FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mackey, RH Sutton-Tyrrell, K Vaitkevicius, PV Spurgeon, HA Smith, VE Kuller, LH AF Mackey, RH Sutton-Tyrrell, K Vaitkevicius, PV Spurgeon, HA Smith, VE Kuller, LH TI Correlates of aortic stiffness by carotid-femoral pulse wave velocity in a subgroup of the Cardiovascular Health Study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Univ, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. Albany Med Coll, Albany, NY 12208 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P57 BP 828 EP 828 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800108 ER PT J AU O'Donnell, CJ Cupples, LA Kauppila, LI Kiel, DP Hannan, MT Polak, JF Wilson, PWF AF O'Donnell, CJ Cupples, LA Kauppila, LI Kiel, DP Hannan, MT Polak, JF Wilson, PWF TI Risk factors associated with progression of lumbar aortic calcification SO CIRCULATION LA English DT Meeting Abstract C1 Boston Univ, Med Ctr, Boston, MA USA. Framingham Heart Study, Framingham, MA USA. NHLBI, Framingham, MA USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P59 BP 829 EP 829 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800110 ER PT J AU Feng, DL Lindpaintner, K Larson, MG O'Donnell, CJ Lipinska, I Schimitz, C Sutherland, PA Johnstone, MT Muller, JE Levy, D Tofler, GH AF Feng, DL Lindpaintner, K Larson, MG O'Donnell, CJ Lipinska, I Schimitz, C Sutherland, PA Johnstone, MT Muller, JE Levy, D Tofler, GH TI Genetic and environmental influence on factor VII levels: the Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BI Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Univ Kentucky, Med Ctr, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P67 BP 830 EP 830 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800118 ER PT J AU O'Donnell, CJ Larson, MG Feng, DL Myers, RH Levy, D Tofler, GH AF O'Donnell, CJ Larson, MG Feng, DL Myers, RH Levy, D Tofler, GH TI Heritability of platelet aggregation in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Study, Framingham, MA USA. NHLBI, Framingham, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P66 BP 830 EP 830 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800117 ER PT J AU Meigs, JB Ordovas, JM Cupples, LA Singer, DE Nathan, DM Schaefer, EJ Wilson, PWF AF Meigs, JB Ordovas, JM Cupples, LA Singer, DE Nathan, DM Schaefer, EJ Wilson, PWF TI Insulin resistance is unrelated to the apolipoprotein E polymorphism: the Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Human Nutr Res Ctr Aging, JM, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P72 BP 831 EP 831 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800123 ER PT J AU Sharp, DS Burchfiel, CM Rodriguez, BL Sorlie, PD AF Sharp, DS Burchfiel, CM Rodriguez, BL Sorlie, PD TI Apo-A1 predicts incident coronary heart disease (CHD) only at low concentrations of high density lipoprotein (HDL) cholesterol: a threshold effect SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P71 BP 831 EP 831 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800122 ER PT J AU Wilson, PWF Garrison, RJ Sawin, CT Cupples, A Ordovas, JM Schaefer, EJ AF Wilson, PWF Garrison, RJ Sawin, CT Cupples, A Ordovas, JM Schaefer, EJ TI Cigarette use, serum estradiol and a propensity toward dyslipidemia: The framingham offspring study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Tennessee, Memphis, TN USA. NHLBI, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 3 PY 1998 VL 97 IS 8 MA P75 BP 831 EP 831 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YY916 UT WOS:000072200800126 ER PT J AU Candi, E Tarcsa, E Digiovanna, JJ Compton, JG Elias, PM Marekov, LN Steinert, PM AF Candi, E Tarcsa, E Digiovanna, JJ Compton, JG Elias, PM Marekov, LN Steinert, PM TI A highly conserved lysine residue on the head domain of type II keratins is essential for the attachment of keratin intermediate filaments to the cornified cell envelope through isopeptide crosslinking by transglutaminases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CROSS-LINKING; EPIDERMAL-KERATINOCYTES; HUMAN LORICRIN; PROTEINS; DIFFERENTIATION; DESMOSOMES; COMPONENTS; MECHANISM; MUTATION AB We have addressed the question of how keratin intermediate filaments are associated with the cell envelope at the periphery of cornified epidermal cells. Many peptides from human epidermal cell envelopes containing isopeptide crosslinks inserted by transglutaminases in vivo have been characterized. A major subset involves the type II keratin chains keratin 1, 2e, 5, or 6 crosslinked to several protein partners through a lysine residue located in a conserved region of the V1 subdomain of their head domains. This sequence specificity was confirmed in in vitro crosslinking experiments, Previously the causative mutation in a family with diffuse nonepidermolytic palmar-plantar keratoderma was shown to be the loss in one allele of the same lysine residue of the keratin 1 chain. Ultrastructural studies of affected palm epidermis have revealed abnormalities in the organization of keratin filaments subjacent to the cell envelope and in the shape of the cornified cells. Together, these data suggest a mechanism for the coordination of cornified cell structure by permanent covalent attachment of the keratin intermediate filament cytoskeleton to the cell envelope by transglutaminase crosslinking, Furthermore, these studies identify the essential role of a conserved lysine residue on the head domains of type II keratins in the supramolecular organization of keratin filaments in cells. C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Dept Dermatol, San Francisco, CA 94121 USA. RP Steinert, PM (reprint author), NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. EM pemast@helix.nih.gov NR 34 TC 85 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 MAR 3 PY 1998 VL 95 IS 5 BP 2067 EP 2072 DI 10.1073/pnas.95.5.2067 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600025 PM 9482839 ER PT J AU Ferrin, LJ Camerini-Otero, RD AF Ferrin, LJ Camerini-Otero, RD TI Sequence-specific ligation of DNA using RecA protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDONUCLEASE RARE CLEAVAGE; MONO-VALENT CATIONS; ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; POLYETHYLENE-GLYCOL; GENE; EXPRESSION; SITE; TRANSFORMATION; TELOMERES AB A method is described that allows the sequence-specific ligation of DNA, The method is based on the ability of RecA protein from Escherichia coli to selectively pair oligonucleotides to their homologous sequences at the ends of fragments of duplex DNA. These three-stranded complexes were protected from the action of DNA polymerase. When treated with DNA polymerase, unprotected duplex fragments were converted to fragments with blunt ends, whereas protected fragments retained their cohesive ends. By using conditions that greatly favored ligation of cohesive ends, a second DNA fragment could be selectively ligated to a previously protected fragment of DNA, When this second DNA was a vector, selected fragments were preferentially cloned. The method had sufficient power to be used for the isolation of single-copy genes directly from yeast or human genomic DNA, and potentially could allow the isolation of much longer fragments with greater fidelity than obtainable by using PCR. C1 NIDDKD, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Ferrin, LJ (reprint author), NIDDKD, Genet & Biochem Branch, Bldg 10,Room 9D20,10 Ctr Dr,MSC 1810, Bethesda, MD 20892 USA. NR 48 TC 5 Z9 5 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2152 EP 2157 DI 10.1073/pnas.95.5.2152 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600040 PM 9482854 ER PT J AU Walker, H Ferretti, JA Stadtman, TC AF Walker, H Ferretti, JA Stadtman, TC TI Isotope exchange studies on the Escherichia coli selenophosphate synthetase mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE phosphorylated enzyme; P-31 NMR; [8-C-14]ADP; (H2O)-O-18 ID SELD GENE-PRODUCT; SELENOCYSTEINE SYNTHASE; SELENOPROTEIN SYNTHESIS; SELENIUM DONOR; TRANSFER-RNA; ENZYME; PURIFICATION; 5-METHYLAMINOMETHYL-2-SELENOURIDINE; SEQUENCE AB Selenophosphate synthetase, the Escherichia coli selD gene product, is a 37-kDa protein that catalyzes the synthesis of selenophosphate from ATP and selenide, In the absence of selenide, ATP is converted quantitatively to AMP and two orthophosphates in a very slow partial reaction, A monophosphorylated enzyme derivative containing the gamma-phosphoryl group of ATP has been implicated as an intermediate from the results of positional isotope exchange studies, Conservation of the phosphate bond energy in the final selenophosphate product is indicated by its ability to phosphorylate alcohols and amines to form O-phosphoryl- and N-phosphoryl-derivatives. To further probe the mechanism of action of selenophosphate synthetase, isotope exchange studies with [8-C-14]ADP or [8-C-14]AMP and unlabeled ATP were carried out, and P-31 NMR analysis of reaction mixtures enriched in (H2O)-O-18 was performed, A slow enzyme-catalyzed exchange of ADP with ATP observed in the absence of selenide implies the existence of a phosphorylated enzyme and further supports an intermediary role of ADP in the reaction, Under these conditions ADP is slowly converted to AMP. Incorporation of O-18 from (H2O)-O-18 exclusively into orthophosphate in the overall selenide-dependent reaction indicates that the beta-phosphoryl group of the enzyme-bound ADP is attacked by water with liberation of orthophosphate and formation of AMP, Based on these results and the failure of the enzyme to catalyze an exchange of labeled AMP with ATP, the existence of a pyrophosphorylated enzyme intermediate that was postulated earlier can be excluded. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 17 Z9 19 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 MAR 3 PY 1998 VL 95 IS 5 BP 2180 EP 2185 DI 10.1073/pnas.95.5.2180 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600045 PM 9482859 ER PT J AU Crino, P Khodakhah, K Becker, K Ginsberg, S Hemby, S Eberwine, J AF Crino, P Khodakhah, K Becker, K Ginsberg, S Hemby, S Eberwine, J TI Presence and phosphorylation of transcription factors in developing dendrites SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CREB PHOSPHORYLATION; HIPPOCAMPAL-NEURONS; C-FOS; EXPRESSION; CULTURE; GENE; RNA; TRANSPORT; SYNAPSE; NUCLEUS AB In screening amplified poly(A) mRNA from hippocampal dendrites and growth cones in culture to determine candidates for local translation, we found that select transcription factor mRNAs were present, We hypothesized that synthesis of transcription factor proteins within dendrites would provide a direct signaling pathway between the distal dendrite and the nucleus resulting in modulation of gene expression important for neuronal differentiation. To evaluate this possibility, radiolabelled amplified antisense RNA was used to probe slot blots of transcription factor cDNAs as well as arrayed blots of zinc finger transcription factors, The mRNAs encoding the cAMP response element binding protein (CREB), zif 268, and one putative transcription factor were detected, We expanded upon these results showing that CREB protein is present in dendrites, that translation of CREB mRNA in isolated dendrites is feasible and that CREB protein found in dendrites can interact with the cis-acting cyclic AMP response element DNA sequence by using an in situ Southwestern assay. Further, CREB protein in dendrites is not transported to this site from the cell body because fluorescently tagged CREB microperfused into the soma did not diffuse into the dendrites, In addition, CREB protein microperfused into dendrites was rapidly transported to the nucleus, its likely site of bioactivity, Lastly, by using the isolated dendrite system we show that phosphorylation of Ser-133 on CREB protein can occur in isolated dendrites independent of the nucleus, These data provide a regulatory pathway in which transcription factors synthesized and posttranslationally modified in dendrites directly alter gene expression bypassing the integration of signal transduction pathways that converge on the nucleus. C1 Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Eberwine, J (reprint author), Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. EM eberwine@mscf.med.upenn.edu RI Eberwine, James/B-2247-2010 FU NIA NIH HHS [R01 AG009900, AG9900, R37 AG009900] NR 27 TC 113 Z9 114 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2313 EP 2318 DI 10.1073/pnas.95.5.2313 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600068 PM 9482882 ER PT J AU Blaschke, RJ Monaghan, AP Schiller, S Schechinger, B Rao, E Padilla-Nash, H Ried, T Rappold, GA AF Blaschke, RJ Monaghan, AP Schiller, S Schechinger, B Rao, E Padilla-Nash, H Ried, T Rappold, GA TI SHOT, a SHOX-related homeobox gene, is implicated in craniofacial, brain, heart, and limb development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic development; transcription factor; Cornelia de Lange syndrome ID MOUSE; DROSOPHILA; MUTATIONS; TRANSCRIPTION; PATTERNS; CLONING; SUBSET; CELLS; CNS AB Deletion of the SHOX region on the human sex chromosomes has been shown to result in idiopathic short stature and proposed to play a role in the short stature associated with Turner syndrome. We have identified a human paired-related homeobox gene, SHOT, by virtue of its homology to the human SHOX and mouse OG-12 genes. Two different isoforms were isolated, SHOTa and SHOTb, which have identical homeodomains and share a C-terminal 14-amino acid residue motif characteristic for craniofacially expressed homeodomain proteins. Differences between SHOTa and b reside within the N termini and an alternatively spliced exon in the C termini. In situ hybridization of the mouse equivalent, OG-12, on sections from staged mouse embryos detected highly restricted transcripts in the developing sinus venosus (aorta), female genitalia, diencephalon, mes- and myelencephalon, nasal capsula, palate, eyelid, and in the limbs. SHOT was mapped to human chromosome 3q25-q26 and OG-12 within a syntenic region on chromosome 3. Based on the localization and expression pattern of its mouse homologue during embryonic development, SHOT represents a candidate for the Cornelia de Lange syndrome. C1 Univ Heidelberg, Inst Human Genet, D-69120 Heidelberg, Germany. Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Rappold, GA (reprint author), Univ Heidelberg, Inst Human Genet, Neuenheimer Feld 328, D-69120 Heidelberg, Germany. EM Gudrun_Rappold@krzmail.krz.uni-heidelberg.de NR 39 TC 74 Z9 78 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2406 EP 2411 DI 10.1073/pnas.95.5.2406 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600084 PM 9482898 ER PT J AU Zhang, SL Ramsay, ES Mock, BA AF Zhang, SL Ramsay, ES Mock, BA TI Cdkn2a, the cyclin-dependent kinase inhibitor encoding p16(INK4a) and p19(ARF), is a candidate for the plasmacytoma susceptibility locus, Pctr1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-PRODUCT PRB; CELL-CYCLE; RETINOBLASTOMA PROTEIN; TUMOR-SUPPRESSOR; TRANSCRIPTION FACTOR; MUTATIONAL ANALYSIS; FAMILIAL MELANOMA; HUMAN CANCERS; EXPRESSION AB Plasma cell tumor induction in mice by pristane is under multigenic control. BALB/c mice are susceptible to tumor development; whereas DBA/2 mice are resistant, Restriction fragment length polymorphisms between BALB/c and DBA/2 for Cdkn2a(p16) and Cdkn2b (p15), and between BALB/c and Mus spretus for Cdkn2c(p18(INK4C)) were used to position these loci with respect to the Pctr1 locus. These cyclin-dependent kinase (CDK) inhibitors mapped to a 6 cM interval of chromosome 4 between Ifna and Tall. C.D2-Chr 4 congenic strains harboring DBA/2 alleles associated with the Pctr1 locus contained DBA/2 "resistant" alleles of the CDK4/CDK6 inhibitors p16 and p15. On sequencing p16 and p18 cDNAs, two different allelic variants within ankyrin repeat regions of p16 were found between BALB/c and DBA/2 mice, By using an assay involving PCR amplification and restriction enzyme digestion, allelic variants were typed among several inbred strains of mice. One of the variants, G232A, was specific to two inbred strains, BALB/cAn and ABP/Le, of mice and occurred in a highly conserved amino acid in both human and rat p16, When tested with wild-type (DBA/2) p16, both A134C and G232A BALB/c-specific variants of p16 were inefficient in their ability to inhibit the activity of cyclin D2/CDK4 in kinase assays with retinoblastoma protein, suggesting this defective, inherited allele plays an important role in the genetic susceptibility of BALB/c mice for plasmacytoma induction and that p16(INK4a) is a strong candidate for the Pctr1 locus. C1 NCI, Genet Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Mock, BA (reprint author), NCI, Genet Lab, Div Basic Sci, NIH, Bldg 37,Room 2B08,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM bev@helix.nih.gov NR 57 TC 104 Z9 106 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2429 EP 2434 DI 10.1073/pnas.95.5.2429 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600088 PM 9482902 ER PT J AU Azimi, N Brown, K Bamford, RN Tagaya, Y Siebenlist, U Waldmann, TA AF Azimi, N Brown, K Bamford, RN Tagaya, Y Siebenlist, U Waldmann, TA TI Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-kappa B site SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HTLV-I; NUCLEAR FACTOR; KILLER-CELLS; BETA-CHAIN; PROGENITOR CELLS; LEUKEMIA; RECEPTOR; INDUCTION; CYTOKINE; IL-15 AB Interleukin 15 (IL-15) mRNA is expressed in a wide variety of tissue types. However, with the exception of some T cell lines, IL-15 transcript expression has not been described in T cells. Herein we demonstrate that IL-15 mRNA can be detected in freshly isolated normal T cells and T cell lines. Furthermore, its expression is 3- to 4-fold higher in human T cell lymphotropic virus type I (HTLV-I)-infected T cells. By using reporter constructs bearing the 5' regulatory region of the IL-15 gene, we observed a positive correlation between HTLV-I Tax protein expression and IL-15 promoter activity in HTLV-I-infected T cells. Additionally, by using a Jurkat T cell transfectant that expresses Tax under an inducible promoter, we demonstrated that the expression of IL-15 mRNA increased 3-fold as Tax was expressed, suggesting that the Tax protein activates IL-15 transcription. An NF-kappa B consensus sequence is located at the -75 and -65 region of the IL-15 5' regulatory region. Mutations in the NF-kappa B motif or deletion of this sequence abrogated the promoter activity in both HTLV-I-positive and Jurkat Tax-transfectant cells. These data represent evidence for trans-activation of the IL-15 gene by the HTLV-I Tax protein through an NF-kappa B motif and suggest a potential role for IL-15 in HTLV-I-associated diseases such as adult T cell leukemia and HTLV-I-associated myopathy/tropical spastic paraparesis. C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Azimi, N (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, Bldg 10,Room 4N-102,9000 Rockville Pike, Bethesda, MD 20892 USA. EM nazli@helix.nih.gov NR 44 TC 123 Z9 127 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2452 EP 2457 DI 10.1073/pnas.95.5.2452 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600092 PM 9482906 ER PT J AU Liu, YJ Suzuki, K Reed, JD Grinberg, A Westphal, H Hoffmann, A Doring, T Sandhoff, K Proia, RL AF Liu, YJ Suzuki, K Reed, JD Grinberg, A Westphal, H Hoffmann, A Doring, T Sandhoff, K Proia, RL TI Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure (SIMP) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene targeting; mouse model; sphingolipidosis; lysosomal storage disease ID EMBRYONIC STEM-CELLS; HOMOLOGOUS RECOMBINATION; TARGETED DISRUPTION; GLUCOCEREBROSIDASE GENE; DOUBLE-REPLACEMENT; MOUSE MODEL; TAY-SACHS; STRATEGY; SITE; PHENOTYPE AB Gaucher disease is caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GC). Three clinical types of Gaucher disease have been defined according to the presence (type 2 and 3) or absence (type 1) of central nervous system disease and severity of clinical manifestations. The clinical course of the disease correlates with the mutation carried by the GC gene. To produce mice with point mutations that correspond to the clinical types of Gaucher disease, we have devised a highly efficient one-step mutagenesis method--the single insertion mutagenesis procedure (SIMP)--to introduce human disease mutations into the mouse GC gene. By using SIMP, mice were generated carrying either the very severe RecNciI mutation that can cause type 2 disease or the less severe L444P mutation associated with type 3 disease. Mice homozygous for the RecNciI mutation had little GC enzyme activity and accumulated glucosylceramide in brain and liver. In contrast, the mice homozygous for the L444P mutation had higher levels of GC activity and no detectable accumulation of glucosylceramide in brain and liver. Surprisingly, both point mutation mice died within 48 hr of birth, apparently of a compromised epidermal permeability barrier caused by defective glucosylceramide metabolism in the epidermis. C1 NIDDKD, Sect Biochem Genet, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mamalian Genese & Dev, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-53121 Bonn, Germany. RP Proia, RL (reprint author), NIDDKD, Sect Biochem Genet, Genet & Biochem Branch, NIH, Bldg 10,Room 9D-20,10 Ctr Dr MSC 1810, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [P30 HD003110, P30-HD 03110]; NINDS NIH HHS [R01 NS024453, R01-NS 24453] NR 35 TC 65 Z9 65 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 MAR 3 PY 1998 VL 95 IS 5 BP 2503 EP 2508 DI 10.1073/pnas.95.5.2503 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600101 PM 9482915 ER PT J AU Licinio, J Negrao, AB Mantzoros, C Kaklamani, V Wong, ML Bongiorno, PB Mulla, A Cearnal, L Veldhuis, JD Flier, JS McCann, SM Gold, PW AF Licinio, J Negrao, AB Mantzoros, C Kaklamani, V Wong, ML Bongiorno, PB Mulla, A Cearnal, L Veldhuis, JD Flier, JS McCann, SM Gold, PW TI Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EARLY FOLLICULAR PHASE; MENSTRUAL-CYCLE; APPROXIMATE ENTROPY; OBESE GENE; SECRETION; SLEEP; SIGNAL; SYSTEM; REGULARITY; ALGORITHM AB Leptin, an adipocyte hormone, is a trophic factor for the reproductive system; however, it is still unknown whether there is a dynamic relation between fluctuations in circulating leptin and hypothalamic-pituitary-ovarian (HPO) axis hormones. To test the hypothesis that fluctuations in plasma leptin concentrations are related to the levels of luteinizing hormone (LH) and estradiol, we sampled plasma from six healthy women every 7 min for 24 h during days 8-11 of the menstrual cycle. Cross-correlation analysis throughout the 24-h cycle revealed a relation between release patterns of leptin and LH, with a lag of 42-84 min but no significant cross-correlation between LH and estradiol. The ultradian fluctuations in leptin levels showed pattern synchrony with those of both LH and estradiol as determined by cross-approximate entropy (cross-ApEn). At night, as leptin levels rose to their peak, the pulsatility profiles of LH changed significantly and became synchronous with those of leptin, LH pulses were fewer, of longer duration, higher amplitude, and larger area than during the day. Moreover, the synchronicity of LH and leptin occurred late at night, at which time estradiol and leptin also exhibited significantly stronger pattern coupling than during the day. We propose that leptin may regulate the minute-to-minute oscillations in the levels of LH and estradiol, and that the nocturnal rise in leptin may determine the change in nocturnal LH profile in the mid-to-late follicular phase that precedes ovulation. This may explain the disruption of hypothalamic-pituitary-ovarian function that is characteristic of states of low leptin release, such as anorexia nervosa and cachexia. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol,Dept Med, Boston, MA 02215 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Natl Sci Fdn Ctr Biol Timing, Charlottesville, VA 22908 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Licinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. EM licinio@nih.gov RI Wong, Ma-Li/D-7903-2011; Negrao, Andre Brooking/C-9526-2014; Licinio, Julio/L-4244-2013; OI Negrao, Andre Brooking/0000-0002-8133-6723; Licinio, Julio/0000-0001-6905-5884; Mulla, Abeda/0000-0002-0364-7972 FU NCRR NIH HHS [M01 RR001032]; NICHD NIH HHS [HD 28934, P30 HD028934, P50 HD028934, U54 HD028934]; PHS HHS [1R01 147991, R01 43900] NR 56 TC 199 Z9 207 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2541 EP 2546 DI 10.1073/pnas.95.5.2541 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600108 PM 9482922 ER PT J AU Zimmer, A Zimmer, AM Baffi, J Usdin, T Reynolds, K Konig, M Palkovits, M Mezey, E AF Zimmer, A Zimmer, AM Baffi, J Usdin, T Reynolds, K Konig, M Palkovits, M Mezey, E TI Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DORSAL HORN NEURONS; SUBSTANCE-P RECEPTOR; PRIMARY SENSORY NEURONS; SPINAL-CORD; MOLECULAR CHARACTERIZATION; BEHAVIORAL-RESPONSE; FUNCTIONAL CDNA; MESSENGER-RNAS; NERVOUS-SYSTEM; MET-ENKEPHALIN AB The tachykinin neuropeptides, substance P and substance K, are produced in nociceptive primary sensory neurons and in many brain regions involved in pain signaling, However, the precise role and importance of these neuropeptides in pain responses has been debated. We now show that mice that cannot produce these peptides display no significant pain responses following formalin injection and have an increased pain threshold in the hotplate test. On the other hand, the mutant mice react normally in the tail flick assay and acetic acid-induced writhing tests. These results demonstrate that substance P and/or substance K have essential functions in specific responses to pain. C1 NIMH, Genet Sect, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. RP Zimmer, A (reprint author), NIMH, Genet Sect, Bldg 36,Room 3D06, Bethesda, MD 20892 USA. EM zimmer@codon.nih.gov RI Zimmer, Andreas/B-8357-2009; Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 59 TC 151 Z9 151 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 MAR 3 PY 1998 VL 95 IS 5 BP 2630 EP 2635 DI 10.1073/pnas.95.5.2630 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600124 PM 9482938 ER PT J AU Nonaka, S Hough, CJ Chuang, DM AF Nonaka, S Hough, CJ Chuang, DM TI Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N-methyl-D-aspartate receptor-mediated calcium influx SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CEREBELLAR GRANULE CELLS; GLUTAMATE; DISEASE; ACID; NEUROTOXICITY; DISORDERS; APOPTOSIS; GROWTH; DEATH; CA-2+ AB Lithium is the most commonly used drug for the treatment of manic depressive illness, The precise mechanisms underlying its clinical efficacy remain unknown. Re Pound that long-term exposure to lithium chloride dramatically protects cultured fat cerebellar, cerebral cortical, and hippocampal neurons against glutamate-induced excitotoxicity, which involves apoptosis mediated by N-methyl-D-aspartate (NMDA) receptors, This neuroprotection is longlasting, occurs at therapeutically relevant concentrations of lithium with an EC50 of approximately 1.3 mM, and requires treatment for 6-7 days for complete protection to occur, In contrast, a 24-h treatment with lithium is ineffective. The protection in cerebellar neurons is specific for glutamate-induced excitotoxicity and can be attributed to inhibition of NMDA receptor-mediated calcium influx measured by Ca-45(2+) uptake studies and fura-2 fluorescence microphotometry, The long-term effects of lithium are not caused by down-regulation of NMDA receptor subunit proteins and are unlikely related to its known ability to block inositol monophosphatase activity, Our results suggest that modulation of glutamate receptor hyperactivity represents at least part of the molecular mechanisms by which lithium alters brain function and exerts its clinical efficacy in the treatment for manic depressive illness. These actions of lithium also suggest that abnormality of glutamatergic neurotransmission as a pathogenic mechanism underlying bipolar illness warrants future investigation. C1 NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, 10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 34 TC 330 Z9 344 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 3 PY 1998 VL 95 IS 5 BP 2642 EP 2647 DI 10.1073/pnas.95.5.2642 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZA471 UT WOS:000072366600126 PM 9482940 ER PT J AU Mitz, A AF Mitz, A TI Workstation war SO EDN LA English DT Letter C1 NIH, Anim Ctr, Poolesville, MD 20837 USA. RP Mitz, A (reprint author), NIH, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAHNERS-DENVER PUBLISHING CO PI OAK BROOK PA 2000 CLEARWATER DR, OAK BROOK, IL 60523-8809 USA SN 0012-7515 J9 EDN JI EDN PD MAR 2 PY 1998 VL 43 IS 5 BP 52 EP 52 PG 1 WC Engineering, Electrical & Electronic SC Engineering GA YY713 UT WOS:000072176300014 ER PT J AU Ban, C Yang, W AF Ban, C Yang, W TI Structural basis for MutH activation in E-coli mismatch repair and relationship of MutH to restriction endonucleases SO EMBO JOURNAL LA English DT Article DE activation; DNA repair; evolution; MutH structures; restriction enzymes ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; PVUII ENDONUCLEASE; ECORV ENDONUCLEASE; COGNATE DNA; SEQUENCE; ALIGNMENT; COMPLEXES; BINDING; PRODUCT AB MutS, MutL and MutH are the three essential proteins for initiation of methyl-directed DNA mismatch repair to correct mistakes made during DNA replication in Escherichia coli, MutH cleaves a newly synthesized and unmethylated daughter strand 5' to the sequence d(GATC) in a hemi-methylated duplex, Activation of MutH requires the recognition of a DNA mismatch by MutS and MutL. We have crystallized MutH in two space groups and solved the structures at 1.7 and 2.3 Angstrom resolution, respectively, The active site of MutH is located at an interface between two subdomains that pivot relative to one another, as revealed by comparison of the crystal structures, and this presumably regulates the nuclease activity, The relative motion of the two subdomains in MutH correlates with the position of a protruding C-terminal helix, This helix appears to act. as a molecular lever through which MutS and MutL may communicate the detection of a DNA mismatch and activate MutH, With sequence homology to Sau3AI and structural similarity to PvuII endonuclease, MutH is clearly related to these enzymes by divergent evolution, and this suggests that type II restriction endonucleases evolved from a common ancestor. C1 NIDDKD, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Yang, Wei/D-4926-2011; Ban, Changill/F-5426-2013 OI Yang, Wei/0000-0002-3591-2195; NR 32 TC 156 Z9 162 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 2 PY 1998 VL 17 IS 5 BP 1526 EP 1534 DI 10.1093/emboj/17.5.1526 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC380 UT WOS:000072572100035 PM 9482749 ER PT J AU Borrego, F Ulbrecht, M Weiss, EH Coligan, JE Brooks, AG AF Borrego, F Ulbrecht, M Weiss, EH Coligan, JE Brooks, AG TI Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NK CELL; CD94; EXPRESSION; MOLECULES; RECEPTOR; KP43; IDENTIFICATION; TRANSCRIPTS; PROTEIN; BINDING AB Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical HLA class I molecule, the gene for which is transcribed in most tissues. It has recently been reported that this molecule binds peptides derived from the signal sequence of HLA class I proteins; however, no function for HLA-E has yet been described. We show that natural killer (NK) cells can recognize target cells expressing HLA-E molecules on the cell surface and this interaction results in inhibition of the lytic process. Furthermore, HLA-E recognition is mediated primarily through the CD94/NKG2-A heterodimer, as CD94-specific, but not killer cell inhibitory receptor (KIR)-specific mAbs block HLA-E-mediated protection of target cells. Cell surface HLA-E could be increased by incubation with synthetic peptides corresponding to residues 3-11 from the signal sequences of a number of HLA class I molecules; however, only peptides which contained a Met at position 2 were capable of conferring resistance to NK-mediated lysis, whereas those having Thr at position 2 had no effect. Interestingly, HLA class I molecules previously correlated with CD94/NKG2 recognition all have Met at residue 4 of the signal sequence (position 2 of the HLA-E binding peptide), whereas those which have been reported not to interact with CD94/NKG2 have Thr at this position. Thus, these data show a function for HLA-E and suggest an alternative explanation for the apparent broad reactivity of CD94/NKG2 with HLA class I molecules; that CD94/NKG2 interacts with HLA-E complexed with signal sequence peptides derived from "protective" HLA class I alleles rather than directly interacting with classical HLA class I proteins. C1 NIAID, Mol Struct Lab, NIH, Rockville, MD 20852 USA. Univ Munich, Inst Anthropol & Humangenet, D-80333 Munich, Germany. RP Coligan, JE (reprint author), NIAID, Mol Struct Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 34 TC 462 Z9 470 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 MAR 2 PY 1998 VL 187 IS 5 BP 813 EP 818 DI 10.1084/jem.187.5.813 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZB183 UT WOS:000072444700017 PM 9480992 ER PT J AU Umland, TC Wingert, L Swaminathan, S Schmidt, JJ Sax, M AF Umland, TC Wingert, L Swaminathan, S Schmidt, JJ Sax, M TI Crystallization and preliminary X-ray analysis of tetanus neurotoxin C fragment SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID BOTULINUM NEUROTOXINS; TOXIN; TRANSPORT; MEMBRANES; BINDING AB Two crystal forms of recombinant tetanus neurotoxin C fragment have been obtained. The C fragment corresponds to the C-terminal 451 amino-acid residues of tetanus neurotoxin and is the subunit responsible for receptor binding by the toxin. Both forms belong to space group P2(1)2(1)2(1) Form I has unit-cell dimensions of a = 71.3, b = 79.7, c = 94.0 Angstrom and produces thin plate crystals. Form II has unit-cell dimensions of a = 67.4, b = 79.7, c = 91.1 Angstrom and produces thick rod-shaped crystals. Diffraction data to 2.6 Angstrom have been collected from form II crystals. C1 Vet Adm Med Ctr, Biocrystallog Lab, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Crystallog, Pittsburgh, PA 15260 USA. NCI, Toxinol Div, Med Res Inst Infect Dis, Ft Detrick, Frederick, MD 21702 USA. RP Umland, TC (reprint author), NIH, Bldg 5,Room 335, Bethesda, MD 20892 USA. OI Umland, Timothy/0000-0002-0772-9510 NR 30 TC 10 Z9 10 U1 0 U2 0 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 MAR 1 PY 1998 VL 54 BP 273 EP 275 DI 10.1107/S0907444997009025 PN 2 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA ZD256 UT WOS:000072667000011 PM 9761892 ER PT J AU Heishman, SJ AF Heishman, SJ TI What aspects of human performance are truly enhanced by nicotine? SO ADDICTION LA English DT Editorial Material ID HUMAN PSYCHOPHARMACOLOGY; SUBCUTANEOUS NICOTINE; ALZHEIMERS-DISEASE; CIGARETTE-SMOKING; ACUTE TOLERANCE; ATTENTION; VALIDITY; MEMORY; TESTS; TASK C1 NIDA, Clin Pharmacol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Heishman, SJ (reprint author), NIDA, Clin Pharmacol Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 72 Z9 72 U1 0 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 1998 VL 93 IS 3 BP 317 EP 320 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZB501 UT WOS:000072478900001 PM 10328040 ER PT J AU Herek, GM Mitnick, L Burris, S Chesney, M Devine, P Fullilove, MT Fullilove, R Gunther, HC Levi, J Michaels, S Novick, A Pryor, J Snyder, M Sweeney, T AF Herek, GM Mitnick, L Burris, S Chesney, M Devine, P Fullilove, MT Fullilove, R Gunther, HC Levi, J Michaels, S Novick, A Pryor, J Snyder, M Sweeney, T TI Workshop report: AIDS and stigma: A conceptual framework and research agenda SO AIDS & PUBLIC POLICY JOURNAL LA English DT Editorial Material C1 Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. NIMH, Div Mental Disorders Behav Res & AIDS, Rockville, MD 20857 USA. Temple Univ, Sch Law, Philadelphia, PA 19122 USA. Univ Calif San Francisco, Ctr Aids Prevent Studies, San Francisco, CA USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. New York State Psychiat Inst, New York, NY 10032 USA. Columbia Univ, Sch Publ Hlth, New York, NY USA. Publ Media Ctr, San Francisco, CA USA. INSERM, Natl Inst Hlth & Med Res, Bethesda, MD USA. Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06520 USA. Illinois State Univ, Coll Arts, Normal, AL USA. Illinois State Univ, Sci Res Off, Normal, AL USA. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. Empire State Pride Agenda Fdn, New York, NY USA. RP Herek, GM (reprint author), Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. RI Herek, Gregory/F-9856-2011; OI Burris, Scott/0000-0002-6013-5842 NR 1 TC 91 Z9 96 U1 0 U2 8 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 USA SN 0887-3852 J9 AIDS PUBLIC POLICY J JI Aids Public Policy J. PD SPR PY 1998 VL 13 IS 1 BP 36 EP 47 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 107NU UT WOS:000075216000004 PM 10915271 ER PT J AU Knuchel, MC Spira, TJ Neumann, AU Xiao, LH Rudolph, DL Phair, J Wolinsky, SM Koup, RA Cohen, OJ Folks, TM Lal, RB AF Knuchel, MC Spira, TJ Neumann, AU Xiao, LH Rudolph, DL Phair, J Wolinsky, SM Koup, RA Cohen, OJ Folks, TM Lal, RB TI Analysis of a biallelic polymorphism in the tumor necrosis factor a promoter and HIV type 1 disease progression SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID FACTOR-ALPHA; INFECTION; RELEVANCE; ALLELES; REGION AB The relevance of a TNF-alpha promoter polymorphism, a G-to-A polymorphic sequence at position-308, was examined to test whether variant alleles of TNF-alpha affect susceptibility to infection with HIV-1 and progression to AIDS. Analysis of specimens from cohorts of HIV-1 positive homosexual men demonstrated that 3 of the 32 (9.4%) HIV-1-infected long-term nonprogressors (LTNPs) were homozygous for the uncommon TNF-2 allele compared with 3 of the 196 (1.5%) HIV-1-seronegative blood donors and uninfected homosexual men (p < 0.05), There was no difference in heterozygosity among HIV-1-seropositive or -seronegative groups, although some of the seropositive men heterozygous for the TNF2 genotype were also heterozygous for CCR5 Delta 32. However, no significant association was found between TNF genotypes and time of survival, CD4 slopes, or viral loads when seroincident (n = 109) and seroprevalent cases (n = 442) from the Chicago MACS were analyzed, Functional analysis of lymphocytes from the seronegative group revealed no difference in endogenous or mitogen-induced TNF-alpha production, as well as susceptibility to in vitro HIV-1 infection between different TNF-genotype donors, These data suggest that TNF genotypes do not play a direct role in HIV-1 disease progression; however, they could potentially be part of a multigenic linkage that may be involved in delaying progression to AIDS. C1 Ctr Dis Control, Natl Ctr Infect Dis, HIV Retrovirus Dis Branch, DASTLR, Atlanta, GA 30333 USA. Ctr Dis Control, Natl Ctr Infect Dis, Immunol Branch, DASTLR,DPD, Atlanta, GA 30333 USA. Bar Ilan Univ, Dept Life Sci, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Human Biol Res Ctr, IL-91120 Jerusalem, Israel. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20895 USA. RP Knuchel, MC (reprint author), Ctr Dis Control, Natl Ctr Infect Dis, HIV Retrovirus Dis Branch, DASTLR, Atlanta, GA 30333 USA. RI Wolinsky, Steven/B-2893-2012; Xiao, Lihua/B-1704-2013; Infektiologie, USZ/A-6921-2011 OI Xiao, Lihua/0000-0001-8532-2727; NR 15 TC 21 Z9 22 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 MAR 1 PY 1998 VL 14 IS 4 BP 305 EP 309 DI 10.1089/aid.1998.14.305 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZA585 UT WOS:000072379300003 PM 9519891 ER PT J AU Piacentini, GL Kaulbach, H Scott, T Kaliner, MA AF Piacentini, GL Kaulbach, H Scott, T Kaliner, MA TI Evaluation of nasal cytology: a comparison between methods SO ALLERGY LA English DT Article DE lavage; nasal cytology; nasal inflammatory cells; nasal provocation; scraping ID MUCOSA; CELLS C1 Univ Verona, Policlin Borgo Roma, Pediat Clin, I-37134 Verona, Italy. NIAID, Allerg Dis Sect, NIH, Bethesda, MD 20892 USA. RP Piacentini, GL (reprint author), Univ Verona, Policlin Borgo Roma, Pediat Clin, I-37134 Verona, Italy. NR 7 TC 5 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD MAR PY 1998 VL 53 IS 3 BP 326 EP 328 DI 10.1111/j.1398-9995.1998.tb03898.x PG 3 WC Allergy; Immunology SC Allergy; Immunology GA ZB685 UT WOS:000072497300018 PM 9542618 ER PT J AU Cohen, SG AF Cohen, SG TI The Jewish physician in the post-Columbus era - Supplement SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 1998 VL 19 IS 2 BP 89 EP 93 DI 10.2500/108854188778607237 PG 5 WC Allergy SC Allergy GA ZJ558 UT WOS:000073228800006 PM 9578918 ER PT J AU Cohen, SG AF Cohen, SG TI Max Brodel (1870-1941) - German-American anatomist and medical illustrator SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Biographical-Item C1 NIAID, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 1998 VL 19 IS 2 BP 96 EP 101 PG 8 WC Allergy SC Allergy GA ZJ558 UT WOS:000073228800007 PM 9578919 ER PT J AU Weed, DL Hursting, SD AF Weed, DL Hursting, SD TI Biologic plausibility in causal inference: Current method and practice SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review ID CERVICAL INTRAEPITHELIAL NEOPLASIA; PROSTATE-CANCER RISK; UNITED-STATES MEN; CIGARETTE-SMOKING; UTERINE CERVIX; MOLECULAR EPIDEMIOLOGY; ALCOHOL-CONSUMPTION; CARCINOMA INSITU; LANGERHANS CELLS; BLACK-BOX C1 NCI, Prevent Oncol Branch, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Carcinogenesis, Houston, TX 77030 USA. RP Weed, DL (reprint author), NCI, Prevent Oncol Branch, EPS-T41,6130 Execut Blvd,MSC 7105, Bethesda, MD 20892 USA. NR 179 TC 46 Z9 47 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 MAR 1 PY 1998 VL 147 IS 5 BP 415 EP 425 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC309 UT WOS:000072564200001 PM 9525527 ER PT J AU Garcia-Closas, M Thompson, WD Robins, JM AF Garcia-Closas, M Thompson, WD Robins, JM TI Differential misclassification and the assessment of gene-environment interactions in case-control studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; epidemiologic methods; misclassification ID SUSCEPTIBILITY AB In case-control studies of interactions between genetic and environmental exposures, differential misclassification of the environmental exposure with respect to disease status can introduce spurious heterogeneity of the stratum-specific odds ratios. In this paper, the authors identify conditions under which differential misclassification does not introduce bias in the interaction parameter when no multiplicative interaction is present, and it biases the interaction parameter toward the null value when a multiplicative interaction is present. The conditions are that (i) conditional on potential confounders, the environmental exposure is independent of the genotype among the controls, and (ii) misclassification of the environmental exposure is nondifferential with respect to the genotype. These conditions can be tested from the misclassified data in the control group, since a test of the independence of the genotype and the misclassified environmental exposure among the controls is a test of the joint hypothesis that conditions (i) and (ii) are both true. Therefore, the authors propose a two-step test for interaction which first tests conditions (i) and (ii) and then goes on to test for interaction, provided the first step hypothesis is not rejected. A summary test procedure to test for gene-environment interactions in the presence of misclassification, based on both a conventional test for interaction and the two-step test, is recommended, and is illustrated with data from a case-control study of the role of diet as a modifier of the association between a metabolic polymorphism and lung cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ So Maine, Sch Appl Sci, Portland, ME 04103 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Garcia-Closas, M (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, EPN-443,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NIEHS NIH HHS [ES/CA PO1 06409] NR 10 TC 55 Z9 55 U1 0 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 MAR 1 PY 1998 VL 147 IS 5 BP 426 EP 433 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC309 UT WOS:000072564200002 PM 9525528 ER PT J AU Edwards, KL Burchfiel, CM Sharp, DS Curb, JD Rodriguez, BL Fujimoto, WY LaCroix, AZ Vitiello, MV Austin, MA AF Edwards, KL Burchfiel, CM Sharp, DS Curb, JD Rodriguez, BL Fujimoto, WY LaCroix, AZ Vitiello, MV Austin, MA TI Factors of the insulin resistance syndrome in nondiabetic and diabetic elderly Japanese-American men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; Asian Americans; diabetes mellitus; non-insulin-dependent; insulin resistance; men ID IMPAIRED GLUCOSE-TOLERANCE; BODY-FAT DISTRIBUTION; CARDIOVASCULAR-DISEASE; SEGREGATION ANALYSIS; PIMA-INDIANS; MELLITUS; PREVALENCE; OBESITY; NIDDM; WOMEN AB Factor analysis has previously identified four independent factors that characterize the insulin resistance syndrome in women, interpreted as 1) weight/waist, 2) lipids, 3) insulin/glucose, and 4) systolic and diastolic blood pressure. Because it is not known whether similar factors emerge for men, or for diabetics, factor analysis was used to investigate the clustering of features characterizing the insulin resistance syndrome using data from 3,159 elderly (71-93 years) Japanese-American men participating in the fourth examination of the Honolulu Heart Program during 1991-1993. Consistent with previous results, factor analysis reduced eight risk factors (insulin, glucose, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, weight, and waist circumference) to four uncorrelated factors that explained 78.2% and 74.7% of the variance in nondiabetics (n = 2,760) and diabetics (n = 399), respectively. These factors were interpreted as I)weight/waist, 2) blood pressure, 3) lipids, and 4) insulin/glucose. Modest differences in the associations between fasting insulin and factors 1, 3, and 4 were noted for diabetics. These consistently identified composite factors may represent markers for underlying pathophysiologic mechanisms of the insulin resistance syndrome and risk of non-insulin-dependent diabetes mellitus. C1 Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. NHLBI, Honolulu Epidemiol Res Sect, Epidemiol & Biometry Program, Honolulu, HI USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96817 USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Div Clin Epidemiol, Honolulu, HI 96822 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Edwards, KL (reprint author), Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Box 358770, Seattle, WA 98195 USA. NR 40 TC 66 Z9 67 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 MAR 1 PY 1998 VL 147 IS 5 BP 441 EP 447 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC309 UT WOS:000072564200004 PM 9525530 ER PT J AU Ioannidis, JPA McQueen, PG Goedert, JJ Kaslow, RA AF Ioannidis, JPA McQueen, PG Goedert, JJ Kaslow, RA TI Use of neural networks to model complex immunogenetic associations of disease: Human leukocyte antigen impact on the progression of human immunodeficiency virus infection SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; HIV; HLA antigens; logistic models; major histocompatibility complex; neural networks (computer) ID MAJOR HISTOCOMPATIBILITY COMPLEX; HIV-1 INFECTION; AIDS; MOLECULES; PREDICTION; COHORT AB Complex immunogenetic associations of disease involving a large number of gene products are difficult to evaluate with traditional statistical methods and may require complex modeling. The authors evaluated the performance of feed-forward backpropagation neural networks in predicting rapid progression to acquired immunodeficiency syndrome (AIDS) for patients with human immunodeficiency virus (HIV) infection on the basis of major histocompatibility complex variables. Networks were trained on data from patients from the Multicenter AIDS Cohort Study (n = 139) and then validated on patients from the DC Gay cohort (n = 102). The outcome of interest was rapid disease progression, defined as progression to AIDS in <6 years from seroconversion. Human leukocyte antigen (HLA) variables were selected as network inputs with multivariate regression and a previously described algorithm selecting markers with extreme point estimates for progression risk. Network performance was compared with that of logistic regression. Networks with 15 HLA inputs and a single hidden layer of five nodes achieved a sensitivity of 87.5% and specificity of 95.6% in the training set, vs. 77.0% and 76.9%, respectively, achieved by logistic regression. When validated on the DC Gay cohort, networks averaged a sensitivity of 59.1% and specificity of 74.3%, vs, 53.1% and 61.4%, respectively, for logistic regression. Neural networks offer further support to the notion that HIV disease progression may be dependent on complex interactions between different class I and class II alleles and transporters associated with antigen processing variants, The effect in the current models is of moderate magnitude, and more data as well as other host and pathogen variables may need to be considered to improve the performance of the models. Artificial intelligence methods may complement linear statistical methods for evaluating immunogenetic associations of disease. C1 NIAID, HIV Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. NIH, Div Comp Res & Technol, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. RP Ioannidis, JPA (reprint author), NIAID, HIV Res Branch, Div Aids, NIH, Solar Bldg Room 2C31,6003 Execut Blvd, Bethesda, MD 20892 USA. RI Ioannidis, John/G-9836-2011 NR 30 TC 14 Z9 16 U1 0 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 MAR 1 PY 1998 VL 147 IS 5 BP 464 EP 471 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC309 UT WOS:000072564200007 PM 9525533 ER PT J AU Umhau, JC AF Umhau, JC TI Heart rate variability from short electrographic recordings predicts mortality from all causes in middle-aged and elderly men: The Zutphen Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Umhau, JC (reprint author), NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 3 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 MAR 1 PY 1998 VL 147 IS 5 BP 511 EP 511 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZC309 UT WOS:000072564200013 PM 9525539 ER PT J AU Lebowitz, BD Harris, HW AF Lebowitz, BD Harris, HW TI Treatment research in geriatric psychiatry: From regulatory to public health considerations SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material C1 NIMH, Adult & Geriatr Treatment & Prevent Intervent Res, Geriatr Psychopharmacol Program, Rockville, MD 20857 USA. RP Lebowitz, BD (reprint author), NIMH, Adult & Geriatr Treatment & Prevent Intervent Res, Geriatr Psychopharmacol Program, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SPR PY 1998 VL 6 IS 2 BP 101 EP 103 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA ZJ524 UT WOS:000073224800003 PM 9581205 ER PT J AU Sunderland, T AF Sunderland, T TI Alzheimer's disease - Cholinergic therapy and beyond SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 02-05, 1997 CL ORLANDO, FLORIDA SP Amer Assoc Geriatr Psychiat ID E TYPE-4 ALLELE; APOLIPOPROTEIN-E; DOUBLE-BLIND; MULTICENTER; DEMENTIA; TACRINE; PROTEIN; MEMORY; TRIAL; RISK AB While much of the Alzheimer's disease (AD) research community turns its spotlight on genetics, molecular biology, and the neurotoxicity of beta-amyloid, there is a more subtle but equally significant shift in focus emerging within AD therapeutic circles Once devoid of specific treatment options, the field now enjoys a choice of two Food and Drug Administration (FDA)-approved cholinesterase inhibitors and the prospect of several more in the near future. In addition, therapy for AD is rapidly expanding beyond the central cholinergic hypothesis to include neuroprotective agents and the possibility of interfering with basic mechanisms involved in the pathogenesis of this disorder. Clinically, we have entered the era of viable cholinergic therapies, and we are already moving beyond that starting point to an era of effective combination approaches. This article provides a clinical framework for these current and potential new therapies. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, 10-3N228,10 Ctr Dr,MSC 1275, Bethesda, MD 20892 USA. NR 26 TC 7 Z9 7 U1 3 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SPR PY 1998 VL 6 IS 2 SU 1 BP S56 EP S63 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA ZK320 UT WOS:000073307300008 PM 9581222 ER PT J AU Tadmouri, GO Tuzmen, S Ozcelik, H Ozer, A Baig, SM Senga, EB Basak, A AF Tadmouri, GO Tuzmen, S Ozcelik, H Ozer, A Baig, SM Senga, EB Basak, A TI Molecular and population genetic analyses of beta-thalassemia in Turkey SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE Turkey; beta-thalassemia; sickle cell anemia ID SICKLE-CELL ANEMIA; PRENATAL-DIAGNOSIS; TURKISH PATIENT; AMPLIFIED DNA; GLOBIN GENES; MUTATIONS; DELETION; PROBES; BP AB In this report we describe the molecular analysis of 795 chromosomes derived from unrelated Turkish beta-thalassemia and sickle cell anemia carriers identified in hematology clinics in Istanbul, Ankara, Izmir, Adana, and Antalya, The determination of the molecular pathology of 754 beta-thalassemia and 42 abnormal hemoglobin genes and analysis of the frequency distribution in six distinct regions of Turkey was accomplished, The experimental strategy, based on PCR amplification of the beta-globin gene, included dot-blot hybridization with 18 probes specific for the Mediterranean populations, denaturing gradient gel electrophoresis, and genomic sequencing. When the regional results are compared with the overall frequency of mutations in the country, it is observed that the frequencies in the western and southern parts of Turkey are in good accordance with the overall distribution, whereas the northern and eastern parts have a more region/population-specific profile with some rare mutations having a significantly high occurrence in these regions, Further evaluation of the data with respect to region- or population-dependent differences will contribute to a better understanding of the mechanisms leading to the marked genetic heterogeneity in Turkey, but could also be extremely valuable in facilitating rapid identification of mutations in families at risk for different hemoglobinopathies. (C) 1998 Wiley-Liss, Inc. C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. Bogazici Univ, Dept Mol Biol & Genet, Istanbul, Turkey. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Marmara Univ, Dept Med Biol, Istanbul, Turkey. Univ Malawi, Coll Med, Blantyre, Malawi. RP Tuzmen, S (reprint author), NIDDK, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. RI Tuzmen, Sukru/I-5663-2013; Baig, Shahid Mahmood /I-7309-2015; OI Tuzmen, Sukru/0000-0003-4822-396X; Tadmouri, Ghazi/0000-0002-3895-5609 NR 36 TC 56 Z9 58 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 1998 VL 57 IS 3 BP 215 EP 220 DI 10.1002/(SICI)1096-8652(199803)57:3<215::AID-AJH6>3.0.CO;2-Y PG 6 WC Hematology SC Hematology GA YZ477 UT WOS:000072258000006 PM 9495372 ER PT J AU Yoe, J Gause, BL Curti, BD Longo, DL Bagg, A Kopp, WC Janik, JE AF Yoe, J Gause, BL Curti, BD Longo, DL Bagg, A Kopp, WC Janik, JE TI Development of rheumatoid arthritis after treatment of large granular lymphocyte leukemia with deoxycoformycin SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE Felty's syndrome; autoimmunity; HLA-DR4; T-cell receptor; neutropenia ID COLONY-STIMULATING FACTOR; FELTYS-SYNDROME; GENE REARRANGEMENT; CSF TREATMENT; FLARE-UP; NEUTROPENIA; CELLS; PATIENT; GAMMA; SUPERANTIGEN AB The association of T-cell large granular lymphocyte (LGL) leukemia and rheumatoid arthritis is well described and it is now recognized that these patients and patients with Felty's syndrome represent different aspects of a single disease process, Most patients have rheumatoid arthritis at the time of diagnosis of LGL leukemia. This is the first detailed report of the development of rheumatoid arthritis after the diagnosis and treatment of LGL leukemia as well as the first report of rheumatoid arthritis that occurred in association with deoxycoformycin treatment, It is likely that the beneficial sustained normalization of neutrophil counts as a result of deoxycoformycin treatment played a significant role in the development of this complication, Hematological improvement occurred despite molecular genetic evidence of persistence of the abnormal T-cell clone, The role of the clonally expanded T cells in the pathogenesis of neutropenia and rheumatoid arthritis is discussed. (C) 1998 Wiley-Liss, Inc. C1 Loudoun Canc Care Ctr, Sterling, VA 20165 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD USA. Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. NCI, SAIC Frederick, Clin Serv Program, FCRDC, Frederick, MD USA. RP Janik, JE (reprint author), Loudoun Canc Care Ctr, 14 Pidgeon Hill Dr,Suite 130, Sterling, VA 20165 USA. NR 33 TC 9 Z9 10 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 1998 VL 57 IS 3 BP 253 EP 257 DI 10.1002/(SICI)1096-8652(199803)57:3<253::AID-AJH14>3.0.CO;2-B PG 5 WC Hematology SC Hematology GA YZ477 UT WOS:000072258000014 PM 9495380 ER PT J AU Brinkmann, U AF Brinkmann, U TI CAS, the human homologue of the yeast chromosome-segregation gene CSE1, in proliferation, apoptosis, and cancer SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY GENE; BREAST-CANCER; PROTEIN; CLONING; CELLS; 20Q13 C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Brinkmann, U (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37-4B20,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM uli@helix.nih.gov NR 27 TC 55 Z9 55 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1998 VL 62 IS 3 BP 509 EP 513 DI 10.1086/301773 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZF407 UT WOS:000072894400002 PM 9497270 ER PT J AU Hejtmancik, JF AF Hejtmancik, JF TI The genetics of cataract: Our vision becomes clearer SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID HEAT-SHOCK PROTEIN; TRANSGENIC MICE; CRYSTALLIN GENE; CONGENITAL CATARACT; ALPHA-CRYSTALLIN; BETA-CRYSTALLIN; HEREDITARY CATARACT; ECTOPIC EXPRESSION; LENS; GAMMA C1 NEI, OGCSB, NIH, Bethesda, MD 20892 USA. RP Hejtmancik, JF (reprint author), NEI, OGCSB, NIH, Bldg 10,Room 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov NR 57 TC 74 Z9 78 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1998 VL 62 IS 3 BP 520 EP 525 DI 10.1086/301774 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZF407 UT WOS:000072894400004 PM 9497271 ER PT J AU Norman, RA Tataranni, PA Pratley, R Thompson, DB Hanson, RL Prochazka, M Baier, L Ehm, MG Sakul, H Foroud, T Garvey, WT Burns, D Knowler, WC Bennett, PH Bogardus, C Ravussin, E AF Norman, RA Tataranni, PA Pratley, R Thompson, DB Hanson, RL Prochazka, M Baier, L Ehm, MG Sakul, H Foroud, T Garvey, WT Burns, D Knowler, WC Bennett, PH Bogardus, C Ravussin, E TI Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BODY-MASS INDEX; DEPENDENT DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; OB GENE REGION; FAT MASS; INSULIN-RESISTANCE; GLUCOSE-TRANSPORT; MARKERS FLANKING; EXTREME OBESITY; COMPLEX TRAITS AB An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in;a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint met:hods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores greater than or equal to 2 were found at 11q21-q22, for percent body fat (LOD = 2.1; P = .001), at 11q23-q24, for 24-h energy expenditure (LOD = 2.0; P = .001), and at 1p31-p21 (LOD = 2.0) and 20q11.2 (LOD = 3.0; P = .0001), for 24RQ, by pointwise and multipoint analysts. With the variance-components method, the highest LOD score (LOD = 2.3 P = .0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD = 2.8; P = .0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Sequana Therapeut Inc, Dept Stat Genet, La Jolla, CA USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN 46202 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ravussin, E (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Room 541,4212 N 16th St, Phoenix, AZ 85016 USA. EM eric_ravussin@nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1 P41 RR03655]; NIDDK NIH HHS [DK-47461] NR 59 TC 157 Z9 157 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1998 VL 62 IS 3 BP 659 EP 668 DI 10.1086/301758 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZF407 UT WOS:000072894400020 PM 9497255 ER PT J AU Ford, D Easton, DF Stratton, M Narod, S Goldgar, D Devilee, P Bishop, DT Weber, B Lenoir, G Chang-Claude, J Sobol, H Teare, MD Struewing, J Arason, A Scherneck, S Peto, J Rebbeck, TR Tonin, P Neuhausen, S Barkardottir, R Eyfjord, J Lynch, H Ponder, BAJ Gayther, SA Birch, JM Lindblom, A Stoppa-Lyonnet, D Bignon, Y Borg, A Hamann, U Haites, N Scott, RJ Maugard, CM Vasen, H AF Ford, D Easton, DF Stratton, M Narod, S Goldgar, D Devilee, P Bishop, DT Weber, B Lenoir, G Chang-Claude, J Sobol, H Teare, MD Struewing, J Arason, A Scherneck, S Peto, J Rebbeck, TR Tonin, P Neuhausen, S Barkardottir, R Eyfjord, J Lynch, H Ponder, BAJ Gayther, SA Birch, JM Lindblom, A Stoppa-Lyonnet, D Bignon, Y Borg, A Hamann, U Haites, N Scott, RJ Maugard, CM Vasen, H CA Breast Cancer Linkage Consortium TI Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OVARIAN-CANCER; SUSCEPTIBILITY GENE; LINKAGE ANALYSIS; RAPID DETECTION; MUTATIONS; CHROMOSOME-17Q21; CARRIERS AB The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers, Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes, The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due To BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes tvas found in families with four or five cases of female breast cancer only, These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated bg maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions, The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 pears. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years, The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age. C1 Inst Publ Hlth, CRC, Genet Epidemiol Unit, Strangeways Res Labs, Cambridge CB1 4RN, England. Canc Res Inst, Epidemiol Sect, Sutton, Surrey, England. Canc Res Inst, Sect Mol Carcinogenesis, Sutton, Surrey, England. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge CB2 1TN, England. Ctr Res Womens Hlth, Toronto, ON, Canada. Int Agcy Res Canc, F-69372 Lyon, France. Leiden Univ, Dept Pathol, NL-2300 RA Leiden, Netherlands. Leiden Univ, Dept Human Genet, NL-2300 RA Leiden, Netherlands. Imperial Canc Res Fund, Genet Epidemiol Lab, Leeds, W Yorkshire, England. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Inst J Paoli I Calmettes, Dept Oncol Genet, INSERM CRI9703, F-13009 Marseille, France. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Hosp, Cell Biol Lab, Reykjavik, Iceland. Iceland Canc Soc, Reykjavik, Iceland. Max Delbruck Ctr Mol Med, Berlin, Germany. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Univ Utah, Genet Epidemiol Grp, Salt Lake City, UT 84112 USA. Creighton Univ, Sch Med, Dept Preventat Med & Publ Hlth, Omaha, NE USA. Christie Hosp & Holt Radium Inst, CRC, Paediat & Familial Canc Res Grp, Manchester M20 9BX, Lancs, England. Karolinska Inst, Dept Clin Genet, Stockholm, Sweden. Inst Curie, Unite Genet Oncol, Paris, France. Ctr Jean Perrin, Mol Oncol Lab, Clermont Ferrand, France. Univ Hosp, Dept Oncol, Lund, Sweden. Univ Aberdeen, Aberdeen AB9 1FX, Scotland. Kantonsspital, CH-4031 Basel, Switzerland. Ctr Rene Gauducheau, F-44035 Nantes, France. Fdn Detect Hereditary Tumors, Leiden, Netherlands. RP Easton, DF (reprint author), Inst Publ Hlth, CRC, Genet Epidemiol Unit, Strangeways Res Labs, Worts Causeway, Cambridge CB1 4RN, England. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Bishop, Tim/0000-0002-8752-8785; albright, lisa/0000-0003-2602-3668 FU NCI NIH HHS [CA55914] NR 39 TC 1836 Z9 1864 U1 17 U2 138 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1998 VL 62 IS 3 BP 676 EP 689 DI 10.1086/301749 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA ZF407 UT WOS:000072894400022 PM 9497246 ER PT J AU Kaplan, NL Martin, ER Morris, RW Weir, BS AF Kaplan, NL Martin, ER Morris, RW Weir, BS TI Marker selection for the transmission/disequilibrium test, in recently admixed populations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; INSULIN GENE; SUSCEPTIBILITY; LOCI; INDEPENDENCE; ADMIXTURE; IDDM; TDT AB Recent admixture between genetically differentiated populations can result in high levels of association between alleles at loci that are less than or equal to 10 cM apart. The transmission/disequilibrium test (TDT) proposed by Spielman et al. (1993) can be a powerful test of linkage between disease and marker loci in the presence of association and therefore could be a useful test of linkage in admired populations. The degree of association between alleles at two loci depends on the differences in allele frequencies, at the two loci, in the founding populations; therefore, the choice of marker is important. For a multiallelic marker, one strategy that may improve the power of the TDT is to group marker alleles within a locus, on the basis of information about the founding populations and the admired population, thereby collapsing the marker into one with fewer alleles. We ha cie examined the consequences of collapsing a microsatellite into a two-allele marker, when two founding populations are assumed for the admired population, and have found that if there is random mating in the admired population, then typically there is a collapsing for which the power of the TDT is greater than that for the original microsatellite marker. A method is presented for finding the optimal collapsing that has minimal dependence on the disease and that uses estimates either of marker allele frequencies in the two founding populations or of marker allele frequencies in the current, admired population and in one of the founding populations. Furthermore, this optimal collapsing is not always the collapsing with the largest difference in allele frequencies in the founding populations. To demonstrate this strategy, we considered a recent data set, published previously, that provides frequency estimates for 30 microsatellites in 13 populations. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Program Biomath, Dept Stat, Raleigh, NC 27695 USA. N Carolina State Univ, Program Stat Genet, Dept Stat, Raleigh, NC 27695 USA. Analyt Sci Inc, Durham, NC USA. RP Kaplan, NL (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIGMS NIH HHS [GM 45344]; NINDS NIH HHS [NS 23760] NR 20 TC 28 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1998 VL 62 IS 3 BP 703 EP 712 DI 10.1086/301760 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZF407 UT WOS:000072894400025 PM 9497257 ER PT J AU Cocco, P Dosemeci, M Heineman, EF AF Cocco, P Dosemeci, M Heineman, EF TI Occupational risk factors for cancer of the central nervous system: A case-control study on death certificates from 24 US States SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE neoplasms; socio-economic status; occupation; industry; epidemiology; job-exposure matrices ID ELECTRIC UTILITY WORKERS; CAUSE-SPECIFIC MORTALITY; LOS-ANGELES COUNTY; BRAIN-TUMORS; NEW-ZEALAND; ELECTROMAGNETIC-FIELDS; MAGNETIC-FIELDS; RUBBER WORKERS; VINYL-CHLORIDE; EXPOSURE AB The risk of cancer of the central nervous system (CNS) by industry and occupation was investigated with a case-control analysis of the death certificates of 28,416 cases and 113,664 controls, selected from over 4.5 million deaths in 24 U.S. states between 1984 and 1992. Industries showing consistent increases in risk by gender and race included textile mills, paper mills, printing and publishing industries, petroleum refining, motor vehicles manufacturing, telephone and electric utilities, department stores, health care services, elementary, and secondary schools, and colleges and universities. CNS cancer risk was increased for administrators in education and related fields, secondary school teachers, and other education-and health-related occupations. The application of job-exposure matrices to the industry/occupation combinations revealed a modest increase in risk for potential contact with the public at work and exposure to solvents. Occupational exposure to electromagnetic fields (EMF) was not associated with CNS cancer, although an association was observed with a few EMF-related occupations and industries. Agricultural exposures were associated with significant risk increases among white women and white men. Further work is required to investigate in more detail specific occupational exposures or possible confounders responsible for the observed associations. (C) 1998 Wiley-Liss, Inc. C1 Univ Cagliari, Ist Med Lavoro, I-09124 Cagliari, Italy. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Cocco, P (reprint author), Univ Cagliari, Ist Med Lavoro, Via S Giorgio 12, I-09124 Cagliari, Italy. EM coccop@pacs.unica.it NR 68 TC 29 Z9 29 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1998 VL 33 IS 3 BP 247 EP 255 DI 10.1002/(SICI)1097-0274(199803)33:3<247::AID-AJIM6>3.0.CO;2-T PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YV298 UT WOS:000071809200006 PM 9481423 ER PT J AU Nussenblatt, RB Lane, HC AF Nussenblatt, RB Lane, HC TI Human immunodeficiency virus disease: Changing patterns of intraocular inflammation SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; AIDS; CYTOMEGALOVIRUS; TOXOPLASMOSIS; SAQUINAVIR; INFECTION AB PURPOSE: To evaluate and put into perspective five articles in this issue of the AMERICAN JOURNAL OF OPHTHALMOLOGY that discuss ocular inflammatory disorders in patients with human immunodeficiency virus (HIV) disease. METHODS: We drew upon recent observations concerning the effect of HIV disease on the immune system in an attempt to understand the current reports describing intraocular inflammation. RESULTS: Intraocular inflammation appears to be dependent on several factors, including specific antigenic stimuli and the state of the host immune system. During dynamic changes in these factors, conditions may arise that favor inflammatory reactions. Use of antiretroviral therapies is one mechanism zthat can effect these dynamics. CONCLUSIONS: As the immune system equilibrates at one extreme or the other (depletion or reconstitution), conditions favoring inflammation appear to dissipate. Restoration of immune function by the use of combination antiretroviral therapy, including protease inhibitors, may lead to additional cases of transient intraocular inflammation in the future. (C) 1998 by Elsevier Science Inc. All rights reserved. C1 NEI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, Bldg 10,Room 10N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM mq@helix.nih.gov NR 26 TC 40 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 1998 VL 125 IS 3 BP 374 EP 382 DI 10.1016/S0002-9394(99)80149-4 PG 9 WC Ophthalmology SC Ophthalmology GA ZA590 UT WOS:000072379800013 PM 9512156 ER PT J AU Malide, D Davies-Hill, TM Levine, M Simpson, IA AF Malide, D Davies-Hill, TM Levine, M Simpson, IA TI Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived macrophages: effects of cell activation SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose transporter targeting; recycling pathways; phagocytic cells; protein kinase C; confocal microscopy ID GLUCOSE TRANSPORTER EXPRESSION; FRUCTOSE TRANSPORTER; SMALL-INTESTINE; FUNCTIONAL-CHARACTERIZATION; PERITONEAL-MACROPHAGES; SKELETAL-MUSCLE; INSULIN; TRANSLOCATION; TISSUE; COLOCALIZATION AB We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human monocytes differentiate into macrophages in culture, and effects of the activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). Western blot analysis demonstrated progressively increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5 expression during differentiation, Confocal microscopy revealed that each isoform displayed a unique subcellular distribution and cell-activation response. GLUT-1 was localized primarily to the cell surface but was also detected in the perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3 exhibited predominantly a distinct vesicle-like staining but was present only in monocytes. GLUT-5 was found primarily at the cell surface but was detectable intracellularly. Activation with fMLP induced similar GLUT-1 and GLUT-5 redistributions from intracellular compartments toward the cell surface. PMA elicited a similar translocation of GLUT-1, but GLUT-5 was redistributed from the plasma membrane to a distinct intracellular compartment that appeared connected to the cell surface. These results suggest specific subcellular targeting of each transporter isoform and differential regulation of their trafficking pathways in cultured macrophages. C1 NIDDK, EDMNS, DB, NIH, Bethesda, MD 20892 USA. RP Malide, D (reprint author), NIDDK, EDMNS, DB, NIH, Bldg 10,Rm 5N102,10 Ctr Dr MSC 1420, Bethesda, MD 20892 USA. NR 41 TC 49 Z9 50 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 1998 VL 274 IS 3 BP E516 EP E526 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA ZA602 UT WOS:000072381100019 PM 9530136 ER PT J AU Eisenhofer, G Rundqvist, B Friberg, P AF Eisenhofer, G Rundqvist, B Friberg, P TI Determinants of cardiac tyrosine hydroxylase activity during exercise-induced sympathetic activation in humans SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE dihydroxyphenylalanine; norepinephrine; sympathetic nerves; transmitter turnover ID PLASMA DIHYDROXYPHENYLALANINE; NOREPINEPHRINE TURNOVER; ANESTHETIZED DOG; DOPA; NORADRENALINE; METABOLISM; RESPONSES; 3,4-DIHYDROXYPHENYLALANINE; METANEPHRINES; DESIPRAMINE AB This study assessed whether the mechanisms regulating cardiac norepinephrine (NE) synthesis with changes in NE release are influenced by functions of sympathetic nerves affecting transmitter turnover independently of transmitter release. Differences in arterial and coronary venous plasma concentrations of NE and its metabolites and of dihydroxyphenylalanine (DOPA), the immediate product of tyrosine hydroxylase (TH), were examined before and during cycling exercise. Relative increases during exercise in cardiac tyrosine hydroxylation (as reflected by the %increase in cardiac DOPA spillover) matched closely corresponding increases in NE turnover, but were much lower than increases in NE release. The much larger relative increases in release than turnover of NE were largely attributable to the extensive contribution to transmitter turnover from intraneuronal metabolism of NE leaking from storage vesicles. This contribution remains unchanged during sympathetic activation so that the relative increase in NE turnover is much smaller than that in exocytotic release of NE. To replenish the NE lost from stores during sympathetic activation, TH activity need increase only in proportion to the smaller increase in turnover rather than the larger relative increase in release. The ability to "gear down" increases in tyrosine hydroxylation relative to increases in NE release provides sympathetic nerves the capacity for a more extended range of sustainable release rates than otherwise possible. C1 NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Gothenburg Univ, Dept Cardiol, S-41390 Gothenburg, Sweden. Gothenburg Univ, Dept Clin Physiol, S-41390 Gothenburg, Sweden. RP Eisenhofer, G (reprint author), NINDS, Clin Neurosci Branch, NIH, Bldg 10,Rm 4D20,10 Ctr Dr,MSC 1424, Bethesda, MD 20892 USA. NR 32 TC 16 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 1998 VL 274 IS 3 BP R626 EP R634 PG 9 WC Physiology SC Physiology GA ZA600 UT WOS:000072380900007 PM 9530227 ER PT J AU Chou, CL Rapko, SI Knepper, MA AF Chou, CL Rapko, SI Knepper, MA TI Phosphoinositide signaling in rat inner medullary collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE inositol 1,4,5-trisphosphate; protein kinase C; vasopressin; muscarinic; phorbol ester ID PROTEIN-KINASE-C; RENAL TISSUE; VASOPRESSIN; CELLS; RECEPTOR; KIDNEY; HYDROLYSIS; ACTIVATION; STIMULATION; INNERVATION AB Previous studies in microdissected rat inner medullary collecting duct (IMCD) segments have demonstrated that carbachol, arginine vasopressin (AVP), and the V(2) vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) induce a similar increase in intracellular Ca(2+) The present study tested whether these agents activate the phosphoinositide hydrolysis pathway. In intracellular inositol 1,4,5-trisphosphate (IP(3)) measurements, we found that IMCD suspensions incubated with AVP or DDAVP (10(-8) M) displayed no measurable increase in IP(3), whereas IMCD suspensions incubated with the muscarinic cholinergic agent carbachol (100 mu M) induced a significant increase in IP(3) production. Similarly, carbachol, but not AVP or DDAVP, induced a significant increase in membrane-associated protein kinase C (PKC) enzyme activity. To test what specific PKC isoforms are activated by carbachol in IMCD, we first characterized the PKC isoforms in IMCD suspensions by immunoblotting using affinity-purified antibodies against different PKC isoforms. We identified one classic PKC isoform (alpha), three novel PKC isoforms (delta, epsilon, eta), and one atypical PKC isoform (zeta) in the IMCD. Carbachol induced a cytosol-to-membrane translocation of the PKC-eta isoform but did not alter the distribution of any other isoform. In contrast, AVP had no effect on the distribution of any PKC isoform tested. These data, taken together, demonstrate that carbachol is an activator of the phosphoinositide hydrolysis pathway in IMCD but do not demonstrate signaling via this pathway in response to AVP or DDAVP. These results suggest that the previously observed AVP-stimulated Ca(2+) mobilization in IMCD may be due to a mechanism other than activation of the phosphoinositide hydrolysis pathway. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Chou, CL (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, RM 6N260,10 Ctr Dr,MSC 1603,Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 39 Z9 39 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 1998 VL 274 IS 3 BP F564 EP F572 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA ZB651 UT WOS:000072493900017 PM 9530273 ER PT J AU Yang, TX Singh I Pham, H Sun, DQ Smart, A Schnermann, JB Briggs, JP AF Yang, TX Singh, I Pham, H Sun, DQ Smart, A Schnermann, JB Briggs, JP TI Regulation of cyclooxygenase expression in the kidney by dietary salt intake SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE prostaglandin H synthase; inner medulla; renal interstitial cell; macula densa; prostaglandins; sodium chloride ID RENOMEDULLARY INTERSTITIAL-CELLS; RAT MESANGIAL CELLS; PROSTAGLANDIN SYNTHESIS; SYNTHASE CYCLOOXYGENASE; COMPLEMENTARY-DNA; ANGIOTENSIN-II; MESSENGER-RNA; SODIUM-INTAKE; MACULA DENSA; HYPERTENSION AB The present studies were undertaken to determine the effect of dietary salt intake on the renal expression of cyclooxygenase-l (COX-1) and -2 (COX-2). Protein levels were assessed by Western blotting, and mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) on cDNA prepared from kidney regions, dissected nephron segments, and cultured renal cells. Both isoforms were expressed at high levels in inner medulla (IM), with low levels detected in outer medulla and cortex. COX-1 mRNA was present in the glomerulus and all along the collecting duct, whereas COX-2 mRNA was restricted to the macula densa-containing segment (MD), cortical thick ascending limb (CTAL), and, at significantly lower levels, in the inner medullary collecting duct. Both isoforms were highly expressed at high levels in cultured medullary interstitial cells and at lower levels in primary mesangial cells and collecting duct cell lines. Maintaining rats on a low-or high-NaCl diet for 1 wk did not affect expression of COX-1. In IM of rats treated with a high-salt diet, COX-2 mRNA increased 4.5-fold, and protein levels increased 9.5-fold. In contrast, cortical COX-2 mRNA levels decreased 2.9-fold in rats on a high-salt diet and increased 3.3-fold in rats on a low-salt diet. A low-salt diet increased COX-2 mRNA 7.7-fold in MD and 3.3-fold in CTAL. Divergent regulation of COX-2 in cortex and medulla by dietary salt suggests that prostaglandins in different kidney regions Serve different functions, with medullary production playing a role in promoting the excretion of salt and water in volume overload, whereas cortical prostaglandins may protect glomerular circulation in volume depletion. C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48104 USA. Univ Michigan, Dept Physiol, Ann Arbor, MI 48104 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Yang, TX (reprint author), George M OBrien Renal Ctr, Dept Internal Med, Div Nephrol, 1150 W Med Ctr Dr,1560 Med Sci Res Bldg II, Ann Arbor, MI 48109 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [DK-37448, DK-39255, DK-40042] NR 43 TC 175 Z9 182 U1 0 U2 2 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 MAR PY 1998 VL 274 IS 3 BP F481 EP F489 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA ZB651 UT WOS:000072493900007 PM 9530264 ER PT J AU Breslow, RA Ross, SA Weed, DL AF Breslow, RA Ross, SA Weed, DL TI Quality of reviews in epidemiology SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SYSTEMATIC REVIEWS; PHYSICAL-ACTIVITY; BREAST-CANCER; BRAIN-TUMORS; ARTICLES; HEALTH; RISK; TRANSMISSION; ASSOCIATION; MORTALITY AB Objectives. This study examined the quality of recent reviews in epidemiology. Methods. All 1995 issues of 7 widely read epidemiology journals were searched to identify reviews. Results. Twenty-nine reviews were identified. Methodology was not specified or incomplete for literature searches in 79% of reviews; the same was true for inclusion criteria in 83% and for combining studies in 62%. More than 60% of the reviews were not methodologically systematic. Conclusions. There is a need to improve the quality of review papers in epidemiology. If systematic methodology were followed more frequently, epidemiologic science and its application could be improved. C1 NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Breslow, RA (reprint author), NCI, Canc Prevent Fellowship Program, 6130 Execut Blvd,EPN-313, Bethesda, MD 20892 USA. NR 46 TC 25 Z9 25 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 MAR PY 1998 VL 88 IS 3 BP 475 EP 477 DI 10.2105/AJPH.88.3.475 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT680 UT WOS:000074113800032 PM 9518988 ER PT J AU Adachi, H Preston, G Harvat, B Dawson, MI Jetten, AM AF Adachi, H Preston, G Harvat, B Dawson, MI Jetten, AM TI Inhibition of cell proliferation and induction of apoptosis by the retinoid AHPN in human lung carcinoma cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TRACHEAL EPITHELIAL-CELLS; CYCLIN-DEPENDENT KINASES; VITAMIN-A-DEFICIENCY; ACID RECEPTOR-ALPHA; GENE-EXPRESSION; SQUAMOUS DIFFERENTIATION; HAMSTER TRACHEA; CANCER; LINES; P53 AB In this study, we investigated the effect of the novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN/CD437) on the growth of human lung carcinoma cell lines. AHPN inhibits the proliferation of all cell lines tested, irrespective of the lung tumor type, in a concentration-and time-dependent manner. A dramatic reduction in cell number was observed in adenocarcinoma H460 cells, and was shown to be related to an induction of apoptosis. Bromodeoxyuridine (BrdU) incorporation and flow-cytometric analyses indicated that treatment of H460 cells with AHPN induces cell-cycle arrest at the G(1) phase. We therefore investigated the effect of AHPN on several regulatory proteins of the CI phase of the cell-cycle. The cell-cycle arrest induced by AHPN was accompanied by an inhibition of the hyperphosphorylation of the retinoblastoma (Rb) protein, an indication of G, arrest. Furthermore, two cyclin-dependent kinases, cdk2 and cdk4, which are normally involved in the phosphorylation of Rb, were shown to have decreased activity. In some cell lines, the decrease in cdk activity may be partly related to an increase in p21(WAF1/Cip1) (p21), an inhibitor of cyclin-dependent kinases. No changes were observed in the cyclin-dependent kinase inhibitor p27(Kip1). Th, observed increase in p53 in response to AHPN could at least to some extent be responsible for the increased levels of p21. The increase in p53 expression was found to be regulated at a post-transcriptional level. Our results suggest that the growth inhibition of certain lung carcinoma noma cell lines by AHPN is at least partly related to an increase in p21. However, in other cell lines, different mechanisms appear to be involved. The specificity with which AKPN and other retinoids induce growth arrest and p21 expression indicates that the action of AHPN is not mediated by RAR or RXR receptors, but involves a novel signaling pathway. C1 NIEHS, Lab Pulm Pathobiol & Mol Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA. SRI Int, Retinoid Program, Menlo Park, CA 94025 USA. RP Jetten, AM (reprint author), NIEHS, Lab Pulm Pathobiol & Mol Carcinogenesis, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 NR 56 TC 52 Z9 54 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1998 VL 18 IS 3 BP 323 EP 333 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA ZB187 UT WOS:000072445100004 PM 9490650 ER PT J AU Fogt, F Vortmeyer, AO Senderowicz, AM AF Fogt, F Vortmeyer, AO Senderowicz, AM TI Sodium polystyrene sulfonate damage SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter C1 NCI, DTP Clin Trials Unit, Med Branch, NIH, Bethesda, MD 20892 USA. RP Fogt, F (reprint author), NCI, DTP Clin Trials Unit, Med Branch, NIH, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 1998 VL 22 IS 3 BP 379 EP 380 DI 10.1097/00000478-199803000-00016 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA ZA177 UT WOS:000072336700015 PM 9500782 ER PT J AU Saroff, HA AF Saroff, HA TI From glycine to glutamic acid: Analysis of the proton-binding isotherm of glutamic acid SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB The process of the analysis of the protonation of glycine is extended to the three-site molecule of glutamic acid with its amino and two carboxyl groups. Detailed data on the binding of protons to glutamic acid are available not only for protonation of the three groups simultaneously but also for derivatives in which the alpha and beta carboxyl groups are esterified. These data plus data on the protonation of glutaric acid provide the necessary information for a complete description of the protonation process with a limited number of reasonable assumptions. The assumptions lead to the conclusion that stabilization of the molecule of glutamic acid occurs on all steps of the protonation with the predominant stabilization occurring in the early steps of the reaction. An Appendix is included showing that the experimental data for both glycine and glutamic acid can be generated with hypothetical molecules, For glycine, identical experimental isotherms can result from protonation of two different nitrogen groups as well as two different negative groups, With glutamic acid three hypothetical molecules are capable of generating the identical experimental isotherms. They are (i) three nitrogen groups, (ii) three negative groups, and (iii) two nitrogen groups combined with one negative group. Interpretation of binding data requires explicit assumptions defining both the interactions and the nature of the binding sites. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Saroff, HA (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 8 TC 2 Z9 2 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 MAR 1 PY 1998 VL 257 IS 1 BP 71 EP 79 DI 10.1006/abio.1997.2511 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YZ767 UT WOS:000072289600011 PM 9512775 ER PT J AU Katsetos, CD Karkavelas, G Herman, MM Vinores, SA Provencio, J Spano, AJ Frankfurter, A AF Katsetos, CD Karkavelas, G Herman, MM Vinores, SA Provencio, J Spano, AJ Frankfurter, A TI Class III beta-tubulin isotype (beta III) in the adrenal medulla: I. Localization in the developing human adrenal medulla SO ANATOMICAL RECORD LA English DT Article DE class III beta-tubulin isotype; tubulin; S-100 protein, adrenal gland; development; immunohistochemistry; cytoskeleton ID IMMUNOHISTOCHEMICAL OBSERVATIONS; POSTTRANSLATIONAL MODIFICATION; MONOCLONAL-ANTIBODIES; CHROMAFFIN CELLS; PALE ISLANDS; MEDULLOBLASTOMAS; DIFFERENTIATION; IDENTIFICATION; SYNAPTOPHYSIN; CHROMOGRANIN AB Background: The class III beta-tubulin isotype (beta III) is present in neurons of the central and peripheral nervous systems at the earliest stages of morphological differentiation (Easter et al., J Neurosci 13:285-299, 1993; Katsetos et al., J Neuropathol Exp Neurol 52:655-666, 1993), The localization of this protein by immunohistochemistry in the different cell types of the developing human adrenal medulla is described, Methods: A mouse monoclonal antibody, TuJ1, was used to localize beta III in formalin-fixed, paraffin-embedded sections from 18 human fetal and adult adrenal glands, Tissue sections were also studied with rabbit antisera recognizing either S-100 protein or glial fibrillary acidic protein (GrFAP), Results: In the developing human adrenal medulla, beta III immunoreactivity was maximal in migrating sympathoadrenal neuroblasts/immature neurons through the end of the second trimester, Clusters of beta III-positive migrating cells, focally forming Homer Wright rosettes, could be identified in a gradient of adrenocortical invasion, i.e., through the permanent cortex and within sinusoids of the fetal cortex en route to the medulla, Outside the adrenal gland, strong beta III staining was observed in peripheral nerve bundles, sympathetic ganglia, and paraganglia at various developmental stages, In adrenal glands from 23 weeks of gestation on, and throughout adult life, all ganglion cells were beta III immunoreactive, In contrast, not all chromaffin cells exhibited beta III staining, but when present, the staining was finely granular, Sustentacular and satellite cells, adrenocortical cells and other mesenchymal elements were beta III-negative. In sections of fetal and adult adrenal glands, S-100 protein had a sustentacular localization, No GFAP staining was present in sustentacular cells from either fetal or adult adrenals. Conclusions: In the developing human adrenal medulla, there is a peak of beta III expression during the active wave of migration of sympathetic neuroblasts. In the mature medulla, beta III is invariably present in adrenergic neurons. However, not all chromaffin-like cells express beta III, suggesting that the presence or absence of this protein identifies two subpopulations of chromaffin cells. (C) 1998 Wiley-Liss, Inc. C1 Med Coll Penn & Hahnemann Univ, Neuropathol Lab, Philadelphia, PA USA. NIMH, Clin Brain Disorders Branch, Ctr Neurosci, IRP NIH, Washington, DC USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22908 USA. RP Katsetos, CD (reprint author), St Christophers Hosp Children, Div Neurol, Erie Ave & Front St, Philadelphia, PA 19134 USA. FU NEI NIH HHS [EY10017]; NINDS NIH HHS [NS21142] NR 35 TC 18 Z9 20 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAR PY 1998 VL 250 IS 3 BP 335 EP 343 DI 10.1002/(SICI)1097-0185(199803)250:3<335::AID-AR8>3.0.CO;2-Z PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA YZ783 UT WOS:000072291200008 PM 9517850 ER PT J AU Karkavelas, G Katsetos, CD Geddes, JF Herman, MM Vinores, SA Cooper, HS Provencio, J Frankfurter, A AF Karkavelas, G Katsetos, CD Geddes, JF Herman, MM Vinores, SA Cooper, HS Provencio, J Frankfurter, A TI Class III beta-tubulin isotype (beta III) in the adrenal medulla: II. Localization in primary human pheochromocytomas SO ANATOMICAL RECORD LA English DT Article DE class III beta-tubulin; tubulin, S-100 protein; immunohistochemistry; pheochromocytoma; carcinoma; adrenal gland ID NEURO-ENDOCRINE TUMORS; IMMUNOHISTOCHEMICAL OBSERVATIONS; NEUROENDOCRINE TUMORS; CHROMAFFIN CELLS; S-100 PROTEIN; S100 PROTEIN; EXPRESSION; IMMUNOREACTIVITY; SYNAPTOPHYSIN; NEUROBLASTOMA AB Background: The Class III beta-tubulin isotype (beta III) is expressed specifically in central and peripheral nervous system neurons at various stages of neuronal differentiation. We have shown previously that beta III is expressed in a differentiation-dependent manner in human neuroblastomas arising in the adrenal medulla and sympathetic chains (Katsetos et al., Clin Neuropathol 13:241-255, 1994), The neuronal distribution of beta III in the developing and mature human adrenal medullae is detailed in the companion article (Katsetos et al., 1998A), Methods: We have compared the localization of the neuronal beta III to S-100 protein, a sustentacular cell marker, in 14 formalin-fixed, paraffin-embedded primary human pheochromocytomas of the adrenal medulla and 14 adrenocortical tumors (adenomas and carcinomas), Results: In pheochromocytomas, beta III staining was present in all tumors, but the number of stained cells varied in the two neural neoplastic phenotypes, Although the majority of chromaffin-like cells were beta III-positive, there was a lack of beta III in one-third of the tumor cells, Compared to chromaffin-like phenotypes, neuronal (ganglion-like cells) were invariably beta III-positive, Stromal sustentacular cells, stromal fibroblasts, and tumor blood vessels were beta III-negative, Sustentacular cells in pheochromocytomas were S-100 protein-positive, but beta III-negative. Primary adrenocortical tumors were beta III-negative with the exception of rare beta III-positive cells demonstrated in one case. Conclusions: The distribution of beta III in human pheochromocytomas of the adrenal gland is differentiation-dependent, closely recapitulating chromaffin cell and neuronal phenotypes of the normal adrenal medulla. Our findings indicate that beta III may be used as one of the adjuvant neural markers in the differential diagnosis of adrenal tumors, i.e., pheochromocytoma versus adrenocortical carcinoma. The occurrence of rare beta III-positive cells in cortical carcinomas is exceptional and probably represents the acquisition of a divergent neuroendocrine phenotype. The significance of the latter is unclear, although it may constitute a marker for malignancy. (C) 1998 Wiley-Liss, Inc. C1 Med Coll Penn & Hahnemann Univ, Neuropathol Lab, Philadelphia, PA USA. Med Coll Penn & Hahnemann Univ, Dept Pathol & Lab Med, Philadelphia, PA 19129 USA. St Bartholomews & Royal London Sch Med & Dent, Dept Morbid Anat & Histopathol, London, England. NIMH, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, IRP,NIH, Washington, DC 20032 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22908 USA. RP Katsetos, CD (reprint author), St Christophers Hosp Children, Div Neurol, Erie Ave & Front St, Philadelphia, PA 19134 USA. FU NEI NIH HHS [EY10017]; NINDS NIH HHS [NS21142] NR 49 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAR PY 1998 VL 250 IS 3 BP 344 EP 350 PG 7 WC Anatomy & Morphology SC Anatomy & Morphology GA YZ783 UT WOS:000072291200009 PM 9517851 ER PT J AU Katsetos, CD Herman, MM Balin, BJ Vinores, SA Hessler, RB Arking, EJ Karkavelas, G Frankfurter, A AF Katsetos, CD Herman, MM Balin, BJ Vinores, SA Hessler, RB Arking, EJ Karkavelas, G Frankfurter, A TI Class III beta-tubulin isotype (beta III) in the adrenal medulla: III. Differential expression of neuronal and glial antigens identifies two distinct populations of neuronal and glial-like (sustentacular) cells in the PC12 rat pheochromocytoma cell line maintained in a Gelfoam matrix system SO ANATOMICAL RECORD LA English DT Article DE PC12; pheochromocytoma; glial differentiation; sustentacular cell differentiation; neuronal differentiation; glial fibrillary acidic protein; S-100 protein; class III beta-tubulin; tubulin; cytoskeleton ID NERVE GROWTH-FACTOR; MICROTUBULE-ASSOCIATED PROTEIN; FIBRILLARY ACIDIC PROTEIN; INDUCED NEURITE OUTGROWTH; ORGAN-CULTURE SYSTEMS; CHROMAFFIN CELLS; CYCLIC-AMP; COMPARATIVE IMMUNOBLOT; IMMUNOHISTOCHEMICAL OBSERVATIONS; MONOCLONAL-ANTIBODIES AB Background: The rat PC12 pheochromocytoma cell line provides an established system for the study of neuronal differentiation. To our knowledge, glial differentiation has not been reported in this cell line. Methods: We have studied, by immunohistochemistry and immunoblotting, the presence of neuronal cytoskeletal antigens [class III beta-tubulin isotype (beta III), microtubule associated proteins MAP2, MAP1B and tau, and different neurofilament (NF) protein components], and synaptophysin in comparison with the glial fibrillary acidic protein (GFAP) and S-100 protein in the PC12 cell line, In three different experiments, PC12 cells were maintained in a three-dimensional gelatin foam (Gelfoam) matrix system for up to 34 days with and without treatment with 1 mM dibutyryl cyclic (dc)AMP, Immunohistochemistry was performed on explants ranging from 2 to 32 days-in vitro, which were fixed in either Bouin's solution, 70% ethanol, or 10% neutral-buffered formalin and embedded in paraffin. Immunoblotting was performed on Gelfoam explants with a panel of antibodies against all aforementioned neuronal and glial markers, Additional immunoblot experiments using anti-GFAP and anti-beta III monoclonal antibodies in cell suspensions and homogenates from PC12 monolayer cultures were carried out to compare growth conditions in relation to the expression of these proteins. Results: beta III and MAP2 were demonstrated by immunohistochemistry and immunoblotting of PC12 explants maintained for up to 32 days in Gelfoam matrices with and without treatment with dcAMP, Intense filamentous and granular beta III staining of PC12 cells was observed in dcAMP-treated cultures concomitant with neuronal morphologic alterations (neuritogenesis and ganglionic phenotype), In untreated cultures, beta III staining was present in less differentiated cells, as well in cells undergoing neuritic development, The neuronal phenotype of PC12 cells was confirmed by staining for MAP2, tau, and NF proteins, as well as for synaptophysin, The presence of beta III, MAP2, MAP1B, tau, and NF proteins was confirmed by immunoblotting, Clusters of GFAP-positive and S-100 protein-positive spindle cells, phenotypically distinct from the chromaffin-like or neuronal cells, were demonstrated in Gelfoam explants at 5-30 days in vitro, In 30-day-old cultures treated with dcAMP, there was strong filamentous GFAP and diffuse S-100 protein staining in an increased number of sustentacular-like PC12 cells. GFAP staining was corroborated by immunoblotting of explants maintained under identical conditions in vitro, In contrast, immunoblots performed on homogenates from PC12 suspension and monolayer cultures were GFAP-negative. Conclusions: Neuronal and glial-like, presumed sustentacular, phenotypes were demonstrated in PC12 cells grown in Gelfoam matrices with and without treatment with dcAMP for up to 34 days. To our knowledge, the occurrence of glial differentiation in the PC12 line is a hitherto unreported finding, Adult rat medullary sustentacular cells are known to express S-100 and GFA proteins (Suzuki and Kachi, Kaibogaku Zasshi-J Anat 70(2): 130-139, 1995), and the organ culture system employed in our study may well have favored this direction of differentiation. (C) 1998 Wiley-Liss, Inc. C1 Med Coll Penn & Hahnemann Univ, Neuropathol Lab, Philadelphia, PA USA. Med Coll Penn & Hahnemann Univ, Dept Pathol & Lab Med, Philadelphia, PA 19129 USA. Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22908 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. NIMH, Neurosci Ctr St Elizabeths, Clin Brain Disorders Branch, NIH, Washington, DC 20032 USA. RP Katsetos, CD (reprint author), St Christophers Hosp Children, Div Neurol, Erie Ave & Front St, Philadelphia, PA 19134 USA. FU NEI NIH HHS [EY10017]; NINDS NIH HHS [NS21142] NR 95 TC 19 Z9 19 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAR PY 1998 VL 250 IS 3 BP 351 EP 365 PG 15 WC Anatomy & Morphology SC Anatomy & Morphology GA YZ783 UT WOS:000072291200010 PM 9517852 ER PT J AU Mastana, SS Calderon, R Pena, J Reddy, PH Papiha, SS AF Mastana, SS Calderon, R Pena, J Reddy, PH Papiha, SS TI Anthropology of the apolipoprotein E (apo E) gene: low frequency of apo E4 allele in Basques and in tribal (Baiga) populations of India SO ANNALS OF HUMAN BIOLOGY LA English DT Article ID E POLYMORPHISM AB The distribution of apolipoprotein E (ape E) polymorphism was examined in 11 population groups not previously studied for this system. There is a marked difference in phenotype and gene frequency between the populations of England and Spain. The south European populations of Basques and Spanish non-Basques showed greater similarity to the populations of South Asia. The study clearly indicates that the distribution pf apo E alleles does match with regions showing a high mortality rate of coronary heart disease. The data presented also indicate that authochthon groups such as Basques in Europe and tribals in India may throw better light on the role of apolipoproteins in the regulation of lipid levels in disease. C1 Loughborough Univ Technol, Dept Human Sci, Human Genet Lab, Loughborough LE11 3TU, Leics, England. Univ Basque Country, E-48080 Bilbao, Spain. NCHGR, NIH, Lab Gene Transfer, Bethesda, MD USA. Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Mastana, SS (reprint author), Loughborough Univ Technol, Dept Human Sci, Human Genet Lab, Loughborough LE11 3TU, Leics, England. RI Mastana, Sarabjit/A-1405-2011; Calderon, Rosario/K-2514-2014; Pena, Jose/L-5855-2014 OI Mastana, Sarabjit/0000-0002-9553-4886; Calderon, Rosario/0000-0001-9196-5323; Pena, Jose/0000-0002-2952-8461 NR 12 TC 27 Z9 27 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0301-4460 J9 ANN HUM BIOL JI Ann. Hum. Biol. PD MAR-APR PY 1998 VL 25 IS 2 BP 137 EP 143 DI 10.1080/03014469800005512 PG 7 WC Anthropology; Biology; Public, Environmental & Occupational Health SC Anthropology; Life Sciences & Biomedicine - Other Topics; Public, Environmental & Occupational Health GA ZB363 UT WOS:000072464200004 PM 9533513 ER PT J AU Wittes, RE Yoder, O AF Wittes, RE Yoder, O TI One community - The B. Chevalier Lecture, held at the EORTC New Drugs Meeting, Lugano, Switzerland, 19-21 June 1997 SO ANNALS OF ONCOLOGY LA English DT Article DE cancer research; clinical trials; communication; drug development; international cooperation C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Wittes, RE (reprint author), NCI, Div Canc Treatment & Diag, Bldg 31,Room 3A44,31 Ctr Dr,MSC 2440, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 1998 VL 9 IS 3 BP 251 EP 254 DI 10.1023/A:1008207304355 PG 4 WC Oncology SC Oncology GA ZW794 UT WOS:000074449000010 PM 9602257 ER PT J AU Danforth, DN Zujewski, J O'Shaughnessy, J Riseberg, D Steinberg, SM McAtee, N Noone, M Chow, C Chaudhry, U Lippman, M Jacobson, J Okunieff, P Cowan, KH AF Danforth, DN Zujewski, J O'Shaughnessy, J Riseberg, D Steinberg, SM McAtee, N Noone, M Chow, C Chaudhry, U Lippman, M Jacobson, J Okunieff, P Cowan, KH TI Selection of local therapy after neoadjuvant chemotherapy in patients with stage IIIA,B breast cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE neoadjuvant chemotherapy; stage III breast cancer; breast radiotherapy; mastectomy; inflammatory breast cancer ID RADIATION-THERAPY; INDUCTION CHEMOTHERAPY; SURGERY; CARCINOMA; RADIOTHERAPY; DOXORUBICIN; MASTECTOMY; MANAGEMENT AB Background: Stage IIIA,B breast cancer is commonly treated with neoadjuvant chemotherapy because of high objective response rates and improved operability. Criteria for subsequent selection of local therapy-mastectomy, radiotherapy, or both-are not well defined. We adopted a policy of selective local therapy based on rebiopsy of the breast and clinical axillary lymph node status at the time of best response to chemotherapy. Methods: Between 1980 and 1993, 126 patients with stage IIIA,B breast cancer were treated with neoadjuvant chemotherapy and definitive local therapy. The long-term incidence of locoregional failure (in-breast, chest wall, axilla, supraclavicular, neck), relapse-free survival, and overall survival was determined. Results: The overall clinical objective response rate to chemotherapy was 95.2%. Eighty-three patients underwent mastectomy, with negative margins achieved in 91.6%. Forty-two patients had breast preservation; the overall in-breast recurrence rate was 19.0% (8 of 42 patients). The overall locoregional recurrence rate by site was: chest wall-8.7% (11 of 126 patients), axilla-8.7% (11 of 126 patients), supraclavicular-5.6% (7 of 126 patients), and neck-4.0% (5 of 126 patients). The axillary recurrence rate was 6.6% (5 of 76 patients) for clinically negative axilla treated with radiotherapy only, and 12.0% (6 of 50 patients) for clinically positive axilla treated with surgery only. The overall long-term survival probabilities (6 years) according to stage were: stage IIIA-58.0%, stage IIIBnoninflam-58.0%, stage IIIBinflam-36.0%. Conclusions: These findings support a selective approach to local therapy in patients with stage IIIA,B boast cancer. This approach provides local control in most patients, and allows for breast preservation and elimination of axillary dissection in selected patients. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, Bldg 10,Room 2B38, Bethesda, MD 20892 USA. NR 27 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 1998 VL 5 IS 2 BP 150 EP 158 DI 10.1007/BF02303848 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA ZA601 UT WOS:000072381000010 PM 9527268 ER PT J AU White, EL Ross, LJ Steele, VE Kelloff, GJ Hill, DL AF White, EL Ross, LJ Steele, VE Kelloff, GJ Hill, DL TI Screening of potential cancer preventing chemicals as antioxidants in an in vitro assay SO ANTICANCER RESEARCH LA English DT Article DE chemoprevention; antioxidants; fluorescence; Trolox; lazaroid U83836E; glutathione; purpurgallin ID LOW-DENSITY-LIPOPROTEIN; PEROXYL RADICALS; GOMISIN-A; PEROXIDATION; INHIBITOR; BRAIN; ACIDS AB We used an azo-initiated fluorescence assay to rank a series of antioxidants, with the objective of selecting compounds for further evaluation as chemopreventive agents. Trolox was the positive control for the assay and with an IC50 of 0.50 mu M, was more active than any of the other 16 compounds examined. Three compounds, U83836E, glutathione, and purpurgallin, were only slightly less active with IC50's in cite 1-3 mu M range. Four other compounds were almost as active: protochatechuic acid, N-acetyl-L-cysteine, U74389G, and lipoic acid (reduced). This fluorescence-based assay for antioxidant activity is a rapid economical way of ranking antioxidants for further development in the National Cancer Institute's chemoprevention program. C1 So Res Inst, Birmingham, AL 35205 USA. NCI, Rockville, MD 20852 USA. RP White, EL (reprint author), So Res Inst, 2000 9th Ave S, Birmingham, AL 35205 USA. FU NCI NIH HHS [N0 1-CN-65116, N0 1-CN-55139] NR 19 TC 4 Z9 4 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1998 VL 18 IS 2A BP 769 EP 773 PG 5 WC Oncology SC Oncology GA ZQ150 UT WOS:000073827300012 PM 9615718 ER PT J AU Hida, T Leyton, J Makheja, AN Ben-Av, P Hla, T Martinez, A Mulshine, J Malkani, S Chung, P Moody, TW AF Hida, T Leyton, J Makheja, AN Ben-Av, P Hla, T Martinez, A Mulshine, J Malkani, S Chung, P Moody, TW TI Non-small cell lung cancer cycloxygenase activity and proliferation are inhibited by non-steroidal antiinflammatory drugs SO ANTICANCER RESEARCH LA English DT Article DE non-small cell lung cancer; prostaglandin E-2; cyclooxygenase-2; proliferation; NSAIDs ID PROSTAGLANDIN-G/H SYNTHASE; FAMILIAL ADENOMATOUS POLYPOSIS; COLON CARCINOGENESIS; ENDOPEROXIDE SYNTHASES; UP-REGULATION; REDUCED RISK; ASPIRIN USE; GROWTH; EXPRESSION; LINES AB The effects of non-steroidal antiinflammatory drugs (NSAIDs) on non-small cell lung cancer (NSCLC) were investigated. Arachidonic acid (AA) was metabolized to prostaglandin E2 (PGE2) in NSCLC cells. NSAIDs such as aspirin or indomethacin reduced PGE2 levels in NCI-H157 and H1263 cells, and the dea ease caused by PGE2 was reversed by epidermal growth factor (EGF). By RT-PCR, both cyclooxygenase (COX)-1 and COX-2 mRNAs are detected in NCI-H157 and H1264 cells. By Northern analysis, COX-2 mRNA was induced by EGF and phorbol ester: By immunocytochemistry COX-1 and COX-2 enzymes were localized to NSCLC tumors. Aspirin, indomethacin and ibuprofen decreased NSCLC growth in vitro. Aspirin and indomethacin inhibited proliferation of NSCLC xenografts in nude mice. These data suggest that COX enzymes may be important regulatory components of NSCLC. C1 NCI, Dept Cell & Canc Biol, Med Branch, BPRB, Rockville, MD 20850 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. Amer Red Cross, Jerome H Holland Lab, Dept Mol Biol, Rockville, MD 20855 USA. RP Moody, TW (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, BPRB, Bldg KWC,Rm 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. RI Hla, Timothy/G-5873-2012; Martinez, Alfredo/A-3077-2013 OI Hla, Timothy/0000-0001-8355-4065; Martinez, Alfredo/0000-0003-4882-4044 NR 51 TC 97 Z9 98 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1998 VL 18 IS 2A BP 775 EP 782 PG 8 WC Oncology SC Oncology GA ZQ150 UT WOS:000073827300013 PM 9615719 ER PT J AU Turpin, JA Buckheit, RW Derse, D Hollingshead, M Williamson, K Palamone, C Osterling, MC Hill, SA Graham, L Schaeffer, CA Bu, M Huang, MJ Cholody, WM Michejda, CJ Rice, WG AF Turpin, JA Buckheit, RW Derse, D Hollingshead, M Williamson, K Palamone, C Osterling, MC Hill, SA Graham, L Schaeffer, CA Bu, M Huang, MJ Cholody, WM Michejda, CJ Rice, WG TI Inhibition of acute-, latent-, and chronic-phase human immunodeficiency virus type 1 (HIV-1) replication by a bistriazoloacridone analog that selectively inhibits HIV-1 transcription SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DYNAMICS IN-VIVO; RNA-POLYMERASE; ZINC FINGERS; PROTEIN; POTENT; CELLS; BISIMIDAZOACRIDONES; INTEGRATION; LYMPHOCYTES; GENERATION AB Nanomolar concentrations of temacrazine (1,4-bis[3-(6-oxo-6H-v-triazolo[4,5,1-de]acridin-5-yl)amino- propyl]piperazine) were discovered to inhibit acute human immunodeficiency virus type 1 (HIV-1) infections and suppress the production of virus from chronically and latently infected cells containing integrated proviral DNA. This bistriazoloacridone derivative exerted its mechanism of antiviral action through selective inhibition of HIV-1 transcription during the postintegrative phase of virus replication. Mechanistic studies revealed that temacrazine blocked HIV-1 RNA formation without interference with the transcription of cellular genes or,vith events associated with the HIV-1 Tat and Rev regulatory proteins. Although temacrazine inhibited the in vitro 3' processing and strand transfer activities of HIV-1 integrase, with a 50% inhibitory concentration of approximately 50 nM, no evidence of an inhibitory effect on the intracellular integration of proviral DNA into the cellular genome during the early phase of infection could be detected. Furthermore, temacrazine did not interfere with virus attachment or fusion to host cells or the enzymatic activities of HIV-1 reverse transcriptase or protease, and the compound was not directly virucidal. Demonstration of in vivo anti-HIV-l activity by temacrazine identifies bistriazoloacridones as a new class of pharmaceuticals that selectively blocks HIV-1 transcription. C1 NCI, Lab Antiviral Drug Mech, Dev Therapeut Program, Frederick Canc Res & Dev Ctr,SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Biol Testing Branch,Dev Therapeut Program, Div Canc Treatment Diag & Ctr, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Macromol Struct Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Frederick Res Ctr, Virol Res Grp, So Res Inst, Frederick, MD 21701 USA. RP Rice, WG (reprint author), NCI, Lab Antiviral Drug Mech, Dev Therapeut Program, Frederick Canc Res & Dev Ctr,SAIC Frederick, Bldg 431T-B,POB B, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-56000, N01-C0-46000] NR 41 TC 46 Z9 48 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 MAR PY 1998 VL 42 IS 3 BP 487 EP 494 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YZ945 UT WOS:000072311000001 PM 9517921 ER PT J AU Hafner, R Bethel, J Power, M Landry, B Banach, M Mole, L Standiford, HC Follansbee, S Kumar, P Raasch, R Cohn, D Mushatt, D Drusano, G AF Hafner, R Bethel, J Power, M Landry, B Banach, M Mole, L Standiford, HC Follansbee, S Kumar, P Raasch, R Cohn, D Mushatt, D Drusano, G TI Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MYCOBACTERIUM-AVIUM COMPLEX; PERFORMANCE LIQUID-CHROMATOGRAPHY; ANTIMICROBIAL AGENTS; AIDS; INTRACELLULARE; UVEITIS; AZITHROMYCIN; PROPHYLAXIS; COMBINATION; MACROLIDES AB This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of <200 cells/mm(3). Thirty-four subjects were randomized equally to either regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received clarithromycin and subjects assigned to regimen B received rifabutin, and then both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15 regimen B subjects who started combination therapy, 1 subject in each group prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11 regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for single-agent therapy (day 14) and combination therapy (day 42) were compared. Regimen A resulted in a mean decrease of 44% (P = 0.003) in the clarithromycin area under the plasma concentration-time curve (AUG), while there aas a mean increase of 57% (P = 0.004) in the AUC of the clarithromycin metabolite 14-OH-clarithromycin. Regimen B resulted in a mean increase of 99% (P = 0.001) in the rifabutin AUC and a mean increase of 375% (P < 0.001) in the AUC of the rifabutin metabolite 25-O-desacetyl-rifabutin. The usefulness of this combination for prophylaxis of Mycobacterium avium infections is limited by frequent gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin results in significant bidirectional pharmacokinetic interactions. The resulting increase in rifabutin levels may explain the increased frequency of uveitis observed with concomitant use of these drugs. C1 NIAID, Div Aids, NIH, Rockville, MD 20852 USA. Westat, Rockville, MD USA. Social & Sci Syst Inc, Rockville, MD USA. Vet Adm Med Ctr, Palo Alto, CA 94304 USA. Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. Vet Adm Med Ctr, Baltimore, MD 21218 USA. Davies Med Ctr, San Francisco, CA USA. Georgetown Univ, Washington, DC USA. Univ N Carolina, Chapel Hill, NC USA. Denver Dis Control Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Albany Med Coll, Albany, NY 12208 USA. RP Hafner, R (reprint author), NIAID, Div Aids, NIH, 6003 Execut Blvd,Room 2B35, Rockville, MD 20852 USA. FU NIAID NIH HHS [N01-AI-15123] NR 43 TC 50 Z9 54 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 MAR PY 1998 VL 42 IS 3 BP 631 EP 639 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YZ945 UT WOS:000072311000024 PM 9517944 ER PT J AU Rogers, MJ Cundliffe, E McCutchan, TF AF Rogers, MJ Cundliffe, E McCutchan, TF TI The antibiotic micrococcin is a potent inhibitor of growth and protein synthesis in the malaria parasite SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID 23S RIBOSOMAL-RNA; PLASMODIUM-FALCIPARUM; THIOSTREPTON; INVITRO; DRUGS AB The antibiotic microfoccin is a potent growth inhibitor of the human malaria parasite Plasmodium falciparum, with a 50% inhibitory concentration of 35 nM. This is comparable to or less than the corresponding levels of commonly used antimalarial drugs. Micrococcin, like thiostrepton, putatively targets protein synthesis in the plastid-like organelle of the parasite. C1 NIAID, Growth & Dev Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP McCutchan, TF (reprint author), NIAID, Growth & Dev Sect, Parasit Dis Lab, NIH, Bldg 4,Room B1-28, Bethesda, MD 20892 USA. EM mcutchan@helix.nih.gov NR 20 TC 65 Z9 67 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 MAR PY 1998 VL 42 IS 3 BP 715 EP 716 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YZ945 UT WOS:000072311000041 PM 9517961 ER PT J AU Colarusso, P Kidder, LH Levin, IW Fraser, JC Arens, JF Lewis, EN AF Colarusso, P Kidder, LH Levin, IW Fraser, JC Arens, JF Lewis, EN TI Infrared spectroscopic imaging: From planetary to cellular systems SO APPLIED SPECTROSCOPY LA English DT Review ID SPECTROMETRY; MICROSCOPY C1 NIDDKD, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. Vanguard Res Inc, Fairfax, VA 22030 USA. Univ Calif Berkeley, Space Sci Lab, Berkeley, CA 94720 USA. RP Lewis, EN (reprint author), NIDDKD, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. NR 31 TC 111 Z9 111 U1 3 U2 11 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD MAR PY 1998 VL 52 IS 3 BP 106A EP 120A PG 15 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA ZH219 UT WOS:000073084900002 ER PT J AU Wink, DA Feelisch, M Fukuto, J Chistodoulou, D Jourd'heuil, D Grisham, MB Vodovotz, Y Cook, JA Krishna, M DeGraff, WG Kim, S Gamson, J Mitchell, JB AF Wink, DA Feelisch, M Fukuto, J Chistodoulou, D Jourd'heuil, D Grisham, MB Vodovotz, Y Cook, JA Krishna, M DeGraff, WG Kim, S Gamson, J Mitchell, JB TI The cytotoxicity of nitroxyl: Possible implications for the pathophysiological role of NO SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID NITRIC-OXIDE PROTECTS; DOUBLE-STRAND BREAKS; SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; GEL-ELECTROPHORESIS; L-ARGININE; OXIDATION; RELEASE; PEROXYNITRITE; ENHANCEMENT AB In addition to the broad repertoire of regulatory functions nitric oxide (NO) serves in mammalian physiology, the L-arginine:NO pathway is also involved in numerous pathophysiological mechanisms. While NO itself may actually protect cells from the toxicity of reactive oxygen radicals in some cases, it has been suggested that reactive nitrogen oxide species formed from nitric oxide synthase (NOS) can be cytotoxic. In addition to NO, the one electron reduction product NO(-) has been proposed to be formed from NOS. We investigated the potential cytotoxic role of nitroxyl (NO(-)), using the nitroxyl donor Angelis's salt, (AS; sodium trioxodinitrate, Na(2)N(2)O(3)) as the source of NO(-). AS was found to be cytotoxic to Chinese hamster V79 lung fibroblast cells over a concentration range of 2-4 mM. The presence of equimolar ferricyanide (Fe(III)-(CN(6))(3-)), which converts NO(-) to NO, afforded dramatic protection against AS-mediated cytotoxicity. Treatment of V79 cells with L-buthionine sulfoximine to reduce intracellular glutathione markedly enhanced AS cytotoxicity, which suggests that GSH is critical for cellular protection against the toxicity of NO(-). Further experiments showed that low molecular weight transition metal complexes associated with the formation of reactive oxygen species are not involved in AS-mediated cytotoxicity since metal chelators had no effect. However, under aerobic conditions, AS was more toxic than under hypoxic conditions, suggesting that oxygen dramatically enhanced AS-mediated cytotoxicity. At a molecular level, AS exposure resulted in DNA double strand breaks in whole cells, and this effect was completely prevented by coincubation of cells with ferricyanide or Tempol. The data in this study suggest that nitroxyl may contribute to the cytotoxicity associated with an enhanced expression of the L-arginine:NO pathway under different biological conditions. (C) 1998 Academic Press. C1 NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Med, Div Cardiol, D-40225 Dusseldorf, Germany. Univ Calif Los Angeles, Dept Mol Pharmacol, Los Angeles, CA 90095 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. RI Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 NR 50 TC 167 Z9 168 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 1 PY 1998 VL 351 IS 1 BP 66 EP 74 DI 10.1006/abbi.1997.0565 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YZ944 UT WOS:000072310900010 PM 9501920 ER PT J AU McCann, UD Kimbrell, TA Morgan, CM Anderson, T Geraci, M Benson, BE Wassermann, EM Willis, MW Post, RM AF McCann, UD Kimbrell, TA Morgan, CM Anderson, T Geraci, M Benson, BE Wassermann, EM Willis, MW Post, RM TI Repetitive transcranial magnetic stimulation for posttraumatic stress disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID HUMAN-BRAIN; LATERALIZATION; EMOTION C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP McCann, UD (reprint author), NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 19 TC 88 Z9 92 U1 1 U2 3 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 MAR PY 1998 VL 55 IS 3 BP 276 EP 279 DI 10.1001/archpsyc.55.3.276 PG 4 WC Psychiatry SC Psychiatry GA ZA892 UT WOS:000072412500012 PM 9510224 ER PT J AU Ginsberg, HN Kris-Etherton, P Dennis, B Elmer, PJ Ershow, A Lefevre, M Pearson, T Roheim, P Ramakrishnan, R Reed, R Stewart, K Stewart, P Phillips, K Anderson, N AF Ginsberg, HN Kris-Etherton, P Dennis, B Elmer, PJ Ershow, A Lefevre, M Pearson, T Roheim, P Ramakrishnan, R Reed, R Stewart, K Stewart, P Phillips, K Anderson, N CA DELTA Res Grp TI Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects - The Delta Study, protocol 1 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE lipids; lipoproteins; cholesterol; diet; saturated fat ID CORONARY HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; CHOLESTEROL-LOWERING DIET; SERUM-LIPIDS; MODERATE HYPERCHOLESTEROLEMIA; CARBOHYDRATE INTAKE; NUTRIENT INTAKE; ARTERY DISEASE; NORMAL MALES; STEP-1 DIET AB Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men greater than or equal to 40 years old. All meals and snacks, except Saturday dinner, were prepared and sewed by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet, Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA, Each diet provided approximate to 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat(both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximate to 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant ill most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced, In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular-disease in the total population. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Chapel Hill, NC USA. Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Mary Imogene Bassett Hosp, Res Inst, Cooperstown, NY 13326 USA. Louisiana State Univ, Sch Med, Dept Physiol, New Orleans, LA USA. Virginia Polytech Inst & State Univ, Dept Biochem & Anaerob Microbiol, Blacksburg, VA 24061 USA. RP Ginsberg, HN (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA. RI Lefevre, Michael/B-5030-2014; OI Lefevre, Michael/0000-0002-2046-3593; Phillips, Katherine/0000-0002-4586-8538 FU NHLBI NIH HHS [5-U01-HL-49644, 5-U01-HL-49648, 5-U01-HL-49649] NR 71 TC 169 Z9 173 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 1998 VL 18 IS 3 BP 441 EP 449 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA ZC969 UT WOS:000072637400015 PM 9514413 ER PT J AU Burchfiel, CM Sharp, DS Curb, JD Rodriguez, BL Abbott, RD Arakaki, R Yano, K AF Burchfiel, CM Sharp, DS Curb, JD Rodriguez, BL Abbott, RD Arakaki, R Yano, K TI Hyperinsulinemia and cardiovascular disease in elderly men - The Honolulu Heart Program SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Asian Americans; cardiovascular diseases; insulin ID DEPENDENT DIABETES-MELLITUS; INSULIN-RESISTANCE SYNDROME; INDEPENDENT RISK FACTOR; SMOOTH-MUSCLE CELLS; PLASMA-INSULIN; GLUCOSE-TOLERANCE; FOLLOW-UP; COMPENSATORY HYPERINSULINEMIA; MYOCARDIAL-INFARCTION; FIBRINOLYTIC-ACTIVITY AB Hyperinsulinemia has been associated with cardiovascular disease (CVD), but whether this relation is independent of other CVD risk factors is uncertain. Most studies have focused on coronary heart disease (CHD), but few have included peripheral vascular disease (PVD) and stroke. Moreover, evidence in elderly and minority populations is limited. Between 1991 and 1993, 3562 elderly (71 to 93 years) Japanese-American men form the Honolulu Heart Program were examined and had fasting insulin levels measured. Hyperinsulinemia, defined as a fasting insulin greater than or equal to 95th percentile among nonobese men with normal glucose tolerance and no diabetic history or medication use, was observed in 22% of the population. Subjects with hyperinsulinemia had a more adverse CVD risk factor profile and had higher age-adjusted prevalences of CHD, angina, PVD, thromboembolic stroke, and hemorrhagic stroke compared with those without hyperinsulinemia. Age-adjusted fasting insulin levels but not 2-hour levels were also significantly elevated (P<.01) in those with prevalent CVD compared with those without. In logistic regression analyses, adjustment for multiple CVD risk factors attenuated the relations of hyperinsulinemia with CHD, angina, and PVD to nonsignificant levels, whereas those involving thromboembolic and hemorrhagic stroke were strengthened and remained significant (odds ratios=2.27 and 7.53, 95% confidence intervals=1.25 to 4.13 and 1.65 to 34.25, respectively). When multivariate analyses were restricted to nondiabetic subjects, associations were slightly weaker and in general nonsignificant. Nondiabetic men with thromboembolic stroke were twice as likely to have hyperinsulinemia as those who were stroke-free, although this association was of borderline significance (odds ratio=1.99, 95% confidence interval=0.95 to 4.17, P=.069). In subjects with elevated total cholesterol levels, somewhat stronger associations were observed for PVD and stroke, these cross-sectional results are consistent with an indirect role for insulin in CVD, wherein hyperinsulinemia or an underlying insulin-resistant state may adversely affect other CVD risk factors or serve as a marker for an atherogenic or thrombogenic state. C1 Honolulu Heart Program, Kuakini Med Ctr, Honolulu, HI USA. NHLBI, Honolulu Epidemiol Res Unit, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Honolulu, HI USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Virginia, Sch Med, Div Biostat, Charlottesville, VA 22908 USA. RP Burchfiel, CM (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Rockledge Ctr 2, 6701 Rockledge Dr MSC 7934, Bethesda, MD 20892 USA. EM BurchfiC@gwgate.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-05102] NR 73 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 1998 VL 18 IS 3 BP 450 EP 457 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA ZC969 UT WOS:000072637400016 PM 9514414 ER PT J AU Villalba, L Hicks, JE Adams, EM Sherman, JB Gourley, MF Leff, RL Thornton, BC Burgess, SH Plotz, PH Miller, FW AF Villalba, L Hicks, JE Adams, EM Sherman, JB Gourley, MF Leff, RL Thornton, BC Burgess, SH Plotz, PH Miller, FW TI Treatment of refractory myositis - A randomized crossover study of two new cytotoxic regimens SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; PLACEBO-CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; CLINICAL-TRIAL; AZATHIOPRINE; POLYMYOSITIS; METHOTREXATE; THERAPY; DERMATOMYOSITIS; PREDNISONE AB Objective. To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Methods. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy? were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (IV MTX) every 2 weeks for 6 months, Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Results. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with TV MTX during the crossover period, Of the 15 patients initially randomized to IV MTX therapy, 3 improved with the IV therapy and 4 with the oral combination during the crossover period, Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with IV therapy (P = 0.09). Conclusion. Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. IV MTX with leucovorin rescue may also benefit some patients with refractory myositis. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), US FDA, Ctr Biol Evaluat & Res, N29B,2G11,HFM-561, Bethesda, MD 20892 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 29 TC 94 Z9 97 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1998 VL 41 IS 3 BP 392 EP 399 DI 10.1002/1529-0131(199803)41:3<392::AID-ART3>3.0.CO;2-X PG 8 WC Rheumatology SC Rheumatology GA ZA910 UT WOS:000072414300002 PM 9506565 ER PT J AU Ginn, LR Lin, JP Plotz, PH Bale, SJ Wilder, RL Mbauya, A Miller, FW AF Ginn, LR Lin, JP Plotz, PH Bale, SJ Wilder, RL Mbauya, A Miller, FW TI Familial autoimmunity in pedigrees of idiopathic inflammatory myopathy patients suggests common genetic risk factors for many autoimmune diseases SO ARTHRITIS AND RHEUMATISM LA English DT Article ID POLYMYOSITIS; MYOSITIS; DERMATOMYOSITIS; AUTOANTIBODIES; PREDISPOSITION; PATHOGENESIS; AGGREGATION; MUSCLE; MODELS; MICE AB Objective, To test the hypothesis that many autoimmune diseases share common genetic risk factors and to define the frequency and distribution of autoimmune diseases in relatives of patients with very rare disorders, the idiopathic inflammatory myopathies (IIM). Methods. We evaluated, in a prospective case-control study, consecutive patients with IIM who were referred to our center and ascertained without regard to family history or known risk factors for autoimmunity, and all available family members, We used a standardized assessment to determine the presence and type of autoimmune disease in each subject, A matched comparison group of control subjects without autoimmune disease who were referred to our center and their families were similarly assessed, Results. Autoimmune diseases were significantly increased in prevalence (21.9%) in the 151 first-degree relatives of the 21 IIM probands compared with the prevalence (4.9%) in the 143 relatives of the 21 control probands (odds ratio [OR] by regression analysis 7.9, 95% confidence interval [95% CI] 2.9-21.9, P < 0.001), Women had more autoimmune disease than men (OR by regression analysis 4.6, 95% CI 2.3-9.0) and the odds ratio for autoimmune disease increased 0.02 per year of age, These disorders tended to follow the frequency distribution of autoimmune diseases in the general population, Genetic modeling studies showed that a non-Mendelian polygenic inheritance pattern for autoimmune disease was most consistent with these data, Conclusion. Autoimmune diseases are significantly increased in frequency in first-degree relatives of IIM patients, affect more women than men, increase with age, and are distributed in a pattern similar to that in the general population, Many autoimmune disorders share genes that together act as polygenic risk factors for autoimmunity. C1 US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 33 TC 58 Z9 60 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1998 VL 41 IS 3 BP 400 EP 405 DI 10.1002/1529-0131(199803)41:3<400::AID-ART4>3.0.CO;2-5 PG 6 WC Rheumatology SC Rheumatology GA ZA910 UT WOS:000072414300003 PM 9506566 ER PT J AU Rodgers, GP AF Rodgers, GP TI Pharmacological therapy SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article DE sickle cell disease; thalassaemia; haemoglobinopathies; gene therapy; fetal haemoglobin ID SICKLE-CELL DISEASE; FETAL HEMOGLOBIN PRODUCTION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; HOMOZYGOUS BETA-THALASSEMIA; BONE-MARROW TRANSPLANTATION; ORAL SODIUM PHENYLBUTYRATE; GAMMA-GLOBIN SYNTHESIS; HYDROXYUREA THERAPY; CLINICAL-TRIAL; HBF PRODUCTION AB Collectively sickle cell disease and beta-thalassaemia are the most commonly inherited single-gene defects world-wide and were the first group of diseases for which DNA-based detection strategies were utilized. Although genotypically distinct, these two groups of diseases exhibit several common clinical features: moderate-to-severe haemolytic anaemia, acute and progressive tissue damage, disease- or treatment-related organ failure and premature death. Within the last two decades, a striking improvement in life expectancy in the two patient populations has been observed, by dint of primary and secondary prevention strategies. However, apart from bone marrow transplantation, a generally applicable, specific and non-toxic form of treatment remains unavailable for these disorders. Nonetheless, a greater appreciation of the developmental control of human globin gene expression coupled with observations of the effects of certain classes of agents to 'reverse' erythroid cellular phenotype in in vitro and animal models have led to pharmacological trials to obtain meaningful increases in haemoglobin F production in patients affected by these two severe beta-globin disorders. Contemporary understanding of the quantitative relationship between the abnormal molecules in the red cells (aggregates of sickle haemoglobin) in the sickle cell syndromes and aggregated alpha-globin polypeptides in the beta-thalassemia syndromes, and the extent of the red cell and/or organ involvement, has now enabled investigators to predict how much inhibition of these intracellular pathogenic processes might be necessary to achieve partial or total abrogation of disease manifestations. The results of the Multicenter Study of Hydroxyurea and other controlled trials now bear out these predictions. C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119, Bethesda, MD 20892 USA. NR 83 TC 4 Z9 5 U1 0 U2 2 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD MAR PY 1998 VL 11 IS 1 BP 239 EP 255 DI 10.1016/S0950-3536(98)80077-2 PG 17 WC Hematology SC Hematology GA 157AR UT WOS:000078037100010 PM 10872480 ER PT J AU Honkakoski, P Negishi, M AF Honkakoski, P Negishi, M TI Protein serine/threonine phosphatase inhibitors suppress phenobarbital-induced Cyp2b10 gene transcription in mouse primary hepatocytes SO BIOCHEMICAL JOURNAL LA English DT Article ID ADULT-RAT HEPATOCYTES; OKADAIC ACID; GROWTH-HORMONE; EXPRESSION; INDUCTION; CYTOCHROME-P-450; PHOSPHORYLATION; LIVER; KINASE; CAMP AB Using a primary hepatocyte culture in which the mouse Cyp2b10 gene transcription is activated by phenobarbital (PB)-type inducers, we examined the cellular signalling mechanisms associated with PB induction. Low nanomolar concentrations of protein serine/threonine phosphatase inhibitors okadaic acid (OA) and calyculin A blocked the induction of CYP2B10 mRNA. Nuclear run-on assays indicated that OA suppressed Cyp2b10 gene transcription. Pretreatment of the cells with an inhibitor of Ca2+/calmodulin-dependent protein kinases {1-[N,O-bis-(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62)} or with a flavonoid, naringin, were completely or partly protective respectively against the OA-mediated suppression of CYP2B10 mRNA. Several other established modulators of protein kinase activities did not greatly affect the induction of CYP2B10 mRNA, nor could they prevent the suppressive effect of OA. Our results indicate that specific protein phosphorylation-dephosphorylation is required for the induction of Cyp2b10 gene expression, which is modulated through multiple endogenous and exogenous signals. C1 Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland. NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Honkakoski, P (reprint author), Univ Kuopio, Dept Pharmaceut, POB 1627, FIN-70211 Kuopio, Finland. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 42 TC 80 Z9 82 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 1998 VL 330 BP 889 EP 895 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD128 UT WOS:000072654200045 PM 9480906 ER PT J AU Koval, AP Blakesley, VA Roberts, CT Zick, Y LeRoith, D AF Koval, AP Blakesley, VA Roberts, CT Zick, Y LeRoith, D TI Interaction in vitro of the product of the c-Crk-II proto-oncogene with the insulin-like growth factor I receptor SO BIOCHEMICAL JOURNAL LA English DT Article ID PHOSPHORYLATION-DEPENDENT MANNER; TYROSINE KINASE DOMAIN; V-CRK; SIGNAL TRANSDUCTION; PC12 CELLS; PROTEINS; IGF; AUTOPHOSPHORYLATION; SUBSTRATE-1; SHC AB The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein. We have previously demonstrated that Crk-II becomes rapidly tyrosine-phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) and might be involved in the IGF-I receptor signalling pathway. To determine whether this involvement includes the direct interaction of Crk-II with the cytoplasmic region of the receptor, studies were performed in vitro with glutathione S-transferase (GST) fusion proteins containing various domains of Crk-II. The kinase assay in vitro showed that activated IGF-I receptors efficiently phosphorylated the GST-Crk-II fusion protein, This phosphorylation was dependent on the presence of the SH2 domain and Tyr-221 located in the spacer region between the two SH3 domains, Mutation of Tyr-221 not only prevented phosphorylation of GST-Crk in vitro, but also significantly increased the ability of GST-Crk proteins to co-precipitate activated IGF-I receptors from total cell lysates. Additional binding experiments in vitro showed that Crk-II might interact with the phosphorylated IGF-I receptor through its SH2 domain. To elucidate which region of the IGF-I receptor interacts with Crk-II, a peptide association assay was used in vitro. Different domains of the IGF-I receptor were expressed as (His)(6)-tagged fusion peptides, phosphorylated with activated wheat germ agglutinin-purified IGF-I receptors and tested for association with GST-Crk-II fusion proteins. Using wild-type as well as mutated peptides, we showed that the SH2 domain of Crk-II preferentially binds the peptide encoding the juxtamembrane region of the IGF-I receptor. Phosphorylation of Tyr-950 and Tyr-943 of the receptor is important for this interaction. These findings allow us to propose a model of direct interaction of Crk-II and the IGF-I receptor in vivo. On activation of the IGF-I receptor, Crk-II binds to phosphorylated tyrosine residues, especially in the juxtamembrane region, As a result of this binding, the IGF-I receptor kinase phosphorylates Tyr-221 of Crk-II, resulting in a change in intramolecular folding and binding of the SH2 domain to the phosphorylated Tyr-221,which causes rapid disassociation of the Crk-II-IGF-I receptor complex. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Clin Immunol, IL-76100 Rehovot, Israel. RP LeRoith, D (reprint author), NIDDKD, Diabet Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 55 TC 31 Z9 31 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 1998 VL 330 BP 923 EP 932 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD128 UT WOS:000072654200050 PM 9480911 ER PT J AU Pommier, Y AF Pommier, Y TI Diversity of DNA topoisomerases I and inhibitors SO BIOCHIMIE LA English DT Review DE DNA topoisomerase I; topoisomerase inhibitors; cancer cells ID SIMIAN VIRUS-40 DNA; COMPOUND 6-N-FORMYLAMINO-12,13-DIHYDRO-1,11-DIHYDROXY-13-(BETA-D-GLUCOPYRANOSYL); LEUKEMIA-CELL LINE; VACCINIA VIRUS; CAMPTOTHECIN ANALOGS; CLEAVAGE ACTIVITY; MAMMALIAN-CELLS; CALF THYMUS; EUKARYOTIC TOPOISOMERASE; DROSOPHILA-MELANOGASTER AB The present review first describes the different type I topoisomerases found in eukaryotic cells: nuclear topoisomerase I (top1), topoisomerase 3 (top3), mitochondrial topoisomerase I and viral topoisomerases I. The second part of the review provides extensive information on the topoisomerase I inhibitors identified to date. These drugs can be grouped in two categories: top 1 poisons and top 1 suppressors. Both inhibit enzyme catalytic activity but top1 poisons trap the top1 catalytic intermediates ('cleavage complexes') while top1 suppressors prevent or reverse top1 cleavage complexes. The molecular interactions of camptothecin with the top1 cleavage complexes are discussed as well as the mechanisms of selective killing of cancer cells. ((C) Society francaise-de biochimie et biologie moleculaire / Elsevier, Paris). C1 NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, Bldg 37,Rm 5D02, Bethesda, MD 20892 USA. NR 197 TC 99 Z9 102 U1 2 U2 8 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD MAR PY 1998 VL 80 IS 3 BP 255 EP 270 DI 10.1016/S0300-9084(98)80008-4 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK038 UT WOS:000073278700007 PM 9615865 ER PT J AU Parekh, PI Ketter, TA Altshuler, L Frye, MA Callahan, A Marangell, L Post, RM AF Parekh, PI Ketter, TA Altshuler, L Frye, MA Callahan, A Marangell, L Post, RM TI Relationships between thyroid hormone and antidepressant responses to total sleep deprivation in mood disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE sleep deprivation; thyroid hormones; thyroid-stimulating hormone; depression; affective disorders ID NEUROENDOCRINOLOGICAL INVESTIGATIONS; THYROTROPIN; DEPRESSION; TSH; PROLACTIN; SECRETION; CORTISOL; TH; LH AB Background: Acute transient antidepressant effects of sleep deprivation are consistently observed in 50% of depressed patients, but the mechanisms of these, at times, dramatic improvements in mood have not been adequately elucidated. Some, but not all, studies suggest a relationship to increased thyroid-stimulating hormone (TSH) secretion. Methods: TSH and other thyroid indices were measured at 8:00 AM after a baseline night's sleep and at 8:00 AM following a night of total sleep deprivation (S.D.) in 34 medication-free, affective disorder patients assessed with Hamilton, Beck, and Bunney-Hamburg depression ratings as well as two hourly self-ratings on a visual analog scale. Results: Compared with baseline, S.D. induced highly significant increases in TSH, levothyroxine, free levothyroxine, and triiodothyronine. The 12 S.D. responders tended to have greater TSH increases than the 15 nonresponders (p < .10). The change in Beck depression ratings significantly correlated with the change in TSH (r = -.40, p = .0496, n = 24). Conclusions: These data are consistent with several other reports of a significant relationship between degree of antidepressant response to S.D. and increases in TSH measured at 8:00 AM near their usual nadir. Acute removal of the sleep-related break on the hypothalamic-pituitary-thyroid axis remains a promising candidate for the mechanism of sleep deprivation-induced improvement in mood in depressed patients. (C) 1998 Society of Biological Psychiatry. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 15 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1998 VL 43 IS 5 BP 392 EP 394 DI 10.1016/S0006-3223(97)00513-1 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YZ497 UT WOS:000072260000013 PM 9513756 ER PT J AU Bunch, DO Welch, JE Magyar, PL Eddy, EM O'Brien, DA AF Bunch, DO Welch, JE Magyar, PL Eddy, EM O'Brien, DA TI Glyceraldehyde 3-phosphate dehydrogenase-S protein distribution during mouse spermatogenesis SO BIOLOGY OF REPRODUCTION LA English DT Article ID RNA-BINDING PROTEIN; INDUCED ACROSOME REACTION; GUINEA-PIG SPERM; ROUND SPERMATIDS; ALPHA-CHLOROHYDRIN; GLYCOLYTIC-ENZYMES; ZONA-PELLUCIDA; FIBROUS SHEATH; MESSENGER-RNAS; RAT TESTES AB The spermatogenic cell-specific isoform of glyceraldehyde 3-phosphate dehydrogenase (GAPD-S) may regulate glycolysis and energy production required for sperm motility. Although the steady-state level of Gapd-s mRNA is maximal at step 9 of mouse spermatogenesis, GAPD-S protein was not detected by immunohistochemistry until steps 12-13. This results suggests that Gapd-s is translationally regulated. Western blot analysis of isolated germ cells confirmed that GAPD-S is not detected in pachytene spermatocytes or round spermatids. A major immunoreactive protein migrating with a molecular weight (M-r) of 69 200 was observed in condensing spermatids and cauda sperm. Additional minor proteins that migrated at M-r 55 200, 32 500, and 27 500 were detected in sperm. The molecular weight of GAPD-S is higher than the predicted molecular weight of 47 445, apparently due to a proline-rich 105-amino acid domain at that N-terminus. Recombinant GAPD-S protein Backing the proline-rich region migrated at M-r 38 250, comparably to somatic GAPD, which also lacks the proline-rich domain. Indirect immunofluorescence demonstrated that GAPD-S is restricted to the principal piece in the sperm flagellum. Western blot analysis indicated that GAPD-S is rightly associated with the fibrous sheath of the flagellum, consistent with a potential role in regulating sperm motility. C1 Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Gamete Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. US EPA, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Dept Pediat, Reprod Biol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell Biol & Anat, Reprod Biol Lab, Chapel Hill, NC 27599 USA. RP Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Gamete Biol Sect, NIH, POB 12233 MD C4-04, Res Triangle Pk, NC 27709 USA. EM bunch@niehs.nih.gov FU NCI NIH HHS [CA16086]; NICHD NIH HHS [U54 HD035041, U54HD35041] NR 71 TC 110 Z9 112 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1998 VL 58 IS 3 BP 834 EP 841 DI 10.1095/biolreprod58.3.834 PG 8 WC Reproductive Biology SC Reproductive Biology GA YY851 UT WOS:000072193100029 PM 9510974 ER PT J AU Fay, MP Graubard, BI Freedman, LS Midthune, DN AF Fay, MP Graubard, BI Freedman, LS Midthune, DN TI Conditional logistic regression with sandwich estimators: Application to a meta-analysis SO BIOMETRICS LA English DT Article DE generalized estimating equations; random effects; robust variance; Satterthwaite's formula; standardized residuals ID RANDOM-EFFECTS MODELS; LONGITUDINAL DATA-ANALYSIS; DIETARY-FAT; CLINICAL-TRIALS; MAMMARY-TUMORS; RATS AB Motivated by a meta-analysis of animal experiments on the effect of dietary fat and total caloric intake on mammary tumorigenesis, we explore the use of sandwich estimators of variance with conditional logistic regression. Classical conditional logistic regression assumes that the parameters are fixed effects across all clusters, while the sandwich estimator gives appropriate inferences for either fixed effects or random effects. However, inference using the standard Wald test with the sandwich estimator requires that each parameter is estimated using information from a large number of clusters. Since our example violates this condition, we introduce two modifications to the standard Wald test. First, we reduce the bias of the empirical variance estimator (the middle of the sandwich) by using standardized residuals. Second, we approximately account for the variance of these estimators by using the t-distribution instead of the normal distribution, where the degrees of freedom are estimated using Satterthwaite's approximation. Through simulations, we show that these sandwich estimators perform almost as well as classical estimators when the true effects are fixed and much better than the classical estimators when the true effects are random. We achieve simulated nominal coverage for these sandwich estimators even when some parameters are estimated from a small number of clusters. C1 NCI, Div Canc Prevent & Control, Biometry Branch, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD 20902 USA. RP Fay, MP (reprint author), NCI, Div Canc Prevent & Control, Biometry Branch, Execut Plaza N,Suite 344,6130 Execut Blvd,MSC 735, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 30 TC 17 Z9 17 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1998 VL 54 IS 1 BP 195 EP 208 DI 10.2307/2534007 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA ZF255 UT WOS:000072879200017 PM 9544516 ER PT J AU Nam, JM AF Nam, JM TI Power and sample size for stratified prospective studies using the score method for testing relative risk SO BIOMETRICS LA English DT Article DE asymptotic power; relative efficiency; relative risk; sample size; score test; stratified prospective studies ID 2 BINOMIAL PROPORTIONS; CONFIDENCE-INTERVALS; 2X2 TABLES; RATIO; ESTIMATORS; COHORT AB We derive the asymptotic power function of the score test for detecting a common relative risk greater than unity from multiple 2 x 2 tables and formulate methods of sample size determination for use when designing stratified prospective studies. The stratified score test is more efficient than the unstratified test when the latter is unbiased. C1 NCI, Biostat Branch, Rockville, MD 20892 USA. RP Nam, JM (reprint author), NCI, Biostat Branch, Execut Plaza N,Room 403,6130 Execut Blvd,MSC 7368, Rockville, MD 20892 USA. NR 22 TC 8 Z9 8 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1998 VL 54 IS 1 BP 331 EP 336 DI 10.2307/2534020 PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA ZF255 UT WOS:000072879200030 PM 9544526 ER PT J AU Shih, JH AF Shih, JH TI A goodness-of-fit test for association in a bivariate survival model SO BIOMETRIKA LA English DT Article DE Clayton model; concordance; conditional hazard ratio; frailty ID FAILURE TIME DATA; SEMIPARAMETRIC ESTIMATION; DISTRIBUTIONS; INFERENCE; FAMILIES AB We propose a-simple test of constant conditional hazard ratio in the Clayton model (1978) by comparing the unweighted and weighted concordance estimators of the association parameter. If the Clayton model holds, the difference of these two estimates converges to zero. The proposed test is consistent against alternatives under which the two concordance estimators converge to different values. We derive an explicit-formula for the asymptotic variance and derive the asymptotic distribution of the test statistic under the Clayton model. Then we extend the test;statistic to incorporate censoring; The proposed test is expected to perform well for a general class of alternatives with monotone conditional hazard ratio. We examine the finite sample properties-of the test ;statistic through simulations. C1 Natl Heart Lung & Blood Inst, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Shih, JH (reprint author), Natl Heart Lung & Blood Inst, Off Biostat Res, Rockledge Ctr 2, Room 8217,6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 22 TC 37 Z9 38 U1 0 U2 2 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 MAR PY 1998 VL 85 IS 1 BP 189 EP 200 DI 10.1093/biomet/85.1.189 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA ZG384 UT WOS:000072996300015 ER PT J AU Lee, YB Folk, JE AF Lee, YB Folk, JE TI Branched-chain and unsaturated 1,7-diaminoheptane derivatives as deoxyhypusine synthase inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE deoxyhypusine synthase inhibitors; branched chain 1,7-diaminoheptanes; unsaturated derivatives of 1,7-diaminoheptane; diamines; diguanidines ID EUKARYOTIC INITIATION FACTOR-5A; SACCHAROMYCES-CEREVISIAE; HYPUSINE DEPLETION; FACTOR EIF-5A; PROLIFERATION; CELLS AB Deoxyhypusine synthase catalyzes the first step in the posttranslational biosynthesis of the unusual amino acid hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine] in eukaryotic translation initiation factor 5A (eIF-SA). eIF-SA and its single hypusine residue are essential for cell proliferation. Two series of 1,7-diaminoheptane derivatives were prepared and tested as inhibitors of human deoxyhypusine synthase. These include branched-chain saturated derivatives and both branched- and straight-chain unsaturated derivatives providing size and positional variation in branching and different torsional constraints. Of the branched-chain compounds, 7-amino-1-guanidinooctane (39) proved to be the most potent inhibitor in vitro (IC50, 34 nM), while 1,7-diamino-trans-hept-3-ene (20a) displayed the greatest inhibition (IC50, 0.7 mu M) among the unsaturated compounds. Compound 39 also provided effective inhibition of hypusine production in Chinese hamster ovary cells in culture. Considerations of the in vitro inhibition data reported here, along with earlier findings, allowed some speculation concerning the conformation of the substrate spermidine during its productive interaction at the active site of deoxyhypusine synthase. Published by Elsevier Science Ltd. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Folk, JE (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM jfolk@yoda.nidr.nih.gov NR 30 TC 21 Z9 21 U1 0 U2 1 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 MAR PY 1998 VL 6 IS 3 BP 253 EP 270 DI 10.1016/S0968-0896(97)10030-X PG 18 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA ZG263 UT WOS:000072983500001 PM 9568280 ER PT J AU Xu, SG Yu, LPC Schoenberg, M AF Xu, SG Yu, LPC Schoenberg, M TI Behavior of N-phenylmaleimide-reacted muscle fibers in magnesium-free rigor solution SO BIOPHYSICAL JOURNAL LA English DT Article ID WEAKLY-BINDING CROSSBRIDGES; RABBIT PSOAS FIBERS; SKELETAL-MUSCLE; ADENOSINE-TRIPHOSPHATASE; MYOSIN HEADS; CONTRACTION; ACTIN; STOICHIOMETRY; NUCLEOTIDE; CHAIN AB Using x-ray diffraction and mechanical stiffness, the response of N-phenylmaleimide (NPM)-reacted crossbridges to solutions containing different amounts of ATP and Mg2+ has been studied, In relaxing solution containing greater than millimolar amounts of ATP and Mg2+, NPM-treated muscle fibers give x-ray diffraction patterns and stiffness records, which are nearly indistinguishable from those of untreated relaxed fibers. In a solution devoid of added ATP, but with Mg2+ (rigor(+ Mg) solution), the muscle fibers still give x-ray diffraction patterns and mechanical responses characteristic of relaxed muscle. The new finding reported here is that in a solution devoid of both ATP and Mg2+ (rigor(-Mg) solution containing EDTA with no added ATP), NPM-reacted cross-bridges do give rigor-like behavior. This is the first report that NPM-reacted cross-bridges, at least in the presence of EDTA, are capable of going into a strongly binding conformation. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schoenberg, M (reprint author), NIAMSD, Phys Biol Lab, NIH, Bldg 6,Room 408, Bethesda, MD 20892 USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1998 VL 74 IS 3 BP 1110 EP 1114 PG 5 WC Biophysics SC Biophysics GA ZL097 UT WOS:000073398500003 PM 9512013 ER PT J AU Paquette, T Clay, JR Ogbaghebriel, A Shrier, A AF Paquette, T Clay, JR Ogbaghebriel, A Shrier, A TI Effects of divalent cations on the E-4031-sensitive repolarization current, I-Kr, in rabbit ventricular myocytes SO BIOPHYSICAL JOURNAL LA English DT Article ID SQUID GIANT-AXONS; TRANSIENT OUTWARD CURRENT; RECTIFIER K+ CURRENT; DELAYED RECTIFIER; INWARD RECTIFICATION; POTASSIUM CHANNEL; ATRIAL MYOCYTES; SURFACE-CHARGE; CELLS; MODULATION AB The effects of divalent cations on the E-4031-sensitive repolarization current (I-Kr) were studied in single ventricular myocytes isolated from rabbit hearts. One group of divalent cations (Cd2+, Ni2+, Co2+, and Mn2+) produced a rightward shift of the I-Kr activation curve along the voltage axis, increased the maximum I-Kr amplitude (i.e., relieved the apparent inward rectification of the channel), and accelerated I-Kr tail current kinetics. Another group (Ca2+, Mg2+ and Sr2+) had relatively little effect on I-Kr. The only divalent cation that blocked I-Kr was Zn2+ (0.1-1 mM). Under steady-state conditions, Ba2+ caused a substantial block of I-K1, as previously reported. However, block by Ba2+ was time dependent, which precluded a study of Ba2+ effects on I-Kr. We conclude that the various effects of the divalent cations can be attributed to interactions with distinct sites associated with the rectification and/or inactivation mechanism of the channel. C1 McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Shrier, A (reprint author), McGill Univ, Dept Physiol, 3655 Drummond St, Montreal, PQ H3G 1Y6, Canada. NR 36 TC 22 Z9 22 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1998 VL 74 IS 3 BP 1278 EP 1285 PG 8 WC Biophysics SC Biophysics GA ZL097 UT WOS:000073398500015 PM 9512025 ER PT J AU Stauber, RH Horie, K Carney, P Hudson, EA Tarasova, NI Gaitanaris, GA Pavlakis, GN AF Stauber, RH Horie, K Carney, P Hudson, EA Tarasova, NI Gaitanaris, GA Pavlakis, GN TI Development and applications of enhanced green fluorescent protein mutants SO BIOTECHNIQUES LA English DT Article ID GENE-EXPRESSION; MAMMALIAN-CELLS; RETROVIRAL VECTORS; LIVING CELLS; HIGH-TITER; MARKER; REV; DROSOPHILA; MUTATIONS; GFP AB The introduction of several mutations resulted in the generation of improved mutants of the green fluorescent protein (GFP). A strong green (GFPsg25) and blue (BFPsg50) Florescent protein, gave 50-fold-100-fold brighter fluorescence compared to wild-type GFP and BFP (Tyr66His), respectively, upon expression in mammalian cells. GFPsg25 and BFPsg50 have different excitation and emission maxima. This allows their use as an efficient dual-color tagging system and their independent detection in living cells. C1 NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. RP Pavlakis, GN (reprint author), NCI, ABL Basic Res Program, FCRDC, Bldg 535,Rm 219,POB B, Frederick, MD 21702 USA. EM pavlakis@ncifcrf.gov OI Stauber, Roland/0000-0002-1341-4523 NR 33 TC 135 Z9 142 U1 1 U2 5 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 1998 VL 24 IS 3 BP 462 EP + PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZA572 UT WOS:000072378000027 PM 9526659 ER PT J AU Mickley, LA Lee, JS Weng, Z Zhan, ZR Alvarez, M Wilson, W Bates, SE Fojo, T AF Mickley, LA Lee, JS Weng, Z Zhan, ZR Alvarez, M Wilson, W Bates, SE Fojo, T TI Genetic polymorphism in MDR-1: A tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors SO BLOOD LA English DT Article ID MULTIDRUG-RESISTANCE GENE; POLYMERASE CHAIN-REACTION; COLON-CARCINOMA CELLS; P-GLYCOPROTEIN; AMPLIFICATION; ADRIAMYCIN; MDR-1/P-GLYCOPROTEIN; GLUTATHIONE; RECEPTOR; INVITRO AB By using RNase protection analysis, residues 2677 and 2995 of MDR-1 were identified as sites of genetic polymorphism. Through use of oligonucleotide hybridization, the genomic content and expression of individual MDR-1 alleles were examined in normal tissues, unselected and drug selected cell lines, and malignant lymphomas, In normal tissues, unselected cell lines, and untreated malignant lymphoma samples, expression of MDR-1 from both alleles was similar. In contrast, in drug selected cell lines, and in relapsed malignant lymphoma samples, expression of one allele was found in a large percentage of samples. To understand how expression of one allele occurs, two multidrug resistant sublines were isolated by exposing a Burkitt lymphoma cell line to increasing concentrations of vincristine. The resistant sublines expressed only one allele and had a hybrid MDR-1 gene composed of non-MDR-1 sequences proximal to MDR-1. Previous studies showing hybrid MDR-1 genes after rearrangements provided a potential explanation for activation and expression of one MDR-1 allele. We conclude that oligonucleotide hybridization can be used as a sensitive tool to examine relative allelic expression of MDR-1, and can identify abnormal expression from a single allele. Acquired drug resistance in vitro and in patients is often associated with expression of a single MDR-1 allele, and this can be a marker of a hybrid MDR-1 gene. (C) 1998 by The American Society of Hematology. C1 NCI, Med Branch, DCS, Bethesda, MD 20892 USA. Gyeongsang Natl Univ, Dept Internal Med, Chinju, Kyungnam, South Korea. RP Fojo, T (reprint author), NCI, Med Branch, DCS, Bldg 10 Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 122 Z9 130 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 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1998 VL 91 IS 5 BP 1749 EP 1756 PG 8 WC Hematology SC Hematology GA YY237 UT WOS:000072127000033 PM 9473242 ER PT J AU Mavroudis, DA Read, EJ Molldrem, J Raptis, A Plante, M Carter, CS Phang, S Dunbar, CE Barrett, AJ AF Mavroudis, DA Read, EJ Molldrem, J Raptis, A Plante, M Carter, CS Phang, S Dunbar, CE Barrett, AJ TI T cell-depleted granulocyte colony-stimulating factor (G-CSF) modified allogeneic bone marrow transplantation for hematological malignancy improves graft CD34(+) cell content but is associated with delayed pancytopenia SO BONE MARROW TRANSPLANTATION LA English DT Article DE G-CSF; allogeneic BMT; T cell depletion; pancytopenia; graft failure ID STEM-CELL; PERIPHERAL-BLOOD; IN-VIVO; CYTOMEGALOVIRUS; RECONSTITUTION; SURVIVAL; RECOVERY; MURINE AB To increase the stem cell content of T cell-depleted bone marrow transplants (BMT), we treated 12 patients with hematological malignancies with BMT from HLA-identical sibling donors given G-CSF 10 mu g/kg/day for 5 days before marrow harvest, After CD34(+) cell selection, patients received a median of 1.7 (range, 0.82-3.1) x 10(6) CD34(+) cells/kg and 2.3 (range, 0.25-4.0) x 10(5) CD3(+) cells/kg, All patients had initial engraftment but four developed pancytopenia between days 55-130 post-BMT, In two patients, this required a second infusion of G-CSF-mobilized donor peripheral blood progenitor cells, We observed no delayed pancytopenia in a matched historical group of 24 patients receiving T cell-depleted BMT without prior G-CSF stimulation, Compared to this control group, G-CSF-stimulated marrow recipients showed a significant decline in neutrophil and monocyte counts after 8 weeks, However, outcome after BMT was otherwise comparable, with a similar incidence of acute graft-versus-host disease and transplant-related mortality, Disease-free survival was 63 vs 67% for controls matched for CD34(+) cell dose (P = NS). These results indicate that G-CSF stimulation can increase the CD34(+) cell content of T cell-depleted marrow but carries a risk of late graft failure. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bone Marrow Transplant Unit, Bethesda, MD 20892 USA. RP Carter, CS (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NR 27 TC 25 Z9 25 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 1998 VL 21 IS 5 BP 431 EP 440 DI 10.1038/sj.bmt.1701120 PG 10 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA ZB356 UT WOS:000072463500001 PM 9535034 ER PT J AU Barrett, AJ Mavroudis, D Tisdale, J Molldrem, J Clave, E Dunbar, C Cottler-Fox, M Phang, S Carter, C Okunnieff, P Young, NS Read, EJ AF Barrett, AJ Mavroudis, D Tisdale, J Molldrem, J Clave, E Dunbar, C Cottler-Fox, M Phang, S Carter, C Okunnieff, P Young, NS Read, EJ TI T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect SO BONE MARROW TRANSPLANTATION LA English DT Article DE chronic myeloid leukemia; hematological malignancies; graft-versus-host disease; graft-versus-leukemia; T cell-depleted BMT; immune recovery ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; HOST DISEASE; LONG-TERM; HEMATOLOGICAL MALIGNANCIES; CYTOMEGALOVIRUS-INFECTION; DONOR CELLS; RECOVERY; RELAPSE; TRANSFUSIONS AB Thirty-eight patients with hematological malignancies, received T cell-depleted marrow transplants (BMT) and cyclosporine to prevent acute graft-versus-host disease (aGVHD), followed by delayed add-back of donor lymphocytes to prevent leukemia relapse, In 26 patients scheduled for donor T cell add-back of 2 x 10(6) cells/kg on day 30 and 5 x 10(7) cells/kg on day 45 (schedule 1), the overall probability of grade greater than or equal to II aGVHD developing was 31.5%, with a 15.5% probability of aGVHD occurring after T cell add-back, In 12 patients receiving 10(7) donor T cells/kg on day 30 (schedule 2), the probability of grade greater than or equal to II aGVHD was 100 %. The incidence of grade III-IV aGVHD was higher in schedule 2 than in schedule 1 (P=0.02), Of 24 evaluable patients, 10 (46%) developed chronic GVHD which was limited in eight and extensive in two, Current disease-free survival for 18 patients at standard risk for relapse (chronic myeloid leukemia (CML) in chronic or accelerated phase, acute myeloid leukemia in remission) vs 20 patients with more advanced leukemia or multiple myeloma were respectively 72% vs 12% (P < 0.01) with a 29% vs 69% probability of relapse (P = 0.08), In 12 CML patients surviving more than 3 months, PCR analysis of the BCR/ABL transcript showed that minimal residual disease after T cell add-back was transient except in two patients who developed hematological relapse, Results indicate that the risk of acute GVHD is low following substantial T cell doses, transfused 45 days after transplant, using cyclosporine prophylaxis, Furthermore a graft-versus-leukemia effect was conserved. C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 105 Z9 105 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 1998 VL 21 IS 6 BP 543 EP 551 DI 10.1038/sj.bmt.1701131 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA ZD120 UT WOS:000072653400002 PM 9543057 ER PT J AU Simpson, PB Russell, JT AF Simpson, PB Russell, JT TI Role of mitochondrial Ca2+ regulation in neuronal and glial cell signalling SO BRAIN RESEARCH REVIEWS LA English DT Article DE intracellular calcium mobilization; inositol 1,4,5-trisphosphate receptor; transporter; Ca2+ wave; mitochondrion; mitochondrial impairment ID RAT HIPPOCAMPAL-NEURONS; PERMEABILITY TRANSITION; HEART-MITOCHONDRIA; CALCIUM-TRANSPORT; CORTICAL-NEURONS; SMOOTH-MUSCLE; FREE-RADICALS; DOMINANT ROLE; LIVING CELLS; BRAIN AB It is becoming increasingly clear that mitochondrial Ca2+ uptake from and release into the cytosol has important consequences for neuronal and glial activity. Ca2+ regulates mitochondrial metabolism, and mitochondrial Ca2+ uptake and release modulate physiological and pathophysiological cytosolic responses. In glial cells, inositol 1,4,5-trisphosphate-dependent Ca2+ responses are faithfully translated into elevations in mitochondrial Ca2+ levels, which modifies cytosolic Ca2+ wave propagation and may activate mitochondrial enzymes. The location of mitochondria within neurones may partially determine their role in Ca2+ signalling, Neuronal death due to NMDA-evoked Ca2+ entry can be delayed by an inhibitor of the mitochondrial permeability transition pore, and mitochondrial dysfunction is being increasingly implicated in a number of neurodegenerative conditions. These findings are illustrative of an emerging realization by neuroscientists of the importance of mitochondrial Ca2+ regulation as a modulator of cellular energetics, endoplasmic reticulum Ca2+ release and neurotoxicity. (C) 1998 Elsevier Science B.V. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. RP Russell, JT (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. EM james@helix.nih.gov NR 80 TC 96 Z9 100 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAR PY 1998 VL 26 IS 1 BP 72 EP 81 DI 10.1016/S0165-0173(97)00056-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZJ394 UT WOS:000073210600005 PM 9600625 ER PT J AU Sagawa, M Saito, Y Fujimura, S Linnoila, RI AF Sagawa, M Saito, Y Fujimura, S Linnoila, RI TI K-ras point mutation occurs in the early stage of carcinogenesis in lung cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE K-ras; lung cancer; preneoplastic lesion; genetic heterogeneity; selective ultraviolet radiation fractionation ID ONCOGENE ACTIVATION; P53 MUTATIONS; ADENOCARCINOMA; HETEROGENEITY; PATHOGENESIS; CARCINOMA; BRONCHUS; LESIONS; EVENT AB In order to determine the topographical distribution of the K-ras codon 12 mutations in carcinoma and preneoplastic lesions of the lung, selective ultraviolet radiation fractionation, as well as microdissection followed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP), was performed. Fourteen of 61 samples amplified (23.0%) had a mutation in the K-ras codon 12. Of 41 adenocarcinoma, 12 samples (29.3%) had a mutation, whereas none of the squamous cell carcinomas had a mutation, One of six large-cell carcinomas, one of three carcinoid rumours and none of three other carcinomas had a mutation. Direct sequencing revealed that K-ras codon 12 of six samples were TGT (Cys), five samples were GTT (Val), two samples were GCT (Ala) and one sample was TTT (Phe). A total of 113 lesions of 13 cases covered by dot were amplified after UV radiation. All of 74 carcinoma lesions had the mutation, and intratumour heterogeneity was not observed. Of 39 non-malignant lesions, one type II cell hyperplasia had the mutation, which suggests that the K-ras mutation occurs in the early stage of carcinogenesis. The lack of intratumour heterogeneity supports the hypothesis. C1 Tohoku Univ, Dept Thorac Surg, Ins Dev Aging & Canc, Aoba Ku, Sendai, Miyagi 98077, Japan. NCI, Biomarkers & Prevent Res Branch, Rockville, MD 20850 USA. RP Sagawa, M (reprint author), Tohoku Univ, Dept Thorac Surg, Ins Dev Aging & Canc, Aoba Ku, 4-1 Sieryo Machi, Sendai, Miyagi 98077, Japan. NR 15 TC 40 Z9 42 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 MAR PY 1998 VL 77 IS 5 BP 720 EP 723 DI 10.1038/bjc.1998.118 PG 4 WC Oncology SC Oncology GA ZA343 UT WOS:000072354000005 PM 9514049 ER PT J AU Bradshaw, TD Wrigley, S Shi, DF Schultz, RJ Paull, KD Stevens, MFG AF Bradshaw, TD Wrigley, S Shi, DF Schultz, RJ Paull, KD Stevens, MFG TI 2-(4-aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity SO BRITISH JOURNAL OF CANCER LA English DT Article DE 2-(4-aminophenyl)benzothiazole; biphasic dose response; selective anti-tumour activity ID IN-VITRO; ANTITUMOR BENZOTHIAZOLES; BREAST-CANCER; APOPTOSIS AB 2-(4-Aminophenyl)benzothiazole (CJM 126) elicits biphasic growth-inhibitory effects against a panel of oestrogen receptor-positive (ER+) and oestrogen receptor-negative (ER-) human mammary carcinoma cell lines in vitro, yielding IC50 values in the nan range. Substitutions adjacent to the amino group in the 2-phenyl ring with a halogen atom or methyl group enhance potency in sensitive breast lines (pM IC50 values). Transient biphasic dose responses were induced but rapidly eradicated after specific drug exposure periods. Two human prostate carcinoma cell lines were refractory to the growth-inhibitory properties of 2-(4-aminophenyl)benzothiazoles; IC50 values > 30 mu M were obtained. Potency and selectivity were confirmed when compounds were examined in the National Cancer Institute's Developmental Therapeutics screen; the spectrum of activity included specific ovarian, renal, colon al; well as breast carcinoma cell lines. Moreover, comparing 6-day and 48-h incubations, the exposure time-dependent nature of the biphasic: response was corroborated. Differential perturbation of cell cycle distribution followed treatment of MCF-7 and MDA 468 cells with substituted 2-(4-aminophenyl)benzothiazoles. In MDA 468 populations only, accumulation of events in G(2)/M phase was observed. Two MCF-7 cell lines were established with acquired resistance to CJM 126 (IC50 values > 20 mu M), which exhibit cross-resistance to substituted benzothiazoles, but equal sensitivity to tamoxifen and doxorubicin. Compared with standard anti-tumour agents evaluated in the National Cancer Institute in vitro cell panel, benzothiazoles revealed unique profiles of growth inhibition, suggesting a models) of action shared with no known clinically active class of chemotherapeutic agents. C1 Univ Nottingham, Canc Res Labs, Dept Pharmaceut Sci, Nottingham NG7 2RD, England. NCI, Bethesda, MD 20902 USA. RP Bradshaw, TD (reprint author), Univ Nottingham, Canc Res Labs, Dept Pharmaceut Sci, Nottingham NG7 2RD, England. NR 18 TC 167 Z9 168 U1 0 U2 6 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 MAR PY 1998 VL 77 IS 5 BP 745 EP 752 DI 10.1038/bjc.1998.122 PG 8 WC Oncology SC Oncology GA ZA343 UT WOS:000072354000009 PM 9514053 ER PT J AU Clifford, JJ Tighe, O Croke, DT Drago, J Sibley, DR Waddington, JL AF Clifford, JJ Tighe, O Croke, DT Drago, J Sibley, DR Waddington, JL TI Behavioural responsivity to the selective D-1-like agonist A 68930 in transgenic mice with D-1A dopamine receptor 'knockout' SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Biochem, Dublin 2, Ireland. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. NINDS, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1998 VL 123 SU S MA 20P BP U29 EP U29 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ675 UT WOS:000073240800021 ER PT J AU Masereeuw, R Moons, MM Miller, DA Russel, FGM AF Masereeuw, R Moons, MM Miller, DA Russel, FGM TI Active secretion and intracellular disposition of Lucifer Yellow in renal proximal tubules SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Nijmegen, Dept Pharmacol, Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1998 VL 123 SU S MA 336P BP U187 EP U187 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ675 UT WOS:000073240800337 ER PT J AU Safrany, ST Shears, SB AF Safrany, ST Shears, SB TI Bis-diphosphoinositol tetrakisphosphate (IP8) levels are mediated by a cyclic AMP-dependent, protein kinase A-independent pathway in smooth muscle cells SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 NIEHS, Inositide Signaling Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1998 VL 123 SU S MA 108P BP U73 EP U73 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ675 UT WOS:000073240800109 ER PT J AU DuPont, RL AF DuPont, RL TI Addiction: A new paradigm SO BULLETIN OF THE MENNINGER CLINIC LA English DT Article; Proceedings Paper CT 19th Annual Menninger Winter Psychiatry Conference CY MAR 09-14, 1997 CL PARK CITY, UTAH SP Menninger Clin, SmithKline Beecham Pharm AB The older view of addiction was that people became addicted because they were ignorant of the risks of addiction, they were unhappy, or they lacked healthy opportunities. Once addicted, they were hooked by physical dependence, causing them to continue use despite wanting to quit. The new paradigm of addiction focuses on reward and the powerful experience of falling in love with the feelings that addictive behaviors produce. Potential addicts seek brain reward and are heedless of the risks, of which they are seldom ignorant. Withdrawal is largely irrelevant. The problem of addiction is the power of brain reward. The neu, view of addiction has important implications for prevention, treatment, public policy, and medical treatment with controlled substances. C1 Inst Behav & Hlth Inc, Rockville, MD 20852 USA. NIDA, Lexington, KY USA. Georgetown Univ, Sch Med, Washington, DC 20057 USA. RP DuPont, RL (reprint author), Inst Behav & Hlth Inc, 6191 Execut Blvd, Rockville, MD 20852 USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU MENNINGER FOUNDATION PI TOPEKA PA BOX 829, TOPEKA, KS 66601 USA SN 0025-9284 J9 B MENNINGER CLIN JI Bull. Menninger Clin. PD SPR PY 1998 VL 62 IS 2 BP 231 EP 242 PG 12 WC Psychiatry; Psychology, Psychoanalysis SC Psychiatry; Psychology GA ZL349 UT WOS:000073424000006 PM 9604518 ER PT J AU Weihe, E Hartschuh, W Schafer, MKH Romeo, H Eiden, LE AF Weihe, E Hartschuh, W Schafer, MKH Romeo, H Eiden, LE TI Cutaneous Merkel cells of the rat contain both dynorphin A and vesicular monoamine transporter type 1 (VMAT1) immunoreactivity SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE skin; opioid; neuropeptide; neuroendocrine; pain ID GENE-RELATED PEPTIDE; ENKEPHALIN-LIKE IMMUNOREACTIVITY; KAPPA-OPIOID RECEPTORS; CHROMOGRANIN-A; NERVE-FIBERS; SYNAPTIC VESICLES; MULTIPLE PEPTIDES; ENDOCRINE-CELLS; SUBSTANCE-P; SPINAL-CORD AB To delineate fully opioid peptide function in cutaneous inflammatory and nociceptive responses, it is necessary to know first which opioid peptides are present in the skin and which cellular elements in the skin store and secrete them. Merkel cells are cutaneous neuroendocrine cells, which may derive from the neural crest or from undifferentiated keratinocytes with stem cell character. The neuroendocrine character of Merkel cells is supported by their immunoreactivity for chromogranin A (CGA) and a variety of neuropeptides, among them the opioid peptide [Met]enkephalin as shown in guinea-pig and mouse. This study investigates in the rat whether the preprodynorphin derived opioid peptide dynorphin A is expressed in cutaneous Merkel cells and possibly related to an aminergic phenotype. Light microscopic immunohistochemistry revealed dynorphin A immunoreactivity in Merkel cells to be codistributed with immunoreactivity for calcitonin gene-related peptide (CGRP) and CGA,two well-established marker peptides of mammalian Merkel cells. Vibrissal Merkel cells stained for the neuroendocrine vesicular monoamine transporter isoform 1 (VMAT1) but not for the predominantly neuronal isoform 2 (VMAT2). Merkel cell staining for dynorphin A, VMAT1, CGA, and CGRP was unaffected by experimental denervation. Dynorphin A and a still unidentified monoamine, possibly serotonin, may cofunction as autocrine or paracrine mediators in the mechanosensory Merkel cell - axon complex and are potentially involved in peripheral analgesia. C1 Philipps Univ Marburg, Inst Anat & Cell Biol, Sect Mol Neuroimmunol, D-35033 Marburg, Germany. Univ Heidelberg, Dermatol Clin, D-69115 Heidelberg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Recognit, NIH, Bethesda, MD 20892 USA. RP Weihe, E (reprint author), Philipps Univ Marburg, Inst Anat & Cell Biol, Sect Mol Neuroimmunol, Robert Koch Str 6, D-35033 Marburg, Germany. EM weihe@mailer.uni-marburg.de OI Eiden, Lee/0000-0001-7524-944X NR 46 TC 11 Z9 11 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAR PY 1998 VL 76 IS 3 BP 334 EP 339 DI 10.1139/cjpp-76-3-334 PG 6 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA ZZ671 UT WOS:000074754900013 PM 9673797 ER PT J AU Chow, WH AF Chow, WH TI Colorectal cancer incidence trends: Good news and bad news SO CANCER CAUSES & CONTROL LA English DT Editorial Material ID UNITED-STATES; COLON-CANCER; PHYSICAL-ACTIVITY; PATTERNS; ADULTS; RISK C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Chow, WH (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 1998 VL 9 IS 2 BP 127 EP 129 DI 10.1023/A:1008818818899 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZD613 UT WOS:000072704400001 PM 9578288 ER PT J AU Mellemkjaer, L Johansen, C Linet, MS Gridley, G Olsen, JH AF Mellemkjaer, L Johansen, C Linet, MS Gridley, G Olsen, JH TI Cancer risk following appendectomy for acute appendicitis (Denmark) SO CANCER CAUSES & CONTROL LA English DT Article DE appendicitis; appendectomy; cancer risk; Denmark ID CARCINOMA AB Objective: Epidemiologic studies have not been able definitely to exclude that appendectomy carries a cancer risk. This study was conducted to clarify whether appendectomy is associated with a subsequent increase in cancer risk, since appendectomy is frequently an elective procedure. Methods: The present study included more than 82,000 persons who underwent appendectomy for acute appendicitis during 1977-89 according to the nation-wide Danish Hospital Discharge Register. During a follow-up interval of up to 17 years, cancer incidence was assessed by linkage to the Danish Cancer Registry and compared with the incidence in the general population of Denmark. Results: The total number of malignancies among appendectomized persons was 1.05 times higher than expected with 95 percent confidence intervals of 0.99-1.11. There was no clear significant excess of any specific cancer type. Conclusion: During a postsurgery period of nearly two decades, results of our study did not support the hypothesis that either appendectomy or acute appendicitis are likely to be associated with malignant neoplasms. C1 Inst Canc Epidemiol, Danish Canc Soc, DK-2100 Copenhagen O, Denmark. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mellemkjaer, L (reprint author), Inst Canc Epidemiol, Danish Canc Soc, Strandblvd 49, DK-2100 Copenhagen O, Denmark. FU NCI NIH HHS [N01-CP-85639-04] NR 28 TC 11 Z9 11 U1 0 U2 0 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 MAR PY 1998 VL 9 IS 2 BP 183 EP 187 DI 10.1023/A:1008834311514 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZD613 UT WOS:000072704400008 PM 9578295 ER PT J AU Madigan, MP Troisi, R Potischman, N Dorgan, JF Brinton, LA Hoover, RN AF Madigan, MP Troisi, R Potischman, N Dorgan, JF Brinton, LA Hoover, RN TI Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE body size; lifestyle factors; postmenopausal women; reproductive history; sex hormones; United States ID POST-MENOPAUSAL WOMEN; BREAST-CANCER RISK; ENDOMETRIAL CANCER; SEX-HORMONES; CIGARETTE-SMOKING; URINE ESTROGENS; ENDOGENOUS HORMONES; BINDING GLOBULIN; PROLACTIN LEVELS; AGE AB Objectives: Endogenous sex hormones are thought to be involved in breast and endometrial cancers, but few studies have evaluated the relationships between hormones and risk factors for these diseases. Methods: We related serum hormone and sex-hormone binding globulin (SHBG) levels to reproductive and lifestyle risk factors in a cross-sectional study of 125 postmenopausal women in five geographic regions of the United States. Results: The estrogens were associated positively, while SHBG was associated negatively with body mass index (wt/ht(2)). Estrone, (E1), estrone sulfate, and bioavailable estradiol (BioE2) were inversely associated with height. Androstenedione was positively associated with age at menopause, while androstenedione, E1, estradiol, and BioE2 were inversely associated with age at menarche. Weekly alcohol drinkers had higher hormone levels, and lower SHBG levels than those who abstained. Androstenedione and E1 decreased with increasing levels of nonrecreational activity. Conclusions: Several of these findings support the hypothesis that breast and endometrial cancer risk factors are mediated, in part, through increased endogenous hormone levels. The androstenedione findings are of interest in light of studies relating androstenedione to endometrial and possibly breast cancer. An association of age at menarche with E2, independent of androstenedione, may reflect increased aromatase activity in women with earlier menarche. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Bethesda, MD 20892 USA. RP Madigan, MP (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, EPN 443, Bethesda, MD 20892 USA. RI Perez , Claudio Alejandro/F-8310-2010; Brinton, Louise/G-7486-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Brinton, Louise/0000-0003-3853-8562 NR 56 TC 94 Z9 96 U1 0 U2 2 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 MAR PY 1998 VL 9 IS 2 BP 199 EP 207 DI 10.1023/A:1008838412423 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZD613 UT WOS:000072704400010 PM 9578297 ER PT J AU Moysich, KB Ambrosone, CB Vena, JE Shields, PG Mendola, P Kostyniak, P Greizerstein, H Graham, S Marshall, JR Schisterman, EF Freudenheim, JL AF Moysich, KB Ambrosone, CB Vena, JE Shields, PG Mendola, P Kostyniak, P Greizerstein, H Graham, S Marshall, JR Schisterman, EF Freudenheim, JL TI Environmental organochlorine exposure and postmenopausal breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; ADIPOSE-TISSUE; HEXACHLOROBENZENE HCB; BLOOD-LEVELS; FEMALE RAT; SERUM; MIREX; EPIDEMIOLOGY; PESTICIDES; TOXICITY AB Environmental exposure to organochlorine compounds has been associated with a potential role in breast cancer etiology, but results from previous investigations yielded inconsistent results. In this case-control study, we examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethyl (DDE), hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls (PCBs) on postmenopausal breast cancer risk. The study sample included 154 primary, incident, histologically confirmed, postmenopausal breast cancer cases and 192 postmenopausal community controls. Usual diet, reproductive and medical histories, and other lifestyle information was obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, mirex, and 73 PCB congeners were determined by gas chromatography with electron capture. PCB exposure was examined as total measured PCB levels, total number of detected PCB peaks, and three PCB congener groups. In the total sample, there was no evidence of an adverse effect of serum levels of DDE [odds ratio (OR), 1.34; 95% confidence interval (CI) 0.71-2.55], HCB (OR, 0.81; 95% CI, 0.43-1.53), or mirex (OR, 1.37; 95% CI, 0.78-2.39). Further, higher serum levels of total PCBs (OR, 1.14; 95% CI, 0.61-2.15), moderately chlorinated PCBs (OR, 1.37; 95% CI, 0.73-2.59), more highly chlorinated PCBs (OR, 1.19; 95% CI, 0.60-2.36), or greater number of detected peaks (OR, 1.34; 95% CI, 0.72-2.47) were not associated with increased risk. There was some indication of a modest increase in risk for women with detectable levels of less chlorinated PCBs (OR, 1.66; 95% CI, 1.07-2.88). Among parous women who had never lactated, there was some evidence for increased risk, associated with having detectable levels of mirex (OR, 2.42; 95% CI, 0.98-4.32), higher serum concentrations of total PCBs (OR, 2.87; 95% CI, 1.01-7.29), moderately chlorinated PCBs (OR, 3.57; 95% CI, 1.10-8.60), and greater numbers of detected PCB congeners (OR, 3.31; 95% CI, 1.04-11.3). These results suggest that an increase in risk of postmenopausal breast cancer associated with environmental exposure to PCBs and mirex, if at all present, is restricted to parous women who had never breast-fed an infant. Future studies should consider lactation history of participants, as well as use similar epidemiological and laboratory methodologies, to ensure comparability of results across studies. C1 SUNY Buffalo, Dept Prevent & Social Med, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. SUNY Buffalo, Toxicol Res Ctr, Buffalo, NY 14214 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Moysich, KB (reprint author), SUNY Buffalo, Dept Prevent & Social Med, Sch Med & Biomed Sci, 270 Farber Hall, Buffalo, NY 14214 USA. EM kmoyisch@ubmedg.buffalo.edu RI Shields, Peter/I-1644-2012; OI Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA/ES 62995, CA11535] NR 47 TC 130 Z9 133 U1 0 U2 8 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 MAR PY 1998 VL 7 IS 3 BP 181 EP 188 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA627 UT WOS:000072384000001 PM 9521429 ER PT J AU Shaw, GL Falk, RT Frame, JN Weiffenbach, B Nesbitt, JC Pass, HI Caporaso, NE Moir, DT Tucker, MA AF Shaw, GL Falk, RT Frame, JN Weiffenbach, B Nesbitt, JC Pass, HI Caporaso, NE Moir, DT Tucker, MA TI Genetic polymorphism of CYP2D6 and lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DEBRISOQUINE OXIDATION PHENOTYPE; POOR METABOLIZER PHENOTYPE; DRUG-METABOLISM; SPARTEINE POLYMORPHISM; POINT MUTATIONS; HYDROXYLATION; POPULATION; SUSCEPTIBILITY; ALLELE; IDENTIFICATION AB Previous reports of the association of extensive debrisoquine metabolism, controlled by the cytochrome P450 CYP2D6, with increased lung cancer risk have been conflicting, We examined the hypothesis that genetic polymorphism at the CYP2D6 locus identifies individuals at increased risk for lung cancer in a case-control study of 98 incident Caucasian lung cancer patients and 110 age-, race-, and sex-matched controls conducted at the National Naval Medical Center, Bethesda, MD. Using germ line DNA, we identified inactivating mutations at the CYP2D6 locus (CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6A), as well as those mutations that impair but do not abolish enzyme activity (CYP2D6*9 and CYP2D6*10A), Compared to subjects with homozygous inactivating mutations, no association with lung cancer was observed for those with homozygous or heterozygous functional alleles (odds ratios were 0.4 and 0.7, respectively), Furthermore, no excess risk was seen in any histological group or smoking category, and adjustment for smoking and sociodemographic characteristics did not alter the findings, Although the concept that genetic polymorphisms may contribute to differential lung cancer susceptibility is sound, these data do not support the role of CYP2D6 as a marker for elevated lung cancer risk. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. NCI, NIH, Bethesda, MD 20892 USA. Geneome Therapeut Corp, Waltham, MA 02154 USA. Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Shaw, GL (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA. RI Tucker, Margaret/B-4297-2015 FU NCI NIH HHS [N01-CP0-5684, N01-CP1-5672] NR 50 TC 26 Z9 29 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 MAR PY 1998 VL 7 IS 3 BP 215 EP 219 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA627 UT WOS:000072384000008 PM 9521436 ER PT J AU Chen, MJ Longnecker, MP Morgenstern, H Lee, ER Frankl, HD Haile, RW AF Chen, MJ Longnecker, MP Morgenstern, H Lee, ER Frankl, HD Haile, RW TI Recent use of hormone replacement therapy and the prevalence of colorectal adenomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LARGE-BOWEL-CANCER; EXOGENOUS FEMALE HORMONES; COLON-CANCER; REPRODUCTIVE FACTORS; RISK-FACTORS; POSTMENOPAUSAL ESTROGEN; UNITED-STATES; BILE-ACID; WOMEN; PREVENTION AB The etiological role of hormone replacement therapy (HRT) (including estrogen only, combined estrogen-progesterone, and progesterone only) in colorectal neoplasia remains unclear, Several large studies have reported a reduced risk of colorectal cancer among HRT users; however, other studies have given inconsistent results, We examined the association between HRT and colorectal adenomatous polyps, precursors of colorectal cancer, among female participants in a case-control study. Subjects were members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy in 1991-1993, Participants received an in-person interview and completed a food frequency questionnaire, A total of 187 histologically confirmed cases and 188 controls, ages 50-75 years, were included in the analysis, Compared with women who did not use HRT during the year before sigmoidoscopy, recent users had an adjusted odds ratio of 0.57 (95% confidence interval, 0.35-0.94), Duration of use was inversely related to the prevalence of colorectal adenomas, with a multivariate-adjusted odds ratio of 0.49 (95% confidence interval, 0.25-0.97) for use of 5 years or more, These results support a protective effect of HRT on colorectal adenomatous polyps. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Sch Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Bellflower Kaiser Permanente, Div Gastroenterol, Los Angeles, CA 91765 USA. Sunset Kaiser Permanente Med Ctr, Div Gastroenterol, Los Angeles, CA 90027 USA. RP Haile, RW (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Sch Med, 1441 Eastlake Ave,Ms 44,Room 4430,POB 33800, Los Angeles, CA 90033 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 41 TC 25 Z9 25 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 MAR PY 1998 VL 7 IS 3 BP 227 EP 230 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA627 UT WOS:000072384000010 PM 9521438 ER PT J AU Sturgeon, SR Sherman, ME Kurman, RJ Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD Brinton, LA AF Sturgeon, SR Sherman, ME Kurman, RJ Berman, ML Mortel, R Twiggs, LB Barrett, RJ Wilbanks, GD Brinton, LA TI Analysis of histopathological features of endometrioid uterine carcinomas and epidemiologic risk factors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN USE; CANCER; HYPERPLASIA AB A large case-control study was performed to determine whether risk factors for endometrioid carcinoma, the most common type of endometrial cancer, vary according to the histological features of the tumor, Study subjects consisted of 328 women with newly diagnosed endometrioid adenocarcinoma and 320 population-based control subjects, Variables studied included age at menarche, menopausal estrogen use, weight, parity, cigarette smoking, and oral contraceptive use, The risk factor profile for endometrioid carcinomas with and without squamous differentiation was very similar. No striking differences in risk factors were observed between endometrioid canters with and without adjacent endometrial hyperplasia. Finally, none of the risk factors varied substantially between early-stage and late-stage tumors or low-grade and high-grade tumors, In summary, this study indicates that risk factors for endometrioid carcinomas are not related to the morphological features of the tumor. C1 NCI, NIH, Environm Epidemiol Branch, Rockville, MD 20852 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Univ Calif Irvine, Irvine Med Ctr, Dept Obstet & Gynecol, Orange, CA 92668 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, Hershey, PA 17033 USA. Univ Minnesota, Hlth Sci Ctr, Dept Obstet & Gynecol, Minneapolis, MN 55455 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA. Rush Med Coll, Dept Obstet & Gynecol, Chicago, IL 60612 USA. RP Sturgeon, SR (reprint author), NCI, NIH, Environm Epidemiol Branch, Execut Plaza N 443,6130 Execut Blvd, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 14 TC 6 Z9 6 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 MAR PY 1998 VL 7 IS 3 BP 231 EP 235 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA627 UT WOS:000072384000011 PM 9521439 ER PT J AU Lerman, C Shields, PG Audrain, J Main, D Cobb, B Boyd, NR Caporaso, N AF Lerman, C Shields, PG Audrain, J Main, D Cobb, B Boyd, NR Caporaso, N TI The role of the serotonin transporter gene in cigarette smoking SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Data from twin studies have suggested that cigarette smoking has a significant heritable component, The serotonin transporter gene (5-HTT) is a plausible candidate gene for smoking predisposition because of its association with psychological traits relevant to smoking behavior, The present investigation evaluated the associations of smoking practices and smoking cessation with a common polymorphism in the upstream regulatory region of 5-HTT that is manifested as either an inserted (long) variant or a deleted (short) variant, The short variant of the polymorphism is associated with reduced transcription of the gene promoter and diminished uptake, A case-control study design (268 smokers and 230 controls) was used to evaluate the associations of 5-HTT genotype with smoking status, Case series analysis of smokers was used to evaluate the role of 5-HTT in age at smoking initiation, previous quitting history, current smoking rate, and 12-month quit rate following a minimal-contact smoking cessation program, There were no significant differences in the distribution of 5-HTT genotypes in smokers as compared with nonsmokers in either Caucasians or African Americans, nor was the 5-HTT genotype associated with the smoking outcome variables, However, the results did reveal significant racial differences in the distribution of 5-HTT genotypes: Caucasians were significantly more likely to carry the short variant of the 5-HTT gene than mere African Americans (P = 0.005), These findings suggest that the 5-HTT gene may not play a significant role in cigarette smoking practices. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Canc Genet Program, Washington, DC 20007 USA. NCI, Mol Epidemiol Sect, Human Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Lerman, C (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Canc Genet Program, 2233 Wisconsin Ave NW,Suite 535, Washington, DC 20007 USA. RI Shields, Peter/I-1644-2012 NR 18 TC 68 Z9 73 U1 0 U2 2 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 MAR PY 1998 VL 7 IS 3 BP 253 EP 255 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA627 UT WOS:000072384000014 PM 9521442 ER PT J AU Shrayer, DP Kouttab, N Hearing, VJ Wanebo, HJ AF Shrayer, DP Kouttab, N Hearing, VJ Wanebo, HJ TI Immunization of mice with melanoma cells transfected to secrete the superantigen, staphylococcal enterotoxin A SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE enterotoxin; immunization; melanoma; B700 ID FORMALINIZED EXTRACELLULAR ANTIGENS; MHC CLASS-II; SHOCK SYNDROME TOXIN-1; RECEPTOR BETA-CHAIN; T-CELLS; MURINE MELANOMA; MICROBIAL SUPERANTIGENS; BACTERIAL SUPERANTIGENS; LEWIS CARCINOMA; SPLEEN-CELLS AB Immunization of mice with a melanoma vaccine coupled with staphylococcal enterotoxin A (SEA) inhibits the growth of primary melanoma tumors in mice. We have now successfully transfected B16 cells with the sea gene and have immunized C57BL/6 mice subcutaneously once per week for 4 weeks prior to tumor challenge with vaccines of irradiated B16 cells or, 4 weeks following tumor challenge of naive mice with B16 cells, with irradiated B16 cells transfected with the sea gene. Primary tumor growth following both types of treatments was inhibited significantly. To characterize immune responses to these immunogens, we examined the production of antibodies to the B700 melanoma antigen, the stimulation of endogenous IL-2 production, the expression of CD4, CD8, V beta and CD25 T cell markers, and the induction of NK activity. At 4 weeks following immunization of mice, there was a significant increase (P<0.05) in levels of interleukin-2 production by splenocytes from mice immunized with SEA-secreting B16 cells or with the parental B16 cells, compared to controls. Levels of antibodies to the B700 melanoma antigen were also significantly higher in mice immunized with the SEA-secreting B16 cells, as was expression of CD4, CD8, CD25 and V beta T cell antigens, particularly CD4. Natural killer cell activity (at various E:T ratios) was tenfold higher in splenocytes of mice immunized with SEA-secreting B16 cells, and fivefold higher in mice immunized with the parental B16 cells, compared to controls. These data confirm the possibility of using irradiated murine melanoma cells transfected to secrete SEA in vaccines targeted at preventing the development and growth of melanoma. C1 Brown Univ, Roger Williams Med Ctr, Dept Surg, Providence, RI 02908 USA. Brown Univ, Roger Williams Med Ctr, Dept Pathol, Providence, RI 02908 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Shrayer, DP (reprint author), Brown Univ, Roger Williams Med Ctr, Dept Surg, 825 Chalkstone Ave, Providence, RI 02908 USA. NR 56 TC 9 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAR PY 1998 VL 46 IS 1 BP 7 EP 13 DI 10.1007/s002620050453 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA ZB263 UT WOS:000072453500002 PM 9520286 ER PT J AU Lee, DS White, DE Hurst, R Rosenberg, SA Yang, JC AF Lee, DS White, DE Hurst, R Rosenberg, SA Yang, JC TI Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE immunotherapy; interleukin-2; melanoma; metastasectomy; relapse; renal cell cancer ID TUMOR-INFILTRATING LYMPHOCYTES; CANCER; THERAPY AB PURPOSE The purpose of this study was to examine the pattern of relapse and the treatment of relapse with either surgery or repeat immunotherapy in patients with metastatic melanoma or renal cell carcinoma who had previously responded to interleukin-2-based therapy. PATIENTS AND METHODS Over a 10-year period 1051 patients with metastatic melanoma or renal cell carcinoma were treated with interleukin-2-based immunotherapy at a single institution. One hundred fifty-nine patients who relapsed after an initial partial response or complete response to interleukin-2-based immunotherapy formed the study population for this retrospective review. Medical records, physical examination forms, and relevant radiographs were reviewed to determine response, relapse site(s), and response to treatment for relapse. RESULTS Relapse after an initial response to interleukin-2-based therapy occurred in 84 (80%) of 105 patients with metastatic melanoma and in 75 (70%) of 107 patients with metastatic renal cell carcinoma Relapse after an initial partial response involved 71 (97%) of 73 patients with metastatic melanoma and 55 (86%) of 64 patients with metastatic renal cell carcinoma. The initial site(s) of relapse after a partial response involved a new site(s), old site(s), or both old and new sites with relatively even distribution. Relapse after an initial complete response occurred in 13 (41%) of 32 patients with metastatic melanoma and in 20 (47%) of 43 completely responding patients with metastatic renal cell carcinoma Surprisingly, the initial site of relapse after a complete response involved only new sites of disease in 70% of patients. Retreatment of relapses with the same interleukin-2-based therapy originally used was effective in only one (2%) of 54 selected patients, but a different interleukin-2-based therapy in 35 patients resulted in five responders (a 14% secondary response rate). Most re-responders, however, responded to treatment with tumor-infiltrating lymphocytes and interleukin-2, and only one of 20 patients responded to retreatment with interleukin-2 alone. Surgical metastasectomy with therapeutic intent in 25 selected melanoma patients and in 31 selected renal cell cancer patients resulted in a 2-year progression-free survival of 18% in patients with metastatic melanoma and 37% in patients with metastatic renal cell carcinoma. DISCUSSION In patients with metastatic melanoma or renal cell carcinoma, tumor relapse was common after a partial response to an interleukin-2-based therapy and included previously identified sites of disease in most patients. Relapse after a complete response was less frequent and involved only new sites in a majority of patients. In selected patients who relapsed, repeat treatment with the same interleukin-2-based therapy that provided the initial response was rarely effective. However, with a different interleukin-2-based therapy, usually using tumor-infiltrating lymphocytes, repeat treatment induced secondary responses in some patients. In addition, salvage metastasectomy resulted in durable progression-free survival in selected patients. C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, 9000 Rockville Pike,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 14 TC 27 Z9 28 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD MAR-APR PY 1998 VL 4 IS 2 BP 86 EP 93 PG 8 WC Oncology SC Oncology GA ZD934 UT WOS:000072740400006 PM 9532410 ER PT J AU Brown, JK Hartmuller, VW AF Brown, JK Hartmuller, VW TI Nutritional resources for patients with cancer and health professionals SO CANCER PRACTICE LA English DT Editorial Material C1 SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA. NCI, Off Canc Informat Commun & Educ, Patient Educ Branch, Bethesda, MD 20892 USA. RP Brown, JK (reprint author), SUNY Buffalo, Sch Nursing, Buffalo, NY 14260 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD MAR-APR PY 1998 VL 6 IS 2 BP 125 EP 128 DI 10.1046/j.1523-5394.1998.1998006125.x PG 4 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA ZG095 UT WOS:000072965100008 PM 9573912 ER PT J AU Lubet, RA Gordon, GB Prough, RA Lei, XD You, M Wang, Y Grubbs, CJ Steele, VE Kelloff, GJ Thomas, CF Moon, RD AF Lubet, RA Gordon, GB Prough, RA Lei, XD You, M Wang, Y Grubbs, CJ Steele, VE Kelloff, GJ Thomas, CF Moon, RD TI Modulation of methylnitrosourea-induced breast cancer in Sprague Dawley rats by dehydroepiandrosterone: Dose-dependent inhibition, effects of limited exposure, effects on peroxisomal enzymes, and lack of effects on levels of Ha-ras mutations SO CANCER RESEARCH LA English DT Article ID DIETARY DEHYDROEPIANDROSTERONE; MAMMARY-GLAND; INDUCTION; MICE; TUMORIGENESIS; METHYLUREA; MECHANISM; SULFATE AB Dehydroepiandrosterone (DHEA), the major steroid precursor of androgens and estrogens produced in peripheral tissues in primates, is an effective chemopreventive agent in the N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor model, Dietary DHEA (5-600 ppm; 600 mg/kg diet) was administered beginning 1 week before MNU and administered continually throughout the duration of the experiment, The highest dose of DHEA (600 ppm) significantly decreased tumor incidence from 95 to 45% and increased tumor latency and decreased tumor multiplicity from 4.1 to 0.5 tumors/rat, Lower doses of DHEA (5, 24, and 120 ppm) were also effective, decreasing tumor multiplicity by 28, 40, and 55%, respectively, increasing tumor latency in a dose-dependent manner but only minimally affecting final tumor incidence, DHEA in the diet caused a dose-dependent increase in serum levels of DHEA, The 120-ppm dietary dose of DHEA resulted in serum levels of DHEA of similar to 42 pmol/ml levels, similar to those seen in young humans, When we examined whole mounts of mammary glands derived from rats exposed to higher levels of DHEA (600 ppm), we observed a striking increase in lobular development. The doses of DHEA used in these studies (less than or equal to 600 ppm) had minimal effects on the induction of fatty acid CoA synthetase, a peroxisome-associated enzyme, In contrast, a dose of 2000 ppm substantially increased Levels of peroxisome-associated fatty acid CoA synthetase. The varied and striking efficacy of DHEA was achieved in the absence of any significant effect on body weight gain in the treated rats, Furthermore, tumors from rats treated with MNU alone or rats treated with MNU plus DHEA were examined for the presence of mutations in the Ha-Ras oncogene, There was a slight decrease in the percentage of tumors bearing Ha-Rns mutations in tumors derived from MNU-control rats as contrasted with tumors from MNU-DHEA (120 and 600 ppm)-treated rats, Based on the striking chemopreventive efficacy of continual exposure to DHE,I, we examined the effects of more limited exposure to DHEA, Rats were treated with DHEA for a period of 7 weeks immediately before and after MNU injection, Rats were then placed on the control diet for the ensuing 15 weeks, Even this limited exposure to DHEA for a period of 7 weeks profoundly decreased final tumor incidence and multiplicity, Additionally, we examined the effects of intermittent dosing with DHEA, Rats were treated alternatively at 3-week intervals either with diet containing DHEA or with control diet, It was found that this intermittent dosing with DHEA also substantially inhibited the formation of mammary tumors. C1 NCI, DCPC, Chemoprevent Branch, Bethesda, MD 20892 USA. GD Searle & Co, Skokie, IL 60077 USA. Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Univ Louisville, Sch Med, Dept Biochem, Louisville, KY 40202 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. Univ Alabama, Dept Nutr, Birmingham, AL 35294 USA. Univ Illinois, Chicago, IL 60612 USA. RP Lubet, RA (reprint author), NCI, DCPC, Chemoprevent Branch, EPN-201,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CN-35535-02, CA43839, N01-CN-35535-03] NR 31 TC 39 Z9 39 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 MAR 1 PY 1998 VL 58 IS 5 BP 921 EP 926 PG 6 WC Oncology SC Oncology GA YZ422 UT WOS:000072252800014 PM 9500451 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, RJ Pastan, I TI Accumulation of a recombinant immunotoxin in a tumor in vivo: Fewer than 1000 molecules per cell are sufficient for complete responses SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN IMMUNOTOXIN; DISULFIDE-STABILIZED FV; GROWTH-FACTOR RECEPTOR; PSEUDOMONAS-EXOTOXIN; INTERLEUKIN-2 RECEPTOR; DIPHTHERIA-TOXIN; HUMAN CARCINOMA; ANTI-TAC; T-CELL; COMPLETE REGRESSION AB Recombinant immunotoxins have been shown to cure human tumor xenografts in mice, but their biodistribution to both tumors and normal organs has not been reported. Anti-Tac(Fv)-PE38 is a single-chain recombinant immunotoxin composed of the variable heavy and light domains of the anti-Tac monoclonal antibody that reacts with the primate interleukin 2 (IL2) receptor alpha subunit (IL2R alpha or CD25) fused to a truncated form of Pseudomonas exotoxin (PE). I-125-labeled anti-Tac(Fv)-PE38 was given i.v. to immunodeficient mice each bearing two A431 tumors, one that: expresses IL2R alpha (ATAC-4) and one that does not (A431, parental), A single i.v. dose of 4 mu g/mouse caused complete regression of the IL2R alpha + tumor. At 6 h, over 6% of the injected dose/g was found in the ATAC-4 tumor, and 2% was in the A431 tumor. Uptake in the ATAC-4 tumor was higher than in any other tissue. Sections of tumor examined by autoradiography indicated that anti-Tac(Fv)-PE38 was distributed throughout the entire tumor, with some portions having higher uptake I-hen others, By subtracting uptake in tumors without receptor (A431) from uptake in receptor-containing tumors (ATAC-4), ne calculated that at least 400 molecules/cell specifically bound to IL2R alpha-positive tumor cells at 90 min and 750 molecules/cell bound at 360 min. This is similar to the 400-570 molecules/cell required for >99.9% killing of ATAC-4 cells growing as a monolayer. The results show that solid tumors in mice can be eradicated like cells in tissue culture, and that delivery of less than 1000 molecules/cell is sufficient to cause complete tumor regressions. C1 NCI, Mol Biol Lab, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Canc Biol, NIH, 37-4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 44 TC 81 Z9 83 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 MAR 1 PY 1998 VL 58 IS 5 BP 968 EP 975 PG 8 WC Oncology SC Oncology GA YZ422 UT WOS:000072252800021 PM 9500458 ER PT J AU Hodosi, G Kovac, P AF Hodosi, G Kovac, P TI Glycosylation via locked anomeric configuration: stereospecific synthesis of oligosaccharides containing the beta-D-mannopyranosyl and beta-L-rhamnopyranosyl linkage SO CARBOHYDRATE RESEARCH LA English DT Article DE stereospecific beta-D-mannosylation; stereospecific beta-L-rhamnosylation; cis-1,2-O-stannylene acetals; stereospecific glycosylation; oligosaccharide synthesis AB cis-1,2-Stannylene acetals of D-mannose and L-rhamnose, formed preferentially from the free sugars treated with dibutyltin oxide, are capable of displacing the trifluoromethanesulfonyl (triflyl) leaving groups in carbohydrates to give, with retention of configuration at the anomeric center in the nucleophile, cis-1,2-linked oligosaccharides. In the case of secondary triflates, the new glycosidic linkage is formed with complete inversion of configuration in the electrophile. Both the reactivity of the electrophile and nucleophilicity of oxygens in the stannylene complex affect the overall outcome of the reaction. From the comparison of results of a number of glycosylations via stannylene acetals, it appears that nucleophilicity of oxygens involved in the cis-1,2-acetals decreases in the order: equatorial anomeric > equatorial non-anomeric > axial anomeric. Consequently, treatment of the stannylene acetal prepared from D-mannose (mainly the cis-1,2-stannylene compound in admixture with a small proportion of the cis-2,3-stannylene acetal) with methyl 2,3,4-tri-O-benzoyl-6-O-trifluoromethanesulfonyl-alpha-D-glucopyranoside yielded, in addition to the expected beta-D-mannopyranoside (major), a product of non-anomeric alkylation at O-3. On the other hand, glycosylation of the stannylene acetal derived from maltose with methyl 2,3,6-tri-O-benzoyl-4-O-trifluoromethanesulfonyl-alpha-D-galactopyranoside gave almost exclusively a non-glycosidically, (2 --> 4)-linked pseudo-trisaccharide. Combination of the glycosylation via locked anomeric configuration with conventional glycosylations, to yield higher oligosaccharides, is also demonstrated. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. EM kpn@heli.u.nih.gov NR 21 TC 45 Z9 45 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR PY 1998 VL 308 IS 1-2 BP 63 EP 75 DI 10.1016/S0008-6215(98)00057-3 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA ZW994 UT WOS:000074469700008 PM 9675357 ER PT J AU Wang, J Kovac, P Sinay, P Glaudemans, CPJ AF Wang, J Kovac, P Sinay, P Glaudemans, CPJ TI Synthetic C-oligosaccharides mimic their natural, analogous immunodeterminants in binding to three monoclonal immunoglobulins SO CARBOHYDRATE RESEARCH LA English DT Article DE monoclonal immunoglobulins; C-oligosaccharides; binding ID DISACCHARIDES; CONFORMATION; GLYCOSIDE; PROTEINS AB The binding of three monoclonal antigalactan immunoglobulins, IgAs X24, J539 and X44 to their natural haptens methyl beta-D-galactopyranosyl-(1 --> 6)-beta-D-galactopyranoside, and the corresponding tri- and tetrasaccharides, was compared to the binding of these immunoglobulins with the comparable C-linked oligosaccharide analogues 1-3. The near identity of affnities of the two sets of oligosaccharides indicated the absence of any hydrogen bond involvement by the intersaccharidic oxygen atoms in the natural immunodeterminants. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIH, Med Chem Lab, Bethesda, MD 20892 USA. Ecole Normale Super, Dept Chim, URA 1686, F-75231 Paris 05, France. RP Glaudemans, CPJ (reprint author), NIH, Med Chem Lab, Bldg 10, Bethesda, MD 20892 USA. EM glau@helix.nih.gov NR 15 TC 39 Z9 40 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR PY 1998 VL 308 IS 1-2 BP 191 EP 193 DI 10.1016/S0008-6215(98)00071-8 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA ZW994 UT WOS:000074469700024 PM 9675360 ER PT J AU Pozsgay, V Sari, N Coxon, B AF Pozsgay, V Sari, N Coxon, B TI Measurement of interglycosidic (3)J(CH) coupling constants of selectively C-13 labeled oligosaccharides by 2D J-resolved H-1 NMR spectroscopy SO CARBOHYDRATE RESEARCH LA English DT Article DE trisaccharide; tetrasaccharide; pentasaccharide; oligosaccharides; carbon-13 labeling; carbon-13-proton coupling constants; Shigella dysenteriae type 1; 2D J-resolved NMR spectroscopy ID SHIGELLA-DYSENTERIAE TYPE-1; NUCLEAR-MAGNETIC-RESONANCE; O-SPECIFIC POLYSACCHARIDE; STEREOSELECTIVE SYNTHESIS; DETECTED MEASUREMENTS; CHEMICAL-SHIFTS; FRAGMENT; CONFORMATION; SACCHARIDES; MOLECULES AB Tri-, tetra-, and penta-saccharide fragments of the O-specific polysaccharide of Shigella dysenteriae type 1 have been prepared in which a D-galactose residue of each oligosaccharide methyl glycoside derivative contains a C-13 label at C-1. The interglycosidic coupling constants ((3)J(CH)) of these C-13 nuclei with the H-3 nuclei of the adjacent 2-acetamido-2-deoxy-D-glucose residues have been measured by two-dimensional, J-resolved H-1 NMR spectroscopy. The magnitudes of these coupling constants indicate that the trisaccharide is conformationally different to the higher oligosaccharide homologs, in agreement with previous studies of C-13 chemical shifts and (1)J(CH) values. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Coxon, B (reprint author), Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. NR 36 TC 7 Z9 7 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR PY 1998 VL 308 IS 1-2 BP 229 EP 238 DI 10.1016/S0008-6215(98)00047-0 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA ZW994 UT WOS:000074469700031 PM 9675362 ER PT J AU Walker, NJ Crofts, FG Li, Y Lax, SF Hayes, CL Strickland, PT Lucier, GW Sutter, TR AF Walker, NJ Crofts, FG Li, Y Lax, SF Hayes, CL Strickland, PT Lucier, GW Sutter, TR TI Induction and localization of cytochrome P4501B1 (CYP1B1) protein in the livers of TCDD-treated rats: detection using polyclonal antibodies raised to histidine-tagged fusion proteins produced and purified from bacteria SO CARCINOGENESIS LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; ADRENAL CYTOCHROME-P450; HYDROCARBON METABOLISM; TUMOR PROMOTION; SEQUENCE; TISSUE; DIOXIN; DIBENZOFURANS; EXPRESSION; SUBFAMILY AB Knowledge of the response of cytochrome P450 1B1 (CYP1B1) to exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in both humans and rodents is limited. To improve the analysis of CYP1 proteins, specific CYP1B1 and CYP1A1 polypeptides were expressed as hexahistidine-tagged fusion proteins in Escherichia coli, purified to homogeneity and used to produce polyclonal antibodies in rabbits. Immunoblot analyses showed that these antibodies were specific and sensitive, detecting both the human and rat forms of the respective isozymes and exhibiting negligible cross-reactivity between the two known CYP1 subfamilies. We show that CYP1B1, CYP1A1 and CYP1A2 protein levels were induced in the livers of female Sprague-Dawley rats following either acute (single dose of 25 mu g TCDD/kg) or chronic (125 ng TCDD/kg/day for 30 weeks) exposure to TCDD, CYP1B1 protein exhibited a dose-response to TCDD that was different from those of CYP1A1 and CYP1A2, CYP1B1 induction appeared to be less sensitive to TCDD exposure, with induction occurring at higher doses of TCDD than that required for induction of CYP1A1 or CYP1A2. Immunohistochemical analysis showed that in animals chronically exposed to TCDD (35 ng/kg/day for 30 weeks), CYP1B1 was induced only in centrilobular hepatocytes, a pattern of expression similar to that of CYP1A1 and CYP1A2. These observations of cellular co-localization of the CYP1 cytochromes in livers of TCDD-treated rats and apparent differences in both protein amounts and dose-response are indicative of both common and unique regulation of CYP1 induction. C1 Johns Hopkins Med Inst, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Sutter, TR (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Div Toxicol Sci, 615 N Wolfe St, Baltimore, MD 21205 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIEHS NIH HHS [ES03819, ES07141, ES06701] NR 25 TC 34 Z9 36 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1998 VL 19 IS 3 BP 395 EP 402 DI 10.1093/carcin/19.3.395 PG 8 WC Oncology SC Oncology GA ZB523 UT WOS:000072481100003 PM 9525272 ER PT J AU Pauly, GT Hughes, SH Moschel, RC AF Pauly, GT Hughes, SH Moschel, RC TI Comparison of mutagenesis by O-6-methyl- and O-6-ethylguanine and O-4-methylthymine in Escherichia coli using double-stranded and gapped plasmids SO CARCINOGENESIS LA English DT Article ID SITE-SPECIFIC MUTAGENESIS; 3 O-6-SUBSTITUTED GUANINES; SINGLE O6-ALKYLGUANINE; DNA-REPAIR; INVIVO; O6-METHYLGUANINE; OLIGODEOXYNUCLEOTIDES; O4-METHYLTHYMINE; FREQUENCY; DEFICIENT AB To compare mutagenesis by O-6-methylguanine (m(6)G), O-4-methylthymine (m(4)T) and O-6-ethylguanine (e(6)G), and assess their genotoxicity in Escherichia coli, double-stranded and gapped plasmids were constructed containing a single m(6)G, e(6)G or m(4)T in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations were scored by the loss of lacZ' activity on X-gal-containing media resulting in formation of white or sectored (mutant) rather than blue (non-mutant) colonies. Genotoxicity experiments with gapped plasmids containing the modified bases indicated that m(4)T produced a greater number of bacterial colonies than m(6)G or e(6)G, m(4)T was more mutagenic (45% mutant colonies) than m(6)G (6%) or e(6)G (11%) in repair competent (w.t.) E. coli when incorporated in double-stranded plasmids. In gapped plasmids, m(4)T produced 99% mutant colonies (as was observed previously for e(6)G) in both w.t. E. coli or E. coli deficient in both O-6-alkylguanine-DNA alkyltransferases as well as methylation-directed mismatch repair (ada(-)-ogt(-)-mutS(-)). m(6)G in gapped plasmids produced 62% mutant colonies in wt. E. coli, but this percentage increased to 94% in the ada(-)-ogt(-)-mutS(-)strain. In double-stranded plasmids both m(4)T and m(6)G produced very similar distributions of mutant and non-mutant colonies in the ada(-)-ogt(-)-mutS(-) strain. These observations led to the conclusion that differences in the mutagenicity of m(6)G and m(4)T in w.t. E. coli were a result of preferential repair of m(6)G compared to m(4)T by alkyltransferase and mismatch repair mechanisms, and did not reflect differences in their respective coding efficiency or their inherent obstructiveness to DNA synthesis as was observed with e(6)G. The combination of alkyltransferase and mismatch repair was concluded to be primarily responsible for the apparent genotoxicity of m(6)G compared to m(4)T in double-stranded plasmids. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Basis Carcinogenesis Lab, Frederick, MD 21702 USA. RP Moschel, RC (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, POB B, Frederick, MD 21702 USA. NR 25 TC 31 Z9 31 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1998 VL 19 IS 3 BP 457 EP 461 DI 10.1093/carcin/19.3.457 PG 5 WC Oncology SC Oncology GA ZB523 UT WOS:000072481100011 PM 9525280 ER PT J AU Ramakrishna, G Anderson, LM AF Ramakrishna, G Anderson, LM TI Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of different genetic strains and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254 SO CARCINOGENESIS LA English DT Article ID LIVER-TUMORS; MOUSE LUNG; HA-RAS; POLYCHLORINATED-BIPHENYLS; ACTIVATED PROTOONCOGENES; CELL-LINES; EXPRESSION; PROMOTION; MUTATIONS; ONCOGENE AB Mutational activation of the K-ras oncogene often occurs in human and mouse lung adenocarcinomas. Since K-ras p21 functions in trans-membrane signaling, we have investigated whether the amount of this protein in lung cell membranes is a variable that could influence lung tumorigenesis, either due to genetic differences or in response to tumor promoters. The six mouse strains assessed showed little difference in the total lung K-ras p21 after immunoprecipitation and immunoblotting. However, amount of ras p21 in the membrane fraction showed significant differences, with C57BL/6 and BALB/c having 3-5-fold more than NIH Swiss, AKR and DBA mice, Interestingly, a congenic AKR strain having the Ahr(b-1) Ah receptor allele from C57BL/6 mice (designated AKR.B6Ah) had high lung membrane K-ras p21 similar to that of C57BL/6. To test for possible changes related to lung tumor promotion, mice were treated with a promotional dose of TCDD (5 nmol/kg). After 48 h C57BL/6 lungs showed an increase in p21 in both total and membrane fractions, BALB/c, DBA and Swiss mice showed an increase only in membranes. There was no change in the AKR and AKR.B6Ah. Aroclor 1254 (250 mg/kg) caused an increase in membrane/cytosol ratio in Swiss mice. Thus the membrane:cytosol K-ras p21 ratio may be influenced by the Ahr phenotype, and TCDD and PCBs can induce p21 or increase its membrane level in certain strains, but these properties are not fully dependent on Ahr receptor type, In confirmation of the relevance of these findings for the tumor target cell type, the immortalized alveolar type 2 E10 cell line presented K-ras p21 in membrane, and this was increased 4-fold by treatment with 10 nM TCDD. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Ramakrishna, G (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NR 48 TC 14 Z9 14 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 MAR PY 1998 VL 19 IS 3 BP 463 EP 470 DI 10.1093/carcin/19.3.463 PG 8 WC Oncology SC Oncology GA ZB523 UT WOS:000072481100012 PM 9525281 ER PT J AU London, SJ Idle, JR Daly, AK Navidi, WC AF London, SJ Idle, JR Daly, AK Navidi, WC TI Re: London,S.J. et al (1997) - Genetic polymorphism of CYP2D6 and lung cancer risk in African-Americans and Caucasians in Los Angeles County. Carcinogenesis, 18,1203-1214 - Reply SO CARCINOGENESIS LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. Norwegian Univ Sci & Technol, N-7048 Trondheim, Norway. Univ Newcastle Upon Tyne, Sch Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. Colorado Sch Mines, Golden, CO 80401 USA. RP London, SJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 6 TC 0 Z9 0 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 MAR PY 1998 VL 19 IS 3 BP 534 EP 535 PG 2 WC Oncology SC Oncology GA ZB523 UT WOS:000072481100024 ER PT J AU Zheng, JS O'Neill, L Long, XL Webb, TE Barnard, EA Lakatta, EG Boluyt, MO AF Zheng, JS O'Neill, L Long, XL Webb, TE Barnard, EA Lakatta, EG Boluyt, MO TI Stimulation of P2Y receptors activates c-fos gene expression and inhibits DNA synthesis in cultured cardiac fibroblasts SO CARDIOVASCULAR RESEARCH LA English DT Article DE P2Y receptor; rat cardiac fibroblast; cell proliferation; c-fos ID URIDINE NUCLEOTIDE RECEPTOR; EXTRACELLULAR ATP; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; CHROMOSOMAL LOCALIZATION; ADENOSINE-TRIPHOSPHATE; VENTRICULAR MYOCYTES; SIGNAL-TRANSDUCTION; ANGIOTENSIN-II; MESSENGER-RNA AB Objectives: The aims of this study were to determine (1) whether neonatal rat cardiac fibroblasts (CAFB) express P2Y receptors; (2) whether CAFE respond to extracellular ATP by inducing expression of c-Sos mRNA; and (3) whether extracellular ATP modulates norepinephrine (NE)-stimulated cell growth in CAFE. Methods: Expression of P2Y(1) and P2Y(2) receptors and induction of c-Sos were examined by Northern blot analysis. CAFB growth was assessed by measuring [H-3]thymidine incorporation and DNA content. P2Y receptor pharmacology was studied using various ATP analogues. Results: Northern blot analysis of polyA enriched RNA confirmed that at least 2 subtypes of P2Y receptors (P2Y(1) and P2Y(2)) an expressed in cultured CAFE. Extracellular ATP induced the expression of c-foss mRNA through a pathway that was sensitive to inhibitors of protein kinase C (PKC), but not to inhibitors of intracellular Ca2+ signaling. Extracellular ATP inhibited the NE-stimulated increases in DNA content and in [3H]thymidine incorporation into DNA. Whereas the potency order for stimulation of c-fos expression was ATP = UTP > ADP > adenosine, the potency order to inhibit the NE-induced increase of [H-3]thymidine incorporation into DNA was ATP > ADP > UTP > adenosine. Conclusions: These data demonstrate that CAFE express both P2Y(1) and P2Y(2) receptor mRNA and that CAFE respond to P2Y receptor stimulation by induction of c-fos and inhibition of DNA synthesis. These findings suggest that the effects of ATP on [H-3]thymidine incorporation into DNA and on expression of c-Sos mRNA are exerted via distinct P2Y receptor subtypes. (C) 1998 Elsevier Science B.V. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Royal Free Hosp, Sch Med, Mol Neurobiol Unit, Div Basic Med Sci, London NW3 2PF, England. RP Boluyt, MO (reprint author), Univ Michigan, Dept Movement Sci, 401 Washtenaw Ave, Ann Arbor, MI 48109 USA. EM boluytm@umich.edu FU Wellcome Trust NR 54 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR PY 1998 VL 37 IS 3 BP 718 EP 728 DI 10.1016/S0008-6363(97)00245-9 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZQ246 UT WOS:000073838100021 PM 9659456 ER PT J AU Austin, S Medvedev, A Yan, ZH Adachi, H Hirose, T Jetten, AM AF Austin, S Medvedev, A Yan, ZH Adachi, H Hirose, T Jetten, AM TI Induction of the nuclear orphan receptor ROR gamma during adipocyte differentiation of D1 and 3T3-L1 cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID REV-ERBA-ALPHA; GENE-EXPRESSION; PPAR-GAMMA; TRANSCRIPTIONAL REPRESSION; HORMONE RECEPTORS; SIGNATURE MOTIF; MESSENGER-RNAS; CO-REPRESSOR; PROTEIN; LIGAND AB Here, we analyzed the expression of the three members of the retinoid-like orphan receptor (ROR) nuclear receptor subfamily during adipocyte differentiation, ROR alpha and ROR gamma mRNA were up-regulated during adipocyte differentiation in preadipocyte D1 and 3T3-L1 cells, whereas ROR beta mRNA could not be detected, The induction of ROR alpha and ROR gamma mRNA succeeded the induction of peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein alpha and occurred at a similar time interval as did the increase in aP2 and lipoprotein lipase mRNA. Like the expression of PPAR gamma and aP2, the induction of ROR gamma mRNA was repressed by tumor necrosis factor alpha and transforming growth factor beta. The induction of adipogenesis by prostaglandin D2 and two thiazolidinediones in the multipotent stem cells C3H10T1/2 was also accompanied by an induction in ROR gamma mRNA, In contrast to parental cells, clofibrate induces adipogenesis and ROR alpha and ROR gamma mRNA in BALB/ c3T3 cells that ectopically express PPAR gamma, ROR gamma mediates its effect on transcription through specific response elements. Cotransfection of ROR alpha or ROR gamma and (ROR gamma response element)(4)-chloramphenicol acetyltransferase into preadipocyte D1 cells induced transactivation of chloramphenicol acetyltransferase about 100-fold, suggesting that ROR plays a role in the regulation of gene expression in adipocytes, The nuclear orphan receptor Rev-ErbA alpha, which did not exhibit transactivation function, was able to inhibit transactivation by ROR gamma at two different levels. Our results show that ROR gamma is induced during adipocyte differentiation in D1 and 3T3-L1 cells and functions as an active transcription factor, suggesting a role for ROR gamma in the regulation of gene expression during this differentiation process. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. Osaka Univ, Sch Med, Dept Med 3, Osaka 565, Japan. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 51 TC 37 Z9 39 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1998 VL 9 IS 3 BP 267 EP 276 PG 10 WC Cell Biology SC Cell Biology GA ZB255 UT WOS:000072452700008 PM 9543393 ER PT J AU Borlongan, CV Koutouzis, TK Poulos, SG Saporta, S Sanberg, PR AF Borlongan, CV Koutouzis, TK Poulos, SG Saporta, S Sanberg, PR TI Bilateral fetal striatal grafts in the 3-nitropropionic acid-induced hypoactive model of Huntington's disease SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 6th International Neural Transplant Meeting CY 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Neural Transplantat DE 3-nitropropionic acid; Huntington's disease; neural transplantation; locomotor activity; rat model ID TRANSPLANTATION; ACETYLCHOLINESTERASE; DISORDERS; TISSUE; ZONES AB We investigated the 3-nitropropionic acid (3-NP)-induced hypoactive model of Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can ameliorate behavioral deficits associated with a more advanced stage of HD, Twelve-week-old Sprague-Dawley rats were introduced to the 3-NP dosing regimen (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested for general spontaneous locomotor activity in the Digiscan locomotor apparatus, All rats displayed significant hypoactivity compared to their pre-3-NP injection locomotor activity, Randomly selected rats then received bilateral intrastriatal solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from embryonic day 14 rat fetuses, Approximately 1/3 of each LGE in hibernation medium was infused into each lesioned host striatum, In control rats, medium alone mas infused intrastriatally. A 3-mo posttransplant maturation period was allowed prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited a significant increase in locomotor activity compared to their post-3-NP injection activity or to the controls' posttransplant activity, Surviving striatal grafts mere noted in functionally recovered animals, This observation supports the use of fetal striatal transplants to correct the akinetic stage of HD, To the best of our knowledge, this is the first study that has investigated the effects of fetal striatal transplantation in a hypoactive model of HD, (C) 1998 Elsevier Science Inc. C1 Univ S Florida, Coll Med, Div Neurol Surg, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Program Neurosci, Dept Surg, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Program Neurosci, Dept Neurol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Program Neurosci, Dept Psychiat, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Program Neurosci, Dept Psychol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Program Neurosci, Dept Pharmacol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Anat, Tampa, FL 33612 USA. RP Borlongan, CV (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 20 TC 26 Z9 26 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAR-APR PY 1998 VL 7 IS 2 BP 131 EP 135 DI 10.1016/S0963-6897(97)00170-X PG 5 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA ZG806 UT WOS:000073041700006 PM 9588595 ER PT J AU Butera, RJ AF Butera, RJ TI Multirhythmic bursting SO CHAOS LA English DT Article ID MODEL; NEURON; OSCILLATIONS; BISTABILITY; SEROTONIN; DYNAMICS; APLYSIA; MEMORY; SYSTEM; DISSECTION AB A complex modeled bursting neuron [C. C. Canavier, J. W. Clark, and J. H. Byrne, J. Neurophysiol. 66, 2107-2124 (1991)] has been shown to possess seven coexisting limit cycle solutions at a given parameter set [Canavier et at, J. Neurophysiol 69, 2252-2259 (1993); 72, 872-882 (1994)]. These solutions are unique in that the limit cycles are concentric in the space of the slow variables. We examine the origin of these solutions using a minimal 4-variable bursting cell model. Poincare maps are constructed using a saddle-node bifurcation of a fast subsystem such as our Poincare section. This bifurcation defines a threshold between the active and silent phases of the burst cycle in the space of the slow variables. The maps identify parameter spaces with single limit cycles, multiple limit cycles, and two types of chaotic bursting. To investigate the dynamical features which underlie the unique shape of the maps, the maps are further decomposed into two submaps which describe the solution trajectories during the active and silent phases of a single burst. From these findings we postulate several necessary criteria for a bursting model to possess multiple stable concentric limit cycles. These criteria are demonstrated in a generalized 3-variable model. Finally, using a less direct numerical procedure, similar return maps are calculated for the original complex model [C. C. Canavier, J. W. Clark, and J. H. Byrne, J. Neurophysiol. 66, 2107-2124 (1991)], with the resulting mappings appearing qualitatively similar to those of our 4-variable model. These multistable concentric bursting solutions cannot occur in a bursting model with one slow variable. This type of multistability arises when a bursting system has two or more slow variables and is viewed as an essentially second-order system which receives discrete perturbations in a state-dependent manner. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20814 USA. RP Butera, RJ (reprint author), NIDDKD, Math Res Branch, NIH, 9190 Wisconsin Ave,Suite 350, Bethesda, MD 20814 USA. NR 35 TC 24 Z9 25 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 1054-1500 J9 CHAOS JI Chaos PD MAR PY 1998 VL 8 IS 1 BP 274 EP 284 DI 10.1063/1.166358 PG 11 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA ZC947 UT WOS:000072635100024 ER PT J AU Ware, JA Graf, MLM Martin, BM Lustberg, LR Pohl, LR AF Ware, JA Graf, MLM Martin, BM Lustberg, LR Pohl, LR TI Immunochemical detection and identification of protein adducts of diclofenac in the small intestine of rats: Possible role in allergic reactions SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ANTIINFLAMMATORY DRUG DICLOFENAC; SUCRASE-ISOMALTASE COMPLEX; ORAL TOLERANCE; COVALENT BINDING; EPITHELIAL-CELLS; INDUCED HEPATOTOXICITY; MEMBRANE-PROTEINS; ACYL GLUCURONIDES; AMINOPEPTIDASE-N; SODIUM VOLTAREN AB Idiosyncratic adverse drug reactions are unpredictable, target multiple organ systems, and often become life-threatening events. Although the causes of idiosyncratic adverse drug reactions are not known in most cases, evidence suggests that they may be mediated through immunological mechanisms, It is generally thought that for a drug to lead to an immune response, it must first become covalently bound to a carrier protein. Since most drugs are unreactive, it is usually a reactive metabolite that is expected to form covalent adducts, However, it is not clear why more people do not develop immune reactions against drug-protein adducts. One possible explanation is that orally administered drugs may lead to oral tolerance in most individuals through mechanisms similar to that found with orally administered antigens. However, very little is known regarding the interaction of drugs with gut-associated lymphoid tissue of the small intestine, where oral tolerance call develop. As an initial step to test this hypothesis, we have investigated whether diclofenac, a commonly used nonsteroidal antiinflammatory drug, call lead to protein adducts in rat small intestine. Diclofenac was administered to rats by gastric gavage. Immunoblot analysis of small intestine homogenates and isolated enterocyte subcellular fractions with drug-specific antiserum revealed 142-, 130-, 110-, and 55-kDa protein adducts of diclofenac. The 142- and 130-kDa adducts of diclofenac were identified as aminopeptidase N (CD13) and sucrase-isomaltase, respectively, by amino acid sequence analyses and by their reactions with protein-specific antibodies. The adducts were localized by immunohistochemistry and found primarily in the mid-villus and villus-tip enterocytes and also in the dome overlying Peyer's patches. Similar adducts were detected immunochemically in villus-tip enterocytes of animals treated with halothane or acetaminophen. These results show that intestinal protein adducts of drugs can be formed in gut-associated lymphoid tissue where they may lead to the down-regulation of drug-induced allergic reactions in many individuals. C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bldg 10,Rm 8N110, Bethesda, MD 20892 USA. EM warej@gwgate.nhlbi.nih.gov NR 64 TC 50 Z9 50 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1998 VL 11 IS 3 BP 164 EP 171 DI 10.1021/tx970182j PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA ZD197 UT WOS:000072661100002 PM 9544613 ER PT J AU Misra, RR Page, JE Smith, GT Waalkes, MP Dipple, A AF Misra, RR Page, JE Smith, GT Waalkes, MP Dipple, A TI Effect of cadmium exposure on background and anti-5-methylchrysene-1,2-dihydrodiol 3,4-epoxide-induced mutagenesis in the supF gene of pS189 in human Ad293 cells SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CHINESE-HAMSTER CELLS; CULTURED-MAMMALIAN-CELLS; OXYGEN RADICALS; METAL-IONS; DNA-REPAIR; SPECIFICITY; INDUCTION; CHLORIDE; MUTATIONS; 5-METHYLCHRYSENE AB Cadmium is a toxic environmental contaminant that is carcinogenic in humans and rodents. Although cadmium has proven to be mutagenic in a variety of assay systems, exactly how cadmium achieves gentoxicity is poorly understood. To define the mechanism(s) underlying the mutagenicity and comutagenicity of cadmium, human Ad293 cells were exposed to subtoxic doses of the metal and transfected with untreated or anti-5-methylchrysene-3,4-dihydrodiol 1,2-epoxide (5-MCDE)-treated pS189 shuttle vector. Alterations in the frequency, types, and distribution of mutations were subsequently assessed in the supF gene of pS189 that was replicated in Ad293 cells and screened in indicator bacteria. Doses of 0.5 and 1 mu M CdCl2 increased the mutation frequency of untreated pS189 by approximately 4- and 8-fold, respectively, with no apparent effect on the types of mutations generated. In contrast, host-cell exposure to cadmium had little or no effect on the frequency, types, or distribution of mutations generated with 5-MCDE-treated pS189. These results indicate that cadmium increases mutagenesis of untreated pS189 by affecting a process that is not involved in mutagenesis of the 5-MCDE-treated vector. Although it is not clear exactly how host-cell exposure to cadmium increases background mutagenesis, presumably, the mutagenic effect does not involve cadmium interaction with the cellular machinery used to replicate past bulky DNA lesions. C1 NCI, Frederick Canc Res & Dev Ctr, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab,Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. RP Misra, RR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab,Div Basic Sci, Bldg 538,Rm 205E, Frederick, MD 21702 USA. NR 39 TC 8 Z9 8 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1998 VL 11 IS 3 BP 211 EP 216 DI 10.1021/tx970183b PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA ZD197 UT WOS:000072661100008 PM 9544619 ER PT J AU Wiener, LS Battles, HB Heilman, NE AF Wiener, LS Battles, HB Heilman, NE TI Factors associated with parents' decision to disclose their HIV diagnosis to their children SO CHILD WELFARE LA English DT Article AB Parents report that trying to decide whether or not to disclose their HIV diagnosis to their children is as emotionally charged as learning of the diagnosis itself. As part of a larger study, interviews were conducted with 17 parent-child dyads recruited from patients being treated at the National Cancer Institute to understand the factors that affect the process of disclosure of a parent's HIV diagnosis and its consequences. Parents and HIV-infected children were also interviewed and were administered several standardized measures for collecting information on parental depression, family environment, and social support satisfaction. The factors associated with a parent's decision to disclose his or her diagnosis to the children, and implications for clinical practice and future research, are discussed. C1 NCI, Pediat HIV Psychosocial Support Program, Bethesda, MD 20892 USA. NCI, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA. Good Samaritan Hosp, Puyallup, WA USA. RP Wiener, LS (reprint author), NCI, Pediat HIV Psychosocial Support Program, Bethesda, MD 20892 USA. NR 21 TC 41 Z9 43 U1 0 U2 0 PU CHILD WELFARE LEAGUE AMER, INC PI WASHINGTON PA 440 FIRST ST, NW, THIRD FLOOR, WASHINGTON, DC 20001-2085 USA SN 0009-4021 J9 CHILD WELFARE JI Child Welf. PD MAR-APR PY 1998 VL 77 IS 2 BP 115 EP 135 PG 21 WC Family Studies; Social Work SC Family Studies; Social Work GA YZ850 UT WOS:000072300400004 PM 9513994 ER PT J AU Deng, XY Cao, Y Cao, L Lee, LM Yao, KT AF Deng, XY Cao, Y Cao, L Lee, LM Yao, KT TI Point mutation of 2.8 kb EcoRI fragment of the NPC transforming gene in NPC cell lines SO CHINESE MEDICAL JOURNAL LA English DT Article C1 Hunan Med Univ, Canc Res Inst, Lab Tumor Mol Biol, Changsha 410078, Hunan, Peoples R China. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Deng, XY (reprint author), Hunan Med Univ, Canc Res Inst, Lab Tumor Mol Biol, Changsha 410078, Hunan, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHINESE MEDICAL ASSOCIATION PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD MAR PY 1998 VL 111 IS 3 BP 247 EP 247 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZC040 UT WOS:000072533500021 ER PT J AU Langford, CA AF Langford, CA TI The diagnostic utility of c-ANCA in Wegener's granulomatosis SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; CRESCENTIC GLOMERULONEPHRITIS; INDIRECT IMMUNOFLUORESCENCE; AUTOANTIBODIES; VASCULITIS; BIOPSIES; ANTIGEN AB Anti-neutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) have been found to have a high degree of sensitivity and specificity for Wegener's granulomatosis. Nevertheless, despite the attraction of using this autoantibody as a diagnostic test, in almost all instances it should not be used in place of a biopsy to diagnose Wegener's granulomatosis. C1 NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, Lab Immunoregulat, NIH, Bldg 10,Room 11B-13, Bethesda, MD 20892 USA. NR 29 TC 27 Z9 28 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD MAR PY 1998 VL 65 IS 3 BP 135 EP 140 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZB467 UT WOS:000072474900003 PM 9540246 ER PT J AU Conley, BA Egorin, MJ Tait, N Rosen, DM Sausville, EA Dover, G Fram, RJ Van Echo, DA AF Conley, BA Egorin, MJ Tait, N Rosen, DM Sausville, EA Dover, G Fram, RJ Van Echo, DA TI Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID CARCINOMA CELL-PROLIFERATION; ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; CHAIN FATTY-ACIDS; DIFFERENTIATION THERAPY; SODIUM-BUTYRATE; HEXAMETHYLENE BISACETAMIDE; PHENYLACETATE; COMBINATION; ENHANCEMENT AB Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines irt vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mw. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day. C1 Univ Maryland, Sch Med, Dept Med, Div Hematol Oncol, Baltimore, MD 21201 USA. Univ Maryland, Div Dev Therapeut, Baltimore, MD 21201 USA. Univ Maryland, Greenebaum Canc Ctr, Program Oncol, Baltimore, MD 21201 USA. NCI, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. RP Conley, BA (reprint author), NCI, Clin Invest Branch, Canc Therapy Evaluat Program, 741 Execut Plaza N,6130 Execut Blvd, Rockville, MD 20852 USA. FU NCI NIH HHS [U01-CA-69854] NR 24 TC 103 Z9 104 U1 0 U2 4 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 MAR PY 1998 VL 4 IS 3 BP 629 EP 634 PG 6 WC Oncology SC Oncology GA ZC038 UT WOS:000072533300013 PM 9533530 ER PT J AU Budd, GT Adamson, PC Gupta, M Homayoun, P Sandstrom, SK Murphy, RF McLain, D Tuason, L Peereboom, D Bukowski, RM Ganapathi, R AF Budd, GT Adamson, PC Gupta, M Homayoun, P Sandstrom, SK Murphy, RF McLain, D Tuason, L Peereboom, D Bukowski, RM Ganapathi, R TI Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; GROWTH-FACTOR-I; GENE-EXPRESSION; CELL-LINES; DIFFERENTIATION THERAPY; CARCINOMA CELLS; INHIBITION; PHARMACOKINETICS; PLASMA; BIOAVAILABILITY AB Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer, Patients with potentially hormone-responsive advanced breast cancer were enrolled, All received 20 mg of tamoxifen by mouth daily, Consecutive cohorts of 3-6 patients were treated on odd-numbered weeks with ATRA at doses of 70, 110, 150, 190, or 230 mg/m(2)/day, Twenty-six patients were entered in this trial; 25 were evaluable, A dose of 230 mg/m(2) ATRA produced unacceptable headache and dermatological toxicity, but doses less than or equal to 190 mg/m(2) were tolerable. Two of 7 patients with measurable disease responded, Seven of 18 patients with evaluable, nonmeasurable disease achieved disease stability for more than 6 months, Plasma AUCs on day 1 of successive weeks of treatment were stable over time, A nonsignificant decrease in serum insulin-like growth factor I levels was noted during treatment, but this trend was similar to that observed in three "control" patients treated with tamoxifen alone, When given with daily tamoxifen, the maximum tolerated dose of ATRA that could be given on alternate weeks was 190 mg/m(2)/day, This schedule of ATRA resulted in repeated periods of exposure to potentially therapeutic concentrations of ATRA, Declines in the serum insulin-like growth factor I concentrations observed in patients treated with tamoxifen and ATRA were similar to those observed in patients treated with tamoxifen alone, Objective responses were observed, some in patients who had previously progressed while receiving tamoxifen, suggesting that further studies would be of interest. C1 Cleveland Clin Fdn, Dept Med Oncol, Cleveland, OH 44195 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. RP Budd, GT (reprint author), Cleveland Clin Fdn, Dept Med Oncol, Desk T-40,9500 Euclid Ave, Cleveland, OH 44195 USA. EM buddg@cesmtp.ccf.org NR 49 TC 61 Z9 62 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 MAR PY 1998 VL 4 IS 3 BP 635 EP 642 PG 8 WC Oncology SC Oncology GA ZC038 UT WOS:000072533300014 PM 9533531 ER PT J AU Slovin, SF Scher, HI Divgi, CR Reuter, V Sgouros, G Moore, M Weingard, K Pettengall, R Imbriaco, M El-Shirbiny, A Finn, R Bronstein, J Brett, C Milenic, D Dnistrian, A Shapiro, L Schlom, J Larson, SM AF Slovin, SF Scher, HI Divgi, CR Reuter, V Sgouros, G Moore, M Weingard, K Pettengall, R Imbriaco, M El-Shirbiny, A Finn, R Bronstein, J Brett, C Milenic, D Dnistrian, A Shapiro, L Schlom, J Larson, SM TI Interferon-gamma and monoclonal antibody I-131-labeled CC49: Outcomes in patients with androgen-independent prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; CARCINOEMBRYONIC ANTIGEN; ENDOTHELIAL-CELLS; BREAST-CANCER; BONE; CARCINOMA; TAG-72; TRIAL; ADENOCARCINOMAS; CHEMOTHERAPY AB To assess the tumor targeting, safety, and efficacy of monoclonal antibody I-131-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m(2) of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining, Fourteen patients received I-131-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used, The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects, In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain, No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months, The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity, For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response. C1 Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Radiol, Nucl Med Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Med Phys, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Pathol, Lab Dev Hematopoiesis, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Clin Chem, New York, NY 10021 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Dept Med, New York, NY 10021 USA. RP Scher, HI (reprint author), Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Med, Genitourinary Oncol Serv, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [CA05826, CA09512] NR 35 TC 52 Z9 53 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 MAR PY 1998 VL 4 IS 3 BP 643 EP 651 PG 9 WC Oncology SC Oncology GA ZC038 UT WOS:000072533300015 PM 9533532 ER PT J AU Srivastava, RK Srivastava, AR Cho-Chung, YS AF Srivastava, RK Srivastava, AR Cho-Chung, YS TI Synergistic effects of 8-chlorocyclic-AMP and retinoic acid on induction of apoptosis in Ewing's sarcoma CHP-100 cells SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; REGULATORY SUBUNIT; ANTISENSE OLIGODEOXYNUCLEOTIDE; DIFFERENTIATION; GROWTH; CANCER; BIOSYNTHESIS; ACTIVATION; RECEPTOR; THERAPY AB The enhanced expression of the regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase type I, RIalpha, has been correlated with cancer cell growth. Retinoic acid (RA) has been shown to play an important role in the regulation of proliferation and differentiation in neoplastic cells, In the present study, the effects of cAMP analogue 8-chlorocyclic-AMP (8-Cl-cAMP) and RA (both singly and combined) on growth inhibition and apoptosis in Ewing's sarcoma CHP-100 cells were evaluated. The inhibitory effects of 8-Cl-cAMP and RA (9-cis-RA, 13-cis-RA, and all-trans-RA) on cell viability were time and dose related. The degree of growth inhibition induced by 9-cis-RA was the greatest among all of the RA analogues (13-cis-RA and all-trans-RA) examined. The combined effects of 8-Cl-cAMP and RA on the induction of growth arrest at the G(0)-G(1) stage of the cell cycle, apoptosis, down-regulation of RIalpha, and cleavage of poly(ADP-ribose) polymerase were synergistic. In conclusion, it is clear that RA and 8-Cl-cAMP act in a synergistic fashion and have potential for combination chemotherapy for the treatment of malignant disease. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 28 TC 17 Z9 17 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 MAR PY 1998 VL 4 IS 3 BP 755 EP 761 PG 7 WC Oncology SC Oncology GA ZC038 UT WOS:000072533300028 PM 9533545 ER PT J AU Ming, JE Muenke, M AF Ming, JE Muenke, M TI Holoprosencephaly: from Homer to Hedgehog SO CLINICAL GENETICS LA English DT Review DE holoprosencephaly; brain development; Sonic Hedgehog; cholesterol ID SONIC-HEDGEHOG; SIGNALING PATHWAY; GENE; INDUCTION; MICE; PERSPECTIVES; DROSOPHILA; MUTATIONS; POLARITY; RECEPTOR AB Holoprosencephaly (HPE), a common developmental defect affecting the forebrain and face, is etiologically heterogeneous and exhibits wide phenotypic variation. Graded degrees of severity of the brain malformation are also reflected in the highly variable craniofacial malformations associated with HPE. In addition, Individuals with microforms of HPE, who usually have normal cognition and normal brain imaging, are at risk for having children with HPE. Some obligate carriers fbr HPE may not have any phenotypic abnormalities. Recurrent chromosomal rearrangements in individuals with HPE suggest loci containing genes important for brain development, and abnormalities in these genes may result in HPE, Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in humans. Proper function of SHH depends on cholesterol modification. Other candidate genes that may be involved in HPE include components of the SHH pathway, elements involved in cholesterol metabolism, and genes expressed in the: developing forebrain. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10-C-101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD 29862, HD28732, 5T32HD07107] NR 70 TC 94 Z9 95 U1 1 U2 2 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 MAR PY 1998 VL 53 IS 3 BP 155 EP 163 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA ZL556 UT WOS:000073446200001 PM 9630065 ER PT J AU Henderson, DK AF Henderson, DK TI Editorial response: Occupational infection with hepatitis B virus - Waging war against an insidious, intractable, intolerable foe SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HEALTH-CARE WORKERS; VACCINATION; PERSONNEL C1 NIH, Warren G Magnuson Clin Ctr, Clin Care, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Warren G Magnuson Clin Ctr, Clin Care, Bldg 10,Room 2C146, Bethesda, MD 20892 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1998 VL 26 IS 3 BP 572 EP 574 DI 10.1086/514574 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YZ745 UT WOS:000072287400004 PM 9524824 ER PT J AU Weng, DE Wilson, WH Little, R Walsh, TJ AF Weng, DE Wilson, WH Little, R Walsh, TJ TI Successful medical management of isolated renal zygomycosis: Case report and review SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID AIDS PATIENT; MUCORMYCOSIS; INFECTIONS; PHYCOMYCOSIS; LYMPHOMA AB We describe the medical management of isolated renal zygomycosis in an adult patient with AIDS during chemotherapy for AIDS-related lymphoma. After initial presentation during the first cycle of chemotherapy, the infection was contained within the kidney following recovery of the neutrophil count without medical or surgical intervention. Since he was not considered to be a candidate for nephrectomy, his infection was treated with amphotericin B lipid complex during subsequent chemotherapy. Neutropenia was minimized by the addition of cytokine support therapy with granulocyte colony-stimulating factor and reduced doses of chemotherapy. Following this strategy, his lymphoma completely resolved, and renal zygomycosis was controlled. At the time of this writing, he had been in complete remission for 18 months without evidence of progressive fungal infection, This report and our literature review indicate that isolated renal zygomycosis can be associated with a favorable prognosis, occurs with greatest frequency in patients with AIDS, is associated with parenteral access, and may be managed by medical therapy alone. C1 NCI, Med Branch, Div Clin Sci, HIV & AIDS Malignancy Branch,NIH, Bethesda, MD USA. NCI, Pediat Branch, Div Clin Sci, NIH, Bethesda, MD USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, NIH, Bldg 10,Room 13N-240, Bethesda, MD 20892 USA. NR 29 TC 41 Z9 42 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1998 VL 26 IS 3 BP 601 EP 605 DI 10.1086/514562 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YZ745 UT WOS:000072287400010 PM 9524830 ER PT J AU Goelz, MF Dixon, D Myers, PH Clark, JA Forsythe, DB AF Goelz, MF Dixon, D Myers, PH Clark, JA Forsythe, DB TI Ganglioneuroma in the adrenal gland of a rat SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article AB Necropsy was performed on a 22-month-old male Fischer 344 rat (Rattus norvegicus) that had weight loss and was icteric. Examination revealed a large, smooth, circumscribed, tan mass located at the cranial border of the right kidney. Microscopically, the mass consisted almost entirely of well-differentiated ganglion cells mixed with satellite and Schwann cells within a neurofibrillar matrix. The cells displaced the adrenal medulla and were partially surrounded by a thin rim of compressed adrenal cortex. Focal areas of hemorrhage and infiltrates of leukemic mononuclear cells were evident throughout the mass, but pheochromocytes were not detected. On the basis of finding during histologic examination, a diagnosis of adrenal medullary ganglioneuroma was made. Mononuclear cell leukemia was also diagnosed in the adrenal gland and was evident in lymphoid organs such as the spleen and mesenteric lymph nodes. Ganglioneuroma is rarely seen in rats and can be differentiated from more common complex pheochromocytomas, which consist of fewer neural components (<80% of the mass). In rats, ganglioneuromas can develop in the central nervous system, pituitary gland, and thyroid gland. Differential diagnoses for a primary neoplasm of the adrenal gland should include carcinomas and adenomas of the adrenal cortex, and pheochromocytomas, neuroblastomas, and ganglioneuromas of the adrenal medulla. C1 NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Goelz, MF (reprint author), NIEHS, Comparat Med Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 20 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAR PY 1998 VL 37 IS 2 BP 75 EP 77 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA ZD396 UT WOS:000072681000012 PM 12456176 ER PT J AU Anglade, E Csaky, KG AF Anglade, E Csaky, KG TI Recombinant adenovirus-mediated gene transfer into the adult rat retina SO CURRENT EYE RESEARCH LA English DT Article DE adenovirus; gene therapy; rodent; beta-galactosidase ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; INFLAMMATORY RESPONSE; OCULAR-TISSUES; LIGHT DAMAGE; EFFICIENCY; CELLS; DEGENERATION; EPITHELIUM; EXPRESSION; STABILITY AB Purpose. The present study was designed to evaluate the feasibility of gene transfer into the retina of adult rats, using a recombinant replication-defective adenovirus vector expressing a reporter gene. Methods. Purified recombinant adenovirus expressing beta-galactosidase (lacZ) (Ad5.hCMV.lacZ) at doses ranging from 1.4 X 10(2) to 1.4 x 10(6) plaque-forming units (pfu) were injected into the subretinal space of adult Lewis rats. The presence of lacZ was determined by histochemical assay and reverse transcription and polymerase chain reaction analysis (RT PCR) of total RNA extracted from eyes injected with recombinant adenovirus expressing lacZ. Results. As assessed by biomicroscopy, the expression of lacZ was highest in the retinal pigment epithelium in a localized area corresponding to the site of injection. The level of lacZ expression was correlated with the amount of virus delivered to the subretinal space. Persistent but decreasing expression of lacZ was noted over time. RT PCR revealed the expression of messenger RNA for at least sixty days. Conclusions. The results of this study demonstrate that efficient and stable transfer of genetic material into the subretinal space of adult fats may be achieved using a recombinant adenoviral vector The use of such vectors should prove useful in developing novel applications and approaches to the study of recombinant protein expression in vivo. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Csaky, KG (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N-119,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kcsaky@helix.nih.gov NR 40 TC 27 Z9 28 U1 0 U2 0 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAR PY 1998 VL 17 IS 3 BP 316 EP 321 DI 10.1076/ceyr.17.3.316.5221 PG 6 WC Ophthalmology SC Ophthalmology GA ZB521 UT WOS:000072480900013 PM 9543641 ER PT J AU Savage, PJ AF Savage, PJ TI Treatment of diabetes mellitus to reduce its chronic cardiovascular complications SO CURRENT OPINION IN CARDIOLOGY LA English DT Review ID INSULIN-RESISTANCE; HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; TRIAL; DYSLIPIDEMIA; MORTALITY AB Cardiovascular complications are a major cause of morbidity and mortality in patients with diabetes mellitus, Diabetes is a heterogeneous, complex metabolic disorder, and it is unlikely that control of hyperglycemia alone will eliminate the excess of cardiac, cerebral, and peripheral vascular diseases found in diabetic patients. In the care of the diabetic patient, glucose levels should be reduced to normal ii possible. In addition, however, it is crucial to evaluate and, if necessary, to correct abnormalities in lipids, blood pressure, and hemostasis. The importance of reducing levels of insulin and insulin resistance is not yet clear. Although many questions remain to be answered, available data strongly suggest that patients with diabetes benefit from more aggressive and comprehensive treatment. (C) 1998 Rapid Science Publishers. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20817 USA. RP Savage, PJ (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Room 8104,Rockledge II,6701 Rockledge Dr, Bethesda, MD 20817 USA. NR 38 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAR PY 1998 VL 13 IS 2 BP 131 EP 138 DI 10.1097/00001573-199803000-00010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZH474 UT WOS:000073114200010 PM 9593553 ER PT J AU Park, MS Eanes, ED Antonucci, JM Skrtic, D AF Park, MS Eanes, ED Antonucci, JM Skrtic, D TI Mechanical properties of bioactive amorphous calcium phosphate/methacrylate composites SO DENTAL MATERIALS LA English DT Article ID PHOSPHATE CEMENTS AB Objectives. The aim of this study was to determine whether amorphous calcium phosphate (ACP)-containing composites, which have the ability to release mineralizing levels of Ca and PO4 ions, have appropriate mechanical properties for use as base and lining materials. Methods. Composites of pyrophosphate-stabilized ACP particulates (mass fraction of 40%) and photo-activated methacrylate resins (mass fraction of 60%) were tested for biaxial flexure strength (BFS), diametral tensile strength (DTS), and compressive strength (CS). Hydroxyapatite (HAP; mass fraction of 40%), and micro-sized glass (mass fraction of 50%) composites as well as a commercial visible light curable base/liner were also tested. The significance between mean values was determined by Student-Newman-Keuls multiple comparisons (p < 0.05). Results. BFS of dry and wet (24 h at 37 degrees C in water) ACP composites (60.3 and 62.0 MPa, respectively) were significantly lower than those of the comparison materials (79.2-109.3 MPa). CS values were likewise lower (62.9 MPa dry and 67.6 MPa wet vs 80.6-196.8 MPa) except for the wet base/liner (58.5 MPa). DTS of the dry ACP composite (21.8MPa) was comparable with that of the HAP (22.8 MPa) and glass (25.5 MPa) composites, but tower than that of the base/liner (36.2 MPa). DTS decreased significantly when the ACP composite was wet (17.8 MPa). Significance. These results suggest that the remineralizing ACP polymeric composites, although mechanically weaker in some respects than other polymeric composites, have properties suitable for use as base and lining materials. (C) 1998 Academy of Dental Materials. Published by Elsevier Science Ltd. C1 Natl Inst Stand & Technol, DMMG, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, PRC, ADAHF, Gaithersburg, MD 20899 USA. Phil Dent Clin, Kyung Ki Do, South Korea. NIDR, NIH, Bethesda, MD 20892 USA. RP Antonucci, JM (reprint author), Natl Inst Stand & Technol, DMMG, Bldg 224,Room A143, Gaithersburg, MD 20899 USA. NR 19 TC 40 Z9 41 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD MAR PY 1998 VL 14 IS 2 BP 137 EP 141 DI 10.1016/S0109-5641(98)00020-7 PG 5 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA 149QX UT WOS:000077617800007 PM 10023203 ER PT J AU Boyce, WT Frank, E Jensen, PS Kessler, RC Nelson, CA Steinberg, L AF Boyce, WT Frank, E Jensen, PS Kessler, RC Nelson, CA Steinberg, L CA MacArthur Fdn Res Network Psychopathology Dev TI Social context in developmental psychopathology: Recommendations for future research from the MacArthur network on psychopathology and development SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID JUVENILE RHESUS-MONKEYS; SOCIOECONOMIC-STATUS; PRENATAL STRESS; ADOLESCENT DEVELOPMENT; AFFECTIVE-DISORDER; LIFE EVENTS; CHILDREN; FAMILY; DEPRESSION; ENVIRONMENT AB Accumulating evidence suggests that social contexts in early life have important and complex effects on childhood psychopathology. Spurred by the lack of an explicit operational definition that could guide the study of such effects, we define a social context operationally as "a set of interpersonal conditions, relevant to a particular behavior or disorder and external to, but shaped and interpreted by, the individual child." Building on this definition, we offer a series of recommendations for future research, based on five theoretically derived propositions: (a) Contexts are nested and multidimensional; (b) contexts broaden, differentiate, and deepen with age, becoming more specific in their effects; (c) contexts and children are mutually determining; (d) a context's meaning to the child determines its effects on the child and arises from the context's ability to provide for fundamental needs; and (e) contexts should be selected for assessment in light of specific questions or outcomes. As reflected in an increasingly rich legacy of literature on child development and psychopathology, social contexts appear to influence emerging mental disorders through dynamic, bidirectional interactions with individual children. Future research will benefit from examining not only statistical interactions between child-and context-specific factors, but also the actual transactions between children and contexts and the transduction of contextual influences into pathways of biological mediation. Because adverse contexts exert powerful effects on the mental health of children, it is important for the field to generate new, more theoretically grounded research addressing the contextual determinants of psychological well-being and disorder. C1 Univ Calif Berkeley, Sch Publ Hlth, Div Hlth & Med Sci, Berkeley, CA 94720 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIMH, Rockville, MD 20857 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Temple Univ, Philadelphia, PA 19122 USA. RP Boyce, WT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Hlth & Med Sci, 570 Univ Hall,1190, Berkeley, CA 94720 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 157 TC 110 Z9 111 U1 2 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 1998 VL 10 IS 2 BP 143 EP 164 DI 10.1017/S0954579498001552 PG 22 WC Psychology, Developmental SC Psychology GA ZT229 UT WOS:000074063500002 PM 9635219 ER PT J AU Drago, J Padungchaichot, P Accili, D Fuchs, S AF Drago, J Padungchaichot, P Accili, D Fuchs, S TI Dopamine receptors and dopamine transporter in brain function and addictive behaviors: Insights from targeted mouse mutants SO DEVELOPMENTAL NEUROSCIENCE LA English DT Review DE dopamine receptors; dopamine transporter; addiction; cocaine; amphetamine; striatum; nucleus accumbens; neuropeptide ID VENTRAL TEGMENTAL AREA; IMMEDIATE-EARLY GENE; INSITU HYBRIDIZATION HISTOCHEMISTRY; FREELY MOVING RATS; D2 D2A RECEPTORS; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; PARKINSONS-DISEASE; MOLECULAR-CLONING; TRANSGENIC MICE AB Recent advances in molecular biology have resulted in a number of genetically manipulated mice with defined changes at dopamine receptor and the dopamine transporter (DAT) loci. Mice with targeted mutations at the D1 receptor (D1R) are growth-retarded and show down-regulated expression of dynorphin and substance P. Behavioral assessment indicates that mutants have deficiencies in spatial learning and initiating movement, as well as in responding to novel stimuli. DIR mutants do not become locomotor activated with cocaine or show upregulated immediate early gene (IEG) expression, but D2 receptor-dependent IEG changes are intact. Acute cocaine administration increases substance P levels, suggesting that striatal expression of this neuropeptide can be modulated by D1R-independent processes. Failure of locomotor activation is also seen With repeated amphetamine treatment, Surprisingly, D1R-deficient mice retain cocaine-conditioned place preference, In contrast, D2 receptor knockout mice are bradykinetic, show increased striatal enkephalin expression and an absence of opiate rewarding effects. D3 receptor mutants are hyperactive when assessed in an exploratory assay and display reduced anxiety-associated behavior in an elevated plus maze test. The recently described D4 receptor homozygous mutants exhibit a reduction in baseline locomotor activity and were shown to be super-sensitive to the locomotor activating effects of alcohol and psychostimulant drugs. As expected, DAT knockout mice are hyperactive and do not respond to cocaine or amphetamine. The observation that D2 and D4 dopamine receptor and DAT mutants show compensatory effects, together with the complicating issue of their hybrid genetic background may temper conclusions regarding the direct effects of the targeted mutation on phenotype. C1 Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. Natl Inst Child Hlth & Human Dev, Dev Endocrinol Branch, Bethesda, MD USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Drago, J (reprint author), Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. EM John.Drago@med.monash.edu.au NR 127 TC 72 Z9 76 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAR-JUN PY 1998 VL 20 IS 2-3 BP 188 EP 203 DI 10.1159/000017313 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 110PZ UT WOS:000075390700009 PM 9691193 ER PT J AU Ariano, MA Drago, J Sibley, DR Levine, MS AF Ariano, MA Drago, J Sibley, DR Levine, MS TI Striatal excitatory amino acid receptor subunit expression in the D-1A-dopamine receptor-deficient mouse SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE dopamine receptor knockout; excitatory amino acid receptors; immunofluorescence; striatum ID SELECTIVE GLUTAMATE RECEPTORS; NEUROMODULATORY ACTIONS; NEOSTRIATAL NEURONS; MOLECULAR-CLONING; NMDA RECEPTOR; RAT-BRAIN; DOPAMINE; LOCALIZATION; SUBTYPES; LIGHT AB The influence of dopamine receptor deletion on the expression and distribution of striatal excitatory amino acid (EAA) receptor subunits comprising the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtypes were examined in the D-1A dopamine (DA) receptor-deficient mouse. EAA receptor subunit immunofluorescent staining was altered by the DA receptor genetic mutation. The NMDA-R-1 subunit was used as a marker for NMDA-type receptors, The number of striatal neurons expressing this subunit decreased and there was a modest attenuation in the neuropil staining in the mutants in contrast to littermate controls. The R-1 subunit for the glutamate receptor (GluR(1)) was used as an indicator of the AMPA receptor subtype, Immunostaining for this subunit also showed changes induced by deletion of the DA receptor subtype, In contrast to the NMDA-R-1 subunit, neuropil staining for the GluR1 subunit was elevated in the mutant in comparison to littermate controls, such that the immunofluorescent reaction obscured detection of the subunit protein in striatal interneurons. The results are discussed in relation to the potential impact on functional interactions between the EAA and DA systems in the striatum. C1 Finch Univ Hlth Sci Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA. NINDS, ETB, Mol Neuropharmacol Unit, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA USA. Monash Univ, Dept Anat, Clayton, Vic 3168, Australia. RP Ariano, MA (reprint author), Finch Univ Hlth Sci Chicago Med Sch, Dept Neurosci, 3333 Green Bay Rd, N Chicago, IL 60064 USA. EM arianom@mis.finchcms.edu FU NINDS NIH HHS [NS 23079, NS 32277, NS 33538] NR 27 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAR-JUN PY 1998 VL 20 IS 2-3 BP 237 EP 241 DI 10.1159/000017317 PG 5 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 110PZ UT WOS:000075390700013 PM 9691197 ER PT J AU Harris, MI Eastman, RC AF Harris, MI Eastman, RC TI Is there a glycemic threshold for mortality risk? SO DIABETES CARE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; DIABETIC-PATIENTS; COMPLICATIONS; DISEASE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Harris, MI (reprint author), NIDDKD, NIH, Bldg 45,Room 5AN24, Bethesda, MD 20892 USA. NR 25 TC 27 Z9 27 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 1998 VL 21 IS 3 BP 331 EP 333 DI 10.2337/diacare.21.3.331 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YX917 UT WOS:000072093600001 PM 9540010 ER PT J AU Roumain, J Charles, MA de Courten, MP Hanson, RL Brodie, TD Pettitt, DJ Knowler, WC AF Roumain, J Charles, MA de Courten, MP Hanson, RL Brodie, TD Pettitt, DJ Knowler, WC TI The relationship of menstrual irregularity to type 2 diabetes in Pima Indian women SO DIABETES CARE LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; BODY-FAT DISTRIBUTION; INSULIN-RESISTANCE; OBESITY; MELLITUS; HYPERINSULINEMIA; HYPERANDROGENISM; ANDROGEN AB OBJECTIVE- Menstrual irregularity is associated with hyperinsulinemia and hyperandrogenemia in nondiabetic Pima Indian women of child-bearing age. In this population-based study, we determined the relationship of menstrual irregularity to type 2 diabetes in Pima Indian women. RESEARCH DESIGN AND METHODS- Participants for this cross-sectional analysis were 695 nonpregnant Pima Indian women, aged 18-44 years, involved in an ongoing epidemiologic study of diabetes among residents of the Gila River Indian Community of Arizona. Clinical data were collected by questionnaire and an examination that included a 75-g oral glucose tolerance test; diabetes was diagnosed by World Health Organization criteria. Menstrual irregularity was defined as an interval of 3 months or more between menses, when not pregnant, since age 18 years. RESULTS- History of menstrual irregularity was significantly associated with a high prevalence of diabetes (37 vs, 13%; odds ratio = 4.2, 95% CI = 1.6-10.8) in the least obese women (BMI < 30 kg/m(2)), adjusted for the effects of age and overall obesity. This association was, in part, because of greater central obesity in women with irregular menses. In more obese women, there was little association with menstrual irregularity, and diabetes was frequent regardless of menstrual history. CONCLUSIONS- Prevalence of type 2 diabetes is higher among Pima Indian women with a history of menstrual irregularity. The difference is most pronounced among the least obese group of women. This association may be because of insulin resistance and hyperinsulinemia, which predict type 2 diabetes, also causing hyperandrogenism and menstrual irregularity. The findings reinforce the need to evaluate women with menstrual irregularity for hyperglycemia. C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix, AZ 85014 USA. NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. Maricopa Med Ctr, Dept Med, Div Endocrinol, Phoenix, AZ USA. RP Roumain, J (reprint author), NIDDKD, Diabet & Arthrit Epidemiol Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM janine_roumain@nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 27 TC 21 Z9 22 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 1998 VL 21 IS 3 BP 346 EP 349 DI 10.2337/diacare.21.3.346 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YX917 UT WOS:000072093600005 PM 9540014 ER PT J AU Eastman, RC AF Eastman, RC TI Cost-effectiveness of treatment of type 2 diabetes SO DIABETES CARE LA English DT Letter C1 NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Eastman, RC (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bldg 31,Room 9A16,31 Ctr Dr,MSC 2560, Bethesda, MD 20892 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 1998 VL 21 IS 3 BP 464 EP 465 DI 10.2337/diacare.21.3.464 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YX917 UT WOS:000072093600030 PM 9540039 ER PT J AU Notkins, AL Lan, MS Leslie, RDG AF Notkins, AL Lan, MS Leslie, RDG TI IA-2 and IA-2 beta: The immune response in IDDM SO DIABETES-METABOLISM REVIEWS LA English DT Review DE IA-2; protein tyrosine phosphatase (PTP); insulin-dependent diabetes mellitus (IDDM); autoantibodies; genes ID PROTEIN-TYROSINE-PHOSPHATASE; DEPENDENT DIABETES-MELLITUS; GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIBODIES; FIRST-DEGREE RELATIVES; TRANSMEMBRANE PROTEIN; MOLECULAR-CLONING; EXTRACELLULAR REGION; TRYPTIC FRAGMENTS; HUMAN INSULINOMA AB Pancreatic islet cell autoantigens associated with insulin-dependent diabetes mellitus (IDDM) include a recently identified family of protein tyrosine phosphatase-like molecules, notably IA-2 and IA-2 beta. IA-2 is a 979 amino acid transmembrane protein located on human chromosome 2q35, whereas IA-2 beta is 986 amino acids long located on human chromosome 7q36. Comparison of human IA-2 and IA-2 beta showed 74% identity within the intercellular domains, but only 27% indentify within the extracellular domains. These IA-2 molecules are expressed predominantly in cells of neuroendocrine origin, particularly pancreatic islets and brain. Radioimmunoprecipitation with recombinant IA-2 and IA-2 beta has been used to measure autoantibodies to these molecules and their intracellular fragments. Autoantibodies to IA-2 are detected in the majority (60% to 80%) of newly diagnosed IDDM patients and in less than 2% of controls. The major antigenic determinants of both IA-2 and IA-2 beta reside within the C-terminus of their intracellular domains. In first-degree relatives of IDDM patients, the presence of autoantibodies to IA-2 is predictive of IDDM and in combination with autoantibodies to glutamic acid decarboxylase (GAD) the positive predictive value is in the 50% range. The role of IA-2 and IA-2 beta in the pathogenesis of IDDM is still unclear. Identification of these antigens has extended our ability to predict the disease and may be valuable in the search for antigen-specific therapies to prevent IDDM. (C) 1998 John Wiley & Sons, Ltd. C1 NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Med Ctr, Childrens Hosp, Res Inst Children,Dept Pediat & Biometry & Genet, New Orleans, LA USA. St Bartholomews Hosp, Dept Diabet & Metab, London, England. RP Notkins, AL (reprint author), NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 67 TC 16 Z9 17 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD MAR PY 1998 VL 14 IS 1 BP 85 EP 93 DI 10.1002/(SICI)1099-0895(199803)14:1<85::AID-DMR205>3.0.CO;2-I PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 101FN UT WOS:000074859100005 PM 9605631 ER PT J AU Notkins, AL AF Notkins, AL TI Intervention for diabetes prevention at neonatal age SO DIABETES-METABOLISM REVIEWS LA English DT Editorial Material C1 NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD MAR PY 1998 VL 14 IS 1 BP 109 EP 110 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 101FN UT WOS:000074859100012 PM 9605636 ER PT J AU Gong, DW Bi, S Weintraub, BD Reitman, M AF Gong, DW Bi, S Weintraub, BD Reitman, M TI Rat mitochondrial glycerol-3-phosphate dehydrogenase gene: Multiple promoters, high levels in brown adipose tissue, and tissue-specific regulation by thyroid hormone SO DNA AND CELL BIOLOGY LA English DT Article ID GLYCEROL-PHOSPHATE DEHYDROGENASE; 3-PHOSPHATE DEHYDROGENASE; ALTERNATIVE PROMOTERS; MAMMALIAN-CELLS; CO-REPRESSOR; EXPRESSION; SEQUENCE; CDNA; THERMOGENESIS; LOCALIZATION AB Mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mtGPDH) is one of the two enzymes of the glycerol phosphate shuttle, This shuttle transfers reducing equivalents from the cytoplasm to the mitochondria in a unidirectional, exothermic manner, Here, the isolation and characterization of the rat nuclear gene (Gpd2) encoding mtGPDH is reported, The mtGPDH gene spans 100 kb and consists of 17 exons, The use of alternate promoters was suggested by the presence of three different first exons and confirmed by transient expression for two of them, The first exons are expressed in a tissue-restricted manner, Exon la was found primarily in brain, exon 1b was used in all tissues examined, and exon Ic was detected predominantly in testis, Depending on the tissue, different transcript lengths were also observed: 5.9 kb (all tissues), 3.6 kb (skeletal muscle), and 2.5 kb (testis), The length isoforms are attributable to alternate splicing and polyadenylation site use, Very high mtGPDH mRNA levels were found in brown adipose tissue, 75 fold greater than in white adipose tissue, Thyroid hormone increased mtGPDH mRNA levels in liver and heart but not in brown adipose tissue, brain, or testis, This pattern corresponds to that of thyroid hormone-induced oxygen consumption and is consistent with a role for mtGPDH in thyroid hormone-induced thermogenesis, Both thyroid-responsive and nonresponsive tissues used promoter 1b, suggesting that tissue-specific factor(s) contribute to the tissue-restricted responsiveness to thyroid hormone. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Mol & Cellular Biol Branch, NIH, Bethesda, MD 20892 USA. RP Gong, DW (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Room 8S-235,10 Ctr Dr MSC 1770, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 40 TC 34 Z9 34 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAR PY 1998 VL 17 IS 3 BP 301 EP 309 DI 10.1089/dna.1998.17.301 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA ZE949 UT WOS:000072847700010 PM 9539110 ER PT J AU Deev, SM Yazynin, SA Kuznetsov, DA Korneva, IN Jukovich, M Hartley, RW AF Deev, SM Yazynin, SA Kuznetsov, DA Korneva, IN Jukovich, M Hartley, RW TI Ribonuclease gene - a base of "zero background" vectors SO DOKLADY AKADEMII NAUK LA Russian DT Article ID POSITIVE-SELECTION VECTOR; EXPRESSION; BARNASE C1 VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. NIH, Bethesda, MD 20892 USA. RP Deev, SM (reprint author), VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RI Deyev, Sergey/F-8191-2014 OI Deyev, Sergey/0000-0002-3952-0631 NR 12 TC 0 Z9 0 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0869-5652 J9 DOKL AKAD NAUK+ JI Dokl. Akad. Nauk PD MAR PY 1998 VL 359 IS 2 BP 263 EP 266 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZK083 UT WOS:000073283200031 PM 9608909 ER PT J AU Fudala, PJ Yu, E Macfadden, W Boardman, C AF Fudala, PJ Yu, E Macfadden, W Boardman, C TI Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 20-22, 1996 CL ORLANDO, FLORIDA SP Amer Soc Clin Pharmcol & Therapeut DE buprenorphine; naloxone; opioid-dependence; treatment ID METHADONE-MAINTAINED VOLUNTEERS; ACUTE PHYSICAL-DEPENDENCE; PRECIPITATED WITHDRAWAL; HUMANS; MAINTENANCE; EXPOSURE; ABUSE AB The present study, conducted as part of the development of a buprenorphine/naloxone combination product, was designed to evaluate the individual and combined effects of intravenously administered buprenorphine and naloxone. This in-patient trial used a randomized, double-blind: crossover design. Ten opioid-dependent male subjects were stabilized and maintained on morphine, lj mg given intramuscularly four times daily. Then, at 48- to 72-h intervals, subjects received one of the following by intravenous injection: (1) placebo, (2) morphine 15 mg, (3) buprenorphine 2 mg, (4) buprenorphine 2 mg/naloxone 0.5 mg, and (5) naloxone 0.5 mg. Both naloxone and buprenorphine/naloxone produced significant (P < 0.005) opioid withdrawal effects compared to placebo as assessed with the CINA scale, an instrument which utilizes subject-and observer-reported, as well as physiological parameters. The combination of buprenorphine with naloxone in a 4:1 ratio produced opioid antagonist-like effects which should limit its potential for intravenous abuse by opioid addicts. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Sch Med, Dept Psychiat, Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIDA, Medicat Dev Div, Rockville, MD USA. RP Fudala, PJ (reprint author), Univ Penn, Sch Med, Dept Psychiat, Dept Vet Affairs Med Ctr, Bldg 15,Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [YO1-DA30011] NR 36 TC 69 Z9 71 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 1998 VL 50 IS 1 BP 1 EP 8 DI 10.1016/S0376-8716(98)00008-8 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZG913 UT WOS:000073052600001 PM 9589267 ER PT J AU Blaisdell, J Goldstein, JA Bai, SA AF Blaisdell, J Goldstein, JA Bai, SA TI Isolation of a new canine cytochrome P450 cDNA from the cytochrome P450 2C subfamily (CYP2C41) and evidence for polymorphic differences in its expression SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; AMINO-ACID-SEQUENCES; S-TRANSFERASE M1; SACCHAROMYCES-CEREVISIAE; GENE; METABOLISM; CLONING; 2,2',4,4',5,5'-HEXACHLOROBIPHENYL; PURIFICATION; DEBRISOQUINE AB Two members of the canine cytochrome P4502C subfamily [CYP2C21 and CYP2C41 (sequence has been submitted to Genbank with accession number AF016248)] were cloned from three beagle liver cDNA libraries. The two canine CYP2C cDNAs exhibited 70% nucleotide and amino acid identity as well as 74-83% nucleotide and 67-76% amino acid identity with the human CYP2Cs, Canine CYP2C41 is more homologous to the human CYP2Cs than CYP2C21, The two canine CYP2C cDNAs exhibited a slightly lower nucleotide and amino acid identity (66-77%) with the rat P450CYPs, 2C11 and 2C12, Reverse transcription-polymerase chain reaction-based restriction enzyme tests for CYP2C21 and 2C41 mRNAs as well as polymerase chain reaction-based tests for genomic DNA were developed, CYP2C21 cDNA was present in the livers of all dogs tested (N = 9), but CYP2C41 was present in only 1 of the 9 (11%), Genomic tests found that the gene coding for CYP2C21 was also present in all dogs tested (N = 25), of which 15 were beagles and 10 mixed breeds. In contrast, the gene coding for CYP2C41 was present in only 16% (4 out of 25) of the dogs. An even distribution of the CYP2C41 gene was found between the sexes and between beagles and mixed breeds, This unique polymorphism in the canine CYP2C subfamily may be a source of variability in the metabolic clearance in dogs of xenobiotics that are metabolized by the cytochrome P450 2C subfamily of enzymes. C1 N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Bai, SA (reprint author), N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, 4700 Hillsborough St, Raleigh, NC 27606 USA. NR 24 TC 35 Z9 38 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR PY 1998 VL 26 IS 3 BP 278 EP 283 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA775 UT WOS:000072400500015 PM 9492393 ER PT J AU Russian, DA Kovacs, JA AF Russian, DA Kovacs, JA TI Pneumocystis carinii: a fungus resistant to antifungal therapies - mechanisms of action of antipneumocystis drugs SO DRUG RESISTANCE UPDATES LA English DT Review ID SUBSTITUTED BIS-BENZIMIDAZOLES; MAJOR SURFACE GLYCOPROTEIN; DNA-BINDING AFFINITY; DIHYDROPTEROATE SYNTHASE; PLASMODIUM-FALCIPARUM; ANTIGIARDIAL ACTIVITY; GIARDIA-LAMBLIA; PNEUMONIA; SEQUENCE; GENE AB Pneumocystis carinii is a pathogen that causes a potentially lethal pneumonia in patients with AIDS and other immunodeficiency states. This review discusses the mechanisms of action of four- classes of antipneumocystis agents: inhibitors of ergosterol synthesis and function, 1,3-beta-glucan synthase inhibitors, antifolates and DNA binding agents. Investigations of Fl carinii's biologic pathways affected by the antipneumocystis actions of each of these classes of agents has generated important insights into the organism's basic biology and supports the organism's classification as a fungus, In addition, this review discusses some recent P. carinii research and its potential impact on drug development. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Russian, DA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7043,MSc 1662, Bethesda, MD 20892 USA. NR 43 TC 7 Z9 7 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD MAR PY 1998 VL 1 IS 1 BP 16 EP 20 DI 10.1016/S1368-7646(98)80210-0 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 127PN UT WOS:000076359900004 PM 17092792 ER PT J AU Camaioni, L Longobardi, E Venuti, P Bornstein, MH AF Camaioni, L Longobardi, E Venuti, P Bornstein, MH TI Maternal speech to 1-year-old children in two Italian cultural contexts SO EARLY DEVELOPMENT & PARENTING LA English DT Article DE maternal speech; cultural differences; maternal communicative functions; speech styles ID UNITED-STATES; LANGUAGE; MOTHER; FRANCE AB The present study examines maternal speech to 1-year-old children in two cultural contexts in the same nation: an urban industrial town (Padua) and a small rural village (Ruoti). The aim was to evaluate if and how intranational cultural variation influences the ways in which Italian-speaking mothers use language when addressing their children. We hypothesized that mothers in the rural context would adopt speech acts with a control function ('directive' speech style) more than mothers in the urban context, whereas urban mothers would use speech acts with a didactic and a tutorial function more than rural mothers ('child-centred' speech style). Forty primiparous mothers and their 13-month-old children were videotaped at home in a play session. Maternal speech from transcripts was examined in terms of five different communicative functions (Tutorial, Didactic, Conversational, Control, and Asynchronous) using a 21-category coding scheme validated in previous studies. Parents also completed a demographic and living standards questionnaire. The results showed systematic cultural differences in a variety of maternal communicative functions, presumably related to different life environments and childrearing practices in the two sites. (C) 1998 John Wiley & Sons, Ltd. C1 Univ Rome La Sapienza, Dept Dev & Social Psychol, I-00185 Rome, Italy. Univ Padua, Dept Dev Psychol, I-35100 Padua, Italy. NICHHD, Bethesda, MD 20892 USA. RP Camaioni, L (reprint author), Univ Rome La Sapienza, Dept Dev & Social Psychol, Via Marsi 78, I-00185 Rome, Italy. EM camaioni@axrma.uniroma1.it NR 29 TC 16 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-3593 J9 EARLY DEV PARENTING JI Early Dev. Parent. PD MAR PY 1998 VL 7 IS 1 BP 9 EP 17 DI 10.1002/(SICI)1099-0917(199803)7:1<9::AID-EDP159>3.0.CO;2-T PG 9 WC Psychology, Developmental SC Psychology GA ZJ379 UT WOS:000073208700002 ER PT J AU Lyon, GR AF Lyon, GR TI Why reading is not a natural process SO EDUCATIONAL LEADERSHIP LA English DT Article AB Nearly four decades of scientific research on how children learn to read supports an emphasis on phonemic awareness and phonics in a literature-rich environment. These findings challenge the belief that children learn to read naturally. C1 NICHHD, Child Dev & Behav Branch, NIH, US Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lyon, GR (reprint author), NICHHD, Child Dev & Behav Branch, NIH, US Hlth & Human Serv, Bldg 6100,Rm 4B05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 15 Z9 15 U1 0 U2 3 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD MAR PY 1998 VL 55 IS 6 BP 14 EP + PG 6 WC Education & Educational Research SC Education & Educational Research GA 150YY UT WOS:000077694700004 ER PT J AU Oletsky, H Greenfield, J Sato, S AF Oletsky, H Greenfield, J Sato, S TI 14 and 6 Hz positive spikes preceding 3 Hz generalized spike and wave in a 15 year old patient with absence: a case report SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE 14 Hz positive spikes; 6 Hz positive spikes; three per second spike-wave; generalized discharges; sleep stage AB A 15 year old girl with a history of childhood absence seizures underwent a prolonged EEG recording. Twelve bursts of 3 Hz generalized spike and wave were recorded during drowsiness and light sleep, all of which were preceded by 14 and 6 Hz positive spikes with a latency of under 1 s. Nine bursts of polyspike wave, not preceded by 14 and 6 Hz positive spikes, were recorded during deeper sleep (stage 3). The bursts of polyspike-wave were significantly longer when preceded by 14 and 6 Hz spikes than when observed in isolation. The close association between these paroxysmal events in our patient is intriguing, may be coincidental, and has never before been reported. (C) 1998 Elsevier Science Ireland Ltd. C1 NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. RP Sato, S (reprint author), NINDS, EEG Sect, NIH, Bldg 10,Room 5C-101,10 Ctr Dr, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD MAR PY 1998 VL 106 IS 3 BP 262 EP 264 DI 10.1016/S0013-4694(97)00127-2 PG 3 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA ZF715 UT WOS:000072924800013 PM 9743286 ER PT J AU Qian, XH Tomer, KB AF Qian, XH Tomer, KB TI Affinity capillary electrophoresis investigation of an epitope on human immunodeficiency virus recognized by a monoclonal antibody SO ELECTROPHORESIS LA English DT Article DE affinity capillary electrophoresis; human immunodeficiency virus; epitope; monoclonal antibody; binding ID ZONE ELECTROPHORESIS; MASS-SPECTROMETRY; HIV-1; BINDING; PROTEIN; SPECIFICITY; PEPTIDES; P24; CONSTANTS; ANTIGENS AB Affinity capillary electrophoresis (ACE) has been used to investigate the epitope on the human immunodeficiency virus (HIV) core protein p24 recognized by the monoclonal antibody (mAb) 13-102-100. The affinity of a series of peptides with N- and C-terminal truncations of the epitope sequence determined by mass spectrometry was studied. The peak area change assay was used for the study of the interactions of the mAb with those peptides, exhibiting tight binding to the mAb, and the migration time shift assay was used to probe the relative affinities of peptides showing weak binding to the mAb. The experimental results show that the monoclonal antibody 13-102-100 recognizes the peptide VHPVHAGPIAP with highest affinity. Smaller peptides incorporating only part of the epitope, however, are recognized to some extent in the ACE experiments. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 31 TC 34 Z9 36 U1 0 U2 7 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 MAR PY 1998 VL 19 IS 3 BP 415 EP 419 DI 10.1002/elps.1150190309 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZD713 UT WOS:000072716000008 PM 9551794 ER PT J AU Begay, V Falcon, J Cahill, GM Klein, DC Coon, SL AF Begay, V Falcon, J Cahill, GM Klein, DC Coon, SL TI Transcripts encoding two melatonin synthesis enzymes in the teleost pineal organ: Circadian regulation in pike and Zebrafish, but not in trout SO ENDOCRINOLOGY LA English DT Article ID SEROTONIN N-ACETYLTRANSFERASE; XENOPUS-LAEVIS RETINA; MESSENGER-RNA LEVELS; TRYPTOPHAN-HYDROXYLASE; PHOTORECEPTOR CELLS; INSERTIONAL MUTAGENESIS; CHICKEN RETINA; IN-VITRO; CLOCK; RHYTHM AB In this report the photosensitive teleost pineal organ was studied in three teleosts, in which melatonin production is known to exhibit a daily rhythm with higher levels at night; in pike and zebrafish this increase is driven by a pineal clock, whereas in trout it occurs exclusively in response to darkness. Here we investigated the regulation of messenger RNA (mRNA) encoding serotonin N-acetyltransferase (AA-NAT), the penultimate enzyme in melatonin synthesis, which is thought to be primarily responsible for changes in melatonin production. AA-NAT mRNA was found in the pineal organ of all three species and in the zebrafish retina. A rhythm in AA-NAT mRNA occurs in vivo in the pike pineal organ in a light/dark (L/D) lighting environment, in constant lighting (L/L), or in constant darkness (DID) and in vitro in the zebrafish pineal organ in L/D and L/L, indicating that these transcripts are regulated by a circadian clock. In contrast, trout pineal AA-NAT mRNA levels are stable in. vivo and in vitro in LID, L/L, and D/D. Analysis of mRNA encoding the first enzyme in melatonin synthesis, tryptophan hydroxylase, reveals that the in vivo abundance of this transcript changes on a circadian basis in pike, but not in trout. A parsimonious hypothesis to explain the absence of circadian rhythms in both AA-NAT and tryptophan hydroxylase mRNAs in the trout pineal is that one circadian System regulates the expression of both genes and that this system has been disrupted by a single mutation in this species. C1 NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Fac Sci Poitiers, Dept Neurosci, Lab Neurobiol Cellulaire, CNRS,UMR 6558, F-86022 Poitiers, France. Univ Houston, Dept Biol, Houston, TX 77204 USA. RP Coon, SL (reprint author), NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. EM coon@codon.nih.gov RI FALCON, Jack/I-5302-2013 OI FALCON, Jack/0000-0002-7572-6581 NR 42 TC 84 Z9 88 U1 0 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 MAR PY 1998 VL 139 IS 3 BP 905 EP 912 DI 10.1210/en.139.3.905 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YZ845 UT WOS:000072299800013 PM 9492019 ER PT J AU Mason, MM He, YF Chen, H Quon, MJ Reitman, M AF Mason, MM He, YF Chen, H Quon, MJ Reitman, M TI Regulation of leptin promoter function by Sp1, C/EBP, and a novel factor SO ENDOCRINOLOGY LA English DT Article ID BINDING-PROTEIN-ALPHA; OB GENE-EXPRESSION; MOUSE OBESE GENE; ACTIVATED RECEPTOR-GAMMA; RNA POLYMERASE-II; TRANSCRIPTION FACTOR; 3T3-L1 ADIPOCYTES; ANTIDIABETIC THIAZOLIDINEDIONE; TRANSFECTED ADIPOCYTES; MESSENGER-RNA AB Leptin is a hormone produced in adipose cells that regulates energy expenditure, food intake, and adiposity. To understand leptin's transcriptional regulation, we are studying its promoter. Four conserved and functional regions were identified. Mutations in the C/EBP and TATA motifs each caused an approximately 10-fold decrease in promoter activity. The C/EBP motif bound recombinant C/EBP alpha and mediated trans-activation by C/EBP alpha, -beta, and -delta. Mutation of a consensus Spl site reduced promoter activity 2.5-fold and abolished binding of Spl. Mutation of a fourth factor-binding site, denoted LPI, abolished protein binding and reduced promoter activity 2-fold. Factor binding to the LP1 motif was observed with adipocyte, but not with nonadipocyte extracts. Adipocytes from fa/fa Zucker rats transcribed the reporter plasmids more efficiently than did control adipocytes. No effect on the transient expression of leptin was noted upon treatment with a thiazolidinedione, BRL49653, or upon cotransfection with peroxisome proliferator-activated receptor-gamma/retinoid X receptor-alpha or sterol response element-binding protein-1. Mutations of the Spl, LP1, and C/EBP sites in pairwise combinations diminished promoter activity to the extent predicted assuming these motifs contribute independently to leptin promoter function. Our identification of motifs regulating leptin transcription is an important step in the elucidation of the mechanisms underlying hormonal and metabolic regulation of this gene. C1 NIDDKD, NIH, Diabet Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Hypertens Endocrine Branch, Bethesda, MD 20892 USA. RP Reitman, M (reprint author), NIDDKD, NIH, Diabet Branch, Bldg 10,Room 8N-250,10 Ctr Dr,MSC 1770, Bethesda, MD 20892 USA. EM mlr@helix.nih.gov RI Quon, Michael/B-1970-2008; Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 61 TC 92 Z9 97 U1 0 U2 6 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 MAR PY 1998 VL 139 IS 3 BP 1013 EP 1022 DI 10.1210/en.139.3.1013 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YZ845 UT WOS:000072299800027 PM 9492033 ER PT J AU Ohlsson, C Kley, N Werner, H LeRoith, D AF Ohlsson, C Kley, N Werner, H LeRoith, D TI p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: Interaction between p53 and Sp1 SO ENDOCRINOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; WILD-TYPE; PROMOTER REGION; APOPTOSIS; TRANSCRIPTION; PRODUCT; BINDING; TUMORIGENESIS; REPRESSION; WT1 AB The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. A functional and physical interaction between p53 and Spl, in the regulation of the IGF-R, was studied in osteosarcoma cells. Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Spl expressed alone. However, Spl counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Spl, indicating a physical interaction between p53 and Spl. In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. Furthermore, data supporting an interaction between p53 and Spl in the regulation of the promoter activity of IGF-IR are presented. C1 NIDDKD, NIH, Diabet Branch, Bethesda, MD 20892 USA. Bristol Myers Squibb Pharmaceut Res Inst, Dept Mol Genet & Cell Biol, Princeton, NJ 08540 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Ohlsson, C (reprint author), NIDDKD, NIH, Diabet Branch, Bldg 10,Room 8S235A,10 Ctr Dr,MCS-1770, Bethesda, MD 20892 USA. EM claes@ss.gu.se NR 44 TC 127 Z9 129 U1 0 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 MAR PY 1998 VL 139 IS 3 BP 1101 EP 1107 DI 10.1210/en.139.3.1101 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YZ845 UT WOS:000072299800037 PM 9492043 ER PT J AU Reiter, LW DeRosa, C Kavlock, RJ Lucier, G Mac, MJ Melillo, J Melnick, RL Sinks, T Walton, BT AF Reiter, LW DeRosa, C Kavlock, RJ Lucier, G Mac, MJ Melillo, J Melnick, RL Sinks, T Walton, BT TI The US federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE carcinogenicity; developmental toxicity; endocrine disruptor; immunotoxicity; neurotoxicity; risk assessment AB The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disrupter issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disrupters. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals: 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and polychlorinated biphenyls are the most commonly studied chemical classes. Comparison of the inventory with the research needs should allow identification of underrepresented research areas in need of attention. C1 US EPA, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. Agcy Tox Substance & Dis Registry, Atlanta, GA 30333 USA. NIEHS, Res Triangle Pk, NC 27709 USA. US Geol Survey, Biol Resources Div, Reston, VA 20192 USA. Execut Off President, Off Sci & Technol Policy, Washington, DC 20500 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP Reiter, LW (reprint author), US EPA, Natl Hlth & Environm Effects Lab, Res Triangle Pk, NC 27711 USA. NR 1 TC 22 Z9 24 U1 2 U2 12 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1998 VL 106 IS 3 BP 105 EP 113 DI 10.1289/ehp.98106105 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110JX UT WOS:000075378600014 PM 9443998 ER PT J AU Barkan, SE Melnick, SL Preston-Martin, S Weber, K Kalish, LA Miotti, P Young, M Greenblatt, R Sacks, H Feldman, J AF Barkan, SE Melnick, SL Preston-Martin, S Weber, K Kalish, LA Miotti, P Young, M Greenblatt, R Sacks, H Feldman, J CA WIHS Collaborative Study Grp TI The Women's Interagency HIV Study SO EPIDEMIOLOGY LA English DT Article DE HIV; AIDS; disease progression; women; epidemiologic methods; cohort study ID AIDS AB The Women's Interagency HIV Study comprises the largest U.S. cohort to date of human immunodeficiency virus (HIV)-seropositive women (N = 2,058) with a comparison cohort of seronegative women (N = 568). The methodology, training, and quality assurance activities employed are described. The study population, enrolled between October 1994 and November 1995 through six clinical consortia throughout the United States (totaling 23 sites) represents a typically hard-to-reach study population. More than half of the women in each cohort were living below the federally defined levels of poverty. The women ranged in age from 16 to 73 years; approximately one-quarter self-identified as Latina or Hispanic, over one half as African-American not of Hispanic origin, and less than 20% as white, non-Hispanic origin. Self-reporting of HIV exposure risk included injection drug use by 34% of the seropositive women and 28% of the seronegative women, heterosexual contact (42% ets 26%), transfusion risk (4% us 3%) and no identified risk (20% vs 43%). Demographic and HIV exposure risk characteristics of the seropositive cohort were comparable with characteristics of nationally reported AIDS cases in U.S. women. This well characterized cohort of HIV seropositive and high-risk seronegative women represents a rich opportunity for future studies of HIV disease progression and pathogenesis. C1 New England Res Inst, Watertown, MA 02172 USA. NCI, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA 90089 USA. Cook Cty Hosp, Chicago, IL 60612 USA. NIAID, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Barkan, SE (reprint author), Seattle King Cty Dept Publ Hlth, 400 Yesler Way,3rd Floor, Seattle, WA 98104 USA. NR 21 TC 519 Z9 520 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1998 VL 9 IS 2 BP 117 EP 125 DI 10.1097/00001648-199803000-00004 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YX941 UT WOS:000072096000004 PM 9504278 ER PT J AU Marcus, PM Savitz, DA Millikan, RC Morgenstern, H AF Marcus, PM Savitz, DA Millikan, RC Morgenstern, H TI Female breast cancer and trihalomethane levels in drinking water in North Carolina SO EPIDEMIOLOGY LA English DT Article DE breast neoplasms; chlorination; epidemiologic methods; risk factors; environmental exposures; drinking water ID STANDARDIZED REGRESSION-COEFFICIENTS; MORTALITY; LOUISIANA AB Some studies indicate that chlorination by-products in drinking water may contribute slightly to breast cancer risk. This ecologic study describes the association between total trihalomethane levels in publicly supplied water and the incidence of female invasive breast cancer. We included 71 North Carolina water suppliers serving at least 10,000 customers in the summer of 1995 as the units of analysis. We estimated incidence rates using 6,462 cases who were either white or black and between 35 and 84 years old and were linked by zip codes to the water supplier. We treated ecologic measurements of age, income, education, urban status, and race as potential confounders. Total trihalomethane levels were not associated materially with breast cancer risk, adjusting for potential confounders. The rate ratio for 80.0 parts per billion (ppb) or more us less than 40.0 ppb total trihalomethanes was 1.1 [95% confidence interval (CI) = 0.9-1.2]. When stratified by race, the observed association for the aforementioned total trihalomethane category was not very different in black women (rate ratio = 1.2; 95% CI = 0.8-1.8) than in white women (rate ratio = 1.1; 95% CI = 0.9-1.3). These ecologic data are compatible with trihalomethanes in drinking water being either unrelated or weakly related to breast cancer risk. C1 NCI, Prevent Oncol Branch, Div Canc Prevent & Control, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Ctr Environm & Occupat Hlth, Los Angeles, CA 90024 USA. RP Marcus, PM (reprint author), NCI, Prevent Oncol Branch, Div Canc Prevent & Control, NIH, Execut Plaza N,Room 344,MSC 7354, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA66201] NR 25 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1998 VL 9 IS 2 BP 156 EP 160 DI 10.1097/00001648-199803000-00009 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YX941 UT WOS:000072096000009 PM 9504283 ER PT J AU Hornsby, PP Wilcox, AJ Weinberg, CR AF Hornsby, PP Wilcox, AJ Weinberg, CR TI Cigarette smoking and disturbance of menstrual function SO EPIDEMIOLOGY LA English DT Article DE tobacco; menstrual cycle; menstrual disorders; dysmenorrhea ID LUTEINIZING-HORMONE; DYSMENORRHEA; PREVALENCE; EXPOSURE; CYCLE; WOMEN; PAIN AB We sought to determine the effects of cigarette smoking on menstrual function using prospectively recorded menstrual data in a cohort study of women ages 37-39 years. Eighty-three current smokers and 275 nonsmokers provided menstrual data for analysis. Smoking was associated with decreased duration of bleeding, increased daily amount of bleeding (subjectively scored), and increased duration of dysmenorrhea. These effects were most pronounced in the heaviest smokers. Smoking was not associated with cycle length, but we found some evidence for increased variability of cycle length among heavier smokers. We conclude that cigarette smoking affects menstrual function, most importantly by increasing the duration of dysmenorrhea. C1 Univ Virginia, Hlth Sci Ctr, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. NIEHS, Stat & Biomath Branch, Res Triangle Pk, NC 27709 USA. RP Hornsby, PP (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Hlth Evaluat Sci, Box 600, Charlottesville, VA 22908 USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 23 TC 48 Z9 50 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1998 VL 9 IS 2 BP 193 EP 198 DI 10.1097/00001648-199803000-00016 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YX941 UT WOS:000072096000016 PM 9504290 ER PT J AU Shea, KM Wilcox, AJ Little, RE AF Shea, KM Wilcox, AJ Little, RE TI Postterm delivery: A challenge for epidemiologic research SO EPIDEMIOLOGY LA English DT Review DE postterm birth; perinatal mortality; neonatal morbidity; pregnancy; incidence ID GESTATIONAL-AGE; PROLONGED PREGNANCY; POSTDATE PREGNANCY; BIRTH-WEIGHT; PERINATAL-MORTALITY; TERM; PARTURITION; POSTMATURE; MANAGEMENT; INDUCTION AB About 5% of babies are born postterm (that is, delivered after 42 completed weeks of gestation). Postterm infants experience more morbidity and mortality than term infants, prompting routine (and expensive) antenatal testing and active management of postterm pregnancies. This article reviews the epidemiology of postterm delivery. A few congenital conditions associated with disruption of the fetal-pituitary adrenal axis as well as a rare maternal enzyme deficiency have long been identified with postterm delivery. In recent literature, environmental pollution, diet, and pharmaceutical agents have been associated with postterm birth. Very little systematic research has focused on identifying risk factors for this poorly understood birth outcome. C1 UNC Hosp, Gen Clin Res Ctr, UNC NIEHS Program, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Shea, KM (reprint author), 1 Buttons Lane, Chapel Hill, NC 27514 USA. FU NIEHS NIH HHS [N01-ES-3535] NR 82 TC 39 Z9 41 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1998 VL 9 IS 2 BP 199 EP 204 DI 10.1097/00001648-199803000-00017 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YX941 UT WOS:000072096000017 PM 9504291 ER PT J AU Ziemann, U Steinhoff, BJ Tergau, F Paulus, W AF Ziemann, U Steinhoff, BJ Tergau, F Paulus, W TI Transcranial magnetic stimulation: its current role in epilepsy research SO EPILEPSY RESEARCH LA English DT Review DE transcranial magnetic stimulation; motor cortex excitability; antiepileptic drugs; mode of action; epilepsy ID HUMAN MOTOR CORTEX; DORSAL INTEROSSEOUS MUSCLE; DORSOLATERAL PREFRONTAL CORTEX; PERIPHERAL-NERVE STIMULATION; TEMPORAL-LOBE EPILEPSY; BRAIN-STIMULATION; CORTICAL STIMULATION; SILENT PERIOD; GENERALIZED EPILEPSY; ELECTRICAL-STIMULATION AB This paper reviews the current role of transcranial magnetic stimulation (TMS) in epilepsy research. After a brief introduction to the technical principles, the physiology and the safety aspects of TMS, emphasis is put on how human cortex excitability can be assessed by TMS and how this may improve our understanding of pathophysiological mechanisms in epilepsy and the mode of action of antiepileptic drugs (AEDs). Also, potential therapeutical applications of TMS are reviewed. For all aspects of this paper, a clear distinction was made between single-/paired-pulse TMS and repetitive TMS, since these two techniques have fundamentally different scopes and applications. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NINDS, Human Cortex Physiol Unit, NIH, Bethesda, MD 20892 USA. Univ Gottingen, Dept Clin Neurophysiol, D-37075 Gottingen, Germany. RP Ziemann, U (reprint author), NINDS, Human Cortex Physiol Unit, NIH, Bldg 10,Room 5N242,10 Ctr Dr, Bethesda, MD 20892 USA. RI Paulus, Walter/A-3544-2009 OI Paulus, Walter/0000-0001-5549-8377 NR 174 TC 124 Z9 126 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAR PY 1998 VL 30 IS 1 BP 11 EP 30 DI 10.1016/S0920-1211(97)00079-X PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA ZD593 UT WOS:000072702100002 PM 9551841 ER PT J AU Hammerschmidt, K Fischer, J AF Hammerschmidt, K Fischer, J TI The vocal repertoire of Barbary macaques: A quantitative analysis of a graded signal system SO ETHOLOGY LA English DT Article ID MACACA-SYLVANUS; VOCALIZATIONS; COMMUNICATION; RECRUITMENT; SCREAMS; CALLS AB The vocal behavior of Barbary macaques (Macaca sylvanus) was studied in an outdoor enclosure at Rocamadour, France. Ad libitum recordings were made across a broad array of socioecological contests from 92 individually identified subjects from all age-sex classes. From the recordings, 8479 calls were sampled and submitted to a Fourier transform. A custom software program was used to determine 35 acoustic parameters describing the call in terms of its frequency and time dynamics. On these parameters a cluster analysis was used to examine the acoustic morphology of the Barbary macaque vocal repertoire. The analysis revealed a highly graded structure with intergraded variations between different clusters ('call types'). There were clear age-related preferences in usage of different clusters, but animals of all ages were potentially able to produce the whole array of call types. The major sex difference was a differential use of certain call types in specific situations. Despite a clear sex dimorphism in body size no significant sex differences in the acoustic structure of calls in adults was found. There were no unidirectional relationships between the acoustic structure of a call and the context in which it was uttered, although call usage was more specific in some contexts than in others. The results suggest that the major factor underlying the variation in acoustic structure reflect the internal state of the caller. C1 Deutsch Primatenzentrum, Abt Neurobiol, D-37077 Gottingen, Germany. NICHD, NIH, Poolesville, MD USA. FU Berlin, Inst Verhaltensbiol, Berlin, Germany. RP Hammerschmidt, K (reprint author), Deutsch Primatenzentrum, Abt Neurobiol, Kellnerweg 4, D-37077 Gottingen, Germany. EM Khammer@www.dpz.gwdg.de RI Fischer, Julia/B-6674-2008 OI Fischer, Julia/0000-0002-5807-0074 NR 42 TC 44 Z9 44 U1 2 U2 16 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0179-1613 J9 ETHOLOGY JI Ethology PD MAR PY 1998 VL 104 IS 3 BP 203 EP 216 PG 14 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA ZG595 UT WOS:000073019400003 ER PT J AU Pinet, VM Long, EO AF Pinet, VM Long, EO TI Peptide loading onto recycling HLA-DR molecules occurs in early endosomes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE recycling MHC class II; exogenous antigen presentation; concanamycin B ID MHC CLASS-II; RESTRICTED PRESENTATION; ANTIGEN; VIRUS; COMPARTMENTS AB Presentation of exogenous antigens to MHC class II-restricted T cells can follow two differ ent processing pathways. The classical pathway requires newly synthesized MHC class II molecules, invariant chain and HLA-DM expression, whereas the alternative pathway is independent of protein synthesis, invariant chain and HLA-DM. In both cases, MHC class II molecules associate with peptides derived from exogenous antigens that have been processed in endocytic compartments. Different endosomal/prelysosomal compartments where peptide/MHC class II complexes and HLA-DM molecules accumulate have been described. We show here that the alternative pathway uses an earlier compartment than the classical pathway. Experiments with chemically cross-liniked antigen suggest that recycling MHC class II molecules present rapidly degraded antigens, leading to a rapid immune response to exogenously added influenza virus proteins. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Hop St Eloi, Immunol Lab, INSERM, U475, F-34295 Montpellier 5, France. RP Pinet, VM (reprint author), Hop St Eloi, Immunol Lab, INSERM, U475, F-34295 Montpellier 5, France. EM pinet@montp.inserm.fr RI Long, Eric/G-5475-2011; PINET, Valerie/G-6085-2012 OI Long, Eric/0000-0002-7793-3728; NR 20 TC 65 Z9 66 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1998 VL 28 IS 3 BP 799 EP 804 DI 10.1002/(SICI)1521-4141(199803)28:03<799::AID-IMMU799>3.0.CO;2-5 PG 6 WC Immunology SC Immunology GA ZD715 UT WOS:000072716200004 PM 9541573 ER PT J AU Prasad, SA Yewdell, JW Porgador, A Sadasivan, B Cresswell, P Bennink, JR AF Prasad, SA Yewdell, JW Porgador, A Sadasivan, B Cresswell, P Bennink, JR TI Calnexin expression does not enhance the generation of MHC class I-peptide complexes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen presentation; calnexin; chaperone; MHC; TAP ID MAJOR HISTOCOMPATIBILITY COMPLEX; ENDOPLASMIC-RETICULUM; MOLECULAR CHAPERONE; CELL-LINE; ANTIGEN; PROTEIN; TAP; ASSOCIATION; GLYCOPROTEINS; CALRETICULIN AB We investigated the requirement for calnexin in the biogenesis of MHC class I molecules. Mutant human cells lacking calnexin were infected with recombinant vaccinia viruses encoding mouse MHC class I molecules, K-d, K-b, K-k, D-d, D-b, and L-d. Flow cytometry indicated that each of the six MHC class I allomorphs was transported to the cell surface at similar rates in calnexin-deficient cells and transfectants expressing calnexin. For K-b and K-d, the calnexin-independent biogenesis occurred regardless of whether the MHC class I molecules contained human or mouse beta 2-microglobulin. Also addressed was the effect of calnexin on the surface expression of K-b molecules bearing the immunodominant peptide from ovalbumin (OVA(257-264)). This was detected with a recently described monoclonal antibody specific for the K-b/peptide complex. Calnexin expression had no significant effect on the formation of K-b/peptide complexes generated from full-length OVA, cytosolic OVA(257-264), or endoplasmic reticulum-targeted OVA(257-264), which was expressed in the presence of the herpes simplex virus ICP47 protein to ensure detection of TAP-independent peptide-MHC class I complexes. Complementary results were obtained with TAP-independent formation of K-d/peptide complexes. These findings indicate that calnexin is not required for the efficient assembly of MHC class I molecules with TAP-dependent or independent peptides. C1 NIAID, Viral Dis Lab, Bethesda, MD 20894 USA. NIAID, Immunol Lab, Bethesda, MD 20894 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bldg 4,Rm 213, Bethesda, MD 20894 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 30 TC 20 Z9 20 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1998 VL 28 IS 3 BP 907 EP 913 DI 10.1002/(SICI)1521-4141(199803)28:03<907::AID-IMMU907>3.0.CO;2-4 PG 7 WC Immunology SC Immunology GA ZD715 UT WOS:000072716200017 PM 9541586 ER PT J AU Chen, ZJ Wheeler, CJ Shi, W Wu, AJ Yarboro, CH Gallagher, M Notkins, AL AF Chen, ZJ Wheeler, CJ Shi, W Wu, AJ Yarboro, CH Gallagher, M Notkins, AL TI Polyreactive antigen-binding B cells are the predominant cell type in the newborn B cell repertoire SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE polyreactive antibody; newborn B cell; cord blood; B cell repertoire ID MONOCLONAL AUTOANTIBODIES; RHEUMATOID-ARTHRITIS; HIGH-AFFINITY; ANTIBODIES; LYMPHOCYTES; CIRCULATION; ORGANS; REACT; HEAVY; CHAIN AB Polyreactive antibodies bind to a variety of different self and non-self antigens. The B cells that make these antibodies express the polyreactive Ig receptor on their surface. To determine the frequency of polyreactive antigen-binding B cells in peripheral blood, we incubated two different antigens, one (insulin) labeled with fluorescein isothiocyanate and the other (beta-galactosidase) with phycoerythrin, with peripheral B cells. The percentage of cells that bound these antigens was determined with the fluorescence-activated cell sorter. Approximately 21 % of adult B cells bound insulin, 28 % bound beta-galactosidase, and 11 % bound both antigens. In contrast to B cells in the adult repertoire, 49 % of B cells in cord blood bound insulin, 54 % bound beta-galactosidase, and 33 % bound both antigens. The properties of polyreactive antigen-binding B cells in adult and cord blood were similar, except for the fact that almost all the polyreactive antigen-binding B cells in cord blood were CD5 positive (93 %), whereas only 40 % of the polyreactive antigen-binding B cells in adult peripheral blood were CD5 positive, indicating that the CD5 marker is not directly linked to polyreactivity. The percentage of polyreactive antigen-binding B cells in patients with Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis was equal to or slightly below that found in the normal adult B cell repertoire. It is concluded that polyreactive antigen-binding B cells are a major constituent of the normal adult B cell repertoire and are the predominant cell type in the newborn B cell repertoire. C1 NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sjogrens Syndrome Clin, San Francisco, CA 94143 USA. NIAMSD, Clin Invest Sect, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Dept Obstet & Gynecol, Bethesda, MD USA. RP Notkins, AL (reprint author), NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 20,Room 121,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 18 TC 61 Z9 63 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1998 VL 28 IS 3 BP 989 EP 994 DI 10.1002/(SICI)1521-4141(199803)28:03<989::AID-IMMU989>3.0.CO;2-1 PG 6 WC Immunology SC Immunology GA ZD715 UT WOS:000072716200025 PM 9541594 ER PT J AU Miles, FA AF Miles, FA TI The neural processing of 3-D visual information: evidence from eye movements SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE ocular following; optic flow; preattentive processing; stereomechanisms; vergence eye movements ID OCULAR FOLLOWING RESPONSES; OPTIC FLOW STIMULI; HUMAN OPTOKINETIC NYSTAGMUS; SUPERIOR TEMPORAL AREA; RANDOM-DOT STEREOGRAMS; TERM ADAPTIVE-CHANGES; LINEAR HEAD MOTION; MACAQUE MONKEY; VIEWING DISTANCE; FUNCTIONAL-PROPERTIES AB Primates have several reflexes that generate eye movements to compensate for bodily movements that would otherwise disturb their gaze and undermine their ability to process visual information. Two vestibule-ocular reflexes compensate selectively for rotational and translational disturbances of the head, and each has visual backups that operate as negative feedback tracking mechanisms to deal with any residual disturbances of gaze. Of particular interest here are three recently discovered visual tracking mechanisms that specifically address translational disturbances and operate in machine-like fashion with ultra-short latencies (<60 ms in monkeys, <85 ms in humans). These visual reflexes deal with motions in all three dimensions and operate as automatic servos, using preattentive parallel processing to provide signals that initiate eye movements before the observer is even aware that there has been a disturbance. This processing is accomplished by visual filters each tuned to a different feature of the binocular images located in the immediate vicinity of the plane of fixation. Two of the reflexes use binocular stereo cues and the third is tuned to particular patterns of optic flow associated with the observer's forward motion. Some stereoanomalous subjects show tracking deficits that can be attributed to a lack of just one subtype of cortical cell encoding motion in one particular direction in a narrow depth plane centred on fixation. Despite their rapid, reflex nature, all three mechanisms rely on cortical processing and evidence from monkeys supports the hypothesis that all are mediated by the medial superior temporal (MST) area of cortex. Remarkably, MSI seems to represent the first stage in cortical motion processing at which the visual error signals driving each of the three reflexes are fully elaborated at the level of individual cells. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Miles, FA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2 A50,49 Convent Dr, Bethesda, MD 20892 USA. EM fam@lsr.nei.nih.gov NR 74 TC 116 Z9 117 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 1998 VL 10 IS 3 BP 811 EP 822 DI 10.1046/j.1460-9568.1998.00112.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA ZB073 UT WOS:000072432600001 PM 9753150 ER PT J AU Costa, PT McCrae, RR AF Costa, PT McCrae, RR TI Six approaches to the explication of facet-level traits: examples from conscientiousness SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article; Proceedings Paper CT 8th Conference of the European-Association-for-Personality-Psychology CY JUL 08-12, 1996 CL GHENT, BELGIUM SP European Assoc Personal Psychol ID NEO PERSONALITY-INVENTORY; 5-FACTOR MODEL; BIG-5; EXPERIENCE; ADJECTIVES; LANGUAGE; OPENNESS; ROTATION; VALIDITY; SCALES AB Proponents of the Five-Factor Model (FFM) of personality have argued for somewhat different conceptualizations of the factors. Ultimately, the factors are best understood by a specification of the traits (or facets) that define them, and these facets in turn must be clearly conceptualized Using as examples the Conscientiousness facet scales of the Revised NEO Personality Inventory, we discuss six approaches to understanding facet-level traits: (i) rational analysis of item content, (ii) characterization of the low pole, the psychological opposite; (iii) interpretation of external correlates, (iv) examination of secondary and tertiary factor loadings; (v) translation into the specialized languages of applied psychology; and (vi) case studies. (C) 1998 John Wiley & Sons, Ltd. C1 NIA, Personal Stress & Coping Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Costa, PT (reprint author), NIA, Personal Stress & Coping Sect, Gerontol Res Ctr, NIH, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM PAULC@MVX.GRC.NIA.NIH.GOV OI Costa, Paul/0000-0003-4375-1712 NR 64 TC 58 Z9 60 U1 1 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD MAR-APR PY 1998 VL 12 IS 2 BP 117 EP 134 DI 10.1002/(SICI)1099-0984(199803/04)12:2<117::AID-PER295>3.0.CO;2-C PG 18 WC Psychology, Social SC Psychology GA ZL435 UT WOS:000073432600003 ER PT J AU Lim, SD Bae, SI Kim, IG Park, SC Chung, SI Nomizu, M Kleinman, HK Kim, WH AF Lim, SD Bae, SI Kim, IG Park, SC Chung, SI Nomizu, M Kleinman, HK Kim, WH TI Tissue transglutaminase is not increased during apoptosis of HT-1080 human fibrosarcoma cells SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE apoptosis; transglutaminase; laminin; extracellular matrix; matrix, extracellular; fibrosarcoma cells, HT-1080 ID GTP-BINDING PROTEIN; SER-ARG YIGSR; TUMOR-GROWTH; RAT-LIVER; ACTIVATION; INHIBITION; METASTASIS; LAMININ AB Tissue transglutaminase (tTGase), a cytosolic enzyme which catalyzes the covalent cross-linking of proteins, is thought to be involved in the apoptosis. Here, we tested whether tTGase is involved during HT-1080 fibrosarcoma cell apoptosis induced by the YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide. This sequence is derived from the laminin alpha 1 chain, and its potency is increased by the formation of a 16mer polymerization using a lysine tree structure. Cells were treated with several different concentrations of Ac-Y16 for 16 hours, and apoptosis was increased in dose-dependent manner. When assayed by incorporation of [C-14] putrescine into succinylated casein, total transglutaminase activity was decreased in parallel with the change in the number of attached cells. Western blot analysis using polyclonal antibody against tTGase showed that the tTGase protein level had not been significantly changed when equal amounts of the protein were applied. To confirm this result, we induced apoptosis of these cells by coating the tissue culture plates with non-adhesive poly-hydroxyethyl methacrylate (HEMA). Western blot analysis showed that the tTGase protein level did not change during this process of apoptosis. Although it has been suggested that tTGase is involved in the process of apoptosis of various cells in vitro and in vivo, our data demonstrate that tTGase is not involved in the process of apoptosis of HT-1080 human fibrosarcoma cell induced by either Ac-Y16 or a non-adhesive culture surface. C1 Seoul Natl Univ, Coll Med, Dept Pathol, Chongno Gu, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Dept Biochem, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Ctr Canc Res, Seoul 110799, South Korea. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, WH (reprint author), Seoul Natl Univ, Coll Med, Dept Pathol, Chongno Gu, 29 Yongon Dong, Seoul 110799, South Korea. RI Seoul National University, Pathology/B-6702-2012 NR 17 TC 5 Z9 5 U1 0 U2 1 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD MAR PY 1998 VL 50 IS 1 BP 79 EP 82 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA ZF781 UT WOS:000072932600013 PM 9570506 ER PT J AU Goulet, S Dore, FY Murray, EA AF Goulet, S Dore, FY Murray, EA TI Aspiration lesions of the amygdala disrupt the rhinal corticothalamic projection system in rhesus monkeys SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE mediodorsal nucleus of the thalamus; rhinal cortex; corticothalamic projections; retrograde fluorescent tracer; monkeys ID ENDURING MEMORY IMPAIRMENT; MEDIAL THALAMIC LESIONS; VISUAL RECOGNITION; ENTORHINAL CORTEX; MEDIODORSAL NUCLEUS; PARAHIPPOCAMPAL CORTICES; HIPPOCAMPAL-FORMATION; PREFRONTAL CORTEX; TEMPORAL STEM; AMNESIA AB In macaque monkeys, aspiration but not excitotoxic lesions of the medial temporal lobe limbic structures, the amygdala and hippocampus, produce a severe impairment in visual recognition memory. Furthermore, certain ventromedial cortical regions, namely the rhinal (i.e., entorhinal and perirhinal) cortex, are now known to be critical for visual recognition memory. Because the route taken by temporal cortical efferent fibers, especially perirhinar efferents, passes nearby the amygdala, it is possible that inadvertent damage to these fibers is produced by the aspirative but not the excitotoxic process, thereby accounting at least in part for the different behavioral outcomes of the two types of lesion. To test this idea, we assessed the integrity of the rhinal corticothalamic projection system after aspiration lesions of the amygdala. Three rhesus monkeys with unilateral amygdala removals received bilaterally symmetrical injections of a retrograde fluorescent tracer into the medial portion of the mediodorsal nucleus of the thalamus. Retrogradely labeled cells were identified using conventional fluorescence microscopy techniques. In all three cases, the rhinal cortex of the intact hemispheres contained moderate numbers of retrogradely labeled cells. By contrast, the rhinal cortex of the amygdalectomized hemispheres consistently contained few retrogradely labeled cells, and a direct comparison of the two hemispheres showed this difference to be statistically significant. A similar asymmetric pattern was observed for area TE but not for the cortex lining the dorsal bank of the superior temporal sulcus, nor for the rostral cingulate motor area, which was examined as a control. The results indicate that aspiration lesions of the amygdala not only remove the cell bodies of the amygdala, as intended, but also inadvertently disrupt projection fibers arising from cells in the rhinal cortex and area TE that pass nearby or through the amygdala en route to the thalamus. Behavioral studies examining the effects of aspiration lesions of the amygdala in nonhuman primates need to take these findings into consideration. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Laval, Ecole Psychol, Quebec City, PQ, Canada. RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 53 TC 40 Z9 40 U1 0 U2 0 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 MAR PY 1998 VL 119 IS 2 BP 131 EP 140 DI 10.1007/s002210050326 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZB077 UT WOS:000072433000001 PM 9535562 ER PT J AU Kirshenbaum, AS Worobec, AS Davis, TA Goff, JP Semere, T Metcalfe, DD AF Kirshenbaum, AS Worobec, AS Davis, TA Goff, JP Semere, T Metcalfe, DD TI Inhibition of human mast cell growth and differentiation by interferon gamma-1b SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE IFN gamma-1b; IFN alpha-2b; mast cells; Fc(epsilon)RI ID MARROW PROGENITOR CELLS; BLOOD MONONUCLEAR-CELLS; BONE-MARROW; PERIPHERAL-BLOOD; C-KIT; MASTOCYTOSIS; MUTATION; DISEASES; LEUKEMIA AB In an effort to identify cytokines that inhibit human mast cell growth, we cultured HMC-1 cells and recombinant human stem cell factor (rhSCF)-dependent human bone marrow-derived mast cells (HBMCs) in the presence of interferon gamma (IFN gamma)-1b and interferon alpha (IFN alpha)-2b. HMC-1 cell numbers decreased in the presence of 1000 U/mL IFN gamma-1b but were unaffected by 1000 UlmL of IFN alpha-2b. HBMCs were then cultured for 0 to 7 days with 100 ng/mL rhSCF and 10 ng/mL recombinant human IL-3 (rhIL-3), followed by culture in rhSCF and administration of either 1000 U/mL IFN alpha-2b or 1000 U/mL IFN gamma-1b. HBMCs appearing in cultures with rhSCF alone or in combination with IFN alpha-2b were virtually identical in number through 8 weeks of culture. In cultures supplemented with IFN gamma-1b, HBMCs significantly decreased in number and incidence of granular metachromasia by 4 to 5 weeks (p < 0.001). Similar results were obtained when human marrow was cultured from day 0 with rhSCF and IFN gamma-1b. Mature rhSCF-dependent HBMCs were also cultured at 5 weeks with rhSCF alone or in combination with IFN gamma-1b. Compared with cells cultured in rhSCF, mature 5-week HBMC cultures treated with rhSCF plus IFN gamma-1b revealed a decrease in mast cells, and those mast cells that remained had fewer toluidine blue- and tryptase-positive granules after 5 to 8 weeks. FACS analysis of rhSCF plus IFN gamma-1b-treated mature HBMCs revealed increased c-kit and Fc(epsilon)RI expression. Mast cell releasibility was not increased. IFN gamma-1b was thus able to suppress mast cell growth from CD34(+) cells, suggesting that this agent should be considered as a candidate cytokine for the treatment of disorders of mast cell proliferation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. USN, Med Res Inst, Immune Cell Biol Program, Stem Cell Biol Branch, Bethesda, MD USA. Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA USA. RP Kirshenbaum, AS (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C 208,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 28 TC 40 Z9 40 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 1998 VL 26 IS 3 BP 245 EP 251 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA YZ911 UT WOS:000072306900010 PM 9502621 ER PT J AU Tirkkonen, M Tanner, M Karhu, R Kallioniemi, A Isola, J Kallioniemi, OP AF Tirkkonen, M Tanner, M Karhu, R Kallioniemi, A Isola, J Kallioniemi, OP TI Molecular cytogenetics of primary breast cancer by CGH SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CLONAL CHROMOSOME-ABNORMALITIES; AMPLIFIED DNA-SEQUENCES; COPY NUMBER CHANGES; B-CELL LYMPHOMA; IN-SITU; CARCINOMAS; AMPLIFICATION; REGIONS; TUMORS AB Comparative genomic hybridization (CGH) reveals DNA sequence copy number changes that are shared among the different cell subpopulations present in a tumor and may help to delineate the average progression pathways of breast cancer. Previous CGH studies of breast cancer have concentrated on selected subgroups of breast cancer. Here, 55 unselected primary breast carcinomas were analyzed using optimized quality-controlled CGH procedures. Gains of 1q (67%) and 8q (49%) were the most frequent aberrations. Other recurrent gains were found at 33 chromosomal regions, with 16p, 5p 12-14, 19q, 11q13-14, 17q12, 17q22-24, 19p, and 20q13 being most often (> 18%) involved. Losses found in > 18% of the tumors involved 8p, 16q, 13q, 17p, 9p, Xq, 6q, 11q, and 18q. The total number of aberrations per tumor was highest in poorly differentiated (P = 0.01) and in DNA aneuploid (P = 0.05) tumors. The high frequency of 1q gains and presence of + 1q as the sole abnormality suggest that it is an early genetic event. In contrast, gains of 8q were most common in genetically and phenotypically advanced breast cancers. The vast majority of breast cancers (80%) have gains of 1q, 8q, or both, and 3 changes (+ 1q, +8q, or -13q) account for 91 % of the tumors. In conclusion, CGH results indicate that certain chromosomal imbalances are very often selected for, sometimes in a preferential order, during the progression of breast cancer. Further studies of such common changes may form the basis for a molecular cytogenetic classification of breast cancer. (C) 1998 Wiley-Liss, Inc. C1 Tampere Univ Hosp, Canc Genet Lab, FIN-33521 Tampere, Finland. Univ Tampere, Canc Genet Lab, Inst Med Technol, FIN-33101 Tampere, Finland. Natl Human Genome Res Inst, Canc Genet Lab, NIH, Bethesda, MD USA. RP Tirkkonen, M (reprint author), Tampere Univ Hosp, Canc Genet Lab, POB 2000, FIN-33521 Tampere, Finland. EM Mika.Tirkkonen@uta.fi RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 NR 32 TC 308 Z9 309 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 1998 VL 21 IS 3 BP 177 EP 184 DI 10.1002/(SICI)1098-2264(199803)21:3<177::AID-GCC1>3.0.CO;2-X PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YZ589 UT WOS:000072269200001 PM 9523192 ER PT J AU Derr, LK AF Derr, LK TI The involvement of cellular recombination and repair genes in RNA-mediated recombination in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID YEAST DNA-REPAIR; HOMOLOGOUS RECOMBINATION; MITOTIC RECOMBINATION; NUCLEOTIDE-SEQUENCE; ILLEGITIMATE RECOMBINATION; PLASMID RECOMBINATION; NONHOMOLOGOUS DNA; TY RECOMBINATION; RAD51 PROTEIN; INTEGRATION AB We previously demonstrated that a reverse transcript of a cellular reporter gene (his3-AI) can serve as the donor for gene conversion of a chromosomal his3-Delta MscI target sequence, and that this process requires the yeast recombination gene RAD52. In this study, we examine the involvement of other recombination and repair genes in RNA-mediated recombination, and gain insight into the nature of the recombination intermediate. We find that mutation of the mitotic RecA homologs RAD51, RAD55, and RAD57 increases the rate of RNA-mediated recombination relative to the wild type, and that these gene functions are not required for RNA-mediated gene conversion. Interestingly, RAD1 is required for RNA-mediated gene conversion of chromosomal his3-Delta MscI sequences, suggesting that the cDNA intermediate has a region of nonhomology that must be removed during recombination with target sequences. The observation that both RAD1 and RAD52 are required for RNA-mediated gene conversion of chromosomal but not plasmid sequences indicates a clear difference between these two pathways of homologous RNA-mediated recombination. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Derr, LK (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 311,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. NR 51 TC 29 Z9 30 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1998 VL 148 IS 3 BP 937 EP 945 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA ZC975 UT WOS:000072638000003 PM 9539415 ER PT J AU Cuesta, R Hinnebusch, AG Tamame, M AF Cuesta, R Hinnebusch, AG Tamame, M TI Identification of GCD14 and GCD15, novel genes required for translational repression of GCN4 mRNA in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; INITIATION FACTOR-II; AMINO-ACID BIOSYNTHESIS; PROTEIN-KINASE GCN2; MESSENGER-RNA; CELL-CYCLE; TRANSCRIPTIONAL ACTIVATOR; NEGATIVE REGULATOR; YEAST; EXPRESSION AB In Saccharomyces cerevisiae, expression of the transcriptional activator GCN4 increases at the translational level in response to starvation for an amino acid. The products of multiple GCD, genes are required for efficient repression of GCN4 mRNA translation under nonstarvation conditions. The majority of the known GCD genes encode subunits of the general translation initiation factor eIF-2 or eIF-2B. To identify additional initiation factors in yeast, we characterized 65 spontaneously arising Gcd(-) mutants. In addition to the mutations that were complemented by known GCD genes or by GCN3, we isolated mutant alleles of two new genes named GCD14 and GCD15. Recessive mutations in these two genes led to highly unregulated GCN4 expression and to derepressed transcription of genes in the histidine biosynthetic pathway under GCN4 control. The derepression of GCN4 expression in gcd14 and gcd15 mutants occurred with little or no increase in GCN4 mRNA levels, and it was dependent on upstream open reading frames (uORFs) in GCN4 mRNA that regulate its translation. We conclude that GCD14 and GCD15 are required for repression of GCN4 mRNA translation by the uORFs under conditions of amino acid sufficiency. The gcd14 and gcd15 mutations confer a slow-growth phenotype on nutrient-rich medium, and gcd15 mutations are lethal when combined with a mutation in gcd13. Like other known GCD genes, GCD14 and GCD15 are therefore probably required for general translation initiation in addition to their roles in GCN4-specific translational control. C1 Univ Salamanca, CSIC, Inst Microbiol Bioquim, Edificio Dept Biol, Salamanca 37007, Spain. NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. RP Tamame, M (reprint author), Univ Salamanca, CSIC, Inst Microbiol Bioquim, Edificio Dept Biol, Campus Miguel Unamuno, Salamanca 37007, Spain. EM tamame@gugu.usal.es NR 51 TC 19 Z9 21 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1998 VL 148 IS 3 BP 1007 EP 1020 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA ZC975 UT WOS:000072638000008 PM 9539420 ER PT J AU Slattery, JP O'Brien, SJ AF Slattery, JP O'Brien, SJ TI Patterns of Y and X chromosome DNA sequence divergence during the Felidae radiation SO GENETICS LA English DT Article ID SEX-DETERMINING REGION; DRIVEN MOLECULAR EVOLUTION; FINGER PROTEIN; GENES; ZFY; RODENTS; MOUSE; POLYMORPHISM; MAMMALS; ENCODES AB The 37 species of modern cats have evolved from approximately eight phylogenetic lineages within the past 10 to 15 million years. The Felidae family has been described with multiple measures of morphologic and molecular evolutionary methods that serve as a framework for cracking gene divergence during brief evolutionary periods. In this report, we compare the mode and tempo of evolution of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp), homologous genes located on the felid Y and X chromosomes, respectively. Zfy sequence variation evolves at about twice the rate of Zfx, and both gene intron sequences track feline hierarchical topologies accurately. As homoplasies are infrequent in patterns of nucleotide substitution, the Y chromosome sequence displays a remarkable degree of phylogenetic consistency among cat species and provides a highly informative glimpse of divergence of sex chromosome sequences in Felidae. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. RP Slattery, JP (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Bldg 560, Frederick, MD 21702 USA. EM slattery@fcrfv2.ncifcrf.gov NR 43 TC 58 Z9 63 U1 2 U2 10 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1998 VL 148 IS 3 BP 1245 EP 1255 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA ZC975 UT WOS:000072638000027 PM 9539439 ER PT J AU Wheelan, SJ Boguski, MS AF Wheelan, SJ Boguski, MS TI Late-night thoughts on the sequence annotation problem SO GENOME RESEARCH LA English DT Article C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. Johns Hopkins Univ, Sch Med, Dept Genet & Mol Biol, Baltimore, MD 21205 USA. RP Boguski, MS (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. NR 10 TC 20 Z9 22 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAR PY 1998 VL 8 IS 3 BP 168 EP 169 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZE853 UT WOS:000072838200004 PM 9521919 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to the Baylor College of Medicine Human Genome Sequencing Center's web site SO GENOME RESEARCH LA English DT Article C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAR PY 1998 VL 8 IS 3 BP 170 EP 174 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZE853 UT WOS:000072838200005 PM 9521920 ER PT J AU Agarwala, R Biesecker, LG Hopkins, KA Francomano, CA Schaffer, AA AF Agarwala, R Biesecker, LG Hopkins, KA Francomano, CA Schaffer, AA TI Software for constructing and verifying pedigrees within large genealogies and an application to the old order Amish of Lancaster County SO GENOME RESEARCH LA English DT Article ID LINKAGE ANALYSIS; PROGRAMS AB This paper describes PedHunter, a software package that facilitates creation and verification of pedigrees within large genealogies. A frequent problem in medical genetics is to connect distant relatives with a pedigree. PedHunter uses methods from graph theory to solve two versions of the pedigree connection problem for genealogies as well as other pedigree analysis problems. The pedigrees are produced by PedHunter as files in LINKAGE format ready for linkage analysis. PedHunter uses a relational database of genealogy data, with tables in specified format, for all calculations. The functionality and utility of PedHunter are illustrated by examples using the Amish Genealogy Database (AGDB), which was created for the Old Order Amish community of Lancaster County, Pennsylvania. C1 NIH, NHGRI, LGDR, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Immunogenet Lab,Div Med Genet, Baltimore, MD 21205 USA. NIH, NHGRI, MGB, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Ctr Genet Med, Baltimore, MD 21205 USA. RP Schaffer, AA (reprint author), NIH, NHGRI, LGDR, Bethesda, MD 20892 USA. RI Schaffer, Alejandro/F-2902-2012 FU NHGRI NIH HHS [P01HG00373] NR 25 TC 77 Z9 77 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAR PY 1998 VL 8 IS 3 BP 211 EP 221 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZE853 UT WOS:000072838200010 PM 9521925 ER PT J AU Salamon, C Chervenak, M Piatigorsky, J Sax, CM AF Salamon, C Chervenak, M Piatigorsky, J Sax, CM TI The mouse transketolase (TKT) gene: Cloning, characterization, and functional promoter analysis SO GENOMICS LA English DT Article ID CLASS-3 ALDEHYDE DEHYDROGENASE; WERNICKE-KORSAKOFF SYNDROME; PENTOSE-PHOSPHATE PATHWAY; ESCHERICHIA-COLI K-12; TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; CORNEAL EPITHELIUM; ULTRAVIOLET-LIGHT; 2ND TRANSKETOLASE; OXIDATIVE STRESS AB The transketolase (TKT) gene is expressed 30-50 times more highly in the mature mouse cornea than in other tissues. Here, we have cloned and characterized the 30- to 40-kb single-copy mouse TKT gene, Sequence analysis supports the suggestion that present-day TKT and TKT-like genes arose from the duplication of a single common ancestral gene. A 6-bp polymorphism is present between different mouse strains in the noncoding region of exon 2. 5' RACE and primer extension analyses indicated that two regions separated by 630 bp are used as transcription initiation sites; both mRNAs appear to use a common initiator ATG codon, The minor distal transcription initiation site, preceded by a TATA sequence, is utilized in liver and is followed by an untranslated exon (exon 1), The major proximal transcription initiation site lies within intron 1, is used in cornea and liver, lacks a TATA sequence, is GC rich, and initiates at multiple sites within a 10-bp span, resembling the promoters of other housekeeping genes. In transfected cornea and lens cell lines, the -49/+90 fragment fused to the CAT gene acted as a minimal promoter, with higher activity noted for the -510/+91 fragment. TKT mRNA levels increased sixfold in the mouse cornea in vivo within 1-2 days of eye opening and were elevated in a lens cell line exposed to H2O2 or the glutathione-specific oxidizing agent diamide and in whole newborn mouse eyes incubated in the presence of light, consistent with multiple consensus stress-inducible control sequences in the TKT promoter regions, Taken together, these observations suggest that oxidative stress may play a role in the regulation of this gene in the cornea. (C) 1998 Academic Press. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sax, CM (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 208,MSC 2730,6 Ctr Dr, Bethesda, MD 20892 USA. NR 70 TC 15 Z9 17 U1 0 U2 0 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 MAR 1 PY 1998 VL 48 IS 2 BP 209 EP 220 DI 10.1006/geno.1997.5187 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZD327 UT WOS:000072674100009 PM 9521875 ER PT J AU Han, P Fletcher, CF Copeland, NG Jenkins, NA Yaremko, LM Michaeli, T AF Han, P Fletcher, CF Copeland, NG Jenkins, NA Yaremko, LM Michaeli, T TI Assignment of the mouse Pde7A gene to the proximal region of chromosome 3 and of the human PDE7A gene to chromosome 8q13 SO GENOMICS LA English DT Article ID PHOSPHODIESTERASES C1 Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Michaeli, T (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 5 TC 8 Z9 8 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 MAR 1 PY 1998 VL 48 IS 2 BP 275 EP 276 DI 10.1006/geno.1997.5168 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZD327 UT WOS:000072674100019 PM 9521885 ER PT J AU Ajmani, RS Rifkind, JM AF Ajmani, RS Rifkind, JM TI Hemorheological changes during human aging SO GERONTOLOGY LA English DT Article DE blood viscosity; fibrinogen; coagulation; blood flow; erythrocyte deformability ID CORONARY HEART-DISEASE; FIBRIN DEGRADATION PRODUCTS; PLASMA-FIBRINOGEN; RISK-FACTORS; ERYTHROCYTE DEFORMABILITY; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; FACTOR-VII; AGE AB Various researchers have reported an association of hemorheological, hematological and metabolic changes with human aging, In this article an attempt has been made to review the present understanding of hemorheological changes and their probable role in the development of certain disorders/diseases during aging, The rise in fibrinogen, blood viscosity, plasma viscosity, red cell rigidity, fibrin degradation products and early activation of the coagulation system are some of the most prominent findings, It is generally agreed that a rise in blood viscosity factors leads to a state of hypoperfusion which results in impaired microcirculation. The cumulative effect of these changes appears in the form of a disturbed blood flow profile in older subjects leading to the development or aggravation of various circulatory disorders, Many studies indicate that hemorheological parameters that change in a number of diseases prevalent during aging include hypertension, stroke, diabetes. In addition correlations found between hemorheological parameters in the aged and decrements in certain cognitive functions and behavioral patterns suggest that hemorheological changes contribute to nonclinical aging changes. C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Room No 4-B-09,4940 Eastern Ave, Baltimore, MD 21224 USA. EM rifkind@lcmbsgi.nia.nih.gov NR 82 TC 38 Z9 42 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD MAR-APR PY 1998 VL 44 IS 2 BP 111 EP 120 DI 10.1159/000021993 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA YZ298 UT WOS:000072240400009 PM 9523223 ER PT J AU Taylor, SM Ross, NA Cummings, KM Glasgow, RE Goldsmith, CH Zanna, MP Corle, DK AF Taylor, SM Ross, NA Cummings, KM Glasgow, RE Goldsmith, CH Zanna, MP Corle, DK TI Community Intervention Trial for Smoking Cessation (COMMIT): changes in community attitudes toward cigarette smoking SO HEALTH EDUCATION RESEARCH LA English DT Article ID HEALTH PROMOTION; PUBLIC-OPINION; SELF-INTEREST; RESTRICTIONS; PREVENTION; SMOKERS; DESIGN AB The success of the Community Intervention Trial for Smoking Cessation (COMMIT) in changing smoking attitudes is examined by testing two primary hypotheses: (1) the priority of smoking as a public health problem increased more in the intervention communities than in the comparison communities, and (2) norms and values that support non-smoking increased more in the intervention than in the comparison communities, One community within each of 11 matched pairs was randomly assigned to receive a 4-year (1989-92) community-based smoking control intervention, Community attitudes towards smoking were measured primarily by cross-sectional surveys in 1989 (n = 9875) and 1993 (n = 14117) but a cohort (n = 5450) also provided attitude information. The main trial effect was on heavy smokers in the intervention communities who showed significantly snore change in their beliefs about smoking as a public health problem, Despite the absence of an intervention-comparison difference, the magnitude of change in community-wide norms and values was related to the level of smoking control activities, In the cohort, light-to-moderate smokers in the intervention communities came to have: stronger beliefs about smoking as a serious public health problem, COMMIT's impact on the beliefs of heavy smokers about the seriousness of smoking as a public health problem has important public health implications. C1 McMaster Univ, Hamilton, ON L8S 4K1, Canada. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Oregon Res Inst, Eugene, OR 97401 USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. NCI, Div Canc Biol & Diag, Biometry Branch, Bethesda, MD 20892 USA. RP Taylor, SM (reprint author), McMaster Univ, Hamilton, ON L8S 4K1, Canada. NR 26 TC 11 Z9 11 U1 0 U2 2 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 MAR PY 1998 VL 13 IS 1 BP 109 EP 122 DI 10.1093/her/13.1.109 PG 14 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA ZE514 UT WOS:000072800500010 PM 10178333 ER PT J AU Bergasa, NV Schmitt, JM Talbot, TL Alling, DW Swain, MG Turner, ML Jenkins, JB Jones, EA AF Bergasa, NV Schmitt, JM Talbot, TL Alling, DW Swain, MG Turner, ML Jenkins, JB Jones, EA TI Open-label trial of oral nalmefene therapy for the pruritus of cholestasis SO HEPATOLOGY LA English DT Article ID NALOXONE INFUSIONS; RAT-BRAIN; ANTAGONIST; BINDING; OPIOIDS AB The aims of this study were to determine whether long-term oral administration of the opiate antagonist nalmefene is associated with any beneficial effects in patients with pruritus secondary to cholestatic liver disease and to assess the safety of long-term administration of this drug to these patients. Fourteen patients with unrelieved chronic pruritus of cholestasis were studied. Scratching activity, independent of limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The dose of nalmefene, which initially was 2 mg orally twice daily, was increased during the study, usually until a satisfactory clinical response was achieved. Five patients experienced a transient opioid withdrawal-like reaction that did not preclude continuing with nalmefene therapy. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perception of pruritus on nalmefene. In 5 patients, exacerbations of pruritus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the dose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbation of pruritus after nalmefene therapy was suddenly discontinued, Blood levels of nalmefene were consistent with normal pharmacokinetics of the drug. These results suggest that nalmefene may have a favorable risk-to-benefit ratio when it is administered orally long-term to patients with the pruritus of cholestasis. C1 Beth Israel Med Ctr, Div Gastroenterol & Liver Dis, New York, NY 10003 USA. NIDDK, Liver Dis Sect, Digest Dis Branch, Bethesda, MD 20892 USA. NIH, Appl Clin Engn Sect, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NIAID, Div Intramural Res, Bethesda, MD 20892 USA. NCI, Div Dermatol, Bethesda, MD 20892 USA. NIH, Pharmaceut Dev Branch, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. Univ Calgary, Div Gastroenterol, Calgary, AB, Canada. Univ Amsterdam, Acad Med Ctr, Dept Gastrointestinal & Liver Dis, NL-1105 AZ Amsterdam, Netherlands. RP Bergasa, NV (reprint author), Beth Israel Med Ctr, Div Gastroenterol & Liver Dis, 18 Baird Hall,1st Ave & 16th St, New York, NY 10003 USA. NR 29 TC 106 Z9 108 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 1998 VL 27 IS 3 BP 679 EP 684 DI 10.1002/hep.510270307 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YZ384 UT WOS:000072249000007 PM 9500694 ER PT J AU Mast, EE Alter, MJ Holland, PV AF Mast, EE Alter, MJ Holland, PV TI Evaluation of assays for antibody to hepatitis E virus by a serum panel SO HEPATOLOGY LA English DT Article ID NON-B-HEPATITIS; LINKED-IMMUNOSORBENT-ASSAY; OPEN-READING FRAME-2; TRANSMITTED NON-A; SYNTHETIC PEPTIDES; ENZYME-IMMUNOASSAY; MOLECULAR-CLONING; FUSION PROTEINS; HEV; EPIDEMIC AB Few data are available to evaluate the performance of existing assays for antibody to the hepatitis E virus (anti-HEV), A panel of 164 randomized and coded sera was tested for anti-HEV by 12 different assays. The panel included a dilution series of an early convalescent human serum, known-positive sera (undiluted human sera obtained 2 months to 13 years after acute hepatitis E, and postinoculation chimpanzee sera), known-negative sera (preinoculation chimpanzee sera; sera from chimpanzees with hepatitis A virus, hepatitis B virus, or hepatitis C virus infection; and normal human sera), and sera obtained from previously tested U.S. blood donors without a history of hepatitis. Six tests detected anti-HEV in greater than or equal to 90% of undiluted known-positive sera, The sensitivity of all of the assays with known-positive sera ranged from 17% to 100%, and the limit of detection by endpoint dilution ranged from 1:5 to 1:160, Ten tests were nonreactive for all of the 22 known-negative sera, one test was reactive for one serum, and one test was reactive for 5 sera, In pairwise comparisons of different tests in blood donor sera, the overall concordance ranged from 49% to 94% (median, 69%) and the concordance among reactive sera ranged from 0% to 89% (median, 32%), Several of these tests performed well in detecting anti-HEV in known positive sera, However, highly discrepant results among U.S. blood donor sera indicate that anti-HEV seroprevalence data in non-HEV-endemic countries may be unreliable and should be interpreted with caution. C1 Ctr Dis Control & Prevent, Hepatitis Branch, Atlanta, GA 30333 USA. Sacramento Med Fdn, Sacramento, CA USA. NIH, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. RP Mast, EE (reprint author), Ctr Dis Control & Prevent, Hepatitis Branch, Mailstop G37,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 32 TC 154 Z9 178 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 1998 VL 27 IS 3 BP 857 EP 861 DI 10.1002/hep.510270331 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YZ384 UT WOS:000072249000031 PM 9500718 ER PT J AU Stone, DL Agarwala, R Schaffer, AA Weber, JL Vaske, D Oda, T Chandrasekharappa, SC Francomano, CA Biesecker, LG AF Stone, DL Agarwala, R Schaffer, AA Weber, JL Vaske, D Oda, T Chandrasekharappa, SC Francomano, CA Biesecker, LG TI Genetic and physical mapping of the McKusick-Kaufman syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID BARDET-BIEDL-SYNDROME; LINKAGE ANALYSIS; SYNDROME LOCUS; REPEAT POLYMORPHISMS; STRATEGIES; MARKERS AB McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos, This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity, Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978, The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons, Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894, an area that includes the Alagille syndrome critical region, The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21, The physical map of this region has been defined, and additional polymorphic markers have been isolated, The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome, Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease-causing mutations. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Lab Gene Transfer, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. Johns Hopkins Univ, Ctr Genet Med, Baltimore, MD 21287 USA. RP Biesecker, LG (reprint author), Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. RI Schaffer, Alejandro/F-2902-2012 NR 37 TC 33 Z9 36 U1 0 U2 0 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 MAR PY 1998 VL 7 IS 3 BP 475 EP 481 DI 10.1093/hmg/7.3.475 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZB845 UT WOS:000072513800021 PM 9467007 ER PT J AU Gould, TD Pfeifer, K AF Gould, TD Pfeifer, K TI Imprinting of mouse Kvlqt1 is developmentally regulated SO HUMAN MOLECULAR GENETICS LA English DT Article ID H19 GENE; POTASSIUM CHANNEL; K(V)LQT1; PROTEINS; FORM AB Mouse distal chromosome 7 contains a cluster of at least five imprinted genes, The syntenic region in humans, at 11p15.5, has been implicated in several genetic disorders, Consistent with the imprinted status of the genes in the region, Beckwith-Wiedemann syndrome (BWS) and Wilms tumor are each associated with loss of maternal information, Also mapping to 11p15.5 are long QT and Jervell and Lange-Nielsen (JLN) syndromes, In contrast to BWS and Wilms tumor, these syndromes do not show any parent of origin bias, Recently positional cloning has identified KVLQT1 as the 11p15.5 gene responsible for increased susceptibility to long QT and JLN syndromes. Other studies associate KVLQT1 with BWS, Human KVLQT1 is paternally imprinted in embryos, In this study we present a contig and transcript map of distal mouse 7 and we physically and genetically map mouse Kvlqt1 to the region, Mouse Kvlqt1 is strongly expressed in heart, lung, gut, kidney and uterus, While its early developmental expression is maternal in origin, the paternal allele becomes increasingly active during development, Late juvenile and adult animals show complete biallelism, suggesting an explanation for the lack of parent of origin bias in JLN and long QT. C1 NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), NICHHD, Lab Mammalian Genes & Dev, Bldg 6B,Room 2B206,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kpfeifer@helix.nih.gov OI Pfeifer, Karl/0000-0002-0254-682X NR 23 TC 87 Z9 87 U1 0 U2 0 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 MAR PY 1998 VL 7 IS 3 BP 483 EP 487 DI 10.1093/hmg/7.3.483 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZB845 UT WOS:000072513800022 PM 9467008 ER PT J AU Marsh, DJ Coulon, V Lunetta, KL Rocca-Serra, P Dahia, PLM Zheng, ZM Liaw, D Caron, S Duboue, B Lin, AY Richardson, AL Bonnetblanc, JM Bressieux, JM Cabarrot-Moreau, A Chompret, A Demange, L Eeles, RA Yahanda, AM Fearon, ER Fricker, JP Gorlin, RJ Hodgson, SV Huson, S Lacombe, D LePrat, F Odent, S Toulouse, C Olopade, OI Sobol, H Tishler, S Woods, CG Robinson, BG Weber, HC Parsons, R Peacocke, M Longy, M Eng, C AF Marsh, DJ Coulon, V Lunetta, KL Rocca-Serra, P Dahia, PLM Zheng, ZM Liaw, D Caron, S Duboue, B Lin, AY Richardson, AL Bonnetblanc, JM Bressieux, JM Cabarrot-Moreau, A Chompret, A Demange, L Eeles, RA Yahanda, AM Fearon, ER Fricker, JP Gorlin, RJ Hodgson, SV Huson, S Lacombe, D LePrat, F Odent, S Toulouse, C Olopade, OI Sobol, H Tishler, S Woods, CG Robinson, BG Weber, HC Parsons, R Peacocke, M Longy, M Eng, C TI Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation SO HUMAN MOLECULAR GENETICS LA English DT Article ID LHERMITTE-DUCLOS DISEASE; ENDOCRINE NEOPLASIA TYPE-2; RILEY-RUVALCABA-SYNDROME; CONSORTIUM; POLYPOSIS; FAMILY AB The tumour suppressor gene PTEN, which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase: PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) anti Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations, These mutations were scattered over the entire length of PTEN with the exception of the first, fourth and last exons. A 'hot spot' for; PTEN mutation In CD was identified in exon 5 that contains the PTPase, core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region, Germline PTEN mutations were identified int four of seven (57%) BZS families studied, interestingly, none of these mutations was observed in the PTPase core motif. II is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family Genotype-phenotype studies were not performed on this small group of BZS families, However genotype-phenotype analysis in the group of CD families revealed two possible associations worthy of follow-up in independent analyses, The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvememt (unaffected versus benign versus malignant), Specifically and more directly an association was also observed between the presence of a PTEN mutation and malignant breast disease, Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families. C1 Harvard Univ, Charles A Dana Human Canc Genet Unit, Richard & Susan Smith Labs, Dana Farber Canc Inst,Sch Med,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Inst Bergoni, Mol Oncol Lab, F-33076 Bordeaux, France. