT J AU Song, R Porgador, A Harding, CV AF Song, R Porgador, A Harding, CV TI Peptide-receptive class I major histocompatibility complex molecules on TAP-deficient and wild-type cells and their roles in the processing of exogenous antigens SO IMMUNOLOGY LA English DT Article ID RMA-S CELLS; MHC PRESENTATION; SURFACE-ANTIGEN; T-CELLS; LYMPHOCYTES; PATHWAY; TRANSPORTER; BACTERIAL; MONITOR; INVIVO AB These studies addressed the nature and origin of peptide-receptive class I major histocompatibility complex (MHC-I) molecules used to present exogenous antigens. Peptide-receptive Kb molecules in transporter for antigen presentation (TAP)1(-/-) and TAP1(+/+) macrophages were quantitated by exposing cells to exogenous ovalbumin (OVA)(257-264) peptide and then measuring OVA(257-264):Kb complexes with a T hybridoma assay or flow cytometry (using a complex-specific antibody). Relative to TAP1(+/+) cells, TAP1(-/-) cells had decreased levels of pre-existing cell-surface peptide-receptive MHC-I molecules at 37 degrees. With continued exposure of viable cells to peptide, however, TAP1(-/-) and TAP1(+/+) cells formed similar levels of OVA(257-264):K-b complexes, suggesting that nascent labile MHC-I molecules were captured and stabilized by exogenous peptide. Brefeldin A inhibited generation of OVA(257-264) : K-b complexes on TAP1(-/-) (but not TAP1(+/+)) cells at 37 degrees, confirming the importance of a flux of unstable nascent MHC-I molecules in TAP1(-/-) cells at 37 degrees. In contrast, at 26 degrees both TAP1(-/-) and TAP1(+/+) cells expressed brefeldin A-resistant, peptide-receptive MHC-I molecules at similar levels. Alternate MHC-I processing of exogenous particulate antigen correlated with ability to present exogenous peptide. Thus, processing was brefeldin A-sensitive with TAP1(-/-) macrophages at 370, but brefeldin A-resistant with TAP1(+/+) cells at 37 degrees, as well as with TAP1(+/+) or TAP1(-/-) cells at 26 degrees. We conclude that alternate MHC-I antigen processing normally utilizes pre-existing MHC-I molecules, but TAP1(-/-) cells at 37 degrees mainly use nascent MHC-I molecules, because of a lack of pre-existing, stable, peptide-receptive MHC-I molecules. The results support a vacuolar processing mechanism with binding of peptides to MHC-I molecules in post-Golgi compartments or on the cell surface. C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Harding, CV (reprint author), Case Western Reserve Univ, Inst Pathol, 2085 Adelbert Rd, Cleveland, OH 44106 USA. FU NCI NIH HHS [CA70149]; NIAID NIH HHS [AI34343, AI35726, R01 AI034343, R01 AI035726] NR 32 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUN PY 1999 VL 97 IS 2 BP 316 EP 324 PG 9 WC Immunology SC Immunology GA 209BM UT WOS:000081027500019 PM 10447748 ER PT J AU Heeney, JL Beverley, P McMichael, A Shearer, G Strominger, J Wahren, B Weber, J Gotch, F AF Heeney, JL Beverley, P McMichael, A Shearer, G Strominger, J Wahren, B Weber, J Gotch, F TI Immune correlates of protection from HIV and AIDS - more answers but yet more questions SO IMMUNOLOGY TODAY LA English DT Article ID T-CELL RESPONSES; IMMUNODEFICIENCY-VIRUS TYPE-1; APOPTOTIC CELLS; BETA-CHEMOKINES; INFECTION; DISEASE; LYMPHOCYTES; RESISTANCE; MACAQUES; NEUTRALIZATION AB Ar an international symposium*, specific clinical and preclinical settings were examined in order to increase our understanding of immunity to HIV. This data might help the design of more effective vaccine strategies for protection from HIV ou the treatment of AIDS. C1 Biomed Primate Res Ctr, Dept Virol, NL-2288 GJ Rijswijk, Netherlands. Edward Jenner Inst, Newbury RG20 7NN, Berks, England. John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DS, England. NCI, Dept Expt Immunol Branch, NIH, Bethesda, MD 20817 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Karolinska Inst, Dept Virol, S-10521 Stockholm, Sweden. Univ London Imperial Coll Sci Technol & Med, Jefferis Trust Labs, Dept Genitourinary Med & Communicable Dis, London W2 1NY, England. Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept Immunol, London SW10 9NH, England. RP Heeney, JL (reprint author), Biomed Primate Res Ctr, Dept Virol, Lange Kleiweg 157, NL-2288 GJ Rijswijk, Netherlands. OI Heeney, Jonathan/0000-0003-2702-1621 NR 34 TC 38 Z9 40 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUN PY 1999 VL 20 IS 6 BP 247 EP 251 DI 10.1016/S0167-5699(98)01437-6 PG 5 WC Immunology SC Immunology GA 222JG UT WOS:000081780700001 PM 10354547 ER PT J AU Roilides, E Tsaparidou, S Kadiltsoglou, I Sein, T Walsh, TJ AF Roilides, E Tsaparidou, S Kadiltsoglou, I Sein, T Walsh, TJ TI Interleukin-12 enhances antifungal activity of human mononuclear phagocytes against Aspergillus fumigatus: Implications for a gamma interferon-independent pathway SO INFECTION AND IMMUNITY LA English DT Article ID ANTIGEN-PRESENTING CELLS; NATURAL-KILLER-CELLS; IMMUNOREGULATORY FUNCTIONS; INVASIVE ASPERGILLOSIS; HUMAN-MONOCYTES; IL-12 RECEPTOR; CYTOKINE; POLYMORPHONUCLEAR; MACROPHAGES; MECHANISMS AB The potential of recombinant human interleukin-12 (IL-12) to enhance the capacity of human monocytes (MNC) to elicit an oxidative burst and damage hyphae of Aspergillus:fumigatus was investigated. Incubation of peripheral blood mononuclear cells (PBMC) from healthy adults with 10 to 100 ng of IL-12/ml at 37 degrees C for 2 to 3 days enhanced the production of superoxide anion (O-2(-)) in response to phorbol myristate acetate (PMA) (P = 0.04) and unopsonized A. fumigatus hyphae (P = 0.03) and further enhanced hyphal damage (P = 0.009). Anti-gamma interferon (anti-IFN-gamma) blocked secretion of IFN-gamma by IL-12-treated PBMC but did not inhibit IL-12-induced O-2(-) production by these cells in response to PMA. In addition, IL-12-treated elutriated MNC secreted no IFN-gamma or tumor necrosis factor alpha but exhibited enhanced O-2(-),- production compared to controls (P = 0.013). These findings demonstrate that IL-12 augments oxidative antifungal activities of MNC via an IFN-gamma-independent route, suggesting a novel pathway of IL-12 action in antifungal defense. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Thessaloniki, Dept Pediat 3, GR-54642 Salonika, Greece. Hippokration Hosp, GR-54642 Salonika, Greece. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 25 TC 29 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1999 VL 67 IS 6 BP 3047 EP 3050 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 199GX UT WOS:000080473600049 PM 10338518 ER PT J AU Tang, GQ Leppla, SH AF Tang, GQ Leppla, SH TI Proteasome activity is required for anthrax lethal toxin to kill macrophages SO INFECTION AND IMMUNITY LA English DT Article ID UBIQUITIN-DEPENDENT DEGRADATION; BACILLUS-ANTHRACIS; PROTEIN-DEGRADATION; THYMOCYTE APOPTOSIS; CELL-DEATH; C-JUN; PHOSPHORYLATION; KINASE; ACTIVATION; INHIBITORS AB Anthrax lethal toxin (LeTx), consisting of protective antigen (PA) and lethal factor (LF), rapidly kills primary mouse macrophages and macrophage-like cell lines such as RAW 264.7. LF is translocated by PA into the cytosol of target cells, where it acts as a metalloprotease to cleave mitogen-activated protein kinase kinase 1 (MEK1) and possibly other proteins. In this study, we show that proteasome inhibitors such as acetyl-Leu-Leu-norleucinal, MG132, and lactacystin efficiently block LeTx cytotoxicity, whereas other protease inhibitors do not. The inhibitor concentrations that block LF cytotoxicity are similar to those that inhibit the proteasome-dependent I kappa B-alpha degradation induced by lipopolysaccharide. The inhibitors did not interfere with the proteolytic cleavage of MEK1 in LeTx-treated cells, indicating that they do not directly block the proteolytic activity of LF. However, the proteasome inhibitors did prevent ATP depletion, an early effect of LeTx. No overall activation of the proteasome by LeTx was detected, as shown by the cleavage of fluorogenic substrates of the proteasome. All of these results suggest that the proteasome mediates a toxic process initiated by LF in the cell cytosol. This process probably involves degradation of unidentified molecules that are essential for macrophage homeostasis. Moreover, this proteasome-dependent process is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), Bldg 30,Room 316,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 81 Z9 83 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1999 VL 67 IS 6 BP 3055 EP 3060 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 199GX UT WOS:000080473600051 PM 10338520 ER PT J AU D'Amico, R Pinto, LA Meyer, P Landay, AL Harris, AA Clerici, M Berzofsky, JA Shearer, GM Kessler, HA AF D'Amico, R Pinto, LA Meyer, P Landay, AL Harris, AA Clerici, M Berzofsky, JA Shearer, GM Kessler, HA TI Effect of zidovudine postexposure prophylaxis on the development of HIV-specific cytotoxic T-lymphocyte responses in HIV-exposed healthcare workers SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CARE WORKERS; TRANSMISSION; TYPE-1 AB We evaluated the effects of zidovudine postexposure prophylaxis (PEP) on the development of human immunodeficiency virus (HIV) envelope-specific cytotoxic T-lymphocyte responses in 20 healthcare workers with occupational exposures to HIV. Seven healthcare workers were treated with zidovudine PEP. Only 1 of 7 treated, versus 6 of 13 not treated, developed an HN envelope-specific cytotoxic T-lymphocyte response. These data suggest that zidovudine abrogated HIV-specific cytotoxic T-lymphocyte responses. HIV-specific cytotoxic T-lymphocyte responses may be useful as a surrogate marker of HIV replication in the evaluation of new regimens for PEP of occupational HIV exposures (Infect Control Hosp Epidemiol 1999;20:428-430). C1 Rush Med Coll, Dept Med, Chicago, IL 60612 USA. Rush Med Coll, Dept Prevent Med, Chicago, IL 60612 USA. Rush Med Coll, Dept Immunol Microbiol, Chicago, IL 60612 USA. Natl Canc Inst, Natl Inst Hlth, Bethesda, MD USA. Univ Milan, Catteredra Immunol, Milan, Italy. RP Kessler, HA (reprint author), Rush Presbyterian St Lukes Med Ctr, Infect Dis Sect, 600 S Paulina,Ste 143 AAF, Chicago, IL 60612 USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 1999 VL 20 IS 6 BP 428 EP 430 DI 10.1086/501646 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 208LL UT WOS:000080992500012 PM 10395147 ER PT J AU Parent, C Eichacker, PQ AF Parent, C Eichacker, PQ TI Neutrophil and endothelial cell interactions in sepsis - The role of adhesion molecules SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE LUNG INJURY; TUMOR-NECROSIS-FACTOR; SOLUBLE E-SELECTIN; INFLAMMATORY RESPONSE SYNDROME; MURINE ENDOTOXIN-SHOCK; DISSEMINATED INTRAVASCULAR COAGULATION; RESPIRATORY-DISTRESS-SYNDROME; FUNCTION-ASSOCIATED ANTIGEN-1; AERUGINOSA-INDUCED PNEUMONIA; LEUKOCYTE INTEGRIN BETA(2) AB Although adhesion molecules present on circulating neutrophils and endothelial cells are essential for normal host defense, generalized activation of these molecules has been implicated in the inflammatory tissue injury occurring during sepsis and septic shack. A review of both preclinical and clinical studies suggests, however, that although these molecules mediate tissue injury related to a variety of microbial and host inflammatory mediators, their predominant role during sepsis with infection is a protective one. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC-1662, Bethesda, MD 20892 USA. NR 205 TC 67 Z9 70 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1999 VL 13 IS 2 BP 427 EP + DI 10.1016/S0891-5520(05)70084-2 PG 22 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 197WZ UT WOS:000080390500011 PM 10340176 ER PT J AU French, JE Spalding, JW Dunnick, JK Tice, RR Furedi-Machacek, M Tennant, RW AF French, JE Spalding, JW Dunnick, JK Tice, RR Furedi-Machacek, M Tennant, RW TI The use of transgenic animals in cancer testing SO INHALATION TOXICOLOGY LA English DT Article C1 NIEHS, Res Triangle Pk, NC 27709 USA. Integrated Syst Lab, Res Triangle Pk, NC USA. RP French, JE (reprint author), NIEHS, MD-F1-05,POB 12233, Res Triangle Pk, NC 27709 USA. NR 2 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD JUN-JUL PY 1999 VL 11 IS 6-7 BP 541 EP 544 PG 4 WC Toxicology SC Toxicology GA 212UX UT WOS:000081236900007 PM 11202994 ER PT J AU Barreau, C Conrad, J Fischer, E Lujan, HD Vernick, KD AF Barreau, C Conrad, J Fischer, E Lujan, HD Vernick, KD TI Identification of surface molecules on salivary glands of the mosquito, Aedes aegypti, by a panel of monoclonal antibodies SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE insect vectors; malaria; salivary glands; basal lamina; sporozoites; monoclonal antibodies; Plasmodium gallinaceum ID ELECTRON-MICROSCOPE; MALARIA SPOROZOITES; VECTOR MOSQUITO; GENE AB Malaria transmission by the mosquito vector requires sporozoite invasion into mosquito salivary glands. Parasites probably enter the glands by specific receptor-ligand interactions with molecules on the surface of the glands. We have undertaken the characterization of salivary gland surface molecules of Aedes aegypti to identify candidate receptors for Plasmodium gallinaceum sporozoite invasion. Monoclonal antibodies (mAbs) were generated against antigen enriched for salivary gland membranes and basal lamina. A panel of 44 mAbs were generated that bound to surface molecules of mosquito tissues. Twenty-four mAbs bound exclusively to salivary glands, six bound to salivary glands and ovaries, one bound to salivary gland and midgut, and 13 bound to all tissues tested. We present data on the immunolocalization and biochemical characteristics of the antigens. Many of the salivary gland-specific mAbs bound preferentially to the median and distal lateral lobes of the salivary glands, indicating that there are anatomical region-specific biochemical differences on the gland surface. These lobes of the salivary glands are the preferential sites of malaria sporozoite invasion. Therefore, antigens specific for these regions are promising candidate receptors for sporozoite invasion. The present identification of surface molecules of mosquito salivary glands by means of monoclonal antibodies represents the first description of individual molecules on the mosquito salivary gland surface. This work lays the basis for further studies on the molecular mechanisms involved in malaria sporozoite invasion of mosquito salivary glands. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NYU, Sch Med, Dept Med & Mol Parasitol, New York, NY 10010 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Rocky Mt Lab, Hamilton, MT 59840 USA. RP Vernick, KD (reprint author), NYU, Sch Med, Dept Med & Mol Parasitol, 341 E 25th St, New York, NY 10010 USA. FU NIAID NIH HHS [AI-42361] NR 22 TC 17 Z9 20 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JUN PY 1999 VL 29 IS 6 BP 515 EP 526 DI 10.1016/S0965-1748(99)00025-9 PG 12 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 212WT UT WOS:000081241200003 PM 10406090 ER PT J AU Yoshimura, T Takeya, M Ogata, H Yamashiro, S Modi, WS Gillitzer, R AF Yoshimura, T Takeya, M Ogata, H Yamashiro, S Modi, WS Gillitzer, R TI Molecular cloning of the guinea pig GRO gene and its rapid expression in the tissues of lipopolysaccharide-injected guinea pigs SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE chemokine; cytokine; inflammation; neutrophil infiltration ID AMINO-ACID-SEQUENCE; NF-KAPPA-B; STIMULATORY ACTIVITY; HUMAN MONOCYTES; RABBIT GRO; ALPHA GENE; IN-VIVO; INTERLEUKIN-8; TRANSCRIPTION; CYTOKINES AB Background: CXC chemokines, IL-8 and GRO, play a role in the recruitment of neutrophils in the human. The functional orthologues in the rat and mouse are CINC/KC and MIP-2. The lack of IL-8 made these animals less useful to study the role of IL-8 and GRO. methods: Guinea pig (gp) cDNA libraries were screened for GRO and IL-1 beta. A gp-genomic library was screened with a gpGRO cDNA probe. Expression of gpIL-8, gpGRO, gpTNF alpha, and gpIL-1 beta was investigated by Northern analysis and/or by in situ hybridization. Results:Two gpGRO cDNAs, a 3.0-kb gpGRO genomic DNA, and a gpIL-1 beta cDNA were cloned, gpGRO and gpIL-8 mRNA were detected in different tissues including lungs 1 h after intraperitoneal injection of lipopolysaccharide (LPS) into guinea pigs, gpGRO, gpIL-8, gpTNF alpha, and gpIL-1 beta expression peaked at 3 h in the lungs. Both gpGRO and gpIL-8 mRNA were detected in the cells in alveolar spaces and bronchial epithelial cells. However, gpGRO mRNA, but not gplL-8, was also expressed in endothelial cells and vascular smooth muscle cells. Conclusions: gpGRO and gpIL-8 mRNA rapidly accumulated in the lungs of guinea pigs after LPS injection. Expression of gpIL-8 and gpGRO mRNA appeared to be independent from TNF alpha- or IL-1 beta-stimulation in this model. A high level expression of gpGRO in vascular cells suggest an important role of GRO in the sequestration of neutrophils and multi-organ injuries induced by LPS. The guinea pig will provide an excellent model to study the roles of IL-8 and GRO, important inflammatory mediators in the human. C1 NCI, Immunobiol Lab, Immunopathol Sect, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 860, Japan. Univ Wurzburg, Sch Med, Dept Dermatol, Wurzburg, Germany. RP Yoshimura, T (reprint author), NCI, Immunobiol Lab, Immunopathol Sect, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 12-71, Frederick, MD 21702 USA. NR 40 TC 12 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD JUN PY 1999 VL 119 IS 2 BP 101 EP 111 DI 10.1159/000024184 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 214EK UT WOS:000081315300004 PM 10394101 ER PT J AU Zhang, WG Irvin, BJ Trible, RP Abraham, RT Samelson, LE AF Zhang, WG Irvin, BJ Trible, RP Abraham, RT Samelson, LE TI Functional analysis of LAT in TCR-mediated signaling pathways using a LAT-deficient Jurkat cell line SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE LAT; TCR; tyrosine phosphorylation; palmitoylation ID ANTIGEN-RECEPTOR; MEMBRANE DOMAINS; TYROSINE KINASE; ACTIVATION; TRANSDUCTION; PROTEINS; PALMITOYLATION; PLC-GAMMA-1; STIMULATION; LCK AB The adaptor molecule LAT (linker for activation of I cells) is a palmitoylated integral membrane protein that localizes to the glycolipid-enriched microdomains in the plasma membrane. Upon TCR engagement, LAT becomes phosphorylated on multiple tyrosine residues and then binds several critical signaling molecules. Here, we describe the generation and characterization of a LAT-deficient cell line, Using this cell line, we demonstrate that LAT is required for TCR-mediated Ca2+ mobilization and optimal tyrosine phosphorylation of phospholipase C-gamma 1,Vav and SLP-76, LAT is also required for Erk activation, CD69 up-regulation, and AP- and NFAT-mediated gene transcription. We also demonstrate, by reconstituting this cell line with LAT mutants, that the LAT transmembrane domain and palmitoylation at Cys26, but not Cys29, are required for LAT function and TCR signaling. These studies provide further evidence for the crucial role of the LAT molecule, and demonstrate the use of a LAT-deficient cell line for the analysis of LAT structure and function. C1 NICHHD, Cell Biol & Metab Branch, Sect Lymphocyte Signaling, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. RP Samelson, LE (reprint author), NICHHD, Cell Biol & Metab Branch, Sect Lymphocyte Signaling, NIH, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM47286] NR 23 TC 206 Z9 210 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1999 VL 11 IS 6 BP 943 EP 950 DI 10.1093/intimm/11.6.943 PG 8 WC Immunology SC Immunology GA 210FL UT WOS:000081094400010 PM 10360968 ER PT J AU Schmitz, S Fulker, DW Plomin, R Zahn-Waxler, C Emde, RN DeFries, JC AF Schmitz, S Fulker, DW Plomin, R Zahn-Waxler, C Emde, RN DeFries, JC TI Temperament and problem behaviour during early childhood SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article; Proceedings Paper CT 8th International Twin Congress CY MAY, 1995 CL RICHMOND, VIRGINIA ID INFANT TEMPERAMENT; PARENTAL RATINGS; MIDDLE CHILDHOOD; SEX-DIFFERENCES; SCHOOL AGE; FOLLOW-UP; CHILDREN; PREDICTORS; PRESCHOOLERS; PERSONALITY AB Some evidence exists for the phenotypic association of problem behaviour in early childhood with temperament in infancy, but little is known about the genetic and environmental mechanisms mediating this association. At the ages of 14, 20, 24, and 36 months, mothers of twins completed the Colorado Childhood Temperament Inventory (CCTI; Buss & Plomin, 1984; Rowe & Plomin, 1977). At age 4, problem behaviour was assessed using maternal reports on the Child Behavior Checklist (CBCL/4-18; Achenbach, 1991). The temperamental trait of Emotionality at all four prior age points correlated significantly with the CBCL Total Problem Score at 4 years as well as with the broad-band groupings of Internalising the Externalising. In addition, Shyness at all four ages correlated significantly with the broad-band grouping of Internalising. Longitudinal behavioural genetic analyses indicated that these phenotypic predictions from early temperament to later behaviour problems are largely due to genetic factor. C1 Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Inst Psychiat, London, England. NIMH, Bethesda, MD 20892 USA. RP Schmitz, S (reprint author), Univ Colorado, Inst Behav Genet, Campus Box 447, Boulder, CO 80309 USA. RI Plomin, Robert/B-8911-2008; OI Plomin, Robert/0000-0002-0756-3629 NR 52 TC 44 Z9 45 U1 4 U2 11 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD JUN PY 1999 VL 23 IS 2 BP 333 EP 355 PG 23 WC Psychology, Developmental SC Psychology GA 208CN UT WOS:000080972800004 ER PT J AU Byrne, G Suomi, SJ AF Byrne, G Suomi, SJ TI Social separation in infant Cebus apella: Patterns of behavioral and cortisol response SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article ID SQUIRREL-MONKEYS; RHESUS-MONKEYS; MOTHER; BIRTH AB 34 infant tufted capuchins (Cebus apella) were separated from their social groups for a 2-hour period and videotaped in isolation at the ages of 6 months and 1 year. Baseline and 2-hour blood samples were measured for levels of serum cortisol. Compared to homecage baseline levels, passivity, locomotion and vocalizations increased during separation, while self-directed behavior and environmental exploration decreased. Both behavioral and cortisol responses to separation showed individual stability over the 6 month period, although both responses were somewhat attenuated at the later age. There was little correlation between cortisol and behavior during separations Females vocalized more than did males during separations and showed greater cortisol increases at 6 months of age. The pattern of behavioral response seen in the 2 hours following separation appeared to be more passive than the typical 'protest' response described in many nonhuman primates, and may reflect either the physical circumstances of the separation or a characteristic of species with relaxed social bonds and considerable allomothering available to infants. Published by Elsevier Science Ltd. C1 NICHD, Comparat Ethol Lab, Anim Ctr, NIH, Poolesville, MD 20837 USA. RP Byrne, G (reprint author), NICHD, Comparat Ethol Lab, Anim Ctr, NIH, POB 529, Poolesville, MD 20837 USA. NR 24 TC 15 Z9 15 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUN PY 1999 VL 17 IS 3 BP 265 EP 274 DI 10.1016/S0736-5748(99)00015-5 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 222PF UT WOS:000081793400011 PM 10452369 ER PT J AU Wollman, SH AF Wollman, SH TI Histological changes in TSH-dependent tumours of the thyroid gland during serial transplantation in Fischer 344 rats SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Article DE thyroid tumour transplant; histology; growth tumour nodules; cell immortalization ID GROWTH; HYPERPLASIA; ORIGIN AB Transplantable tumours were induced in the thyroids of Fischer 344 rats fed thiouracil (TU) in a moderately low iodine diet for 8-13 months. Pieces of hyperplastic thyroid were implanted subcutaneously into rats fed a TU containing diet. Almost all implants gave rise to very small vascularized transplants but there were three significantly larger, pieces of which were transplanted again and gave rise to the tumour lines. From the third transplantation generation on, pieces of tumours were implanted into rats treated to have elevated circulating thyrotropin and a group fed a high iodine diet. With some exceptions, the implants grew only in rats fed the TU or a low iodine diet and yielded TSH-dependent tumours. Almost all the tumours observed initially were papillary, and most of the remainder had colloid-filled follicles bounded by columnar cells. One line of tumours was of the latter type for eight generations. The others had more complex histories, in which there were sublines that were papillary for eight or nine generations, whereas, others became progressively more cellular or follicular, and more heterogenous with respect to histological types present per section at rates that varied with the subline. The large number of population doublings necessary to make a one gram tumour from a single original tumour cell indicates that the cells of dependent papillary tumours were immortalized. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Wollman, SH (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 1E20,37 CONVENT DR,MSC 4255, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD JUN PY 1999 VL 80 IS 3 BP 151 EP 167 DI 10.1046/j.1365-2613.1999.00109.x PG 17 WC Pathology SC Pathology GA 219WM UT WOS:000081631100006 PM 10469271 ER PT J AU Reitman, ML He, Y Gong, DW AF Reitman, ML He, Y Gong, DW TI Thyroid hormone and other regulators of uncoupling proteins SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT Symposium on Uncoupling Proteins and Obesity CY NOV 20-21, 1998 CL QUEBEC CITY, CANADA DE thyroid hormone; free fatty acids ID BROWN ADIPOSE-TISSUE; MESSENGER-RNA EXPRESSION; THERMOGENESIS; GENE; FAT; RECEPTOR; RAT; CLONING; MITOCHONDRIA; MEDIATOR AB The role of the thyroid gland in the regulation of metabolic rate has been known since the last century. The knowledge that thyroid hormones increase energy expenditure, in part by lowering metabolic efficiency, dates from the 1950s. Presumably thyroid hormones regulate energy expenditure and efficiency by controlling the rate of transcription of specific genes. However, the number, identity, and relative contributions of these genes are not known. The uncoupling proteins (UCPs) are obvious candidates to mediate thyroid thermogenesis. UCP1 is not a major contributor, since thyrotoxicosis decreases UCP1 expression and inactivates brown fat. Discovery of UCP3 and its regulation by T3 in muscle is an exciting observation, consistent with a role for UCP3 in thyroid thermogenesis. Since free fatty acids appear to regulate UCP3 expression and T3 stimulates lipolysis, further experiments are required to determine if T3 regulation of UCP3 expression is direct or not. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Reitman, ML (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10 Room 8N-250,10 Ctr Dr,MSC 1770, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 36 TC 24 Z9 25 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 1999 VL 23 SU 6 BP S56 EP S59 DI 10.1038/sj.ijo.0800948 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 215NP UT WOS:000081388000015 PM 10454126 ER PT J AU Wang, M Liu, A Garcia, FU Rhim, JS Stearns, ME AF Wang, M Liu, A Garcia, FU Rhim, JS Stearns, ME TI Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE IL-10; follistatin; activin-A; prostatic intraepithelial neoplasia; prostate-specific antigen; dihydrotestosterone; basal cell keratin ID SEMIAUTOMATED COLORIMETRIC ASSAY; FACTOR RECEPTOR; EPITHELIAL-CELLS; FACTOR-BETA; CANCER; PROTEIN; BENIGN; LOCALIZATION; ADENOCARCINOMA; EXPRESSION AB Cultures from high grade prostatic intraepithelial neoplasia (HGPIN) have been established and immortalized by HPV-18 infection. The cultures were identified as PIN by Western blotting with anti-cytokeratin (34 beta E12) and prostate specific antigen (PSA) antibodies. We examined the growth capabilities of the cultures in the presence of TGF-beta 1, activin-A, follistatin (FS), androgens (DHEA, DHT) and several cytokines (IL-10, IL-2, IL-4). IL-10, FS, and DHT stimulated cell proliferation and colony forming ability, while the other cytokines and growth factors had no discernable effect. In addition, DHT and to a lesser extent IL-10 both stimulated PSA production. Activin-A blocked IL-10, FS, and DHT stimulated growth and PSA production. We interpret the data to mean that IL-IO induction of FS secretion (and FS binding of activin A) restores the normal growth capabilities of HGPIN cultures. C1 MCP Hahnemann Univ, Dept Pathol & Lab Med, Philadelphia, PA 19102 USA. NCI, NIH, Frederick, MD 21701 USA. RP Stearns, ME (reprint author), MCP Hahnemann Univ, Dept Pathol & Lab Med, Broad & Vine St, Philadelphia, PA 19102 USA. NR 46 TC 17 Z9 18 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 1999 VL 14 IS 6 BP 1185 EP 1195 PG 11 WC Oncology SC Oncology GA 199UC UT WOS:000080500900025 PM 10339677 ER PT J AU Cvekl, A Kasanchi, F Brady, JN Piatigorsky, J AF Cvekl, A Kasanchi, F Brady, JN Piatigorsky, J TI Pax-6 interactions with TATA-box-binding protein and retinoblastoma protein SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CELL-CYCLE REGULATION; A-CRYSTALLIN GENE; TRANSCRIPTION FACTOR; ACTIVATION DOMAINS; TRANSGENIC MICE; ZETA-CRYSTALLIN; CHIMERIC MICE; KAPPA-B; LENS; MUTATIONS AB PURPOSE. TO identify proteins that physically interact with Pax-G, a paired domain- and homeodomain (HD)-containing transcription factor that is a key regulator of eye development. METHODS. Protein-protein interactions involving Pax-6, TATA-box-binding protein (TPB), and retinoblastoma protein were studied using affinity chromatography with Pax-G as Ligand, glutathione-S-transferase (GST) pull-down assays, and immunoprecipitations. RESULTS. The authors have shown that Pax-G is a sequence-specific activator of many crystallin genes, all containing a TATA box, in the lens. Others have shown that lens fiber cell differentiation, characterized by temporally and spatially regulated crystallin gene expression, depends on retinoblastoma protein. In the present study it was shown that Pax-6 interacted with the TBP, the DNA-binding subunit of general transcription complex TFIID. GST pull-down assays indicated that this interaction was mediated by the Pax-G HD, with a substantial role for its N-terminal arm and first two alpha-helices. The experiments also indicated a binding role for the C-terminal-activation domain of the protein. In addition, the present study showed that the HD of Pax-G interacted with retinoblastoma protein. Immunoprecipitation experiments confirmed retinoblastoma protein/Pax-6 complexes in lens nuclear extracts. CONCLUSIONS. Blending the present results with those in the literature suggests that Pax-6 and retinoblastoma protein participate in overlapping regulatory pathways controlling epithelial cell division, fiber cell elongation, and crystallin gene expression during lens development. C1 NCI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NCI, Mol Virol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NCI, Mol & Dev Biol Lab, 6 Ctr Dr,Bldg 6,Room 201, Bethesda, MD 20892 USA. RI Cvekl, Ales/B-2427-2013 NR 63 TC 41 Z9 41 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1999 VL 40 IS 7 BP 1343 EP 1350 PG 8 WC Ophthalmology SC Ophthalmology GA 200GU UT WOS:000080531900005 PM 10359315 ER PT J AU Tamm, ER Russell, P Piatigorsky, J AF Tamm, ER Russell, P Piatigorsky, J TI Development and characterization of an immortal and differentiated murine trabecular meshwork cell line SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID H-2K(B)TSA58 TRANSGENIC MOUSE; HUMAN OUTFLOW SYSTEM; OPEN-ANGLE GLAUCOMA; ALPHA-B-CRYSTALLIN; SMOOTH-MUSCLE; CILIARY MUSCLE; CULTURED HUMAN; HUMAN-EYE; HUMAN-FIBROBLASTS; TISSUE-CULTURE AB PURPOSE. TO Study mouse trabecular meshwork (TM) and to develop a murine TM cell line. METHODS. Mouse TM in situ was studied by light and electron microscopy (EM). In addition, TM was isolated from the H-2K(b)-tsA58 transgenic mouse strain in which promoter sequences of the major histocompatibility complex H-2K(b) class 1 gene are fused to sequences of the SV40 mutant temperature-sensitive (ts) strain tsA58. The promoter is inducible by interferon (IFN)-gamma, and the tsA58 gene product is active at 33 degrees C (permissive conditions), but not at 37 degrees C (nonpermissive conditions). The TM explant was cultured in permissive conditions. Outgrowing cells were passaged through two rounds of single-cell cloning. One clonal cell line (MUTM-NEI/1) was characterized in nonpermissive conditions by EM, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and northern blot hybridization. In addition, MUTM-NEI/1 cells were transfected With plasmid DNA. RESULTS. The mouse eye has a circumferentially oriented outflow vessel and a IM that is subdivided in an outer juxtacanalicular or cribriform part and an inner lamellated or trabecular part. From the TM of the H-2K(b)-tsA58 mouse, a clonal cell line (MUTM-NEI/1) was established. In permissive conditions, MUTM-NEI/1 cells remained proliferative through at least 80 generations without change in phenotype. In nonpermissive conditions, proliferation was slower, and MUTM-NEI/1 cells differentiated and synthesized collagen types I, III, TV, and VT; laminin; and fibronectin. MUTM-NEI/1 cells were immunoreactive for vimentin, alpha B-crystallin, and neural cell adhesion molecule (NCAM), but not for desmin or cytokeratin. Less than 10% of MUTM-NEI/1 cells stained for cu-smooth muscle actin, whereas after 3 days of treatment with transforming growth factor-beta(1) almost all cells were positive. MUTM-NEI/1 cells expressed mRNA for NCAM, aquaporin 1, myocilin/trabecular meshwork glucocorticoid-inducible protein, and alpha B-crystallin, which was increased after oxidative stress. MUTM-NEI/1 cells could be successfully transfected with plasmid DNA. CONCLUSIONS. The architecture of the murine outflow system is comparable to that in primates. The MUTM-NEI/1 cell line is a clonal, immortal, and differentiated TM cell line that will be an important tool for study of the expression of TM genes. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Tamm, ER (reprint author), Univ Erlangen Nurnberg, Dept Anat 2, Univ Str 19, D-91054 Erlangen, Germany. NR 70 TC 34 Z9 34 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1999 VL 40 IS 7 BP 1392 EP 1403 PG 12 WC Ophthalmology SC Ophthalmology GA 200GU UT WOS:000080531900011 PM 10359321 ER PT J AU Lederer, SE AF Lederer, SE TI Frankenstein's footsteps: Science, genetics, and popular culture. SO ISIS LA English DT Book Review C1 Penn State Univ, Coll Med, Dept Humanities, University Pk, PA 16802 USA. RP Lederer, SE (reprint author), Natl Lib Med, Bethesda, MD 20209 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0021-1753 J9 ISIS JI Isis PD JUN PY 1999 VL 90 IS 2 BP 375 EP 376 DI 10.1086/384370 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA 219HH UT WOS:000081601500053 ER PT J AU Tosti, ME Traversa, G Bianco, E Mele, A AF Tosti, ME Traversa, G Bianco, E Mele, A TI Multiple sclerosis and vaccination against hepatitis B: analysis of risk benefit profile SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE hepatitis B vaccination; immunisation/adverse effects; multiple sclerosis; risk benefit profile ID IMMUNOGENICITY; EFFICACY AB Background. Since 1994, the hypothesis of a potential Introduction causal relationship between vaccination against hepatitis B and multiple sclerosis (and other demyelinating diseases) was brought to the attention of the French health authority and to public debate. In Italy, since 1991, vaccination against hepatitis B has been mandatory for newborns and 12-year-old children, and also recommended for high-risk groups. Aim. To re-evaluate the risk/benefit profile of the Italian strategy of hepatitis B vaccination. Subjects, The study population is a hypothetical cohort of 100,000 newborns, Methods, We present a simulation of the hepatitis B cases that could be prevented with the vaccination and of the potential excess of multiple sclerosis cases which would occur; assuming different adds ratios of multiple sclerosis among vaccinees, and by effecting the vaccination at different ages. Results. In the cohort, we would expect 1099 hepatitis B cases. that could be prevented,vith vaccination. Assuming that the highest odds ratio of 1.7 reported is true, the excess of "life-time" multiple sclerosis incidence would be 0.3% for 12-year-old subjects, and 2.9% for adults. Conclusions, On the basis of these data, our opinion is that the hepatitis B vaccination strategy presently adopted in Italy for newborns, teen-agers and high risk groups should not be modified. C1 Univ Rome Tor Vergata, Sch Hyg, Rome, Italy. NIH, Lab Epidemiol, Bethesda, MD 20892 USA. RP Mele, A (reprint author), Epidemiol & Biostat Lab, Viale Regina Elena 299, I-00161 Rome, Italy. OI Tosti, Maria Elena/0000-0003-1392-9874 NR 8 TC 10 Z9 11 U1 0 U2 1 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 1125-8055 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD JUN-JUL PY 1999 VL 31 IS 5 BP 388 EP 391 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 222UE UT WOS:000081803000009 PM 10470598 ER PT J AU Ogawa, K Tsuda, H Shirai, T Ogiso, T Wakabayashi, K Dalgard, DW Thorgeirsson, UP Thorgeirsson, SS Adamson, RH Sugimura, T AF Ogawa, K Tsuda, H Shirai, T Ogiso, T Wakabayashi, K Dalgard, DW Thorgeirsson, UP Thorgeirsson, SS Adamson, RH Sugimura, T TI Lack of carcinogenicity of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in cynomolgus monkeys SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE heterocyclic amines; MeIQx; cynomolgus monkey; carcinogenicity ID FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; HETEROCYCLIC AROMATIC-AMINES; NONHUMAN-PRIMATES; BIOASSAY SYSTEM; CHEMICAL CARCINOGENESIS; BROILED SARDINE; CYP1A2 ACTIVITY; HUMAN TISSUES; COOKED FOODS; BEEF EXTRACT AB The carcinogenic potential of 2-amino-3,8-dimethylimidazo[ 4,5-f]quinoxaline (MeIQx) was evaluated in cynomolgus monkeys, The animals received MeIQx, beginning at the age of one year, at doses of 10 or 20 mg/kg body weight by gavage five times a week for 84 months and were autopsied 8 months thereafter. Although sporadic development of aberrant crypt foci in the colon and glutathione S-transferase pi-positive foci in the liver as well as hyperplastic changes of the lymphatic tissue in the lung and gastro-intestinal tract were observed in several monkeys, this was not treatment-related. No neoplastic or preneoplastic lesions were found in other organs. Serum chemistry data and organ weights were also within the normal ranges. From these data, it is concluded that MeIQx is not carcinogenic in the cynomolgus monkey under the conditions examined, This lack of carcinogenicity is probably related to the poor activation of MeIQs due to the lack of constitutive expression of CYP1A2 as well as an inability of other cytochrome P450s to catalyze,N-hydrosylation of MeIQs in the cynomolgus monkey. C1 Nagoya City Univ, Sch Med, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Nagoyashi Kohseiin Geriat Hosp, Meito Ku, Nagoya, Aichi 4650055, Japan. Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 1040045, Japan. Covance Labs Amer, Vienna, VA 22182 USA. NCI, Bethesda, MD 20892 USA. RP Ogawa, K (reprint author), Nagoya City Univ, Sch Med, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan. NR 31 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD JUN PY 1999 VL 90 IS 6 BP 622 EP 628 PG 7 WC Oncology SC Oncology GA 210HK UT WOS:000081098900006 PM 10429653 ER PT J AU Dell'Osso, LF Hertle, RW Williams, RW Jacobs, JB AF Dell'Osso, LF Hertle, RW Williams, RW Jacobs, JB TI A new surgery for congenital nystagmus: Effects of tenotomy on an achiasmatic canine and the role of extraocular proprioception SO JOURNAL OF AAPOS LA English DT Article ID RECTUS MUSCLE RECESSIONS; SEE-SAW NYSTAGMUS; AFFERENT SIGNALS; SPATIAL LOCALIZATION; FOVEATION DYNAMICS; ACQUIRED NYSTAGMUS; SMOOTH-PURSUIT; CAT; NUCLEUS; PIGEON AB Purpose:Human eye-movement recordings have documented that surgical treatment of congenital nystagmus (CN) also produces a broadening of the null zone and changes in foveation that allow increased acuity. We used the achiasmatic Belgian sheepdog, a spontaneously occurring animal model of human CN and see-saw nystagmus (SSN), to test the hypothesis that changes induced by surgical interruption of the extraocular muscle afference without a change in muscle-length tension could damp both oscillations. Methods:An achiasmatic dog with CN and SSN underwent videotaping and infrared oculography in a sling apparatus and head restraints before and after all extraocular muscles (stage 1: 4 horizontal rectus muscles and stage 2 [4 months later]: 4 vertical rectus muscles and 4 oblique muscles) were surgically tenotomized and immediately reattached at their original insertions. Results: The dog had immediate and persistent visible, behavioral, and oculographic changes after each stage of this new procedure. These included damped CN and SSN, increased ability to maintain fixation, and increased periods of maintaining the target image on the area centralis over a broad range of gaze angles. Conclusions: Severing and reattaching the tendons of the extraocular muscles affect some as-yet-unknown combination of central nervous system processes producing the above results. This new procedure may prove effective in patients with CN with either no null, a null at primary position, or a time-varying null (due to asymmetric, (a)periodic, alternating nystagmus). We infer from our results in an achiasmatic dog that tenotomy is the probable cause of the damping documented in human CN after Anderson-Kestenbaum procedures and should also damp CN and SSN in achiasma in humans. It may also prove useful in acquired nystagmus to reduce oscillopsia. The success of tenotomy in damping nystagmus in this animal suggests that the proprioceptive feedback loop has a more important role in ocular-motor control than has been appreciated. Finally, we propose a modified bimedial recession procedure, on the basis of the damping effects of tenotomy. C1 Vet Affairs Med Ctr 127A, Ocular Motor Neurophysiol Lab, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN 38163 USA. RP Dell'Osso, LF (reprint author), Vet Affairs Med Ctr 127A, Ocular Motor Neurophysiol Lab, 10701 E Blvd, Cleveland, OH 44106 USA. OI Williams, Robert/0000-0001-8924-4447 FU PHS HHS [R01-6627] NR 67 TC 62 Z9 68 U1 1 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD JUN PY 1999 VL 3 IS 3 BP 166 EP 182 DI 10.1016/S1091-8531(99)70063-7 PG 17 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 207AT UT WOS:000080913700007 PM 10428591 ER PT J AU Sher, L Goldman, D Ozaki, N Rosenthal, NE AF Sher, L Goldman, D Ozaki, N Rosenthal, NE TI The role of genetic factors in the etiology of seasonal affective disorder and seasonality SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE seasonal affective disorder; seasonality; depression; genetics ID SEROTONIN TRANSPORTER GENE; META-CHLOROPHENYLPIPERAZINE; FUNCTIONAL POLYMORPHISM; BEHAVIORAL-RESPONSES; WINTER DEPRESSION; BIPOLAR DISORDER; PREVALENCE; PROMOTER; LIGHT; MOOD AB The study of the genetic basis of seasonal affective disorder (SAD), a condition where depressions in fall and winter alternate with nondepressed periods in the spring and summer, has recently received attention. The data on the genetics of seasonal affective disorders are of three types: 1. Familiality: Studies on the prevalence of psychiatric disorders among relatives of patients with SAD suggested a familial contribution to the development of SAD; 2. Heritability: A survey of a cohort of twins showed that genetic effects exert a global influence across a variety of behavioral traits and accounted for at least 29% of the variance in seasonality in men and women; 3. Molecular genetic research: two genetic variants related to serotonergic transmission, the 5-HTTLPR and the 5-HT2A-1438G/A gene promoter polymorphisms, are associated with SAD; the former but not the latter polymorphism is related to seasonality Future research may clarify the role of different genes in the development of SAD. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. RP Sher, L (reprint author), NIMH, Clin Psychobiol Branch, 10 Ctr Dr,Bldg 10,Room 3S-231, Bethesda, MD 20892 USA. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 50 TC 45 Z9 46 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN PY 1999 VL 53 IS 3 BP 203 EP 210 DI 10.1016/S0165-0327(98)00194-3 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 208RY UT WOS:000081006500001 PM 10404705 ER PT J AU Dastych, J Walczak-Drzewiecka, A Wyczolkowska, J Metcalfe, DD AF Dastych, J Walczak-Drzewiecka, A Wyczolkowska, J Metcalfe, DD TI Murine mast cells exposed to mercuric chloride release granule-associated N-acetyl-beta-D-hexosaminidase and secrete IL-4 and TNF-alpha SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE mast cell; mercuric chloride; IL-4; TNF-alpha ID FC-EPSILON-RI; TUMOR-NECROSIS-FACTOR; BROWN-NORWAY RAT; T-CELLS; TYROSINE PHOSPHORYLATION; AMALGAM FILLINGS; DENTAL AMALGAM; IGE ANTIBODY; INTERLEUKIN-4; CHILDREN AB Background: Mast cells, by virtue of their location within the skin, respiratory tract, and gastrointestinal system, are considered as potential targets for environmental agents with immunotoxic effects, Mercuric chloride (HgCl2), is a xenobiotic, which induces autoimmune glomerulonephritis and stimulates polyclonal IgE production. Objective: We sought to determine the ability of HgCl2 to degranulate murine mast cells and promote cytokine secretion and whether this was an active biologic process. Methods: Bone marrow-derived murine mast cells were exposed to HgCl2, and the release of N-acetyl-beta-D-hexosaminidase and secretion of IL-4 and TNF-alpha were measured. Results: HgCl2 was found to directly activate murine mast cells to release the granule-associated enzyme N-acetyl-beta-D-hexosaminidase and to secrete the proinflammatory cytokines IL-4 and TNF-alpha. Cytokine secretion occurred hours after exposure to HgCl2 and required transcription and protein synthesis. The secretion of cytokines mediated by HgCl2 was additive to that which followed Fc epsilon RI-induced mast cell activation. The IL-4 secretion by mast cells occurred at concentrations of HgCl2 (10(-6) mol/L to 10(-5) mol/L) comparable with those required to induce upregulation of IgE production in experimental animals. Conclusion: These findings demonstrate that HgCl2 will directly activate mast cells, which is followed by degranulation and IL-4 and TNF-alpha synthesis and secretion. These findings are consistent with recognition of HgCl2 as a biologically important environmentally derived immunotoxic agent for mast cells. C1 Polish Acad Sci, Dept Biogen Amines, PL-90950 Lodz, Poland. NIAID, Lab Allerg Dis, NIH, Bethesda, MD USA. RP Dastych, J (reprint author), Polish Acad Sci, Dept Biogen Amines, POB 225, PL-90950 Lodz, Poland. NR 26 TC 27 Z9 29 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1999 VL 103 IS 6 BP 1108 EP 1114 DI 10.1016/S0091-6749(99)70186-7 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 207GT UT WOS:000080929500020 PM 10359893 ER PT J AU Tangsinmankong, N Day, NK Nelson, RP Puck, J Good, RA AF Tangsinmankong, N Day, NK Nelson, RP Puck, J Good, RA TI Severe combined immunodeficiency in an infant with multiple congenital abnormalities SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article C1 Univ S Florida, All Childrens Hosp, Dept Allergy Immunol, St Petersburg, FL 33701 USA. Natl Human Genome Res Inst, Bethesda, MD USA. RP Tangsinmankong, N (reprint author), Univ S Florida, All Childrens Hosp, Dept Allergy Immunol, 801 6th St S, St Petersburg, FL 33701 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1999 VL 103 IS 6 BP 1222 EP 1223 DI 10.1016/S0091-6749(99)70207-1 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 207GT UT WOS:000080929500041 PM 10359914 ER PT J AU Roth, SM Martel, GF Ivey, FM Lemmer, JT Tracy, BL Hurlbut, DE Metter, EJ Hurley, BF Rogers, MA AF Roth, SM Martel, GF Ivey, FM Lemmer, JT Tracy, BL Hurlbut, DE Metter, EJ Hurley, BF Rogers, MA TI Ultrastructural muscle damage in young vs. older men after high-volume, heavy-resistance strength training SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE aging; muscle fiber hyper-contraction; muscle injury; regeneration; resistance training ID HUMAN SKELETAL-MUSCLE; ECCENTRIC EXERCISE; HYPERTROPHY; CONTRACTION; DISRUPTION; RECOVERY; INJURY; PEOPLE; MICE; RATS AB This study assessed ultrastructural muscle damage in young (20-30 yr old) vs. older (65-75 yr old) men after heavy-resistance strength training (HRST). Seven young and eight older subjects completed 9 wk of unilateral leg extension HRST. Five sets of 5-20 repetitions were performed 3 days/wk with variable resistance designed to subject the muscle to near-maximal loads during every repetition. Biopsies were taken from the vastus lateralis of both legs, and muscle damage was quantified via electron microscopy. Training resulted in a 27% strength increase in both groups (P < 0.05). In biopsies before training in the trained leg and in all biopsies from untrained leg, 0-3% of muscle fibers exhibited muscle damage in both groups (P = not significant). After HRST, 7 and 6% of fibers in the trained leg exhibited damage in the young and older men, respectively (P < 0.05, no significant group differences). Myofibrillar damage was primarily focal, confined to one to two sarcomeres. Young and older men appear to exhibit similar levels of muscle damage at baseline and after chronic HRST. C1 Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD 20742 USA. Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD 21853 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Rogers, MA (reprint author), Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD 20742 USA. OI Roth, Stephen/0000-0002-7841-3695 FU NIA NIH HHS [1AG-42148] NR 29 TC 54 Z9 55 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 1999 VL 86 IS 6 BP 1833 EP 1840 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 204TV UT WOS:000080781400018 PM 10368346 ER PT J AU Maclaren, N Lan, M Coutant, R Schatz, D Silverstein, J Muir, A Clare-Salzer, M She, JX Malone, J Crockett, S Schwartz, S Quattrin, T DeSilva, M Vander Vegt, P Notkins, A Krischer, J AF Maclaren, N Lan, M Coutant, R Schatz, D Silverstein, J Muir, A Clare-Salzer, M She, JX Malone, J Crockett, S Schwartz, S Quattrin, T DeSilva, M Vander Vegt, P Notkins, A Krischer, J TI Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2 beta predict immune-mediated (type 1) diabetes in relatives SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE type 1 diabetes; relatives; autoantibodies; IA-2; IA-2 beta; GAD65; HLA-DR/DQ; prediction ID GLUTAMIC-ACID DECARBOXYLASE; PROTEIN-TYROSINE-PHOSPHATASE; GAD(65) AUTOANTIBODIES; TRANSMEMBRANE PROTEIN; MELLITUS; ANTIBODIES; IDDM; ANTIGEN; RISK; AUTOANTIGEN AB We report here our prospective,study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined,islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2 beta autoantibodies (ICA, IAA, GAD65A, LA-2A and IA-2 beta A), on the first available serum samples. The latter three autoantibodies were-however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2 beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing. (C) 1999 Academic Press. C1 Res Inst Children, Louisiana State Univ, Sch Med, Dept Pediat, Harahan, LA 70123 USA. Res Inst Children, Louisiana State Univ, Sch Med, Dept Biometry & Genet, Harahan, LA 70123 USA. Univ Florida, Coll Med, Dept Pathol Ummunol & Lab Med, Gainesville, FL USA. Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. Human Colunbia Hosp, San Antonio, TX USA. SUNY Buffalo, Dept Pediat, Buffalo, NY 14260 USA. NIH, Inst Dent, Bethesda, MD 20892 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Maclaren, N (reprint author), Res Inst Children, Louisiana State Univ, Sch Med, Dept Pediat, 520 Elmwood Pk Blvd,Suite 160, Harahan, LA 70123 USA. FU NCRR NIH HHS [MO1 RR00082]; NICHD NIH HHS [R01 HD 19469] NR 44 TC 68 Z9 71 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1999 VL 12 IS 4 BP 279 EP 287 DI 10.1006/jaut.1999.0281 PG 9 WC Immunology SC Immunology GA 200ME UT WOS:000080543400007 PM 10330299 ER PT J AU Dussurget, O Timm, J Gomez, M Gold, B Yu, SW Sabol, SZ Holmes, RK Jacobs, WR Smith, I AF Dussurget, O Timm, J Gomez, M Gold, B Yu, SW Sabol, SZ Holmes, RK Jacobs, WR Smith, I TI Transcriptional control of the iron-responsive fxbA gene by the mycobacterial regulator IdeR SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DIPHTHERIA-TOXIN REPRESSOR; OXIDATIVE-STRESS RESPONSE; CORYNEBACTERIUM-DIPHTHERIAE; EXTRACELLULAR SIDEROPHORE; IDENTIFICATION; SMEGMATIS; DTXR; TUBERCULOSIS; BINDING; EXPRESSION AB Exochelin is the primary extracellular siderophore of Mycobacterium smegmatis, and the iron-regulated fxbA gene encodes a putative formyltransferase, an essential enzyme in the exochelin biosynthetic pathway (E, H. Fiss, Y. Yu, and W. R. Jacobs, Jr., Mel. Microbiol. 14:557-569, 1994). We investigated the regulation of fxbA by the mycobacterial IdeR, a homolog of the Corynebacterium diphtheriae iron regulator DtxR (M. P. Schmitt, R I. Predich, L. Doukhan, I. Smith, and R. K. Holmes, Infect. Immun. 63:4284-4289, 1995). Gel mobility shift experiments showed that IdeR binds to the fxbA regulatory region in the presence of divalent metals. DNase I footprinting assays indicated that IdeR binding protects a 28-bp region containing a palindromic sequence of the fxbA promoter that was identified in primer extension assays. fxbA regulation was measured in M. smegmatis wild-type and ideR mutant strains containing fxbA promoter-lacZ fusions. These experiments confirmed that fxbA expression is negatively regulated by iron and showed that inactivation of ideR results in iron-independent expression of fxbA. However, the levels of its expression in the ideR mutant were approximately 50% lower than those in the wild-type strain under iron limitation, indicating an undefined positive role of IdeR in the regulation of fxbA. C1 Publ Hlth Res Inst, TB Ctr, New York, NY 10016 USA. NYU, Med Ctr, Dept Microbiol, New York, NY 10016 USA. Univ Paris 07, UFR Biochim, F-75251 Paris, France. Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Immunol & Microbiol, Bronx, NY 10461 USA. NCI, Gene Struct & Regulat Sect, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. RP Smith, I (reprint author), Publ Hlth Res Inst, TB Ctr, 455 1st Ave, New York, NY 10016 USA. RI Gomez, Manuel/F-8854-2016 OI Gomez, Manuel/0000-0002-4111-4835 FU NIAID NIH HHS [AI-14107, AI-26170, R01 AI014107, R01 AI026170, R37 AI014107, R37 AI026170]; NIGMS NIH HHS [GM 32651] NR 48 TC 67 Z9 70 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1999 VL 181 IS 11 BP 3402 EP 3408 PG 7 WC Microbiology SC Microbiology GA 201NQ UT WOS:000080602000011 PM 10348851 ER PT J AU London, RE Allen, DL Gabel, SA DeRose, EF AF London, RE Allen, DL Gabel, SA DeRose, EF TI Carbon-13 nuclear magnetic resonance study of metabolism of propionate by Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CITRATE SYNTHASE MUTANT; SACCHAROMYCES-CEREVISIAE; COUPLING-CONSTANTS; CLOSTRIDIUM-PROPIONICUM; TCA CYCLE; C-13; SPECTROSCOPY; NMR; BIOSYNTHESIS; DEHYDRATASE AB We have evaluated the use of [1,2-C-13(2)] propionate for the analysis of propionic acid metabolism, based on the ability to distinguish between the methylcitrate and methylmalonate pathways. Studies using propionate-adapted Escherichia coli MG1655 cells were performed. Preservation of the C-13-C-13-C-12 carbon skeleton in labeled alanine and alanine-containing peptides involved in cell wall recycling is indicative of the direct formation of pyruvate from propionate via the methylcitrate cycle, the enzymes of which have recently been demonstrated in E. coli. Additionally, formation of C-13-labeled formate from pyruvate by the action of pyruvate-formate lyase is also consistent with the labeling of pyruvate C-l. Carboxylation of the labeled pyruvate leads to formation of [1,2-C-13(2)] oxaloacetate and to multiply labeled glutamate and succinate isotopomers, also consistent with the flux through the methylcitrate pathway, followed by the tricarboxylic acid (TCA) cycle. Additional labeling of TCA intermediates arises due to the formation of [1-C-13]acetyl coenzyme A from the labeled pyruvate, formed via pyruvate-formate lyase. Labeling patterns in trehalose and glycine are also interpreted in terms of the above pathways. The information derived from the [1,2-C-13(2)] propionate label is contrasted with information which can be derived from singly or triply labeled propionate and shown to be more useful for distinguishing the different propionate utilization pathways via nuclear magnetic resonance analysis. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, MR-01,POB 12233, Res Triangle Pk, NC 27709 USA. NR 40 TC 20 Z9 21 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1999 VL 181 IS 11 BP 3562 EP 3570 PG 9 WC Microbiology SC Microbiology GA 201NQ UT WOS:000080602000030 PM 10348870 ER PT J AU Wu, WF Zhou, YN Gottesman, S AF Wu, WF Zhou, YN Gottesman, S TI Redundant in vivo proteolytic activities of Escherichia coli lon and the ClpYQ (HslUV) protease SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CELL-DIVISION INHIBITOR; ATP-DEPENDENT PROTEASE; DNA-REPLICATION; BINDING-PROTEIN; FTSZ; GENE; SULA; MUTAGENESIS; SUPPRESSES; COMPONENT AB The ClpYQ (HslUV) ATP-dependent protease of Escherichia coli consists of an ATPase subunit closely related to the Clp ATPases and a protease component related to those found in the eukaryotic proteasome. We found that this protease has a substrate specificity overlapping that of the Lon protease, another ATP-dependent protease in which a single subunit contains both the proteolytic active site and the ATPase. Lon is responsible for the degradation of the cell division inhibitor SulA; ion mutants are UV sensitive, due to the stabilization of SulA, ion mutants are also mucoid, due to the stabilization of another Lon substrate, the positive regulator of capsule transcription, RcsA, The overproduction of ClpYQ suppresses both of these phenotypes, and the suppression of UV sensitivity is accompanied by a restoration of the rapid degradation of SulA Inactivation of the chromosomal copy of clpY or clpQ leads to further stabilization of SulA in a Eon mutant but not in lon(+) cells. While either ion, ion clpY, or ion clpQ mutants are UV sensitive at low temperatures, at elevated temperatures the ion mutant loses its UV sensitivity, while the double mutants do not. Therefore, the degradation of SulA by ClpYQ at elevated temperatures is sufficient to lead to UV resistance. Thus, a protease with a structure and an active site different from those of Lon is capable of recognizing and degrading two different Lon substrates and appears to act as a backup for Lon under certain conditions. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37 Rm,2E18, Bethesda, MD 20892 USA. OI WU, WHI-FIN/0000-0002-9526-6287 NR 54 TC 65 Z9 66 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1999 VL 181 IS 12 BP 3681 EP 3687 PG 7 WC Microbiology SC Microbiology GA 205YR UT WOS:000080849100010 PM 10368141 ER PT J AU Murphy, LD Rosner, JL Zimmerman, SB Esposito, D AF Murphy, LD Rosner, JL Zimmerman, SB Esposito, D TI Identification of two new proteins in spermidine nucleoids isolated from Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID RECBC AB The Escherichia coli nucleoid contains DNA in a condensed but functional form. Analysis of proteins released from isolated spermidine nucleoids after treatment with DNase I reveals significant amounts of two proteins not previously detected in wild-type E. coli, Partial amino-terminal sequencing has identified them as the products of rdgC and yejK. These proteins are strongly conserved in gram-negative bacteria, suggesting that they have important cellular roles. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zimmerman, SB (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 328W,5 Ctr Dr,MSC0560, Bethesda, MD 20892 USA. NR 14 TC 14 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1999 VL 181 IS 12 BP 3842 EP 3844 PG 3 WC Microbiology SC Microbiology GA 205YR UT WOS:000080849100032 PM 10368163 ER PT J AU Matsui, M Breau, WC Iwasaki, S Hagiwara, S Tamai, Y Mori, C Bloom, ML Jerry, MB Eddy, EM Taketo, MM AF Matsui, M Breau, WC Iwasaki, S Hagiwara, S Tamai, Y Mori, C Bloom, ML Jerry, MB Eddy, EM Taketo, MM TI Retrovirus integration site Mintb encoding the mouse homolog of hnRNP U SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE embryonal carcinoma cell; retrovirus; ribonucleoprotein; spermatogenesis; testis ID EMBRYONAL CARCINOMA-CELLS; DNA-BINDING-PROTEIN; BIDIRECTIONAL PROMOTER; GENE-EXPRESSION; MESSENGER-RNA; TRANSCRIPTION UNITS; SAF-A; INVITRO; VIRUS; ACID AB Retroviral genes are not usually expressed in mouse embryonal carcinoma (EC) cells, but they are readily expressed upon differentiation of these cells. We previously reported the isolation of EC cell lines that express a neomycin resistance (neo) gene introduced by a recombinant transducing Moloney murine leukemia virus from specific integration sites, Minta, Mintb, Mintc, or Mintd, In some of these clones, the entire 5' long terminal repeat (LTR) was deleted, and the neo gene was expressed by read-through transcription from upstream cellular promoters in a "promoter-trap" fashion, One such promoter ("promoter B" at the Mintb locus) was found in a CPG island, associated with an upstream enhancer ("enhancer B"), Although enhancer B caused expression of the neo gene in the transductant EC cell line, no endogenous transcription from promoter B was detected in the parental EC or NIH3T3 cells. In contrast, we found a strong counter-flow endogenous transcription unit ("R" for reverse), which apparently interfered with transcription from promoter B, Promoter R turned out to have a bidirectional activity in transfection assays. In normal tissues, promoter R activates gene R, which encodes an 800-residue protein that is highly homologous to the rat and human heterogeneous nuclear ribonucleoprotein U (hnRNP U), Northern and in situ hybridization analyses revealed that gene R was abundantly expressed in the testis, especially in the pachytene spermatocytes and round spermatids. C1 Univ Tokyo, Lab Biomed Genet, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. Banyu Tsukuba Res Inst Merck, Tsukuba, Ibaraki 3002611, Japan. Natl Inst Environm Hlth Sci, Natl Inst Hlth, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Taketo, MM (reprint author), Univ Tokyo, Lab Biomed Genet, Grad Sch Pharmaceut Sci, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. FU NCI NIH HHS [CA39652] NR 46 TC 2 Z9 2 U1 0 U2 2 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD JUN PY 1999 VL 125 IS 6 BP 1104 EP 1114 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 205GZ UT WOS:000080814100018 PM 10348913 ER PT J AU Soriano, GM Ponamarev, MV Carrell, CJ Xia, D Smith, JL Cramer, WA AF Soriano, GM Ponamarev, MV Carrell, CJ Xia, D Smith, JL Cramer, WA TI Comparison of the cytochrome bc(1) complex with the anticipated structure of the cytochrome b(6)f complex: De plus ca change de plus c'est la meme chose SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE quinone; cytochrome b(6); cytochrome f; cytochrome complexes, membrane-bound; electron transfer, intraprotein; iron-sulfur protein; membranes, energy transduction; proton translocation ID IRON-SULFUR PROTEIN; LUMEN-SIDE DOMAIN; CHLAMYDOMONAS-REINHARDTII; ELECTRON-TRANSFER; BOVINE HEART; RHODOBACTER-SPHAEROIDES; BF COMPLEX; IN-VIVO; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE AB Structural alignment of the integral cytochrome b(6)-SU IV subunits with the solved structure of the mitochondrial bc(1) complex shows a pronounced asymmetry. There is a much higher homology on the p-side of the membrane, suggesting a similarity in the mechanisms of intramembrane and interfacial electron and proton transfer on the p-side, but not necessarily on the n-side. Structural differences between the bc(1) and b(6)f complexes appear to be larger the farther the domain or subunit is removed from the membrane core, with extreme differences between cytochromes c(1) and f: A special role for the dimer may involve electron sharing between the two hemes b(p), which is indicated as a probable event by calculations of relative rate constants for intramonomer heme b(p) --> heme b(n), or intermonomer heme b(p) --> heme b(p) electron transfer. The long-standing observation of flash-induced oxidation of only similar to 0.5 of the-chemical content of cyt f may be partly a consequence of the statistical population of ISP bound to cyt f on the dimer. It is proposed that the p-side domain of cyt f is positioned with its long axis parallel to the membrane surface in order to: (i) allow its large and small domains to carry out the functions of cyt c(1) and suVII, respectively, of the bc(1) complex, and (ii) provide maximum dielectric continuity with the membrane. (iii) This position would also allow the internal water chain (("proton wire") of cyt f to serve as the p-side exit port for an intramembrane H+ transfer chain that would deprotonate the semiquinol located in the myxothiazol/MOA-stilbene pocket near heme b(p). A hypothesis is presented for the identity of the amino acid residues in this chain. C1 Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Soriano, GM (reprint author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. FU NIGMS NIH HHS [GM-18457] NR 69 TC 46 Z9 47 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD JUN PY 1999 VL 31 IS 3 BP 201 EP 213 DI 10.1023/A:1005463527752 PG 13 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 258TB UT WOS:000083854300005 PM 10591526 ER PT J AU Yu, L Tso, SC Shenoy, SK Quinn, BN Xia, D AF Yu, L Tso, SC Shenoy, SK Quinn, BN Xia, D TI The role of the supernumerary subunit of Rhodobacter sphaeroides cytochrome bc(1) complex SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE nonredox subunit; the supernumerary subunit; subunit interaction; activity restoration ID UBIQUINONE-BINDING PROTEINS; BOVINE HEART-MITOCHONDRIA; C OXIDOREDUCTASE COMPLEX; SACCHAROMYCES-CEREVISIAE; ENERGY TRANSDUCTION; ELECTRON-TRANSFER; BC1 COMPLEX; GENE; IV; IDENTIFICATION AB The smallest molecular weight subunit (subunit IV), which contains no redox prosthetic group, is the only supernumerary subunit in the four-subunit Rhodobacter sphaeroides bc(1) complex. This subunit is involved in Q binding and the structural integrity of the complex. When the cytochrome bc(1) complex is photoaffinity labeled with [H-3]azido-Q derivative, radioactivity is found in subunits IV and I (cytochrome b), indicating that these two subunits are responsible for Q binding in the complex. When the subunit IV gene (fbcQ) is deleted from the R. sphaeroides chromosome, the resulting,strain(RS Delta IV) requires a period of adaptation before the start of photosynthetic growth. The cytochrome bc(1) complex in adapted RS Delta IV chromatophores is labile to detergent treatment (60-75% inactivation), and shows a four-fold increase in the K-m for Q(2)H(2). The first two changes indicate a structural role of subunit IV; the third change supports its Q-binding function. Tryptophan-79 is important for structural and Q-binding functions of subunit IV. Subunit IV is overexpressed in Escherichia coli as a GST fusion protein using the constructed expression vector, pGEX/IV. Purified recombinant subunit IV is functionally active as it can restore the bc(1) complex activity from the three-subunit core complex to the same level as that of wild-type or complement complex. Three regions in the subunit IV sequence, residues 86-109,:77-85, and 41-55, are essential for interaction with the core complex because deleting one of these regions yields a subunit completely or partially unable to restore cytochrome bc(1) from the core complex. C1 Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74074 USA. NIH, Natl Canc Inst, Cell Biol Lab, Bethesda, MD 20892 USA. RP Yu, L (reprint author), Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74074 USA. NR 30 TC 13 Z9 14 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD JUN PY 1999 VL 31 IS 3 BP 251 EP 257 DI 10.1023/A:1005423913639 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 258TB UT WOS:000083854300010 PM 10591531 ER PT J AU Wang, YX Jacob, J Cordier, F Wingfield, P Stahl, SJ Lee-Huang, S Torchia, D Grzesiek, S Bax, A AF Wang, YX Jacob, J Cordier, F Wingfield, P Stahl, SJ Lee-Huang, S Torchia, D Grzesiek, S Bax, A TI Measurement of (3h)J(NC ') connectivities across hydrogen bonds in a 30 kDa protein SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE hydrogen bond; J coupling; MAP30; perdeuteration; relaxation rates; TROSY ID CHEMICAL-SHIFT ANISOTROPY; IMPROVED LINEAR PREDICTION; QUANTITATIVE MEASUREMENT; RELAXATION; NMR; COUPLINGS; SIGNALS; PAIR AB A method is described which permits detection of (3h)J(NC') scalar couplings across hydrogen bonds in larger, perdeuterated proteins. The experiment is demonstrated for the uniformly H-2/C-13/N-15-enriched 30 kDa ribosome inactivating protein MAP30. The (3)hJ(NC') interactions are smaller than 1 Hz, but their detection in an HNCO experiment is made possible through the use of constructive interference between the N-15 chemical shift anisotropy and H-1-N-15 dipole-dipole relaxation mechanisms in a manner similar to that of recently proposed TROSY schemes. Sensitivity of the HNCO experiment depends strongly on the N-15 transverse relaxation rate of the downfield N-15 multiplet component and on the amide proton T-1. In perdeuterated MAP30 at 40 degrees C, the average TROSY T-2 was 169 ms at 750 MHz H-1 frequency, and a wide range of longitudinal relaxation rates was observed for the amide protons. C1 NIDR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. Forschungszentrum Julich, Inst Biol Struct, D-52425 Julich, Germany. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Univ Dusseldorf, Inst Phys Biol, D-40225 Dusseldorf, Germany. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Wang, YX (reprint author), NIDR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NR 20 TC 103 Z9 104 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUN PY 1999 VL 14 IS 2 BP 181 EP 184 DI 10.1023/A:1008346517302 PG 4 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 213YJ UT WOS:000081300600010 PM 10427744 ER PT J AU Walsh, S Stewart, K Jefferris, C Kuznetsov, S Robey, P Gehron, P Beresford, JN AF Walsh, S Stewart, K Jefferris, C Kuznetsov, S Robey, P Gehron, P Beresford, JN TI Characterisation of conditionally immortalised cell lines derived from adult human bone marrow. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1999 VL 14 IS 6 MA P31 BP 1045 EP 1045 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 201UY UT WOS:000080615500085 ER PT J AU Bianco, P Riminucci, M Robey, PG AF Bianco, P Riminucci, M Robey, PG TI Cellular and molecular pathology of fibrous dysplasia of bone (McCune-Albright syndrome). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Aquila, I-67100 Laquila, Italy. NIDCR, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1999 VL 14 IS 6 MA IS01 BP 1053 EP 1053 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 201UY UT WOS:000080615500116 ER PT J AU Bianco, P Simmons, PJ Gehron-Robey, P Oreffo, ROC AF Bianco, P Simmons, PJ Gehron-Robey, P Oreffo, ROC TI Marrow stromal cells: Concepts and controversies. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ La Sapienza, Rome, Italy. Hanson Ctr Canc Res, Adelaide, SA, Australia. NIDR, NIH, Bethesda, MD 20892 USA. Univ Southampton, Univ Orthopaed, Southampton, Hants, England. RI Oreffo, Richard/A-4615-2011 OI Oreffo, Richard/0000-0001-5995-6726 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1999 VL 14 IS 6 MA W02 BP 1057 EP 1057 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 201UY UT WOS:000080615500131 ER PT J AU Grossman, E Shenkar, A Peleg, E Thaler, M Goldstein, DS AF Grossman, E Shenkar, A Peleg, E Thaler, M Goldstein, DS TI Renal effects of L-DOPA in heart failure SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE L-DOPA; dopamine; congestive heart failure; natriuresis; diuresis ID ORAL LEVODOPA; METABOLISM; RECEPTORS; THERAPY; AGENTS AB We examined whether low-dose L-DOPA treatment induces natriuresis and diuresis in patients with congestive heart failure who have cardiac decompensation despite treatment with digoxin, a diuretic, and an angiotensin-converting enzyme inhibitor and who respond acutely to intravenously infused dopamine. In a randomized, double-blind, placebo-controlled crossover study, 11 patients with severe congestive heart failure received L-DOPA (0.10 g, p.o., t.i.d., for 1 day and then 0.25 g, p.o., t.i.d., for 2 days after a washout period of greater than or equal to 1 day), with assessments of plasma and urinary levels of catechols, urinary volume, and sodium content, and clinical and laboratory measures of improvement of congestive heart failure. L-DOPA elicited short-term, dose-related increases in urinary volume and sodium excretion. At the 0.10-g dose, L-DOPA increased plasma L-DOPA levels and urinary L-DOPA excretion by about fivefold, whereas at the 0.25-g dose, L-DOPA increased plasma and urinary L-DOPA by >50-fold. Twenty-four-hour urinary dopamine excretion increased by about fivefold after the low dose of L-DOPA and similar to 50-fold after the high dose. The results demonstrate that oral L-DOPA treatment can produce beneficial natriuretic and diuretic effects in selected patients with congestive heart failure. The bioavailability of oral L-DOPA appears to vary with the dose. These results support findings from previous studies about beneficial cardiac functional effects of L-DOPA in patients with refractory heart failure. C1 Chaim Sheba Med Ctr, Dept Internal Med D, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Grossman, E (reprint author), Chaim Sheba Med Ctr, Dept Internal Med D, IL-52621 Tel Hashomer, Israel. NR 25 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUN PY 1999 VL 33 IS 6 BP 922 EP 928 DI 10.1097/00005344-199906000-00013 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 199YD UT WOS:000080510900013 PM 10367596 ER PT J AU Zamir, E Katz, BZ Aota, S Yamada, KM Geiger, B Kam, Z AF Zamir, E Katz, BZ Aota, S Yamada, KM Geiger, B Kam, Z TI Molecular diversity of cell-matrix adhesions SO JOURNAL OF CELL SCIENCE LA English DT Article DE focal contact; cell adhesion; ratio imaging; computerized microscopy ID INTERFERENCE REFLECTION MICROSCOPY; SIGNAL-TRANSDUCTION; MICROFILAMENT SYSTEM; FOCAL ADHESIONS; PROTEIN; FIBROBLASTS; INTEGRINS; CONTACTS; VINCULIN; PHOSPHORYLATION AB In this study we have examined for molecular heterogeneity of cell-matrix adhesions and the involvement of actomyosin contractility in the selective recruitment of different plaque proteins. For this purpose, we have developed a novel microscopic approach for molecular morphometry, based on automatic identification of matrix adhesions, followed by quantitative immunofluorescence and morphometric analysis. Particularly informative was fluorescence ratio imaging, comparing the local labeling intensities of different plaque molecules, including vinculin, paxillin, tensin and phosphotyrosine-containing proteins. Ratio imaging revealed considerable molecular heterogeneity between and within adhesion sites. Most striking were the differences between focal contacts, which are vinculin- and paxillin-rich and contain high levels of phosphotyrosine, and fibrillar adhesions, which are tensin-rich and contain little or no phosphotyrosine, Ratio imaging also revealed considerable variability in the molecular substructure of individual focal contacts, pointing to a non-uniform distribution of phosphotyrosine and the different plaque constituents. Studying the quantitative relationships between the various components of the submembrane plaque indicated that the levels of vinculin, paxillin and phosphotyrosine in adhesion sites are positively correlated with each other and negatively correlated with the levels of tensin, Tyrosine phosphorylation of focal contacts was highly sensitive to cellular contractility, and was diminished within 5 minutes after treatment with the kinase inhibitor H-7, an inhibitor of actomyosin contractility. This was followed by the loss of paxillin and vinculin from the focal adhesions. Tensin-rich fibrillar adhesions were relatively insensitive to H-7 treatment. These findings suggest a role for contractility in the generation of matrix adhesion diversity. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Biomol Engn Res Inst, Osaka, Japan. RP Geiger, B (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. OI Yamada, Kenneth/0000-0003-1512-6805 NR 35 TC 314 Z9 317 U1 1 U2 26 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 1999 VL 112 IS 11 BP 1655 EP 1669 PG 15 WC Cell Biology SC Cell Biology GA 207UE UT WOS:000080953500003 PM 10318759 ER PT J AU Ostlund, C Ellenberg, J Hallberg, E Lippincott-Schwartz, J Worman, HJ AF Ostlund, C Ellenberg, J Hallberg, E Lippincott-Schwartz, J Worman, HJ TI Intracellular trafficking of emerin, the Emery-Dreifuss muscular dystrophy protein SO JOURNAL OF CELL SCIENCE LA English DT Article DE nuclear envelope; membrane protein; protein targeting; fluorescence photobleaching; muscle disease ID INNER NUCLEAR-MEMBRANE; LAMIN-B-RECEPTOR; INTERMEDIATE FILAMENT PROTEINS; LIVING CELLS; INTEGRAL PROTEIN; BREFELDIN-A; CHROMODOMAIN PROTEINS; TARGETING DOMAIN; GOLGI PROTEINS; ENVELOPE AB Emerin is an integral protein of the inner nuclear membrane that is mutated or not expressed in patients with Emery-Dreifuss muscular dystrophy. Confocal immunofluorescence microscopy studies of the intracellular targeting of truncated forms of emerin, some of which are found in patients with Emery-Dreifuss muscular dystrophy, show that the nucleoplasmic, aminoterminal domain is necessary and sufficient for nuclear retention. When this domain is fused to a transmembrane segment of an integral membrane protein of the ER/plasma membrane, the chimeric protein is localized in the inner nuclear membrane. The transmembrane segment of emerin is not targeted to the inner nuclear membrane. Fluorescence photobleaching experiments of emerin fused to green fluorescent protein demonstrate that the diffusional mobility (D) of emerin is decreased in the inner nuclear membrane (D=0.10+/-0.01 mu m(2)/second) compared to the ER membrane (D=0.32+/-0.01 mu m(2)/second). This is in agreement with a model where integral proteins reach the inner nuclear membrane by lateral diffusion and are retained there by association with nucleoplasmic components. Some overexpressed emerin-green fluorescent protein also reaches the plasma membrane of transfected cells, where its diffusion is similar to that in the inner nuclear membrane, suggesting that emerin may also associate with non-nuclear structures. C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Karolinska Inst, NOVUM, Ctr Biotechnol, S-14157 Huddinge, Sweden. RP Worman, HJ (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X FU NCI NIH HHS [5 P30-CA13696, R01-CA66974]; NCRR NIH HHS [1S10-RR10506] NR 55 TC 131 Z9 135 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 1999 VL 112 IS 11 BP 1709 EP 1719 PG 11 WC Cell Biology SC Cell Biology GA 207UE UT WOS:000080953500007 PM 10318763 ER PT J AU Wang, WG Passaniti, A AF Wang, WG Passaniti, A TI Extracellular matrix inhibits apoptosis and enhances endothelial cell differentiation by a NF kappa B-dependent mechanism SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE apoptosis; endothelial cells; extracellular matrix; nuclear factor; estradiol ID ANGIOGENESIS INVITRO; BASEMENT-MEMBRANE; ESTROGEN-RECEPTOR; DEATH; BETA; ACTIVATION; EXPRESSION; FILAMENTS; MUSCLE; GROWTH AB Hormonal and environmental factors that control the growth, differentiation, and regression of the vasculature are of fundamental importance in tumorigenesis and in the choice of therapeutic strategies. To test the hypothesis that estradiol (E-2) and basement membrane proteins would affect the survival of vascular endothelial cells (EC), immortalized human umbilical vein endothelial cells (ECV304) were examined for their response to the chemotherapeutic drugs taxol and etoposide. ECV cell apoptosis was inhibited by E-2 (taxol only) or attachment to extracellular matrix (ECM) (taxol or etoposide). E-2 increased ECV growth, while ECM binding resulted in growth arrest and differentiation. Apoptosis was associated with decreased levels of Bcl-2 and p21 proteins. E-2 prevented down-regulation of p21 and Bcl-2 induced by taxol but did not prevent the down-regulation of p21 induced by etoposide, consistent with the failure of E-2 to inhibit etoposide-induced cell death. However, ECM prevented p21 and Bcl-2 down-regulation induced by taxol or etoposide. Persistent activation of NF kappa B occurred after attachment of ECV cells to ECM, suggesting a role in survival or differentiation. I kappa B alpha levels were not affected by taxol but were reduced by etoposide treatment while I kappa B beta levels did not change with drug treatment. E2 did not alter the levels of I kappa B alpha or I kappa B beta. Interestingly, levels of I kappa B alpha and I kappa B beta declined in etoposide-treated ECV cells on ECM concomitant with the elevation of NF kappa B, suggesting that in these cells degradation of I kappa B may be responsible for NF kappa B activation. In agreement with these data, anti-sense NF kappa B treatment of ECV cells inhibited differentiation on ECM, but did not affect cell survival. In conclusion, culture of ECV cells on ECM or treatment with E-2 inhibited apoptosis. NF kappa B activation by ECM was necessary for cellular differentiation, rather than inhibition, of apoptosis. J. Cell. Biochem. 73:321-331, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Passaniti, A (reprint author), Univ Maryland, Dept Pathol, Greenebaum Canc Ctr, Bressler Res Bldg 7-021,655 W Baltimore St, Baltimore, MD 21201 USA. NR 31 TC 31 Z9 33 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 1 PY 1999 VL 73 IS 3 BP 321 EP 331 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188HG UT WOS:000079840300004 PM 10321832 ER PT J AU Peterkofsky, B Gosiewska, A Singh, K Pearlman, S Mahmoodian, F AF Peterkofsky, B Gosiewska, A Singh, K Pearlman, S Mahmoodian, F TI Species differences in cis-elements of the Pro alpha 1(I) procollagen promoter and their binding proteins SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE type I collagen; promoter elements; DNA binding; species specificity; glucocorticoid response element ID GROWTH-FACTOR-BETA; ALPHA-1(I) COLLAGEN PROMOTER; GENE-EXPRESSION; I COLLAGEN; GLUCOCORTICOID RECEPTOR; EXTRACELLULAR-MATRIX; ALPHA-2(I) COLLAGEN; TRANSCRIPTIONAL REGULATOR; RESPONSE ELEMENTS; OSTEOCALCIN GENE AB Previous studies suggest that there may be species differences in the utilization of cis-elements of the type I collagen genes. The present study was designed to examine this possibility by focusing on two regions of the pro alpha 1(I) collagen promoter. One is the GC-rich A1 region (-194/168) that modulates transcriptional activity or the mouse promoter. The other contains a glucocorticoid response element (GRE) implicated in negative glucocorticoid regulation of the rat promoter. Unlike mouse A1 probes, probes representing the analogous human (-195/-168) and rat (-193/-179) regions failed to bind nuclear proteins in gel shift assays. Binding assays with mouse A1 probes containing base substitutions indicated that this behavior could be ascribed to five bases in the human, and two in the rat sequences. In addition, the pattern of expression of c-Krox, a protein that alters transcriptional activity via the mouse A1 clement, differed in mouse and human tissues. Computer analysis revealed differences in the arrangement of CRE half-sites in human and rat pro alpha 1(I) collagen promoters. in a region of the human promoter (-700/673) analogous to the rat (-672/-633), there are three half-sites, each separated by two nucleotides, that cooperate in binding of glucocorticoid receptor. There also is a proximal half site at position -335 of the human promoter that binds glucocorticoid receptor, but it is not present in the rat promoter. This study has defined several species-specific differences in the sequences and nuclear protein binding activity of regions involved in transcriptional activity of the pro alpha 1(I) collagen promoter. The results suggest that the A1 regions of the human and rat promoters examined here are unlikely to function as regulatory cis-elements, and they provide a framework for investigating the role of GREs in transcriptional regulation. They also suggest that species differences in cis-elements and transcription factors should be taken into consideration when using heterologous systems to study collagen gene regulation. J. Cell. Biochem. 73:408-422, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Peterkofsky, B (reprint author), NCI, Biochem Lab, Bldg 37,Room 4-18,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 41 TC 18 Z9 19 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 1 PY 1999 VL 73 IS 3 BP 408 EP 422 DI 10.1002/(SICI)1097-4644(19990601)73:3<408::AID-JCB12>3.0.CO;2-D PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188HG UT WOS:000079840300012 PM 10321840 ER PT J AU Dawson, DA Furuya, K Gotoh, J Nakao, Y Hallenbeck, JM AF Dawson, DA Furuya, K Gotoh, J Nakao, Y Hallenbeck, JM TI Cerebrovascular hemodynamics and ischemic tolerance: Lipopolysaccharide-induced resistance to focal cerebral ischemia is not due to changes in severity of the initial ischemic insult, but is associated with preservation of microvascular perfusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ischemic tolerance; lipopolysaccharide; microvascular perfusion; cerebral blood flow; spontaneously hypertensive rat ID NITRIC-OXIDE SYNTHASE; FACTOR-KAPPA-B; SPONTANEOUSLY HYPERTENSIVE RAT; NECROSIS-FACTOR-ALPHA; ORGAN BLOOD-FLOW; ENDOTOXIN TOLERANCE; SUPEROXIDE-DISMUTASE; GENE-EXPRESSION; BRAIN-DAMAGE; WISTAR RAT AB Lipopolysaccharide (LPS), administered 72 hours before middle cerebral artery (MCA) occlusion, confers significant protection against ischemic injury. For example, in the present study, LPS (0.9 mg/kg intravenously) induced a 31% reduction in infarct volume (compared with saline control) assessed 24 hours after permanent MCA occlusion. To determine whether LPS induces true tolerance to ischemia, or merely attenuates initial ischemic severity by augmenting collateral blood flow, local CBF was measured autoradiographically 15 minutes after MCA occlusion. Local CBF did not differ significantly between LPS- and saline-pretreated rats (e.g., 34 +/- 10 and 29 +/- 15 mL.100 g(-1).min(-1) for saline and LPS pretreatment in a representative region of ischemic cortex), indicating that the neuroprotective action of LPS is not attributable to an immediate reduction in the degree of ischemia induced by MCA occlusion, and that LPS does indeed induce a state of ischemic tolerance. In contrast to the similarity of the initial ischemic insult between tolerant (LPS-pretreated) and nontolerant (saline-pretreated) rats, microvascular perfusion assessed either 4 hours or 24 hours after MCA occlusion was preserved at significantly higher levels in the LPS-pretreated rats than in controls. Furthermore, the regions of preserved perfusion in tolerant animals were associated with regions of tissue sparing. These results suggest that LPS-induced tolerance to focal ischemia is at least partly dependent on the active maintenance of microvascular patency and hence the prevention of secondary ischemic injury. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), Cerebus Ltd, 613 Reading Rd, Wokingham RG41 5UA, England. NR 43 TC 75 Z9 75 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 1999 VL 19 IS 6 BP 616 EP 623 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 277TB UT WOS:000084948700004 PM 10366191 ER PT J AU Zahn, TP Mirsky, AF AF Zahn, TP Mirsky, AF TI Reaction time indicators of attention deficits in closed head injury SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID TRAUMATIC BRAIN INJURY; VISUAL DOMINANCE; SCHIZOPHRENIA; DYSFUNCTION AB The nature of deficits in attention in closed head injury (CHI) was studied by three reaction time RT) paradigms given to 20 patients who had a CHI 2 or more years previously and to 25 controls. We studied the effects of temporal uncertainty by varying the length and regularity of the preparatory interval, the effects of stimulus modality uncertainty on simple RT to tones and lights, and the effects of response selection in choice RT. The CHI group showed slower and more variable RT than controls under all conditions. In addition, a long preparatory interval on the preceding trial retarded RT more in the CHI group, and they showed greater effects of stimulus modality uncertainty. Both of these findings suggest a difficulty in shifting attention to unexpected stimuli. These greater effects on RT of variations of attention or preparation in CHI may account for their greater within-subject variability possibly due to frontal lobe damage. C1 NIMH, Lab Brain & Cognit, Sect Clin & Expt Neuropsychol, Bethesda, MD 20892 USA. RP Zahn, TP (reprint author), NIMH, Lab Brain & Cognit, Sect Clin & Expt Neuropsychol, Bldg 10,Room 4C104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. NR 28 TC 32 Z9 35 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD JUN PY 1999 VL 21 IS 3 BP 352 EP 367 DI 10.1076/jcen.21.3.352.924 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 234FW UT WOS:000082474700007 PM 10474174 ER PT J AU Rossouw, JE AF Rossouw, JE TI Does estrogen have a role in the prevention of cardiovascular disease? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CORONARY-HEART-DISEASE; HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; MYOCARDIAL-INFARCTION; VENOUS THROMBOEMBOLISM; SERUM-CHOLESTEROL; CLINICAL-TRIALS; BETA-CAROTENE; RISK; REDUCTION C1 NHLBI, Womens Hlth Initiat, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, Bldg 10, Bethesda, MD 20892 USA. NR 45 TC 3 Z9 3 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 JUN PY 1999 VL 84 IS 6 BP 1806 EP 1810 DI 10.1210/jc.84.6.1806 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000009 ER PT J AU Yanovski, JA Miller, KD Kino, T Friedman, TC Chrousos, GP Tsigos, C Falloon, J AF Yanovski, JA Miller, KD Kino, T Friedman, TC Chrousos, GP Tsigos, C Falloon, J TI Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-FAT DISTRIBUTION; PITUITARY-ADRENAL AXIS; INSULIN-RESISTANCE; PERIPHERAL LIPODYSTROPHY; CORTISOL SECRETION; ABDOMINAL OBESITY; HIV-1 INFECTION; HYPERLIPIDEMIA; INDINAVIR; THERAPY AB Multidrug antiretroviral regimens that include human immunodeficiency virus-1 (HIV-1) protease inhibitors are associated with distinct lipodystrophy, hypertriglyceridemia, hyperinsulinemia, and deposition of visceral abdominal adipose tissue. To determine whether these findings are related to abnormalities of adrenal function, we compared the hypothalamic-pituitary-adrenal axes of HIV-positive patients who had evidence of protease inhibitor-associated lipodystrophy (PIAL), control volunteers (CON), and patients with Cushing's syndrome (CS). To elucidate the metabolic consequences of the observed lipodystrophy, we measured basal serum lipids and compared glucose and insulin concentrations during an oral glucose tolerance test. Spontaneous plasma cortisol showed normal diurnal variation in PIAL. Cortisol levels were similar in CON and PIAL, and levels in these groups were less than those in CS at all times of the night or day (P < 0.005). Ovine CRH-stimulated morning plasma cortisol levels were similar in PIAL and CON. ACTH was significantly greater in PIAL than CON (P < 0.05) at 0, 15, and 30 min after CRH stimulation. Urinary free cortisol in PIAL(mean +/- SD, 76 +/- 51 nmol/day) was significant lower than those in CON (165 +/- 64 nmol/day; P < 0.001) and CS (1715 +/- 1203 nmol/day; P < 0.001). However, 17-hydroxycorticosteroid excretion was significantly greater in PIAL (43 +/- 23 mu mol/day) than in CON (17 +/- 8 mu mol/day; P < 0.001), although lower than that in CS (74 +/- 47 mu mol/day; P < 0.01). Scatchard analysis revealed normal glucocorticoid receptor number and affinity in PIAL. Serum triglycerides were significantly greater in PIAL (6.57 +/- 5.63 mmol/L) than in CS (1.78 +/- 0.83 mmol/L; P < 0.001) or CON (1.36 +/- 0.84 mmol/L; P < 0.001). Although triglyceride levels were significantly correlated with body mass index for CON and CS, these were not correlated for PIAL. During an oral glucose tolerance test, similar glucose and insulin values were found in PIAL and CS that were greater (P < 0.05) than CON values at 30, 60, 90, and 120 min. We conclude that the lipodystrophy associated with use of HIV-1 protease inhibitors is a syndrome of increased intraabdominal adiposity with concomitant dyslipidemia and insulin resistance, but without total body weight gain and is distinct from any known form of hypercortisolism. Although urinary cortisol disposition seems to be altered in HIV-infected patients who are being treated with multidrug regimens that include protease inhibitors, the decreased free cortisol and increased 17-hydroxycorticosteroid excretion appear to be unlikely explanations for the observed lipodystrophy. The cause remains to be elucidated. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Dept Crit Care, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr,Burns & Allen Res Inst, Sch Med, Dept Med,Div Endocrinol, Los Angeles, CA 90048 USA. RP Yanovski, JA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, 10 Ctr Dr,MSC 1862,Bldg 10,Room 10N262,9000 Rockv, Bethesda, MD 20892 USA. EM jyl5i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 NR 38 TC 119 Z9 124 U1 2 U2 3 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 JUN PY 1999 VL 84 IS 6 BP 1925 EP 1931 DI 10.1210/jc.84.6.1925 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000037 PM 10372688 ER PT J AU Singh, A Petrides, JS Gold, PW Chrousos, GP Deuster, PA AF Singh, A Petrides, JS Gold, PW Chrousos, GP Deuster, PA TI Differential hypothalamic-pituitary-adrenal axis reactivity to psychological and physical stress SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; CORTISOL RESPONSES; MARKED DIFFERENCES; EXERCISE; HUMANS; ACTH; DEXAMETHASONE; ACTIVATION; MEN AB Healthy men exhibit a differential hypothalamic-pituitary-adrenal axis (HPA) response to exercise stress and fall into two groups: high responders (HR) and low responders (LR). The present study examined whether HR to physical stress also exhibit higher HPA reactivity to psychological stress than LR. We examined 14 HR and 13 LR classified based on their ACTH responses to high intensity exercise after pretreatment with dexamethasone. Both groups were of similar age, height, weight, and fitness level. Trait anxiety scores on the Spielberger Trait Anxiety Scale were not different. Subjects underwent a psychological stress test consisting of an interview and mental arithmetic. This test raised heart rate, blood pressure, and plasma ACTH and cortisol levels in both HR and LR. HR tended to have higher heart rates and blood pressures in anticipation of the psychological stress test than LR. ACTH responses of Wi were higher, although not significantly, throughout the psychological stress test than LR. HR had a significantly (P < 0.05) greater net integrated cortisol response to the psychological stress than LR. This suggests that the adrenal cortexes of the HR are hypertropic and/or hypersensitive to ACTH. We conclude that men who are highly responsive to exercise stress are also highly responsive to psychological stress. C1 Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. Duke Univ, Med Ctr, Dept Phys & Occupat Med, Durham, NC USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM asingh@usuhs.mil RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 22 TC 92 Z9 95 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1944 EP 1948 DI 10.1210/jc.84.6.1944 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000040 PM 10372691 ER PT J AU Weise, M Abad, V Considine, RV Nieman, L Rother, KI AF Weise, M Abad, V Considine, RV Nieman, L Rother, KI TI Leptin secretion in Cushing's syndrome: Preservation of diurnal rhythm and absent response to corticotropin-releasing hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMA LEPTIN; BODY-FAT; NORMAL-WEIGHT; SERUM LEPTIN; INSULIN SENSITIVITY; CIRCULATING LEPTIN; CIRCADIAN-RHYTHM; OBESE CHILDREN; IN-VIVO; HUMANS AB The normal inverse relationship between leptin and cortisol is lost in chronic hypercortisolism. We studied this apparent dysregulation in patients with Cushing's syndrome to investigate 1) the effect of chronic hypercortisolemia on the circadian rhythm of leptin secretion, 2) the response of leptin after administration of CRH, and 3) the short term effect of curative surgery on leptin. The preoperative morning leptin concentration was 54.2 +/- 8.1 ng/mL, and the nighttime value was 68.6 +/- 9.8 ng/mL, reflecting a mean rise of 32.8 +/- 7.6%, similar to the nocturnal increase observed in normal subjects. By contrast, cortisol's diurnal variation (21.8 +/- 1.7 vs. 16.9 +/- 1.1 mg/dL) was blunted. In women, but not men, body mass index correlated with leptin (P = 0.001). Preoperative ACTH and cortisol (both P < 0.0001), but not leptin levels increased after CRH. Ten days after surgery, basal cortisol values were subnormal (1.1 +/- 0.6 mg/dL), but leptin levels remained unchanged and did not increase after CRH. Body mass index and insulin also remained unchanged. Insulin, but not age, urinary free cortisol, or plasma cortisol correlated with leptin (P < 0.05). In summary, patients with Cushing's syndrome have moderately elevated leptin levels that maintain an intact circadian rhythm but do not respond to acute or subacute alterations of cortisol. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Indianapolis, Sch Med, Div Endocrinol, Indianapolis, IN 46227 USA. RP Rother, KI (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM rotherk@mail.nih.gov NR 39 TC 19 Z9 19 U1 2 U2 2 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 JUN PY 1999 VL 84 IS 6 BP 2075 EP 2079 DI 10.1210/jc.84.6.2075 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000063 PM 10372713 ER PT J AU Montuori, N Muller, F De Riu, S Fenzi, G Sobel, ME Rossi, G Vitale, M AF Montuori, N Muller, F De Riu, S Fenzi, G Sobel, ME Rossi, G Vitale, M TI Laminin receptors in differentiated thyroid tumors: Restricted expression of the 67-kilodalton laminin receptor in follicular carcinoma cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INTEGRIN EXPRESSION; BINDING PROTEIN; CANCER-CELLS; PRECURSOR; METASTASIS; ATTACHMENT; PLATELETS; ACYLATION; INVASION; BETA(1) AB The expression of integrin laminin receptors was investigated in normal thyroid primary cultures; immortalized normal thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic (ARO) thyroid tumor cell lines; seven thyroid tumors (four papillary and three follicular carcinomas); and normal thyroid glands. The expression of alpha(1)beta(1), alpha(2)beta(1), alpha(3)beta(1), alpha(6)beta(1), and alpha(6)beta(4) was found in all tumor specimens and in tumor cell lines, whereas normal thyroid cells and TAD-2 cells lacked the expression of alpha(6)beta(4). Despite the presence of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO cells to immobilized laminin-l was poor, whereas WRO cells and follicular carcinoma-derived cells displayed a strong adhesion, indeed, WRO and follicular carcinoma-derived cells showed expression of a nonintegrin laminin receptor, the 67-kDa high affinity laminin receptor (67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic adenoma, follicular adenoma, and papillary carcinoma-derived cells did not express the 67LR. Adhesion of WRO and follicular carcinoma-derived cells to laminin-l was specifically inhibited by a recombinant polypeptide containing laminin-binding domains of 67LR, demonstrating that this receptor confers to follicular carcinoma cells attachment capacity to laminin. Moreover, tissue specimens from follicular carcinomas expressed the 67LR, whereas follicular adenomas and normal thyroid tissues were negative. in thyroid tumors, integrin receptors, although abundant, participate weakly in adhesion to laminin. The expression in follicular carcinoma cells of a functional, high affinity 67LR together with nonfunctional integrin LM receptors could be responsible for the tendency of follicular carcinoma cells to metastasize by mediating stable contacts with basal membranes. C1 Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy. Univ Naples Federico II, CNR, Ctr Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy. Univ Naples Federico II, Dipartimento Endocrinol & Oncol Mol & Clin, I-80131 Naples, Italy. NCI, Mol Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Via S Pansini 5, I-80131 Naples, Italy. EM mavitale@cds.unina.it RI Montuori, Nunzia/J-8542-2013; OI Montuori, Nunzia/0000-0001-8697-986X NR 38 TC 16 Z9 18 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 2086 EP 2092 DI 10.1210/jc.84.6.2086 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000065 PM 10372715 ER PT J AU Orban, Z Remaley, AT Sampson, M Trajanoski, Z Chrousos, GP AF Orban, Z Remaley, AT Sampson, M Trajanoski, Z Chrousos, GP TI The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; INDUCED INSULIN-RESISTANCE; IN-VIVO; PLASMA LEPTIN; TNF-ALPHA; LIPOPROTEIN-LIPASE; 3T3-L1 ADIPOCYTES; GENE-EXPRESSION; OBESE SUBJECTS; TISSUE AB We determined whether the physiologic changes that accompany food intake or sympathetic activation by beta-adrenergic stimulation result in alterations in the secretion of leptin, tumor necrosis factor-cu (TNF alpha), or interleukin-6 (IL-6) by serially sampling sc abdominal adipose interstitial fluid by open-flow microperfusion before and after a standardized meal and in response to isoproterenol (1 mu mol/L) delivered locally. Post cibum IL-6 rose up to 5-fold, whereas leptin and TNF alpha secretion did not change; TNF alpha, but not IL-6, correlated positively with indices of lipolysis. Isoproterenol-induced lipolysis was accompanied by a transient 40% reduction in leptin and a parallel 85% elevation of TNF alpha concentration, whereas IL-6 levels did not change; again, TNF alpha correlated positively with lipolysis. These data show that secretion of some, but not all, metabolically relevant polypeptides by adipose tissue is modulated within a short time frame by food or stress stimuli, suggesting a role of these peptides in local autocrine/paracrine or distant endocrine effects on fat metabolism TNF alpha's close correlation with lipolysis suggests that this cytokine participates in a local positive autocrine feedback loop, potentiating lipolysis and inhibiting insulin's antilipolytic actions. The regulations of adipose leptin, TNF alpha, and IL-6 secretion seem distinct from each other and different in the fed vs. fasting state. C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. Graz Univ Technol, Inst Biomed Engn, A-8010 Graz, Austria. RP Orban, Z (reprint author), NICHHD, Dev Endocrinol Branch, Bldg 10,Room 10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM orbanz@cc1.nichd.nih.gov NR 50 TC 141 Z9 145 U1 0 U2 2 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 JUN PY 1999 VL 84 IS 6 BP 2126 EP 2133 DI 10.1210/jc.84.6.2126 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000071 PM 10372721 ER PT J AU Nieto, FJ Diez-Roux, A Szklo, M Comstock, GW Sharrett, AR AF Nieto, FJ Diez-Roux, A Szklo, M Comstock, GW Sharrett, AR TI Short- and long-term prediction of clinical and subclinical atherosclerosis by traditional risk factors SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE atherosclerosis; bias (epidemiology); coronary disease; hypertension; cholesterol; smoking ID CORONARY HEART-DISEASE; B-MODE ULTRASOUND; POPULATION-BASED ULTRASONOGRAPHY; BLOOD-PRESSURE; CAROTID ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; ARTERIAL-WALL; DETERMINANTS; CHOLESTEROL; THICKNESS AB This study compares the cross-sectional and longitudinal associations of cardiovascular risk factors with clinical coronary heart disease (CHD) and with subclinical carotid atherosclerosis measured by ultrasound. The study population were 1410 participants in the Atherosclerotic Risk in Community (ARIC) Study (1987-1989) who also participated in a 1974 community hearth survey. Smoking in 1974 was associated with increased CHD prevalence in 1987-1989 (adjusted prevalence ratio = 2.2), whereas the corresponding cross-sectional association was practically absent. For hypercholesterolemia and hypertension, the longitudinal associations with CHD were also stronger than the cross sectional associations. In contrast, the strength of the longitudinal and cross sectional associations with carotid atherosclerosis was generally similar; These results underscore the advantages of using subclinical measures of atherosclerosis in cross-sectional studies. In addition, they suggest that the presence of smoking, hypertension, or hypercholesterolemia in mid-adulthood may have some persisting effects on the development of atherosclerotic disease in later life. (C) 1999 Elsevier Science Inc. C1 Johns Hopkins Univ, Dept Epidemiol, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. Columbia Univ Coll Phys & Surg, Div Gen Med, New York, NY 10032 USA. Columbia Sch Publ Hlth, Div Epidemiol, New York, NY USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Nieto, FJ (reprint author), Johns Hopkins Univ, Dept Epidemiol, Sch Hyg & Publ Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55016, N01-HC-55015] NR 31 TC 17 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 1999 VL 52 IS 6 BP 559 EP 567 DI 10.1016/S0895-4356(99)00030-X PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 208WR UT WOS:000081015300011 PM 10408996 ER PT J AU Kersten, S Seydoux, J Peters, JM Gonzalez, FJ Desvergne, B Wrahli, W AF Kersten, S Seydoux, J Peters, JM Gonzalez, FJ Desvergne, B Wrahli, W TI Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACID-BINDING PROTEIN; PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; FATTY-ACIDS; PPAR-ALPHA; DIABETES-MELLITUS; REGULATORY GENES; LIPID-METABOLISM; GAMMA ACTIVATORS; DEFICIENT MICE; SUCKLING RATS AB Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPAR alpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPAR alpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPAR alpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPAR alpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPAR alpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free Fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPAR alpha mRNA is induced during fasting in wildtype mice. The data indicate that PPARa plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPAR alpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues. C1 Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. Univ Geneva, Fac Med, Dept Physiol, CH-1211 Geneva, Switzerland. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Wrahli, W (reprint author), Univ Lausanne, Inst Biol Anim, Batiment Biol, CH-1015 Lausanne, Switzerland. RI Peters, Jeffrey/D-8847-2011; Kersten, Sander/A-1116-2011; Wahli, Walter/B-1398-2009; Desvergne, Beatrice/C-8892-2016 OI Kersten, Sander/0000-0003-4488-7734; Wahli, Walter/0000-0002-5966-9089; Desvergne, Beatrice/0000-0001-5483-288X NR 51 TC 964 Z9 990 U1 12 U2 46 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1999 VL 103 IS 11 BP 1489 EP 1498 DI 10.1172/JCI6223 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VY UT WOS:000083468100004 PM 10359558 ER PT J AU Casanova, ML Bravo, A Ramirez, A de Escobar, GM Were, F Merlino, G Vidal, M Jorcano, JL AF Casanova, ML Bravo, A Ramirez, A de Escobar, GM Were, F Merlino, G Vidal, M Jorcano, JL TI Exocrine pancreatic disorders in transsgenic mice expressing human keratin 8 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MOUSE EPIDERMAL-KERATINOCYTES; SIMPLE EPITHELIAL KERATIN-8; TRANSGENIC MICE; INTERMEDIATE FILAMENTS; ACINAR-CELLS; DIFFERENTIATION MARKERS; MONOCLONAL-ANTIBODIES; TGF-ALPHA; NEOPLASIA; PROTEINS AB Kerarins K8 and K18 are the major components of the intermediate-filament cytoskeleton of simple epithelia. Increased levels of these keratins have been correlated with various tumor cell characteristics, including progression to malignancy, invasive behavior, and drug sensitivity, although a role for K8/K18 in tumorigenesis has not yet been demonstrated. To examine the function of these keratins, we generated mice expressing the human K8 (hk8) gene, which leads to a moderate keratin-content increase in their simple epithelia. These mice displayed progressive exocrine pancreas alterations, including dysplasia and loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine by adipose tissue, as well as increased cell proliferation and apoptosis. Histological changes were not observed in other simple epithelia, such as the Liver. Electron microscopy showed that transgenic acinar cells have keratins organized in abundant filament bundles dispersed throughout the cytoplasm, in contrast to control acinar cells, which have scarce and apically concentrated filaments. The phenotype found was very similar to that reported for transgenic mice expressing a dominant-negative mutant TGF-beta type II receptor (TGF beta RII mice). We show that these TGF beta RII mutant mice also have elevated K8/K18 levels. These results indicate that simple epithelial keratins play a relevant role in the regulation of exocrine pancreas homeostasis and support the idea that disruption of mechanisms that normally regulate keratin expression in vivo could be related to inflammatory and neoplastic pancreatic disorders. C1 Ctr Invest Energet Medioambientales & Technol, E-28040 Madrid, Spain. Univ Santiago de Compostela, Sch Vet, Dept Anim Pathol, E-27002 Lugo, Spain. CSIC, Inst Invest Biomed, Unidad Endocrinol Mol, E-28029 Madrid, Spain. Ctr Invest Biol, Dept Dev & Cell Biol, E-28006 Madrid, Spain. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Jorcano, JL (reprint author), Ctr Invest Energet Medioambientales & Technol, Av Complutense 22, E-28040 Madrid, Spain. EM jorcano@ciemat.es OI Vidal, Miguel/0000-0003-4374-6761 NR 54 TC 55 Z9 57 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1999 VL 103 IS 11 BP 1587 EP 1595 DI 10.1172/JCI5343 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VY UT WOS:000083468100014 PM 10359568 ER PT J AU Finkel, T AF Finkel, T TI Myocyte hypertrophy: the long and winding RhoA'd SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID RAT VENTRICULAR MYOCYTES; ACTIVATED PROTEIN-KINASES; MUSCLE CELL HYPERTROPHY; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; ALPHA(1)-ADRENERGIC RECEPTOR; PATHWAY; ORGANIZATION; DISSOCIATION; GTPASE C1 NIH, Cardiol Branch, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NIH, Cardiol Branch, Bldg 10,7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 20 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1999 VL 103 IS 12 BP 1619 EP 1620 DI 10.1172/JCI7459 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VZ UT WOS:000083468200002 PM 10377166 ER PT J AU Bi, S Gavrilova, O Gong, DW Marcus-Samuels, B Mason, MM Reitman, ML AF Bi, S Gavrilova, O Gong, DW Marcus-Samuels, B Mason, MM Reitman, ML TI Leptin and reproduction SO JOURNAL OF CLINICAL LIGAND ASSAY LA English DT Article ID RECEPTOR MESSENGER-RNA; NORMAL FEMALE MICE; SERUM LEPTIN; GESTATIONAL PROFILE; ONSET; PLACENTA; PUBERTY; GENE; EXPRESSION; STERILITY AB Leptin is a hormone that regulates metabolic efficiency, energy expenditure, and food intake (I). Leptin is secreted by adipose tissue in proportion to its degree of adiposity, and thus indicates the level of body fat stores. A low leptin level, signifying a paucity of fat, serves as a warning of food scarcity and causes animals to conserve fuel. High leptin levels, indicating excess fuel stores, signal that adipose stores are sufficient for energy-demanding activities. Many of the actions of leptin are thought to occur due to its effects on hypothalamic neurons. In this review we will analyze how these hypotheses apply to reproduction. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Reitman, ML (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 26 TC 0 Z9 0 U1 0 U2 1 PU CLINICAL LIGAND ASSAY SOC PI WAYNE PA 3139 S WAYNE RD, WAYNE, MI 48184 USA SN 1081-1672 J9 J CLIN LIGAND ASSAY JI J. Clin. Ligand Assay PD SUM PY 1999 VL 22 IS 2 BP 236 EP 238 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 235YK UT WOS:000082571300018 ER PT J AU Woods, GL Bergmann, JS Witebsky, FG Fahle, GA Wanger, A Boulet, B Plaunt, M Brown, BA Wallace, RJ AF Woods, GL Bergmann, JS Witebsky, FG Fahle, GA Wanger, A Boulet, B Plaunt, M Brown, BA Wallace, RJ TI Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; RESISTANCE; CLARITHROMYCIN; INFECTIONS; CEFOXITIN; SUBGROUPS; ORGANISM; AMIKACIN; FEATURES; THERAPY AB A multicenter study was conducted to assess the interlaboratory reproducibility of broth microdilution testing of the more common rapidly growing pathogenic mycobacteria. Ten isolates (four Mycobacterium fortuitum group, three Mycobacterium abscessus, and three Mycobacterium chelonae isolates) were tested against amikacin, cefoxitin, ciprofloxacin, clarithromycin, doxycycline, imipenem, sulfamethoxazole, and tobramycin (M. chelonae only) in four laboratories. At each site, isolates were tested three times on each of three separate days (nine testing events per isolate) with a common lot of microdilution trays. Agreement among MICs (i.e., mode +/- 1 twofold dilution) varied considerably for the different drug-isolate combinations and overall was best for cefoxitin (91.7 and 97.2% for one isolate each and 100% for all others), followed by doxycycline, amikacin, and ciprofloxacin. Agreement based on the interpretive category, using currently suggested breakpoints, also varied and overall was best for doxycycline (97.2% for one isolate and 100% for the rest), followed by ciprofloxacin and clarithromycin. Reproducibility among MICs and agreement by interpretive category was most variable for imipenem. Based on results reported from the individual sites, it appears that inexperience contributed significantly to the aide range of MICs of several drugs, especially clarithromycin, ciprofloxacin, and sulfamethoxazole. New interpretive guidelines are presented fur the testing of M. fortuitum against clarithromycin; M. abscessus and M. chelonae against the aminoglycosides; and all three species against cefoxitin, doxycycline, and imipenem. C1 Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. NIH, Microbiol Serv, Dept Clin Pathol, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Texas, Houston Med Sch, Dept Pathol, Houston, TX 77030 USA. StatProbe, Ann Arbor, MI 48108 USA. Univ Texas, Ctr Hlth, Dept Microbiol, Tyler, TX 75710 USA. RP Woods, GL (reprint author), Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. NR 24 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1999 VL 37 IS 6 BP 1676 EP 1682 PG 7 WC Microbiology SC Microbiology GA 197BN UT WOS:000080344900003 PM 10325306 ER PT J AU Sears, JF Repaske, R Khan, AS AF Sears, JF Repaske, R Khan, AS TI Improved Mg2+-based reverse transcriptase assay for detection of primate retroviruses SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT DNA POLYMERASE; VIRIONS; AIDS; TYPE-1; GENE AB The reverse transcriptase (RT) assay is a simple, relatively inexpensive, widely used assay that can detect all retroviruses (known and novel retroviruses as well as infectious and defective retroviruses) on the basis of the divalent cation requirement of their RT enzyme, i.e., Mg2+ or Mn2+. Descriptions of various RT assays have been published; however, they cannot be directly applied to the analysis of biological products or clinical samples without further standardization to determine the lower limit of virus detection (sensitivity), assay variability (reproducibility), or ability to detect different retroviruses (specificity). We describe the detection of type E and type D primate retroviruses, which may be pathogenic for humans, by a new P-32-based, Mg2+-containing RT assay. The results show that the sensitivity of detection is <3.2 50% tissue culture infective doses (TCID(50)s) for human immunodeficiency virus type 1 (HIV-1) and <1 TCID50 for simian immunodeficiency virus isolated from a rhesus macaque (SIVmac). Analysis of recombinant HIV-1 RT enzyme indicated that 10(-5) U, which is equivalent to 4.25 x 10(4) virions, could be detected. Additionally, genetically distinct type D retroviruses such as simian AIDS retrovirus and squirrel monkey retrovirus were also detected in the assay with similar sensitivities. Thus, the improved RT assay can be used to detect genetically divergent Mg2+-dependent retroviruses of human and simian origin that can infect human cells and that therefore pose a potential health risk to humans. C1 US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIAID, Mol Med Lab, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, 1404 Rockville Pike,HFM-454, Rockville, MD 20852 USA. NR 27 TC 9 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1999 VL 37 IS 6 BP 1704 EP 1708 PG 5 WC Microbiology SC Microbiology GA 197BN UT WOS:000080344900008 PM 10325311 ER PT J AU Amemiya, K Schaefer, H Pachner, AR AF Amemiya, K Schaefer, H Pachner, AR TI Isolation of DNA after extraction of RNA to detect the presence of Borrelia burgdorferi and expression of host cellular genes from the same tissue sample SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LYME NEUROBORRELIOSIS; DISEASE AB We are investigating the neuropathogenesis of Lyme disease caused by Borrelia burgdorferi in a nonhuman primate model. In the past, two separate pieces of tissue had to be used when both analyzing for the presence of the spirochete and examining the host response to infection. We have modified a procedure to purify DNA from the same sample after the extraction of RNA. The remaining material containing the DNA was precipitated, and residual organic reagent was removed prior to deproteinization and extraction of the DNA. This procedure now allows us to both assay for the presence of the Lyme microorganism and analyze the host response in the same tissue preparation. C1 NINDS, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Neurol, Sch Med, Washington, DC 20007 USA. RP Pachner, AR (reprint author), Univ Med & Dent New Jersey, Dept Neurosci, Bldg MSB H506,185 S Orange Ave, Newark, NJ 07103 USA. FU NINDS NIH HHS [R01 NS34715] NR 9 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1999 VL 37 IS 6 BP 2087 EP 2089 PG 3 WC Microbiology SC Microbiology GA 197BN UT WOS:000080344900086 PM 10325389 ER PT J AU Madico, G Quinn, TC Rompalo, A McKee, KT Gaydos, CA AF Madico, G Quinn, TC Rompalo, A McKee, KT Gaydos, CA TI Diagnosis of Trichomonas vaginalis infection by PCR using vaginal swab samples (vol 36, pg 3205, 1998) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Correction C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ Peruana Cayetano Heredia, Lima, Peru. Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Bethesda, MD USA. Womack Army Med Ctr, Ft Bragg, NC USA. RP Madico, G (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, 615 N Wolfe St, Baltimore, MD 21218 USA. RI Gaydos, Charlotte/E-9937-2010 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1999 VL 37 IS 6 BP 2124 EP 2124 PG 1 WC Microbiology SC Microbiology GA 197BN UT WOS:000080344900106 ER PT J AU Wadler, S Damle, S Haynes, H Kaleya, R Schechner, R Berkenblit, R Ladner, RD Murgo, A AF Wadler, S Damle, S Haynes, H Kaleya, R Schechner, R Berkenblit, R Ladner, RD Murgo, A TI Phase II pharmacodynamic trial of dose-intensive, weekly parenteral hydroxyurea and fluorouracil administered with interferon alfa-2a in patients with refractory malignancies of the gastrointestinal tract SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PREVIOUSLY UNTREATED PATIENTS; ADVANCED GASTRIC-CANCER; HUMAN TUMOR-CELLS; DNA-DAMAGE; DEOXYURIDINE TRIPHOSPHATE; RIBONUCLEOTIDE REDUCTASE; ADVANCED ADENOCARCINOMA; BIOCHEMICAL MODULATION; 5-FLUOROURACIL; CYTOTOXICITY AB Purpose: Combined depletion of pyrimidine and purine DNA precursors has resulted in therapeutic synergism in vitro. The aims of the current study were to test this strategy in patients with refractory tumors and to assess ifs effects on selected nucleotide pools. Patients and Methods: A single-institution phase II trial was initiated in patients with advanced carcinomas of the stomach and pancreas. Patients had measurable disease and had no prior chemotherapy except adjuvant fluorouracil (5FU) or gemcitabine. 5FU was administered by CADD + pump at 2.6 g/m(2) intravenously by 24-hour infusion on days 1, 8, 15, 22, 29, and 36. parenteral hydroxyurea (HU) was administered at 4.3 g/m(2) as a 24-hour infusion concurrently with 5FU, Interferon alfa aa (IFN-alpha 2a) wets administered at 9 million units subcutaneously on days 1, 3, and 5 each week, No drug was administered in weeks 7 and 8, Pharmacodynamic studies were performed to assess drug effects on levels of deoxyuridine triphosphate (dUTP) and thymidine triphosphate (TTP) pools in peripheral-blood mononuclear cells (PBMCs) before and 6 hours after-treatment using a highly sensitive DNA polymerase assay. Results: There were 53 patients enrolled onto the study (gastric carcinoma, 31; pancreatic carcinoma, 22). The median age was 61 years, with 22% of patients greater than or equal to 70 years old. The predominant grade 3 to 4 toxicities were leukopenia (49%), granulocytopenia (55%), and thrombocytopenia (22%), Severe diarrhea occurred in 12%, mucositis in 0%, and vomiting in 10% of patients. Patients greater than or equal to 70 years had no greater incidence of toxicities, Among the 30 assessable patients with gastric carcinoma, there were two (7%) complete responders and 11 (37%) partial responders (median duration, 7 months). Among the 21 assessable patients with pancreatic carcinoma, there was one responder. Median survival among all patients with gastric carcinoma was 10 months and 13 months far patients with pancreatic carcinoma. Twenty-three patients herd samples studied for levels of dUTP and TTP. There was no change in the levels of TTP before and after treatment, Furthermore, dUTP was detected in only five of 28 samples after treatment with no increase in the dUTP/TTP ratio. Conclusion: Combination therapy with high-dose, weekly infusional HU and 5FU with IFM-alpha 2a modulation wets well-tolerated with activity in gastric cancer, patients greater than or equal to 70 years tolerated therapy as well as younger patients. This was the first study to correlate levels of TTP and dUTP after treatment with clinical outcome. In PBMCs used as a surrogate tissue, HU abrogated the 5FU-induced increase in dUTP levels without reversing the overall efficacy of the regimen. (C) 1999 by American Society of Clinical Oncology. C1 Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Surg, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Radiol, Bronx, NY 10467 USA. Albert Einstein Canc Ctr, Bronx, NY USA. Univ Med & Dent New Jersey, Dept Biol Mol, Newark, NJ 07103 USA. Sch Osteopath Med, Stratford, NJ USA. NCI, Investigat Drug Branch, NIH, Bethesda, MD USA. RP Wadler, S (reprint author), Montefiore Med Ctr, Dept Oncol, 111 E 210Th St, Bronx, NY 10467 USA. FU NCI NIH HHS [R21CA72443-01, CA 13330] NR 43 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 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1999 VL 17 IS 6 BP 1771 EP 1778 PG 8 WC Oncology SC Oncology GA 206AA UT WOS:000080852800015 PM 10561214 ER PT J AU Chute, JP Chen, T Feigal, E Simon, R Johnson, BE AF Chute, JP Chen, T Feigal, E Simon, R Johnson, BE TI Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: Perceptible progress SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; RANDOMIZED CLINICAL-TRIAL; CISPLATIN PLUS ETOPOSIDE; LEUKEMIA GROUP-B; QUALITY-OF-LIFE; ALTERNATING CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; DOSE CYCLOPHOSPHAMIDE; CARCINOMA; DOXORUBICIN AB Purpose: All cooperative group studies performed in North America for patients with extensive-stage small-cell lung cancer (SCLC) were evaluated to determine the pattern of the clinical trials and the outcome of patients over the past 20 years. Patient and Methods: Phase III trials for patients with extensive-stage SCLC were identified through a search of the National Cancer Institute Cancer Therapy Evaluation Program database from 1972 to 1993. Patients with extensive-stage SCLC treated during a similar rime interval listed in the Surveillance, Epidemiology, and End Results (SEER) database were also examined. Trends were tested in the number of trials over time, the number and sex of patients entered onto the trials, and the survival time of patients treated over time, Results: Twenty-one phase III trials far patients with extensive-stage SCLC were initiated between 1972 and 1990. The median of the median survival times of patients treated on the control arms of the phase III trials initiated between 1972 and 1981 was 7.0 months; for those patients enrolled onto control arms between 1982 and 1990, the median survival rime was 8.9 months (P = .001). Analysis of the SEER database of patients with extensive-stage SCLC over the same time period shows a similar 2-month prolongation in median survival time. Conclusion: Analysis of 21 phase III trials initiated in North America and the SEER database from 1972 Po 1994 demonstrates that there has been a modest improvement in the survival time of patients with expensive-stage SCLC. (C) 1999 by American Society of Clinical Oncology. C1 Natl Naval Med Ctr, Naval Med Res Inst, Bethesda, MD USA. Natl Naval Med Ctr, Div Hematol Oncol, Bethesda, MD USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Clin Invest Branch, Bethesda, MD 20892 USA. NCI, Lung Canc Biol Sect, Med Branch, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Johnson, BE (reprint author), NCI, Lung Canc Biol Sect, Med Branch, Natl Naval Med Ctr, Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 37 TC 227 Z9 239 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1999 VL 17 IS 6 BP 1794 EP 1801 PG 8 WC Oncology SC Oncology GA 206AA UT WOS:000080852800018 PM 10561217 ER PT J AU Schulz, SC Thompson, PA Jacobs, M Ninan, PT Robinson, D Weiden, PJ Yadalam, K Glick, ID Odbert, CL AF Schulz, SC Thompson, PA Jacobs, M Ninan, PT Robinson, D Weiden, PJ Yadalam, K Glick, ID Odbert, CL TI Lithium augmentation fails to reduce symptoms in poorly responsive schizophrenic outpatients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; PSYCHOTIC SYMPTOMS; HALOPERIDOL; CARBAMAZEPINE; CARBONATE; CHLORPROMAZINE; NEUROLEPTICS; FLUPHENAZINE; PROPRANOLOL; THERAPY AB Background: Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study. Method: Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study. Results: Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium. Conclusion: Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation. C1 Case Western Reserve Univ, Dept Psychiat, Sch Med, Cleveland, OH 44106 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. Emory Univ, Grady Mem Hosp, Dept Psychiat, Atlanta, GA 30322 USA. Hillside Hosp, Glen Oaks, NY 11004 USA. St Lukes Roosevelt Hosp, Dept Psychiat, New York, NY USA. Eastern Penn Psychiat Inst, Med Coll Penn, Dept Psychiat, Philadelphia, PA USA. Stanford Univ, Dept Psychiat & Behav Sci, San Francisco, CA USA. NIMH, Rockville, MD 20857 USA. RP Schulz, SC (reprint author), Case Western Reserve Univ, Dept Psychiat, Sch Med, 11100 Euclid Ave,Hanna Pavil, Cleveland, OH 44106 USA. FU NIMH NIH HHS [U01 MH40007, U01 MH39992, U01 MH39998] NR 47 TC 20 Z9 20 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1999 VL 60 IS 6 BP 366 EP 372 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 211XN UT WOS:000081187300003 PM 10401914 ER PT J AU Lavori, PW Bloch, DA Bridge, PT Leiderman, DB LoCastro, JS Somoza, E AF Lavori, PW Bloch, DA Bridge, PT Leiderman, DB LoCastro, JS Somoza, E TI Plans, designs, and analyses for clinical trials of anti-cocaine medications: Where we are today SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID TO-TREAT ANALYSIS; RELAPSE PREVENTION; INSTRUMENTAL VARIABLES; MULTIPLE IMPUTATION; REGRESSION-MODELS; LONGITUDINAL DATA; PATIENT DATA; PSYCHOTHERAPY; DEPENDENCE; ABUSERS AB Increased interest in addiction psychopharmacology has raised unique methodologic issues in the design, conduct, and analysis of outcomes in clinical trials of therapeutic agents for drug dependence. This article summarizes issues raised at a meeting in Pale Alto, California, on November 4, 1996, that was sponsored by the Medication Development Division of the National Institute on Drug Abuse and the Department of Veterans Affairs Cooperative Studies Program to discuss the methodologic issues in clinical trials of cocaine pharmacotherapy. C1 Palo Alto VAHCS 151K, VA Cooperat Studies Program, Coordinating Ctr, Palo Alto, CA 94304 USA. Stanford Univ, Palo Alto, CA 94304 USA. NIDA, Bethesda, MD USA. Boston VAMC, Boston, MA USA. Cincinnati VAMC, Cincinnati, OH USA. RP Lavori, PW (reprint author), Palo Alto VAHCS 151K, VA Cooperat Studies Program, Coordinating Ctr, 3801 Miranda Ave, Palo Alto, CA 94304 USA. FU NIDA NIH HHS [Y01DA 40032] NR 59 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1999 VL 19 IS 3 BP 246 EP 256 DI 10.1097/00004714-199906000-00008 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 197BP UT WOS:000080345000007 PM 10350031 ER PT J AU Pang, XL Joensuu, J Hoshino, Y Kapikian, AZ Vesikari, T AF Pang, XL Joensuu, J Hoshino, Y Kapikian, AZ Vesikari, T TI Rotaviruses detected by reverse transcription polymerase chain reaction in acute gastroenteritis during a trial of rhesus-human reassortant rotavirus tetravalent vaccine: implications for vaccine efficacy analysis SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article; Proceedings Paper CT 1998 European-Society-for-Clinical-Virology Meeting on Progress in Clinical Virology IV CY 1998 CL HAMBURG, GERMANY SP European Soc Clin Virol DE rotavirus; gastroenteritis; rhesus rotavirus vaccine; RT-PCR ID YOUNG-CHILDREN; RIT-4237; INFANTS; SAFETY AB Background: Rotaviruses are routinely diagnosed by detection of rotavirus antigen in stools using an enzyme immunoassay (EIA). A sensitive method, like reverse transcription polymerase chain reaction (RT-PCR), may reveal more rotaviruses, but the clinical significance of such findings is not well established. Objectives: To study whether RT-PCR can detect more episodes of rotavirus-associated gastroenteritis than EIA and to determine how rotavirus RT-PCR findings might change efficacy analysis of a rotavirus vaccine trial, in which the outcome measure was rotavirus gastroenteritis diagnosis with EIA. Study design: We applied RT-PCR for detection of rotaviruses in gastroenteritis episodes encountered in an efficacy trial of rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine, in a total of 2398 infants. During a follow-up, covering two rotavirus epidemic seasons, 256 cases of rotavirus associated gastroenteritis were detected by EIA; 226 were in the primary efficacy analysis period that included children who had received three doses of vaccine or placebo. Results: With RT-PCR, 84 (33%) more cases of rotavirus gastroenteritis were diagnosed than with EIA, 65 of these were in the primary efficacy analysis period. Clinically, cases of rotavirus gastroenteritis diagnosed by RT-PCR were much milder (median severity score 6 on a 20-point scale) than those diagnosed by EIA (median score 11), P < 0.0001. RT-PCR revealed proportionally more G2 and G4 rotaviruses than EIA. GI rotaviruses detected by RT-PCR were almost equally divided between RRV-TV (25) vaccine and placebo (28) groups, whereas an apparent vaccine protective effect was seen in the distribution of G2 tone in the RRV-TV and eight in the placebo group) and G4 rotaviruses (six in the RRV-TV and 14 in the placebo group). Conclusion: RT-PCR is a useful tool in the diagnosis of rotavirus gastroenteritis, particularly for cases associated with other than the epidemiologically dominant G-type. Application of RT-PCR contributes to the overall appraisal of performance of rotavirus vaccine. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Tampere Univ, Sch Med, Dept Virol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Pediat, Tampere, Finland. NIAID, Infect Dis Lab, NIH, Bethesda, MD USA. RP Pang, XL (reprint author), Tampere Univ, Sch Med, Dept Virol, POB 607, FIN-33101 Tampere, Finland. EM llxipa@uta.fi NR 28 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUN PY 1999 VL 13 IS 1-2 BP 9 EP 16 DI 10.1016/S1386-6532(98)00013-4 PG 8 WC Virology SC Virology GA 211TU UT WOS:000081178600002 PM 10405887 ER PT J AU Wang, JTL Rozen, S Shapiro, BA Shasha, D Wang, ZY Yin, MS AF Wang, JTL Rozen, S Shapiro, BA Shasha, D Wang, ZY Yin, MS TI New techniques for DNA sequence classification SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE algorithms; consensus sequence; DNA sequence recognition; pattern matching; tools for computational biology ID ESCHERICHIA-COLI PROMOTERS; MESSENGER-RNA PRECURSORS; NUCLEIC-ACID SEQUENCES; PROTEIN SEQUENCES; BINDING SITES; RECOGNITION; IDENTIFICATION; PREDICTION; SEARCH; SIMILARITY AB DNA sequence classification is the activity of determining whether or not an unlabeled sequence S belongs to an existing class C. This paper proposes two new techniques for DNA sequence classification. The first technique works by comparing the unlabeled sequence S with a group of active motifs discovered from the elements of C and by distinction with elements outside of C. The second technique generates and matches gapped fingerprints of S with elements of C. Experimental results obtained by running these algorithms on long and well conserved Alu sequences demonstrate the good performance of the presented methods compared with FASTA. When applied to less conserved and relatively short functional sites such as splice-junctions, a variation of the second technique combining fingerprinting with consensus sequence analysis gives better results than the current classifiers employing text compression and machine learning algorithms. C1 New Jersey Inst Technol, Dept Comp & Informat Sci, Newark, NJ 07102 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA USA. NCI, Image Proc Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Frederick, MD 21701 USA. NYU, Courant Inst Math Sci, New York, NY USA. Wyeth Ayerst Res, Princeton, NJ 08543 USA. RP New Jersey Inst Technol, Dept Comp & Informat Sci, Univ Hts, Newark, NJ 07102 USA. EM jason@cis.njit.edu OI Rozen, Steven G./0000-0002-4288-0056 NR 42 TC 20 Z9 22 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PD SUM PY 1999 VL 6 IS 2 BP 209 EP 218 DI 10.1089/cmb.1999.6.209 PG 10 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 214TN UT WOS:000081343800004 PM 10421523 ER PT J AU Ribeiro, JMC Katz, O Pannell, LK Waitumbi, J Warburg, A AF Ribeiro, JMC Katz, O Pannell, LK Waitumbi, J Warburg, A TI Salivary glands of the sand fly Phlebotomus papatasi contain pharmacologically active amounts of adenosine and 5 '-AMP SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE protein phosphatase; phosphorylase a; AMP; adenosine; HPLC; electrospray mass spectrometry; bioassay; platelet; aorta; haemostasis; sand fly; Phlebotomus papatasi ID ENDOTHELIUM-DEPENDENT RELAXATION; OXIDE SYNTHASE EXPRESSION; NITRIC-OXIDE; LUTZOMYIA-LONGIPALPIS; PLATELET-AGGREGATION; MURINE MACROPHAGES; RECEPTOR AGONISTS; RAW-264.7 MACROPHAGES; TNF-ALPHA; AORTA AB Salivary gland homogenates of the sand fly Phlebotomus papatasi contain large amounts of adenosine and 5'-AMP, of the order of 1 nmol per pair of glands, as demonstrated by liquid chromatography, ultraviolet spectrometry, mass spectrometry and bioassays. These purines, 75-80 % of which are secreted from the glands following a blood meal, hare vasodilatory and anti-platelet activities and probably help the fly to obtain a blood meal. Salivary 5'-AMP is also responsible for the previously reported protein phosphatase inhibitor in the salivary glands of P, papatasi, which is shown to be artifactual in nature as a result of allosteric modification by AMP of the phosphatase substrate used (phosphorylase a). C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Dept Parasitol, Kuvin Ctr Study Infect & Trop Dis, Hadassah Med Sch, IL-91120 Jerusalem, Israel. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [AI36382] NR 34 TC 48 Z9 48 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JUN PY 1999 VL 202 IS 11 BP 1551 EP 1559 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 207HE UT WOS:000080930700010 PM 10229701 ER PT J AU LeBeau, AP Yule, DI Groblewski, GE Sneyd, J AF LeBeau, AP Yule, DI Groblewski, GE Sneyd, J TI Agonist-dependent phosphorylation of the inositol 1,4,5-trisphosphate receptor - A possible mechanism for agonist-specific calcium oscillations in pancreatic acinar cells SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE inositol 1,4,5-trisphosphate receptor phosphorylation; protein kinase A; mathematical model; calcium oscillations ID CYTOPLASMIC CA2+ OSCILLATIONS; INSP(3) RECEPTOR; PROTEIN-KINASE; TRISPHOSPHATE RECEPTORS; CYTOSOLIC CA2+; DIFFERENTIAL REGULATION; DIFFERENT PATTERNS; WAVE-PROPAGATION; RELEASE; CA-2+ AB The properties of inositol 1,4,5 -trisphosphate (IP3,)-dependent intracellular calcium oscillations in pancreatic acinar cells depend crucially on the agonist used to stimulate them. Acetylcholine or carbachol (CCh) cause high-frequency (10-12-s period) calcium oscillations that are superimposed on a raised baseline, while cholecystokinin (CCK) causes long-period (>100s period) baseline spiking. We show that physiological concentrations of CCK induce rapid phosphorylation of the IP3 receptor, which is not true of physiological concentrations of CCh. Based on this and other experimental data, we construct a mathematical model of agonist-specific intracellular calcium oscillations in pancreatic acinar cells. Model simulations agree with previous experimental work on the rates of activation and inactivation of the IF, receptor by calcium (DuFour, J.-F., I.M. Arias, and T.J. Turner. 1997. J. Biol. Chem. 272:2675-2681), and reproduce both short-period, raised baseline oscillations, and long-period baseline spiking. The steady state open probability curve of the model IF, receptor is an increasing function of calcium concentration, as found for type-III IF, receptors by Hagar et al. (Hagar, R.E., A.D. Burgstahler, M.H. Nathanson, and B.E. Ehrlich. 1998. Nature. 396:81-84). We use the model to predict the effect of the removal of external calcium, and this prediction is confirmed experimentally. We also predict that, for type-III IP3 receptors, the steady state open probability curve will shift to lower calcium concentrations as the background IP3 concentration increases. We conclude that the differences between CCh- and CCK-induced calcium oscillations in pancreatic acinar cells can be explained by two principal mechanisms: (a) CCK causes more phosphorylation of the IP3 receptor than does CCh, and the phosphorylated receptor cannot pass calcium current; and (b) the rate of calcium ATPase pumping and the rate of calcium influx from the outside the cell are greater in the presence of CCh than in the presence of CCK. C1 Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA. NIH, Math Res Branch, Bethesda, MD 20892 USA. RP Sneyd, J (reprint author), Univ Michigan, Dept Math, 525 E Univ Ave,E Hall, Ann Arbor, MI 48109 USA. RI Sneyd, James/C-8995-2009 OI Sneyd, James/0000-0001-7305-2862 FU NIDDK NIH HHS [R01 DK054568, R01 DK54568]; NIGMS NIH HHS [R01 GM56126] NR 74 TC 83 Z9 83 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUN PY 1999 VL 113 IS 6 BP 851 EP 871 DI 10.1085/jgp.113.6.851 PG 21 WC Physiology SC Physiology GA 205GW UT WOS:000080813800010 PM 10352035 ER PT J AU Etzioni, RD Feuer, EJ Sullivan, SD Lin, DY Hu, CC Ramsey, SD AF Etzioni, RD Feuer, EJ Sullivan, SD Lin, DY Hu, CC Ramsey, SD TI On the use of survival analysis techniques to estimate medical care costs SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE survival analysis techniques; treatment costs; medical interventions ID CONFIDENCE-INTERVALS; ECONOMIC-EVALUATION; CANCER; HOSPITALIZATION; ISSUES; RATIOS AB Measurement of treatment costs is important in the evaluation of medical interventions. Accurate cost estimation is problematic, when cost records are incomplete. Methods from the survival analysis literature have been proposed for estimating costs using available data. In this article, we clarify assumptions necessary for validity of these techniques. We demonstrate how assumptions needed for valid survival analysis may be violated when these methods are applied to cost estimation. Our observations are confirmed through simulations and empirical data analysis. We conclude that survival analysis approaches are not generally appropriate for the analysis of medical costs and review several valid alternatives. (C) 1999 Elsevier Science B.V. All rights reserved. JEL classification: C000 Mathematical and quantitative methods: general; C100 Econometric and statistical methods: general; C400 Econometric and statistical methods: special topics: general. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Bethesda, MD 20892 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Etzioni, RD (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP-665,POB 19024, Seattle, WA 98109 USA. RI Hu, Chengcheng/A-8391-2017 FU NCI NIH HHS [NCI N01-CN-05230] NR 30 TC 67 Z9 67 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD JUN PY 1999 VL 18 IS 3 BP 365 EP 380 DI 10.1016/S0167-6296(98)00056-3 PG 16 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 200EP UT WOS:000080526900005 PM 10537900 ER PT J AU Tichelaar, JW Wert, SE Costa, RH Kimura, S Whitsett, JA AF Tichelaar, JW Wert, SE Costa, RH Kimura, S Whitsett, JA TI HNF-3/Forkhead homologue-4 (HFH-4) is expressed in ciliated epithelial cells in the developing mouse lung SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE HFH-4; lung; cilia; beta-tubulin IV ID SURFACTANT PROTEIN-B; THYROID TRANSCRIPTION FACTOR-1; HEPATOCYTE NUCLEAR FACTOR-3; FACTOR-I; TRACHEAL EPITHELIUM; SECRETORY PROTEIN; PROGENITOR CELLS; GENE-EXPRESSION; FORK HEAD; DIFFERENTIATION AB HNF-3/forkhead homologue-4 (HFH-4), a transcription factor of the winged-helix/forkhead family, was detected by immunohistochemistry in tissue of the developing mouse. HFH-4 protein was present in epithelial cells of the lung, trachea, oviduct, and embryonic esophagus, and in ependymal cells lining the spinal column and ventricles of the brain. In lung, trachea, acid nose, HFH-4 was expressed in a distinct subset of epithelial cells that also expressed beta-tubulin IV, a ciliated cell marker. Cellular sites of HFH-4 and beta-tubulin IV expression were distinct from that of Clara cell secretory protein (CCSP), which was detected in nonciliated epithelial cells in the conducting airway of the lung. HFH-4 and beta-tubulin IV, but not CCSP, were detected in the respiratory epithelium of thyroid transcription factor-1 (TTF-1) gene-targeted mice. The presence of HFH-4 and beta-tubulin IV in TTF-1 gene-targeted mice demonstrates that differentiation of ciliated epithelium does not require TTF-1. Co-localization of HFH-4 and beta-tubulin IV staining in various tissues during mouse development supports a role for HFH-4 in the differentiation of ciliated cell lineages. C1 Childrens Hosp, Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA. Univ Illinois, Dept Biochem & Mol Biol, Chicago, IL USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Whitsett, JA (reprint author), Childrens Hosp, Med Ctr, Div Neonatol & Pulm Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. RI Tichelaar, Jay/B-9148-2011 FU NHLBI NIH HHS [HL 41496, HL 56387] NR 29 TC 65 Z9 65 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 1999 VL 47 IS 6 BP 823 EP 831 PG 9 WC Cell Biology SC Cell Biology GA 198YH UT WOS:000080451800012 PM 10330459 ER PT J AU Sousa, CRE Germain, RN AF Sousa, CRE Germain, RN TI Analysis of adjuvant function by direct visualization of antigen presentation in vivo: Endotoxin promotes accumulation of antigen-bearing dendritic cells in the T cell areas of lymphoid tissue SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II COMPLEXES; IN-VIVO; MONOCLONAL-ANTIBODY; DEVELOPMENTAL REGULATION; SURFACE EXPRESSION; INDUCED APOPTOSIS; INNATE IMMUNITY; B-LYMPHOCYTES; SELF-PEPTIDE; SPLEEN AB T cell activation requires exposure to processed Ag and signaling by cytokines and costimulatory ligands, Adjuvants are thought to enhance immunity primarily through up-regulation of the latter signals, Here, we explore the effect of the bacterial adjuvant, endotoxin, on Ag presentation by B cells and dendritic cells (DC), Using an mAb (C4H3) specific for the hen egg lysozyme (HEL) 46-61 determinant bound to I-A(k), we analyze processed Ag expression and the tissue distribution of presenting cells following systemic administration of soluble HEL to mice. In both LPS-responsive and -hyporesponsive mice given endotoxin-containing HEL, B cells rapidly display surface 46-61/I-A(k) complexes. In marked contrast, in LPS-hyporesponsive mice, splenic DC show little gain in C4H3 staining. In LPS-responsive animals, interdigitating DC in T cell areas show no staining above background at early times after HEL administration, but C4H3(+) DC rapidly accumulate in the outer periarteriolar lymphoid sheaths (PALS) and in follicular areas. Within a few hours, C4H3(+) DC appear in the T cell areas,concomitant with a decline in C4H3(+) cells in the outer PALS, suggesting migration between these two sites. Endotoxin enhancement of C4H3 staining is seen for both CD8 alpha(-) and CD8 alpha(+) DC subsets. These data suggest that a major effect of adjuvants is to promote mobilization of Ag-bearing DC to the T areas of lymphoid tissue, and possibly also to enhance Ag processing by these DC. Thus; microbial products promote T cell immunity not only through DC activation for cosignaling,,but through improvement in signal 1 delivery. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM ronald_germain@nih.gov NR 55 TC 94 Z9 95 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1999 VL 162 IS 11 BP 6552 EP 6561 PG 10 WC Immunology SC Immunology GA 198VC UT WOS:000080444100033 ER PT J AU Manca, C Tsenova, L Barry, CE Bergtold, A Freeman, S Haslett, PAJ Musser, JM Freedman, VH Kaplan, G AF Manca, C Tsenova, L Barry, CE Bergtold, A Freeman, S Haslett, PAJ Musser, JM Freedman, VH Kaplan, G TI Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; BACILLUS-CALMETTE-GUERIN; INTERFERON-GAMMA; HUMAN MONOCYTES; IMMUNE-RESPONSE; FACTOR-ALPHA; IN-VITRO; INTERLEUKIN-12; MICE; INFECTION AB Mycobacterium tuberculosis CDC1551, a clinical isolate reported to be hypervirulent and to grow faster than other isolates, was compared with two other clinical isolates (HN60 and HN878) and two laboratory strains (H37Rv and Erdman), The initial (2-14 days) growth of CDC1551; HN60, HN878, and H37Rv was similar in the lungs of aerosol-infected mice, but growth of Erdman was slower, Thereafter, the growth rate of CDC1551 decreased relative to the other strains which continued to grow at comparable rates up to day 21, In-the lungs of CDC1551-infected mice, small well-organized granulomas with high levels of TNF-alpha, IL-6, IL-10, IL-12, and IFN-gamma mRNA were apparent sooner than in lungs of mice infected with the other strains. CDC1551-infected mice survived significantly longer. These findings were confirmed in vitro. The growth rate of HR37Rv and CDC1551 in human monocytes were the same, but higher levels of TNF-alpha IL-10, IL-6, and IL-12 were induced in monocytes after infection with CDC1551 or by exposure of monocytes to lipid fractions from CDC1551, CD14 expression on the surface of the monocytes was up-regulated to a greater extent by exposure to the lipids of CDC1551. Thus, CDC1551 is not more virulent than other M. tuberculosis isolates in terms-of growth in vivo and in vitro, but it induces a more rapid and robust host response. C1 Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA. NIAID, TB Res Sect, LHD, Rockville, MD 20852 USA. Baylor Coll Med, Dept Pathol, Inst Study Human Bacterial Pathogenesis, Houston, TX 77030 USA. RP Kaplan, G (reprint author), Rockefeller Univ, Cellular Physiol & Immunol Lab, 1230 York Ave, New York, NY 10021 USA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [R01 AI054338, AI42056]; NIDA NIH HHS [DA09238] NR 34 TC 200 Z9 201 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1999 VL 162 IS 11 BP 6740 EP 6746 PG 7 WC Immunology SC Immunology GA 198VC UT WOS:000080444100055 PM 10352293 ER PT J AU Hendel, H Caillat-Zucman, S Lebuanec, H Carrington, M O'Brien, S Andrieu, JM Schachter, F Zagury, D Rappaport, J Winkler, C Nelson, GW Zagury, JF AF Hendel, H Caillat-Zucman, S Lebuanec, H Carrington, M O'Brien, S Andrieu, JM Schachter, F Zagury, D Rappaport, J Winkler, C Nelson, GW Zagury, JF TI New class I and IIHLA alleles strongly associated with opposite patterns of progression to AIDS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; HIV-INFECTION; DISEASE PROGRESSION; CELL EPITOPES; HLA; RESPONSES; GENES; PATHOGENESIS; RECOGNITION AB The genetics of resistance to infection by HIV-1 cohort consists of 200 slow and 75 rapid progressors to AIDS corresponding to the extremes of HIV disease outcome of 20,000 Caucasians of European descent. A comprehensive analysis of HLA class I and class II genes in this highly informative cohort has identified HLA alleles associated with fast or slow progression, including several not described previously. A quantitative analysis shows an overall HLA influence independent of and equal in magnitude (for the protective effect) to the effect of the CCR5-Delta 32 mutation. Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression, The class I alleles B27, B57, C14 (protective), and C16, as well as B35 (susceptible), are also influential, but their effects are less robust. Influence of class II alleles was only observed for DR11, These results confirm the influence of the immune system on disease progression and may have implications on peptide-based vaccine development. C1 Univ Paris 06, Lab Physiol Cellulaire, F-75005 Paris, France. Hop Necker Enfants Malad, Immunol Lab, Paris, France. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Lab Genomic Divers, Ft Detrick, MD 21702 USA. Hop Laennec, Serv Cancerol, SIDA, F-75340 Paris, France. MCP Hahnemann Univ Hlth Sci, Ctr Neurovirol & Neurooncol, Philadelphia, PA 19102 USA. RP Zagury, JF (reprint author), Univ Paris 06, Lab Physiol Cellulaire, 4 Pl Jussieu, F-75005 Paris, France. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 231 Z9 236 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1999 VL 162 IS 11 BP 6942 EP 6946 PG 5 WC Immunology SC Immunology GA 198VC UT WOS:000080444100079 PM 10352317 ER PT J AU Durbin, AP Cho, CJ Elkins, WR Wyatt, LS Moss, B Murphy, BR AF Durbin, AP Cho, CJ Elkins, WR Wyatt, LS Moss, B Murphy, BR TI Comparison of the immunogenicity and efficacy of a replication-defective vaccinia virus expressing antigens of human parainfluenza virus type 3 (HPIV3) with those of a live attenuated HPIV3 vaccine candidate in rhesus monkeys passively immunized with PIV3 antibodies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 17th Meeting of the American-Society-for-Virology CY JUL 11-15, 1998 CL VANCOUVER, CANADA SP Amer Soc Virol ID PARA-INFLUENZA; RECOMBINANT VIRUSES; FUSION F; INFANTS; CHILDREN; BOVINE; GLYCOPROTEINS; INFECTION; PROTEINS; HEMAGGLUTININ AB Two parainfluenza virus type 3 (PIV3) vaccine candidates-cp45, a live attenuated derivative of the JS wild type (wt), and a replication-defective vaccinia virus recombinant expressing the hemagglutinin-neuraminidase or fusion glycoprotein of human PIV3 (modified vaccinia virus Ankara [MVA]/PIV3 recombinants)-were evaluated in rhesus monkeys to determine whether successful immunization could be achieved in the presence of passively transferred PIV3 antibodies. The cp45 virus, administered intranasally (in) and intratracheally (it) in the presence of high levels of PIV3 antibodies, replicated efficiently in the nasopharynx and protected against challenge with wt human PIV3, The MVA recombinants, administered in, it, and intramuscularly in the absence of passive antibody, conferred protection against replication of PIV3 wt challenge virus, but this was largely abrogated when immunization occurred in the presence of passive antibodies. Because immunization for the prevention of HPIV3 disease must occur in early infancy when maternal antibodies are present, the live attenuated cp45 virus continues to be a promising vaccine candidate for this age group. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Durbin, AP (reprint author), 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 44 TC 28 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1999 VL 179 IS 6 BP 1345 EP 1351 DI 10.1086/314769 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 200VQ UT WOS:000080561100005 PM 10228053 ER PT J AU Montenegro, SML Miranda, P Mahanty, S Abath, FGC Teixeira, KM Coutinho, EM Brinkman, J Goncalves, I Domingues, LAW Domingues, ALC Sher, A Wynn, TA AF Montenegro, SML Miranda, P Mahanty, S Abath, FGC Teixeira, KM Coutinho, EM Brinkman, J Goncalves, I Domingues, LAW Domingues, ALC Sher, A Wynn, TA TI Cytokine production in acute versus chronic human schistosomiasis mansoni: The cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Congress for Schistosomiasis Research CY OCT, 1997 CL BELO HORIZONT, BRAZIL ID HUMAN LYMPHATIC FILARIASIS; MURINE SCHISTOSOMIASIS; IMMUNE-RESPONSES; IN-VIVO; HEPATOSPLENIC DISEASE; GRANULOMA-FORMATION; DOWN-REGULATION; TH2 CYTOKINES; KALA-AZAR; IFN-GAMMA AB The contribution of interleukin (IL)-10 and interferon (IFN)-gamma to the regulation of type 1 and type 2 cytokine responses was investigated in Brazilians with different clinical forms of schistosomiasis mansoni. Cells from members of a family with acute intestinal schistosomiasis responded to schistosomal soluble egg antigen (SEA) or soluble adult worm antigen preparation (SWAP) with greater amounts of IFN-gamma than did cells from several patients with chronic intestinal schistosomiasis; IL-10 levels were similar, Neutralization of IL-10 had no effect on the SEA-specific IFN-gamma response in patients with acute infection, whereas SWAP-induced IFN-gamma was increased in both groups. Anti-IL-10 also up-regulated SEA-specific IFN-gamma protein and mRNA responses in most splenocyte cultures from hepatosplenic schistosomiasis patients but had no effect on antigen-specific IL-4 or IL-5 production. Neutralization of IFN-gamma resulted in a comparable increase in SWAP-specific IL-10 and IL-5, while IL-4 was not affected. These studies demonstrate that early disease in schistosomiasis is associated with a significant IFN-gamma response and that IL-10 contributes to the suppression of that response during both early and chronic infection. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Fed Pernambuco, Dept Imunol, Ctr Pesquisas Aggeu Magalhaes, FIOCRUZ, Recife, PE, Brazil. Univ Fed Pernambuco, Lab Imunopatol Keizo Asami, Recife, PE, Brazil. Ctr Dis Control & Prevent, Special Pathogens Branch, Atlanta, GA USA. RP Wynn, TA (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4-126, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 46 TC 81 Z9 85 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1999 VL 179 IS 6 BP 1502 EP 1514 DI 10.1086/314748 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 200VQ UT WOS:000080561100025 PM 10228073 ER PT J AU Ashkenazi, S Passwell, JH Harlev, E Miron, D Dagan, R Farzan, N Ramon, R Majadly, F Bryla, DA Karpas, AB Robbins, JB Schneerson, R AF Ashkenazi, S Passwell, JH Harlev, E Miron, D Dagan, R Farzan, N Ramon, R Majadly, F Bryla, DA Karpas, AB Robbins, JB Schneerson, R CA Israel Pediat Shigella Study Grp TI Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-for-Pediatric-Research CY MAY 02-06, 1997 CL WASHINGTON, D.C. SP Soc Pediat Res ID VACCINES; ANTIBODIES; LIPOPOLYSACCHARIDE; IMMUNITY; ISRAEL AB O-specific polysaccharide conjugates of shigellae were safe and immunogenic in young adults, and a Shigella sonnei conjugate conferred protection [1-3], Shigellosis is primarily a disease of children; therefore, the safety and immunogenicity of S. sonnei and Shigella flexneri 2a conjugates were studied in 4- to 7-year-old children. Local and systemic reactions were minimal. The first injection of both conjugates elicited significant rises in geometric mean levels of serum IgG only to the homologous lipopolysaccharide (LPS) (S, sonnei, 0.32-8.25 ELISA units [EU]; S. flexneri 2a, 1.15-20.5 EU; P < .0001), Revaccination at 6 weeks induced a booster response to S. flexneri 2a LPS (20.5-30.5 EU, P = .003). Six months later, the geometric mean levels of Ige anti-LPS for both groups were higher than the prevaccination levels (P < .0001). Similar, but lesser, rises were observed for IgM and IgA anti-LPS, The investigational Shigella conjugates were safe and immunogenic in children and merit evaluation of their efficacy. C1 Schneider Childrens Med Ctr Israel, Felsenstein Res Ctr, Petah Tiqwa, Israel. Haemek Med Ctr, Chaim Sheba Med Ctr, Dept Pediat, Samuel Jared Kushnick Pediat Immunol Lab, Afula, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Soroka Med Ctr, Pediat Infect Dis Unit, Beer Sheva, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NICHHD, NIH, Bethesda, MD 20892 USA. Hadassah Med Ctr, IL-91120 Jerusalem, Israel. Carmel Med Ctr, Haifa, Israel. Community Clin, Daliat El Carmel, Israel. Community Clin, Petah Tiqwa, Israel. Community Clin, Kibbutz Yagur, Israel. Community Clin, Kibbutz Hulda, Israel. Community Clin, Kibbutz Givat Hayim, Israel. Community Clin, Kibbutz Ein Hahoresh, Israel. RP Passwell, JH (reprint author), Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. FU NIOSH CDC HHS [OH94-CH29A] NR 15 TC 45 Z9 47 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1999 VL 179 IS 6 BP 1565 EP 1568 DI 10.1086/314759 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 200VQ UT WOS:000080561100036 PM 10228084 ER PT J AU Saunders, NA Smith, RJ Jetten, AM AF Saunders, NA Smith, RJ Jetten, AM TI Regulation of guanylate-binding protein expression in interferon-gamma-treated human epidermal keratinocytes and squamous cell carcinoma cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cancer; epithelium; squamous differentiation ID TRACHEAL EPITHELIAL-CELLS; CROSS-LINKED ENVELOPE; RETINOIC ACID; GENE-EXPRESSION; GROWTH-FACTOR; FACTOR-ALPHA; PHORBOL ESTERS; MESSENGER-RNA; IFN-GAMMA; DIFFERENTIATION AB Interferon-gamma is a potent inducer of growth arrest and squamous differentiation of human epidermal keratinocytes in vitro, In order to understand the proximate events regulating interferon-gamma action we studied the relationship between interferon-gamma-mediated induction of a cytoplasmic guanylate-binding protein and the expression of growth and differentiation marker genes in normal and transformed keratinocytes, Induction of guanylate-binding protein mRNA by interferon-gamma was detectable at 4 h, was transcription dependent, and preceded changes in the expression of markers of growth arrest (E2F-1 mRNA downregulation) and differentiation (SQ37 mRNA induction). The Ec(50) Value for guanylate-binding protein induction (4 units interferon-gamma per mi) was lower than previously reported for SQ37 (40 units interferon-gamma per mi). Guanylate-binding protein mRNA appeared to be only moderately downregulated by modulators of the squamous phenotype such as retinoic acid and transforming growth factor-beta 1. In addition, mRNA levels of E2F-1 or SQ37 were not altered in several squamous carcinoma cell lines treated with interferon-gamma, In contrast, guanylate-binding protein mRNA was highly induced in all these cell lines following interferon-gamma treatment. Further analysis of the signal transduction pathway mediating interferon-gamma responses using protein kinase inhibitors indicated that guanylate-binding protein induction in normal human epidermal keratinocyte cells was most likely protein kinase C independent. Our data suggest that more than one postreceptor interferon-gamma signaling pathway exists in keratinocytes and that at least one of these pathways is defective in squamous carcinoma cells. Furthermore, our data demonstrated that the failure of the squamous carcinoma cells to undergo interferon-gamma-induced growth arrest and differentiation is not due to an inherent defect in interferon-gamma receptor activation, but most likely is due to a defect in a non-guanylate-binding protein-dependent signaling pathway. C1 Univ Queensland, Princess Alexandra Hosp, Dept Med, Epithelial Pathobiol Grp,Ctr Immunol & Canc Res, Brisbane, Qld 4102, Australia. NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Saunders, NA (reprint author), Univ Queensland, Princess Alexandra Hosp, Dept Med, Epithelial Pathobiol Grp,Ctr Immunol & Canc Res, Ipswich Rd, Brisbane, Qld 4102, Australia. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 39 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1999 VL 112 IS 6 BP 977 EP 983 DI 10.1046/j.1523-1747.1999.00611.x PG 7 WC Dermatology SC Dermatology GA 203QC UT WOS:000080717500022 PM 10383748 ER PT J AU Kirken, RA Erwin, RA Taub, D Murphy, WJ Behbod, F Wang, LH Pericle, F Farrar, WL AF Kirken, RA Erwin, RA Taub, D Murphy, WJ Behbod, F Wang, LH Pericle, F Farrar, WL TI Tyrphostin AG-490 inhibits cytokine-mediated JAK3/STAT5a/b signal transduction and cellular proliferation of antigen-activated human T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE JAKs; Stats; kinase inhibitors; interleukin-2 ID INTERLEUKIN-2 RECEPTOR-GAMMA; TYROSINE KINASE; FUNCTIONAL COMPONENT; TARGETED DISRUPTION; CHAIN; JAK2; EXPRESSION; STAT5; GENE; LYMPHOCYTES AB Janus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)). Genetic inactivation of JAK3 is manifested as severe combined immunodeficiency disease (SCID) in humans and mice. These findings have suggested that JAK3 represents a pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence that AG-490 potently inhibits the autokinase activity of JAK3 and tyrosine phosphorylation and DNA binding of signal transducer and activator of transcription 5a and 5b (STAT5a/b), Similar inhibitory effects were observed with other cytokines that use gamma(c). AG-490 also inhibited IL-2-mediated proliferative growth in human T cells with an IC50 = 25 mu M that was partially recoverable. Moreover, we demonstrate that this inhibitor prevented tetanus toroid antigen-specific T cell proliferation and expansion but failed to block activation of Zap70 or p56Lck after anti-CD3 stimulation of human T cells. Taken together, these findings suggest that AG-490 inhibits the JAK3-mediated Type II signaling pathway but not the T cell receptor-derived Type I pathway and possesses therapeutic potential for T cell-derived pathologies such as graft-versus-host disease, allergy, and autoimmune disorders. C1 Univ Texas, Hlth Sci Ctr, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA. Frederick Canc Res & Dev Ctr, SAIC Frederick, IRSP, Frederick, MD USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci,Cytokine Mol Mechanisms Sect, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Kirken, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Integrat Biol & Pharmacol, MSB Rm 4-218, Houston, TX 77030 USA. NR 35 TC 95 Z9 96 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 1999 VL 65 IS 6 BP 891 EP 899 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 206LY UT WOS:000080881600025 PM 10380915 ER PT J AU Coucke, PJ Van Hauwe, P Everett, LA Demirhan, O Kabakkaya, Y Dietrich, NL Smith, RJH Coyle, E Reardon, W Trembath, R Willems, PJ Green, ED Van Camp, G AF Coucke, PJ Van Hauwe, P Everett, LA Demirhan, O Kabakkaya, Y Dietrich, NL Smith, RJH Coyle, E Reardon, W Trembath, R Willems, PJ Green, ED Van Camp, G TI Identification of two different mutations in the PDS gene in an inbred family with Pendred syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE PDS gene; Pendred syndrome ID SENSORINEURAL HEARING-LOSS; SMALL GEOGRAPHIC AREA; SULFATE TRANSPORTER; RECESSIVE DEAFNESS; MULTIPLE MUTATIONS; MOLECULAR ANALYSIS; LINKAGE; REGION; GOITER AB Recently the gene responsible for Pendred syndrome (PDS) was isolated and several mutations in the PDS gene have been identified in Pendred patients. Here we report the occurrence of two different PDS mutations in an extended inbred Turkish family. The majority of patients in this family are homozygous for a splice site mutation (1143-2A-->G) affecting the 3' splice site consensus sequence of intron 7. However, two affected sibs with nonconsanguineous parents are compound heterozygotes for the splice site mutation and a missense mutation (1558T-->G), substituting an evolutionarily conserved amino acid. The latter mutation has been found previously in two Pendred families originating from The Netherlands, indicating that the 1558T-->G mutation may be a common mutation. C1 Univ Antwerp UIA, Dept Med Genet, B-2610 Antwerp, Belgium. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. Univ London, Inst Child Hlth, Div Clin Genet & Fetal Med, London WC1E 7HU, England. Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA. Cukurova Univ, Fac Med, Dept Med Biol, TR-01330 Adana, Turkey. Orta Dogu Private Hosp, Dept Otolaryngol, Adana, Turkey. RP Van Camp, G (reprint author), Univ Antwerp UIA, Dept Med Genet, Univ Plein 1, B-2610 Antwerp, Belgium. RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 FU NIDCD NIH HHS [R01DCO2842] NR 20 TC 39 Z9 48 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 1999 VL 36 IS 6 BP 475 EP 477 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 204ZY UT WOS:000080797600009 PM 10874637 ER PT J AU Hahn, H Wojnowski, L Miller, G Zimmer, A AF Hahn, H Wojnowski, L Miller, G Zimmer, A TI The patched signaling pathway in tumorigenesis and development: lessons from animal models SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE tumorigenesis; embryogenesis; basal cell carcinoma; medulloblastoma ID BASAL-CELL CARCINOMA; PRIMITIVE NEUROECTODERMAL TUMORS; CENTRAL-NERVOUS-SYSTEM; SONIC-HEDGEHOG; GORLIN-SYNDROME; HUMAN HOMOLOG; CHOLESTEROL HOMEOSTASIS; CAENORHABDITIS-ELEGANS; TRANSDUCING HEDGEHOG; MOLECULAR ANALYSIS C1 GSF Forschungszentrum Umwelt & Gesundheit, Inst Pathol, D-85758 Neuherberg, Germany. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Epidauros Biotechnol AG, D-82347 Bernried, Germany. NIH, Off Director, Vet Resources Program, Bethesda, MD 20892 USA. RP Hahn, H (reprint author), GSF Forschungszentrum Umwelt & Gesundheit, Inst Pathol, Ingolstadter Landstr 1, D-85758 Neuherberg, Germany. RI Zimmer, Andreas/B-8357-2009 NR 101 TC 84 Z9 85 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JUN PY 1999 VL 77 IS 6 BP 459 EP 468 DI 10.1007/s001099900018 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 221PR UT WOS:000081735900003 PM 10475061 ER PT J AU Cirielli, C Inyaku, K Capogrossi, MC Yuan, X Williams, JA AF Cirielli, C Inyaku, K Capogrossi, MC Yuan, X Williams, JA TI Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of experimental intracranial human malignant glioma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE adenoviral gene transfer; p53; apoptosis; experimental malignant gliomas ID THYMIDINE KINASE GENE; BRAIN-TUMORS; IN-VIVO; GLIOBLASTOMA-MULTIFORME; THERAPY; CELLS; GROWTH; CANCER; RAT; RADIOTHERAPY AB Adenoviral-mediated gene transfer for the treatment of experimental intrinsic malignant brain neoplasms holds promise. The role, however, of intracellular, adenoviral-mediated p53 expression to inhibit growth of experimental human intracranial malignant gliomas remains largely unexplored. Using the AdCMV.p53 vector we measured the in vitro expression of p53 and the resultant effect upon U251 human malignant glioma cellular proliferation. We further measured the survival of nude mice after intracranial injection of the infected vs. control U251 cells. The growth of the infected U251 cells was inhibited when compared to both the uninfected cells and cells infected with the control vector (AdCMV.Null). Agarose gel electrophoresis confirmed the AdCMV.p53-dependent cellular apoptosis. Nude mice having intracranial injections of the U251 cells infected with the control (AdCMV.Null) vector showed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship measured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas. C1 Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. NIA, Gene Therapy Unit, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Ist Dermopat Immacolata, Lab Patol Vasc, Rome, Italy. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Williams, JA (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosurg, Harvey 811,600 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA70379-01] NR 52 TC 25 Z9 25 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUN PY 1999 VL 43 IS 2 BP 99 EP 108 DI 10.1023/A:1006289505801 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 234XK UT WOS:000082509500001 PM 10533721 ER PT J AU Zeng, FY Soldner, A Schoneberg, T Wess, J AF Zeng, FY Soldner, A Schoneberg, T Wess, J TI Conserved extracellular cysteine pair in the M-3 muscarinic acetylcholine receptor is essential for proper receptor cell surface localization but not for G protein coupling SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE muscarinic receptors; G protein-coupled receptors; receptor G protein coupling; disulfide bond; receptor folding; site-directed mutagenesis ID 3RD CYTOPLASMIC LOOP; NEPHROGENIC DIABETES-INSIPIDUS; SITE-DIRECTED MUTAGENESIS; DISULFIDE BOND; ENDOPLASMIC-RETICULUM; LIGAND-BINDING; BETA-2-ADRENERGIC RECEPTOR; CHOLINERGIC RECEPTOR; ANTAGONIST BINDING; FUNCTIONAL RESCUE AB Most G protein-coupled receptors contain a conserved pair of extracellular cysteine residues that are predicted to form a disulfide bond linking the first and second extracellular loops. Previous studies have shown that this disulfide bond may be critical for ligand binding, receptor activation, and/or proper receptor folding. However, the potential importance of the two conserved cysteine residues for proper receptor cell surface localization has not been investigated systematically. To address this issue, we used the rat M-3 muscarinic receptor as a model system. Most studies were carried out with a modified version of this receptor subtype (lacking potential N-glycosylationsites and the central portion of the third intracellular loop) that could be readily detected via western blot analysis. Cys-->Ala mutant receptors were generated, transiently expressed in COS-7 cells, and then examined for their subcellular distribution and functional properties. ELISA and immunofluorescence studies showed that the presence of both conserved cysteine residues (corresponding to C140 and C220 in the rat M-3 muscarinic receptor sequence) is required for efficient expression of the M-3 muscarinic receptor on the cell surface. On the other hand, these residues were found not to be essential for protein stability (determined via immunoblotting) and receptor-mediated G protein activation (studied in second messenger assays). These results shed new light on the functional role of the two extracellular cysteine residues present in most G protein-coupled receptors. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Inst Pharmakol, Fachbereich Human Med, D-1000 Berlin, Germany. RP NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05, Bethesda, MD 20892 USA. NR 42 TC 56 Z9 56 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1999 VL 72 IS 6 BP 2404 EP 2414 DI 10.1046/j.1471-4159.1999.0722404.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 198QE UT WOS:000080434800021 PM 10349850 ER PT J AU Jiang, H Bielekova, B Okazaki, H Clarence-Smith, K Johnson, KP Bergey, G Martin, R Dhib-Jalbut, S AF Jiang, H Bielekova, B Okazaki, H Clarence-Smith, K Johnson, KP Bergey, G Martin, R Dhib-Jalbut, S TI The effect of vesnarinone on TNF alpha production in human peripheral blood mononuclear cells and microglia: a preclinical study for the treatment of multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE vesnarinone; TNF alpha; IFN gamma; mononuclear cells; microglia; multiple sclerosis ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CYTOKINE PRODUCTION; PHOSPHODIESTERASE INHIBITOR; GAMMA-INTERFERON; INOTROPIC AGENT; MESSENGER-RNA; HEART-FAILURE; LEWIS RATS; EXPRESSION AB Vesnarinone (OPC-8212) is a synthetic quinolinone derivative with inotropic and immunomodulatory effects. Vesnarinone has been shown to inhibit tumor necrosis factor-alpha (TNF alpha) produced by mitogen stimulated macrophages. and to inhibit phosphodiesterase (PDE) type III in cardiac muscle. TNF alpha and interferon-gamma (IFN gamma) have been implicated in the pathogenesis of autoimmune diseases, and both cytokines are targets for therapeutic intervention. IFN gamma can enhance autoimmune disease through direct effects, and indirectly by priming macrophages to produce TNF alpha. In this study, we demonstrate that while vesnarinone enhances basal TNF alpha levels, it inhibits TNF alpha production in peripheral blood mononuclear cells from multiple sclerosis (MS) patients and healthy donors stimulated with lipopolysaccharide (LPS) or primed with IFN gamma and stimulated with suboptimal doses of LPS. In addition, vesnarinone inhibited TNF alpha production in primary adult human microglial cultures. However, in contrast to rolipram, another TNF alpha inhibiting agent, vesnarinone failed to inhibit TNF alpha production by myelin basic protein specific T-cell lines. As oral TNF inhibitors are currently being considered in the USA for clinical application in MS, the implications of our findings on the development of vesnruinone for treatment of hlS are discussed. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20842 USA. Otsuka Pharmaceut Co Ltd, Tokushima 7710192, Japan. RP Dhib-Jalbut, S (reprint author), Univ Maryland Hosp, Dept Neurol, Room N4W46,22 S Greene St, Baltimore, MD 21201 USA. NR 26 TC 10 Z9 10 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 JUN 1 PY 1999 VL 97 IS 1-2 BP 134 EP 145 DI 10.1016/S0165-5728(99)00037-5 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 209PY UT WOS:000081058000016 PM 10408967 ER PT J AU Qiu, JX Kai, MK Padlan, EA Marcus, DM AF Qiu, JX Kai, MK Padlan, EA Marcus, DM TI Structure-function studies of an anti-asialo GM1 antibody obtained from a phage display library SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE asialo GM1; anti-ganglioside antibodies; phage display libraries ID MURINE MONOCLONAL-ANTIBODIES; CODON-BASED MUTAGENESIS; GUILLAIN-BARRE-SYNDROME; MILLER FISHER SYNDROME; CENTRAL-NERVOUS-SYSTEM; HYPERVARIABLE LOOPS; COMBINING SITE; IGM ANTIBODIES; LIGHT CHAIN; VH-GENE AB Although gangliosides elicit human autoantibodies, they are extremely weak immunogens in mice. We obtained a monoclonal antibody Fab fragment (clone 10) that is specific for asialo GM1 (GA1), from a phage display library. The V-kappa domain of clone 10 could be replaced by two different V-kappa domains without changing the specificity of the antibody. Mutagenesis of the third hypervariable regions of the heavy and light chains of clone 10 yielded three mutants that exhibited a 3 to 4 times increase in avidity for GA1. A molecular model of clone 10 indicated that the putative antigen-binding site contained a shallow surface pocket. These data illustrate the use of recombinant DNA techniques to obtain anti-ganglioside antibodies, and to explore the molecular basis of their antigen-binding activity. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Canc Biol & Mol Immunol, Bunkyo Ku, Tokyo 1130033, Japan. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Marcus, DM (reprint author), Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. EM dmarcus@bcm.tmc.edu FU NIAID NIH HHS [AI 17712] NR 60 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUN 1 PY 1999 VL 97 IS 1-2 BP 172 EP 181 DI 10.1016/S0165-5728(99)00056-9 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 209PY UT WOS:000081058000020 PM 10408972 ER PT J AU Proescholdt, MA Heiss, JD Walbridge, S Muhlhauser, J Capogrossi, MC Oldfield, EH Merrill, MJ AF Proescholdt, MA Heiss, JD Walbridge, S Muhlhauser, J Capogrossi, MC Oldfield, EH Merrill, MJ TI Vascular endothelial growth factor (VEGF) modulates vascular permeability and inflammation in rat brain SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE adenovirus; blood-brain barrier; brain edema; inflammation; major histocompatibility complex; vascular permeability factor; VEGF ID CENTRAL-NERVOUS-SYSTEM; IN-VIVO; GENE-TRANSFER; ADENOVIRUS VECTORS; TUMOR ANGIOGENESIS; TYROSINE KINASE; BLOOD-VESSELS; UP-REGULATION; EXPRESSION; RECEPTOR AB Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that also induces vascular permeability and macrophage migration. VEGF expression is weak in normal adult brain, but is strongly upregulated in glioma cells and reactive astrocytes, suggesting that chronic overexpression of VEGF in the brain contributes to blood-brain barrier (BBB) breakdown. We examined the effects of chronic VEGF overexposure on the integrity of the BBB using the following approaches: 1) continuous intracerebral infusion of VEGF via miniosmotic pump; and 2) intracerebral injection of an adenoviral vector encoding the VEGF(165) gene (AdCMV.VEGF). After 6 days both treatments produced similar to 10-fold breakdown of the BBB las measured by transport of C-14-aminoisobutyric acid (AIB) from blood into brain) compared with the respective controls (albumin infusion or AdCMV.beta gal virus). BBB disruption in AdCMV.VEGF-treated brains was accompanied by a severe inflammatory response not observed in brains receiving AdCMV.beta gal or VEGF protein infusion, indicating that neither VEGF nor viral particles alone were responsible for the inflammatory response. However, injection of AdCMV.beta gal followed by VEGF infusion to the same site also elicited inflammation. Chronic overexposure of normal brain to VEGF also increased intercellular adhesion molecule-1 (ICAM-1) and major histocompatibility complex (MHC) class I and II expression. Although VEGF itself is not inflammatory, VEGF may modulate immune responses in the central nervous system (CNS) by opening the BBB, altering the immunoprivileged status of the brain, and allowing contact between normally sequestered CNS antigens and blood-borne immune mediators. C1 NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. IRCC, Ist Dermopat Immacolatat, Lab Patol Vasc, Rome, Italy. RP Merrill, MJ (reprint author), NINCDS, Surg Neurol Branch, NIH, Bldg 10,Rm 5D-37, Bethesda, MD 20892 USA. NR 64 TC 136 Z9 142 U1 1 U2 7 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 1999 VL 58 IS 6 BP 613 EP 627 PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 205HB UT WOS:000080814300006 PM 10374752 ER PT J AU Hatanpaa, K Isaacs, KR Shirao, T Brady, DR Rapoport, SI AF Hatanpaa, K Isaacs, KR Shirao, T Brady, DR Rapoport, SI TI Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE beta-tubulin; cytochrome oxidase; drebrin; energy metabolism; GAP-43; neuron specific-enolase; synaptophysin ID CYTOCHROME-OXIDASE ACTIVITY; DENDRITIC SPINES; OXIDATIVE-PHOSPHORYLATION; NEUROFIBRILLARY TANGLES; ENERGY-METABOLISM; GENE-EXPRESSION; NEURONS; RAT; DREBRIN; CORTEX AB Recent studies suggest that the cognitive impairment associated with normal aging is due to neuronal dysfunction rather than to loss of neurons or synapses. To characterize this dysfunction, molecular indices of neuronal function were quantified in autopsy samples of cerebral cortex. During normal aging, the most dramatic decline was found in levels of synaptic proteins involved in structural plasticity (remodeling) of axons and dendrites. Alzheimer disease, the most common cause of dementia in the elderly, was associated with an additional 81% decrease in levels of drebrin, a protein regulating postsynaptic plasticity. Disturbed mechanisms of plasticity may contribute to cognitive dysfunction during aging and in Alzheimer disease. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Gunma Univ, Sch Med, Dept Neurobiol & Behav, Maebashi, Gumma 371, Japan. RP Hatanpaa, K (reprint author), Yale Univ, Sch Med, Dept Pathol, E Pavil,Room 2-631,20 York St,Box 20870, New Haven, CT 06520 USA. NR 43 TC 115 Z9 124 U1 0 U2 4 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 1999 VL 58 IS 6 BP 637 EP 643 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 205HB UT WOS:000080814300008 PM 10374754 ER PT J AU Oram, MW Wiener, MC Lestienne, R Richmond, BJ AF Oram, MW Wiener, MC Lestienne, R Richmond, BJ TI Stochastic nature of precisely timed spike patterns in visual system neuronal responses SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; SPATIOTEMPORAL FIRING PATTERNS; LATERAL GENICULATE NEURONS; TWO-DIMENSIONAL PATTERNS; SINGLE NEURONS; 2-DIMENSIONAL PATTERNS; REPLICATING PATTERNS; SENSITIVE NEURONS; BEHAVING PRIMATES; FAVORED PATTERNS AB It is not clear how information related to cognitive or psychological processes is carried by or represented in the responses of single neurons. One provocative proposal is that precisely timed spike patterns play a role in carrying such information. This would require that these spike patterns have the potential for carrying information that would not be available from other measures such as spike count or latency. We examined exactly timed (I-ms precision) triplets and quadruplets of spikes in the stimulus-elicited responses of lateral geniculate nucleus (LGN) and primary visual cortex (V1) neurons of the awake fixating rhesus monkey. Large numbers of these precisely timed spike patterns were found. information theoretical analysis showed that the precisely timed spike patterns carried only information already available from spike count, suggesting that the number of precisely timed spike patterns was related to firing rate. We therefore examined statistical models relating precisely timed spike patterns to response strength. Previous statistical models use observed properties of neuronal responses such as the peristimulus time histogram, interspike interval, and/or spike count distributions to constrain the parameters of the model. We examined a new stochastic model, which unlike previous models included all three of these constraints and unlike previous models predicted the numbers and types of observed precisely timed spike patterns. This shows that the precise temporal structures of stimulus-elicited responses in LGN and V1 can occur by chance. We show that any deviation of the spike count distribution, no matter how small, from a Poisson distribution necessarily changes the number of precisely timed spike patterns expected in neural responses. Overall the results indicate that the fine temporal structure of responses can only be interpreted once all the coarse temporal statistics of neural responses have been taken into account. C1 NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Paris 06, Inst Neurosci, Ctr Natl Rech Sci, Unite Mixte Rech 7624, F-75005 Paris, France. RP Richmond, BJ (reprint author), NIMH, Natl Inst Hlth, Bldg 49,room 1B80,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Oram, Michael/A-2558-2010 NR 66 TC 150 Z9 151 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1999 VL 81 IS 6 BP 3021 EP 3033 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 208RR UT WOS:000081005800038 PM 10368417 ER PT J AU Deiber, MP Honda, M Ibanez, V Sadato, N Hallett, M AF Deiber, MP Honda, M Ibanez, V Sadato, N Hallett, M TI Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: Effect of movement type and rate SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; PRECEDING VOLUNTARY MOVEMENT; SEQUENTIAL FINGER MOVEMENTS; PARKINSONS-DISEASE; NEURONAL-ACTIVITY; CORTICAL AREAS; FRONTAL-LOBE; CORTICOSPINAL PROJECTIONS; PREFRONTAL CORTEX AB The human frontomesial cortex reportedly contains at least four cortical areas that are involved in motor control: the anterior supplementary motor area (pre-SMA), the posterior SMA (SMA proper, or SMA), and, in the anterior cingulate cortex, the rostral cingulate zone (RCZ) and the caudal cingulate zone (CCZ). We used functional magnetic resonance imaging (fMRI) to examine the role of each of these mesial motor areas in self-initiated and visually triggered movements. Healthy subjects performed self-initiated movements of the right fingers (self-initiated task, SI). Each movement elicited a visual signal that was recorded. The recorded sequence of visual signals was played back, and the subjects moved the right fingers in response to each signal (visually triggered task, VT). There were two types of movements: repetitive (FIXED) or Sequential (SEQUENCE), performed at two different rates: SLOW or FAST. The four regions of interest (pre-SMA, SMA, RCZ, CCZ) were traced on a high-resolution MRI of each subject's brain. Descriptive analysis, consisting of individual assessment of significant activation, revealed a bilateral activation in the four mesial structures for all movement conditions, but SI movements were more efficient than VT movements. The more complex and more rapid the movements, the smaller the difference in activation efficiency between the SI and the VT tasks, which indicated an additional processing role of the mesial motor areas involving both the type and rate of movements. Quantitative analysis was performed on the spatial extent of the area activated and the percentage of change in signal amplitude. In the pre-SMA, activation was more extensive for SI than for VT movements, and for fast than for slow movements; the extent of activation was larger in the ipsilateral pre-SMA. In the SMA, the difference was not significant in the extent and magnitude of activation between SI and VT movements, but activation was more extensive for sequential than for fixed movements. In the RCZ and CCZ, both the extent and magnitude of activation were larger for SI than for VT movements. In the CCZ, both indices of activation were also larger for sequential than for fixed movements, and for fast than for slow movements. These data suggest functional specificities of the frontomesial motor areas with respect not only to the mode of movement initiation (self-initiated or externally triggered) but also to the movement type and rate. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Ctr Explorat & Rech Med Emiss Positons, INSERM, F-69003 Lyon, France. Fukui Med Sch, Dept Radiol, Fukui 91011, Japan. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC-1428, Bethesda, MD 20892 USA. RI Deiber, Marie-Pierre/M-5949-2014 NR 64 TC 310 Z9 312 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1999 VL 81 IS 6 BP 3065 EP 3077 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 208RR UT WOS:000081005800042 PM 10368421 ER PT J AU Frye, MA Gary, KA Marangell, LB George, MS Callahan, AM Little, JT Huggins, T Cora-Locatelli, G Osuch, EA Winokur, A Post, RM AF Frye, MA Gary, KA Marangell, LB George, MS Callahan, AM Little, JT Huggins, T Cora-Locatelli, G Osuch, EA Winokur, A Post, RM TI CSF thyrotropin-releasing hormone gender difference: Implications for neurobiology and treatment of depression SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CEREBROSPINAL-FLUID; MESSENGER-RNA; TRH; RATS; BRAIN; RECEPTORS; EXPRESSION; TOLERANCE; ILLNESS AB In light of the postulated role of thyrotropin-releasing hormone (TRH) as an endogenous antidepressant, 56 refractory mood-disordered patients and 34 healthy adult control subjects underwent lumbar puncture for cerebrospinal fluid (CSF) TRH analysis. By two-way analysis of variance, there was no difference between CSF TRH in patients (as a group or by diagnostic subtype) and control subjects (n = 90, F = 0.91, df = 2,84, P = 0.41). There was, however, a CSF TRH gender difference (females, 2.95 pg/ml; males, 3.98 pg/ml; n = 90, F = 4.11, df = 1,84, P<0.05). A post hoc t-test revealed the greatest gender difference in the bipolar group (t = 2.52, P<0.02). There wits no significant difference in CSF TRH in "ill" vs. "well" state (n = 20, P = 0.41). The role of elevated levels of CSF TRH in affectively ill men-or the role of decreased levels of CSF TRH in affectively ill women-remains to be investigated but could be of pathophysiological relevance. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Baylor Sch Med, Houston, TX USA. Med Univ S Carolina, Charleston, SC 29425 USA. Brown Univ, Sch Med, Vet Adm Med Ctr, Providence, RI 02912 USA. Univ Pittsburgh, Western Psychiat Inst, Pittsburgh, PA 15260 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Frye, MA (reprint author), 300 UCLA Med Plaza,Suite 2341, Los Angeles, CA 90095 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 30 TC 9 Z9 10 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1999 VL 11 IS 3 BP 349 EP 353 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 222CG UT WOS:000081765400008 PM 10440011 ER PT J AU Bolla, KI Rothman, R Cadet, JL AF Bolla, KI Rothman, R Cadet, JL TI Dose-related neurobehavioral effects of chronic cocaine use SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID NEUROPSYCHOLOGICAL DEFICITS; INORGANIC LEAD; ABUSERS; ALCOHOLICS; EXPOSURE; SOLVENTS; MEMORY AB Although cocaine use is a significant public health problem, there is a paucity of scientific data on long-term neurobehavioral effects. This study examined the dose-related association between chronic cocaine use and neurobehavioral performance. A battery of neuropsychological tests was administered to 30 abstinent chronic cocaine abusers and 21 non-drug-using control subjects matched for age, education, and intelligence. After controlling for age, education, and intellectual ability, greater use of cocaine (grams per week) was associated with larger decrements on tests measuring executive functioning, visuoperception, psychomotor speed, and manual dexterity. These results suggest that chronic cocaine use is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Knowledge of specific cognitive processing deficits in chronic cocaine users would be useful for designing individually tailored drug treatment programs. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. NIDA, Mol Neuropsychiat Sect, IRP, NIH, Baltimore, MD 21224 USA. NIDA, Clin Psychopharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA. RP Bolla, KI (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 38 TC 131 Z9 131 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1999 VL 11 IS 3 BP 361 EP 369 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 222CG UT WOS:000081765400010 PM 10440013 ER PT J AU Behar, TN Scott, CA Greene, CL Wen, XL Smith, SV Maric, D Liu, QY Colton, CA Barker, JL AF Behar, TN Scott, CA Greene, CL Wen, XL Smith, SV Maric, D Liu, QY Colton, CA Barker, JL TI Glutamate acting at NMDA receptors stimulates embryonic cortical neuronal migration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mouse; chemotaxis; cortex; development; slice; chemoattractant ID DEVELOPING CEREBRAL-CORTEX; CELL-MIGRATION; SPINAL-CORD; EXPRESSION; GABA; CHEMOTAXIS; CALCIUM; CHEMOKINESIS; NEUROGENESIS; CHANNELS AB During cortical development, embryonic neurons migrate from germinal zones near the ventricle into the cortical plate, where they organize into layers. Mechanisms that direct neuronal migration may include molecules that act as chemoattractants. In rats, GABA, which localizes near the target destination for migrating cortical neurons, stimulates embryonic neuronal migration in vitro. In mice, glutamate is highly localized near the target destinations for migrating cortical neurons. Glutamate-induced migration of murine embryonic cortical cells was evaluated in cell dissociates and cortical slice cultures. In dissociates, the chemotropic effects of glutamate were IO-fold greater than the effects of GABA, demonstrating that for murine cortical cells, glutamate is a more potent chemoattractant than GABA. Thus, cortical chemoattractants appear to differ between species. Micromolar glutamate stimulated neuronal chemotaxis that was mimicked by mu M NMDA but not by other ionotropic glutamate receptor agonists (AMPA, kainate, quisqualate). Responding cells were primarily derived from immature cortical regions [ventricular zone (vz)/subventricular zone (svz)]. Bromodeoxyuridine (BrdU) pulse labeling of cortical slices cultured in NMDA antagonists (mu M MK801 or APV) revealed that antagonist exposure blocked the migration of BrdU-positive cells from the vz/svz into the cortical plate. PCR confirmed the presence of NMDA receptor expression in vz/svz cells, whereas electrophysiology and Ca2+ imaging demonstrated that vz/svz cells exhibited physiological responses to NMDA. These studies indicate that, in mice, glutamate may serve as a chemoattractant for neurons in the developing cortex, signaling cells to migrate into the cortical plate via NMDA receptor activation. C1 NINCDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Behar, TN (reprint author), Bldg 36,Room 2C02,36 Convent Dr, Bethesda, MD 20892 USA. NR 32 TC 181 Z9 190 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 1999 VL 19 IS 11 BP 4449 EP 4461 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 198ND UT WOS:000080429600025 PM 10341246 ER PT J AU Dionne, RA AF Dionne, RA TI Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID CODEINE COMBINATION; INTRAMUSCULAR OXYCODONE; POSTOPERATIVE PAIN; DENTAL PAIN; SUPPRESSION; ACETAMINOPHEN; FLURBIPROFEN; MORPHINE; PLACEBO; CANCER AB Purpose: A traditional approach to achieve greater analgesic efficacy is to combine an efficacious dose of a nonopioid with a dose of an opioid sufficient to produce additive analgesia without a substantial increase in the incidence of adverse effects. This study evaluated the additive analagesic effects of the combination of ibuprofen and oxycodone. Patients and Methods: A dose of 400 mg ibuprofen mas compared with 400 mg ibuprofen with oxycodone in doses of 2.5, 5, or 10 mg II the oral surgery model of acute pain. Analgesic efficacy was measured with category and visual analog scales at 15, 30, 45, and 60 minutes and hourly up to G hours. Results: Ibuprofen plus 10 mg oxycodone produced significantly greater analgesia compared with the other three groups, as measured by the visual analog scale from 15 minutes after drug administration up to the 2-hour observation. All four treatments were similar from 3 to 6 hours, with the area under the pain intensity difference curve being similar across groups. Neither the 2.5-mg nor the 5-mg oxycodone dose provided any additive analgesia over ibuprofen at any points. Addition of oxycodone resulted in a dose-related increase in the number of patients reporting adverse effects, with significantly greater drowsiness and vomiting at the 10-mg dose. Conclusions: These results indicate that additive analgesia can be achieved for the combination of a nonsteroidal anti-inflammatory drug and an orally effective opioid, with faster onset of relief for the combination of 400 mg ibuprofen and 10 mg oxycodone over the first 2 hours after administration, but at the expense of an increased incidence of adverse events. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mechanisms Branch, NIH, 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. NR 20 TC 17 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 1999 VL 57 IS 6 BP 673 EP 678 DI 10.1016/S0278-2391(99)90429-9 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 201YR UT WOS:000080625300011 PM 10368091 ER PT J AU Dionne, R AF Dionne, R TI Critical commentary 1 - Central nervous system plasticity and persistent pain SO JOURNAL OF OROFACIAL PAIN LA English DT Editorial Material ID POSTHERPETIC NEURALGIA; POSTOPERATIVE PAIN; IBUPROFEN; PLACEBO C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Dionne, R (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. NR 10 TC 3 Z9 3 U1 0 U2 1 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 1064-6655 J9 J OROFAC PAIN JI J. Orofac. Pain PD SUM PY 1999 VL 13 IS 3 BP 164 EP 165 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 227MF UT WOS:000082083600005 ER PT J AU McSherry, GD Shapiro, DE Coombs, RW McGrath, N Frenkel, LM Britto, P Culnane, M Sperling, RS AF McSherry, GD Shapiro, DE Coombs, RW McGrath, N Frenkel, LM Britto, P Culnane, M Sperling, RS CA Pediat AIDS Clin Trials Grp Protocol 076 Study TI The effects of zidovudine in the subset of infants infected with human immunodeficiency virus type-1 (Pediatric AIDS Clinical Trials Group Protocol 076) SO JOURNAL OF PEDIATRICS LA English DT Article ID POLYMERASE CHAIN-REACTION; HIV-1 INFECTION; VIRAL LOAD; RNA; TRANSMISSION; DIDANOSINE; CHILDREN; RESISTANCE; PLASMA; LAMIVUDINE AB Objective: To describe the effect of zidovudine on human immunodeficiency virus type I (HIV-1) and on the course of disease in infants who became infected while they and their mothers received zidovudine preventive therapy or placebo in Pediatric AIDS Clinical Trials Group Protocol 076. Study design: Observational substudy of a multicenter, randomized, double-blind, placebo-controlled trial. Methods: We compared the progression of disease, timing of HIV-1 transmission, and the plasma HIV-1 RNA level in infected infants of mother-infant pairs who were randomly assigned to receive zidovudine (n = 14) or placebo (n = 43). The development of genotypic zidovudine resistance was assessed among infected infants in the zidovudine treatment group. Results: In this limited study, zidovudine therapy during pregnancy and labor and in the neonatal period for 6 weeks failed to have a major effect on rapid progression of disease, timing of transmission, and viral replication in HIV-infected infants. When the zidovudine treatment regimen failed to prevent maternal-infant transmission of HIV-1, resistance to zidovudine did not develop during study treatment. Conclusions: Our study supports the safety of zidovudine use in pregnancy and in the newborn period but demonstrates the continued need for more potent antiretroviral treatment of the infected infant. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NIAID, Div Aids, Pediat Med Branch, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Obstet Gynecol & Reprod Sci, New York, NY USA. RP McSherry, GD (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, MSB F-570A,185 S Orange Ave, Newark, NJ 07103 USA. FU NIAID NIH HHS [AI-95030, AI-25883, AI-41110] NR 32 TC 19 Z9 19 U1 1 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 JUN PY 1999 VL 134 IS 6 BP 717 EP 724 DI 10.1016/S0022-3476(99)70287-8 PG 8 WC Pediatrics SC Pediatrics GA 205KV UT WOS:000080820900011 PM 10356140 ER EF