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Columbia Univ, Ctr Canc, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Ctr Canc, Dept Med, New York, NY 10032 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, Sydney, NSW 2006, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. CHRU Dupuytren, Dept Dermatol, Limoges, France. CHU, Dept Dermatol, Troyes, France. CHU Rangueil, F-31054 Toulouse, France. Inst Gustave Roussy, Dept Dermatol, Villejuif, France. Inst Jean Godinoi, Oncogenet Unit, Reims, France. Royal Marsden Hosp, Inst Canc Res, Sutton SM2 5PT, Surrey, England. Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA. Univ Michigan, Sch Med, Div Med & Mol Genet, Ann Arbor, MI USA. Ctr Paul Strauss, Oncogenet Unit, Strasbourg, France. Univ Minnesota, Dept Oral Pathol & Genet, Minneapolis, MN USA. Guys & St Thomas Hosp, Dept Clin Genet, London SE1 9RT, England. Churchill Hosp, Oxford Radcliffe Hosp Trust, Dept Clin Genet, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. CHU, Dept Med Genet, Bordeaux, France. CHU Bordeaux, Dept Endocrinol, Pessac, France. CHRU Rennes, Dept Med Genet, Pontchaillou, France. Inst Bergoni, Oncogenet Unit, Bordeaux, France. Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Inst J Paoli I Calmettes, INSERM CRI 9703, Dept Oncogenet, F-13009 Marseille, France. Harvard Pilgrim Hlth Plan, Boston, MA 02215 USA. St James Univ Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. Boston Univ, Sch Med, Gastroenterol Sect, Boston, MA 02118 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Dermatol, New York, NY USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Harvard Univ, Charles A Dana Human Canc Genet Unit, Richard & Susan Smith Labs, Dana Farber Canc Inst,Sch Med,Dept Med, SM822,1 Jimmy Fund Way, Boston, MA 02115 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 36 TC 406 Z9 416 U1 1 U2 8 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 MAR PY 1998 VL 7 IS 3 BP 507 EP 515 DI 10.1093/hmg/7.3.507 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZB845 UT WOS:000072513800025 PM 9467011 ER PT J AU Travis, WD Gal, AA Colby, TV Klimstra, DS Falk, R Koss, MN AF Travis, WD Gal, AA Colby, TV Klimstra, DS Falk, R Koss, MN TI Reproducibility of neuroendocrine lung tumor classification SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 23-29, 1996 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol DE lung; neuroendocrine; carcinoid; atypical carcinoid; large-cell neuroendocrine carcinoma; small-cell carcinoma; reproducibility ID SMALL-CELL-CARCINOMA; INTEROBSERVER REPRODUCIBILITY; HISTOPATHOLOGIC CLASSIFICATION; BRONCHOPULMONARY TRACT; ATYPICAL CARCINOIDS; CANCER; NEOPLASMS; CRITERIA; SPECTRUM; LESIONS AB For a tumor classification scheme to he useful, ii. must be reproducible and it must show clinical significance. Classification of neuroendocrine lung tumors is a difficult problem with little information about interobserver reproducibility. We sought to evaluate the classification of typical carcinoid (TC), atypical carcinoid (AC), large-cell neuroendocrine carcinoma (LCNEC), and small-cell carcinoma (SCC) tumors as proposed by W.D. Travis et al (Am J Surg Pathol 15:529, 1991). Forty neuroendocrine tumors were retrieved from the Armed Forces institute of Pathology (AFIP) files and independently evaluated by five lung: pathologists and classified as TC, ACI LCNEC, or SCC (pure SCC, mixed small cell/large cell, and combined SCC). A single hematoxylin and cosin-stained slide from each case was reviewed. Each participant was provided a set of tables summarizing the criteria for separation of the four major categories. Agreement was regarded as unanimous if all fire pathologists agreed, a majority if four agreed, and a consensus if three or more pathologists agreed. The kappa statistic was calculated to measure the degree of agreement between two observers. A consensus diagnosis was achieved in all 40 cases (100%), a majority agreement in 31 of 40 (78%), and unanimous agreement in 22 of 40 (55%) of cases. Unanimous agreement occurred in seven of SCC (70%), seven of TC (58%), four of AC (50%), and four of LCNEC (40%). A majority diagnosis was achieved in 11 of 12 (92%) of TC, 9 of 10 (90%) of SCC, 6 of 8 (75%) of AC, and 5 of 10 (50%) of LCNEC. Most of the kappa values were 0.70 or greater, falling into the substantial agreement category. The most common disagreements fell between LCNEC and SCC, followed by TC and AC, and AC and LCNEC. The highest reproducibility occurred for SCC and TC, with disagreement in 8% and 10% of the diagnoses, respectively. For TC, 10% of the diagnoses rendered were AC. For AC, 15% of the diagnoses were rendered as TC, with 2.5% called LCNEC: and 2.5% called SCC. For LCNEC, 18% and 4% of the diagnoses were called SCC and AC, respectively. For SCC, 4% of the diagnoses were called AC and 4% were called LCNEC. Thus, using the classification scheme tested, a consensus diagnosis can be achieved for virtually all neuroendocrine hmg tumors viith substantial agreement between experienced lung pathologists. Classification of NE tumors is most reproducible for classification of TC and SCC but less reproducible for AC and LCNEC. These results indicate a need for more careful definition and application of criteria for TC versus AC and SCC versus LCNEC. Copyright (C) 1998 by W.B. Saunders Company. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Mayo Clin, Dept Pathol, Scottsdale, AZ USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NCI, Environm Epidemiol Branch, NIH, Rockville, MD USA. RP Travis, WD (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Bldg 54,Rm M003B, Washington, DC 20306 USA. NR 34 TC 152 Z9 155 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1998 VL 29 IS 3 BP 272 EP 279 DI 10.1016/S0046-8177(98)90047-8 PG 8 WC Pathology SC Pathology GA YZ606 UT WOS:000072270900012 PM 9496831 ER PT J AU Yap, TK Frieder, O Martino, RL AF Yap, TK Frieder, O Martino, RL TI Parallel computation in biological sequence analysis SO IEEE TRANSACTIONS ON PARALLEL AND DISTRIBUTED SYSTEMS LA English DT Article DE sequence; comparison; alignment; search; retrieval; database; algorithm; parallel; speculative; computation ID PROTEIN SEQUENCES; SPECULATIVE COMPUTATION; MULTIPLE ALIGNMENT; LINEAR-SPACE; DATA-BANK; ALGORITHM; STRATEGY; IDENTIFICATION; MICROCOMPUTER; SUBSEQUENCES AB A massive volume of biological sequence data is available in over 36 different databases worldwide, including the sequence data generated by the Human Genome project. These databases, which also contain biological and bibliographical information, are growing at an exponential rate. Consequently, the computational demands needed to explore and analyze the data contained in these databases is quickly becoming a great concern. To meet these demands, we must use high performance computing systems, such as parallel computers and distributed networks of workstations. We present two parallel computational methods for analyzing these biological sequences. The first method is used to retrieve sequences that are homologous to a query sequence. The biological information associated with the homologous sequences found in the database may provide important clues to the structure and function of the query sequence. The second method, which helps in the prediction of the function, structure, and evolutionary history of biological sequences, is used to align a number of homologous sequences with each other. These two parallel computational methods were implemented and evaluated on an Intel iPSC/860 parallel computer. The resulting performance demonstrates that parallel computational methods can significantly reduce the computational time needed to analyze the sequences contained in large databases. C1 NIH, Div Comp Res & Technol, Bethesda, MD 20892 USA. Florida Inst Technol, Div Elect & Comp Sci & Engn, Melbourne, FL 32901 USA. RP Yap, TK (reprint author), NIH, Div Comp Res & Technol, Bldg 12A Room 2033,12 South Dr, Bethesda, MD 20892 USA. EM yap@helix.nih.gov; ophir@ee.fit.edu; martino@alw.nih.gov NR 51 TC 28 Z9 31 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1045-9219 EI 1558-2183 J9 IEEE T PARALL DISTR JI IEEE Trans. Parallel Distrib. Syst. PD MAR PY 1998 VL 9 IS 3 BP 283 EP 294 DI 10.1109/71.674320 PG 12 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA ZF310 UT WOS:000072884700006 ER PT J AU Pospisil, R Mage, RG AF Pospisil, R Mage, RG TI CD5 and other superantigens as 'ticklers' of the B-cell receptor SO IMMUNOLOGY TODAY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTIBODY REPERTOIRE; ANTIGEN; SURFACE; EXPRESSION; SELECTION; SURVIVAL; BINDING; STAGE AB The exact roles of endogenous and exogenous ligands as stimuli for B-cell survival through 'tickling' the B-cell receptor are unclear. This article considers die contribution of unconventional interactions with the variable heavy chain by CD5 and other superantigens. C1 NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. Inst Microbiol, Div Immunol & Gnotobiol, Prague 14200 4, Czech Republic. RP Pospisil, R (reprint author), NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. EM rpospisil@niaid.nih.gov; rm3Z@nih.gov RI Pospisil, Richard/B-7467-2012 NR 28 TC 24 Z9 24 U1 0 U2 1 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 MAR PY 1998 VL 19 IS 3 BP 106 EP 108 DI 10.1016/S0167-5699(97)01215-2 PG 3 WC Immunology SC Immunology GA ZB687 UT WOS:000072497500003 PM 9540267 ER PT J AU Harry, GJ AF Harry, GJ TI Mechanisms of axonal transport: Target sites for neurotoxicants SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Mechanisms of Toxicity CY SEP 08-10, 1997 CL BALTIMORE, MARYLAND SP Ctr Alternat Animal Testing, Ind In Vitro Toxicol Grp ID DIFFERENTIATING N1E.115 NEUROBLASTOMA; NEURITE OUTGROWTH; MOLECULAR MOTORS; VIDEO MICROSCOPY; NERVOUS-SYSTEM; SCIATIC-NERVE; ACRYLAMIDE; KINESIN; NEUROPATHY; VESICLES AB The process of axonal transport is critical for maintenance of the axonal membrane and nerve endings. Various toxicants produce morphological alterations in the axon of the peripheral nervous system. Thus, alterations in axonal transport have been a major research focus in toxicant-induced peripheral axonopathies. Axonal transport can be altered at a specific step in the mechanism by the movement of a specific component, or by more general biochemical alterations. This manuscript presents basic principles of axonal transport in the nervous system and the complicated interdependent nature of the biological process. This information is presented to give a mechanistic framework in which one can evaluate data from in vitro studies. While information obtained about the process in either type of system is important in the understanding of the pathogenesis and progression of toxicant-induced. neuropathies, an emphasis is placed on the need for in vivo studies to determine biological relevance and the causative nature of axonal transport deficits in peripheral neuropathies. C1 NIEHS, Toxicol Lab, Neurotoxicol Grp, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Toxicol Lab, Neurotoxicol Grp, MD-C1-04,POB 12233, Res Triangle Pk, NC 27709 USA. NR 47 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD SPR PY 1998 VL 11 IS 1 BP 83 EP 93 PG 11 WC Toxicology SC Toxicology GA ZQ716 UT WOS:000073895900010 ER PT J AU Amano, KI Williams, JC Dasch, GA AF Amano, KI Williams, JC Dasch, GA TI Structural properties of lipopolysaccharides from Rickettsia typhi and Rickettsia prowazekii and their chemical similarity to the lipopolysaccharide from Proteus vulgaris OX19 used in the Weil-Felix test SO INFECTION AND IMMUNITY LA English DT Article ID PHASE-I; COXIELLA-BURNETII; TEST ANTIGENS; IMMUNOLOGICAL CHARACTERIZATION; TSUTSUGAMUSHI; PEPTIDOGLYCAN; REACTIVITY; COMPONENTS; SERA AB The lipopolysaccharides (LPSs) isolated from typhus group (TG) rickettsiae Rickettsia typhi and Rickettsia prowazekii were characterized by chemical analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by silver staining. LPSs from two species of TG rickettsiae contained glucose, 3-deoxy-D-manno-octulosonic acid, glucosamine, quinovosamine, phosphate, and fatty acids (beta-hydroxylmyristic acid and heneicosanoic acid) but not heptose. The O-polysaccharides of these LPSs were composed of glucose, glucosamine, quinovosamine, and phosphorylated hexosamine. Resolution of these LPSs by their apparent molecular masses by SDS-PAGE showed that they have a common ladder-like pattern. Based on the results of chemical composition and SDS-PAGE pattern, we suggest that these LPSs act as group-specific antigens. Furthermore, glucosamine, quinovosamine, and phosphorylated hexosamine were also found in the O-polysaccharide of the LPS from Proteus vulgaris OX19 used in the Weil-Felix test, suggesting that they may represent the antigens common to LPSs from TG rickettsiae and P. vulgaris OX19. C1 USA, Med Res Inst Infect Dis, Rickettsial Dis Lab, Airborne Dis Div, Frederick, MD 21701 USA. NIAID, Off Sci Director, Bethesda, MD 20204 USA. USN, Med Res Inst, Bethesda, MD 20014 USA. RP Amano, KI (reprint author), Akita Univ, Sch Med, Cent Res Lab, Hondo 1-1-1, Akita 010, Japan. EM amanocrl@med.akita-u.ac.jp NR 34 TC 16 Z9 16 U1 0 U2 4 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 MAR PY 1998 VL 66 IS 3 BP 923 EP 926 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YY565 UT WOS:000072160900006 PM 9488376 ER PT J AU Su, H Caldwell, HD AF Su, H Caldwell, HD TI Sulfated polysaccharides and a synthetic sulfated polymer are potent inhibitors of Chlamydia trachomatis infectivity in vitro but lack protective efficacy in an in vivo murine model of chlamydial genital tract infection SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; HIV AGENT INVITRO; DEXTRAN SULFATE; ECTOPIC PREGNANCY; EPITHELIAL-CELLS; HEPARAN-SULFATE; REPLICATION; INFERTILITY; ANTIBODIES; MECHANISM AB Heparin, dextran sulfate, pentosan polysulfate, and a sulfated synthetic copolymer of acrylic acid and vinyl alcohol were shown to be potent inhibitors of Chlamydia trachomatis infectivity for cultured human epithelial cells. Despite their potent antichlamydial activity in vitro, neither heparin nor dextran sulfate mas effective in inhibiting the infectivity of C. trachomatis in a murine model of chlamydial infection of the female genital tract. C1 NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Immunol Sect,NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Immunol Sect,NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 23 TC 16 Z9 16 U1 0 U2 0 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 MAR PY 1998 VL 66 IS 3 BP 1258 EP 1260 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YY565 UT WOS:000072160900053 PM 9488423 ER PT J AU Perry, LL Feilzer, K Caldwell, HD AF Perry, LL Feilzer, K Caldwell, HD TI Neither interleukin-6 nor inducible nitric oxide synthase is required for clearance of Chlamydia trachomatis from the murine genital tract epithelium SO INFECTION AND IMMUNITY LA English DT Article ID T-CELL CONTROL; IN-VIVO; L-ARGININE; LISTERIA-MONOCYTOGENES; ACTIVATED MACROPHAGES; IL-6-DEFICIENT MICE; MOLECULAR MECHANISM; INTERFERON-GAMMA; INFECTION; RESPONSES AB Female mice bearing targeted mutations in the interleukin-6 or inducible nitric oxide synthase locus mounted effective immune responses following vaginal infection with Chlamydia trachomatis. Chlamydial clearance rates, local Th1 cytokine production, and host antibody responses were similar to those of immunocompetent control mice. Therefore, neither gene product appears to be critical for the resolution of chlamydial infections of the urogenital epithelium. C1 NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Immunol Sect,NIH, Hamilton, MT 59840 USA. RP Perry, LL (reprint author), NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Immunol Sect,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM Linda_Perry@nih.gov NR 43 TC 34 Z9 34 U1 0 U2 0 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 MAR PY 1998 VL 66 IS 3 BP 1265 EP 1269 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YY565 UT WOS:000072160900055 PM 9488425 ER PT J AU Henderson, DK AF Henderson, DK TI Bacillus of Calmette and Guerin vaccination for tuberculosis prevention in healthcare workers: How good is good enough? SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID PUBLISHED LITERATURE; BCG VACCINATION; CARE WORKERS; EFFICACY; METAANALYSIS C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Warren G Magnuson Clin Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 1998 VL 19 IS 3 BP 159 EP 161 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA ZE874 UT WOS:000072840300006 PM 9552182 ER PT J AU Walsh, TJ Hiemenz, J AF Walsh, TJ Hiemenz, J TI Lipid formulations of amphotericin B: Recent developments in improving the therapeutic index of a gold standard SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; BONE-MARROW TRANSPLANT; COLLOIDAL DISPERSION; PULMONARY ASPERGILLOSIS; DEOXYCHOLATE SUSPENSION; NEUTROPENIC PATIENTS; ANTIFUNGAL ACTIVITY; CANDIDA-ALBICANS; MURINE COCCIDIOIDOMYCOSIS; CRYPTOCOCCAL MENINGITIS C1 NCI, Immunocompromised Host Sect, Bethesda, MD 20892 USA. Florida Hosp, Walt Disney Mem Canc Inst, Div Hematol Oncol, Orlando, FL USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. NR 93 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAR-APR PY 1998 VL 7 SU 1 BP S16 EP S27 DI 10.1097/00019048-199803000-00004 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZG460 UT WOS:000073004800004 ER PT J AU Francis, DA Sen, RJ Rice, N Rothstein, TL AF Francis, DA Sen, RJ Rice, N Rothstein, TL TI Receptor-specific induction of NF-kappa B components in primary B cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B cell antigen receptor; B lymphocytes; CD40 receptor; DNA-binding proteins; I kappa B proteins; RelB protein; transcription factors ID UBIQUITIN-PROTEASOME PATHWAY; TRANSCRIPTION FACTOR; NUCLEAR EXPRESSION; DNA-BINDING; PRECURSOR P105; B/REL FAMILY; ACTIVATION; RELB; PROTEINS; STIMULATION AB The NF-kappa B transcription factor complex plays a key role in the expression of genes involved in immune responses. Nuclear NF-kappa B is induced in B lymphocytes by engagement of either the antigen receptor (sig) or the CD40 receptor for a T cell activation antigen, although different intracellular pathways appear to be involved. In the present study the protein composition of NF-kappa B complexes triggered by sig and CD40 was probed by electrophoretic mobility shift, supershift, shift-Western, and Western blot analyses. At the time of peak NF-kappa B induction (2 h), the NF-kappa B components detected in the complexes induced through sig and through CD40 were the same. However, with continued stimulation RelB completely disappeared from anti-Ig-stimulated kappa B binding material, but remained a component of CD40L-induced NF-kappa B. The toss of DNA-binding RelB from anti-Ig-induced NF-kappa B did not result from depletion of RelB from B cell nuclei, suggesting specific regulation of RelB function which is not directly attributed to I kappa B function. These results indicate that NF-kappa B complexes may undergo protein-specific alterations in a time- and receptor-dependent fashion that may be associated with differences in the outcomes of B cell stimulation through sig and CD40. C1 Boston Univ, Med Ctr, Dept Med & Microbiol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Evans Mem Dept Clin Res, Boston, MA 02118 USA. Brandeis Univ, Dept Biol, Rosenstiel Ctr, Waltham, MA 02254 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Frederick, MD USA. RP Rothstein, TL (reprint author), Boston Univ, Med Ctr, Dept Med & Microbiol, Room E-556,88 E Newton St, Boston, MA 02118 USA. FU NCI NIH HHS [CA66626]; NIGMS NIH HHS [F31 GM16395] NR 52 TC 33 Z9 33 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 MAR PY 1998 VL 10 IS 3 BP 285 EP 293 DI 10.1093/intimm/10.3.285 PG 9 WC Immunology SC Immunology GA ZF698 UT WOS:000072923100005 PM 9576616 ER PT J AU Shi, YB Su, Y Li, Q Damjanovski, S AF Shi, YB Su, Y Li, Q Damjanovski, S TI Auto-regulation of thyroid hormone receptor genes during metamorphosis: Roles in apoptosis and cell proliferation SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Review DE thyroid hormone receptor; apoptosis; transcriptional regulation; xenopus; postembryonic development ID NUCLEOSOME REMODELING FACTOR; RETINOIC ACID RECEPTORS; TUMOR VIRUS PROMOTER; ANURAN TADPOLE TAIL; AMPHIBIAN METAMORPHOSIS; XENOPUS-LAEVIS; TRANSCRIPTIONAL ACTIVATION; NUCLEAR RECEPTORS; SMALL-INTESTINE; MOLECULAR MECHANISMS C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 105 TC 16 Z9 16 U1 0 U2 2 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD MAR PY 1998 VL 42 IS 2 BP 107 EP 116 PG 10 WC Developmental Biology SC Developmental Biology GA YY845 UT WOS:000072192200001 PM 9551856 ER PT J AU Mishra, L Cai, T Levine, A Weng, D Mezey, E Mishra, B Gearhart, J AF Mishra, L Cai, T Levine, A Weng, D Mezey, E Mishra, B Gearhart, J TI Identification of elf1, a beta-spectrin, in early mouse liver development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE spectrin; liver development; in situ hybridization ID CDNA LIBRARIES; EXPRESSION; CELLS AB beta-spectrins play essential roles in cell-cell interactions and in the maintenance of cell polarity. Our aim was to identify beta-spectrin genes important for the establishment of hepatocyte polarity and differentiation. Using subtractive screening of cDNA libraries from early embryonic mouse livers (post-coital days 10,11, and 12), we have isolated elf1 (embryonic liver fodrin 1), a differentially expressed beta-spectrin or fodrin (beta SpII Sigma I). Elf7 encodes a 220-amino acid protein with an NH2 terminal actin-binding domain. In situ hybridization studies demonstrate elf1 expression initially in day 10 embryonic heart tissue, then in day 11-11.5 hepatic tissue. These studies suggest that elf1 may play a role in the emergence of hepatocyte polarity during liver development. C1 Vet Affairs Med Ctr, Dept Med, Washington, DC 20422 USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. RP Mishra, L (reprint author), Vet Affairs Med Ctr, Dept Med, 151W,50 Irving St NW, Washington, DC 20422 USA. EM mishra.lopa@washington.va.gov FU NIDDK NIH HHS [DK 50458] NR 20 TC 19 Z9 20 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD MAR PY 1998 VL 42 IS 2 BP 221 EP 224 PG 4 WC Developmental Biology SC Developmental Biology GA YY845 UT WOS:000072192200013 PM 9551868 ER PT J AU Murata, T Obiri, NI Puri, RK AF Murata, T Obiri, NI Puri, RK TI Structure of and signal transduction through interleukin-4 and interleukin-13 receptors (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Review DE signal transduction; interleukin-4; interleukin-13 receptors ID HUMAN B-CELLS; TUMOR-NECROSIS-FACTOR; JAK-3 JANUS KINASE; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; IL-4 RECEPTOR; CARCINOMA-CELLS; ALPHA-CHAIN; PSEUDOMONAS EXOTOXIN; HIGH-AFFINITY AB We have recently demonstrated that two different forms of IL-4R exist; classical or alternative. The classical IL-4R is predominantly expressed in hematopoietic cells and consist of IL-4R beta and IL-2R gamma(c) (gamma(c)) chains. On the other hand, alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and IL-13R alpha' chains. Moreover, the alternative form of lL-4R is also utilized as a functional component IL-13R complex. It has been shown that the phosphorylation and activation of JAK3 tyrosine kinase is crucial for IL-4 activation of STAT6 in hematopoietic cells. However, we have recently demonstrated that nonhematopoietic cells lack JAK3 expression. We also demonstrated that in these cells, STAT6 activation is mediated through JAK1 and JAK2 tyrosine kinases instead. Furthermore, our results show that IL-4 and IL-13 signals are transmitted through the alternative form of IL-4R in these cells. Thus, major differences exist between hematopoietic and non-hematopoietic cells with regard to structure and signal transduction through IL-4R and IL-13R systems. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 95 TC 112 Z9 114 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 1998 VL 1 IS 3 BP 551 EP 557 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117DV UT WOS:000075766100005 PM 9852261 ER PT J AU Li, QD Tsang, B Ding, L Ding, ZR AF Li, QD Tsang, B Ding, L Ding, ZR TI Vertical transmission of human immunodeficiency virus type 1: Frequency and correlation of transmission (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE HIV; vertical transmission ID POLYMERASE CHAIN-REACTION; HIV-1 INFECTION; MATERNAL TRANSMISSION; RETROVIRAL DISEASE; MOTHER; INFANT; RISK; CHILDREN; DNA AB Child bearing age women constitute the fastest growing subset of the human immunodeficiency virus (HIV) infected population. Consistent with this fact is the increasing number of HN infected children. Vertical transmission from mother to child is the most common route of infection. Because of the nature of the virus, it is difficult to determine the timing of infection. There are three time periods during which infection can occur: prenatally, perinatally, or postnatally. Evidence for each is presented within this review. C1 NCI, Med Branch, Dev Therapeut Dept,Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Antiepidem Ctr Guangxi, Nanning 530021, Guangxi, Peoples R China. RP Li, QD (reprint author), NCI, Med Branch, Dev Therapeut Dept,Div Clin Sci, NIH, Bldg 10,Room 13N248,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 5 Z9 5 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 1998 VL 1 IS 3 BP 589 EP 591 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117DV UT WOS:000075766100012 PM 9852268 ER PT J AU Yu, JJ Mu, CJ Dabholkar, M Guo, Y Bostick-Bruton, F Reed, E AF Yu, JJ Mu, CJ Dabholkar, M Guo, Y Bostick-Bruton, F Reed, E TI Alternative splicing of ERCC1 and cisplatin-DNA adduct repair in human tumor cell lines SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE alternative splicing; ERCC1; DNA adduct repair ID EXCISION-REPAIR; MESSENGER-RNA; GENE ERCC-1; EXPRESSION; RESISTANCE; SENSITIVITY; DEFICIENCY; YEAST AB Alternative splicing is a common natural tool for the inhibition of function of full length gene products. We explored whether there was evidence that alternative splicing of ERCC1 may serve such a function for nucleotide excision repair. The ratio of alternatively spliced species to full length species was assessed for the protein and/or for the mRNA, for a series of human cell lines and tissues. This ratio was plotted against the amount of cisplatin-DNA adduct repair in each cell line (n = 9), as measured by atomic absorbance spectrometry. As the percentage of alternatively spliced protein and/or mRNA increased, the amount of cisplatin-DNA adduct that was repaired was reduced. This inverse relationship was associated with a substantial amount of scatter (r = 0.635), particularly at low levels of repair. These data demonstrate an association between alternative splicing of ERCC1, and reduction in cellular capability to repair cisplatin-DNA adduct. C1 NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch, 10-12N226, Bethesda, MD 20892 USA. NR 21 TC 21 Z9 21 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 1998 VL 1 IS 3 BP 617 EP 620 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117DV UT WOS:000075766100019 PM 9852275 ER PT J AU Frye, MA Ketter, TA Altshuler, LL Denicoff, K Dunn, RT Kimbrell, TA Cora-Locatelli, G Post, RM AF Frye, MA Ketter, TA Altshuler, LL Denicoff, K Dunn, RT Kimbrell, TA Cora-Locatelli, G Post, RM TI Clozapine in bipolar disorder: treatment implications for other atypical antipsychotics SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE clozapine; bipolar disorder; neuroleptics ID MIDBRAIN DOPAMINE NEURONS; MANIC-DEPRESSIVE ILLNESS; PSYCHOTIC MOOD DISORDERS; CAUDATE NUCLEI VOLUMES; FOS PROTEIN EXPRESSION; LONG-TERM TREATMENT; SCHIZOPHRENIC-PATIENTS; SCHIZOAFFECTIVE DISORDER; TARDIVE-DYSKINESIA; RISPERIDONE TREATMENT AB Traditional neuroleptics are often utilized clinically for the management of bipolar disorder. Although effective as antimanic agents, their mood stabilizing properties are less clear. Additionally, their acute clinical side effect profile and long term risk of tardive dyskinesia, particularly in mood disorder patients, portend significant liability. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder focusing on clozapine as the prototypical agent. Although, preclinical research and clinical experience suggest that the atypical antipsychotics are distinctly different from typical antipsychotics, they themselves are heterogeneous in profiles of neuropharmacology, clinical efficacy, and tolerability. The early clinical experience of clozapine as a potential mood stabilizer suggests greater antimanic than antidepressant properties. Conversely, very preliminary clinical experience with risperidone suggests greater antidepressant than antimanic properties and some liability for triggering or exacerbating mania. Olanzapine and sertindole are under investigation in psychotic mood disorders. The foregoing agents and future drugs with atypical neuroleptic properties should come to play an increasingly important role, compared to the older classical neuroleptics, in the acute and long term management of bipolar disorder. (C) 1998 Elsevier Science B.V. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Frye, MA (reprint author), NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. EM maf@helix.nih.gov NR 147 TC 93 Z9 97 U1 2 U2 3 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 MAR PY 1998 VL 48 IS 2-3 BP 91 EP 104 DI 10.1016/S0165-0327(97)00160-2 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZC526 UT WOS:000072589200001 PM 9543198 ER PT J AU Richardson, LL Kleinman, HK Dym, M AF Richardson, LL Kleinman, HK Dym, M TI Altered basement membrane synthesis in the testis after tissue injury SO JOURNAL OF ANDROLOGY LA English DT Article DE efferent duct ligation; gene expression; protein synthesis; rat; animal model ID MESSENGER-RNA LEVELS; TESTICULAR PERITUBULAR CELLS; IMMUNE-COMPLEX ORCHITIS; RIBONUCLEIC-ACID LEVELS; GROWTH FACTOR-BETA; SERTOLI-CELL; EXTRACELLULAR-MATRIX; RAT TESTIS; SEMINIFEROUS TUBULES; GENE-EXPRESSION AB The basement membrane plays an important role in maintaining the structural and functional integrity of tissues. Altered basement membrane structure has been associated with severe functional impairment of the testis in several conditions, including vasectomy, autoimmune orchitis, cryptorchidism, and following x-irradiation. We have used efferent duct ligation as a model to examine seminiferous tubular basement membrane morphology, synthesis, and gene expression to determine whether altered basement membrane synthesis is responsible for the aberrant structures noted after tissue injury. On days 2 and 3 after ligation, both the seminiferous epithelium and the basement membrane appeared normal, but 7 days after ligation, the seminiferous epithelium began to degenerate. The basement membrane appeared detached from the epithelium, and redundant patches of basement membrane were observed adjacent to the Sertoli cells at 14 and 21 days postligation. Immunoprecipitation indicated an increase in laminin protein synthesis in the ligated tubules at the same time. Northern blot analysis showed increases in transcript levels for laminin as well as collagen IV and heparan sulfate proteoglycan. These data show that new protein synthesis is responsible, at least in part, for the duplication of the basement membrane coincident with the tissue damage caused by efferent duct ligation. C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dym, M (reprint author), Georgetown Univ, Med Ctr, Dept Cell Biol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. FU NICHD NIH HHS [HD16260] NR 48 TC 16 Z9 19 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 1998 VL 19 IS 2 BP 145 EP 155 PG 11 WC Andrology SC Endocrinology & Metabolism GA ZH107 UT WOS:000073072900003 PM 9570737 ER PT J AU Powell, BS Court, DL AF Powell, BS Court, DL TI Control of ftsZ expression, cell division, and glutamine metabolism in Luria-Bertani medium by the alarmone ppGpp in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PENICILLIN-BINDING PROTEIN-2; TRANSCRIPTIONAL UNITS; GENE-EXPRESSION; RNA; NITROGEN; K-12; OVEREXPRESSION; PROMOTER; OPERON; SUPPRESSION AB Inactivation of transcription factor sigma(54), encoded by rpoN (glnF), restores high-temperature growth in Luria-Bertani (LB) medium to strains containing the heat-sensitive cell division mutation ftsZ84. Mutational defects in three other genes involved in general nitrogen control (glnD, glnG, and glnL) also suppress lethal filamentation. Since addition of glutamine to LB medium fully blocks suppression by each mutation, the underlying cause of suppression likely derives from a stringent response to the limitation of glutamine. This model is supported by several observations, The glnL mutation requires RelA-directed synthesis of the nutrient alarmone ppGpp to suppress filamentation. Artificially elevated levels of ppGpp suppress ftsZ84, as do RNA polymerase mutations that reproduce global effects of the ppGpp-induced state. Both the glnF null mutation and an elevated copy number of the relA gene similarly affect transcription from the upstream (pQ) promoters of the ftsQAZ operon, and both of these genetic conditions increase the steady-state level of the FtsZ84 protein, Physiological suppression of ftsZ84 by a high salt concentration was also shown to involve RelA. Additionally, we found that the growth of a glnF or glnD strain on LB medium depends on RelA or supplemental glutamine in the absence of RelA function, These data expand the roles for ppGpp in the regulation of glutamine metabolism and the expression of FtsZ during cell division. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Court, DL (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 72 TC 33 Z9 34 U1 0 U2 5 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 MAR PY 1998 VL 180 IS 5 BP 1053 EP 1062 PG 10 WC Microbiology SC Microbiology GA YZ357 UT WOS:000072246300006 PM 9495742 ER PT J AU Joo, DM Nolte, A Calendar, R Zhou, YN Jin, DJ AF Joo, DM Nolte, A Calendar, R Zhou, YN Jin, DJ TI Multiple regions on the Escherichia coli heat shock transcription factor sigma(32) determine core RNA polymerase binding specificity SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SIGMA-70 SUBUNIT; CONSERVED REGION-3; BACILLUS-SUBTILIS; DNAK; PROTEIN; PROMOTER; GENE AB We have analyzed the core RNA polymerase (RNAP) binding activity of the purified products of nine defective alleles of the rpoH gene, which encodes sigma(32) in Escherichia coli, All mutations studied here lie outside of the putative core RNAP binding regions 2.1 and 2.2, Based on the estimated K(s)s for the mutant sigma and core RNAP interaction determined by in vitro transcription and by glycerol gradient sedimentation, we have divided the mutants into three classes, The class III mutants showed greatly decreased affinity for core RNAP, whereas the class II mutants' effect on core RNAP interaction was only clearly seen in the presence of sigma(70) competitor, The class I mutant behaved nearly identically to the wild type in core RNAP binding. Two point mutations in class III altered residues that were distant from one another, One was found in conserved region 4.2, and the other was in a region conserved only among heat shock sigma factors, These data suggest that there is more than one core RNAP binding region in sigma(32) and that differences in contact sites probably exist among sigma factors. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Calendar, R (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. FU NIAID NIH HHS [AI-08722] NR 36 TC 46 Z9 46 U1 0 U2 1 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 MAR PY 1998 VL 180 IS 5 BP 1095 EP 1102 PG 8 WC Microbiology SC Microbiology GA YZ357 UT WOS:000072246300010 PM 9495746 ER PT J AU Grimaud, R Toussaint, A AF Grimaud, R Toussaint, A TI Assembly of both the head and tail of bacteriophage Mu is blocked in Escherichia coli groEL and groES mutants SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MOLECULAR CHAPERONES; IN-VIVO; LAMBDA; PROTEIN; INVOLVEMENT; MORPHOGENESIS; MUTATIONS; CLEAVAGE; GROWTH; PHAGE AB Like several other Escherichia coli bacteriophages, transposable phage Mu does not develop normally in groE hosts (M, Pato, M, Banerjee, L. Desmet, and A, Toussaint, J, Bacteriol, 169:5504-5509, 1987), We show here that lysates obtained upon induction of groE Mu lysogens contain free inactive tails and empty heads, GroEL and GroES are thus essential for the correct assembly of both Mu heads and Mu tails, Evidence is presented that groE mutations inhibit processing of the phage head protein gpH as well as the formation of a 25S complex suspected to be an early Mu head assembly intermediate. C1 Free Univ Brussels, Unite Transposit Bacterienne, Lab Genet Procaryotes, B-1640 Rhode St Genese, Belgium. Univ Grenoble 1, Microbiol Lab, F-38041 Grenoble 9, France. RP Grimaud, R (reprint author), NCI, Cell Biol Lab, Bldg 37,Room 1B09, Bethesda, MD 20892 USA. EM regis@helix.nih.gov NR 48 TC 8 Z9 11 U1 0 U2 1 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 MAR PY 1998 VL 180 IS 5 BP 1148 EP 1153 PG 6 WC Microbiology SC Microbiology GA YZ357 UT WOS:000072246300016 PM 9495752 ER PT J AU Zhou, YN Gottesman, S AF Zhou, YN Gottesman, S TI Regulation of proteolysis of the stationary-phase sigma factor RpoS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DEPENDENT CLP PROTEASE; ESCHERICHIA-COLI; RNA-POLYMERASE; UPSTREAM REGION; GENE; DEGRADATION; SUBUNIT; BACTERIOPHAGE; STABILITY; COMPONENT AB RpoS, the stationary-phase sigma factor of Escherichia coli, is responsible for increased transcription of an array of genes when cells enter stationary phase and under certain stress conditions. RpoS is rapidly degraded during exponential phase and much more slowly during stationary phase; the resulting changes in RpoS accumulation play an important role in providing differential expression of RpoS-dependent gene expression, It has previously been shown that rapid degradation gradation of RpoS during exponential growth depends on RssB (also called SprE and MviA), a protein with homology to the family of response regulators, and on the ClpXP protease, We find that RssB regulation of proteolysis does not extend to another ClpXP substrate, bacteriophage lambda O protein, suggesting that RssB acts on the specific substrate RpoS rather than on the protease, In addition, the activity of RpoS is down-regulated by RssB when degradation is blocked, In cells blocked for RpoS degradation by a mutation in clpP, cells devoid of RssB show a four- to fivefold-higher activity of an RpoS-dependent reporter fusion than cells overproducing RssB, Therefore, RssB allows specific environmental regulation of RpoS accumulation and may also modulate activity, The regulation of degradation provides an irreversible switch, while the regulation of activity may. provide a second, presumably reversible level of control. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 35 TC 130 Z9 131 U1 1 U2 6 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 MAR PY 1998 VL 180 IS 5 BP 1154 EP 1158 PG 5 WC Microbiology SC Microbiology GA YZ357 UT WOS:000072246300017 PM 9495753 ER PT J AU Jonczyk, P Nowicka, A Fijalkowska, IJ Schaaper, RM Ciesla, Z AF Jonczyk, P Nowicka, A Fijalkowska, IJ Schaaper, RM Ciesla, Z TI Vivo protein interactions within the Escherichia coli DNA polymerase III core SO JOURNAL OF BACTERIOLOGY LA English DT Article ID EPSILON-SUBUNIT; MISMATCH REPAIR; MUTATOR; EXONUCLEASE; MUTD5; REPLICATION; HOLOENZYME; GENE; PURIFICATION; MUTAGENESIS AB The mechanisms that control the fidelity of DNA replication are being investigated by a number of approaches, including detailed kinetic and structural studies. Important tools in these studies are mutant versions of DNA polymerases that affect the fidelity of DNA replication. It has been suggested that proper interactions within the core of DNA polymerase III (Pol III) of Escherichia coli could be essential for maintaining the optimal fidelity of DNA replication (H. Maki and A. Kornberg, Proc. Natl. Acad. Sci. USA 84:4389-4392, 1987). We have been particularly interested in elucidating the physiological role of the interactions between the DnaE (alpha subunit [possessing DNA polymerase activity]) and DnaQ (epsilon subunit [possessing 3'-->5' exonucleolytic proofreading activity]) proteins. In an attempt to achieve this goal, we have used the Saccharomyces cerevisiae two-hybrid system to analyze specific in vivo protein interactions. In this report, we demonstrate interactions between the DnaE and DnaQ proteins and between the DnaQ and HolE (theta subunit) proteins. We also tested the interactions of the wild-type DnaE and HolE proteins with three well-known mutant forms of DnaQ (MutD5, DnaQ926, and DnaQ49), each of which leads to a strong mutator phenotype. Our results show that the mutD5 and dnaQ926 mutations do not affect the epsilon subunit-alpha subunit and epsilon subunit-theta subunit interactions. However, the dnaQ49 mutation greatly reduces the strength of interaction of the epsilon subunit with both the or and the theta subunits. Thus, the mutator phenotype of dnaQ49 may be the result of an altered conformation of the epsilon protein, which leads to altered interactions within the Pol III core. C1 Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Jonczyk, P (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland. RI Skoneczna, Adrianna/H-1734-2011; Fijalkowska, Iwona/I-7796-2016 OI Skoneczna, Adrianna/0000-0003-4059-2146; NR 31 TC 24 Z9 24 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 MAR PY 1998 VL 180 IS 6 BP 1563 EP 1566 PG 4 WC Microbiology SC Microbiology GA ZC522 UT WOS:000072588800030 PM 9515927 ER PT J AU Leffers, GG Gottesman, S AF Leffers, GG Gottesman, S TI Lambda Xis degradation in vivo by lon and ftsH SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; PROTEOLYTIC CLEAVAGE; PROTEIN-DEGRADATION; GENE-PRODUCT; CLP PROTEASE; CII PROTEIN; BACTERIOPHAGE; STABILITY; REPRESSOR; MEMBRANE AB Lambda Xis, which is required for site-specific excision of phage lambda from the bacterial chromosome, has a much shorter functional half-life than Int, which is required for both integration and excision (R. A. Weisberg and M. E. Gottesman, p. 489-500, in A. D. Hershey, ed., The Bacteriophage Lambda, 1971). We found that Xis is degraded in vivo by two ATP-dependent proteases, Lon and FtsH (HflB). Xis was stabilized two-to threefold more than in the wild type in a ion mutant and as much as sixfold more in a ion ftsH double mutant at the nonpermissive temperature for the ftsH mutation. Integration of lambda into the bacterial chromosome was delayed in the ion ftsH background, suggesting that accumulation of Xis in vivo interferes with integration. Overexpression of Xis in wild-type cells from a multicopy plasmid inhibited integration of lambda and promoted curing of established lysogens, confirming that accumulation of Xis interferes with the ability of Int to establish and maintain an integrated prophage. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37,Rm 2E18,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 31 TC 48 Z9 49 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 MAR PY 1998 VL 180 IS 6 BP 1573 EP 1577 PG 5 WC Microbiology SC Microbiology GA ZC522 UT WOS:000072588800033 PM 9515930 ER PT J AU Krajcikova, D Hartley, RW Sevcik, J AF Krajcikova, D Hartley, RW Sevcik, J TI Isolation and purification of two novel streptomycete RNase inhibitors, SaI14 and SaI20, and cloning, sequencing, and expression in Escherichia coli of the gene coding for SaI14 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEINS; BARSTAR; AUREOFACIENS; BARNASE; ALLOWS AB Two new RNase inhibitors, SaI14 (M-r, similar to 14,000) and SaI20 (M-r, similar to 20,000), were isolated and purified from a Streptomyces aureofaciens strain. The gene sai14, coding for SaI14 protein, was cloned and expressed in Escherichia coli. The alignment of the deduced amino acid sequence of SaI14 with that of barstar, the RNase inhibitor from Bacillus amyloliquefaciens, showed significant similarity between them, especially in the region which contains most of the residues involved in barnase-barstar complex formation. C1 Slovak Acad Sci, Inst Mol Biol, Bratislava 84251, Slovakia. NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Krajcikova, D (reprint author), Slovak Acad Sci, Inst Mol Biol, Dubravska Cesta 21, Bratislava 84251, Slovakia. EM umbidana@savba.savba.sk OI Krajcikova, Daniela/0000-0002-4024-2384 NR 19 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1998 VL 180 IS 6 BP 1582 EP 1585 PG 4 WC Microbiology SC Microbiology GA ZC522 UT WOS:000072588800035 PM 9515932 ER PT J AU Erlacher, L Mccartney, J Piek, E Ten Dijke, P Yanagishita, M Oppermann, H Luyten, FP AF Erlacher, L Mccartney, J Piek, E Ten Dijke, P Yanagishita, M Oppermann, H Luyten, FP TI Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; SERINE/THREONINE KINASE RECEPTORS; GROWTH/DIFFERENTIATION FACTOR-5; I RECEPTORS; BONE; SUPERFAMILY; ACTIVIN; INVITRO; CELLS; LIMB AB Cartilage-derived morphogenetic proteins-1 and -2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family, which play important roles in embryonic skeletal development, We studied the biological activities of recombinant CDMP-1 and CDMP-2 in chondrogenic and osteogenic differentiation and investigated their binding properties to type I and type II serine/threonine kinase receptors, In vivo, CDMP-1 and CDMP-2 were capable of inducing dose-dependently de novo cartilage and bone formation in an ectopic implantation assay, In vitro studies using primary chondrocyte cultures showed that both CDMP-1 and CDMP-2 stimulated equally de novo synthesis of proteoglycan aggrecan in a concentration-dependent manner. This activity was equipotent when compared with osteogenic protein-1 (OP-1), In contrast, CDMPs were less stimulatory than OP-1 in osteogenic differentiation as evaluated by alkaline phosphatase activity and expression levels of bone markers in ATDC5, ROB-C26, and MC3T3-E1 cells, CDMP-2,vas the least osteogenic in these assays, Receptor binding studies of CDMP-1 and CDMP-2 revealed that both have affinity for the BMP receptor type IB (BMPR-IB) and BMPR-II, and weakly for BMPR-IA, Moreover, using a promoter/reporter construct, transcriptional activation signal was transduced by BMPR-IB in the presence of BMPR-II. upon CDMP-1 and CDMP-2 binding, Our data show that distinct members of the BMP family differentially regulate the progression in the osteogenic lineage, and this may be due to their selective affinity for specific receptor complexes. C1 NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Creat Biomol Inc, Hopkinton, MA USA. Ludwig Inst Canc Res, S-75124 Uppsala, Sweden. RP Luyten, FP (reprint author), UZ Pellenberg, Div Rheumatol, Weligerveld 1, B-3212 Pellenberg, Belgium. NR 25 TC 106 Z9 113 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 1998 VL 13 IS 3 BP 383 EP 392 DI 10.1359/jbmr.1998.13.3.383 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YZ967 UT WOS:000072313100006 PM 9525338 ER PT J AU Gallagher, JC Kinyamu, HK Fowler, SE Dawson-Hughes, B Dalsky, GP Sherman, SS AF Gallagher, JC Kinyamu, HK Fowler, SE Dawson-Hughes, B Dalsky, GP Sherman, SS TI Calciotropic hormones and bone markers in the elderly SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 07-11, 1996 CL SEATTLE, WASHINGTON SP Amer Soc Bone & Mineral Res ID IMMUNOREACTIVE PARATHYROID-HORMONE; GAMMA-CARBOXYGLUTAMIC ACID; AGE-RELATED-CHANGES; VITAMIN-D STATUS; SERUM 1,25-DIHYDROXYVITAMIN-D; OSTEOPOROTIC WOMEN; PROTEIN; MENOPAUSE; TURNOVER; DENSITY AB There is a lack of substantial data on changes in calciotropic hormones and bone markers in elderly subjects living in North America, Parathyroid hormone (PTH), serum 25-hydroxyvitamin D (25(OH)D) and bone markers (serum osteocalcin and urine N-telopeptide), were measured in 735 Caucasian subjects (235 men and 500 women) aged 65-87 years, There was a significant increase in serum osteocalcin and urine N-telopeptide with age in men, and a significant increase in serum osteocalcin with age in women, Serum PTH and 25(OH)D showed no significant change with age in men or women, After adjusting for age, calcium intake, serum creatinine, season, and weight, mean serum PTH (p = 0.01), serum osteocalcin (p = 0.0001) and 24 h urine N-telopeptide (p = 0.0001) were higher in women than men, and mean serum 25(OH)D (p = 0.0001) and 24 h urine calcium (p = 0.0001) were higher in men than women, Serum PTH was correlated with serum osteocalcin in men and women, r = 0.24, r = 0.17, p < 0.001, but not with urine N-telopeptide. Serum PTH was inversely correlated with serum 25(OH)D (r = -0.25, r = -0.34, p < 0.001), and positively correlated with serum creatinine (r = 0.14, r = 0.17, p < 0.01) in men and women. The prevalence of serum 25(OH)D levels below 12 ng/ml was only 3.3% in females and 0.4% in men, Thus vitamin D deficiency was very uncommon in the U.S.A. compared with Europe, Although mean serum PTH was increased in the elderly, only 4-6% had PTH levels above the normal range, In summary, the increase in serum PTH in the elderly can be explained more by changes in vitamin D status than by declining renal function, These data also show significantly higher (p = 0.001) bone remodeling markers in women. C1 Creighton Univ, Sch Med, Bone Metab Unit, Omaha, NE 68131 USA. Henry Ford Hlth Syst, Detroit, MI USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. NIA, NIH, Bethesda, MD 20892 USA. RP Gallagher, JC (reprint author), Creighton Univ, Sch Med, Bone Metab Unit, 601 N 30th St, Omaha, NE 68131 USA. FU NIA NIH HHS [AG 10382, AG 10353, UO1-AG10373] NR 46 TC 93 Z9 95 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 1998 VL 13 IS 3 BP 475 EP 482 DI 10.1359/jbmr.1998.13.3.475 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YZ967 UT WOS:000072313100016 PM 9525348 ER PT J AU Shi, LM Fan, Y Myers, TG O'Connor, PM Paull, KD Friend, SH Weinstein, JN AF Shi, LM Fan, Y Myers, TG O'Connor, PM Paull, KD Friend, SH Weinstein, JN TI Mining the NCI anticancer drug discovery databases: Genetic function approximation for the QSAR study of anticancer ellipticine analogues SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID TUMOR-CELL-LINES; MOLECULAR-DYNAMICS SIMULATIONS; AUTOMATED STRUCTURE EVALUATION; INFORMATION-SYSTEM; IN-VITRO; TOPOISOMERASE-II; HUMAN BRAIN; ARTIFICIAL-INTELLIGENCE; P53 MUTATIONS; SCREEN AB The U.S. National Cancer Institute (NCI) conducts a drug discovery program in which similar to 10 000 compounds are screened every year in vitro against a panel of 60 human cancer cell lines from different organs of origin. Since 1990, similar to 63 000 compounds have been tested, and their patterns of activity profiled. Recently, we analyzed the antitumor activity patterns of 112 ellipticine analogues using a hierarchical clustering algorithm. Dramatic coherence between molecular structures and activity patterns was observed qualitatively from the cluster tree. In the present study, we further investigate the quantitative structure-activity relationships (QSAR) of these compounds, in particular with respect to the influence of p53-status and the CNS cell selectivity of the activity patterns. Independent variables (i.e., chemical structural descriptors of the ellipticine analogues) were calculated from the Cerius(2) molecular modeling package. Important structural descriptors, including partial atomic charges on the ellipticine ring-forming atoms, were identified by the recently developed genetic function approximation (GFA) method. For our data set, the GFA method gave better correlation and cross-validation results (R-2 and CVR2 were usually similar to 0.3 higher) than did classical stepwise linear regression. A procedure for improving the performance of GFA is proposed, and the relative advantages and disadvantages of using GFA for QSAR studies are discussed. C1 NCI, NIH, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Treatment, Informat Technol Branch, Bethesda, MD 20892 USA. NCI, Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Weinstein, JN (reprint author), NCI, NIH, Div Basic Sci, Mol Pharmacol Lab, Bldg 37,Room 5D02,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 63 TC 94 Z9 94 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAR-APR PY 1998 VL 38 IS 2 BP 189 EP 199 DI 10.1021/ci970085w PG 11 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA ZD935 UT WOS:000072740500012 PM 9538518 ER PT J AU Hold, KM Wilkins, DG Rollins, DE Joseph, RE Cone, EJ AF Hold, KM Wilkins, DG Rollins, DE Joseph, RE Cone, EJ TI Simultaneous quantitation of cocaine, opiates, and their metabolites in human hair by positive ion chemical ionization gas chromatography mass spectrometry SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID ECGONINE METHYL-ESTER; MAJOR METABOLITES; BENZOYLECGONINE; EXTRACTION; DRUGS C1 Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. NIDA, Addict Res Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Hold, KM (reprint author), Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, 112 Skaggs Hall, Salt Lake City, UT 84112 USA. FU NIDA NIH HHS [DA09096] NR 12 TC 26 Z9 30 U1 0 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD MAR PY 1998 VL 36 IS 3 BP 125 EP 130 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YZ475 UT WOS:000072257800004 PM 9514002 ER PT J AU Taymans, SE Pack, S Pak, E Torpy, DJ Zhuang, ZP Stratakis, CA AF Taymans, SE Pack, S Pak, E Torpy, DJ Zhuang, ZP Stratakis, CA TI Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE CYP11B2; aldosterone; radiation hybrid mapping; chromosome 8q; FISH ID RADIATION HYBRID MAP; STEROID 11-BETA-HYDROXYLASE; HUMAN GENOME; GENE; HYPERTENSION; HUMAN-CHROMOSOME-8; HYBRIDIZATION; BIOSYNTHESIS; P450C11AS AB Aldosterone synthase (AS) is encoded by the CYP11B2 gene, a candidate for familial hypertension. CYP11B2 was previous ly mapped to chromosome 8q but its precise localization is necessary for genetic studies of hypertension. The present study reports the genetic mapping of the human CYP11B2 gene by radiation hybrid (RH) analysis, the isolation of a bacterial artificial chromosome (BAG) containing this gene and its physical mapping by fluorescent in situ hybridization (FISH). The CYP11B2 locus is on the most distal segment of the long arm of chromosome 8, proximal to the microsatellite polymorphic marker D8S1704. This location, which was confirmed by FISH, is approximately 60cM telomeric to the currently listed human gene locus (chromosome 8q21-22) and corresponds to cytogenetic band 8q24.3. The BACs containing the gene and a high-resolution map of the CYP11B2 locus are useful for genetic studies of hypertension and other endocrine disorders. C1 NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@ccl.nichd.nih.gov RI Pack, Svetlana/C-2020-2014 NR 24 TC 68 Z9 76 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 MAR PY 1998 VL 83 IS 3 BP 1033 EP 1036 DI 10.1210/jc.83.3.1033 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA804 UT WOS:000072403500060 PM 9506770 ER PT J AU Licinio, J AF Licinio, J TI Longitudinally sampled human plasma leptin and cortisol concentrations are inversely correlated SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID NOCTURNAL RISE C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Licinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. OI Licinio, Julio/0000-0001-6905-5884 NR 8 TC 10 Z9 11 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 MAR PY 1998 VL 83 IS 3 BP 1042 EP 1042 DI 10.1210/jc.83.3.1042 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA804 UT WOS:000072403500064 PM 9506773 ER PT J AU Torpy, DJ Stratakis, CA Gordon, RD AF Torpy, DJ Stratakis, CA Gordon, RD TI Linkage analysis of familial hyperaldosteronism type II - Absence of linkage to the gene encoding the angiotensin II receptor type 1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID PRIMARY ALDOSTERONISM C1 NICHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Queensland, Dept Med, Greenslopes Hosp, Brisbane, Qld 4120, Australia. RP Torpy, DJ (reprint author), NICHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Gordon, Richard/K-2555-2012 NR 5 TC 27 Z9 27 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 MAR PY 1998 VL 83 IS 3 BP 1046 EP 1046 DI 10.1210/jc.83.3.1046 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA804 UT WOS:000072403500071 PM 9506777 ER PT J AU Mozes, E Zinger, H Kohn, LD Singer, DS AF Mozes, E Zinger, H Kohn, LD Singer, DS TI Spontaneous autoimmune disease in (NZB X NZW)F-1 mice is ameliorated by treatment with methimazole SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE autoimmunity; lupus; MHC class I; methimazole ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTI-DNA IDIOTYPE; MONOCLONAL-ANTIBODY; EXPRESSION; INDUCTION; CELLS; IGG3 AB (NZB X NZW)F-1 mice spontaneously develop with age an autoimmune disease that resembles the human disease, systemic lupus erythematosus (SLE). The present study demonstrates that methimazole (MMI), an agent used in the treatment of autoimmune thyroid disease, is effective in mitigating the development of this SLE-like autoimmune disease in (NZB x NZW)F-1 mice. MMI significantly reduces the incidence and severity of proteinuria and deposition of immune complexes in the kidney. Previous studies have demonstrated that development of an experimentally induced SLE, which was prevented by MMI treatment, depended on the expression of MHC class I molecules. We now report that class I levels on both T cells and B cells from old (NZB X NZW)F-1 MHC class I are markedly elevated relative to those from young F-1 mice. Furthermore, treatment of(NZB X NZW)F-1 mice with MMI reduced MHC class I expression on their PBL concomitant with amelioration of disease, raising the possibility that class I molecules may play a role in the generation of spontaneous autoimmune disease in these mice. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-17, Bethesda, MD 20892 USA. NR 24 TC 16 Z9 16 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 1998 VL 18 IS 2 BP 106 EP 113 DI 10.1023/A:1023242732212 PG 8 WC Immunology SC Immunology GA ZA832 UT WOS:000072406500002 PM 9533654 ER PT J AU Smith, M Bernstein, M Bleyer, WA Borsi, JD Ho, P Lewis, IJ Pearson, A Pein, F Pratt, C Reaman, G Riccardi, R Seibel, N Trueworthy, R Ungerleider, R Vassal, G Vietti, T AF Smith, M Bernstein, M Bleyer, WA Borsi, JD Ho, P Lewis, IJ Pearson, A Pein, F Pratt, C Reaman, G Riccardi, R Seibel, N Trueworthy, R Ungerleider, R Vassal, G Vietti, T TI Conduct of phase I trials in children with cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PEDIATRIC-ONCOLOGY-GROUP; REFRACTORY SOLID TUMORS; TRANS-RETINOIC ACID; ANTIVIRAL PROTEIN IMMUNOTOXIN; 24-HOUR CONTINUOUS-INFUSION; COLONY-STIMULATING FACTOR; RELAPSED ACUTE-LEUKEMIA; COMBINED IMMUNODEFICIENT MICE; ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL PRECURSOR LEUKEMIA AB Purpose and Methods: Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. Results and Conclusion: Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. the application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children. C1 NCI, Pediat Sect, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Pediat Oncol Grp Phase 1 Consortium, E Hanover, NJ USA. Childrens Canc Grp Phase 1 Consortium, E Hanover, NJ USA. Novantis Pharmaceut, E Hanover, NJ USA. United Kingdom Childrens Canc Study Grp, Int Soc Pediat Oncol SIOP, Pharmacol Chemotherpay Subcomm, Manchester, Lancs, England. RP Smith, M (reprint author), NCI, Pediat Sect, Clin Invest Branch, Canc Therapy Evaluat Program, Rm 741,Execut Plaza N, Bethesda, MD 20892 USA. EM smithm@ctep.n-ci.nih.gov OI RICCARDI, RICCARDO/0000-0001-7515-6622 NR 142 TC 51 Z9 51 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 MAR PY 1998 VL 16 IS 3 BP 966 EP 978 PG 13 WC Oncology SC Oncology GA YZ486 UT WOS:000072258900019 PM 9508179 ER PT J AU Edwards, MJ Gamel, JW Feuer, EJ AF Edwards, MJ Gamel, JW Feuer, EJ TI Improvement in the prognosis of breast cancer from 1965 to 1984 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MORTALITY; TRENDS; MANAGEMENT; CARCINOMA; SURVIVAL; WOMEN AB Purpose: The prognosis of breast cancer has improved over the past three decades. It is uncertain, however, whether this improvement results from an increase in the cure rate, extension of the life span of uncured patients, or some combination. Methods: From the Connecticut Tumor Registry, we obtained data on 25,091 patients with localized (node-negative) and regionally metastatic (node-positive) breast cancer who were diagnosed over the two decades between 1965 and 1984, with follow-up through 1993. The data for these patients were analyzed using a variety of parametric models to quantitate likelihood of cure and median survival time among uncured patients. These models incorporate the assumption that time to death from breast cancer follows a specific distribution. Results: For patients with node-negative disease, parametric analysis revealed no significant difference in cured-fraction or median survival time over the two decades studied. For patients with node-positive disease, however, a significant increase in median survival time (P < .001) was found during the second decade (1970 to 1979). There was also a trend toward a higher cured-fraction over time, but this was not statistically significant. Conclusion: This study confirms that patients with node-positive disease had an improved prognosis over the two decades studied. Parametric analysis suggests that this improvement reflects primarily an increase in the median survival time for uncured patients, although there is a trend toward an increase in the likelihood of cure. (C) 1998 by American Society of Clinical Oncology. C1 Univ Louisville, Dept Surg, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. Vet Affairs Med Ctr, Louisville, KY USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Edwards, MJ (reprint author), Univ Louisville, Dept Surg, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. EM mjedwa01@ulkyvm.louisville.edu FU NCI NIH HHS [CA57527] NR 13 TC 16 Z9 17 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 MAR PY 1998 VL 16 IS 3 BP 1030 EP 1035 PG 6 WC Oncology SC Oncology GA YZ486 UT WOS:000072258900027 PM 9508187 ER PT J AU Gibril, F Doppman, JL Reynolds, JC Chen, CC Sutliff, VE Yu, F Serrano, J Venzon, DJ Jensen, RT AF Gibril, F Doppman, JL Reynolds, JC Chen, CC Sutliff, VE Yu, F Serrano, J Venzon, DJ Jensen, RT TI Bone metastases in patients with gastrinomas: A prospective study of bone scanning, somatostatin receptor scanning, and magnetic resonance image in their defection, frequency, location, and effect of their detection on management SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ZOLLINGER-ELLISON SYNDROME; PANCREATIC ENDOCRINE TUMORS; ISLET-CELL CARCINOMAS; BREAST-CANCER; GASTROENTEROPANCREATIC TUMORS; OSTEOBLASTIC METASTASES; SPINAL METASTASES; NEUROENDOCRINE TUMORS; VERTEBRAL METASTASES; LONG-TERM AB Purpose: To determine whether bone scan, magnetic resonance imaging (MRI), or somatostatin receptor scintigraphy (SRS) is best for identifying bone metastases in patients with gastrinomas, as well as their frequency and location, whether their detection affects management, and what patient subgroups should be examined. Materials and Methods: One hundred fifteen patients with gastrinoma were prospectively studied. Patients were examined yearly and those with liver metastases were reexamined every 3 months. Based on clinical history, histology, growth pattern, and development of new bone lesions, possible bone metastases were classified as to whether they were or were not bone metastases. Imaging results were correlated at different times in the disease course and with disease extent. Results: Bone scan was positive in 52 patients, MRI in seven, and SRS in six. Eight patients (7%) were determined to have bone metastases and MRI was correctly positive in seven, SRS in six, and bone scan in five. SRS or MRI was positive in all patients with bone metastases. Bone scan had significantly lower specific-ity and sensitivity, and a higher rate (P < .02) of false-negative results than MRI or SRS. Bone metastases occurred in 31% of patients with liver metastases and 0% with only lymph node metastases. The initial bone metastases were in the spine or sacrum (75%) followed in descending order by the pelvis or sacroiliac joints (38%), scapula or shoulder, and ribs. In all cases, detection of bone metastases changed the management. Conclusion: SRS and MRI, because of high sensitivity and specificity, are recommended over bone scanning to screen for bone metastases in patients with gastrinomas. However, because bone metastases can occur initially outside the axial skeleton, SRS is the recommended initial localization method of choice. Bone metastases occur in 7% of all patients and 31% of patients with liver metastases, only occur in patients with liver metastases, are usually in the axial skeleton initially, and their detection changes management in all cases. Patients with pancreatic endocrine tumors with liver metastases should undergo SRS every 6 months to 1 year to detect bone metastases. This is a US government work. There are no restrictions on its use. C1 NIDDKD, NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NCI, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, NIH, Digest Dis Branch, 10 Ctr Dr,MC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Venzon, David/B-3078-2008 NR 97 TC 81 Z9 83 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1998 VL 16 IS 3 BP 1040 EP 1053 PG 14 WC Oncology SC Oncology GA YZ486 UT WOS:000072258900029 PM 9508189 ER PT J AU Welles, L Saville, MW Lietzau, J Pluda, JM Wyvill, KM Feuerstein, I Figg, WD Lush, R Odom, J Wilson, WH Fajardo, MT Humphrey, RW Feigal, E Tuck, D Steinberg, SM Broder, S Yarchoan, R AF Welles, L Saville, MW Lietzau, J Pluda, JM Wyvill, KM Feuerstein, I Figg, WD Lush, R Odom, J Wilson, WH Fajardo, MT Humphrey, RW Feigal, E Tuck, D Steinberg, SM Broder, S Yarchoan, R TI Phase II trial with dose titration of paclitaxel for the therapy of human immunodeficiency virus-associated Kaposi's sarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; BREAST-CANCER; LIPOSOMAL DAUNORUBICIN; PERIPHERAL-BLOOD; CLINICAL-TRIALS; DNA-SEQUENCES; AIDS; TAXOL; DOXORUBICIN; HERPESVIRUS AB Purpose: To investigate the antitumor activity and safety of paclitaxel in patients with advanced human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Patients and Methods: Twenty-nine patients with advanced HIV-associated KS were enrolled. The patients were overall quite immunosuppressed (median CD4 count, 15 cells/mu L). Paclitaxel was initially administered at 135 mg/m(2) over 3 hours every 3 weeks without filgrastim support; the dose was increased as tolerated to ct maximum of 175 mg/m(2). Patients who failed to respond or progressed could then receive filgrastim support or paclitaxel administered over 96 hours. Results: Of 28 assessable patients, 20 had major responses (18 partial responses [PRs], one clinical complete response [CR], and one CR), for a major response rate of 71.4% (95% confidence interval [CI], 51.3% to 86.8%). Each of the five patients with pulmonary KS responded, as did all four assessable patients who had previously received anthracycline therapy for KS. Of six patients who went on to receive a 96-hour infusion of paclitaxel, five had major responses. Neutropenia was the most frequent dose-limiting toxicity; possible novel toxicities included late fevers, late rash, and eosinophilia. Two patients developed an elevated creatinine concentration and one cardiomyopathy. Conclusion: Paclitaxel has substantial activity against advanced HIV-associated KS as a single agent, even in patients with pulmonary involvement or who had previously received anthracyclines. Further research is needed to define the optimal treatment schedule and its role vis-a-vis the other available therapies for this disease. This is a US government work, There are no restrictions on its use. C1 NCI, HIV & AIDS Malgnancy Branch, Med Branch, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Off Director, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Bristol Myers Squibb Pharmaceut Res Inst, Wallingford, CT USA. RP Yarchoan, R (reprint author), NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 49 TC 105 Z9 107 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 MAR PY 1998 VL 16 IS 3 BP 1112 EP 1121 PG 10 WC Oncology SC Oncology GA YZ486 UT WOS:000072258900038 PM 9508198 ER PT J AU Albandar, JM Kingman, A Brown, LJ Loe, H AF Albandar, JM Kingman, A Brown, LJ Loe, H TI Gingival inflammation and subgingival calculus as determinants of disease progression in early-onset periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE adolescents; periodontal diseases diagnosis; periodontal diseases early-onset; periodontal attachment; gingivitis; dental calculus adverse effects ID ADOLESCENTS AB This study was undertaken to test the hypothesis that gingival inflammation and dental calculus are important determinants of the development and progression of early-onset periodontitis. The study sample included 156 individuals who were 13-20 years old at baseline and who were examined 2x during 6 years to assess the attachment loss, gingival state and the presence of dental calculus, 33 (21%), 62 (40%), and 61 (39%) individuals were classified as having localized, generalized, or incidental EOP, respectively. The results showed an increase in the % of teeth with overt gingivitis and subgingival calculus, and also an increase in the % of teeth showing attachment loss during the 6-year period in all classification groups. Of teeth with 0-2 mm attachment loss at the beginning of the study and which developed greater than or equal to 3 mm attachment loss during the following 6 years, there were 2x as many teeth with overt gingival inflammation, and 4x more teeth with subgingival calculus at baseline than teeth without. Gingivitis and subgingival calculus when present at both examinations resulted in a stronger association with the development of new lesions than presence of these variables at baseline. Teeth with gingivitis at baseline had a significantly higher mean attachment loss during 6 years than teeth without gingivitis (p<0.0001), and teeth with subgingival calculus at baseline had a significantly higher mean attachment loss than teeth without subgingival calculus (p<0.0001). The presence of gingivitis and subgingival calculus at baseline and 6 years later was associated with the occurrence of even higher disease progression during this period. The association between gingival inflammation and subgingival calculus and the development and progression of attachment loss during the study period in the generalized and the localized EOP groups was significantly higher than the association in the incidental EOP group. In an appreciable % of the sites in all 3 groups, however, the presence of the 2 factors was not associated with attachment loss during 6 years. The results suggest a significant association between gingival inflammation and subgingival calculus and the development and progression of early-onset periodontitis. C1 NIDR, NIH, Bethesda, MD 20892 USA. Amer Dent Assoc, Chicago, IL USA. Univ Connecticut, Ctr Hlth, Sch Dent Med, Farmington, CT USA. RP Albandar, JM (reprint author), NIDR, NIH, Natcher Bldg,RM 4AS-19B,45 Ctr Dr, Bethesda, MD 20892 USA. OI Albandar, Jasim M./0000-0001-7801-3811 NR 15 TC 46 Z9 49 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAR PY 1998 VL 25 IS 3 BP 231 EP 237 DI 10.1111/j.1600-051X.1998.tb02433.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZA992 UT WOS:000072423600007 PM 9543194 ER PT J AU Chao, LL Knight, RT AF Chao, LL Knight, RT TI Contribution of human prefrontal cortex to delay performance SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED POTENTIALS; MIDDLE-LATENCY; LESIONS; MEMORY; DISTRACTIBILITY; RESPONSES; MONKEYS AB Neurological patients with focal lesions in the dorsolateral prefrontal cortex and age-matched control subjects were tested on an auditory version of the delayed-match-to-sample task employing environmental sounds. Subjects had to indicate whether a cue (S1) and a subsequent target sound (S2) were identical. On some trials, S1 and S2 were separated by a silent period of 5 sec. On other trials, the 5-sec delay between S1 and S2 was filled with irrelevant tone pips that served as distractors. Behaviorally, frontal patients were impaired by the presence of distractors. Electrophysiologically, patients generated enhanced primary auditory cortex-evoked responses to the tone pips, supporting a failure in inhibitory control of sensory processing after prefrontal damage. Intrahemispheric reductions of neural activity generated in the auditory association cortex and additional intrahemispheric reductions of attention-related frontal activity were also observed in the prefrontal patients. Together, these findings suggest that the dorsolateral prefrontal cortex is crucial for gating distracting information as well as maintaining distributed intrahemispheric neural activity during auditory working memory. C1 Univ Calif Davis, Davis, CA USA. RP Chao, LL (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA. NR 37 TC 150 Z9 154 U1 0 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR PY 1998 VL 10 IS 2 BP 167 EP 177 DI 10.1162/089892998562636 PG 11 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZG744 UT WOS:000073035000002 PM 9555105 ER PT J AU Westergaard, GC Kuhn, HE Suomi, SJ AF Westergaard, GC Kuhn, HE Suomi, SJ TI Bipedal posture and hand preference in humans and other primates SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID CHIMPANZEES PAN-TROGLODYTES; CEREBRAL LATERALIZATION; BIOLOGICAL MECHANISMS; GALAGO-SENEGALENSIS; MACACA-MULATTA; PONGO-PYGMAEUS; BIMANUAL TASK; HANDEDNESS; ORANGUTANS; ASSOCIATIONS AB Hand preference for quadrupedal and bipedal reaching in humans and rhesus macaques (Macaca mulatta) was examined. and the data were compared with postural reaching data that have been reported for 8 other primate species. Population-level biases were found toward use of the right hand for quadrupedal and bipedal reaching in humans and use of the left hand for quadrupedal reaching in rhesus macaques. Rhesus macaques showed a significant shift toward greater use of the right hand for bipedal vs. quadrupedal reaching. Comparisons with other species showed significant variance in the direction and strength of hand preference across reaching postures. The study noted right-hand biases for bipedal reaching in humans, great apes, and tufted capuchins and shifts toward greater use of the right hand for bipedal vs. quadrupedal reaching in great apes, tufted capuchins, and rhesus macaques. These results suggest that posture alters both the direction and strength of primate hand preference and that bipedalism may have facilitated species-typical right-handedness in humans. C1 NICHHD, Comparat Ethol Lab, Anim Ctr, NIH, Poolesville, MD 20837 USA. RP Westergaard, GC (reprint author), NICHHD, Comparat Ethol Lab, Anim Ctr, NIH, POB 529, Poolesville, MD 20837 USA. NR 42 TC 52 Z9 54 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD MAR PY 1998 VL 112 IS 1 BP 55 EP 64 DI 10.1037//0735-7036.112.1.55 PG 10 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA ZB588 UT WOS:000072487600006 PM 9528114 ER PT J AU Knutson, B Burgdorf, J Panksepp, J AF Knutson, B Burgdorf, J Panksepp, J TI Anticipation of play elicits high-frequency ultrasonic vocalizations in young rats SO JOURNAL OF COMPARATIVE PSYCHOLOGY LA English DT Article ID RATTUS-NORVEGICUS; JUVENILE RATS; SMALL RODENTS; COPULATION; BEHAVIOR; MORPHINE; ONTOGENY AB The authors provide initial documentation that juvenile rats emit short, high-frequency ultrasonic vocalizations (high USVs, similar to 55 kHz) during rough-and-tumble play. In an observational study, they further observe that these vocalizations both correlate with and predict appetitive components of the play behavioral repertoire. Additional experiments characterized eliciting conditions for high USVs. Without prior play exposure, rats separated by a screen vocalized less than playing rats, but after only 1 play session, separated rats vocalized more than playing rats. This finding suggested that high USVs were linked to a motivational state rather than specific play behaviors or general activity. Furthermore, individual rats vocalized more in a chamber associated with play than in a habituated control chamber. Finally, congruent and incongruent motivational manipulations modulated vocalization expression. Although play deprivation enhanced high USVs, an arousing but aversive stimulus (bright light) reduced them. Taken together, these findings suggest that high USVs may index an appetitive motivation to play in juvenile rats. C1 NIAAA, Clin Sci Lab, Rockville, MD 20852 USA. Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43403 USA. RP Knutson, B (reprint author), 10 Ctr Dr,Bldg 10,Room 6S420,Mail Stop 1610, Bethesda, MD 20892 USA. EM knutson@odin.niaaa.nih.gov FU NICHD NIH HHS [HD30387]; NIMH NIH HHS [MH18931]; PHS HHS [F3360196MR232] NR 27 TC 204 Z9 207 U1 3 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7036 J9 J COMP PSYCHOL JI J. Comp. Psychol. PD MAR PY 1998 VL 112 IS 1 BP 65 EP 73 DI 10.1037/0735-7036.112.1.65 PG 9 WC Behavioral Sciences; Psychology; Psychology, Multidisciplinary; Zoology SC Behavioral Sciences; Psychology; Zoology GA ZB588 UT WOS:000072487600007 PM 9528115 ER PT J AU Kosaraju, SR Schaffer, AA Biesecker, LG AF Kosaraju, SR Schaffer, AA Biesecker, LG TI Approximation algorithms for a genetic diagnostics problem SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE set cover; genetics; algorithms; monosomy; trisomy; genotyping ID POLYMERASE CHAIN-REACTION; MENTAL-RETARDATION; DNA POLYMORPHISMS; REARRANGEMENTS; PCR AB We define and study a combinatorial problem called WEIGHTED DIAGNOSTIC COVER (WDC) that models the use of a laboratory technique called genotyping in the diagnosis of an important class of chromosomal aberrations. An optimal solution to WDC would enable us to define a genetic assay that maximizes the diagnostic power for a specified cost of laboratory work. We develop approximation algorithms for WDC by making use of the well-known problem SET COVER for which the greedy heuristic has been extensively studied. We prove worst-case performance bounds on the greedy heuristic for WDC and for another heuristic we call directional greedy. We implemented both heuristics. We also implemented a local search heuristic that takes the solutions obtained by greedy and dir-greedy and applies swaps until they are locally optimal, We report their performance on a real data set that is representative of the options that a clinical geneticist faces for the real diagnostic problem. Many open problems related to WDC remain, both of theoretical interest and practical importance. C1 Natl Human Genome Res Inst, NIH, Baltimore, MD 21224 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA. RP Schaffer, AA (reprint author), Natl Human Genome Res Inst, NIH, Suite 2000,333 Cassell Dr, Baltimore, MD 21224 USA. RI Schaffer, Alejandro/F-2902-2012 NR 23 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD SPR PY 1998 VL 5 IS 1 BP 9 EP 26 DI 10.1089/cmb.1998.5.9 PG 18 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 ZD374 UT WOS:000072678800002 PM 9541868 ER PT J AU Kingman, A Albertini, T Brown, LJ AF Kingman, A Albertini, T Brown, LJ TI Mercury concentrations in urine and whole blood associated with amalgam exposure in a US military population SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amalgam exposure; urine Hg; whole blood Hg ID DENTAL AMALGAM; UNITED-STATES; FILLINGS; VAPOR; RESTORATIONS; DENTISTS; EXCRETION; DENTITION; ETHANOL; ADULTS AB Minute amounts of mercury vapor are released from dental amalgams. Since mercury vapor is known to be associated with adverse health effects from occupationally exposed persons, questions regarding the margin of safety for exposure to mercury vapor in the general population continue to be raised. To address this issue, one needs information regarding exposure to mercury vapor from dental amalgam fillings and its possible consequences for health in the general population. The NIDR Amalgam Study is designed to obtain precise information on amalgam exposure and health outcomes for a non-occupationally-exposed population of US adults. One hypothesis was that in a generally healthy population a significant association between amalgam exposure and Hg levels in urine and/or whole blood could be detected. The cohort investigated was an adult military population of 1127 healthy males. Their average age was 52.8 years, and their ages varied from 40 to 78 years. Ninety-five percent of the study participants were white males, and slightly over 50% had some college education. Five percent were edentulous. The dentate participants, on average, had 25 natural teeth, 36.9 decayed or filled surfaces (DFS), and 19.9 surfaces exposed to amalgam, with amalgam exposure varying from 0 to 66 surfaces. Their average total and inorganic urinary mercury concentrations were 3.09 mu g/L and 2.88 mu g/L The average whole-blood total and inorganic mercury concentrations were 2.55 mu g/L and 0.54 mu g/L. Significant correlations were detected between amalgam exposure and the total (r = 0.34, p < 0.001) and inorganic 0.34 (r = 0.34, p < 0.001) urinary mercury concentrations on the original scale. Stronger correlations were found for total (r = 0.44, p < 0.001) and inorganic (r = 0.41, p < 0.001) urinary Hg on the log scale, as well as for creatinine-corrected total (r = 0.43, p < 0.001) and inorganic (r = 0.43, p < 0.001) urine concentrations. In whole blood, statistically significant, but biologically weak, correlations were detected for total (r = 0.09, p = 0.005) and inorganic (r = 0.15, p < 0.001) Hg concentrations, respectively. Based on these cross-sectional data, it is estimated that, on average, each ten-surface increase in amalgam exposure is associated with an increase of 1 mu g/L mercury in urine concentration. C1 Natl Inst Dental Res, Risk Factors & Mol Epidemiol Branch, Bethesda, MD 20892 USA. RP Kingman, A (reprint author), Natl Inst Dental Res, Risk Factors & Mol Epidemiol Branch, Natcher Bldg,Rm4AS-13B,45 Ctr Dr,MSC6401, Bethesda, MD 20892 USA. NR 41 TC 93 Z9 96 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 1998 VL 77 IS 3 BP 461 EP 471 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YZ958 UT WOS:000072312300005 PM 9496919 ER PT J AU Paine, ML Krebsbach, PH Chen, LS Paine, CT Yamada, Y Deutsch, D Snead, ML AF Paine, ML Krebsbach, PH Chen, LS Paine, CT Yamada, Y Deutsch, D Snead, ML TI Protein-to-protein interactions: Criteria defining the assembly of the enamel organic matrix SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelin; ameloblastin; amelogenin; biomineralization; enamel; enamelin; protein matrix assembly; sheathlin; tooth development; tuftelin; yeast two-hybrid system; protein interactions ID LINKED AMELOGENESIS IMPERFECTA; RECOMBINANT AMELOGENIN; 2-HYBRID SYSTEM; GENE; IDENTIFICATION; YEAST; MUTATIONS; BINDING; ANTIGEN; CELLS AB Enamel crystallites form in a protein matrix located proximal to the ameloblast cell layer. This unique organic extracellular matrix is constructed from structural protein components biosynthesized and secreted by ameloblasts. To date, three distinct classes of enamel matrix proteins have been cloned. These are the amelogenins, tuftelin, and ameloblastin, with recent data implicating ameloblastin gene expression during cementogenesis. The organic enamel extracellular matrix undergoes assembly to provide a three-dimensional array of protein domains that carry out the physiologic function of guiding enamel hydroxyapatite crystallite formation. Using the yeast two-hybrid system, we have surveyed these three known enamel gene products for their ability to direct self-assembly. We measured the capacity of the enamel gene products to direct protein-to-protein interactions, a characteristic of enamel proteins predicated to be required for self-assembly. We provide additional evidence for the self-assembly nature of amelogenin and tuftelin. Ameloblastin self-assembly could not be demonstrated, nor were protein-to-protein interactions observed between ameloblastin and either amelogenin or tuftelin. Within the limits of the yeast two-hybrid assay, these findings constrain the emerging model of enamel matrix assembly by helping to define the limits of enamel matrix protein-protein interactions that are believed to guide enamel mineral crystallite formation. C1 Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. NIDR, Lab Craniofacial Dev Biol & Regenerat, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Fac Med Dent, Dent Res Unit, Jerusalem, Israel. RP Paine, ML (reprint author), Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, 2250 Alcazar St,CSA Room 142, Los Angeles, CA 90033 USA. FU NIDCR NIH HHS [DE 11704, DE 06988, DE 08678] NR 43 TC 39 Z9 39 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 1998 VL 77 IS 3 BP 496 EP 502 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YZ958 UT WOS:000072312300009 PM 9496923 ER PT J AU Hser, YI Boyle, K Anglin, MD AF Hser, YI Boyle, K Anglin, MD TI Drug use and correlates among sexually transmitted disease patients, emergency room patients, and arrestees SO JOURNAL OF DRUG ISSUES LA English DT Article ID SECONDARY PREVENTION; SUBSTANCE ABUSE; SEX BEHAVIORS; CRACK COCAINE; INFECTION; AIDS AB This paper reports the results of a study on the use of illicit drugs and related problems in groups that are often considered hidden populations at high risk for drug abuse. Face-to-face interviews were conducted in 1992-94 with 5,168 subjects from sexually transmitted disease (STD) clinics, hospital emergency rooms (ER), and jails in Los Angeles County, California. Extensive drug involvement and other HIV-risk behaviors were reported by all three samples. Excluding marijuana, crack and cocaine were the most prevalent drugs used; the rate of positive cocaine urinalysis was 8.5% for STD subjects, 18.1% for ER subjects, and 52.8% for the arrestees. About 40% of the subjects from both STDs and jails and 27% from ERs reported three or more sex partners in the past year. About 41% of STD and 49% of ER samples also reported having arrest records. Current use of heroin and cocaine was highly associated with multiple sex partners and an arrest record. The study confirmed the high prevalence of drug abuse and other high-risk behaviors in these samples. The importance of targeting these groups for early identification and intervention is underscored. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Drug Abuse Res Ctr, Los Angeles, CA 90024 USA. Natl Inst Drug Abuse, Bethesda, MD USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Hser, YI (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Drug Abuse Res Ctr, 1100 Glendon Ave,Suite 763, Los Angeles, CA 90024 USA. NR 22 TC 12 Z9 12 U1 0 U2 0 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SPR PY 1998 VL 28 IS 2 BP 437 EP 453 PG 17 WC Substance Abuse SC Substance Abuse GA 102EU UT WOS:000074912000009 ER PT J AU Nelson, DB Kotranski, L Semaan, S Collier, K Lauby, J Feighan, K Halbert, J AF Nelson, DB Kotranski, L Semaan, S Collier, K Lauby, J Feighan, K Halbert, J TI The validity of self-reported opiate and cocaine use by out-of-treatment drug users SO JOURNAL OF DRUG ISSUES LA English DT Article AB The objective of this study was (I) to assess the validity of self-report measures of opiate and cocaine use for a sample of out-of-treatment drug users by comparing self-reports to urinalysis results, and (2) to examine the correlates of valid self-reports. Baseline data were collected from 1, 015 out-of-treatment drug users in Philadelphia as part of an HIV risk reduction intervention project funded by the National Institute on Drug Abuse. Agreement rates, sensitivity, and specificity measurements were high, and kappa values were good indicating that out-of-treatment drug users provided moderately valid self-reported drug use. The multivariate analysis revealed that women and younger persons were more likely to validly report opiate use and those who were younger and more educated were more likely to give valid reports of cocaine use. Additional research is needed to better understand differences in the validity of self-reports of opiate and cocaine use and the role that urinalysis plays in influencing the validity of self-reported data. C1 Philadelphia Hlth Management Corp, Philadelphia, PA 19102 USA. NIDA, Cooperat Agreement Community Based Monitoring & A, Rockville, MD USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP Kotranski, L (reprint author), Philadelphia Hlth Management Corp, 260 S Broad St, Philadelphia, PA 19102 USA. NR 17 TC 16 Z9 16 U1 0 U2 0 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SPR PY 1998 VL 28 IS 2 BP 483 EP 494 PG 12 WC Substance Abuse SC Substance Abuse GA 102EU UT WOS:000074912000011 ER PT J AU Bonds, C Frye, MA Coudreaut, MF Cunningham, M Spearing, M McGuire, M Guze, B AF Bonds, C Frye, MA Coudreaut, MF Cunningham, M Spearing, M McGuire, M Guze, B TI Cost reduction with maintenance ECT in refractory bipolar disorder SO JOURNAL OF ECT LA English DT Article DE maintenance electroconvulsive therapy; bipolar depression; life chart ID ELECTROCONVULSIVE-THERAPY; CLINICAL EFFICACY; CONTINUATION ECT AB A case report of outpatient maintenance electroconvulsive therapy (ECT) is presented in a patient with bipolar disorder type I refractory to conventional medication treatment but responsive to ECT. A cost comparison is made showing substantial savings when outpatient maintenance ECT is used in lieu of inpatient hospitalization with ECT. A detailed life chart illustrating multiple medication trials that failed to stabilize the patient accompanies the financial summary. This case highlights the advantages of outpatient maintenance ECT for bipolar depression particularly with regard to safety, efficacy, and significant health care cost reduction. C1 Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Bonds, C (reprint author), Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. NR 17 TC 24 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1095-0680 J9 J ECT JI J. ECT PD MAR PY 1998 VL 14 IS 1 BP 36 EP 41 PG 6 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 104JG UT WOS:000075010500006 PM 9661092 ER PT J AU Reincke, M Beuschlein, F Menig, G Hofmockel, G Arlt, W Lehmann, R Karl, M Allolio, B AF Reincke, M Beuschlein, F Menig, G Hofmockel, G Arlt, W Lehmann, R Karl, M Allolio, B TI Localization and expression of adrenocorticotropic hormone receptor mRNA in normal and neoplastic human adrenal cortex SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SIDE-CHAIN CLEAVAGE; PROTEIN-KINASE-C; MESSENGER-RNA; ACTH RECEPTOR; ANGIOTENSIN-II; CORTICOTROPIN; CELLS; GENE; REDISTRIBUTION; HYBRIDIZATION AB The recent cloning of the ACTH receptor (ACTH-R) gene allows investigation of the tissue localization and relative abundance of ACTH-R mRNA in normal and neoplastic adrenal cortex. Using in situ hybridization (ISH) we studied the expression of ACTH-R mRNA in four adult adrenals of brain-dead patients, two cortisol-producing adenomas (CPA), three aldosterone-producing adenomas (APA), one non-functional adenoma (NFA), and three cat-cinemas. The results were compared with the mRNA expression of key steroidogenic enzymes and of the glucocorticoid receptor (GR) mRNA using Northern blotting. In adult adrenals, messenger RNA encoding ACTH-R was localized in all three zones of the adrenal cortex, in accordance with the stimulatory role of ACTH on mineralocorticoid, glucocorticoid and adrenal androgen secretion. In comparison, expression of side-chain cleavage enzyme (P450scc) showed a similar tissue distribution with mRNA abundance in all three zones, whereas 17-hydroxylase/17-20 lyase (P450c17) mRNA expression was only detected in the zona fasciculata and zona reticularis. All CPAs and APAs expressed significant levels of ACTH-R mRNA whereas an NFA showed low expression of ACTH-II mRNA. Two of three adrenocortical carcinomas expressed ACTH-R mRNA. Northern analysis using dot blot was employed to quantify ACTH-R and GR mRNA expression and confirmed the ISH data: ACTH-R mRNA expression was high in CPAs (275 and 195% iis 100 +/- 25% in adult adrenals), APAs (127, 200 and 221%) and two carcinomas (99 and 132%), but low in the NFA (7%) and in an androgen secreting carcinoma (16%). GR mRNA expression was high in the NFA (195%) and in two of three carcinomas (93, 188, 227%). We conclude that ACTH-R mRNA is up-regulated in functional adenomas by yet unidentified mechanisms. The tissue distribution of ACTH-R and P450 enzyme mRNA expression is highly variable in neoplastic adrenals and does not allow a clear differentiation between benign and malignant tumors. C1 Univ Wurzburg, Med Klin, Schwerpunkt Endokrinol, D-97080 Wurzburg, Germany. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. Univ Wurzburg, Urol Klin, Wurzburg, Germany. RP Reincke, M (reprint author), Univ Wurzburg, Med Klin, Schwerpunkt Endokrinol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. RI Arlt, Wiebke/B-6310-2009 OI Arlt, Wiebke/0000-0001-5106-9719 NR 29 TC 37 Z9 39 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL BS12 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 1998 VL 156 IS 3 BP 415 EP 423 DI 10.1677/joe.0.1560415 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA427 UT WOS:000072362400003 PM 9582497 ER PT J AU Kapas, S Martinez, A Cuttitta, F Hinson, JP AF Kapas, S Martinez, A Cuttitta, F Hinson, JP TI Local production and action of adrenomedullin in the rat adrenal zona glomerulosa SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; MELANOCYTE-STIMULATING HORMONE; HYPOTENSIVE PEPTIDE; INDUCED INHIBITION; INSULIN-SECRETION; RECEPTOR; EXPRESSION; GLAND; CELLS; BINDING AB This study was designed to investigate the synthesis and action of adrenomedullin in the rat adrenal gland. The results obtained from in situ hybridization and immunocytochemical studies suggest that adrenomedullin is synthesized not only in the medulla, but also within the zona glomerulosa of the rat adrenal cortex. Findings from in situ hybridization and binding studies also suggested thai specific adrenomedullin receptors are expressed in the zona glomerulosa, and that low levels are present in the inner zones of the cortex. The K-d of the zona glomerulosa adrenomedullin receptor (5.5 nmol/l) suggests that it may respond to locally produced adrenomedullin rather than circulating concentrations of the peptide, which are in a lower range, It was found thar adrenomedullin acted on zona glomerulosa cells in vitro to stimulate aldosterone release and cAMP formation, but in this tissue did not stimulate inositol phosphate turnover. The effect of adrenomedullin on aldosterone secretion was significantly attenuated by a protein kinase A inhibitor, suggesting that cAMP mediates the effects of adrenomedullin on aldosterone secretion. Adrenomedullin did not significantly affect the response of zona glomerulosa cells to stimulation by either ACTH or angiotensin II. Adrenomedullin did not affect the release of catecholamines, either adrenaline or noradrenaline, by intact adrenal capsular-tissue. These data suggest that both adrenomedullin and its specific receptor are expressed in the rat adrenal zona glomerulosa, leading to the hypothesis that adrenomedullin may have an autocrine/paracrine role in the regulation of the rat adrenal zona glomerulosa. C1 Univ London Queen Mary & Westfield Coll, Fac Basic Med Sci, Dept Biochem, London E1 4NS, England. St Bartholomews & Royal London Sch Med & Dent, Dept Oral Pathol, London E1 2AD, England. NCI, Div Clin Sci, NIH, Rockville, MD 20850 USA. RP Hinson, JP (reprint author), Univ London Queen Mary & Westfield Coll, Fac Basic Med Sci, Dept Biochem, Mile End Rd, London E1 4NS, England. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 32 TC 80 Z9 80 U1 0 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL BS12 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 1998 VL 156 IS 3 BP 477 EP 484 DI 10.1677/joe.0.1560477 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA427 UT WOS:000072362400010 PM 9582504 ER PT J AU Parnas, I Shahrabany-Baranes, O Feinstein, N Grant, P Adelsberger, H Dudel, J AF Parnas, I Shahrabany-Baranes, O Feinstein, N Grant, P Adelsberger, H Dudel, J TI Changes in the ultrastructure of surviving distal segments of severed axons of the rock lobster SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE axon; degeneration; glia; axotomy; rock lobster; Panulirus penicillatus ID LONG-TERM SURVIVAL; SQUID GIANT-AXON; PROTEIN TRANSFER HYPOTHESIS; DECENTRALIZED AXONS; NERVE REGENERATION; SCHWANN-CELLS; CRAYFISH; NEURONS; DEGENERATION; GLIA AB Peripheral axons of lobsters can survive for many months after axotomy. We have investigated the structural and ultrastructural changes seen after axotomy using confocal microscopy and electron microscopy. While the proximal stump had a normal appearance, the distal part of the cut axon became lobulated, and glial cells penetrated the original glial tube (axon tube) in which the axon normally runs. The changes proceeded from the cut end towards the muscle. As time elapsed, the axon tube seemed to be filled with glial cells, but interposed small profiles of the original axon could be identified by injection of a fluorescent dye into the axon. The glial cells send cytoplasmic projections deep into folds of the axolemma, and nuclei were found at the end of these long processes. Proliferation of glial cells was also seen. C1 Hebrew Univ Jerusalem, Otto Loewi Minerva Ctr Cellular & Mol Neurobiol, IL-91905 Jerusalem, Israel. NIH, Neurochem Lab, Washington, DC USA. Tech Univ Munich, Dept Physiol, D-8000 Munich, Germany. RP Parnas, I (reprint author), Hebrew Univ Jerusalem, Otto Loewi Minerva Ctr Cellular & Mol Neurobiol, IL-91905 Jerusalem, Israel. NR 54 TC 11 Z9 11 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD MAR PY 1998 VL 201 IS 6 BP 779 EP 791 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA ZG775 UT WOS:000073038100001 PM 9464959 ER PT J AU Margarino, G Mereu, P Scala, M Comandini, D Nocentini, L Monteghirfo, S AF Margarino, G Mereu, P Scala, M Comandini, D Nocentini, L Monteghirfo, S TI Flow chart for clinical staging of thyroid tumors SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT SICO 1st National Symposium on Guidelines for Diagnosis and Treatment of Thyroid Carcinoma CY 1997 CL ROME, ITALY SP SICO C1 Natl Canc Inst, Dept Surg Oncol, Genoa, Italy. RP Margarino, G (reprint author), Ist Nazl Ric Canc, Div Oncol Chirurg, Lgo R Benzi 10, I-16132 Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APSIT ASSOC PROM STUD IMMUNOL TUMOR PI ROME PA VIALE REGINA ELENA 291, 00161 ROME, ITALY SN 0392-9078 J9 J EXP CLIN CANC RES JI J. Exp. Clin. Cancer Res. PD MAR PY 1998 VL 17 IS 1 BP 121 EP 123 PG 3 WC Oncology SC Oncology GA ZM388 UT WOS:000073534200021 PM 9646247 ER PT J AU Haj-Yahia, MM Dawud-Noursi, S AF Haj-Yahia, MM Dawud-Noursi, S TI Predicting the use of different conflict tactics among Arab siblings in Israel: A study based on social learning theory SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE conflict tactics; witnessing domestic violence; experiencing domestic violence; sibling abuse and violence; Arab youth and violence ID MALTREATMENT; AGGRESSION; CHILD; VIOLENCE; PRESCHOOLERS; BEHAVIOR; ADULTS AB The article presents a study conducted among 832 Arab adolescents from Israel, in an attempt to predict their use of different tactics (i.e., reasoning, verbal abuse, and physical violence) to resolve conflicts with siblings from the perspective of social learning theory. Different forms of the CT Scales were utilized to elicit information on Arab adolescents' exposure to and experience with different conflict tactics in their families of origin. as well as on their use of such tactics with siblings. Results indicate that the more they witnessed reasoning in their families of origin, the greater the likelihood that they would use the same tactic to resolve conflicts with their siblings. At the same time, the more they witnessed or experienced verbal abuse and physical violence the greater their use of verbal and physical violence against their siblings. A detailed discussion of different patterns of violence in Arab families as reported by the adolescents is presented, and several implications of the study are addressed. C1 Hebrew Univ Jerusalem, Paul Baerwald Sch Social Work, IL-91905 Jerusalem, Israel. NICHHD, NIH, Bethesda, MD 20892 USA. RP Haj-Yahia, MM (reprint author), Hebrew Univ Jerusalem, Paul Baerwald Sch Social Work, IL-91905 Jerusalem, Israel. NR 45 TC 25 Z9 25 U1 1 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD MAR PY 1998 VL 13 IS 1 BP 81 EP 103 DI 10.1023/A:1022864801027 PG 23 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA ZE021 UT WOS:000072749200005 ER PT J AU Hoelzel, AR Dahlheim, M Stern, SJ AF Hoelzel, AR Dahlheim, M Stern, SJ TI Low genetic variation among killer whales (Orcinus orca) in the eastern North Pacific and genetic differentiation between foraging specialists SO JOURNAL OF HEREDITY LA English DT Article ID MITOCHONDRIAL-DNA; POPULATIONS; TRANSIENT; BEHAVIOR; ALASKA AB Killer whales from the coastal waters off California through Alaska were compared for genetic variation at three nuclear DNA markers and sequenced for a total of 520 bp from the mitochondrial control region. Two putative sympatric populations that range throughout this region were compared. They can be distinguished by social and foraging behavior and are known as "residents" and "transients." We found low levels of variation within populations compared to other cetacean species. Comparisons between fish (resident) versus marine mammal (transient) foraging specialists indicated highly significant genetic differentiation at both nuclear and mitochondrial loci. This differentiation is at a level consistent with intraspecific variation. A comparison between two parapatric resident populations showed a small but fixed mtDNA haplotype difference. Together these data suggest low levels of genetic dispersal between foraging specialists and a pattern of genetic differentiation consistent with matrifocal population structure and small effective population size. C1 NMFS, Natl Marine Mammal Lab, Seattle, WA USA. Texas A&M Univ, Marine Mammal Res Program, Galveston, TX USA. NCI, Viral Carcinogenesis Lab, Frederick, MD 21701 USA. RP Univ Durham, Dept Biol Sci, South Rd, Durham DH1 3LE, England. NR 32 TC 155 Z9 162 U1 6 U2 48 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PD MAR-APR PY 1998 VL 89 IS 2 BP 121 EP 128 DI 10.1093/jhered/89.2.121 PG 8 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA ZK793 UT WOS:000073364100002 PM 9542159 ER PT J AU Memon, SA Hou, JZ Moreno, MB Zacharchuk, CM AF Memon, SA Hou, JZ Moreno, MB Zacharchuk, CM TI Cutting edge: Apoptosis induced by a chimeric Fas/FLICE receptor: Lack of requirement for Fas- or FADD-binding proteins SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; CD95 FAS/APO-1; PROTEASE; BCL-2 AB Current models for Pas (CD95)-mediated apoptosis suggest that FLICE/caspase-8 is recruited and activated, which results in cell death, However, the role of additional molecules in Pas signaling and FLICE activation is not clear, A chimeric Fas/FLICE (F/F) receptor, containing the extracellular/transmembrane portion of Pas and the caspase region of FLICE, mediated anti-Pas apoptosis. FLICE protease subunits were generated from the F/F precursor, Killing induced by Fas, but not F/F, was blocked by a dominant negative FADD, Apoptosis triggered through Pas and F/F was inhibited by coexpression of CrmA and p35, but not Bcl-xL, F/F bypassed Pas resistance in COS-7 cells and blocking by the death effector domain (DED)-containing viral protein MC159. These results show that: 1) F/F induces cell death, indicating that FLICE activation is sufficient for apoptosis and dots not require additional Pas-or FADD-binding proteins; and 2) F/F bypasses proximal defects in Pas signaling that prevent FLICE recruitment or activation. C1 NCI, Immune Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Zacharchuk, CM (reprint author), NCI, Immune Cell Biol Lab, Div Basic Sci, NIH, Bldg 10,Room 1B40,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 15 TC 33 Z9 34 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1998 VL 160 IS 5 BP 2046 EP 2049 PG 4 WC Immunology SC Immunology GA YY124 UT WOS:000072115700003 PM 9498739 ER PT J AU Shields, MJ Assefi, N Hodgson, W Kim, EJ Ribaudo, RK AF Shields, MJ Assefi, N Hodgson, W Kim, EJ Ribaudo, RK TI Characterization of the interactions between MHC class I subunits: A systematic approach for the engineering of higher Affinity variants of beta(2)-microglobulin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; DISULFIDE BOND FORMATION; DOWN-REGULATION; SURFACE EXPRESSION; PEPTIDE BINDING; DENDRITIC CELLS; HEAVY-CHAIN; BETA-2-MICROGLOBULIN BETA(2)M; VIRAL PEPTIDES; T-LYMPHOCYTES AB Human beta(2)m (h beta(2)m) binds to murine MHC I molecules with higher affinity than does murine beta(2)m and therefore can be used as a model system to define and dissect the interactions between beta(2)m and MHC I heavy chains that promote the stability of the complex. In the present study we compare three-dimensional crystal structures of human and murine MHC I molecules and use functional studies of chimeric human:murine beta(2)m variants to define a region of beta(2)m that is involved in the higher affinity of h beta(2)m for murine MHC I heavy chains. Further examination of the three-dimensional structure in this region revealed conformational differences between human and murine beta(2)m that affect the ability of an aspartic acid residue at position 53 (D53) conserved in both beta(2)ms to form an ionic bond with arginine residues at positions 35 and 48 of the heavy chain. Mutation of residue D53 to either asparagine (D53N) or valine (D53V) largely abrogated the stabilizing effects of h beta(2)m on murine MHC I expression in a predictable manner. Based on this observation a variant of h beta(2)m was engineered to create an ionic bond between the heavy chain and beta(2)m This variant stabilizes cell surface H-2D(d) heavy chains to a greater extent than wild-type h beta(2)m. Studying these interactions in light of the growing database of MHC I crystal structures should allow the rational design of higher affinity h beta(2)m variants for use in novel peptide-based vaccines capable of inducing cell-mediated immune responses to viruses and tumors. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ribaudo, RK (reprint author), NCI, Lab Immune Cell Biol, NIH, Bldg 10,Room 1B43, Bethesda, MD 20892 USA. NR 52 TC 21 Z9 26 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 MAR 1 PY 1998 VL 160 IS 5 BP 2297 EP 2307 PG 11 WC Immunology SC Immunology GA YY124 UT WOS:000072115700034 PM 9498770 ER PT J AU Hu, HM Baer, M Williams, SC Johnson, PF Schwartz, RC AF Hu, HM Baer, M Williams, SC Johnson, PF Schwartz, RC TI Redundancy of C/EBP alpha, -beta, and -delta in supporting the lipopolysaccharide-induced transcription of IL-6 and monocyte chemoattractant protein-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; NF-KAPPA-B; LYMPHOBLASTIC CELL-LINE; INDUCIBLE EXPRESSION; INTERLEUKIN-6 GENE; MEDIATE INDUCTION; FAMILY; NF-IL6; MACROPHAGES; MEMBER AB C/EBP alpha, -beta, and -delta are members of the CCAAT/enhancer binding protein family of transcriptional regulators. All three of these factors are expressed by bone marrow-derived macrophages, with the DNA binding activity of C/EBP beta and -delta increased by treatment with LPS while that of C/EBP alpha is decreased, We have ectopically expressed each C/EBP protein in P388 lymphoblasts, The expression of any of these transcription factors is sufficient to confer the LPS-inducible expression of IL-6 and monocyte chemoattractant protein-1 to lymphoblasts, which normally lack C/EBP factors and do not display LPS induction of proinflammatory cytokines, Thus, the activities of C/EBP alpha, -beta, and -delta are redundant in regard to the expression of IL-6 and monocyte chemoattractant protein-1. Since C/EBP beta-deficient mice have been reported to be largely normal in their expression of proinflammatory cytokines, it is likely that the lark of C/EBP beta is compensated for by the induction of C/EBP delta upon LPS treatment. C1 Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. RP Schwartz, RC (reprint author), Michigan State Univ, Dept Microbiol, Giltner Hall, E Lansing, MI 48824 USA. EM schwart9@pilot.msu.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 37 TC 78 Z9 80 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 MAR 1 PY 1998 VL 160 IS 5 BP 2334 EP 2342 PG 9 WC Immunology SC Immunology GA YY124 UT WOS:000072115700038 PM 9498774 ER PT J AU Bristol, JA Schlom, J Abrams, SI AF Bristol, JA Schlom, J Abrams, SI TI Development of a murine mutant Ras CD8(+) CTL peptide epitope variant that possesses enhanced MHC class I binding and immunogenic properties SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTE; CELLS BEARING; TUMOR-CELLS; ANTIGEN; INDUCTION; RECOGNITION; REPERTOIRE; MOLECULES; EXPANSION; RESIDUES AB We recently identified a murine mutant Ras p21 CD8(+) CTL epitope reflecting residues 4 to 12, containing the mutation of Gly to Val at codon 12, that bound weakly to H-2K(d) in vitro and generated a weak primary CTL response in immunized BALB/c mice, Here, we explored the hypothesis that specific modifications to the Ras(4-12) peptide sequence can improve MHC binding, leading to enhanced immunogenicity without altering immune specificity, We synthesized Ras(4-12) peptides in which Val at residue 12 was replaced with the more dominant H-2K(d) C-terminus anchor residue Leu or ne. In functional H-2K(d) binding assays, Ras(4-12)(L12 or I12) peptide variants competed more effectively than the Ras(4-12)(V12) peptide, Ras(4-12)(L12 or I12) peptide variants enhanced both in vitro cytotoxicity and proliferation responses of anti-Ras(4-12) CTL compared with the mutant Ras(4-12)(V12) peptide, Additionally, the Ras(4-12)(L12) peptide variant induced a quantitatively greater T cell response in vivo compared with that produced by Ras(4-12)(V12) as determined by IFN-gamma production, Mice immunized with Ras(4-12)(L12) peptide elicited CD8(+) CTL activity specific for target cells presenting the Ras(4-12)(V12) epitope exogenously and endogenously, Moreover, both anti-Ras(4-12)(V12)-derived and anti-Ras(4-12)(L12)-derived CTL lines were similar insofar as their TCR usage and amino acid contact residues in the Ras(4-12)(V12) peptide, These experiments demonstrate that modifications can be introduced in tumor-specific peptide epitopes to enhance both in vitro and in vivo immunogenicity. The design of oncogene-specific peptide epitope variants as immunogens may accelerate the generation of anti-tumor T cell responses for cancer immunotherapy. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 8B-07,10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 26 TC 28 Z9 31 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 MAR 1 PY 1998 VL 160 IS 5 BP 2433 EP 2441 PG 9 WC Immunology SC Immunology GA YY124 UT WOS:000072115700051 PM 9498787 ER PT J AU Fenton, RG Turcovski-Corrales, SM Taub, DD AF Fenton, RG Turcovski-Corrales, SM Taub, DD TI Induction of melanoma antigen-specific cytotoxic T lymphocytes in vitro by stimulation with B7-expressing human melanoma cell lines SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE B7; costimulation; T lymphocytes; tumor; immunotherapy ID TUMOR-INFILTRATING LYMPHOCYTES; ANTITUMOR IMMUNITY; DENDRITIC CELLS; COSTIMULATORY LIGANDS; HLA-A2 MELANOMAS; B7 COSTIMULATION; CD28 RECEPTOR; CLONAL ANERGY; IN-VITRO; EXPRESSION AB Crosslinking of CD28 receptors on resting T lymphocytes by B7 costimulatory molecules expressed by antigen-presenting cells (APCs) plays a critical role in T-cell activation. Human melanomas express major histocompatibility complex (MHC)-restricted tumor-associated antigens that can be recognized by cytotoxic T lymphocytes (CTL), yet they remain poorly immunogenic. One mechanism for the failure of T-cell response is the lack of expression of costimulatory molecules by human melanoma cells. We have transfected the B7-1 gene into three HLA-A2-expressing human melanoma cell lines, and studied their capacity to stimulate primary human T cells. B7-expressing melanoma cells were excellent inducers of T-cell proliferation, cytokine production, and cytolytic activity in allogeneic mixed lymphocyte cultures through a process dependent on the function of the T-cell receptor as well as interactions between B7:CD28, CD2:LFA-3, and LFA-1:ICAM-1. Subset analysis demonstrated that CD4(+) T cells or addition of exogenous interleukin-2 was required for the induction of CD8(+) CTL. Untransfected parental melanoma cells were inert as APCs in these cultures. Rotating stimulation of T cells with the three B7-expressing cell Lines led to the generation of T-cell lines that were cytolytic for HLA-A2(+) melanoma cells and other HLA-A2(+) targets that were pulsed with HLA-A2-restricted MART-1 peptides. These data demonstrate that expression of B7-1 by human melanoma cells converts them into effective APCs for the in vitro induction of MHC-restricted, melanoma-specific CTL. C1 NCI, Frederick Canc Res & Dev Ctr, Div Clin Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Clin Serv Program, Frederick, MD 21702 USA. RP Fenton, RG (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Clin Sci, POB B,Bldg 567,Room 207, Frederick, MD 21702 USA. NR 57 TC 21 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1998 VL 21 IS 2 BP 95 EP 108 DI 10.1097/00002371-199803000-00002 PG 14 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA ZC551 UT WOS:000072591900002 PM 9551360 ER PT J AU Yewdell, JW Snyder, HL Bacik, I Anton, LC Deng, YP Behrens, TW Bachi, T Bennink, JR AF Yewdell, JW Snyder, HL Bacik, I Anton, LC Deng, YP Behrens, TW Bachi, T Bennink, JR TI TAP-Independent delivery of antigenic peptides to the endoplasmic reticulum: Therapeutic potential and insights into TAP-dependent antigen processing SO JOURNAL OF IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT 3rd Keystone Symposium on Cellular Immunology and the Immunotherapy of Cancer CY FEB 01-07, 1997 CL COPPER MOUNTAIN, COLORADO DE antigen processing; cytotoxic T lymphocytes; recombinant viruses; vaccine ID T-CELL RECEPTOR; IN-VIVO; TRANSPORTERS; COMPLEX AB We have taken several approaches to investigate the capacity of the secretory pathway to liberate major histocompatibility complex (MHC) class I-restricted antigenic peptides from precursor polypeptides. Cells lacking the peptide transporter (TAP) are unable to deliver peptides from cytosolic antigens to class I molecules. TAP can be bypassed by targeting peptides directly to the endoplasmic reticulum (ER) using NH2-terminal signal sequences. This results in the generation of enormous numbers of MHC class I complexes (50,000 peptides/cell), and recombinant vaccinia viruses expressing such peptides are highly immunogenic. In contrast to signal sequence-targeted peptides, peptides are liberated very inefficiently from internal locations in ER-targeted full-length proteins, indicating that the secretory pathway has a limited capacity for generating antigenic peptides from most polypeptide contexts. We have, however, identified a location in proteins from which peptides can be liberated in numerous contexts in the secretory pathway. Placing a number of different peptides at the COOH termini of a secreted protein and two proteins with type II. membrane anchors resulted in their TAP-independent presentation. These findings demonstrate that the secretory compartment possesses proteases able to liberate COOH-terminal antigenic peptides from virtually any context, entirely consistent with a role for these proteases in the processing of TAP-transported antigenic peptide precursors. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. Univ Zurich, Electron Microscopy Lab, Zurich, Switzerland. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Rm 213,Bldg 4, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 21 TC 21 Z9 22 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1998 VL 21 IS 2 BP 127 EP 131 DI 10.1097/00002371-199803000-00006 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA ZC551 UT WOS:000072591900006 PM 9551364 ER PT J AU Noronha, SB Kaslow, DC Shiloach, J AF Noronha, SB Kaslow, DC Shiloach, J TI Transition phase in the production of recombinant proteins in yeast under the ADH2 promoter: an important step for reproducible manufacturing of a malaria transmission blocking vaccine candidate SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE ADH2, TBV25H; Saccharomyces; malaria ID SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; HANSENULA-POLYMORPHA; CAMP LEVELS; GLUCOSE; GROWTH; ETHANOL; CULTURE; OCCURS; ADR1 AB TBV25H, a malaria transmission blocking vaccine candidate, has been cloned in Saccharomyces cerevisiae under the control of the glucose repressed ADH2 promoter. Available fermentation procedures for production of this protein have been unsatisfactory, mainly because of irreproducibility, This work presents an efficient and reproducible method for the production of this vaccine candidate by implementing a three-stage fermentation process, During the first (glucose fed-batch) phase, the promoter is repressed and the culture is allowed to grow exponentially. In the second stage, the glucose supply is provided at a slower constant rate, In the third (ethanol consumption) stage, accumulated ethanol is first allowed to be consumed and an external ethanol supplement is then added as required. The promoter is fully derepressed in this phase, and TBV25H is synthesized. The period of glucose limitation was concluded to be essential for reproducibility, It is presumed that during this period, the culture moves gradually from glucose to ethanol utilization, derepressing the promoter, activating recombinant protein biosynthesis and consequently resuming metabolism without the typical diauxic phase of batch cultures. C1 NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. NIAID, Mol Vaccine Sect, NIH, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, LCDB, NIH, Bldg 6,Rm B1-33, Bethesda, MD 20892 USA. NR 29 TC 5 Z9 5 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD MAR-APR PY 1998 VL 20 IS 3-4 BP 192 EP 199 DI 10.1038/sj.jim.2900507 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZV710 UT WOS:000074333300011 ER PT J AU Thomas, DL Vlahov, D Alter, HJ Hunt, JC Marshall, R Astemborski, J Nelson, KE AF Thomas, DL Vlahov, D Alter, HJ Hunt, JC Marshall, R Astemborski, J Nelson, KE TI Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-12, 1997 CL CHICAGO, ILLINOIS SP Amer Assoc Study Liver Dis ID INJECTING DRUG-USERS; INFECTION; GENOME AB GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use, Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection, Anti-GBV-C is highly associated with viral clearance and protection from reinfection. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Abbott Labs, Div Diagnost, N Chicago, IL 60064 USA. RP Thomas, DL (reprint author), 1147 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. FU NIDA NIH HHS [DA-04334, DA-08004, DA-23201] NR 15 TC 75 Z9 79 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1998 VL 177 IS 3 BP 539 EP 542 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YY555 UT WOS:000072159900003 PM 9498429 ER PT J AU Gea-Banacloche, JC Weiskopf, EE Hallahan, C de Quiros, JCLB Flanigan, M Mican, JM Falloon, J Baseler, M Stevens, R Lane, HC Connors, M AF Gea-Banacloche, JC Weiskopf, EE Hallahan, C de Quiros, JCLB Flanigan, M Mican, JM Falloon, J Baseler, M Stevens, R Lane, HC Connors, M TI Progression of human immunodeficiency virus disease is associated with increasing disruptions within the CD4(+) T cell receptor repertoire SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT AAAAI/AAI/CIS Joint Meeting CY FEB 21-26, 1997 CL SAN FRANCISCO, CALIFORNIA SP AAAAI, AAI, CIS ID HIV-INFECTION; BETA-CHAIN; CD4+; DIVERSITY; SUPERANTIGENS; EXPRESSION; PATTERNS; SEGMENTS AB The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire, A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection, Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies, The relative usage of the TCRBV subfamilies of patients and controls was not significantly different, The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.24%, 95% CI, 2.34%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies, These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. Univ Autonoma Madrid, Clin Puerta de Hierro, Serv Med Interna 1, Madrid, Spain. Hosp Gen Gregorio Maranon, Microbiol Serv, Madrid, Spain. RP Gea-Banacloche, JC (reprint author), 10 Ctr Dr,Room 11B09, Bethesda, MD 20892 USA. NR 26 TC 32 Z9 32 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1998 VL 177 IS 3 BP 579 EP 585 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YY555 UT WOS:000072159900009 PM 9498435 ER PT J AU Lin, FYC Clemens, JD Azimi, PH Regan, JA Weisman, LE Philips, JB Rhoads, GG Clark, P Brenner, RA Ferrieri, P AF Lin, FYC Clemens, JD Azimi, PH Regan, JA Weisman, LE Philips, JB Rhoads, GG Clark, P Brenner, RA Ferrieri, P TI Capsular polysaccharide types of group B streptococcal isolates from neonates with early-onset systemic infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-16, 1997 CL SAN FRANCISCO, CA SP Infect Dis Soc Amer ID SEROTYPE-V; INFANTS; DISEASE; ANTIBODIES; EMERGENCE; ADULTS AB The distribution of serotypes of group B streptococci (GBS) isolated from 67 infants with early-onset sepsis are described. Case-infants were assembled from 13 hospitals across the United States from 15 July 1995 to 5 February 1997 through prospective active surveillance. The distribution of GBS serotypes was Ia, 40%; Ib, 9%; II, 6%; III, 27%; V, 15%; and nontypeable, 3%. Type V occurred more frequently in the northeast region (New York and New Jersey) than in other regions (29% vs. 9%, P = .06). Conversely, type III occurred significantly less frequently in the northeast region than other regions (10% vs. 35%, P = .04). GBS types Ia, III, and V accounted for 82% of the isolates. This report supports previous observations about the emergence of GBS type V, but our data caution that conclusions about serotype distributions based on one geographic location or on a small number of patients may not be generally applicable. Continued monitoring seems necessary for the design of a GBS vaccine. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Childrens Hosp Med Ctr No Calif, Oakland, CA USA. Columbia Univ Hlth Sci, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. Univ Florida, Gainesville, FL USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. RP Lin, FYC (reprint author), Bldg 6100,Room 7B03,9000 Rockville Pike,MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-43214, HD-43215, HD-43217] NR 15 TC 58 Z9 63 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1998 VL 177 IS 3 BP 790 EP 792 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YY555 UT WOS:000072159900040 PM 9498466 ER PT J AU Savarino, SJ Brown, FM Hall, E Bassily, S Youssef, F Wierzba, T Peruski, L El-Masry, NA Safwat, M Rao, M Jertborn, M Svennerholm, AM Lee, YJ Clemens, JD AF Savarino, SJ Brown, FM Hall, E Bassily, S Youssef, F Wierzba, T Peruski, L El-Masry, NA Safwat, M Rao, M Jertborn, M Svennerholm, AM Lee, YJ Clemens, JD TI Safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli - Cholera toxin B subunit vaccine in Egyptian adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 96th Annual General Meeting of the American-Society-for-Microbiology CY MAY 19-24, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Microbiol ID ANTIBODY-SECRETING CELLS; IMMUNOSORBENT-ASSAY; DIARRHEA; IMMUNIZATION AB Enterotoxigenic Escherichia coli (ETEC) is the leading cause of bacterial diarrhea in young children in developing countries. The safety and immunogenicity of a killed, oral ETEC vaccine consisting of whole cells plus recombinantly produced cholera toxin B subunit (rCTB) was evaluated in Egypt, which is endemic for ETEC diarrhea. Seventy-four healthy Egyptian adults (21-45 years old) were randomized and received two doses of the ETEC/rCTB vaccine (E003) or placebo 2 weeks apart. The frequency of adverse events after either dose did not differ by treatment group, and no severe adverse events were reported. After vaccination, peripheral blood IgA B cell responses to CTB (100%) and to vaccine colonization factor antigens CFA/I (94%), CS4 (100%), CS2 (81%), and CS1 (69%) were significantly higher than response rates for the placebo group. These favorable results in Egyptian adults indicate that the ETEC/rCTB vaccine is a promising candidate for evaluation in younger age groups in this setting. C1 USN, Med Res Unit 3, Cairo, Egypt. Eqyptian Minist Hlth, Benha, Egypt. NICHHD, NIH, Bethesda, MD 20892 USA. Gothenburg Univ, Gothenburg, Sweden. RP Savarino, SJ (reprint author), USN, Med Res Unit 3, PSC 452,Box 127, FPO, AE 09835 USA. FU NICHD NIH HHS [HD-0026-01] NR 14 TC 56 Z9 57 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1998 VL 177 IS 3 BP 796 EP 799 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YY555 UT WOS:000072159900042 PM 9498468 ER PT J AU Kenney, RT Sacks, DL Gam, AA Murray, HW Sundar, S AF Kenney, RT Sacks, DL Gam, AA Murray, HW Sundar, S TI Splenic cytokine responses in Indian kala-azar before and after treatment SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 01-05, 1996 CL BALTIMORE, MARYLAND SP Amer Soc Trop Med & Hyg ID LEISHMANIA-DONOVANI INFECTIONS; VISCERAL LEISHMANIASIS; INTERFERON-GAMMA; IFN-GAMMA; ANTIMONY; INTERLEUKIN-10; IL-10 AB Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-gamma (IFN-gamma, n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-gamma was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-gamma treatment alone, levels of IFN-gamma mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-gamma and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Th1-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute. C1 FDA, CBER, OVRR, DAPP, Rockville, MD 20852 USA. NIAID, NIH, Bethesda, MD 20892 USA. Cornell Univ Med Coll, New York, NY USA. Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India. RP Kenney, RT (reprint author), FDA, CBER, OVRR, DAPP, 1401 Rockville Pike,HFM-416, Rockville, MD 20852 USA. FU NIAID NIH HHS [AI-16963] NR 15 TC 95 Z9 96 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1998 VL 177 IS 3 BP 815 EP 819 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YY555 UT WOS:000072159900047 PM 9498473 ER PT J AU Boni, R Matt, D Voetmeyer, A Burg, G Zhuang, ZP AF Boni, R Matt, D Voetmeyer, A Burg, G Zhuang, ZP TI Chromosomal allele loss in primary cutaneous melanoma is heterogeneous and correlates with proliferation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE chromosome 9q; chromosome 1p; loss of heterozygosity; melanoma ID HUMAN-MALIGNANT MELANOMA; EVOLUTION; NEVI AB Loss of heterozygosity at specific loci in neoplastic cells suggests the presence of a tumor suppressor gene within the deleted region. Using the microdissection technique, loss of heterozygosity has been identified in paraffin-embedded primary melanomas on chromosomes 1p and 9q. Our purpose was to determine loss of heterozygosity in primary cutaneous melanomas and to relate chromosomal alterations with cell morphology and proliferation of the tumor. Two to seven morphologic different areas in 12, primary cutaneous high risk melanomas (Breslow > 1.5 mm), as well as adjacent normal tissue, were microdissected and subjected to single step DNA extraction. Extracted genomic DNA was amplified by polymerase chain reaction using two polymorphic markers on chromosomes Ip (D1S450, between D1S548 and D1S228) and 9q (D9S12). Proliferation was evaluated by MIB-1 (Ki67) immunoreactivity and cell morphology, pigmentation and inflammation surrounding microdissected areas were investigated by microscopic inspection of hematoxylin and eosin stained sections. Twelve of 34 different areas (35%) showed loss of heterozygosity with at least one marker. Two of 32 areas showed loss of heterozygosity with D1S450 (two areas noninformative), seven of 30 with D9S12 (four areas noninformative), and three areas showed loss of heterozygosity at both loci. In three of these cases, analysis of different tumor foci revealed areas with/without loss of heterozygosity. In these cases, the percentage of MIB-I-positive cells was at least four times higher in areas with loss of heterozygosity compared with areas without loss of heterozygosity. Most areas with loss of heterozygosity consisted of small cuboidal to epitheloid cells. Spindle shaped and large anaplastic cells showed loss of heterozygosity less frequently. Neither melanization of tumor cells nor the presence of inflammation had an influence on the frequency of loss of heterozygosity. Primary cutaneous melanomas show intratumoral morphologic and chromosomal heterogeneity. Loss of heterozygosity on chromosomes 1p and 9q correlated with cell proliferation, suggesting that selected cell clones are responsible for tumor progression. C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. RP Boni, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. NR 15 TC 41 Z9 43 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 MAR PY 1998 VL 110 IS 3 BP 215 EP 217 DI 10.1046/j.1523-1747.1998.00109.x PG 3 WC Dermatology SC Dermatology GA YZ959 UT WOS:000072312400004 PM 9506438 ER PT J AU Haase, C Budinger, L Borradori, L Yee, C Merk, HF Yancey, K Hertl, M AF Haase, C Budinger, L Borradori, L Yee, C Merk, HF Yancey, K Hertl, M TI Detection of IgG autoantibodies in the sera of patients with bullous and gestational pemphigoid: ELISA studies utilizing a baculovirus-encoded form of bullous pemphigoid antigen 2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoimmunity; B lymphocytes; hemidesmosome ID BENIGN EPIDERMOLYSIS-BULLOSA; INDIRECT IMMUNOFLUORESCENCE; EXTRACELLULAR DOMAIN; STRUCTURAL-ANALYSIS; HERPES-GESTATIONIS; BASEMENT-MEMBRANE; BP180; HEMIDESMOSOMES; KERATINOCYTES; AUTOANTIGEN AB Autoantibodies against the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) are thought to play a key role in the pathogenesis of bullous pemphigoid and their detection may thus be of diagnostic and prognostic value. The aim of this study was to develop a standardized enzyme-linked immunosorbent assay utilizing the baculovirus-derived protein BV13 (extracellular domain of BPAG2 devoid of 68 amino acids at the C terminus linked to glutathione-S-transferase and 6x His tag) to detect BPAG2-specific autoantibodies. For the enzyme-linked immunosorbent assay, nickel agarose affinity-purified BV13 protein was incubated with sera from patients with bullous pemphigoid (n = 39), gestational pemphigoid (n = 10), and pemphigus vulgaris/pemphigus foliaceus (PV/PF; n = 15), or normal human sera (NHS; n = 18). Nickel affinity-purified proteins from wild-type baculovirus-infected insect cells served as a control. A positive enzyme-linked immunosorbent assay value was defined as reactivity (ODBV13-ODWT) > mean reactivity + 1 SD of the negative control sera (PV/PF; NHS). Thirty-five of 39 bullous pemphigoid sera and 10 of 10 gestational pemphigoid sera were reactive to BPAG2 compared with none of 15 PV/PF sera and one of 18 NHS (sensitivity, 91.8%; specificity, 97%). Of 16 BPAG2-reactive sera in the enzyme-linked immunosorbent assay, only six were BPAG2-reactive in the western blot, whereas 14 sera immunoprecipitated BPAG2 from extracts of epidermal keratinocytes. The enzyme-linked immunosorbent assay utilizing an eukaryotic BPAG2 protein thus seems to be highly sensitive and specific in the detection of BPAG2-specific antibodies and, hence, may be useful in the diagnosis of bullous autoimmune diseases, such as bullous pemphigoid and gestational pemphigoid. C1 Rhein Westfal TH Aachen, Hautklin, D-52074 Aachen, Germany. NCI, Dermatol Branch, Bethesda, MD 20892 USA. Hop Cantonal Univ Geneva, Dermatol Clin, Geneva, Switzerland. RP Hertl, M (reprint author), Rhein Westfal TH Aachen, Hautklin, Pauwelsstr 30, D-52074 Aachen, Germany. NR 36 TC 83 Z9 83 U1 0 U2 5 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 MAR PY 1998 VL 110 IS 3 BP 282 EP 286 DI 10.1046/j.1523-1747.1998.00126.x PG 5 WC Dermatology SC Dermatology GA YZ959 UT WOS:000072312400016 PM 9506450 ER PT J AU Yancey, KB Yee, C AF Yancey, KB Yee, C TI Localization of the extracellular domain of BPAG2 in human epidermal basement membrane SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Yancey, KB (reprint author), NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 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 MAR PY 1998 VL 110 IS 3 BP 302 EP 302 DI 10.1046/j.1523-1747.1998.00117.x PG 1 WC Dermatology SC Dermatology GA YZ959 UT WOS:000072312400021 PM 9506455 ER PT J AU DebBurman, SK Caughey, B Lindquist, SL AF DebBurman, SK Caughey, B Lindquist, SL TI Molecular chaperones and prion formation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. NIH, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 191A EP 191A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300008 ER PT J AU Amano, N Yamada, Y Levine, M AF Amano, N Yamada, Y Levine, M TI Concurrent ultrasensitive HPLC measurement of hydroxyproline and proline. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 209A EP 209A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300113 ER PT J AU Rumsey, SC Zarnowski, M Simpson, IA Levine, M AF Rumsey, SC Zarnowski, M Simpson, IA Levine, M TI DHA transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 209A EP 209A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300114 ER PT J AU Lu-Yao, GL AF Lu-Yao, GL TI Short-term outcomes following radical prostatectomy. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Connecticut, Farmington, CT USA. NCI, Bethesda, MD 20892 USA. Merck & Co Inc, Rahway, NJ 07065 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 211A EP 211A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300130 ER PT J AU Baumert, TF Vergalla, J Thomson, M Ito, S Wong, DT Greenberg, HB Liang, TJ AF Baumert, TF Vergalla, J Thomson, M Ito, S Wong, DT Greenberg, HB Liang, TJ TI Hepatitis C virus-like particles synthesized in insect cells as a potential candidate for HCV vaccine development SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH, Liver Dis Sect, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Electron Microscopy Facil, Boston, MA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 215A EP 215A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300154 ER PT J AU Belyakov, IM Kelsall, B Strober, W Berzofsky, JA AF Belyakov, IM Kelsall, B Strober, W Berzofsky, JA TI Use of rIL-12 for enhancing the mucosal cytotoxic T lymphocyte response to a peptide HIV vaccine. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 216A EP 216A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300157 ER PT J AU Kenney, RT Sacks, DL Sypek, JP Gam, AA Evans-Davis, K AF Kenney, RT Sacks, DL Sypek, JP Gam, AA Evans-Davis, K TI Solid immunity in a primate model of cutaneous leishmaniasis. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 216A EP 216A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300156 ER PT J AU Park, JB Levine, M AF Park, JB Levine, M TI Identification and characterization of a novel glutaredoxin transcript in human neutrophils. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH, Mol & Clin Nutr Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 217A EP 217A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300166 ER PT J AU Holland, SM Dorman, SE AF Holland, SM Dorman, SE TI Interleukin-12 (IL-12) treatment in interferon gamma refractory pulmonary M-abscessus infection: Clinical response and immunologic reconstitution. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 218A EP 218A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300169 ER PT J AU Segal, BH Wynn, TA Doherty, TM Sher, A Cheever, AW Holland, SM AF Segal, BH Wynn, TA Doherty, TM Sher, A Cheever, AW Holland, SM TI Th-1 and Th-2 responses to Mycobacterium avium (MA) and Schistosoma mansoni eggs (SME) are normal in the p47(phox-/-) knockout (KO) mouse model of chronic granulomatous disease (CGD). SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 218A EP 218A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300170 ER PT J AU Levy, LM Henkin, RI AF Levy, LM Henkin, RI TI Human taste phantoms can be related to specific regional areas of decreased brain gamma aminobutyric acid (GABA) by magnetic resonance spectroscopy (MRS). SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NINDS, NB, NIH, Bethesda, MD 20892 USA. Taste & Smell Clin, Washington, DC USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 219A EP 219A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300174 ER PT J AU Costa, PT Herbst, JH Zonderman, AB AF Costa, PT Herbst, JH Zonderman, AB TI Personality models for molecular psychiatry research: II. Cloniger's biosocial model. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIA, Lab Personal & Cognit, GRC, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 220A EP 220A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300183 ER PT J AU Herbst, JH Zonderman, AB Costa, PT AF Herbst, JH Zonderman, AB Costa, PT TI Personality models for molecular psychiatry research: I. The five-factor model. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIA, Lab Personal & Cognit, GRC, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 220A EP 220A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300184 ER PT J AU Licinio, J Negrao, AB Mantzoros, C Kaklamani, V Wong, ML Bongiorno, PB Mulla, A Cearnal, L Veldhuis, JD Flier, JS McCann, SM Gold, PW AF Licinio, J Negrao, AB Mantzoros, C Kaklamani, V Wong, ML Bongiorno, PB Mulla, A Cearnal, L Veldhuis, JD Flier, JS McCann, SM Gold, PW TI Synchronicity of frequently-sampled 24-hour concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 220A EP 220A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300182 ER PT J AU Yao, XL Gladwin, MT Cowan, MJ Shelhamer, JH AF Yao, XL Gladwin, MT Cowan, MJ Shelhamer, JH TI Dexamethasone induces P11 production in human epithelial cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 224A EP 224A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300206 ER PT J AU Kelly, JA Chu, SC Chen, CC Moss, J AF Kelly, JA Chu, SC Chen, CC Moss, J TI Osteoporosis in patients with lymphangioleiomyomatosis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 225A EP 225A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300214 ER PT J AU Dorman, SE Holland, SM AF Dorman, SE Holland, SM TI Interferon-gamma receptor 2 (IFN gamma R2) deficiency: novel gene defect confers susceptibility to mycobacterial infection. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 234A EP 234A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300265 ER PT J AU Segal, BH Kuhns, DB Gallin, JI Holland, SM AF Segal, BH Kuhns, DB Gallin, JI Holland, SM TI Abnormal degradation of leukotriene B-4 (LTB4) in chronic granulomatous disease (CGD) mice SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 234A EP 234A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300266 ER PT J AU Wang, W Wang, S Madara, P Yan, L Danner, RL AF Wang, W Wang, S Madara, P Yan, L Danner, RL TI Human endothelial nitric oxide synthase (ENOS) regulates TNF production in transfected U937 cells via a reactive oxygen species (ROS) signaling pathway. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 234A EP 234A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300264 ER PT J AU Miller, JL Giattina, M Mackie, EJB Dwyer, NK AF Miller, JL Giattina, M Mackie, EJB Dwyer, NK TI Variegated transfer of recombinant glycosylphosphatidylinositol-anchored CD4 among cultured cells: Correlation of flow cytometric and microscopic observations SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID DETERGENT-RESISTANT COMPLEXES; PHOSPHOLIPASE-D; INTERCELLULAR-ADHESION; SIGNAL-TRANSDUCTION; PROTECTIN CD59; HUMAN-PLASMA; PROTEINS; SURFACE; GLYCOPROTEIN; PURIFICATION AB Glycosylphosphatidylinositol-anchored proteins (GPI-proteins) expressed on the outer leaflet of cell membranes are involved in diverse physiologic as well as pathologic processes in humans. Previously, we demonstrated the intercellular transfer of overexpressed CD4-GPI in vitro from transduced HeLa cells to their parental cell line. In this report we present further information on the transfer process and the nature of the transferred GPI-proteins. In mixed-cell populations, the transfer of CD4-GPI was detectable within minutes at levels proportional to the ratio of donor and recipient cells. The amount of CD4-GPI detected with flow cytometry on the surface of the recipient cells varied according to cell type. Microscopy of mixed cell populations revealed discrete CD4-GPI containing aggregates on the target cells, whereas colocalized transfer of cytoplasm was not detected. Separation of cocultivated cells by semipermeable membranes largely prevented CD4-GPI transfer, but aggregates containing CD4-GPI were demonstrated by electron microscopy in supernatants passed through filters of 0.4-mm pore size. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Room 9N308, Bethesda, MD 20892 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAR PY 1998 VL 131 IS 3 BP 215 EP 221 DI 10.1016/S0022-2143(98)90092-0 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA ZD088 UT WOS:000072650200006 PM 9523844 ER PT J AU White, GB McClure, ME AF White, GB McClure, ME TI Introduction: Introducing innovation into practice: Technical and ethical analyses of PGD and ICSI technologies SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Editorial Material C1 Natl Advisory Board Eth Reprod, Washington, DC USA. NICHHD, Reprod Sci Branch, NIH, Bethesda, MD 20892 USA. RP White, GB (reprint author), Natl Advisory Board Eth Reprod, Washington, DC USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 USA SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 1998 VL 26 IS 1 BP 5 EP 6 DI 10.1111/j.1748-720X.1998.tb01900.x PG 2 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 114EK UT WOS:000075596000001 PM 11645357 ER PT J AU Tasca, RJ McClure, ME AF Tasca, RJ McClure, ME TI The emerging technology and application of preimplantation genetic diagnosis SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID IN-SITU HYBRIDIZATION; FIRST POLAR BODIES; COMPLEX DISEASES; LINKAGE DISEQUILIBRIUM; TRANSMISSION TEST; EMBRYOS; FISH; AMPLIFICATION; ANEUPLOIDY; MOSAICISM C1 NICHHD, Preimplantat Biol Program, Reprod Sci Program, NIH, Bethesda, MD 20892 USA. RP Tasca, RJ (reprint author), NICHHD, Preimplantat Biol Program, Reprod Sci Program, NIH, Bethesda, MD 20892 USA. NR 63 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 USA SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 1998 VL 26 IS 1 BP 7 EP 16 DI 10.1111/j.1748-720X.1998.tb01901.x PG 10 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 114EK UT WOS:000075596000002 PM 11067588 ER PT J AU Bhattacharyya, SP Drucker, I Reshef, T Kirshenbaum, AS Metcalfe, DD Mekori, YA AF Bhattacharyya, SP Drucker, I Reshef, T Kirshenbaum, AS Metcalfe, DD Mekori, YA TI Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE heterotypic adhesion; tumor necrosis factor alpha; histamine ID ADHESION; RECEPTORS; PROLIFERATION; BASOPHILS; GROWTH; LFA-1; LINE AB Activated mast cells reside in close apposition to T cells in some inflammatory processes, In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release, Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells, Mast cells cocultured with activated T cells released histamine and beta-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h, Kinetics of histamine release paralleled the formation of heterotypic aggregates, Separation of the two cell populations with a porous membrane prevented mediator release and TNF-alpha production, Addition of the PI3-kinase inhibitor, wortmannin, inhibited the heterotypic adhesion-associated degranulation but not TNF-alpha production. These data thus indicate a novel pathway through which human mast cells are activated to both release granule-associated mediators and to produce cytokines in association with heterotypic adhesion to activated human T cells. C1 NIAID, NIH, LAD, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Med, Meir Gen Hosp,Allergy Clin Immunol Unit, IL-69978 Tel Aviv, Israel. RP Metcalfe, DD (reprint author), NIAID, NIH, LAD, Bldg 10,Room 11C205,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 25 TC 74 Z9 76 U1 0 U2 3 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 MAR PY 1998 VL 63 IS 3 BP 337 EP 341 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA ZA563 UT WOS:000072377100009 PM 9500521 ER PT J AU Clore, GM Gronenborn, AM Tjandra, N AF Clore, GM Gronenborn, AM Tjandra, N TI Direct structure refinement against residual dipolar couplings in the presence of rhombicity of unknown magnitude SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE residual dipolar couplings; rhombicity; solution NMR structure determination; long-range restraints; simulated annealing ID NMR-SPECTRA; PROTEINS; LIQUIDS AB Residual dipolar couplings arising from small degrees of alignment of molecules in a magnetic field provide unique long-range structural information, The potential of this approach for structure refinement has recently been demonstrated for a protein-DNA complex in which the magnetic susceptibility tensor was axially symmetric, For most macromolecules and macromolecular complexes, however, axial symmetry cannot be assumed. Moreover, the presence of significant rhombicity will clearly affect the accuracy of the resulting coordinates. In this Communication we present a simple calculational strategy that makes use of simulated annealing refinement against the residual dipolar couplings in combination with a grid search, to simultaneously refine the structures and ascertain the magnitude of the axial and rhombic components of the tensor. C1 NIDDKD, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. NHLBI, NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, NIH, Chem Phys Lab, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 22 TC 259 Z9 262 U1 1 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 1998 VL 131 IS 1 BP 159 EP 162 DI 10.1006/jmre.1997.1345 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA ZH656 UT WOS:000073133900022 PM 9533920 ER PT J AU Westergaard, GC AF Westergaard, GC TI What capuchin monkeys can tell us about the origins of hominid material culture SO JOURNAL OF MATERIAL CULTURE LA English DT Article DE capuchin; Cebus; evolution; hominid; material culture; tool-use ID CHIMPANZEES PAN-TROGLODYTES; PLIO-PLEISTOCENE HOMINIDS; STONE-TOOL TECHNOLOGY; CEBUS-APELLA; OLDUVAI-GORGE; ARCHAEOLOGICAL EVIDENCE; OBJECT MANIPULATION; WILD CHIMPANZEES; SELF-RECOGNITION; RIGHT-HANDEDNESS AB Capuchin monkeys are well-known for their extensive manipulative propensities which rival those of chimpanzees. This report examines the production and use of tools by capuchins with the aim of gaining insight into the origins of hominid material culture. It is proposed that research examining tool-making and tool-using in extant nonhuman primates can facilitate greater understanding of the mental life of Homo habilis and other early hominid species. C1 NICHHD, Bethesda, MD USA. RP Westergaard, GC (reprint author), NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. RI Davidson, Iain/A-9216-2011 NR 81 TC 8 Z9 8 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON, ENGLAND EC2A 4PU SN 1359-1835 J9 J MAT CULT JI J. Mat. Cult. PD MAR PY 1998 VL 3 IS 1 BP 5 EP 19 DI 10.1177/135918359800300101 PG 15 WC Anthropology; Archaeology; Cultural Studies SC Anthropology; Archaeology; Cultural Studies GA 105NW UT WOS:000075080800001 ER PT J AU Krasnegor, NA Fifer, W Maulik, D McNellis, D Romero, R Smotherman, W AF Krasnegor, NA Fifer, W Maulik, D McNellis, D Romero, R Smotherman, W TI Fetal behavioral development: Measurement of habituation, state transitions, and movement to assess fetal well being and to predict outcome SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Article DE fetus; behavior; habituation; state transition; chaos theory; fetal movements AB Objective: This paper describes the deliberations of an interdisciplinary group of clinical and basic scientists who met at the National Institute of Child Health and Human Development to discuss the potential role of fetal behavior in assessing fetal well being and predicting neonatal outcome. The conference focused on three aspects of fetal behavior: 1) habituation; 2) state transitions; and 3) movement. Methods: The participants consisted of 25 leaders in the fields of obstetrics, perinatal medicine, neonatology, developmental psychobiology, developmental neuroscience, developmental psychology, ethology, and mathematics, The meeting was divided into three parts. In each of these a plenary speaker (a recognized export in his field) began the session with an overview of the scientific theme. Two respondents, with research expertise in fetal research (animal models or human fetuses) followed with remarks on the plenary talk and comments based on their own studies. At the conclusion of these comments, the participants met in small groups to discuss the plenary proceedings and their implications for assessing human fetal well being and predicting outcome. At the conclusion of the small group deliberations all of the participants reconvened in a plenary session, During this part of the meeting a rapporteur from each small group summarized their discussions. Results and Conclusions: 1)Fetal habituation: there was a general consensus that research on this aspect of fetal behavior may have a high payoff for assessing human fetal well being and predicting neonatal outcome. 2) Behavioral state transitions: participants agreed that transitions afford investigators with an indication of when (timing) and how (models) behavior changes within and between developmental periods. Knowledge of transitions during development allows for tracking of behaviors that may be necessary for the fetus to adapt to its in utero environment or prepare for its postnatal life. 3) Chaos theory and fetal movement: participants concluded that non-linear dynamics systems analysis models could be useful to analyze "noise" within a measurement system; better define time scales; and increase resolution and thereby better identify "signals." C1 NICHHD, NIH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY 10027 USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. SUNY Binghamton, Dept Psychiat, Binghamton, NY 13901 USA. RP Krasnegor, NA (reprint author), 2013 Lakewinds Dr, Reston, VA 20191 USA. NR 16 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD SPR PY 1998 VL 8 IS 2 BP 51 EP 57 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZW485 UT WOS:000074415700001 ER PT J AU Risco, C Da Silva, PP AF Risco, C Da Silva, PP TI The fracture-flip technique reveals new structural features of the Escherichia coli cell wall SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE bacterial wall ultrastructure; Escherichia coli; fracture-dip; Gram-negative bacteria; peptidoglycan layer ID BACTERIAL-ENDOTOXINS; OUTER-MEMBRANE; SURFACE; ULTRASTRUCTURE; PEPTIDOGLYCAN; CHEMISTRY; ENVELOPE; BINDING AB With few exceptions, all bacteria possess a wall which protects them and controls their communication with the environment. In Gram-negative bacteria the cell wall exhibits a complex and unique multilayered organization. We hare applied a modification of the freeze-fracture technique known as 'fracture-flip' to visualize the real surfaces of the different wall layers in a Gram-negative bacterium, Escherichia coli, In combination with treatments to weaken the interlayer connections. this technique has provided new insights into the structure of the bacterial wall. Large areas of an intermediate layer (most probably the peptidoglycan-containing matrix) have been visualized for the first time between the plasma membrane and the outer membrane of the wall, Extensive regions corresponding to the cytoplasmic face of the plasma membrane have also been obtained. These images provide new three-dimensional views of the bacterial cell wall and provide the structural framework for the analysis of the molecular relationships between the different cell wall components. C1 NCI, Frederick Canc Res & Dev Ctr, Dyncorp,Program Resources Inc, Biol Carcinogenesis & Dev Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, Membrane Biol Sect, Frederick, MD 21702 USA. RP Risco, C (reprint author), CSIC, Ctr Nacl Biotecnol, Electron Microscopy Unit, Campus Univ Autonoma, E-28049 Madrid, Spain. NR 20 TC 7 Z9 7 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD MAR PY 1998 VL 189 BP 213 EP 218 PN 3 PG 6 WC Microscopy SC Microscopy GA ZH639 UT WOS:000073131900005 PM 9588020 ER PT J AU Dai, JR Hallock, YF Cardellina, JH Boyd, MR AF Dai, JR Hallock, YF Cardellina, JH Boyd, MR TI HIV-inhibitory and cytotoxic oligostilbenes from the leaves of Hopea malibato SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB Three new oligostilbenes, malibatols A (1) and B (2) and dibalanocarpol (3), together with one known oligostilbene balanocarpol (4), were isolated from the organic extract of the leaves of Hopea malibato. The structure elucidation of these compounds was based on the interpretation of their chemical and spectral data. Compounds 3 and 4 exhibited very modest HIV-inhibitory activity, while compounds 1 and 2 were cytotoxic to the host cells (CEM SS) in the antiviral assay. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 9 TC 111 Z9 116 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 1998 VL 61 IS 3 BP 351 EP 353 DI 10.1021/np970519h PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA ZE993 UT WOS:000072852100009 PM 9544565 ER PT J AU Heils, A Wichems, C Mossner, R Petri, S Glatz, K Bengel, D Murphy, DL Lesch, KP AF Heils, A Wichems, C Mossner, R Petri, S Glatz, K Bengel, D Murphy, DL Lesch, KP TI Functional characterization of the murine serotonin transporter gene promoter in serotonergic raphe neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE murine serotonin transporter gene; serotonergic raphe neurons; basal promoter; cis-acting elements; TATA-like motif; cell-selective expression ID CHORIOCARCINOMA CELLS; REGULATORY ELEMENTS; EXPRESSION; MECHANISMS; UPSTREAM AB We have isolated and characterized the 5'-flanking regulatory region of the murine serotonin 5-HT transporter (5-HTT) gene. A TATA-like motif and several potential binding sites for transcription factors, including two AP1, several AP2 and AP4 binding sites, CCAAT and GC boxes (SP1 binding sites), a nuclear factor-kappa B, and a cyclic AMP response element-like motif, are present in the 5'-flanking region. A similar to 2.2-kb fragment (-2,143 to +51 with respect to the transcription start site), which had been fused to the luciferase reporter gene and transiently expressed in a 5-HTT-expressing cell line and in serotonergic raphe neurons derived from embryonic rat brainstem, displayed both constitutive and inducible promoter activity. Functional promoter mapping revealed two clusters of activating elements from bp -82 to -527 and bp -1,001 to -1,937. A cell/neuron-selective silencer element(s) is contained between bp -294 and -527. Our findings suggest that (1) the murine 5-HTT gene promoter is active in serotonergic raphe neurons but significantly repressed in neuronal cells from frontal cortex that do not express 5-HTT, (2) the information contained within similar to 0.5 kb of the 5'-flanking sequence is sufficient to confer its cell-selective expression, (3) the promoter responds to cyclic AMP-and protein kinase C-dependent induction, and (4) the expression of the 5-HTT is regulated by a combination of positive and negative cis-acting elements operating through a basal promoter unit defined by a TATA-like motif. Fusion of the 5-HTT gene promoter unit to a gene of choice may aid its cell-selective expression in transgenic strategies. C1 Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIMH, Clin Sci Lab, NIH, Bethesda, MD USA. RP Lesch, KP (reprint author), Univ Wurzburg, Dept Psychiat, Fuchsleinstr 15, D-97080 Wurzburg, Germany. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 30 TC 33 Z9 33 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1998 VL 70 IS 3 BP 932 EP 939 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YY294 UT WOS:000072132700006 PM 9489712 ER PT J AU Brecher, K Stopa, EG Kenney, K AF Brecher, K Stopa, EG Kenney, K TI Concurrent herpes simplex virus encephalitis and Creutzfeldt-Jakob disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Letter ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; CEREBROSPINAL-FLUID C1 Brown Univ, Sch Med, Providence, RI 02903 USA. NINDS, LCNSS, NIH, Bethesda, MD 20892 USA. RP Stopa, EG (reprint author), Rhode Isl Hosp, Dept Pathol, 593 Eddy St, Providence, RI 02903 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAR PY 1998 VL 64 IS 3 BP 418 EP 419 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZD117 UT WOS:000072653100043 PM 9527177 ER PT J AU Gershon, ED Wiener, MC Latham, PE Richmond, BJ AF Gershon, ED Wiener, MC Latham, PE Richmond, BJ TI Coding strategies in monkey V1 and inferior temporal cortices SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VISUAL-CORTEX; STRIATE CORTEX; NEURONS; CAT; VARIABILITY; INFORMATION; CELLS; FACES AB We would like to know whether the statistics of neuronal responses vary across cortical areas. We examined stimulus-elicited spike count response distributions in V1 and inferior temporal (IT) cortices of awake monkeys. In both areas, the distribution of spike counts for each stimulus was well described by a Gaussian distribution, with the log of the variance in the spike count linearly related to the log of the mean spike count. Two significant differences in response characteristics were found: both the range of spike counts and the slope of the log(variance) versus log(mean) regression were larger in V1 than in IT. However, neurons in the two areas transmitted approximately the same amount of information about the stimuli and had about the same channel capacity (the maximum possible transmitted information given noise in the responses). These results suggest that neurons in V1 use more variable signals over a larger dynamic range than IT neurons, which use less variable signals over a smaller dynamic range. The two coding strategies are approximately as effective in transmitting information. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP NIMH, Neuropsychol Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. NR 26 TC 87 Z9 87 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1998 VL 79 IS 3 BP 1135 EP 1144 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZB955 UT WOS:000072525100003 PM 9497396 ER PT J AU Classen, J Gerloff, C Honda, M Hallett, M AF Classen, J Gerloff, C Honda, M Hallett, M TI Integrative visuomotor behavior is associated with interregionally coherent oscillations in the human brain SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EVENT-RELATED DESYNCHRONIZATION; VOLUNTARY MOVEMENT; VISUAL-CORTEX; SYNCHRONIZATION; MECHANISMS; NETWORKS; SYSTEM; EEG; ERD AB Coherent electrical brain activity has been demonstrated to be associated with perceptual events in mammals. It is unclear whether or not it is also a mechanism instrumental in the performance of sensorimotor tasks requiring the continuous processing of information between primarily executive and receptive brain areas. In particular it is unknown whether or not interregional coherent activity detectable in electroencephalographic (EEG) recordings on the scalp reflects interareal functional cooperativity in humans. We studied patterns of changes in EEG-coherence associated with a visuomotor force-tracking task in seven subjects. Interregional coherence of EEG signals recorded from scalp regions overlying the visual and the motor cortex increased in comparison to a resting condition when subjects tracked a visual target by producing an isometric force with their right index finger. Coherence between visual and motor cortex decreased when the subjects produced a similar motor output in the presence of a visual distracter and was unchanged in a purely visual and purely motor task. Increases and decreases of coherence were best differentiated in the low beta frequency range (13-21 Hz). This observation suggests a special functional significance of low frequency oscillations in information processing in large-scale networks. These findings substantiate the view that coherent brain activity underlies integrative sensorimotor behavior. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 40 TC 144 Z9 144 U1 1 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 MAR PY 1998 VL 79 IS 3 BP 1567 EP 1573 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZB955 UT WOS:000072525100039 PM 9497432 ER PT J AU Ernst, M Zametkin, AJ Phillips, RL Cohen, RM AF Ernst, M Zametkin, AJ Phillips, RL Cohen, RM TI Age-related changes in brain glucose metabolism ia adults with attention-deficit/hyperactivity disorder and control subjects SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT Society-of-Nuclear-Medicine 43rd Annual Meeting CY JUN 03-05, 1996 CL DENVER, COLORADO SP Soc Nucl Med ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION TOMOGRAPHY; DEFICIT DISORDER; PSYCHIATRIC STATUS; OXYGEN-METABOLISM; CHILD PSYCHOPATHOLOGY; COMPUTED-TOMOGRAPHY; GENDER DIFFERENCES; HYPERACTIVE GIRLS; NORMAL VOLUNTEERS AB Using positron emission tomography and [F-18]-2-fluoro-2-deoxy-D-glucose, the authors determined cerebral metabolic rates for glucose (CMRglc) in. 39 adults (18-51 years old) with attention-deficit/hyperactivity disorder (ADHD) and 56 healthy control adults (19-56 years old) during the performance of a continuous attention task. Increased age was associated With reduced global CMRglc in ADHD women, but not in ADHD men, control men, or control women. Better performance on the attention task was significantly associated with increased age only in the ADHD female group. Determining the role of behavioural hormonal, and genetic factors is a challenge for future research. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIMH, Off Clin Director, Bethesda, MD 20892 USA. NIDA, Brain Imaging Ctr, Baltimore, MD USA. RP Ernst, M (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Convent Dr,MSC 4030, Bethesda, MD 20892 USA. NR 70 TC 35 Z9 35 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1998 VL 10 IS 2 BP 168 EP 177 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZN416 UT WOS:000073643700005 PM 9608405 ER PT J AU Li, H Weiss, SRB Chuang, DM Post, RM Rogawski, MA AF Li, H Weiss, SRB Chuang, DM Post, RM Rogawski, MA TI Bidirectional synaptic plasticity in the rat basolateral amygdala: Characterization of an activity-dependent switch sensitive to the presynaptic metabotropic glutamate receptor antagonist 2S-alpha-ethylglutamic acid SO JOURNAL OF NEUROSCIENCE LA English DT Article DE basolateral amygdala; synaptic plasticity; longterm potentiation; long-term depression; NMDA receptor; metabotropic glutamate receptor; 2S-alpha-ethylglutamic acid ID LONG-TERM POTENTIATION; HIPPOCAMPAL CA1 REGION; IN-VIVO; LTD; DEPRESSION; INDUCTION; NMDA; FEAR; TRANSMISSION; ACTIVATION AB This study examines forms of activity-dependent synaptic plasticity in the basolateral amygdala in vitro and demonstrates that a brief high frequency stimulus (HFS) train can induce a switch in the direction of the enduring change in synaptic strength induced by subsequent low-frequency stimulation (LFS). LFS (1 Hz, 15 min) of the external capsule (EC) induced a persistent 1.7-fold enhancement in the amplitude of synaptic potentials recorded intracellularly in basolateral amygdala neurons. The enhancement occurred gradually during the stimulation and was maintained for >30 min after termination of the stimulus train, LFS-induced enduring synaptic facilitation was not affected by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoate (APV; 100 mu M). Brief high-frequency EC stimulation (HFS; 100 Hz, 1 sec) induced APV-sensitive shortterm potentiation (2.5-fold) that generally decayed within 10 min, When LFS was applied after recovery from the short-term potentiating effect of HFS (HFS/LFS), there was an initial transient (<10 min) enhancement of the synaptic response followed by persistent synaptic depression (synaptic potential amplitude reduced by 22% at 30 min). This represents the first demonstration of stimulus-dependent long-lasting synaptic depression in the amygdala. Application of the presynaptic (group II) metabotropic glutamate receptor antagonist 2S-alpha-ethylglutamic acid (EGLU; 50 mu M) prevented the HFS-dependent switch from synaptic facilitation to depression, Thus, LFS in the in vitro amygdala slice can induce either enduring synaptic potentiation or depression, depending on whether a priming HFS train has been applied, This experience-dependent switch, a novel form of metaplasticity, is not dependent on NMDA receptors but may require group II metabotropic glutamate receptors, In the amygdala, experiential modification of activity-dependent long-term synaptic plasticity adds flexibility to the ways in which synaptic strength can be modified and could play a role in diverse amygdala-dependent processes, including the formation, storage, and extinction of emotional memory and the regulation of epileptogenesis. C1 NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP NINDS, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 41 TC 93 Z9 94 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 1 PY 1998 VL 18 IS 5 BP 1662 EP 1670 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YX906 UT WOS:000072092600005 PM 9464991 ER PT J AU Weiss, SW Albers, DS Iadarola, MJ Dawson, TM Dawson, VL Standaert, DG AF Weiss, SW Albers, DS Iadarola, MJ Dawson, TM Dawson, VL Standaert, DG TI NMDAR1 glutamate receptor subunit isoforms in neostriatal, neocortical, and hippocampal nitric oxide synthase neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NMDAR1; alternative splicing; nitric oxide synthase; striatum; hippocampus; cerebral cortex ID STRIATAL MALONATE LESIONS; DENSITY PROTEIN PSD-95; RAT CEREBRAL-CORTEX; MESSENGER-RNA; NADPH-DIAPHORASE; HUNTINGTONS-DISEASE; SYNAPTIC LOCALIZATION; PYRAMIDAL CELLS; SPLICE VARIANTS; NERVOUS-SYSTEM AB Nitric oxide (NO), an unconventional and diffusible neurotransmitter, is synthesized by nitric oxide synthase (NOS). NMDA glutamate receptors are potent regulators of NO synthesis. We have used dual-label immunofluorescence and confocal microscopy to examine forebrain neurons in the rat that contain high levels of neuronal NOS (nNOS) for the presence of the NMDAR1 receptor subunit protein and regions of this protein encoded by three alternative spliced segments of the NMDAR1 mRNA: N1, C1, and C2. In the neostriatum, neocortex, and hippocampus, nNOS-labeled neurons exhibit strong NMDAR1 immunoreactivity (-ir). In all three of these regions, nNOS-positive neurons are characterized by the absence of immunoreactivity for the C1 segment of NMDAR1, whereas C1-ir is abundant in most nNOS-negative neurons, In addition, nNOS-ir neurons exhibit selective staining for the alternative C2' terminus of NMDAR1 that is produced when the C2 segment is absent. These results demonstrate directly that neurons with abundant nNOS-ir contain NMDAR1 receptor subunit proteins and that the NMDAR1 isoforms present in these cells differ from those of most other neurons in these regions. The distinct NMDA receptor phenotype of these nNOS-positive neurons is likely to contribute to both the physiological regulation of NO release by glutamate as well as to NO-mediated excitotoxic injury. C1 Massachusetts Gen Hosp, Dept Neurol, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIDR, Pain & Neurosensory Mech Branch, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. Johns Hopkins Hosp, Sch Med, Dept Physiol, Baltimore, MD 21287 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. OI Dawson, Valina/0000-0002-2915-3970; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS31579, NS33142, NS34361] NR 70 TC 59 Z9 60 U1 0 U2 0 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 MAR 1 PY 1998 VL 18 IS 5 BP 1725 EP 1734 PG 10 WC Neurosciences SC Neurosciences & Neurology GA YX906 UT WOS:000072092600011 PM 9464997 ER PT J AU Self, DW Genova, LM Hope, BT Barnhart, WJ Spencer, JJ Nestler, EJ AF Self, DW Genova, LM Hope, BT Barnhart, WJ Spencer, JJ Nestler, EJ TI Involvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior SO JOURNAL OF NEUROSCIENCE LA English DT Article DE protein kinase A; reward; reinforcement; drug addiction; dopamine; drug craving; reinstatement ID MESOLIMBIC DOPAMINE SYSTEM; RECEPTOR AGONISTS; RHESUS-MONKEYS; CYCLIC-NUCLEOTIDES; DRUG REINFORCEMENT; ADENYLATE-CYCLASE; GENE-EXPRESSION; RAT; D1; HEROIN AB cAMP-dependent protein kinase (PKA) in the nucleus accumbens (NAc) has been implicated in cocaine addiction because (1) cocaine reinforcement is mediated by dopamine receptors that modulate cAMP formation, and (2) repeated exposure to cocaine upregulates the cAMP system in NAc neurons. This study tested PKA involvement in cocaine self-administration and relapse of cocaine-seeking behavior by infusing cAMP analogs that activate or inhibit PKA into the NAc of rats. Bilateral intra-NAc infusions of the PKA inhibitor R-p-cAMPS reduced baseline cocaine self-administration, shifted the dose-response curve for cocaine self-administration to the left, and induced relapse of cocaine-seeking behavior after extinction from cocaine self-administration, consistent with an enhancement of cocaine effects in each paradigm. In contrast, pretreatment with intra-NAc infusions of a PKA activator, S-p-cAMPS or dibutyryl cAMP, increased baseline cocaine self-administration during the second hour of testing and shifted the dose-response curve to the right, consistent with an antagonist-like action. After extinction from cocaine self-administration, similar infusions of Sp-cAMPS induced generalized responding at both drug-paired and inactive levers. As an index of PKA activity in vivo, NAc infusions of Rp-cAMPS reduced basal levels of dopamine-regulated phosphoprotein-32 phosphorylation and blocked amphetamine-induced increases in cAMP response element-binding protein (CREB) phosphorylation. Conversely, NAc infusions of S-p-cAMPS increased phosphorylation of CREB. Together, these results suggest that sustained upregulation of the cAMP system in the NAc after repeated cocaine exposure could underlie tolerance to cocaine reinforcement, whereas acute inhibition of this system may contribute to drug craving and relapse in addicted subjects. C1 Yale Univ, Sch Med, Dept Psychiat, Lab Mol Psychiat,Connecticut Mental Hlth Ctr, New Haven, CT 06508 USA. Yale Univ, Sch Med, Dept Pharmacol, Connecticut Mental Hlth Ctr, New Haven, CT 06508 USA. NINDS, Mol Plast Sect, Bethesda, MD 20892 USA. Harvard Univ, Neurosci Program, Boston, MA 02115 USA. RP Self, DW (reprint author), Yale Univ, Sch Med, Dept Psychiat, Lab Mol Psychiat,Connecticut Mental Hlth Ctr, 34 Pk St, New Haven, CT 06508 USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 FU NIDA NIH HHS [DA 00223, DA 05603, DA 08227] NR 61 TC 234 Z9 243 U1 0 U2 8 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 MAR 1 PY 1998 VL 18 IS 5 BP 1848 EP 1859 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YX906 UT WOS:000072092600023 PM 9465009 ER PT J AU Pluta, RM Afshar, JKB Boock, RJ Oldfield, EH AF Pluta, RM Afshar, JKB Boock, RJ Oldfield, EH TI Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebral vasospasm; oxyhemoglobin; deoxyhemoglobin; methemoglobin; microdialysis; subarachnoid hemorrhage; Macaca cynomolgus ID SMOOTH-MUSCLE CELLS; CEREBRAL VASOSPASM; NITRIC-OXIDE; CEREBROSPINAL-FLUID; BASILAR ARTERIES; BLOOD-FLOW; HEMOGLOBIN; ENDOTHELIUM; RABBIT; CANINE AB Hemoglobin released from hemolysed erythrocytes has I,een postulated to be responsible for delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the evidence is indirect and the mechanisms of action are unclear. Cerebrovascular tone is regulated by a dynamic balance of relaxing and contracting factors. Loss of the endothelium-derived relaxing factor-nitric oxide in the presence of oxyhemoglobin and overproduction of endothelin-1 stimulated by oxyhemoglobin have been postulated as causes of delayed cerebral vasospasm after SAH. Object. The authors aimed to investigate this hypothesis using in vivo microdialysis to examine time-dependent changes in the perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin in a primate model of SAH. Methods. Nine cynomolgus monkeys underwent right-sided frontotemporal craniectomy and placement of a semipermeable microdialysis catheter adjacent to the right middle cerebral artery (MCA). Saline (control group, three animals) or an arterial blood clot (SAH group, six animals) was then placed around the MCA and the catheter. Arteriographically confirmed vasospasm had developed in all animals with SAH but in none of the control animals on Day 7. The dialysate was collected daily for 12 days. Levels of oxyhemoglobin, deoxyhemoglobin, and methemoglobin were measured by means of spectrophotometry. Perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin peaked on Day 2 in the control monkeys and could not be detected on Days 5 to 12. Perivascular concentrations of oxyhemoglobin and deoxyhemoglobin peaked on Day 7 in the SAH group, at which time the concentrations in the dialysate were 100-fold higher than in any sample obtained from the control animals. Methernoglobin levels increased only slightly, peaking between Days 7 and 12, at which time the concentration in the dialysate was 10-fold higher than in samples from the control animals. Conclusions. This study provides in vivo evidence that the concentrations of oxyhemoglobin and deoxyhemoglobin increase in the cerebral subarachnoid perivascular space during the development of delayed cerebral vasospasm. The results support the hypothesis that oxyhemoglobin is involved in the pathogenesis of delayed cerebral vasospasm after SAH and implicate deoxyhemoglobin as a possible vasospastic agent. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,SNB,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 86 Z9 90 U1 0 U2 5 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 1998 VL 88 IS 3 BP 557 EP 561 DI 10.3171/jns.1998.88.3.0557 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YY305 UT WOS:000072133800019 PM 9488312 ER PT J AU Cutrone, JA Yospur, LS Khalkhali, I Tolmos, J Devito, A Diggles, L Vargas, RP Shitabata, P French, S AF Cutrone, JA Yospur, LS Khalkhali, I Tolmos, J Devito, A Diggles, L Vargas, RP Shitabata, P French, S TI Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malignant breast lesions SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE technetium-99m-MIBI; scintimammography; angiogenesis; desmoplasia ID TUMOR ANGIOGENESIS; TC-99M SESTAMIBI; CARCINOMA; CANCER; SCINTIMAMMOGRAPHY; MITOCHONDRIAL; RETENTION; INDICATOR AB This study was undertaken to assess the relationship between the degree of Tc-99m-MIBI uptake in breast lesions and the following histologic factors: neovascularity, desmoplastic reaction, cellular proliferation and mitochondrial density. Methods: Forty-two patients who previously underwent MIBI breast imaging (4 false-negative, 12 false-positive, 15 true-negative, 11 true-positive) were studied. Immunohistochemical staining was performed for neovascularity (Factor VIII antigen), desmoplasia (alpha-actin antigen), mitochondrial density (mitochondrial antigen) and cellular proliferation (MIB-1 antigen). The degree of microscopic staining was correlated with region of interest measurements of MIBI uptake on scintigraphy. Results: There was a poor correlation between MIBI uptake and the degrees of neovascularity (r = 0.08, p > 0.05) and intracellular mitochondrial density (r = 0.04, p > 0.05) while there was a moderate correlation with cellular proliferation (r = 0.4, p < 0.05) and desmoplasia (r = 0.55, p < 0.001). Conclusion: The degree of MIBI uptake in breast lesions is multifactorial, but it appears to be related more to the degree of desmoplastic activity and cellular proliferation than neovascularity and mitochondrial density. C1 Univ Calif Los Angeles, Harbor Med Ctr, Dept Radiol, Torrance, CA 90502 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Pathol, Torrance, CA 90502 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Surg, Torrance, CA 90502 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. Pathol Consultants Med Grp, Torrance, CA USA. RP Khalkhali, I (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Dept Radiol, Profess Bldg,21840 S Normandie Ave,Suite 506, Torrance, CA 90502 USA. NR 16 TC 32 Z9 32 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 1998 VL 39 IS 3 BP 449 EP 453 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZA974 UT WOS:000072421600017 PM 9529290 ER PT J AU Borchardt, PE Quadri, SM Freedman, RS Vriesendorp, HM AF Borchardt, PE Quadri, SM Freedman, RS Vriesendorp, HM TI Indium-111- and Yttrium-90-labeled human monoclonal immunoglobulin M targeting of human ovarian cancer in mice SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE human IgM; intraperitoneal radioimmunotherapy; pharmacokinetics; ovarian carcinoma ID NUDE-MICE; RADIOLABELED HUMAN; INTRAPERITONEAL; ANTIBODY; CHEMOTHERAPY; CARCINOMA; THERAPY; MALIGNANCIES; DOSIMETRY; TUMORS AB Most patients with ovarian cancer have disease in the peritoneal cavity. Treatment of this region is inadequate because recurrences are frequent, Increased radiation doses to tumor and, hence, greater tumor control may be possible with intraperitoneal (i.p.) administration of radiolabeled human monoclonal immunoglobulin M (IgM), which is reactive with tumor-associated antigens. Methods: Biodistribution studies were performed in nude mice bearing i.p. nodules of human ovarian cancer after administration of human monoclonal IgM lambda (AC6C3-2B12), labeled with In-111 or Y-90. Irrelevant In-111-labeled human IgM lambda (CH-IBS) and Y-90-aggregate served as specificity controls, Results: intravenous administration of In-111-labeled AC6C3-2B12 produced low tumor and high liver and spleen uptake. Intraperitoneal administration of AC6C3-2B12 labeled with In-111 or Y-90 resulted in rapid, high tumor uptake (>45% of injected dose per gram of tumor at 3 hr) that was at least three-fold higher than any normal organ, Biodistribution results were similar for In-111- and Y-90-labeled IgM. Tumor uptake of In-111-labeled AC6C3-2B12 was two-fold greater than that of In-111-labeled CH-1B9. Normal organ uptakes were similar for tumor-reactive and irrelevant IgM, Radioimmunoconjugates were retained in the peritoneal cavity for a prolonged period of time. Yttrium-90 aggregate demonstrated high tumor and bone uptake. Conclusion: Higher tumor uptake was observed after i.p. administration of tumor-reactive IgM than after irrelevant IgM. The in vivo behavior of tumor-reactive IgM was similar when it was radiolabeled with either In-111 or Y-90. Therefore, In-111-based imaging studies can be used to predict the biodistribution of subsequently administered Y-90-labeled IgM. Further development of radiolabeled AC6C3-2B12 as a diagnostic and therapeutic agent for patients with advanced ovarian carcinoma is warranted. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. RP Quadri, SM (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 4144, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 16672, CA 51161] NR 34 TC 14 Z9 14 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 1998 VL 39 IS 3 BP 476 EP 484 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZA974 UT WOS:000072421600022 PM 9529295 ER PT J AU Rumsey, SC Levine, M AF Rumsey, SC Levine, M TI Absorption, transport, and disposition of ascorbic acid in humans SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE ascorbic acid; vitamin C; dehydroascorbic acid; transport; pharmacokinetics; ascorbate recycling ID BORDER MEMBRANE-VESICLES; DEPENDENT DEHYDROASCORBATE REDUCTASE; RECOMMENDED DIETARY ALLOWANCE; LOW-DENSITY-LIPOPROTEIN; CRITICALLY ILL PATIENTS; STEADY-STATE TURNOVER; VITAMIN-C; HUMAN-NEUTROPHILS; GUINEA-PIG; LIPID-PEROXIDATION AB L-ascorbic acid (ascorbate or vitamin C) is a required nutrient for humans. Absorption, transport, and disposition of ingested ascorbate involve the following: (1) bioavailability and absorption in the gastrointestinal tract; (2) presence in the circulation; (3) tissue distribution; (4) excretion; and, (5) metabolism. Fundamental to each of the above are ascorbate chemistry and mechanisms of transport of ascorbate across membranes. Ascorbate can be reversibly oxidized to dehydroascorbic acid, which can be irreversible degraded. Both reduced and oxidized forms cross cell membranes. Differences in transport kinetics, tissue specificity, and Na+ and energy dependence strongly support the existence of separate transport mechanisms. An important consideration in the analysis of ascorbate transport iss that of substrate availability. Reduced ascorbate is by far the most predominant form found in plasma and tissues. Dehydroascorbic acid is rapidly reduced intracellularly to ascorbate by both enzymatic and chemical mechanisms. Despite constitutively low levels of dehydroascorbic acid, conditions that promote oxidation of ascorbate can profound alter both the nature and availability of substrate. Elucidation of mechanisms that modulate the delivery of ascorbate to tissues and its utilization under different metabolic conditions will be invaluable for making recommendations for ascorbate ingestion. Published by Elsevier science Inc. 1998. C1 NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, NIH, Bldg 10,Room 4D52,MSC 1372, Bethesda, MD 20892 USA. NR 208 TC 88 Z9 90 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAR PY 1998 VL 9 IS 3 BP 116 EP 130 DI 10.1016/S0955-2863(98)00002-3 PG 15 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA ZD381 UT WOS:000072679500001 ER PT J AU DeNucci, DJ Sobiski, C Dionne, RA AF DeNucci, DJ Sobiski, C Dionne, RA TI Triazolam improves sleep but fails to alter pain in TMD patients SO JOURNAL OF OROFACIAL PAIN LA English DT Article DE chronic orofacial pain; temporomandibular disorders; clinical trial; sleep; triazolam ID DOUBLE-BLIND; DISORDERS; HYPNOTICS; FIBROMYALGIA; BRUXISM; TRIAL AB Patients with chronic ol orofacial pain often report disturbances in sleep, leading to the hypothesis that nocturnal motor hyperactivity of the muscles of mastication may contribute to the nociceptive process. This hypothesis was tested in a controlled study to evaluate the relationship between sleep stages, patient self-report of pain in the orofacial region, and nocturnal masticatory muscle activity. Twenty subjects participating In a two-period, within subject, crossover study received triazolam or placebo for 4 nights. Sleep, pain, and mandibular range of motion were assessed at baseline, following the first period, and again following the second period; a 3-day washout period separated the two treatments. Subjective report of sleep quality was significantly improved following triazolam in comparison to placebo as measured by category scales for sleep qualify, restfulness, and sleep compared to usual. The amount of time spent in stage-2 sleep was also significantly increased by triazolam. No improvement teas seen in pain as measured by palpation with an algometer, in scales for sensory intensity and the affective component of pain, or in daily pain diaries. Mean facial muscle electronmyographic activity for 30-second epochs averaged over the entire period of sleep did not reveal any differences in muscle activity across the three conditions. These data indicate that improvements in sleep quality and alterations in sleep architecture do not affect nocturnal facial muscle activity or subsequent pain report in temporomandibular patients, thereby failing to support the hypothesized relationship between sleep disturbances and chronic orofacial pain. C1 NIDR, Pain & Neurosensory Mech Branch, NIH, Clin Pharmacol Unit, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Orofacial Pain Serv, Washington, DC 20307 USA. RP Dionne, RA (reprint author), NIDR, Pain & Neurosensory Mech Branch, NIH, Clin Pharmacol Unit, 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. EM Dionne@yoda.nidr.nih.gov NR 30 TC 14 Z9 14 U1 1 U2 2 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 SPR PY 1998 VL 12 IS 2 BP 116 EP 123 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 103FR UT WOS:000075147700003 PM 9656889 ER PT J AU Brunelli, C Costantini, M Di Giulio, P Gallucci, M Fusco, F Miccinesi, G Paci, E Peruselli, C Morino, P Piazza , M Tamburini, M Toscani, F AF Brunelli, C Costantini, M Di Giulio, P Gallucci, M Fusco, F Miccinesi, G Paci, E Peruselli, C Morino, P Piazza , M Tamburini, M Toscani, F TI Quality-of-life evaluation: When do terminal cancer patients and health-care providers agree? SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE quality-of-life assessment; proxy; terminal patient AB A multicenter study involving six palliative care units in Italy was carried out on 159 terminal cancer patients seen at home or in hospital. The physician or the nu-se completed independently from the patient the Therapy Impact Questionnaire re (TIQ), a questionnaire devised for quality-of-life evaluation in terminal cancer patients. The patient's assessment was used as the valid reference measurement to compare with the health-care workers' evaluation to assess the validity of the latter. The results showed that percentages of agreement were higher for physical than for psychological and cognitive symptoms, and that there runs a greater agreement on the absence rather than on the presence of a problem. None of the characteristics of the patient nor of the proxy showed any statistically significant relationship with the two disagreement indexes. The results suggest that caution is needed in the use of health-care workers as alternative sources of information regarding patients quality of life. (C) U.S. Cancer Pain Relief Committee, 1998. C1 Natl Canc Inst, Div Psychol Res, I-20133 Milan, Italy. Natl Canc Inst, Unit Clin Epidemiol & Trials, Genoa, Italy. Mario Negri Inst, Milan, Italy. Gen Hosp, Palliat Care Unit, Desio, Italy. Assoc G Ghirotti, Genoa, Italy. Ctr Study & Prevent Canc, Florence, Italy. Gen Hosp, Pain Therapy & Palliat Care Div, Merate, Italy. Gen Hosp, Pain Therapy & Palliat Care Div, Cremona, Italy. Santa Maria Annunziata Hosp, Dept Anesthesia & Reanimat, Florence, Italy. RP Brunelli, C (reprint author), Natl Canc Inst, Div Psychol Res, Via Venezian 1, I-20133 Milan, Italy. RI costantini, massimo/G-1443-2012; Brunelli , Cinzia/B-9361-2017; OI Brunelli , Cinzia/0000-0003-3905-1289; costantini, massimo/0000-0002-5293-7079 NR 16 TC 85 Z9 85 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 1998 VL 15 IS 3 BP 151 EP 158 DI 10.1016/S0885-3924(97)00351-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA ZF229 UT WOS:000072876600008 PM 9564116 ER PT J AU DeBaun, MR Tucker, MA AF DeBaun, MR Tucker, MA TI Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry SO JOURNAL OF PEDIATRICS LA English DT Article ID WILMS-TUMOR; OVERGROWTH AB To determine the incidence and relative risk (RR) of cancer in children with Beck-with-Wiedemann syndrome (BWS), children with BWS were followed up from birth until death, diagnosis of cancer, fourth birthday, or last day of follow-up. A total of 183 children with BWS were followed up for 482 person-years. The end points were incidence of cancer, RR of cancer, and RR associated with specific BWS phenotypic features. Thirteen children were identified with cancers before the fourth year of life in comparison with fewer than one cancer expected in this group on the basis of general population rates over the same period. The average annual incidence of cancer in the first 4 years of life was 0.027 cancer per person-year. The RR of Wilms tumor (RR = 816; 95% confidence interval [CI], 359-1156), neuroblastoma (RR = 197; 95% CI, 22-711), and hepatoblastoma (RR = 2280; 95% CI, 928-11,656) were statistically significant. Asymmetry of the limbs (hemihypertrophy) was the only clinical feature associated with an increased RR of cancer (RR = 4.6; 95% CI, 1.5-14.2). Given the high incidence of cancer in infancy and early childhood of patients with BWS, a prospective study is warranted to address the utility of screening for cancer. C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA. RP DeBaun, MR (reprint author), NCI, Genet Epidemiol Branch, NIH, EPN 400, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 15 TC 223 Z9 228 U1 0 U2 3 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 MAR PY 1998 VL 132 IS 3 BP 398 EP 400 DI 10.1016/S0022-3476(98)70008-3 PN 1 PG 3 WC Pediatrics SC Pediatrics GA ZF241 UT WOS:000072877800008 PM 9544889 ER PT J AU DeBaun, MR Siegel, MJ Choyke, PL AF DeBaun, MR Siegel, MJ Choyke, PL TI Nephromegaly in infancy and early childhood: A risk factor for Wilms tumor in Beckwith-Wiedemann syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID CHILDREN; NEPHROBLASTOMATOSIS; HEMIHYPERTROPHY AB Objective: Beckwith-Wiedemann Syndrome (BWS) is an overgrowth syndrome associated with macrosomia, omphalocele, macroglossia, visceromegaly and Wilms tumor (WT). We conducted a case-control study in children with BWS to examine whether nephromegaly increases the risk of WT. Methods: The BWS Registry was used to identify control and case patients. Control patients were defined as children with BWS who were older than 6 years and had no imaging evidence of renal disease or previous WT and for whom complete records were available; 31 patients met these criteria. Case patients were defined as children with BWS who had WT and screening renal imaging before the diagnosis of WT; 12 of these patients had serial screening images before diagnosis of WT and comprised the study population. Only renal images obtained before the diagnosis of WT was made were used to assess renal length. Results: All 12 patients with WT had nephromegaly (greater than or equal to 95th percentile of age adjusted renal length) on serial screening studies. Only four of 31 control patients (specificity = 86%) had nephromegaly resulting in an odds ratio of 72 (95% confidence interval = 13-391) for the risk of WT with nephromegaly. Conclusions: In patients with BWS, persistent nephromegaly is a strong risk factor for the development of WT. If screening for WT is done in this population, infants with nephromegaly should be considered those at greatest risk for WT, and screening may be best targeted at this group. C1 NCI, Genet Epidemiol Branch, Div Canc Etiol, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, Div Hematol Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. RP DeBaun, MR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Etiol, Bethesda, MD 20892 USA. NR 21 TC 45 Z9 46 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1998 VL 132 IS 3 BP 401 EP 404 DI 10.1016/S0022-3476(98)70009-5 PN 1 PG 4 WC Pediatrics SC Pediatrics GA ZF241 UT WOS:000072877800009 PM 9544890 ER PT J AU Weirich, E Rabin, RL Maldonado, Y Benitz, W Modler, S Herzenberg, LA Herzenberg, LA AF Weirich, E Rabin, RL Maldonado, Y Benitz, W Modler, S Herzenberg, LA Herzenberg, LA TI Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection SO JOURNAL OF PEDIATRICS LA English DT Article ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; FLOW CYTOMETRIC DETERMINATION; HEMATOLOGIC SCORING SYSTEM; REGULATION IN-VIVO; UP-REGULATION; L-SELECTIN; CLINICOPATHOLOGICAL APPROACH; LEUKOTRIENE B-4; CELL-SURFACE AB Objectives: To determine whether neutrophil surface expression of CD11b predicts early-onset infection or suspected infection in at-risk infants. Study design: CD11b expression on peripheral blood neutrophils was' determined by flow cytometry of whole blood samples. Blood (0.1 ml) was obtained from a convenience sample of at-risk infants admitted to the neonatal intensive care unit, stained with antibodies detecting CD11b and CD15, chilled, and analyzed within 8 hours. Blood for culture, blood counts, and C-reactive protein (CRP) determination was obtained simultaneously. Subjects were grouped on the basis of culture results and clinical signs, and investigators were blinded to CD11b level. Results: Of 106 subjects, seven had positive bacterial or viral cultures ("confirmed infection"), 17 had clinical signs of infection but negative cultures ("suspected infection"), and 82 had negative cultures and no clinical signs ("no infection"). Neutrophil CD11b was elevated in all infants with confirmed infection, 94% with suspected infection, and none with no infection. The negative and positive predictive values, sensitivity, and specificity were 100%, 99%, 96%, and 100%, respectively, for diagnosis of neonatal infection at initial evaluation. CD11b levels correlated with peak CRP (r(2) = 0.76, p < 0.0001); however, CD11b was elevated at the time of admission in all five infants with proven bacterial infection, whereas CRP was normal until the second day in the neonatal intensive care unit in three of these five. Both infants with positive viral cultures had elevated CD11b, but the CRP levels remained within normal limits. The negative predictive value of neutrophil CD11b for identifying suspected or confirmed infection was 99%. Conclusion: This assay for neutrophil CD11b is a promising test for exclusion of early-onset neonatal infection. If validated prospectively, this assay may reduce hospital and antibiotic use in the population of neonates at risk for early-onset infection. C1 Stanford Univ, Beckman Ctr, Dept Genet, Div Infect Dis, Stanford, CA 94305 USA. Stanford Univ, Dept Pediat, Div Neonatol, Stanford, CA 94305 USA. NIAID, Clin Invest Lab, Cytokine Biol Unit, Bethesda, MD 20892 USA. RP Herzenberg, LA (reprint author), Stanford Univ, Beckman Ctr, Dept Genet, Div Infect Dis, B-007, Stanford, CA 94305 USA. FU NCI NIH HHS [CA42509]; NCRR NIH HHS [MO1-RR00070]; NIAID NIH HHS [AI34762] NR 67 TC 55 Z9 60 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1998 VL 132 IS 3 BP 445 EP 451 DI 10.1016/S0022-3476(98)70018-6 PN 1 PG 7 WC Pediatrics SC Pediatrics GA ZF241 UT WOS:000072877800018 PM 9544899 ER PT J AU Dancis, A AF Dancis, A TI Genetic analysis of iron uptake in the yeast Saccharomyces cerevisiae SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT Symposium in Honor of Dr Dancis CY MAR 19, 1996 CL NYU MED CTR, NEW YORK, NY HO NYU MED CTR ID FERRIC REDUCTASE; FET3 GENE; CERULOPLASMIN; OXIDASE; DISEASE; COPPER AB Objective: We used the methods of yeast genetics to identify genes involved in acquisition of iron by eukaryotic cells. Methods: Mutants were identified with defects in cellular iron uptake. These were organized into an upstream group and a downstream group. The upstream group was involved in the delivery of copper to the multicopper oxidase FET3. Mutants of this group were characterized by defective iron uptake that could be corrected by exposure of the cells to large amounts of copper, The downstream group was more directly involved in iron uptake. Mutant phenotypes from these genes could not be corrected by copper exposure. Results: Genes in the upstream group encoded the regulator of copper transport, MAC1, and two copper transporters, CTR1 and CCC2. Genes in the downstream group encoded the multicopper oxidase FET3 and its partner the iron permease FTR1. In addition, the downstream genes encoded the surface reductases FRE1 and FRE2 and the iron regulatory protein AFT1. Conclusions: The iron and copper uptake processes in yeast intersect because the FET5 gene encodes a multicopper oxidase that is required for iron transport. In human beings, an analogous function may be served by ceruloplasmin, a multicopper oxidase with a role in iron homeostasis. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Univ Penn, Dept Med, Div Hematol Oncol, 1009 Stellar Chase Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. NR 27 TC 34 Z9 35 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1998 VL 132 IS 3 SU S BP S24 EP S29 DI 10.1016/S0022-3476(98)70524-4 PN 2 PG 6 WC Pediatrics SC Pediatrics GA ZG113 UT WOS:000072966900005 PM 9546033 ER PT J AU Kratz, F Beyer, U Roth, T Tarasova, N Collery, P Lechenault, F Cazabat, A Schumacher, P Unger, C Falken, U AF Kratz, F Beyer, U Roth, T Tarasova, N Collery, P Lechenault, F Cazabat, A Schumacher, P Unger, C Falken, U TI Transferrin conjugates of doxorubicin: Synthesis, characterization, cellular uptake, and in vitro efficacy SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID ADRIAMYCIN; DRUG; DAUNOMYCIN; RETENTION; BINDING; CELLS; LOCALIZATION; MICROSCOPY; RECEPTOR; INVITRO AB One strategy for improving the antitumor selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing suitable carrier proteins. Thus, thiolated human serum transferrin was conjugated with four maleimide derivatives of doxorubicin that differed in the stability of the chemical link between drug and spacer. Of the maleimide derivatives, 3-maleimidobenzoic or 4-maleimidophenylacetic acid was bound to the 3'-amino position of doxorubicin through a benzoyl or phenylacetyl amide bond, and 3-maleimidobenzoic acid hydrazide or 4-maleimidophenylacetic acid hydrazide was bound to the 13-keto position through a benzoyl hydrazone or phenylacetyl hydrazone bond. The acid-sensitive transferrin conjugates prepared with the carboxylic hydrazone doxorubicin derivatives exhibited an inhibitory efficacy in the MDA-MB-468 breast cancer cell line and U937 leukemia cell line comparable to that of the free drug (employing the BrdU (5-bromo-2'-deoxyuridine) incorporation assay and tritiated thymidine incorporation assay, respectively, IC50 approximate to 0.1-1 mM), whereas conjugates with the amide derivatives showed no activity. Furthermore, antiproliferative activity of the most active transferrin conjugate (i.e, the conjugate containing a benzoyl hydrazone link) was demonstrated in the LXFL 529 lung carcinoma cell line employing a sulforhodamine B assay. In contrast to in vitro studies in tumor cells, cell culture experiments performed with human endothelial cells (HUVEC) showed that the acid-sensitive transferrin conjugates of doxorubicin were significantly less active than free doxorubicin (IC50 values approximately 10-40 higher by the BrdU incorporation assay), indicating selectivity of the doxorubicin-transferrin conjugates for tumor cells. Fluorescence microscopy studies in the MDA-MB-468 breast cancer cell showed that free doxorubicin accumulates in the cell nucleus, whereas doxorubicin of the transferrin conjugates is found localized primarily in the cytoplasm. The differences in the intracellular distribution between transferrin-doxorubicin conjugates and doxorubicin were confirmed by laser scanning confocal microscopy in LXFL 529 cells after a 24 h incubation that revealed an uptake and mode of action other than intercalation with DNA. The relationship between stability, cellular uptake, and cytotoxicity of the conjugates is discussed. C1 Tumor Biol Ctr, Dept Med Oncol, D-79106 Freiburg, Germany. Inst Int Rech Ions Met, F-51092 Reims, France. NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. RP Kratz, F (reprint author), Tumor Biol Ctr, Dept Med Oncol, D-79106 Freiburg, Germany. EM felix@tumorbio.uni-freiburg.de NR 43 TC 110 Z9 115 U1 3 U2 28 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD MAR PY 1998 VL 87 IS 3 BP 338 EP 346 DI 10.1021/js970246a PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA ZA792 UT WOS:000072402200013 PM 9523988 ER PT J AU Beekman, M Ungard, JT Gasior, M Carter, RB Dijkstra, D Goldberg, SR Witkin, JM AF Beekman, M Ungard, JT Gasior, M Carter, RB Dijkstra, D Goldberg, SR Witkin, JM TI Reversal of behavioral effects of pentylenetetrazol by the neuroactive steroid ganaxolone SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACID RECEPTOR COMPLEX; GABAA-RECEPTOR; PREGNENOLONE-SULFATE; DRUG DISCRIMINATION; HORMONE METABOLITES; ANXIOLYTIC ACTIVITY; SPINAL NEURONS; ANIMAL-MODELS; RAT-BRAIN; MODULATION AB Neuroactive steroids are naturally occurring or synthetically derived compounds many of which have anticonvulsant, anesthetic, anxiolytic, analgesic or hypnotic properties. The major site of neuronal activity appears to be with a specific steroid-sensitive site on the gamma-aminobutyric acid(A) receptor/chloride ionophore complex. Ganaxolone (3 alpha-hydroxy-3 beta-methyl-5 alpha-pregnan-20-one) is a synthetic neuroactive steroid protected from metabolic attack of the 3 alpha position. Ganaxolone is an efficacious anticonvulsant agent in a variety-of acute seizure models, as well as in electrical and chemical kindling models, and is currently under Phase II clinical investigation for epilepsy. A prior observation that ganaxolone appeared to reverse the marked behavioral changes induced by the convulsant pentylenetetrazol (PTZ) was systematically examined in the present study. A model to quantify PTZ-induced behaviors is described and used to evaluate ganaxolone in comparison with the anticonvulsants valproate, ethosuximide, clonazepam, diazepam and phenobarbital. All compounds were compared using dose equivalents based on their respective ED50 values in preventing convulsions induced by 70 mg/kg PTZ. The ED50 and lower doses of ganaxolone prevented the observed behavioral effects of PTZ as well as its depressant effects on locomotor activity and rearing of mice. In contrast, the other anticonvulsants, if effective, were much less potent. Strikingly, most of the other anticonvulsants were incapable of preventing all the behavioral effects of PTZ. Only phenobarbital prevented all the behavioral effects of PTZ and only at doses 4 to 8 times the anticonvulsant ED50. Rather than normalizing behavior as ganaxolone did, however, phenobarbital resulted in supranormal behavioral responses (e.g., increases in activity). Repeated administration of PTZ did not decrease the protective efficacy of ganaxolone. The results document the unique pharmacological profile of ganaxolone and suggest additional potential benefits from its use as an antiepileptic. Furthermore, because behavioral effects of PTZ have been used to model anxiety and anxiety associated with withdrawal from drugs of abuse, ganaxolone may find additional therapeutic application in those areas. C1 NIDA, Drug Dev Grp, Preclin Pharmacol Lab, Addict Res Ctr,NIH, Baltimore, MD 21224 USA. CoCensys Inc, Dept Pharmacol, Irvine, CA USA. RP Witkin, JM (reprint author), NIDA, Drug Dev Grp, Preclin Pharmacol Lab, Addict Res Ctr,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 51 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1998 VL 284 IS 3 BP 868 EP 877 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA532 UT WOS:000072373700009 PM 9495844 ER PT J AU Vottero, A Kirschner, LS Yue, W Brodie, A Stratakis, CA AF Vottero, A Kirschner, LS Yue, W Brodie, A Stratakis, CA TI P450arom gene expression in peripheral blood lymphocytes: Identification of a cryptic splice site for exon-1 after Epstein-Barr virus transformation SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID AROMATASE CYTOCHROME-P450 CYP19; TISSUE-SPECIFIC EXPRESSION; BREAST-CANCER; ADIPOSE-TISSUE; ALTERNATIVE PROMOTERS; ESTROGEN; CELLS; GYNECOMASTIA; LYMPHOPOIESIS; INTERLEUKIN-6 AB The human aromatase gene (P450arom) is widely expressed, albeit in a tissue-specific manner. In the present study, we measured aromatase activity and investigated the transcribed and translated products of the P450arom gene before and after Epstein-Barr virus (EBV) transformation in peripheral blood lymphocytes (PBLs) from normal individuals. Aromatase activity was determined by [H-3]-Delta(4)-androstenedione (A) to [H-3]-estrone (El) conversion. Cellular total RNA and protein lysates were subjected to RT-PCR and Western analysis, respectively. Rapid amplification of cDNA ends (RACE) was used for the detection of novel 5'-untranslated ends of the P450arom mRNA, which were subsequently sequenced and compared to the known transcripts of this gene. In untransformed PBLs, two known variants of exon 1 of the P450arom gene were expressed, corresponding to promoters PI.3 and PII, or Ic and Id, respectively. In EBV-transformed PBLs, a cryptic splice site was revealed and a new 5'-untranslated product was found. RNase protection assay confirmed that this splice variant is not a RACE artifact. The 53 K P450arom protein was detectable in PBLs both before and after EBV transformation. We conclude that (i) the P450arom mRNA is present in human PBLs and (ii) EBV transformation of the latter leads to novel alternative splicing of the 5' end of this gene. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NICHD, DEB, Sect Pediat Endocrinol, Unit Genet Endocrinol,NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Pediat, Washington, DC 20007 USA. Univ Maryland, Dept Pharmacol, Baltimore, MD 21201 USA. RP Vottero, A (reprint author), NICHD, DEB, Sect Pediat Endocrinol, Unit Genet Endocrinol,NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM votteroa@ccl.nichd.nih.gov FU NCI NIH HHS [CA-62483] NR 34 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD MAR PY 1998 VL 64 IS 5-6 BP 245 EP 250 DI 10.1016/S0960-0760(97)00193-3 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA ZN353 UT WOS:000073637400004 PM 9618025 ER PT J AU Dawson, DA AF Dawson, DA TI Volume of ethanol consumption: Effects of different approaches to measurement SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID ALCOHOL-CONSUMPTION AB Objective: Eight different approaches to measuring alcohol consumption were compared in terms of average daily volume of ethanol intake, selected percentiles of the volume distribution, the proportion of drinkers exceeding a volume-based cutpoint for moderate drinking and the estimated association between volume of intake and alcohol use disorders. Method: Data were drawn from the 1988 National Health Interview Survey and the 1992 National Longitudinal Alcohol Epidemiologic Survey. The eight approaches compared overall and beverage-specific questions, reference periods of varying lengths, and measures based solely on usual intake with those that incorporated different aspects of atypical heavy drinking. Results: Average daily ethanol intake ranged from 0.43 oz based on two questions on current usual frequency and quantity of drinking (assuming 0.5 oz of ethanol per drink) to 0.72 oz based on 21 questions that included usual and heaviest consumption of beer, wine and distilled spirits in the year preceding interview. Conclusions: Estimated volume was highly sensitive to the number and types of questions upon which it was based, and changes in formulation that resulted in relatively small increases in mean volume often were associated with much larger increases in the proportion of drinkers exceeding some specified level of intake and in the estimated association between consumption and alcohol use disorders. These issues should be considered when deciding on the consumption items to be included in alcohol surveys. C1 NIAAA, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Div Biometry & Epidemiol, NIH, Willco Bldg,Suite 514,6000 Execut Blvd,MSC7003, Bethesda, MD 20892 USA. NR 21 TC 51 Z9 51 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD MAR PY 1998 VL 59 IS 2 BP 191 EP 197 PG 7 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA YW482 UT WOS:000071940100008 PM 9500306 ER PT J AU Contoreggi, C Rexroad, VE Lange, WR AF Contoreggi, C Rexroad, VE Lange, WR TI Current management of infectious complications in the injecting drug user SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Review DE injection drug users; infectious disease; HIV; bacterial infections; immune dysfunction ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NEW-YORK-CITY; PNEUMOCYSTIS-CARINII PNEUMONIA; NON-B-HEPATITIS; HTLV-II INFECTION; NON-A-HEPATITIS; METHADONE-MAINTENANCE TREATMENT; IMMUNE-DEFICIENCY-SYNDROME; ALCOHOLIC LIVER-DISEASE; DELTA VIRUS-INFECTION AB The diagnosis and management of infectious complications associated with injection drug use (IDU) are among some of the more challenging aspects of working with substance abusing populations. As the population of injection drug users age, we expect the number and severity of these complications to increase. Commonly seen infections, such as bacterial endocarditis and bacterial infections of bones, joints, and soft tissue, are now frequently complicated by concurrent immunodeficiency. Parenterally and sexually transmitted viral hepatitis is responsible for significant IDU morbidity and mortality. The human leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU with uncertain long-term clinical effects. Immune dysfunction has been described in the IDU for decades, but the impact of host immune compromise on the transmission and the course of HIV-1 has yet to be fully appreciated. The integration of the treatment of substance abuse and its concurrent psychiatric disorders with the management of infectious complications, including immunodeficiency, promises to improve patient compliance with possible savings of overall medical costs. Published by Elsevier Science Inc. C1 NIDA, IRP, Med Affairs Branch, Div Intramural Res,NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Contoreggi, C (reprint author), NIDA, IRP, Med Affairs Branch, Div Intramural Res,NIH, POB 5180, Baltimore, MD 21224 USA. EM ccontore@irp.nida.nih.gov NR 101 TC 41 Z9 41 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR-APR PY 1998 VL 15 IS 2 BP 95 EP 106 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA ZF393 UT WOS:000072893000003 PM 9561947 ER PT J AU Kumra, S Grothe, DR AF Kumra, S Grothe, DR TI Risperidone-induced hepatotoxicity? Reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1998 VL 37 IS 3 BP 247 EP 247 DI 10.1097/00004583-199803000-00004 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YY719 UT WOS:000072177000004 ER PT J AU Weinberg, NZ Rahdert, E Colliver, JD Glantz, MD AF Weinberg, NZ Rahdert, E Colliver, JD Glantz, MD TI Adolescent substance abuse: A review of the past 10 years SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE adolescence; drug abuse; comorbidity; substance abuse; therapy; epidemiology ID DEFICIT HYPERACTIVITY DISORDER; ADDICTION SEVERITY INDEX; DRUG-ABUSE; PSYCHIATRIC-DISORDERS; HIGH-RISK; DEPENDENT DELINQUENTS; MENTAL-DISORDERS; ALCOHOL-ABUSE; GROUP-THERAPY; COMORBIDITY AB Objective: To review and synthesize the recent scientific literature on adolescent substance abuse, covering natural history, epidemiology, etiology, comorbidity, assessment, treatment, and prevention, and to highlight areas for future research. Method: Studies of adolescent substance abuse were reviewed with the focus on substance abuse and dependence rather than substance use. Results: There has been a sharp recent resurgence in adolescent drug use. Biological factors, including genetic and temperament characteristics, as well as family environment factors, are emerging as important etiological variables. Comorbidity with other psychiatric disorders, particularly with conduct disorder, is frequent and complicates treatment. New assessment instruments are available for clinical and research use, Among treatment modalities, family-based interventions have received the most study. Conclusions: The past decade has seen growth in the volume and sophistication of research on adolescent substance abuse and in the conceptualization of this problem. Further research is needed, particularly on the significance of comorbid conditions and on individualized and effective treatment approaches. C1 NIDA, Div Epidemiol & Prevent Res, NIH, Rockville, MD 20857 USA. NIDA, Div Clin & Serv Res, NIH, Rockville, MD 20857 USA. RP Weinberg, NZ (reprint author), 5600 Fishers Lane,Room 9A-53, Rockville, MD 20857 USA. NR 92 TC 228 Z9 232 U1 10 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1998 VL 37 IS 3 BP 252 EP 261 DI 10.1097/00004583-199803000-00009 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YY719 UT WOS:000072177000009 PM 9519629 ER PT J AU Kumra, S Wiggs, E Krasnewich, D Meck, J Smith, ACM Bedwell, J Fernandez, T Jacobsen, LK Lenane, M Rapoport, JL AF Kumra, S Wiggs, E Krasnewich, D Meck, J Smith, ACM Bedwell, J Fernandez, T Jacobsen, LK Lenane, M Rapoport, JL TI Brief report: Association of sex chromosome anomalies with childhood-onset psychotic disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE sex chromosome anomalies; childhood-onset psychotic disorders; neurodevelopmental impairments ID SCHIZOPHRENIA; CHILDREN; INTELLIGENCE; ABNORMALITIES AB Objective: An apparent excess of sex chromosome aneuploidies (XXY, XXX, and possibly XYY) has been reported in patients with adult-onset schizophrenia and with unspecified psychoses. This study describes the results of cytogenetic screening carried out for pediatric patients meeting DSM-III-R criteria for childhood-onset schizophrenia (COS) and a subgroup of patients with childhood-onset psychotic disorder not otherwise specified, provisionally labeled by the authors as multidimensionally impaired (MDI). Method: From August 1990 to July 1997, karyotypes were determined for 66 neuroleptic-nonresponsive pediatric patients (28 MDI, 38 COS), referred to the National Institute of Mental Health for an inpatient treatment trial of clozapine. Results: Four (6.1%) of 66 patients (3 MDI, 1 COS) were found to have sex chromosome anomalies (mosaic 47,XXY; 47,XXY; 47,XYY; mosaic 45,XO, respectively), which is higher than the expected rate of 1 per 426 children or 2.34 per 1,000 in the general population (4/66 versus 1/426, chi(2) = 19.2, df = 1, p = .00001). All cases had been previously undiagnosed. Conclusions: These findings lend support to a hypothesis that a loss of balance of gene products on the sex chromosomes may predispose affected individuals to susceptibility to additional genetic and environmental insults that result in childhood-onset psychotic disorders. Karyotyping of children with psychotic disorders should be routine. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. NIMH, Child Neurosci Branch, Bethesda, MD 20892 USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 6N240,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Fernandez, Thomas/D-4295-2009 OI Fernandez, Thomas/0000-0003-0830-022X NR 22 TC 36 Z9 38 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1998 VL 37 IS 3 BP 292 EP 296 DI 10.1097/00004583-199803000-00014 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YY719 UT WOS:000072177000014 PM 9519634 ER PT J AU King, SB Yeh, WL Holubkov, R Baim, DS Sopko, G Desvigne-Nickens, P Holmes, DR Cowley, MJ Bourassa, MG Margolis, J Detre, KM AF King, SB Yeh, WL Holubkov, R Baim, DS Sopko, G Desvigne-Nickens, P Holmes, DR Cowley, MJ Bourassa, MG Margolis, J Detre, KM CA NHLBI PTCA NACI Registry Investigators TI Balloon angioplasty versus new device intervention: Clinical outcomes - A comparison of the NHLBI PTCA and NACI registries SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; DIRECTIONAL ATHERECTOMY; STENTS; IMPLANTATION; LESIONS AB Objectives, We sought to compare outcomes of patients treated in the National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) and New Approaches to Coronary Intervention (NACI) registries, Background. Coronary angioplasty has numerous shortcomings. New devices for performing coronary interventions hare been introduced in an effort tit improve clinical outcomes. Methods. Under the sponsorship of the NHLBI, a registry of consecutive patients treated with PTCA during 1985 to 1986 was established. In 1990, the NHLBI funded a second registry, the NACI. The two registries used the same data coordinating center to collect detailed baseline and follow-up information. Results. Patients enrolled in the NACI registry were older, had undergone more previous bypass surgery procedures and had more stenoses located in bypass grafts than patients in the NHLBI PTCA registry. Procedural success was achieved in 72.1% and 82.6% of patients in the PTCA and NACI registries, respectively; however, in-hospital and 1-year mortality rates were 1.0% versus 1.8% and 3.1% versus 5.9% for the PTCA versus NACI registries, respectively, After risk adjustment, there was no difference in 1-year mortality, Rates of target lesion revascularization (TLR) were 21.5% for the PTCA registry and 24.2% far the NACI registry. NACI registry patients had a higher risk for TLR and the composite end point of death, myocardial infarction or revascularization (relative risk 1.28 and 1.23, respectively). However, the NACI registry patients who received stents tended to have a lower adjusted TLR rate. Conclusions. This comparative study found no overall superiority of these newer devices in terms of patient survival or freedom from TLR after adjustment for baseline risk profiles. Although technologic improvements (especially improved stenting) continue, these observations highlight the importance of careful assessment of clinical results in the broad population of patients in whom interventions are used. (C) 1998 by the American College of Cardiology. C1 Emory Univ, Andreas Gruentzig Cardiovasc Ctr, Atlanta, GA 30322 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Beth Israel Hosp, Boston, MA 02215 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Med Coll Virginia, Richmond, VA USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Miami Heart Inst, Miami, FL USA. RP King, SB (reprint author), Emory Univ Hosp, Andreas Gruentzig Cardiovasc Ctr, 1364 Clifton Rd NE,Suite F606, Atlanta, GA 30322 USA. OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HL33292, HL44284] NR 20 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1998 VL 31 IS 3 BP 558 EP 566 DI 10.1016/S0735-1097(97)10523-X PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YZ761 UT WOS:000072289000012 PM 9502635 ER PT J AU Arbustini, E Morbini, P Grasso, M Fasani, R Verga, L Bellini, O Dal Bello, B Campana, C Piccolo, G Febo, O Opasich, C Gavazzi, A Ferrans, VJ AF Arbustini, E Morbini, P Grasso, M Fasani, R Verga, L Bellini, O Dal Bello, B Campana, C Piccolo, G Febo, O Opasich, C Gavazzi, A Ferrans, VJ TI Restrictive cardiomyopathy, atrioventricular block and mild to subclinical myopathy in patients with desmin-immunoreactive material deposits SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID UNUSUAL FAMILIAL CARDIOMYOPATHY; HEREDITARY DISTAL MYOPATHY; INTERMEDIATE FILAMENTS; SKELETAL-MUSCLE; IMMUNOLOGICAL CHARACTERIZATION; ACCUMULATION; STORAGE; PROTEINS; CELLS; PHOSPHORYLATION AB Objectives. We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. Background. Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. Methods. Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. Results. Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin-one of normal and another of lower molecular weight-in cardiac and skeletal muscle of the familial cases. Conclusions. Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin. (C) 1998 by the American College of Cardiology. C1 Policlin San Matteo, Dept Pathol Anat, I-27100 Pavia, Italy. Policlin San Matteo, Dept Cardiol, IRCCS, I-27100 Pavia, Italy. Fdn Ist Neurol Casimiro Mondino, Pavia, Italy. Fdn Salvatore Maugeri, Dept Cardiol, Clin Lavoro & Riabilitaz, Ctr Med Montescano, Pavia, Italy. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Arbustini, E (reprint author), Lab Patol Cellulare & Mol, Ist Anat Patol, Dipartimento Patol Umana & Ereditaria, Sez Anat Patol, Via Forlanini 16, I-27100 Pavia, Italy. NR 43 TC 60 Z9 62 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1998 VL 31 IS 3 BP 645 EP 653 DI 10.1016/S0735-1097(98)00026-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YZ761 UT WOS:000072289000025 PM 9502648 ER PT J AU Slavkin, HC AF Slavkin, HC TI Distinguishing Mars from Venus: Emergence of gender biology in health and disease SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID WOMEN C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 1998 VL 129 IS 3 BP 357 EP 361 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZA546 UT WOS:000072375400017 PM 9529812 ER PT J AU Gill, JR AF Gill, JR TI Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis - A new syndrome - Commentary SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 Natl Heart Inst, Clin Endocrinol Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RP Gill, JR (reprint author), Natl Heart Inst, Clin Endocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 1998 VL 9 IS 3 BP 516 EP 517 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA YZ047 UT WOS:000072214900024 ER PT J AU Fay, MP Shih, JH AF Fay, MP Shih, JH TI Permutation tests using estimated distribution functions SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE censored data; randomization test; rank test; repeated measures ID INTERVAL-CENSORED-DATA; KAPLAN-MEIER STATISTICS; MAXIMUM-LIKELIHOOD; COARSE DATA; RANK-TESTS; K-SAMPLES; IGNORABILITY; MODEL AB In this article we develop permutation tests for estimated distribution functions. The tests are formed by averaging a functional of estimated distribution functions that are calculated from independent sampling units, where the units may be a single response, a set of repeated responses, or a censored response. We study primarily two functionals-the difference in means functional and the Mann-Whitney functional, and two types of responses-repeated conditionally independent responses and censored responses. For repeated responses, the permutation test using the difference in means functional produces a permutation form of the corresponding mixed-effects test. A new permutation test is developed when we apply the Mann-Whitney functional to the repeated responses. This is a case in which the rank-transform method does not work. On the other hand, for right-censored or interval-censored data, we obtain permutation forms of standard rank tests using the Mann-Whitney functional (or weighted forms of the functional), and the difference in means functional gives new tests. The latter tests generalize the permutation t-test and the mean-based permutation tests to censored data. These permutation tests are valid for all sample sizes and do not need weights for stabilization like the weighted Kaplan-Meier statistics. We perform the permutation tests on two examples, one with repeated measures and one with interval-censored responses. C1 NCI, Div Canc Prevent & Control, Biometry Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Fay, MP (reprint author), NCI, Div Canc Prevent & Control, Biometry Branch, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 31 TC 12 Z9 12 U1 2 U2 6 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1998 VL 93 IS 441 BP 387 EP 396 DI 10.2307/2669635 PG 10 WC Statistics & Probability SC Mathematics GA ZA356 UT WOS:000072355300039 ER PT J AU Walther, MM Johnson, B Culley, D Shah, R Weber, J Venzon, D Yang, JC Linehan, WH Rosenberg, SA AF Walther, MM Johnson, B Culley, D Shah, R Weber, J Venzon, D Yang, JC Linehan, WH Rosenberg, SA TI Serum interleukin-6 levels in metastatic renal cell carcinoma before treatment with interleukin-2 correlates with paraneoplastic syndromes but not patient survival SO JOURNAL OF UROLOGY LA English DT Article DE carcinoma, renal cell; interleukin-6; interleukin-2; kidney; neoplasm metastasis ID RECOMBINANT HUMAN INTERLEUKIN-6; ADVANCED CANCER; PHASE-I; IMMUNOTHERAPY; MELANOMA; THERAPY; TRIAL; LYMPHOCYTES; COMBINATION; EXPRESSION AB Purpose: We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival. Materials and Methods: Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes. Results: IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2. Conclusions: IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer, Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome), A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Walther, MM (reprint author), NCI, Surg Branch, Bldg 10, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 33 TC 38 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1998 VL 159 IS 3 BP 718 EP 722 DI 10.1016/S0022-5347(01)63709-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA YW252 UT WOS:000071913700020 PM 9474133 ER PT J AU Jackson, AM Ivshina, AV Senko, O Kuznetsova, A Sundan, A O'Donnell, MA Clinton, S Alexandroff, AB Selby, PJ James, K Kuznetsov, VA AF Jackson, AM Ivshina, AV Senko, O Kuznetsova, A Sundan, A O'Donnell, MA Clinton, S Alexandroff, AB Selby, PJ James, K Kuznetsov, VA TI Prognosis of intravesical Bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: Statistically weighted syndromes analysis SO JOURNAL OF UROLOGY LA English DT Article DE bladder cancer; BCG immunotherapy; pattern recognition; ICAM-1; CD14; TNF; prognosis ID TUMOR-NECROSIS-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; EVANS BCG THERAPY; INTERFERON-GAMMA; ICAM-1 EXPRESSION; CARCINOMA INSITU; NEURAL NETWORKS; SOLUBLE CD14; FACTOR-ALPHA; CELL-LINES AB Purpose: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. Patients and Methods: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), CM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. Results: Only one parameter gave significant differences at p<0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5(th)-6(th) installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. Conclusion: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer. C1 Univ Leeds, Imperial Canc Res Fund, Canc Med Res Unit, Leeds, W Yorkshire, England. Univ Edinburgh, Dept Surg, Edinburgh EH8 9YL, Midlothian, Scotland. Inst Biochem Phys, Moscow, Russia. NCI, Frederick Canc & Dev Ctr, Frederick, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Russian Acad Sci, Ctr Comp, Moscow, Russia. Univ Trondheim, Canc Res Inst, N-7034 Trondheim, Norway. Beth Israel Hosp, Dept Urol Surg, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jackson, AM (reprint author), St James Univ Hosp, Imperial Canc Res Fund, Canc Med Res Unit, Beckett St, Leeds LS9 7TF, W Yorkshire, England. RI Jackson, Andrew/I-5929-2013 OI Jackson, Andrew/0000-0003-4739-4804 NR 61 TC 37 Z9 38 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1998 VL 159 IS 3 BP 1054 EP 1063 DI 10.1016/S0022-5347(01)63835-7 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA YW252 UT WOS:000071913700146 PM 9474231 ER PT J AU Quinn, KJ AF Quinn, KJ TI Classical conditioning using vestibular reflexes SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Review DE classical conditioning; VOR; adaptation; vestibulo-ocular reflex; eye blink; nictitating membrane ID PRIMATE VESTIBULOOCULAR REFLEX; ADAPTIVE FILTER MODEL; OCULAR REFLEX; EYE-MOVEMENTS; SHORT-TERM; ADAPTATION; CEREBELLUM; STIMULATION; PLASTICITY; RESPONSES AB Adaptation of the vestibulo-ocular reflex (VOR) is one of the principal models for studying motor learning in the mammalian CNS. However, there has been no previous comprehensive attempt to understand the behavioral characteristics of VOR adaptation in terms of traditional psychological learning theory, To accomplish this objective, the effectiveness of vestibular-evoked responses in serving as the conditioned or unconditioned stimulus in classical conditioning paradigms is first reviewed, Then, the various procedures for eliciting VOR adaptation are reviewed from the perspective of their similarity to standard classical conditioning protocols, A systematic analysis of Western and Russian literature yielded a relatively small number of studies that explicitly used vestibular reflexes in classical conditioning paradigms, and they report a wide range in success, Potential explanations for these diverse findings are discussed A comprehensive categorization of the behavioral parallels between VOR adaptation and classical conditioning is then presented, Viewing VOR adaptation as a form of classical conditioning is a useful heuristic device and leads directly to the description of further behavioral experiments that could throw additional light on general mechanisms for inducing neural plasticity, Such an exercise is of benefit in order to further understand the common framework which might exist between VOR adaptation and other models of motor learning (for example, rabbit eye blink conditioning). (C) 1998 Elsevier Science Inc. C1 NIMH, DBCNR, BINRB, Rockville, MD 20857 USA. RP NIMH, DBCNR, BINRB, 11-C-16,5600 Fishers Lane, Rockville, MD 20857 USA. EM kjquinn@helix.nih.gov FU NINDS NIH HHS [NS31805] NR 73 TC 4 Z9 4 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0957-4271 EI 1878-6464 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PD MAR-APR PY 1998 VL 8 IS 2 BP 117 EP 133 PG 17 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA ZC499 UT WOS:000072586200001 PM 9547487 ER PT J AU Lau, DTY Comanor, L Minor, JM Everhart, JE Wuestehube, LJ Hoffnagle, JH AF Lau, DTY Comanor, L Minor, JM Everhart, JE Wuestehube, LJ Hoffnagle, JH TI Statistical models for predicting a beneficial response to interferon-alpha in patients with chronic hepatitis B SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE cirrhosis; HBV DNA; hepatitis B; linear regression; logistic regression; neural network ID ARTIFICIAL NEURAL-NETWORK; CONTROLLED TRIAL; DIAGNOSIS; VIRUS AB Therapy with interferon-alpha has been reported to induce remissions in 35% of patients with chronic hepatitis B, The ability to identify patients likely to respond would be helpful in making recommendations for treatment, In this statistical analysis we included 82 patients with chronic hepatitis B who received interferon-alpha in clinical trials at the National Institutes of Health between 1984 and 1991, A response was defined as the loss of hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) within 1 year of therapy. Multiple clinical parameters measured at pretreatment (month 0) and after the first month (month 1) of therapy were selected by stepwise regression to support the development of the prognostic models: the two-stage logistic regression model and a neural network that utilized higher-order non-linear interactions between variables, Among the 82 patients, 24 (29%) were responders. The two-stage logistic model using pretreatment variables: sex, hepatic fibrosis and alanine aminotransferase (ALT) levels correctly identified 61% of responders and 76% of non-responders, When HBV DNA at month 1 along with sex, initial ALT and fibrosis was included, the resultant model correctly identified 69% of responders and 77% of non-responders. The neural network, by incorporating interactions between variables, correctly identified 77% and 86% of responders, and 87% and 92% of non-responders, using pretreatment factors alone and the combination of pretreatment and month 1 factors respectively, Hence, the neural network was more accurate than the simple logistic regression model in predicting a response to interferon-a in chronic hepatitis B, The universality of these models needs to be further verified. C1 NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. Chiron Diagnost, Emeryville, CA USA. RP Lau, DTY (reprint author), NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bldg 10,Room 9B16, Bethesda, MD 20892 USA. NR 20 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAR PY 1998 VL 5 IS 2 BP 105 EP 114 DI 10.1046/j.1365-2893.1998.00087.x PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA ZP287 UT WOS:000073737200005 PM 9572035 ER PT J AU Skiadopoulos, MH Durbin, AP Tatem, JM Wu, SL Paschalis, M Tao, T Collins, PL Murphy, BR AF Skiadopoulos, MH Durbin, AP Tatem, JM Wu, SL Paschalis, M Tao, T Collins, PL Murphy, BR TI Three amino acid substitutions in the L protein of human parainfluenza virus type 3 cp45 live attenuated vaccine candidate contribute to its temperature-sensitive and attenuation phenotypes SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; INFLUENZA-A VIRUS; RNA-POLYMERASE; GENE-EXPRESSION; CLONED CDNA; JS STRAIN; MUTATIONS; CHILDREN; MUTANTS AB Studies were initiated to define the genetic basis of the temperature-sensitive (ts), cold adaptation ten), and attenuation (aff) phenotypes of the human parainfluenza virus type 3 (PIV3) cp45 live attenuated vaccine candidate, Genetic data had previously suggested that the L polymerase protein of cp45, which contains three amino acid substitutions at positions 942, 992, and 1558, contributed to its temperature sensitivity (R. Ray, M. S. Galinski, B. R. Heminway, K. Meyer, F. K. Newman, and R. B. Belshe, J. Virol. 70:580-584, 1996; A. Stokes, E. L. Tierney, C. M. Sarris, B. R. Murphy, and S. L. Hall, Virus Res, 30:43-52, 1993). To study the individual and aggregate contributions that these amino acid substitutions make to the ts, att, and ca phenotypes of cp45, seven PIV3 recombinant viruses (three single, three double, and one triple mutant representing all possible combinations of the three amino acid substitutions were recovered from full-length antigenomic cDNA and analyzed for their ts, aft, and ca phenotypes. None of the seven mutant recombinant PIVs was cold adapted, The substitutions at L protein amino acid positions 992 and 1558 each specified a 10(5)-fold reduction in plaque formation in cell culture at 40 degrees C, whereas the substitution at position 942 specified a 300-fold reduction, Thus, each of the three mutations contributes individually to the ts phenotype, The triple recombinant which possesses an L protein with all three mutations was almost as temperature sensitive as cp45, indicating that these mutations are the major contributors to the ts phenotype of cp45. The three individual mutations in the L protein each contributed to restricted replication in the upper or loner respiratory tract of hamsters, and this likely contributes to the observed stability of the ts and att phenotypes of cp45 during replication in vivo. Importantly, the recombinant virus possessing L protein with all three mutations was as restricted in replication as was the cp45 mutant in both the upper and lower respiratory tracts of hamsters, indicating that the L gene of the cp45 virus is a major attenuating component of this candidate vaccine. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Wyeth Lederle Vaccines & Pediat, Pearl River, NY 10965 USA. RP Skiadopoulos, MH (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Rm 100,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 39 TC 64 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 1762 EP 1768 PG 7 WC Virology SC Virology GA YX013 UT WOS:000071997600007 PM 9499025 ER PT J AU Onodera, M Nelson, DM Yachie, A Jagadeesh, GJ Bunnell, BA Morgan, RA Blaese, RM AF Onodera, M Nelson, DM Yachie, A Jagadeesh, GJ Bunnell, BA Morgan, RA Blaese, RM TI Development of improved adenosine deaminase retroviral vectors SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-TRANSFER; CELL-LINES; HEMATOPOIETIC-CELLS; PERIPHERAL-BLOOD; LEUKEMIA-VIRUS; EXPRESSION; TRANSPLANTATION; LYMPHOCYTES; ENGRAFTMENT; GENERATION AB A series of adenosine deaminase (ADA) retroviral vectors were designed and constructed with the goal of improved performance over the PA317/LASN vector currently used in clinical trials. First, the bacterial selectable-marker neomycin phosphotransferase (nea) gene was removed to create a "simplified" vector. Second, the Moloney murine leukemia virus long terminal repeat (LTR) promoter used for ADA expression was replaced with either the myeloproliferative sarcoma virus (MPSV) or SL3-3 LTR Supernatant from each ADA vector was used to transduce ADA-deficient (ADA(-)) B- and T-cell lines as well as primary peripheral blood mononuclear cells (PBMC) from an ADA(-) severe combined immunodeficiency patient. Total ADA enzyme activity and ADA activity per integrant in the transduced cells demonstrated that the MPSV LTR splicing vector design provided the highest level of ADA expression per cell. This ADA(MPSV) vector was then tested in packaging cell lines containing either the gibbon ape leukemia virus envelope (PG13 cells), the murine amphotropic envelope (FLYA13 cells), or the feline endogenous virus RD114 envelope (FLYRD18 cells). The results indicate that FLYRD18/ADA(MPSV), a simplified ADA retroviral vector with the MPSV LTR, provides a 17-fold-higher level of ADA expression in human lymphohematopoietic cells than the PA317/LASN vector currently in use. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Sch Med, Dept Pediat, Kanazawa, Ishikawa 920, Japan. RP Blaese, RM (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103,10 Ctr Dr,MSC 1852, Bethesda, MD 20892 USA. RI Yachie, Akihiro/C-4660-2015 NR 30 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 1769 EP 1774 PG 6 WC Virology SC Virology GA YX013 UT WOS:000071997600008 PM 9499026 ER PT J AU Fisher, RJ Rein, A Fivash, M Urbaneja, MA Casas-Finet, JR Medaglia, M Henderson, LE AF Fisher, RJ Rein, A Fivash, M Urbaneja, MA Casas-Finet, JR Medaglia, M Henderson, LE TI Sequence-specific binding of human immunodeficiency virus type 1 nucleocapsid protein to short oligonucleotides SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RNA IN-VITRO; CYS-HIS BOX; GENOMIC RNA; ZINC-FINGER; VIRAL-RNA; SECONDARY STRUCTURE; HIV-1; DNA; RETROVIRUS AB We have analyzed the binding of recombinant human immunodeficiency virus type 1 nucleocapsid protein (NC) to very short oligonucleotides by using surface plasmon resonance (SPR) technology. Our experiments, which were conducted at a moderate salt concentration (0.15 M NaCl), showed that NC binds more stably to runs of d(G) than to other DNA homopolymers. However, it exhibits far more stable binding with the alternating base sequence d(TG)(n) than with any homopolymeric oligodeoxyribonucleotide; thus, it shows a strong sequence preference under our experimental conditions, We found that the minimum length of an alternating d(TG) sequence required for stable binding was five nucleotides, Stable binding to the tetranucleotide d(TG)(2) was observed only under conditions where two tetranucleotide molecules were held in close spatial proximity. The stable, sequence-specific binding to d(TG)(n) required that both zinc fingers be present, each in its proper position in the NC protein, and was quite salt resistant, indicating a large hydrophobic contribution to the binding, Limited tests with RNA oligonucleotides indicated that the preferential sequence specific binding observed with DNA also occurs with RNA, Evidence was also obtained that NC can bind to nucleic acid molecules in at least two distinct modes, The biological significance of the specific binding we have detected is not known; it may reflect the specificity with which the parent Gag polyprotein packages genomic RNA or may relate to the functions of NC after cleavage of the polyprotein, including its role as a nucleic acid chaperone. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Retroviral Genet Sect,SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Prot Chem Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Dev Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv, Frederick, MD 21702 USA. RP Fisher, RJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Retroviral Genet Sect,SAIC Frederick, POB B,Bldg 469, Frederick, MD 21702 USA. RI Fisher, Robert/B-1431-2009 NR 49 TC 151 Z9 153 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 1902 EP 1909 PG 8 WC Virology SC Virology GA YX013 UT WOS:000071997600024 PM 9499042 ER PT J AU Picchio, GR Gulizia, RJ Wehrly, K Chesebro, B Mosier, DE AF Picchio, GR Gulizia, RJ Wehrly, K Chesebro, B Mosier, DE TI The cell tropism of human immunodeficiency virus type 1 determines the kinetics of plasma viremia in SCID mice reconstituted with human peripheral blood leukocytes SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY HIV-1 INFECTION; DYNAMICS IN-VIVO; T-CELL; MACROPHAGE TROPISM; HU MOUSE; DISEASE PROGRESSION; CD4 LYMPHOCYTES; AIDS; RECEPTOR; VARIANTS AB Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium- inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of hi-tropic, NSI viruses and the slow evolution of T-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry, We have examined plasma viral RNA levels and the extent of CD4(+) T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with hi-tropic, dual-tropic, or T-tropic HIV-1 isolates, The cell tropism was found to determine the course of viremia, with hi-tropic viruses producing sustained high viral RNA levels and sparing some CD4(+) T cells, dual-tropic viruses producing a transient and lon er viral RNA spike and extremely rapid depletion of CD4(+) T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid intermediate rates of CD4(+) T-cell depletion, A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to snitch from hi-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4(+) T cells. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Mosier, DE (reprint author), Scripps Res Inst, Dept Immunol, IMM7,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM dmosier@scripps.edu FU NIAID NIH HHS [AI-29182] NR 64 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 2002 EP 2009 PG 8 WC Virology SC Virology GA YX013 UT WOS:000071997600036 PM 9499054 ER PT J AU Huang, MJ Zensen, R Cho, M Martin, MA AF Huang, MJ Zensen, R Cho, M Martin, MA TI Construction and characterization of a temperature-sensitive human immunodeficiency virus type 1 reverse transcriptase mutant SO JOURNAL OF VIROLOGY LA English DT Article ID ALANINE-SCANNING MUTAGENESIS; SYSTEMATIC MUTATIONAL ANALYSIS; TEMPLATE-PRIMER UTILIZATION; SITE-SPECIFIC MUTAGENESIS; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; MOLECULAR CLONES; HIV-1; RESISTANCE AB A temperature-sensitive (ts) human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) mutant was generated by charged-cluster-to-alanine mutagenesis. The mutant virus, containing three charged residues within the RT finger domain changed to alanine (K64A, K66A, and D67A), replicated normally at 34.5 but not 39.5 degrees C. Quantitating virus particle production qv p24 antigen capture or virion-associated RT activity and virus infectivity by the MAGI cell assay, we found that (i) mutant virions produced at the permissive temperature were indistinguishable from wild-type virus in assays performed at the nonpermissive temperature, suggesting that the ts mutation did not impair early steps in the virus replication cycle and that the mutant RT enzyme was not ts; and (ii) virus particle production in cells transfected with the ts mutant at the nonpermissive temperature was comparable to that of wild-type virus. However, the particle-associated RT activity and infectivity of mutant virions produced at the nonpermissive temperature were greatly reduced when assays were conducted at the permissive temperature. These results are consistent with an irreversible ts event affecting RT that occurs during virus particle production. Radioimmunoprecipitation analyses revealed that both p66 and p51 RT subunits were absent from mutant virions generated at 39.5 degrees C. The presence of normal levels of HIV-1 integrase in mutant particles produced at the nonpermissive temperature was inconsistent with defective Gag-Pol synthesis or Gag-Pol incorporation into progeny virions. Furthermore, wild-type levels of the mutant Pr160(gag-pol) were detected in virions produced at the nonpermissive temperature when the HIV-1 protease was inactivated by site-specific mutagenesis. Taken together, these results are most consistent with a fs defect affecting the degradation or aberrant processing of the mutated RT during its processing maturation within nascent particles. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr,Bldg 4,Room 315, Bethesda, MD 20892 USA. NR 56 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 2047 EP 2054 PG 8 WC Virology SC Virology GA YX013 UT WOS:000071997600041 PM 9499059 ER PT J AU Skiadopoulos, MH McBride, AA AF Skiadopoulos, MH McBride, AA TI Bovine papillomavirus type 1 genomes and the E2 transactivator protein are closely associated with mitotic chromatin SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; DNA-BINDING DOMAIN; E1 PROTEIN; ORIGIN-BINDING; TRANSCRIPTIONAL REPRESSOR; REPLICATION PROTEIN; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; NUCLEAR MATRIX; CELL-LINES AB The bovine papillomavirus type 1 E2 transactivator protein is required for viral transcriptional regulation and DNA replication and may be important for long-term episomal maintenance of viral genomes within replicating cells (M. Piirsoo, E. Ustav, T. Mandel, A.Stenlund, and M. Ustav, EMBO J. 15:1-11, 1996). We have evidence that, in contrast to most other transcriptional transactivators, the E2 transactivator protein is associated with mitotic chromosomes in dividing cells. The shorter E2-TR and E8/E2 repressor proteins do not bind to mitotic chromatin, and the N-terminal transactivation domain of the E2 protein is necessary for the association. However, the DNA binding function of E2 is not required. We have found that bovine papillomavirus type 1 genomes are also associated with mitotic chromosomes, and we propose a model in which E2-bound viral genomes are transiently associated with cellular chromosomes during mitosis to ensure that viral genomes are segregated to daughter cells in approximately equal numbers. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 137,4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. OI McBride, Alison/0000-0001-5607-5157 NR 49 TC 129 Z9 132 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 2079 EP 2088 PG 10 WC Virology SC Virology GA YX013 UT WOS:000071997600045 PM 9499063 ER PT J AU Schubert, U Anton, LC Bacik, I Cox, JH Bour, S Bennink, JR Orlowski, M Strebel, K Yewdell, JW AF Schubert, U Anton, LC Bacik, I Cox, JH Bour, S Bennink, JR Orlowski, M Strebel, K Yewdell, JW TI CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; CYTOPLASMIC DOMAIN; U VPU; HIV-1; INHIBITION; EXPRESSION; GENE; TRANSMEMBRANE; CALNEXIN; ANTIGENS AB The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a type I anchored integral membrane phosphoprotein with two independent functions, First, it regulates virus release from a post-endoplasmic reticulum (ER) compartment by an ion channel activity mediated by its transmembrane anchor, Second, it induces the selective down regulation of host cell receptor proteins (CD4 and major histocompatibility complex class I molecules) in a process involving its phosphorylated cytoplasmic tail, In the present work, we show that the Vpu-induced proteolysis of nascent CD4 can be completely blocked br peptide aldehydes that act as competitive inhibitors of proteasome function and also by lactacystin, which blocks proteasome activity by covalently binding to the catalytic beta subunits of proteasomes. The sensitivity of Vpu-induced CD4 degradation to proteasome inhibitors paralleled the inhibition of proteasome degradation of a model ubiquitinated substrate, Characterization of CD4-associated oligosaccharides indicated that CD-l rescued from Vpu-induced degradation by proteasome inhibitors is exported from the ER to the Golgi complex, This finding suggests that retranslocation of CD4 from the ER to the cytosol may be coupled to its proteasomal degradation, CD4 degradation mediated by Vpu does not require the ER chaperone calnexin and is dependent on an intact ubiquitin-conjugating system, This was demonstrated by inhibition of CD I degradation (i) in cells expressing a thermally inactivated form of the ubiquitin-activating enzyme E-1 or (ii) following expression of a mutant form of ubiquitin (Lys(48) mutated to Arg(48)) known to compromise ubiquitin targeting by interfering with the formation of polyubiquitin complexes, CD4 degradation was also prevented by altering the four Lys residues in its cytosolic domain to Arg, suggesting a role for ubiquitination of one or more of these residues in the process of degradation, The results clearly demonstrate a role for the cytosolic ubiquitin-proteasome pathway in the process of Vpu-induced CD4 degradation, In contrast to other viral proteins (human cytomegalovirus US2 and US11), hoc-ever, whose translocation of host ER molecules into the cytosol occurs in the presence of proteasome inhibitors, Vpu-targeted CD4 remains in the ER in a transport-competent form when proteasome activity is blocked. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA. RP Yewdell, JW (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4, Bethesda, MD 20892 USA. EM ks10z@nih.gov; jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 66 TC 190 Z9 196 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 2280 EP 2288 PG 9 WC Virology SC Virology GA YX013 UT WOS:000071997600069 PM 9499087 ER PT J AU Bates, P Rong, LJ Varmus, HE Young, JAT Crittenden, LB AF Bates, P Rong, LJ Varmus, HE Young, JAT Crittenden, LB TI Genetic mapping of the cloned subgroup A avian sarcoma and leukosis virus receptor gene to the TVA locus SO JOURNAL OF VIROLOGY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; HOST RANGE; ENVELOPE GLYCOPROTEIN; RETROVIRUSES; DETERMINANTS; INFECTION; BINDS AB A chicken gene conferring susceptibility to subgroup A avian sarcoma and leukosis viruses (ASLV-A) was recently identified by a gene transfer strategy. Classical genetic approaches had previously identified a locus, TVA, that controls susceptibility to ASLV-A. Using restriction fragment length polymorphism (RFLP) mapping in inbred susceptible (TVA*S) and resistant (TVA*R) chicken lines, we demonstrate that in 93 F-2 progeny an RFLP for the cloned receptor gene segregates with TVA. From these analyses we calculate that the cloned receptor gene lies within 5 centimorgans of TVA, making it highly probable that the cloned gene is the previously identified locus TVA. The polymorphism that distinguishes the two alleles of TVA in these inbred lines affects the encoded amino acid sequence of the region of Tva that encompasses the viral binding domain. However, analysis of the genomic sequence encoding this region of Tva in randomly bred chickens suggests that the altered virus binding domain is not the basis for genetic resistance in the chicken lines analyzed. C1 Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Michigan State Univ, Dept Microbiol, USDA, Avian Dis & Oncol Lab, E Lansing, MI 48824 USA. RP Bates, P (reprint author), Univ Penn, Sch Med, Dept Microbiol, 225 Johnson Pavil,3610 Hamilton Walk, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA39832, CA63531] NR 22 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 2505 EP 2508 PG 4 WC Virology SC Virology GA YX013 UT WOS:000071997600096 PM 9499114 ER PT J AU Cho, MW Lee, MK Carney, MC Berson, JF Doms, RW Martin, MA AF Cho, MW Lee, MK Carney, MC Berson, JF Doms, RW Martin, MA TI Identification of determinants on a dualtropic human immunodeficiency virus type 1 envelope glycoprotein that confer usage of CXCR4 SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-LINE; HIV-1 ENTRY; PRODUCTIVE INFECTION; SYNCYTIUM FORMATION; PRIMARY MACROPHAGES; MOLECULAR CLONE; V3 DOMAIN; GP120; TROPISM; GENE AB The chemokine receptors CCR5 and CXCR4, in combination with CD4, mediate cellular entry of macrophage-tropic (M-tropic) and T-cell-tropic strains of human immunodeficiency virus type 1 (HIV-1), respectively, while dualtropic viruses can use either receptor. We have constructed a panel of chimeric viruses and envelope glycoproteins in which various domains of the dualtropic HIV-1(DH12) gp160 were introduced into the genetic background of an M-tropic HIV-1 isolate, HIV-1(AD8). These constructs were employed in cell fusion and virus infectivity assays using peripheral blood mononuclear cells, MT4 T cells, primary monocyte-derived macrophages, or HOS-CD4 cell lines, expressing various chemokine receptors, to assess the contributions of different gp120 subdomains in coreceptor usage and cellular tropism. As expected, the dualtropic HIV-1(DH12) gp120 utilized either CCR3, CCR5, or CXCR4, whereas HIV-1(AD8) gp120 was able to use only CCR3 or CCR5. We found that either the V1/V2 or the V3 region of HIV-1(DH12) gp120 individually conferred on HIV-1(AD8) the ability to use CXCR4, while the combination of both the V1/V2 and V3 regions increased the efficiency of CXCR4 use. In addition, while the V4 or the V5 region of HIV-1(DH12) gp120 failed to confer the capacity to utilize CXCR4 on HIV-1(AD8), these regions were required in conjunction with regions V1 to V3 of HIV-1(DH12) gp120 for efficient utilization of CXCR4. Comparison of virus infectivity analyses with various cell types and cell fusion assays revealed assay-dependent discrepancies and indicated that events occurring at the cell surface during infection are complex and cannot always be predicted by any one assay. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Cho, MW (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm 339, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-35383, AI-38225, AI-40880, R01 AI040880] NR 44 TC 136 Z9 138 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1998 VL 72 IS 3 BP 2509 EP 2515 PG 7 WC Virology SC Virology GA YX013 UT WOS:000071997600097 PM 9499115 ER PT J AU Cummings, NB AF Cummings, NB TI Ethical issues and dilemmas SO JOURNAL OF WOMENS HEALTH LA English DT Article C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Cummings, NB (reprint author), NIDDK, NIH, Bldg 45,5AN 32J, Bethesda, MD 20892 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 1998 VL 7 IS 2 BP 173 EP 176 DI 10.1089/jwh.1998.7.173 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA ZG170 UT WOS:000072973900013 PM 9555679 ER PT J AU Basso, A Piantanelli, L Rossolini, G Roth, GS AF Basso, A Piantanelli, L Rossolini, G Roth, GS TI Reduced DNA synthesis in primary cultures of hepatocytes from old mice is restored by thymus grafts SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SUB-MANDIBULAR GLANDS; ADULT-RAT HEPATOCYTES; MECHANISMS; INDUCTION; LIVER AB We previously observed in vivo that a neonatal thymus grafted into old mice can correct age-related changes such as occurrence of hepatocyte tetraploid nuclei and impaired isoproterenol-induced DNA synthesis in submandibular glands. The aim of the present paper was to study the influence of age and thymus on Basal and beta-adrenergic-stimulated DNA synthesis using primary cultures of mouse hepatocytes. In the absence of any adrenergic agents, cells from young mice show peak DNA synthesis Between 36 and 48 h; old mice show a similar time coarse, but the peak is significantly reduced statistically. The main result is represented by the behavior of hepatocytes from old thymus-grafted mice, which recover the levels of [H-3]-thymidine incorporation toward young-like values. Grafted animals also show a correction of total DNA content that is increased in old mice. The addition of isoproterenol does not modify the DNA synthetic pattern, whereas the antagonist propranolol causes a slight But statistically significant decrease. C1 INRCA, Ctr Biochem, Gerontol Res Dept, I-60121 Ancona, Italy. NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH,Hopkins Bayview Med Ctr, Baltimore, MD 21224 USA. RP Piantanelli, L (reprint author), INRCA, Ctr Biochem, Gerontol Res Dept, Via Birarelli 8, I-60121 Ancona, Italy. NR 27 TC 9 Z9 9 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 1998 VL 53 IS 2 BP B111 EP B116 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZB926 UT WOS:000072522200005 PM 9520906 ER PT J AU Garnett, NL DeHaven, WR AF Garnett, NL DeHaven, WR TI A word from the government SO LAB ANIMAL LA English DT Editorial Material C1 NIH, Off Protect Res Risks, Div Anim Welf, Bethesda, MD 20892 USA. USDA, Inspect Serv, Washington, DC USA. RP Garnett, NL (reprint author), NIH, Off Protect Res Risks, Div Anim Welf, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 1998 VL 27 IS 3 BP 21 EP 21 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA ZB086 UT WOS:000072434300011 ER PT J AU Bisgaard, HC Santoni-Rugiu, E Nagy, P Thorgeirsson, SS AF Bisgaard, HC Santoni-Rugiu, E Nagy, P Thorgeirsson, SS TI Modulation of the plasminogen activator plasmin system in rat liver regenerating by recruitment of oval cells SO LABORATORY INVESTIGATION LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; HEPATIC TRANSCRIPTION FACTORS; FACTOR SCATTER FACTOR; UROKINASE-RECEPTOR; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; EARLY RESPONSE; FACTOR-ALPHA; EXPRESSION; GENE AB The proteolytic cascade involving plasminogen activators and plasmin appears to have an important function in tissue regeneration. We have investigated the expression and cellular localization of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator receptor (uPAR), and plasminogen activator inhibitor-1 (PAl-1) as well as plasminogen activation in rat liver regeneration by recruitment of progenitor (oval) cells. Using a model in which surgical partial hepatectomy is combined with feeding of 2-acetylaminofluorene (2-AAF) to induce liver regeneration by proliferation and differentiation of oval cells, expression of uPA, uPAR, and PAl-1 was detected by immunohistochemistry mainly in the duct-like formations of expanding oval cells. Plasminogen activation, as assessed by direct zymography on frozen liver sections, was located over the expanding oval cell populations but not over mature hepatocytes. Plasminogen activation was not detected in control liver. Expression of uPA, uPAR, and PAl-1, as assessed by immunohistochemical and Northern blot analyses, was also observed, when cells located in and in close proximity to the bile epithelial structures were activated to enter DNA-synthesis in response to 2-AAF, and after in vivo infusion of various growth factors. Given the physiologic function of plasminogen activation in fibrinolysis, and plasminogen activators in activation of latent growth factors, the selective expression of the plasminogen activator/plasmin proteolytic cascade in oval cells expanding during liver regeneration in response to the combination of 2-AAF and partial hepatectomy, may confer a proliferative advantage to these cell populations in an extracellular matrix containing both fibrin and latent growth factors. C1 Roskilde Univ Ctr, Dept Life Sci & Chem, DK-4000 Roskilde, Denmark. NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Semmelweis Univ Med, Inst Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. RP Bisgaard, HC (reprint author), Roskilde Univ Ctr, Dept Life Sci & Chem, Bldg 16-1,Marbjergvej 35, DK-4000 Roskilde, Denmark. NR 49 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 1998 VL 78 IS 3 BP 237 EP 246 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA ZB826 UT WOS:000072511900003 PM 9520937 ER PT J AU Zwartjes, RE West, H Hattar, S Ren, XY Noel, F Nunez-Regueiro, M MacPhee, K Homayouni, R Crow, MT Byrne, JH Eskin, A AF Zwartjes, RE West, H Hattar, S Ren, XY Noel, F Nunez-Regueiro, M MacPhee, K Homayouni, R Crow, MT Byrne, JH Eskin, A TI Identification of specific mRNAs affected by treatments producing long-term facilitation in Aplysia SO LEARNING & MEMORY LA English DT Article ID PROTEIN-KINASE-II; SQUID GIANT SYNAPSE; NEURONS INNERVATING TAIL; CAMP-RESPONSIVE ELEMENT; SENSORY NEURONS; PHOSPHOGLYCERATE KINASE; MESSENGER-RNAS; CALMODULIN GENE; NERVOUS-SYSTEM; NEUROTRANSMITTER RELEASE AB Neural correlates of long-term sensitization of defensive withdrawal reflexes in Aplysia occur in sensory neurons in the pleural ganglia and can be mimicked by exposure of these neurons to serotonin (5-HT). Studies using inhibitors indicate that transcription is necessary for production of long-term facilitation by 5-MT. Several mRNAs that change in response to 5-HT have been identified, but the molecular events responsible for long-term facilitation have not yet been fully described. To detect additional changes in mRNAs, we investigated the effects of 5-HT (1.5 hr) on levels of mRNA in pleural-pedal ganglia using in vitro translation. Four mRNAs were affected by 5-MT, three of which were identified as calmodulin (CaM), phosphoglycerate kinase (PGK), and a novel gene product (protein 3). Using RNase protection assays, we found that 5-HT increased all three mRNAs in the pleural sensory neurons. CaM and protein 3 mRNAs were also increased in the sensory neurons by sensitization training. Furthermore, stimulation of peripheral nerves of pleural-pedal ganglia, an in vitro analog of sensitization training, increased the incorporation of labeled amino acids into CaM, PGK, and protein 3. These results indicate that increases in CaM, PGK, and protein 3 are part of the early response of sensory neurons to stimuli that produce long-term facilitation, and that CaM and protein 3 could have a role in the generation of long-term sensitization. C1 Univ Houston, Dept Biochem & Biophys Sci, Houston, TX 77204 USA. Univ Texas, Sch Med, Dept Neurobiol & Anat, Houston, TX 77030 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Eskin, A (reprint author), Univ Houston, Dept Biochem & Biophys Sci, Houston, TX 77204 USA. RI Homayouni, Ramin/B-3547-2009 OI Homayouni, Ramin/0000-0003-0186-5076 FU NIMH NIH HHS [K05 MH00649]; NINDS NIH HHS [NS 19895, NS 28462] NR 95 TC 6 Z9 7 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD MAR-APR PY 1998 VL 4 IS 6 BP 478 EP 495 DI 10.1101/lm.4.6.478 PG 18 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZN026 UT WOS:000073600500004 PM 10701873 ER PT J AU Guida, LC Charlton, P Gilbert, DJ Jenkins, NA Copeland, NG Nicholls, RD AF Guida, LC Charlton, P Gilbert, DJ Jenkins, NA Copeland, NG Nicholls, RD TI Genetic mapping of the galanin-GMAP (Galn) gene to mouse Chromosome 19 SO MAMMALIAN GENOME LA English DT Article ID LINKAGE MAP C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ctr Human Genet, Cleveland, OH 44106 USA. Univ N Carolina, Dept Pediat, Div Endocrinol, Chapel Hill, NC 27599 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Nicholls, RD (reprint author), Case Western Reserve Univ, Dept Genet, 10900 Euclid Ave, Cleveland, OH 44106 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 1998 VL 9 IS 3 BP 240 EP 242 DI 10.1007/s003359900733 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YY759 UT WOS:000072181500012 PM 9501310 ER PT J AU Steingrimsson, E Favor, J Ferre-D'Amare, AF Copeland, NG Jenkins, NA AF Steingrimsson, E Favor, J Ferre-D'Amare, AF Copeland, NG Jenkins, NA TI Mitf(mi-enu122) is a missense mutation in the HLH dimerization domain SO MAMMALIAN GENOME LA English DT Article ID WAARDENBURG SYNDROME; DNA-BINDING; MICROPHTHALMIA; GENE; PROTEIN; LOCUS C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. GSF, Inst Mammalian Genet, D-85764 Neuherberg, Germany. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. RP Steingrimsson, E (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 1998 VL 9 IS 3 BP 250 EP 252 DI 10.1007/s003359900736 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YY759 UT WOS:000072181500015 PM 9501313 ER PT J AU Kopp-Schneider, A Portier, C Bannasch, P AF Kopp-Schneider, A Portier, C Bannasch, P TI A model for hepatocarcinogenesis treating phenotypical changes in focal hepatocellular lesions as epigenetic events SO MATHEMATICAL BIOSCIENCES LA English DT Article ID RAT HEPATIC PRENEOPLASIA; ENZYME-ALTERED FOCI; N-NITROSOMORPHOLINE; CELLULAR PHENOTYPE; TIME-DEPENDENCE; QUANTITATIVE-ANALYSIS; MULTISTAGE MODEL; STOP EXPERIMENTS; ORAL-EXPOSURE; MOUSE SKIN AB The major paradigm for mathematically describing the carcinogenic process has been through the use of multistage models. Multistage models are made up of numerous compartments representing cells in various stages on the way to malignancy and where movement from one cell class to another is assumed to have exponential waiting time. Once a cell is in a particular class, clonal expansion through a linear birth-death process increases the size of the compartment, These models are characterized by movement of single cells from one compartment to another rather than clonal colonies of cells. However, there is some evidence to suggest that, in certain organs for certain types of agents, preneoplastic lesions with different phenotypes arise directly from an entire clonal colony rather than from a single cell within that colony. This manuscript describes a simple mathematical model of carcinogenesis using both persistent changes of single or several cells (to start the process) and shifting of colonies to describe the stages of the model. Likelihoods for the use of the model with data on colonies of preneoplastic lesions are described and applied to real data. (C) 1998 Elsevier Science Inc. All rights reserved. C1 German Canc Res Ctr, Dept Biostat 2070, D-69120 Heidelberg, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. German Canc Res Ctr, Dept Cell Pathol, D-69120 Heidelberg, Germany. RP Kopp-Schneider, A (reprint author), German Canc Res Ctr, Dept Biostat 2070, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 23 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD MAR PY 1998 VL 148 IS 2 BP 181 EP 204 DI 10.1016/S0025-5564(97)10007-4 PG 24 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA ZP323 UT WOS:000073740800005 PM 9610106 ER PT J AU Potosky, AL Breen, N Graubard, BI Parsons, PE AF Potosky, AL Breen, N Graubard, BI Parsons, PE TI The association between health care coverage and the use of cancer screening tests - Results from the 1992 National Health Interview Survey SO MEDICAL CARE LA English DT Article DE access to health care; health insurance; health maintenance organization; breast neoplasms; mammography; cervix neoplasms; Pap smear; colon neoplasms; fecal occult blood test; sigmoidoscopy ID FECAL OCCULT BLOOD; COLORECTAL-CANCER; CERVICAL-CANCER; BREAST-CANCER; CONTROLLED TRIAL; PREVENTIVE CARE; PROSTATE-CANCER; MORTALITY; MAMMOGRAPHY; INSURANCE AB OBJECTIVES. The authors investigated whether utilization of six different cancer screening tests (mammography, clinical breast exam, Pap smear, Fecal Occult Blood Test, and Digital rectal exam) varied according to type of health care coverage. METHODS. Data on the use of cancer screening tests and coverage in two age groups from a 1992 nationally representative cross-sectional survey of approximately 9,400 adults were analyzed. Multiple logistic regression analysis was used to estimate proportions of persons screened according to type and extent of coverage, adjusted for socioeconomic, demographic, and health status characteristics. RESULTS. Persons aged 40 to 64 years with Medicaid coverage were equally as likely to receive five of six cancer screening tests as those with private fee-for-service coverage, and both groups were much more likely to be screened (70% higher for all six tests) than those who had no coverage. In contrast, persons aged 65 years and older who had supplemental private fee-for-service insurance in addition to Medicare were more likely to receive five of six tests than those with Medicare and Medicaid or those with Medicare only. For all six screening tests, managed care enrollees at all ages were approximately 10% more likely to be screened than persons enrolled in private fee-for-service plans. Fecal Occult Blood Test (25% versus 20%) and digital rectal exams (44% versus 38%) in persons aged 40 to 64 years and mammography (59% versus 48%) and Fecal Occult Blood Test screening (38% versus 30%) in the elderly were significantly more frequent for persons in managed care plans. CONCLUSIONS. The extent of fee-for-service insurance coverage in the traditional indemnity US health care system was positively associated with the use of cancer screening tests. The authors found less difference in use of cancer screening between managed care and fee-for-service care in 1992 than we expected based on earlier research comparing use of preventive services in health maintenance organizations with fee-for-service care. C1 NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Interview Stat, Hyattsville, MD 20782 USA. RP Potosky, AL (reprint author), NCI, Appl Res Branch, Div Canc Control & Populat Sci, EPN Room 313,6130 Execut Blvd MSC 7344, Bethesda, MD 20892 USA. NR 50 TC 152 Z9 152 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 1998 VL 36 IS 3 BP 257 EP 270 DI 10.1097/00005650-199803000-00004 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZB388 UT WOS:000072467300004 PM 9520952 ER PT J AU Chung, D Villafania, A Anwar, K Amar, S Rijhwani, K Kung, HF Adler, V Ronai, Z Brandt-Rauf, P Yamaizumi, Z Pincus, MR AF Chung, D Villafania, A Anwar, K Amar, S Rijhwani, K Kung, HF Adler, V Ronai, Z Brandt-Rauf, P Yamaizumi, Z Pincus, MR TI Mutual dependence of jun-N-terminal kinase and protein kinase C on the oncogenic ras-p21 protein-induced mitogenic signalling pathway SO MEDICAL SCIENCE RESEARCH LA English DT Article DE oncogenic p21 protein; jun kinase (JNK) and jun proteins; protein kinase C (PKC); oocyte maturation; PKC inhibitor; JNK inhibitory protein ID OOCYTE MATURATION; RAS PROTEINS; ACTIVATION; INDUCTION AB We have previously presented evidence that there is a distinct oncogenic ras-p21 protein mitogenic signal transduction pathway causing maturation of oocytes. This pathway involves a direct interaction between p21 and jun-N terminal kinase (JNK) and its target, jun protein and activation of protein kinase C (PKC). The question arises as to the relationship between JNK and PKC on the oncogenic ras-p21 signal transduction pathway. We have now found that a selective inhibitor of PKC, CGP 41 251, blocks JNK-induced oocyte maturation and that a newly isolated JNK inhibitory protein of Mr 26 kDa blocks PKC-induced oocyte maturation. This reciprocal inhibition of JNK by a PKC inhibitor and PKC by a JNK inhibitor suggests that each protein requires the activation of the other protein. A possible explanation of the mutual activation requirement is that both proteins activate jun. Phosphorylation of jun by one protein may facilitate phosphorylation by the other protein. That jun is critical on the oncogenic ras pathway is supported by the finding that a dominant negative mutant of jun blocks ras-p21 -induced oocyte maturation in a specific manner. (C) 1998 Chapman & Hall Ltd. C1 Vet Affairs Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Long Isl Univ, Dept Chem, Brooklyn, NY USA. Long Isl Univ, Dept Biol, Brooklyn, NY USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. NCI, Lab Biochem Physiol, Frederick Canc Res Facil, Frederick, MD 21702 USA. CUNY, Mt Sinai Med Ctr, Ruttenberg Canc Ctr, New York, NY 10029 USA. Columbia Univ, Sch Publ Hlth, Div Environm Sci, New York, NY 10032 USA. Natl Canc Inst, Tokyo, Japan. RP Pincus, MR (reprint author), Vet Affairs Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. OI RONAI, ZEEV/0000-0002-3859-0400 NR 12 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-8951 J9 MED SCI RES JI Med. Sci. Res. PD MAR PY 1998 VL 26 IS 3 BP 147 EP 150 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZH854 UT WOS:000073154100002 ER PT J AU Gussio, R Pattabiraman, N Kellogg, GE Zaharevitz, DW AF Gussio, R Pattabiraman, N Kellogg, GE Zaharevitz, DW TI Use of 3D QSAR methodology for data mining the National Cancer Institute repository of small molecules: Application to HIV-1 reverse transcriptase inhibition SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID 3-DIMENSIONAL CHEMICAL STRUCTURES; CONFORMATIONALLY FLEXIBLE MOLECULES; DATABASES; DESIGN; QUERIES; POTENT; FILES AB A three-dimensional (3D) stereoelectronic pharmacophore developed from a 3D quantitative structure-activity relationship (QSAR) investigation formed the basis of the development of a two-phase data-mining methodology to uncover novel leads to inhibit human immunodeficiency virus type 1 (HIV-1) reverse transcriptase at the nonnucleoside binding site. The database searching phase employed a field search for ligand requirements (such as log P, molecular volume) that were accessible from the database keys. Next, a 3D database search was performed that used an automated fitting procedure and the calculation of several binding parameters. These binding parameters were used to test the hits by a discriminant function that was previously trained to recognize active from inactive analogs. During the structural evaluation phase of the methodology, conformational properties and complementary receptor features of the hits were examined by 2D and 3D evaluations, which were followed by molecular modeling investigations. When this method was applied to a test database, an improvement from 6.4% to 100% active analogs was achieved. (C) 1998 Academic Press. C1 NCI, Dev Therapeut Program, Informat Technol Branch, Target Struct Based Drug Discovery Grp, Rockville, MD 20852 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Sch Pharm, Richmond, VA 23298 USA. RP Gussio, R (reprint author), NCI, Dev Therapeut Program, Informat Technol Branch, Target Struct Based Drug Discovery Grp, 811 Execut Plaza N,6130 Execut Blvd, Rockville, MD 20852 USA. EM gussio@ncifcrf.gov RI Kellogg, Glen/A-8008-2011 NR 30 TC 21 Z9 21 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAR PY 1998 VL 14 IS 3 BP 255 EP 263 DI 10.1006/meth.1998.0582 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK966 UT WOS:000073385500003 PM 9571082 ER PT J AU Friedman, A Stanton, JP Gnjidic, M Fant, RV Pickworth, WB AF Friedman, A Stanton, JP Gnjidic, M Fant, RV Pickworth, WB TI Delayed auditory feedback during smoking cessation SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE delayed auditory feedback (DAF); tobacco withdrawal; cognitive performance ID TOBACCO WITHDRAWAL; PERFORMANCE; ABSTINENCE AB Delays between speech production and hearing, delayed auditory feedback (DAF), reduce speech and reading rates. Smoking cessation in heavy smokers causes subjective reports of difficulty in concentration, decrements in cognitive performance, and EEG changes. The purpose of the present study was to determine if tobacco cessation disrupts linguistic processing as modeled by the DAF paradigm. Smokers (n = 14) were tested on 3 d of ad libitum smoking and 3 d no smoking. At each session, they read a word list (24 words) and a story (about 57 words) with and without delay (220 msec). The delay significantly decreased reading speed of the story from 3.4 to 2.9 words per second (wps) and of list from 2.1 to 1.7 wps. However, tobacco cessation had no significant effect on reading speed and no interaction with DAF. Although tobacco withdrawal slows performance on cognitive tasks, linguistic processing modeled by DAF is preserved. DAF may prove useful for the study of other drug classes and drug withdrawal states. (C) 1998 Prous Science. All rights reserved. C1 NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. Coll Notre Dame Maryland, Baltimore, MD USA. RP Pickworth, WB (reprint author), NIDA, Addict Res Ctr, POB 5180, Baltimore, MD 21224 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD MAR PY 1998 VL 20 IS 2 BP 147 EP 153 DI 10.1358/mf.1998.20.2.485654 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZL771 UT WOS:000073469900008 PM 9604857 ER PT J AU Munderloh, UG Hayes, SF Cummings, J Kurtti, TJ AF Munderloh, UG Hayes, SF Cummings, J Kurtti, TJ TI Microscopy of spotted fever rickettsia movement through tick cells SO MICROSCOPY AND MICROANALYSIS LA English DT Article DE Rickettsia; tick; Ixodes scapularis; Rhipicephalus appendiculatus; f-actin; rickettsial dispersal; rickettsial outer membrane protein B (rOmpB); tick cell culture ID LISTERIA-MONOCYTOGENES; ULTRASTRUCTURAL ANALYSIS; INFECTION; ACTIN; FIBROBLASTS; PROWAZEKII; SPREAD AB Spotted fever group (SFG) rickettsiae are obligate intracellular prokaryotes that include tick-borne pathogens of vertebrates as well as nonpathogenic organisms living in symbiotic association with their lick hosts. We investigated the ability of SFG rickettsiae to move between and within host cells using tick cell culture and a SFG rickettsial isolate from a lone star tick (Amblyomma americanum) collected in Missouri. The isolate (MOAa), which is closely related to Rickettsia montana, grew in cell lines from the ticks Ixodes scapularis and Rhipicephalus appendiculatus. Transmission electron microscopy demonstrated that immediately following entry into lick cells, rickettsiae escaped from the host cell membrane, and intracellular rickettsiae came to lie in direct contact with host-cell cytoplasm. There was evidence of damage to the endoplasmic reticulum membrane which was broken down into vesicular structures. When rickettsiae exited host cells, host membrane stretched around them but was lost before re-entry. Use of a fluorescein-tagged monoclonal antibody to rickettsial outer membrane protein B and rhodamine-labeled phalloidin demonstrated association of actin tails with rickettsiae and suggested that SFG rickettsiae utilized host cytoskeletal components for movement. During early stages of infection, when cells harbored only one or a few organisms, "comet tails" of F-actin formed on one end of rickettsial cells, presumably pushing them ahead. Actin tails were not seen during later stages of infection when lick cells became completely filled with rickettsiae. C1 Univ Minnesota, Dept Entomol, St Paul, MN 55108 USA. NIH, Microscopy Branch, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Munderloh, UG (reprint author), Univ Minnesota, Dept Entomol, 1980 Folwell Ave, St Paul, MN 55108 USA. NR 29 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1431-9276 J9 MICROSC MICROANAL JI Microsc. microanal. PD MAR-APR PY 1998 VL 4 IS 2 BP 115 EP 121 PG 7 WC Materials Science, Multidisciplinary; Microscopy SC Materials Science; Microscopy GA ZQ328 UT WOS:000073847500001 ER PT J AU Ma, W Barker, JL AF Ma, W Barker, JL TI GABA, GAD, and GABA(A) receptor alpha 4, beta 1, and gamma 1 subunits are expressed in the late embryonic and early postnatal neocortical germinal matrix and coincide with gliogenesis SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE brain development; mitotic cycle; BrdU; immunocytochemistry; in situ hybridization ID RAT SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; GLUTAMIC-ACID DECARBOXYLASE; MESSENGER-RNAS; PRENATAL DEVELOPMENT; A RECEPTOR; CELLS; BRAIN; PROLIFERATION; NEURONS AB Increasing evidence indicates that the classical, fast-acting neurotransmitter gamma-amino butyric acid (GABA) may initially act as morphogen in cell proliferation and differentiation via specific receptors. In view of the potential roles for GABA in central nervous system development, we examined the expression of GABA, GABA(A) receptor beta(1) and gamma(1) subunits by immunocytochemistry and the expression of transcripts for two GABA-synthesizing enzymes, glutamate decarboxylase (GAD(65), GAD(67) mRNAs), and for alpha 4, beta 1, and gamma 1 subunits of GABA(A) receptor by in situ hybridization in the developing neocortex. Tissue sections were taken from embryonic days (E) 17 and E20 embryos and newborn rats (PO). The embryos' mothers and newborn rats had been injected with 5-bromo-2'-deoxyuridine (BrdU) and had survived for 2 hours. At E17, BrdU-positive cells were largely restricted in the synthetic zone at the ventricular margin when cortical neurogenesis was still active. GAD mRNAs and GABA immunoreactivity were detected in the subventricular zone, while alpha 4, beta(1), and gamma(1) subunits were abundant in the ventricular zone. At E20 and PO, when neurogenesis had largely ceased and gliogenesis had commenced, BrdU-positive cells were found throughout the ventricular zone with GABA, GAD mRNAs, and alpha 4, beta(1), and gamma(1) subunits. GABA, GAD mRNAs and alpha 4, beta 1, and gamma 1 subunit signals intensified in the ventricular zone from E17 to PO as gliogenesis preceded. Thus, specific components of a putative GABAergic circuit are expressed in cells of the ventricular zone during the late embryonic/early postnatal period coincident with gliogenesis, suggesting a role for GABA in glial cell proliferation. (C) 1998 Wiley-Liss, Inc. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Ma, W (reprint author), SAIC, Biotechnol Res & Applicat Div, 6 Taft Court,Suite 300, Rockville, MD 20850 USA. EM wu.ma@cpmx.saic.com NR 41 TC 20 Z9 21 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 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD MAR 1 PY 1998 VL 40 IS 5 BP 398 EP 407 DI 10.1002/(SICI)1097-0029(19980301)40:5<398::AID-JEMT6>3.0.CO;2-N PG 10 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA ZB036 UT WOS:000072428400006 PM 9527049 ER PT J AU Roberts, AB AF Roberts, AB TI Molecular and cell biology of TGF-beta SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Article DE TGF-beta; isoforms; promoters; latent form ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; GENE-EXPRESSION; BREAST-CANCER; PLASMA-LEVELS; AP-1 COMPLEX; BINDING-SITE; HOST-DEFENSE; PROMOTER; MICE AB The TGF-beta s are a remarkable set of peptides consisting of three highly homologous isoforms, TGF-beta 1, 2, and 3. Distinguished initially for their ability to inhibit the growth of most epithelial and hematopoietic cells and to regulate the production of extracellular matrix by mesenchymal cells, these peptides are now known to act via autocrine, paracrine, and endocrine modes to control a wide variety of developmental processes and to play key roles in the pathogenesis of many diseases including especially fibrotic diseases, parasitic diseases, autoimmune diseases, and carcinogenesis. The activity of these peptides is under tight control by processes including regulation of the expression of the isoforms and their receptors and of the trafficking and activation of their latent forms. C1 NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Chemoprevent Lab, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM robertsa@dce41.nci.nih.gov NR 56 TC 257 Z9 268 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD MAR-JUN PY 1998 VL 24 IS 2-3 BP 111 EP 119 DI 10.1159/000057358 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA770 UT WOS:000072399100002 PM 9525693 ER PT J AU Bottinger, EP Kopp, JB AF Bottinger, EP Kopp, JB TI Lessons from TGF-beta transgenic mice SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Article DE TGF-beta; transgenic mice; disease; inflammation; fibrosis; development ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE; CENTRAL-NERVOUS-SYSTEM; EXTRACELLULAR-MATRIX; BREAST-CANCER; PLASMA-LEVELS; IN-VIVO; EXPRESSION; TGF-BETA-1; FACTOR-BETA-1 AB Aberrant expression of TGF-beta and/or receptor/signaling function is present in a wide variety of disease processes, Overexpression of TGF-beta isoforms in transgenic mice using tissue-specific promoters has provided model systems to study the effects of increased activity of TGF-beta in the intact organism. We will review the pertinent features of some of these models, and discuss new insights provided by these studies into regulation and role of TGF-beta in health and disease. C1 Yeshiva Univ Albert Einstein Coll Med, Div Nephrol, Bronx, NY 10461 USA. NIDDKD, Kidney Dis Sect, Metab Dis Branch, Bethesda, MD 20892 USA. RP Bottinger, EP (reprint author), Yeshiva Univ Albert Einstein Coll Med, Div Nephrol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM botting2@aecom.yu.edu NR 52 TC 23 Z9 24 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD MAR-JUN PY 1998 VL 24 IS 2-3 BP 154 EP 160 DI 10.1159/000057364 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA770 UT WOS:000072399100008 PM 9525699 ER PT J AU Letterio, JJ Bottinger, EP AF Letterio, JJ Bottinger, EP TI TGF-beta knockout and dominant-negative receptor transgenic mice SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Article DE TGF-beta; mice; transgenic; knockout; inflammation; development; malignancy ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GROWTH-FACTOR-BETA-1 NULL MICE; TRANSFORMING GROWTH-FACTOR-BETA-1; MESSENGER-RNA; ANTIGEN EXPRESSION; ADULT TISSUES; HOST-DEFENSE; FACTOR-BETA-1; MOUSE AB Use of homologous recombination and transgenic technologies have provided mouse models to study the physiological roles of the three mammalian TGF-beta isoforms, and their regulation in the context of the intact animal. Mice harboring null mutations for TGF-beta isoforms demonstrate that each exerts discrete nonoverlapping functions during development. TGF-beta 1 null mice reveal a crucial role for this cytokine in modulation of the immune system, with evidence for altered development, activation and function of various immune cell populations. New approaches to tissue-and cell-restricted disruption of TGF-beta signaling pathways in transgenic mice carrying dominant-negative mutant TGF-beta receptors will be discussed. C1 NCI, Chemoprevent Lab, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Letterio, JJ (reprint author), NCI, Chemoprevent Lab, NIH, Bldg 41,Room C629, Bethesda, MD 20892 USA. EM Letterio@pop.nci.nih.gov NR 56 TC 43 Z9 68 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD MAR-JUN PY 1998 VL 24 IS 2-3 BP 161 EP 167 DI 10.1159/000057365 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZA770 UT WOS:000072399100009 PM 9525700 ER PT J AU Jakubczak, JL LaRochelle, WJ Merlino, G AF Jakubczak, JL LaRochelle, WJ Merlino, G TI NK1, a natural splice variant of hepatocyte growth factor scatter factor, is a partial agonist in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR AUTOCRINE LOOP; C-MET RECEPTOR; ABNORMAL-DEVELOPMENT; EPITHELIAL-CELLS; CARCINOMA-CELLS; TRANSGENIC MICE; TYROSINE KINASE; FACTOR BINDS; EXPRESSION; HGF AB Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen, motogen, and morphogen for epithelial cells expressing its tyrosine kinase receptor, the c-met proto-oncogene product, and is required for normal development in the mouse. Inappropriate stimulation of Met signal transduction induces aberrant morphogenesis and oncogenesis in mice and has been implicated in human cancer. NK1 is a naturally occurring HGF/SF splice variant composed of only the amino terminus and first kringle domain. While the biological activities of NK1 have been controversial, in vitro data suggest that it may have therapeutic value as an HGF/SF antagonist. Here, we directly test this hypothesis in vivo by expressing mouse NK1 in transgenic mice and comparing the consequent effects with those observed for mice carrying an HGF/SF transgene. Despite robust expression, NK1 did not behave as an HGF/SF antagonist in vivo. Instead, NK1-transgenic mice displayed most of the phenotypic characteristics associated with HGF/SF-transgenic mice, including enlarged livers, ectopic skeletal-muscle formation, progressive renal disease, aberrant pigment cell localization, precocious mammary lobuloalveolar development, and the appearance of mammary, hepatocellular, and melanocytic tumors. And like HGF/SF-transgenic livers, NK1 livers had higher levels of tyrosine-phosphorylated complexes associated with Met, suggesting that the mechanistic basis for the effects of NK1 overexpression in vivo was autocrine activation of Met. We conclude that NK1 acts in vivo as a partial agonist. As such, the efficacy of NK1 as a therapeutic HGF/SF antagonist must be seriously questioned. C1 NCI, Mol Genet Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Mol Genet Sect, Mol Biol Lab, NIH, Bldg 37,Room 2E24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov NR 42 TC 48 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1998 VL 18 IS 3 BP 1275 EP 1283 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YY284 UT WOS:000072131700015 PM 9488442 ER PT J AU Williams, BL Schreiber, KL Zhang, WG Wange, RL Samelson, LE Leibson, PJ Abraham, RT AF Williams, BL Schreiber, KL Zhang, WG Wange, RL Samelson, LE Leibson, PJ Abraham, RT TI Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor: Reconstitution studies in a ZAP-70-deficient jurkat T-Cell line SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; MICE LACKING; PHOSPHOLIPASE C-GAMMA-1; ZAP-70 KINASE; ZETA-CHAIN; ACTIVATION; PHOSPHORYLATION AB T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-cell activation and development, However, progress toward a detailed understanding of the regulation and function of ZAP-70 during TCR signaling has been hampered by the lack of a suitable T-cell model for biochemical and genetic analyses, In this report, we describe the isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from the Jurkat T-cell line. The P116 cell line displays severe defects in TCR-induced signaling functions, including protein tyrosine phosphorylation, intracellular Ca2+ mobilization, and interleukin-2 promoter-driven transcription, These signaling defects were fully reversed by reintroduction of catalytically active versions of either Syk or ZAP-70 into the P116 cells, However, in contrast to ZAP-70 expression, Syk expression triggered a significant degree of cellular activation in the absence of TCR ligation, Transfection experiments with ZAP-70-Syk chimeric proteins indicated that both the amino-terminal regulatory regions and the carboxy-terminal catalytic domains of Syk and ZAP-70 contribute to the distinctive functional properties of these PTKs. These studies underscore the crucial role of ZAP-70 in TCR signaling and offer a powerful genetic model for further analyses of ZAP-70 regulation and function in T cells. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Inst Cardiol Montreal, Montreal, PQ H1T 1C8, Canada. NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Abraham, RT (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, 301 Guggenheim Bldg, Rochester, MN 55905 USA. FU NCI NIH HHS [CA47752, R01 CA047752]; NIGMS NIH HHS [R01 GM047286, GM47286] NR 63 TC 203 Z9 203 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1998 VL 18 IS 3 BP 1388 EP 1399 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YY284 UT WOS:000072131700027 PM 9488454 ER PT J AU Gorospe, M Wang, XT Holbrook, NJ AF Gorospe, M Wang, XT Holbrook, NJ TI p53-dependent elevation of p21(Waf1) expression by UV light is mediated through mRNA stabilization and involves a vanadate-sensitive regulatory system SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID 3' UNTRANSLATED REGION; PROTEIN-KINASE PATHWAY; URIDINE BINDING-FACTOR; P53-INDEPENDENT PATHWAY; MESSENGER-RNA; ANTICANCER AGENTS; GENOTOXIC STRESS; GENE-EXPRESSION; UP-REGULATION; CELL-DEATH AB Exposure of mammalian cells to adverse stimuli triggers the expression of numerous stress response genes, many of which are presumed to enhance cell survival. In this study, we examined the mechanisms contributing to the induction of p21(Waf1) by stress and its influence on the survival of cells subjected to short-wavelength UVC irradiation. UVC was found to elevate p21(Waf1) mRNA expression in mouse embryonal fibroblasts (MEFs) and human colorectal carcinoma (RK0) cells in a p53-dependent manner, The lack of p21(Waf1) induction in p53-deficient MEFs and RKO cells correlated with diminished cell survival following WC irradiation. Unexpectedly, UVC treatment was also found to block the induction of p21(Waf1) by various stress-inducing agents such as mimosine in the p53-deficient cells, Additional studies indicated that induction of p21(Waf1) by UVC occurs primarily through enhanced mRNA stability rather than increased transcription; in p53(-/-) MEFs, failure to elevate p21(Waf1) after treatment with UVC appears to be due to their inability to stabilize the p21(Waf1) transcripts, Treatment of the p53(-/-) MEFs with the protein tyrosine phosphatase inhibitor vanadate reversed the WC-induced block on p21(Waf1) induction and resulted in their enhanced survival following irradiation. Thus, in cells bearing normal p53, UVC augments p21(Waf1) expression by increasing the half-life of p21(Waf1) mRNA; without p53, p21(Waf1) mRNA remains unstable after UVC, apparently due to a pathway involving tyrosine phosphatase activity. C1 NIA, Sect Gene Express Aging, Biol Chem Lab, NIH,GRC, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), NIA, Sect Gene Express Aging, Biol Chem Lab, NIH,GRC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM nikki-holbrook@nih.gov NR 49 TC 98 Z9 98 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1998 VL 18 IS 3 BP 1400 EP 1407 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YY284 UT WOS:000072131700028 PM 9488455 ER PT J AU Drysdale, CM Jackson, BM McVeigh, R Klebanow, ER Bai, Y Kokubo, T Swanson, M Nakatani, Y Weil, PA Hinnebusch, AG AF Drysdale, CM Jackson, BM McVeigh, R Klebanow, ER Bai, Y Kokubo, T Swanson, M Nakatani, Y Weil, PA Hinnebusch, AG TI The Gcn4p activation domain interacts specifically in vitro with RNA polymerase II holoenzyme, TFIID, and the Adap-Gcn5p coactivator complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TATA-BINDING PROTEIN; MEDIATES TRANSCRIPTIONAL ACTIVATION; HYDROPHOBIC AMINO-ACIDS; NF-KAPPA-B; SACCHAROMYCES-CEREVISIAE; IN-VIVO; TRANSACTIVATION DOMAIN; BASAL TRANSCRIPTION; FUNCTIONAL-ANALYSIS; GENETIC-EVIDENCE AB The Gcn4p activation domain contains seven clusters of hydrophobic residues that make additive contributions to transcriptional activation in vivo, We observed efficient binding of a glutathione S-transferase (GST)-Gcn4p fusion protein to components of three different coactivator complexes in Saccharomyces cerevisiae cell extracts, including subunits of transcription factor IID (TFIID) (yeast TAF(II)20 [yTAF(II)20], yTAF(II)60, and yTAF(II)90), the holoenzyme mediator (Srb2p, Srb4p, and Srb7p), and the Adap-Gcn5p complex (Ada2p and Ada3p). The binding to these coactivator subunits was completely dependent on the hydrophobic clusters in the Gcn4p activation domain. Alanine substitutions in single clusters led to moderate reductions in binding, double-cluster substitutions generally led to greater reductions in binding than the corresponding single-cluster mutations, and mutations in four or more clusters reduced binding to all of the coactivator proteins to background levels. The additive effects of these mutations on binding of coactivator proteins correlated with their cumulative effects on transcriptional activation by Gcn4p in vivo, particularly with Ada3p, suggesting that recruitment of these coactivator complexes to the promoter is a cardinal function of the Gcn4p activation domain, As judged by immunoprecipitation analysis, components of the mediator were not associated with constituents of TFIID and Adap-Gcn5p in the extracts, implying that GST-Gcn4p interacted with the mediator independently of these other coactivators. Unexpectedly, a proportion of Ada2p coimmunoprecipitated with yTAF(II)90, and the yTAF(II)20, -60, and -90 proteins were coimmunoprecipitated with Ada3p, revealing a stable interaction between components of TFIID and the Adap-Gcn5p complex. Because GST-Gcn4p did not bind specifically to highly purified TFIID, Gcn4p may interact with TFIID via the Adap-Gcn5p complex or some other adapter proteins. The ability of Gcn4p to interact with several distinct coactivator complexes that are physically and genetically linked to TATA box-binding protein can provide an explanation for the observation that yTAF(II) proteins are dispensable for activation by Gcn4p in vivo. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Bldg 6A,Room B1-A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov FU NCI NIH HHS [T32 CA009385, CA09385]; NIGMS NIH HHS [GM52461, R01 GM052461, R56 GM052461] NR 94 TC 77 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1998 VL 18 IS 3 BP 1711 EP 1724 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YY284 UT WOS:000072131700061 PM 9488488 ER PT J AU Auer, KL Contessa, J Brenz-Verca, S Pirola, L Rusconi, S Cooper, G Abo, A Wymann, MP Davis, RJ Birrer, M Dent, P AF Auer, KL Contessa, J Brenz-Verca, S Pirola, L Rusconi, S Cooper, G Abo, A Wymann, MP Davis, RJ Birrer, M Dent, P TI The Ras/Rac1/Cdc42/SEK/JNK/c-Jun cascade is a key pathway by which agonists stimulate DNA synthesis in primary cultures of rat hepatocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; GLYCOGEN-SYNTHASE KINASE-3; GROWTH-FACTOR; C-JUN; INDUCED APOPTOSIS; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; MAMMALIAN-CELLS; FACTOR-ALPHA; IN-VITRO AB The ability of signaling via the JNK (c-Jun NH2-terminal kinase)/stress-activated protein kinase cascade to stimulate or inhibit DNA synthesis in primary cultures of adult rat hepatocytes was examined. Treatment of hepatocytes with media containing hyperosmotic glucose (75 mM final), tumor necrosis factor alpha (TNF alpha, 1 ng/ml final), and hepatocyte growth factor (HGF, 1 ng/ml final) caused activation of JNK1. Glucose, TNF alpha, or HGF treatments increased phosphorylation of c-Jun at serine 63 in the transactivation domain and stimulated hepatocyte DNA synthesis. Infection of hepatocytes with poly-L-lysine-coated adenoviruses coupled to constructs to express either dominant negatives Ras(N17), Rac1(N17), Cdc42(N17), SEK1(-), or JNK1(-) blunted the abilities of glucose, TNF alpha, or HGF to increase JNK1 activity, to increase phosphorylation of c-Jun at serine 63, and to stimulate DNA synthesis. Furthermore, infection of hepatocytes by a recombinant adenovirus expressing a dominant-negative c-run mutant (TAM67) also blunted the abilities of glucose, TNF alpha, and HGF to stimulate DNA synthesis. These data demonstrate that multiple agonists stimulate DNA synthesis in primary cultures of hepatocytes via a Ras/Rac1/Cdc42/SEK/JNK/c-Jun pathway. Glucose and HGF treatments reduced glycogen synthase kinase 3 (GSK3) activity and increased c-Jun DNA binding. Go-infection of hepatocytes with recombinant adenoviruses to express dominant-negative forms of PI3 kinase (p110 alpha/p110 gamma) increased basal GSK3 activity, blocked the abilities of glucose and HGF treatments to inhibit GSK3 activity, and reduced basal c-Jun DNA binding. However, expression of dominant-negative PI3 kinase (p110 alpha/p110 gamma) neither significantly blunted the abilities of glucose and HGF treatments to increase c-Jun DNA binding, nor inhibited the ability of these agonists to stimulate DNA synthesis. These data suggest that signaling by the JNK/stress-activated protein kinase cascade, rather than by the PI3 kinase cascade, plays the pivotal role in the ability of agonists to stimulate DNA synthesis in primary cultures of rat hepatocytes. C1 Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Dept Radiat Oncol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIH, Bethesda, MD 20892 USA. Univ Fribourg, Inst Biochem, CH-1700 Fribourg, Switzerland. Onyx Pharmaceut, Richmond, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Worcester, MA 01605 USA. RP Dent, P (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Dept Radiat Oncol, Box 980058,401 Coll St, Richmond, VA 23298 USA. EM PDENT@HSC.VCU.EDU RI Wymann, Matthias/C-3227-2008 NR 53 TC 113 Z9 115 U1 2 U2 5 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 1998 VL 9 IS 3 BP 561 EP 573 PG 13 WC Cell Biology SC Cell Biology GA ZC159 UT WOS:000072545800002 PM 9487126 ER PT J AU Kamata, T Subleski, M Hara, Y Yuhki, N Kung, HF Copeland, NG Jenkins, NA Yoshimura, T Modi, W Copeland, TD AF Kamata, T Subleski, M Hara, Y Yuhki, N Kung, HF Copeland, NG Jenkins, NA Yoshimura, T Modi, W Copeland, TD TI Isolation and characterization of a bovine neural specific protein (CRMP-2) cDNA homologous to unc-33, a C-elegans gene implicated in axonal outgrowth and guidance SO MOLECULAR BRAIN RESEARCH LA English DT Article DE neural development; bovine CRMP-2; protein kinase; unc-33; chromosome mapping ID LINKAGE MAP; FAMILY; IDENTIFICATION; LEUKEMIA; RECEPTOR; NEURONS; TOAD-64; KINASE; RAT AB We have cloned the cDNA encoding bovine CRMP-2 from bovine brains. A full length cDNA encoding bovine CRMP-2 was isolated and sequenced. The deduced amino acid sequence reveals that the gene encodes a protein of 572 amino acids and is highly homologous to Caenorhabditis elegans unc-33, which controls the guidance and outgrowth of neuronal axons. The CRMP-2 transcript was present in bovine brains but not non-neural tissues, and its protein product existed in both soluble and membrane-bound forms. The expression of CRMP-2 protein and mRNA was upregulated during neuronal differentiation of rat PC12 cells. Immunoprecipitation of PC12 cell extracts shows that CRMP-2 was co-immunoprecipitated with a 190 kDa protein (p190). Both CRMP-2 and p190 were phosphorylated on serine residues in vivo and in vitro in a kinase assay of CRMP-2 immune complexes. Immunocytochemistry shows that CRMP-2 was exclusively localized in both the central and peripheral nervous systems in mouse embryos and detectable in the adult brain although the level of CRMP-2 decreased. The protein was expressed in the axon, dendrite, and cytoplasm of postmitotic neurons and in the cytoplasm of oligodendrocytes and astrocytes. The CRMP-2 gene maps to the region of mouse chromosome 14 syntenic with human chromosome 8p21. Taken together, these data suggest multi-functional roles for CRMP-2 in developing and adult nervous systems, and the biological activity of CRMP-2 could be regulated by phosphorylation reaction. (C) 1998 Elsevier Science B.V. C1 NCI, Lab Biochem Physiol, FCRDC, Frederick, MD 21702 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NCI, Viral Carcinogenesis Lab, FCRDC, Frederick, MD 21702 USA. NCI, SAIC Frederick, IRSP, FCRDC, Frederick, MD 21702 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. NCI, Immunopathol Lab, FCRDC, Frederick, MD 21702 USA. RP Kamata, T (reprint author), NCI, Lab Biochem Physiol, FCRDC, Bldg 567,Rm 152, Frederick, MD 21702 USA. NR 29 TC 43 Z9 44 U1 0 U2 2 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 MAR 1 PY 1998 VL 54 IS 2 BP 219 EP 236 DI 10.1016/S0169-328X(97)00332-X PG 18 WC Neurosciences SC Neurosciences & Neurology GA ZJ462 UT WOS:000073218100004 ER PT J AU Baldwin, WS Barrett, JC AF Baldwin, WS Barrett, JC TI Melatonin: Receptor-mediated events that may affect breast and other steroid hormone-dependent cancers SO MOLECULAR CARCINOGENESIS LA English DT Article DE electromagnetic fields; light at night; estrogen; proliferation ID IODOMELATONIN-BINDING-SITES; NEONATAL RAT PITUITARY; NUCLEAR RECEPTOR; ELECTROMAGNETIC-FIELDS; OCCUPATIONAL EXPOSURE; MAGNETIC-FIELDS; TUMOR PROMOTION; ELECTRIC-POWER; EXPRESSION; BRAIN AB Epidemiological studies have suggested a possible link between extremely low frequency electromagnetic fields (EM Fs) and increased rates of certain cancers. One cancer that has been postulated to be associated with EMF exposure is breast cancer, for which increased rates have been reported among electricians. These cancer associations are weak, and the link to EMF exposures remains tenuous. Understanding the mechanisms by which EMFs could have biological effects will help in elucidating the risk, if any, from EMFs. One hypothesis that has received considerable attention involves reduction of melatonin levels by EMFs. This hypothesis suggests that loss of melatonin affects a variety of hormonal processes such as estrogen homeostasis and thereby may increase breast cancer rates. Since this theory was first presented, putative melatonin receptors have been cloned, providing new tools with which to examine melatonin's mechanism of action and the melatonin hypothesis. These receptors are found in nuclear and membrane fractions of cells. The nuclear receptors (retinoid Z receptors) are found both in the brain and in non-neural tissues, whereas the membrane-bound receptors are found primarily in neural tissue and have a higher affinity for melatonin. These receptors may control a variety of hormonal and immunological functions, including the release of gonadotropins from the hypothalamus and pituitary and 5-lipoxygenase activity in B lymphocytes. This Working Hypothesis briefly reviews our current knowledge of melatonin receptors and then provides theories on how the inactivation of melatonin receptors may cause cancer and suggests areas of research for addressing this question. (C) 1998 Wiley-Liss, Inc. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,MD C2-15, Res Triangle Pk, NC 27709 USA. NR 46 TC 45 Z9 46 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 1998 VL 21 IS 3 BP 149 EP 155 DI 10.1002/(SICI)1098-2744(199803)21:3<149::AID-MC1>3.0.CO;2-H PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA ZF252 UT WOS:000072878900001 PM 9537645 ER PT J AU Inoue, T Oka, K Yong-Il, H Vousden, KH Kyo, S Jing, P Hakura, A Yutsudo, M AF Inoue, T Oka, K Yong-Il, H Vousden, KH Kyo, S Jing, P Hakura, A Yutsudo, M TI Dispensability of p53 degradation for tumorigenicity and decreased serum requirement of human papillomavirus type 16E6 SO MOLECULAR CARCINOGENESIS LA English DT Article DE human papillomavirus 16; mutant E6 genes; p53 degradation; tumorigenicity ID CARCINOMA CELL-LINES; TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53; CERVICAL-CARCINOMA; E6 PROTEINS; MUTATIONAL ANALYSIS; E7 ONCOPROTEINS; GROWTH ARREST; DNA-BINDING; IN-VIVO AB Certain types of human papillomavirus (HPV), such as types 16 and 18, are etiological agents for carcinogenesis of the uterine cervix. These HPVs have two oncogenes, E6 and E7, that have transforming activities in established murine cells. Tumorigenicity and decreased serum requirement for cell growth are conferred by the E6 gene, whereas anchorage-independent growth is mainly governed by the E7 gene. To understand the mechanism of cellular transformation by the HPV16 E6 gene, we examined three mutant E6 proteins defective for p53 binding, p53 degradation, or transactivation of the adenovirus E2 promoter for the ability to induce tumorigenicity and decreased serum requirement. The results showed that tumorigenicity and decreased serum requirement were associated with the ability of E6 to bind to p53, although the subsequent degradation of p53 was not required for these functions. (C) 1998 Wiley-Liss, Inc. C1 Osaka Univ, Microbial Dis Res Inst, Dept Tumor Virol, Suita, Osaka 565, Japan. NCI, Adv Biosci Labs, Basic Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Yutsudo, M (reprint author), Osaka Univ, Microbial Dis Res Inst, Dept Tumor Virol, 3-1 Yamadaoka, Suita, Osaka 565, Japan. NR 47 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 1998 VL 21 IS 3 BP 215 EP 222 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA ZF252 UT WOS:000072878900009 PM 9537653 ER PT J AU Margottin, F Bour, SP Durand, H Selig, L Benichou, S Richard, V Thomas, D Strebel, K Benarous, R AF Margottin, F Bour, SP Durand, H Selig, L Benichou, S Richard, V Thomas, D Strebel, K Benarous, R TI A novel human WD protein, h-beta TrCP, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif SO MOLECULAR CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; UBIQUITIN-PROTEASOME PATHWAY; ENDOPLASMIC-RETICULUM; CYTOPLASMIC DOMAIN; CELL-CYCLE; PROTEOLYTIC PATHWAY; GENE; PHOSPHORYLATION; IDENTIFICATION; INFECTION AB HIV-1 Vpu interacts with CD4 in the endoplasmic reticulum and triggers CD4 degradation, presumably by proteasomes. Human beta TrCP identified by interaction with Vpu connects CD4 to this proteolytic machinery, and CD4-Vpu-beta TrCP ternary complexes have been detected by coimmunoprecipitation. beta TrCP binding to Vpu and its recruitment to membranes require two phosphoserine residues in Vpu essential for CD4 degradation. In beta TrCP, WD repeats at the C terminus mediate binding to Vpu, and an F box near the N terminus is involved in interaction with Skp1p, a targeting factor for ubiquitin-mediated proteolysis. An F-box deletion mutant of beta TrCP had a dominant-negative effect on Vpu-mediated CD4 degradation. These data suggest that beta TrCP and Skp1p represent components of a novel ER-associated protein degradation pathway that mediates CD4 proteolysis. C1 Univ Paris 05, Inst Cochin Genet Mol, CJF 97 03, INSERM,Fac Med Cochin, F-75014 Paris, France. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. CNRS, Ctr Genet Mol, F-91198 Gif Sur Yvette, France. RP Benarous, R (reprint author), Univ Paris 05, Inst Cochin Genet Mol, CJF 97 03, INSERM,Fac Med Cochin, F-75014 Paris, France. RI Margottin-Goguet, Florence/F-9272-2013 NR 50 TC 464 Z9 471 U1 5 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD MAR PY 1998 VL 1 IS 4 BP 565 EP 574 DI 10.1016/S1097-2765(00)80056-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG146 UT WOS:000072970700009 PM 9660940 ER PT J AU Minucci, S Wong, JM Blanco, JCG Shi, YB Wolffe, AP Ozato, K AF Minucci, S Wong, JM Blanco, JCG Shi, YB Wolffe, AP Ozato, K TI Retinoid receptor-induced alteration of the chromatin assembled on a ligand-responsive promoter in Xenopus oocytes SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; TRANSCRIPTION FACTOR ACCESS; EMBRYONAL CARCINOMA-CELLS; ACID RECEPTOR; IN-VIVO; GENE-EXPRESSION; MMTV PROMOTER; POSITIVE ROLE; BETA-GENE; NUCLEOSOME AB Retinoic acid (RA) stimulates transcription from the retinoic acid receptor beta 2 (RAR beta 2) promoter in mammalian embryonal cells. Evidence by in vivo deoxyribonuclease I (DNase I) hypersensitivity assay indicates that RA treatment of these cells results in an alteration of chromatin structure in and near the promoter. To study the role of chromatin in RA-activated transcription, we assembled the RAR beta 2 promoter into chromatin in Xenopus oocytes. Ectopic expression of RAR and retinoid X receptor (RXR) enhanced transcription without ligand, irrespective of whether chromatin was assembled in a replication-dependent or -independent manner, although ligand addition led to a further, marked increase in transcription. Moreover, expression of RAR and RXR, without ligand addition, induced DNase I-hypersensitive sites in the chromatin-assembled promoter. Futhermore, expression of RAR and RXR in oocytes led to local disruption of chromatin assembled over the promoter without ligand. Similar ligand-independent, but RXR/RAR-dependent nucleosomal disruption was observed in an in vitro chromatin reconstitution system using Drosophila embryonic extracts. Thus, unliganded receptors expressed in oocytes are capable of accessing to the chromatin-assembled promoter and activating transcription without ligand, indicating that chromatin assembly per se is not sufficient to reproduce ligand-dependent chromatin changes and promoter activation seen in mammalian cells. The oocyte system may serve as a model to study mechanisms of RA-dependent alterations of chromatin structure. C1 NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. RP Minucci, S (reprint author), NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RI Minucci, Saverio/J-9669-2012 NR 41 TC 12 Z9 12 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1998 VL 12 IS 3 BP 315 EP 324 DI 10.1210/me.12.3.315 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YZ443 UT WOS:000072254600001 PM 9514149 ER PT J AU de Vries, FP Cole, R Dankert, J Frosch, M van Putten, JPM AF de Vries, FP Cole, R Dankert, J Frosch, M van Putten, JPM TI Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ENDOTHELIAL-CELLS; PHASE VARIATION; SEROGROUP-B; NASOPHARYNGEAL CARRIAGE; HEPARAN-SULFATE; BACTERIAL ENTRY; EXPRESSION; MENINGOCOCCI; GONORRHOEAE AB Neisseria meningitidis possesses a repertoire of surface adhesins that promote bacterial adherence to and entry into mammalian cells. Here, we have identified heparan sulphate proteoglycans as epithelial cell receptors for the meningococcal Opc invasin. Binding studies with radiolabelled heparin and heparin affinity chromatography demonstrated that Opc is a heparin binding protein. Subsequent binding experiments with purified (SO4)-S-35-labelled epithelial cell proteoglycan receptors and infection assays with epithelial cells that had been treated with heparitinase to remove glycosaminoglycans confirmed that Opc-expressing meningococci exploit host cell-surface proteoglycans to gain access to the epithelial cell interior. Unexpectedly, Opa28-producing meningococci lacking Opc also bound proteoglycans. These bacteria also bound CEA receptors in contrast to the Opc-expressing phenotype, suggesting that Opa28 may possess domains with specificity for different receptors. Opa/Opc-negative meningococci did not bind either proteoglycan or CEA receptors. Using a set of genetically defined mutants with different lipopolysaccharide (LPS) and capsular phenotype, we were able to demonstrate that surface sialic acids interfere with the Opc-proteoglycan receptor interaction. This effect may provide the molecular basis for the reported modulatory effect of capsule and LPS on meningococcal adherence to and entry into various cell types. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. Univ Wurzburg, Inst Hyg & Mikrobiol, Wurzburg, Germany. Univ Amsterdam, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. RP van Putten, JPM (reprint author), NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jos_van_putten@nih.gov RI Frosch, Matthias/H-2411-2013; OI van Putten, Jos/0000-0002-4126-8172 NR 56 TC 79 Z9 80 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAR PY 1998 VL 27 IS 6 BP 1203 EP 1212 DI 10.1046/j.1365-2958.1998.00763.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA ZF083 UT WOS:000072860900011 PM 9570405 ER PT J AU Mdluli, K Swanson, J Fischer, E Lee, RE Barry, CE AF Mdluli, K Swanson, J Fischer, E Lee, RE Barry, CE TI Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium SO MOLECULAR MICROBIOLOGY LA English DT Article ID CATALASE-PEROXIDASE GENE; MULTIPLE-DRUG RESISTANCE; BETA-LACTAM ANTIBIOTICS; PERMEABILITY BARRIER; MYCOLIC ACIDS; CELL-WALL; TUBERCULOSIS; COMPLEX; INHA; INTRACELLULARE AB Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria. C1 NIAID, NIH, Rocky Mt Labs, TB Res Unit, Hamilton, MT 59840 USA. NIAID, NIH, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. NIAID, NIH, Rocky Mt Labs, Microscopy Branch, Hamilton, MT 59840 USA. RP Barry, CE (reprint author), NIAID, NIH, Rocky Mt Labs, TB Res Unit, 903 S 4th St, Hamilton, MT 59840 USA. EM e.ciifion_barry@nih.gov RI Barry, III, Clifton/H-3839-2012; Lee, Richard/J-4997-2013 OI Lee, Richard/0000-0002-2397-0443 FU Intramural NIH HHS [Z01 AI000783-11] NR 54 TC 52 Z9 53 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAR PY 1998 VL 27 IS 6 BP 1223 EP 1233 DI 10.1046/j.1365-2958.1998.00774.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA ZF083 UT WOS:000072860900013 PM 9570407 ER PT J AU Licinio, J AF Licinio, J TI Molecular Psychiatry 1996: High immediacy index SO MOLECULAR PSYCHIATRY LA English DT Editorial Material C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Licinio, J (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10,Rm 2D46, Bethesda, MD 20892 USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 1 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 1998 VL 3 IS 2 BP IV EP IV DI 10.1038/sj.mp.4000111 PG 1 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA ZL777 UT WOS:000073470500001 ER PT J AU Pickar, D AF Pickar, D TI The D-2 receptor: love it and leave it SO MOLECULAR PSYCHIATRY LA English DT Editorial Material AB Occupancy of the D-2 receptor has been a foundation for the mechanism of antipsychotic action for over two decades. The introduction of atypical antipsychotics and their multiple receptor profiles coupled with functional brain imaging technology has raised questions about what once was considered to be a very tight concept. We address controversial facets to the D, receptor's involvement in the antipsychotic mechanism and point to future clinical research directions. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Pickar, D (reprint author), NIMH, Expt Therapeut Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 4N212, Bethesda, MD 20892 USA. NR 4 TC 3 Z9 3 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 1998 VL 3 IS 2 BP 101 EP 102 DI 10.1038/sj.mp.4000364 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA ZL777 UT WOS:000073470500003 PM 9577830 ER PT J AU Rosenthal, NE Mazzanti, CM Barnett, RL Hardin, TA Turner, EH Lam, GK Ozaki, N Goldman, D AF Rosenthal, NE Mazzanti, CM Barnett, RL Hardin, TA Turner, EH Lam, GK Ozaki, N Goldman, D TI Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE seasonal affective disorder; seasonality; serotonin transporter gene ID ASSOCIATION; BEHAVIOR; MOOD AB Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT).(1) the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression.(2,3) We hypothesized that this short allele would also be associated with SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non-seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR and compared statistically. Patients with SAD were less likely to have the l/l genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8% vs 32.4%; P < 0.02) as compared to controls. The three 5-HTTLPR genotypes were also differentially distributed in patients and controls (P < 0.03). The SAD patients with the l/l genotype had a lower mean seasonality score than did patients with the other two genotypes (mean +/- s.d. = 15.3+/-2.8 vs 17.1+/-3.4 respectively; P < 0.02). The 5-HTTLPR short allele contributes to the trait of seasonality and is a risk factor for SAD, providing further evidence for a relationship between genetic variation in the 5-HT transporter (5-HTT) and behavior. C1 NIMH, Clin Psychobiol Branch, Sect Environm Psychiat, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. RP Rosenthal, NE (reprint author), NIMH, Clin Psychobiol Branch, Sect Environm Psychiat, 10 Ct Dr,Bldg 10,Rm 3S-231, Bethesda, MD 20892 USA. EM ner@box-n.nih.gov RI Turner, Erick/A-4848-2008; Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Turner, Erick/0000-0002-3522-3357; Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 12 TC 113 Z9 116 U1 3 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 1998 VL 3 IS 2 BP 175 EP 177 DI 10.1038/sj.mp.4000360 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA ZL777 UT WOS:000073470500016 PM 9577843 ER PT J AU van den Munckhof, P Lenz, FA Chase, TN Metman, LV AF van den Munckhof, P Lenz, FA Chase, TN Metman, LV TI Square-wave action dystonia in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article ID POSTEROVENTRAL PALLIDOTOMY; FEATURES C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Hosp, Dept Neurol Surg, Baltimore, MD 21287 USA. RP Metman, LV (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C104,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 1998 VL 13 IS 2 BP 354 EP 356 DI 10.1002/mds.870130228 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA ZB394 UT WOS:000072468100027 PM 9539355 ER PT J AU de Boer, JG Provost, S Gorelick, N Tindall, K Glickman, BW AF de Boer, JG Provost, S Gorelick, N Tindall, K Glickman, BW TI Spontaneous mutation in lacI transgenic mice: a comparison of tissues SO MUTAGENESIS LA English DT Article ID FACTOR-IX GENE; CYTOSINE RESIDUES; MUTAGENESIS ASSAY; REPAIR ACTIVITY; BONE-MARROW; DNA DAMAGE; METHYLATION; INDUCTION; CELLS; 5-METHYLCYTOSINE AB The nature of spontaneous mutations in the lacI transgene of Big Blue (R) mice was determined in selected tissues. The mutant frequencies ranged from 2.5 x 10(-5) to 7.1 x 10(-5) for liver, spleen, bladder, stomach, kidney, bone marrow, lung and skin, We also determined the DNA sequence alterations in the mutants recovered from these tissues, In all tissues the predominant class of mutations was G:C-->A:T transitions, most of which occurred at 5'-CpG-3' dinucleotide sequences. Bladder, kidney and skin display the highest contribution of G:C-->A:T transitions, The second most common class of mutations was G:C-->T:A transversions. All other base substitution classes contributed < 10% each. Of the non-substitution events, the loss of a single base pair was the most frequently occurring event (< 10%). The similarity of mutational spectra (in terms of kinds of mutations detected by the lacI transgenic system) in all tissues examined supports the idea that similar mutational pathways function in these tissues in the absence of chemical or physical stimulus. C1 Univ Victoria, Ctr Environm Hlth, Victoria, BC V8W 2Y2, Canada. Vitrogen Inc, Carlsbad, CA USA. Procter & Gamble Co, Cincinnati, OH USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP de Boer, JG (reprint author), Univ Victoria, Ctr Environm Hlth, Victoria, BC V8W 2Y2, Canada. EM jdboer@uvic.ca NR 44 TC 67 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAR PY 1998 VL 13 IS 2 BP 109 EP 114 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA ZD302 UT WOS:000072671600001 PM 9568581 ER PT J AU Li, XC Everett, LA Lalwani, AK Desmukh, D Friedman, TB Green, ED Wilcox, ER AF Li, XC Everett, LA Lalwani, AK Desmukh, D Friedman, TB Green, ED Wilcox, ER TI A mutation in PDS causes non-syndromic recessive deafness SO NATURE GENETICS LA English DT Letter ID POPULATION C1 Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Med, Div Otol Neurotol & Skullbase Surg, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA. Ichalkaranji Tilawani, Rotary Deaf Sch, Kolhapur 416115, Maharashtra, India. RP Wilcox, ER (reprint author), Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. FU NIDCD NIH HHS [Z01DC00026] NR 13 TC 234 Z9 251 U1 2 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 1998 VL 18 IS 3 BP 215 EP 217 DI 10.1038/ng0398-215 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA ZA061 UT WOS:000072325000017 PM 9500541 ER PT J AU Watanabe, A Takeda, K Ploplis, B Tachibana, M AF Watanabe, A Takeda, K Ploplis, B Tachibana, M TI Epistatic relationship between Waardenburg syndrome genes MITF and PAX3 SO NATURE GENETICS LA English DT Article ID SYNDROME TYPE-I; ALVEOLAR RHABDOMYOSARCOMA; TRANSCRIPTIONAL ACTIVATOR; FUSION PROTEIN; PAIRED DOMAIN; MUTATIONS; EXPRESSION; IDENTIFICATION; MECHANISMS; BINDING AB Waardenburg syndrome (WS) is a hereditary disorder that causes hypopigmentation and hearing impairment. Depending on additional symptoms, WS is classified into four types(1): WS1, WS2, WS3 and WS4. Mutations in MITF (microphthalmia-associated transcription factor) and PAX3, encoding transcription factors, are responsible for WS2 and WS1/WS3, respectively(1). We have previously shown that MITF transactivates the gene for tyrosinase, a key enzyme for melanogenesis, and is critically involved in melanocyte differentiation(2). Absence of melanocytes affects pigmentation in the skin, hair and eyes, and hearing function in the cochlea(3). Therefore, hypopigmentation and hearing loss in WS2 are likely to be the results of an anomaly of melanocyte differentiation caused by MITF mutations(4,5). However, the molecular mechanism by which PAX3 mutations cause the auditory-pigmentary symptoms in WS1/WS3 remains to be explained. Here we show that PAX3, a transcription factor with a paired domain and a homeodomain, transactivates the MITF promoter. We further show that PAX3 proteins associated with WS1 in either the paired domain or the homeodomain fail to recognize and transactivate the MITF promoter. These results provide evidence that PAX3 directly regulates MITF, and suggest that the failure of this regulation due to PAX3 mutations causes the auditory-pigmentary symptoms in at least some individuals with WS1. C1 Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP Tachibana, M (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, 5 Res Court,Rm 2A31, Rockville, MD 20850 USA. NR 25 TC 182 Z9 190 U1 1 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 1998 VL 18 IS 3 BP 283 EP 286 DI 10.1038/ng0398-283 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA ZA061 UT WOS:000072325000030 PM 9500554 ER PT J AU Rosenberg, SA Yang, JC Schwartzentruber, DJ Hwu, P Marincola, FM Topalian, SL Restifo, NP Dudley, ME Schwarz, SL Spiess, PJ Wunderlich, JR Parkhurst, MR Kawakami, Y Seipp, CA Einhorn, JH White, DE AF Rosenberg, SA Yang, JC Schwartzentruber, DJ Hwu, P Marincola, FM Topalian, SL Restifo, NP Dudley, ME Schwarz, SL Spiess, PJ Wunderlich, JR Parkhurst, MR Kawakami, Y Seipp, CA Einhorn, JH White, DE TI Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma SO NATURE MEDICINE LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; LIMITING DILUTION ANALYSIS; CYTOLYTIC T-LYMPHOCYTES; PERIPHERAL-BLOOD; IN-VIVO; AUTOLOGOUS TUMOR; FREQUENCY-ANALYSIS; CELL RESPONSES; ANTIGEN GP100; INTERLEUKIN-2 AB The cloning of the genes encoding cancer antigens has opened new possibilities far the treatment of patients with cancer. In this study, immunodominant peptides from the gp100 melanoma-associated antigen were identified, and a synthetic-peptide, designed to increase binding to HLA-A2 molecules, was used as a cancer vaccine to treat patients with metastatic melanoma. On the basis of immunologic assays, 91% of patients could be successfully immunized with this synthetic peptide, and 13 of 31 patients (42%) receiving the peptide vaccine plus IL-2 had objective cancer responses, and four additional patients had mixed or minor responses. Synthetic peptide vaccines based on the genes encoding cancer antigens hold promise for the development of novel cancer immunotherapies. C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 38 TC 1441 Z9 1468 U1 11 U2 90 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1998 VL 4 IS 3 BP 321 EP 327 DI 10.1038/nm0398-321 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZN163 UT WOS:000073616200038 PM 9500606 ER PT J AU Pantaleo, G Cohen, OJ Schacker, T Vaccarezza, M Graziosi, C Rizzardi, GP Kahn, J Fox, CH Schnittman, SM Schwartz, DH Corey, L Fauci, AS AF Pantaleo, G Cohen, OJ Schacker, T Vaccarezza, M Graziosi, C Rizzardi, GP Kahn, J Fox, CH Schnittman, SM Schwartz, DH Corey, L Fauci, AS TI Evolutionary pattern of human immunodeficiency virus (HIV) replication and distribution in lymph nodes following primary infection: Implications for antiviral therapy SO NATURE MEDICINE LA English DT Article ID TYPE-1; PLASMA; DISEASE; TISSUE; CELLS; AIDS; RESERVOIRS; MACAQUES; VIREMIA; ORGANS AB Evolutionary patterns of virus replication and distribution in lymphoid tissue during the early phases of HIV infection have not been delineated. Lymph node (LN) biopsies were excised from patients at different times after the estimated time of primary infection. Within 3 months of the acute viral syndrome, HIV was mostly present in individual virus-expressing cells in LNs; trapping of virions in the follicular dendritic cell (FDC) network was minimal or absent, but was the predominant form of HIV detected in LNs of subjects with chronic infection, either recent (4-20 months after primary infection) or long-term (>2-3 years after primary infection). Plasma viremia was significantly higher in patients during the first 3 months than in those recently infected; however, there were no significant differences in the number of virus-expressing cells per square millimeter of LN tissue in these two groups. Numbers of virus-expressing cells in lymphoid tissue were significantly lower in the subjects with long-term infection than in the other two groups. Therefore, during the transition from primary to chronic HIV infection, the level of HIV replication in lymphoid tissue remains elevated despite the fact that viremia is significantly downregulated These findings have implications for therapeutic strategies in primary HIV infection and in recent seroconvertors. C1 CHU Vaudois, Lab AIDS Immunopathogenesis, Dept Med, Div Infect Dis, CH-1011 Lausanne, Switzerland. NIAID, Lab Immunoregulat, Bethesda, MD 20892 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Sch Med, San Francisco, CA 94110 USA. Mol Histol Inc, Gaithersburg, MD 20879 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Washington, Virol Res Clin, Seattle, WA 98104 USA. RP Pantaleo, G (reprint author), CHU Vaudois, Lab AIDS Immunopathogenesis, Dept Med, Div Infect Dis, CH-1011 Lausanne, Switzerland. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 23 TC 101 Z9 101 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1998 VL 4 IS 3 BP 341 EP 345 DI 10.1038/nm0398-341 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZN163 UT WOS:000073616200042 PM 9500610 ER PT J AU Glushakova, S Grivel, JC Fitzgerald, W Sylwester, A Zimmerberg, J Margolis, LB AF Glushakova, S Grivel, JC Fitzgerald, W Sylwester, A Zimmerberg, J Margolis, LB TI Evidence for the HIV-1 phenotype switch as a causal factor in acquired immunodeficiency SO NATURE MEDICINE LA English DT Article ID ANTIBODY-RESPONSE; VIRAL BURDEN; B-CELLS; INFECTION; DISEASE; PATHOGENESIS; PROGRESSION; INDIVIDUALS; ACTIVATION; TETANUS AB Both cellular and humoral immunodeficiency develop in vivo after prolonged infection with HIV-1, but the mechanisms are unclear(1). Initial infection with HIV-1 is transmitted by macrophage (M)-tropic/non-syncytia-inducing (NSI) viruses(2,3), which hyperactivate the immune system(4,5), and, in one view, cause immunodeficiency by "exhaustion"(4,6) of lymphoid tissue. An alternative hypothesis is that immunodeficiency is caused by the replacement of M-tropic viruses by T cell (T)-tropic/syncytia-inducing (SI) viruses, which are known to be highly cytopathic in vitro and emerge late in infected individuals around the time of transition to AIDS (refs. 1, 7-9). To test these two possibilities, we have developed an ex vivo model of humoral immunity to recall antigens using human lymphoid tissue. This tissue supports productive infection with both M-and T-tropic HIV-1 isolates when cultured ex vivo(10,11). We found that specific immune responses were enhanced by productive infection of the tissue with M-tropic/NSI HIV-1 isolates, but were blocked by T-tropic/SI HIV-1 isolates. The mechanism involves specific irreversible effect on B-cell activity. Our results support the hypothesis that the phenotype switch to T-tropic viruses is a key determinant of acquired humoral immunodeficiency in patients infected with HIV. C1 NIAID, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Margolis, LB (reprint author), NIAID, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 10D14,10 Ctr Dr, Bethesda, MD 20892 USA. NR 22 TC 88 Z9 89 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 1998 VL 4 IS 3 BP 346 EP 349 DI 10.1038/nm0398-346 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZN163 UT WOS:000073616200043 PM 9500611 ER PT J AU Striker, LJ AF Striker, LJ TI Nephron reduction in man - lessons from the Os mouse SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material ID REDUCED RENAL MASS; GLOMERULOSCLEROSIS; HYPERTENSION; HUMANS C1 NIDDK, Renal Cell Biol Sect, Bethesda, MD 20892 USA. RP Striker, LJ (reprint author), NIDDK, Renal Cell Biol Sect, Bldg 10,Room 3N110, Bethesda, MD 20892 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 1998 VL 13 IS 3 BP 543 EP 545 DI 10.1093/ndt/13.3.543 PG 3 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA ZC757 UT WOS:000072614500003 PM 9550622 ER PT J CA Alzheimers Assoc Natl Inst Aging TI Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease" SO NEUROBIOLOGY OF AGING LA English DT Article ID NEURONAL THREAD PROTEIN; CEREBROSPINAL-FLUID; CYTOCHROME-OXIDASE; FIBROBLASTS; DEMENTIA; BRAIN AB The ideal biomarker for Alzheimer's disease (AD) should detect a fundamental feature of neuropathology and be validatrd in neuropathologically-confirmed cases; it should have a sensitivity >80% for detecting AD and a specificity of >80% for distinguishing other dementias; it should be reliable, reproducible, non-invasive, simple to perform, and inexpensive. Recommended steps to establish a biomarker include confirmation by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. Our review of current candidate markers indicates that for suspected early-onset familial AD, it is appropriate to search fur mutations in the presenilin 1, presenilin 2, and amyloid precursor protein genes. Individuals with these mutations typically have increased levels of the amyloid A beta(42) peptide in plasma and decreased levels of APPs in cerebrospinal fluid. In late-onset and sporadic AD, these measures are nor useful, but detecting an apolipoprotein E el allele can add confidence to the clinical diagnosis. Among the other proposed molecular and biochemical markers for sporadic AD, cerebrospinal fluid assays showing low levels of A beta(42) and high levels of tau come closest to fulfilling criteria for a useful biomarker. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Working Grp Advisory Comm, WACC 830, Boston, MA 02114 USA. Alzheimers Assoc, Ronald & Nancy Reagan Res Inst, Chicago, IL USA. NIA, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. Univ Michigan, Michigan Alzheimers Dis Res Ctr, Dept Neurol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA. Swedish Med Res Council, Stockholm, Sweden. Univ Gothenburg, Dept Clin Neurosci, Unit Psychiat & Neurochem, Gothenburg, Sweden. INSERM, F-59045 Lille, France. Ist Sacro Cuore di Gesu, Geriatr Res Grp, Brescia, Italy. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Univ British Columbia, Biotechnol Lab, Vancouver, BC V6T 1W5, Canada. Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC, Canada. Univ British Columbia, Dept Zool, Vancouver, BC, Canada. Univ Gothenburg, Dept Anat & Cell Biol, Gothenburg, Sweden. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Howard Univ, Coll Med, Dept Pathol, Washington, DC 20059 USA. Brigham & Womens Hosp, Lab Higher Cort Funct, Boston, MA 02115 USA. Vrije Univ Amsterdam, Acad Ziekenhuis, Dept Neurol, Amsterdam, Netherlands. Univ Kuopio, Dept Neurol & Neurosci, FIN-70211 Kuopio, Finland. St James Hosp, Mercers Inst Res Ageing, Dublin 8, Ireland. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Huddinge Univ Hosp, Karolinska Inst, Dept Clin Neurosci & Family Med, S-14186 Huddinge, Sweden. Univ Tokyo, Fac Med, Dept Neuropathol, Tokyo 113, Japan. RP Massachusetts Gen Hosp, Working Grp Advisory Comm, WACC 830, Boston, MA 02114 USA. RI Frisoni, Giovanni B./K-1360-2016; OI Klunk, William/0000-0001-5512-0251; Frisoni, Giovanni B./0000-0002-6419-1753; Feldman, Howard/0000-0002-9258-4538; Litvan, Irene/0000-0002-3485-3445 NR 33 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1998 VL 19 IS 2 BP 109 EP 116 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA ZF836 UT WOS:000072938100002 ER PT J AU Litvan, I AF Litvan, I TI Methodological and research issues in the evaluation of biological diagnostic markers for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; CLINICAL-DIAGNOSIS; APOLIPOPROTEIN-E; CRITERIA; VALIDITY; ACCURACY C1 NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Jackson Fdn Med Educ & Res, Def & Vet Head Injury Program, Neuropharmacol Unit, Bethesda, MD 20892 USA. RP Litvan, I (reprint author), NINDS, Med Neurol Branch, NIH, Fed Bldg,Room 714,7550 Wisconsin Ave, Bethesda, MD 20892 USA. EM litvan1@helix.nih.gov OI Litvan, Irene/0000-0002-3485-3445 NR 23 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1998 VL 19 IS 2 BP 121 EP 123 DI 10.1016/S0197-4580(98)00019-0 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA ZF836 UT WOS:000072938100004 PM 9558145 ER PT J AU Donadel, G Marinos, N DeSilva, MG Lu, J Notkins, AL Lan, MS AF Donadel, G Marinos, N DeSilva, MG Lu, J Notkins, AL Lan, MS TI Molecular cloning and characterization of a highly basic Protein IA-4, expressed in pancreatic islets and brain SO NEUROENDOCRINOLOGY LA English DT Article DE molecular neuroendocrinology; langerhans islets; hippocampus; cortex; cerebellum; spinal cord; mouse ID DEPENDENT DIABETES-MELLITUS; NITRIC-OXIDE SYNTHASE; CANCER CELL-LINES; TYROSINE-PHOSPHATASE; TRANSMEMBRANE PROTEIN; HUMAN INSULINOMA; ENDOCRINE-CELLS; BETA-CELLS; IDENTIFICATION; AUTOANTIGEN AB A substraction library was constructed from mouse insulinoma (beta TC-1) and glucagonoma (alpha TC-1) cell lines. Differential screening and sequencing revealed a novel cDNA clone, IA-4, which was expressed in the islets of Langerhans and the brain. IA-4 cDNA is 1,007 bp in length and predicts a protein of 187 amino acids with a molecular mass of 19,940 D. Examination of the amino acid sequence showed a high content of arginine (18.7%), proline (14.4%), alanine (16.0%), leucine (13.4%) and glycine (9.6%). The deduced pi value is 12.5 indicating a highly basic protein. Northern blot analysis revealed a 1-kb mRNA highly expressed in brain, trigeminal ganglia and cell lines of neuroendocrine origin. Rabbit polyclonal antiserum raised against a synthetic IA-4 peptide, designated Pep-l, not only reacted with IA-4 recombinant protein, but also immunostained the islets of Langerhans and large neurons of the hippocampus, cerebral cortex, spinal cord, dorsal ganglia and Purkinje cells of the cerebellum. The high expression of IA-4 protein in neuroendocrine cells and its unique amino acid sequence suggest that IA-4 may have an important, but still undetermined, function in these special cell types. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Lan, MS (reprint author), NIDR, Oral Infect & Immun Branch, NIH, 30 Convent Dr,Bldg 30,Room 124, Bethesda, MD 20892 USA. NR 26 TC 2 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAR PY 1998 VL 67 IS 3 BP 190 EP 196 DI 10.1159/000054314 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA ZC486 UT WOS:000072584100006 PM 9630436 ER PT J AU Anderson, DW Rocca, WA Rosario, JA AF Anderson, DW Rocca, WA Rosario, JA TI Pitfalls in neuroepidemiologic research SO NEUROEPIDEMIOLOGY LA English DT Review DE pitfall; design; survey; case-control study; cohort study; epidemiology ID PREVALENCE SURVEY AB In neuroepidemiologic research, there are many pitfalls to trap unwary investigators, whether the project is a survey, a case-control study, or some other type of study. We briefly discuss pitfalls relating to: research preliminaries (e.g., failure to decide on study objectives); personnel and training (e.g., deficient training); data collection (e.g., ineffective supervision); data ownership and data sharing (disagreement about how the data will be used), and report preparation (e.g., failure to interpret results in the context of uncertainties arising from the design and implementation of the research). Awareness of these pitfalls will reduce the likelihood of flawed or ineffective neuroepidemiologic research. C1 NINDS, Biometry & Field Studies Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Anderson, DW (reprint author), NINDS, Biometry & Field Studies Branch, NIH, Fed Bldg,Room 7C-16,7550 Wisconsin Ave,MSC 9135, Bethesda, MD 20892 USA. EM dallas_w_anderson@nih.gov NR 17 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD MAR-APR PY 1998 VL 17 IS 2 BP 55 EP 62 DI 10.1159/000026153 PG 8 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA ZK331 UT WOS:000073309000001 PM 9592780 ER PT J AU Wichman, A Bernat, JL Goldblatt, D McQuillen, MP Nelson, RF Pellegrino, TR Snyder, R Taylor, RM AF Wichman, A Bernat, JL Goldblatt, D McQuillen, MP Nelson, RF Pellegrino, TR Snyder, R Taylor, RM CA Ethics and Humanities Subcomm Amer Acad Neurol TI Ethical issues in clinical research in neurology - Advancing knowledge and protecting human research subjects SO NEUROLOGY LA English DT Editorial Material C1 NIH, Off Human Subjects Res, Bethesda, MD 20892 USA. RP Wichman, A (reprint author), NIH, Off Human Subjects Res, Bldg 10,Room 1C116, Bethesda, MD 20892 USA. NR 8 TC 14 Z9 14 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1998 VL 50 IS 3 BP 592 EP 595 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA ZD472 UT WOS:000072689400005 ER PT J AU Brown, P Cervenakova, L McShane, L Goldfarb, LG Bishop, K Bastian, F Kirkpatrick, J Piccardo, P Ghetti, B Gajdusek, DC AF Brown, P Cervenakova, L McShane, L Goldfarb, LG Bishop, K Bastian, F Kirkpatrick, J Piccardo, P Ghetti, B Gajdusek, DC TI Creutzfeldt-Jakob disease in a husband and wife SO NEUROLOGY LA English DT Article ID HUMAN SPONGIFORM ENCEPHALOPATHY; PROTEIN AB A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5-year clinical course. Four and a half years later, his then 55-year-old widow died from CJD after a 1-month illness. Both patients had typical clinical and neuropathologic features of the disease, and pathognomonic proteinase-resistant amyloid protein ("prion" protein, or PrP) was present in both brains. Neither patient had a family history of neurologic disease, and molecular genetic analysis of their PrP genes was normal. No medical, surgical, or dietary antecedent of CJD was identified; therefore, we are left with the unanswerable alternatives of human-to-human transmission or the chance occurrence of sporadic CJD in a husband and wife. C1 NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet, Houston, TX USA. Univ S Alabama, Med Ctr, Dept Pathol, Mobile, AL USA. Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. RP Brown, P (reprint author), NINDS, CNS Studies Lab, NIH, Bldg 36,Room 5B21, Bethesda, MD 20892 USA. NR 11 TC 16 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1998 VL 50 IS 3 BP 684 EP 688 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA ZD472 UT WOS:000072689400021 PM 9521256 ER PT J AU Li, M Dickson, DW Spiro, AJ AF Li, M Dickson, DW Spiro, AJ TI Sarcolemmal defect and subsarcolemmal lesion in a patient with gamma-sarcoglycan deficiency SO NEUROLOGY LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; PLASMA-MEMBRANE AB We report a case of gamma-sarcoglycanopathy with sarcolemmal defects and subsarcolemmal lesions indistinguishable from those in Duchenne muscular dystrophy. Both disorders share certain ultrastructure features that suggest a common pathogenesis related to primary deficiency of transmembrane glycoproteins (e.g., sarcoglycans) or deficiency in dystrophin, which produces a secondary deficiency in sarcoglycans. The lack of transmembrane glycoproteins may contribute to membrane lesions and associated muscle fiber degeneration and necrosis. C1 Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. RP Li, M (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. OI Dickson, Dennis W/0000-0001-7189-7917 NR 6 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 1998 VL 50 IS 3 BP 807 EP 809 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA ZD472 UT WOS:000072689400049 PM 9521284 ER PT J AU Callicott, JH Ramsey, NF Tallent, K Bertolino, A Knable, MB Coppola, R Goldberg, T van Gelderen, P Mattay, VS Frank, JA Moonen, CTW Weinberger, DR AF Callicott, JH Ramsey, NF Tallent, K Bertolino, A Knable, MB Coppola, R Goldberg, T van Gelderen, P Mattay, VS Frank, JA Moonen, CTW Weinberger, DR TI Functional magnetic resonance imaging brain mapping in psychiatry: Methodological issues illustrated in a study of working memory in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fMRI; schizophrenia; prefrontal; memory; cognition ID NEUROLEPTIC-NAIVE PATIENTS; SENSORY STIMULATION; PREFRONTAL CORTEX; BLOOD-FLOW; ACTIVATION; MRI; TASK; FMRI; 1.5-T; FRACTIONATION AB Functional magnetic resonance imaging (fMRI) is a potential paradigm shift in psychiatric neuroimaging. The technique provides individual, rather than group-averaged, functional neuroimaging data, but subtle methodological confounds represent unique challenges for psychiatric research. As an exemplar of the unique potential and problems of fMRI, we present a study of 10 inpatients with schizophrenia and 10 controls performing a novel "n back" working memory (WM) task. We emphasize two key design steps: (1) the use of an internal activation standard (i.e., a physiological control region) to address activation validity, and (2) the assessment of signal stability to control for "activation" artifacts arising from unequal signal variance across groups. In the initial analysis, all but one of the patients failed to activate dorsolateral prefrontal cortex (DLPFC) during the working memory task. However, some patients (and one control) also tended to show sparse control region activation in spite of normal motor performance, a result that raises doubts about the validity of the initial analysis and concerns about unequal subject motion. subjects were then matched for signal variance (voxel stability), producing a subset of six patients and six controls. In this comparison, the internal activation standard (i.e., motor activation) was similar in both groups, and five of six patients, including two whom were neuroleptic-naive, failed to activate DLPFC. In addition, a tendency for overactivation of parietal cortex was seen. These results illustrate some of the promise and pitfalls of fMRI. Although fMRI generates individual brain maps, a specialized survey of the data is necessary to avoid spurious or unreliable findings, related to artifacts such as motion, which are likely to be frequent in psychiatric patients. Published by Elsevier Science Inc. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Washington, DC USA. NIH, In Vivo NMR Ctr, BEIR, NCRR, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, OIR, Bethesda, MD 20892 USA. Univ Utrecht, Dept Psychiat, Utrecht, Netherlands. RP Callicott, JH (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bldg 10,Room 4N-317, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009; Moonen, Chrit/K-4434-2016; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Moonen, Chrit/0000-0001-5593-3121; Bertolino, Alessandro/0000-0002-1251-1380 NR 66 TC 234 Z9 240 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 1998 VL 18 IS 3 BP 186 EP 196 DI 10.1016/S0893-133X(97)00096-1 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA YT626 UT WOS:000071625900003 PM 9471116 ER PT J AU Hallett, M Wassermann, EM Cohen, LG Chmielowska, J Gerloff, C AF Hallett, M Wassermann, EM Cohen, LG Chmielowska, J Gerloff, C TI Cortical mechanisms of recovery of function after stroke SO NEUROREHABILITATION LA English DT Article DE stroke; hemiplegia; plasticity; rehabilitation; corticospinal tract; transcranial magnetic stimulation; positron emission tomography ID TRANSCRANIAL MAGNETIC STIMULATION; CENTRAL MOTOR REORGANIZATION; HUMAN CEREBRAL-CORTEX; CONTROLLED TRIAL; HAND; MODULATION; BRAIN; ARM; RESPONSES; PATHWAYS AB Patients who have suffered hemiplegia from stroke may have some spontaneous recovery that is likely due to reorganization within the cerebral cortex, Understanding this physiology should be useful in devising ways to help patients have better improvement. Techniques, such as transcranial magnetic stimulation and neuroimaging with positron emission tomography, can be used to demonstrate the organization of the human motor system and do reveal plastic reorganization in a number of situations. In relation to stroke, the best recoveries are seen when there is preservation of the corticospinal tract from the hemisphere contralateral to the weakness, but it may well be that areas nearby to the normal motor output areas can partially substitute, There is some evidence for increased corticospinal tract activity originating ipsilateral to the hemiplegia in patients, but this may actually be associated with worse recovery. Patterns of use can influence cortical organization and should play a valuable role in rehabilitation. Certain drugs may affect this process either positively or negatively. (C) 1998 Elsevier Science Ireland Ltd. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 63 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1053-8135 J9 NEUROREHABILITATION JI Neurorehabilitation PD MAR PY 1998 VL 10 IS 2 BP 131 EP 142 DI 10.1016/S1053-8135(97)84781-6 PG 12 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA ZD950 UT WOS:000072742000005 PM 24525881 ER PT J AU Wang, CY Ni, J Jiang, H Hsu, TA Dugich-Djordjevic, M Feng, L Zhang, M Mei, L Gentz, R Lu, B AF Wang, CY Ni, J Jiang, H Hsu, TA Dugich-Djordjevic, M Feng, L Zhang, M Mei, L Gentz, R Lu, B TI Cloning and characterization of glial cell line-derived neurotrophic factor receptor-B: A novel receptor for members of glial cell line-derived neurotrophic factor family of neurotrophic factors SO NEUROSCIENCE LA English DT Article DE neurturin; c-RET; GPI-linked receptors; MAP kinase; PC12 cells ID MICE LACKING GDNF; TYROSINE KINASE; SURVIVAL FACTOR; RET RECEPTOR; NEURONS; EXPRESSION; PROTEIN; NERVE AB Glial cell line-derived neurotrophic factor (GDNF)(14) is a potent neurotrophic factor with diverse biological functions.(3,8,10,16,19,20,22) Signal transduction of GDNF is mediated by binding to a glycosylphosphatidylinositol (GPI)-linked receptor GDNFR-alpha and activation of c-RET tyrosine kinase.(5,11,23,24) The recent discovery of a new GDNF homolog neurturin(13) raises the possibility that multiple receptors exist for the members in the GDNF family, Here we report isolation of the gene encoding a new receptor called GDNFR-beta. Sequence analysis indicated that GDNFR-beta is also a GPI-linked protein, with 47% identity to GDNFR-alpha. The GDNFR-beta transcript was preferentially expressed in the brain, spleen and lung, but moderate levels of GDNFR-beta mRNA mere also found in kidney and the entire gastrointestinal track, In situ hybridization revealed high expression levels in the entorhinal cortex and olfactory bulb, followed by cortex, septum, inferior and superior colliculus, and zona inserta. A laminar pattern of expression was detected in laver III of the cortex, Treatment with GDNF of PC12 cells transfected with the GDNFR-beta gene activated mitogen-activated protein kinase (MAPK) and elicited neurite outgrowth, GDNFR-alpha and GDNFR-beta together form a new family of GPI-linked receptors for GDNF-like molecules. (C) 1997 Published by Elsevier Science Ltd. C1 NICHD, Dev Neurobiol Lab, Bethesda, MD 20892 USA. NICHD, Growth Factors Sect, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. Human Genome Sci Inc, Rockville, MD 20850 USA. Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA. Chinese Acad Sci, Shanghai Res Ctr Life Sci, Shanghai 200031, Peoples R China. RP Lu, B (reprint author), NICHD, Dev Neurobiol Lab, Bethesda, MD 20892 USA. RI Hsu, John Tsu-An/C-1199-2010; Lu, Bai/A-4018-2012; Mei, Lin/G-8755-2012 FU NINDS NIH HHS [NS34062] NR 29 TC 19 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1998 VL 83 IS 1 BP 7 EP 14 DI 10.1016/S0306-4522(97)00462-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YP379 UT WOS:000071271000002 PM 9466395 ER PT J AU Melzer, P Smith, CB AF Melzer, P Smith, CB TI Plasticity of cerebral metabolic whisker maps in adult mice after whisker follicle removal -I. Modifications in barrel cortex coincide with reorganization of follicular innervation SO NEUROSCIENCE LA English DT Article DE regeneration; vibrissa; barrel; deoxyglucose; somatosensory cortex ID SOMATOSENSORY CORTEX; PERIPHERAL DENERVATION; TRIGEMINAL GANGLION; CYTOCHROME-OXIDASE; VIBRISSAL REMOVAL; MYSTACIAL PAD; VISUAL-SYSTEM; RAT; MOUSE; FIELD AB We investigated alterations of the metabolic whisker map of barrel cortex after the removal of the follicles of left whiskers C1, C2 and C3 in adult albino mice. The quantitative autoradiographic [C-14]deoxyglucose method was used to measure local cerebral metabolic rates for glucose in barrel cortex of mice two, four, eight, 64, 160 and 250 days after the lesion. Metabolic rates were measured in three groups of animals: (i) mice with lesions that had all whiskers clipped; (ii) mice with lesions that had left whiskers B1-3 and D1-3 stimulated; and (iii) unoperated mice that had left whiskers B1-3 and D1-3 stimulated. Compared with the metabolic rates in barrels C1-3 of stimulated unoperated mice, barrels C1-3 of stimulated mice with lesions showed the first discernible increase in metabolic rate four days after the lesion. The increase became distinct at 64 days, but attained statistical significance only similar to 160 days after the lesion. The lesion pei se, i.e. without whisker stimulation, caused only a small increase in metabolic rate in barrels C1-3 accounting for not more than one fourth of the increase in metabolic rate measured after whisker deflection. The removal of whisker follicles C1-3 led, therefore, to an enlargement of the metabolic representations of the adjacent whiskers into the barrels deprived by the lesion. The gradual consolidation of the alterations of the metabolic whisker map coincided with the regeneration of follicular nerves in the whiskerpad. We detected anomalous deep nerves innervating follicles surrounding the lesion at similar to 64 days, and the number of myelinated nerve fibres in the deep nerves of these follicles was increasing with increasing time after the lesion. The coincidence of peripheral and central change suggests that the reorganization of the innervation of the sensory periphery plays an important role in the persistent alterations of the cortical somatotopy in adults following a lesion in the sensory periphery. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 Vanderbilt Univ, Inst Dev Neurosci, John F Kennedy Ctr Res Human Dev, Peabody Coll, Nashville, TN 37203 USA. NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), Vanderbilt Univ, Dept Psychol, John F Kennedy Ctr Res Human Dev, Peabody Coll, Box 152, Nashville, TN 37203 USA. NR 44 TC 18 Z9 18 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1998 VL 83 IS 1 BP 27 EP 41 DI 10.1016/S0306-4522(97)00332-1 PG 15 WC Neurosciences SC Neurosciences & Neurology GA YP379 UT WOS:000071271000004 PM 9466397 ER PT J AU Melzer, P Smith, CB AF Melzer, P Smith, CB TI Plasticity of cerebral metabolic whisker maps in adult mice after whisker follicle removal -II. Modifications in the subcortical somatosensory system SO NEUROSCIENCE LA English DT Article DE vibrissa; trigeminal brainstem; ventrobasal complex; deoxyglucose ID STEM SUBNUCLEUS INTERPOLARIS; PERIPHERAL-NERVE INJURY; PRIMARY SENSORY NEURONS; CERVICAL DORSAL HORNS; BRAIN-STEM; TRIGEMINAL SYSTEM; PRIMARY AFFERENTS; DIGIT AMPUTATION; RAT MEDULLARY; SPINAL-CORD AB The follicles of whiskers C1-3 were removed from the left side of the snout of adult mice. Adjacent whiskers B1-3 and D1-3 were stimulated while local rates of glucose utilization were measured with the [C-14]2-deoxyglucose method two, four, eight, 64, 160 and similar to 250 days after follicle removal. Local metabolic activity in the trigeminal sensory brainstem and somatosensory thalamus was compared with that of unoperated mice with the same stimulation and of mice with the same lesion that had all whiskers clipped. Actual rates of glucose utilization were measured in brainstem subnuclei caudalis and interpolaris whereas metabolic activation was only assessable by colour-coded imaging in brainstem nucleus principalis and in the thalamic ventrobasal complex. Whisker stimulation activated the somatotopically appropriate loci in brainstem and thalamus. In addition, the territory deprived by follicle removal was metabolically activated in subnuclei caudalis and interpolaris at all time intervals examined. The activation was statistically significant in subnucleus interpolaris at two days, indicating that the metabolic representations of whiskers neighbouring the lesion rapidly expanded into the deprived territory. Nucleus principalis showed a broad metabolic activation at two and four days that was absent at the longer time intervals examined. Instead, at similar to 250 days the metabolic representations of the whiskers adjacent to the lesion were enlarged into the deprived territory as in the subnuclei. Since metabolic whisker representation in the ventrobasal complex appeared to have changed in the same fashion, follicle removal apparently resulted in congruent modifications of the whisker map in the three nuclei of termination as well as in the thalamic relay at the longest time interval examined. Since metabolic responsiveness of the deprived barrels in barrel cortex of the same animals increased statistically significantly only several months after follicle removal, the novel neural responses in the brainstem were not effectively transmitted to barrel cortex immediately and the slowly evolving cortical modifications are more likely to be associated with regrowth of the connectivity of primary neurons.(28) By contrast, unmasking of hitherto suppressed inputs may underlie the early expansion of metabolic whisker representation in the brainstem. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Melzer, P (reprint author), Vanderbilt Univ, Peabody Coll, Dept Psychol, John F Kennedy Ctr Res Human Dev, Box 152, Nashville, TN 37203 USA. NR 44 TC 7 Z9 7 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1998 VL 83 IS 1 BP 43 EP 61 DI 10.1016/S0306-4522(97)00333-3 PG 19 WC Neurosciences SC Neurosciences & Neurology GA YP379 UT WOS:000071271000005 PM 9466398 ER PT J AU Quan, N Whiteside, M Herkenham, M AF Quan, N Whiteside, M Herkenham, M TI Time course and localization patterns of interleukin-1 beta messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide SO NEUROSCIENCE LA English DT Article DE endotoxin; cytokine; circumventricular organ; blood-brain barrier; glia ID CORTICOTROPIN-RELEASING FACTOR; RAT-BRAIN; IMMUNOREACTIVE INTERLEUKIN-1-BETA; PARAVENTRICULAR NUCLEUS; RECEPTOR ANTAGONIST; RAMIFIED MICROGLIA; NERVOUS-SYSTEM; PREOPTIC AREA; PLASMA ACTH; ENDOTOXIN AB The inflammatory cytokine interleukin-1 has been implicated as a mediator of many centrally controlled responses, such as fever and increased activity of the hypothalamic-pituitary-adrenal axis, after systemic infections. To identify the neuroanatomical loci of brain interleukin-1-producing cells during infection, we investigated interleukin-1 beta messenger RNA expression by ill situ hybridization histochemistry using a 500 nt ribonucleotide probe applied on brain sections from rats injected intraperitoneally with 2.5 mg/kg bacterial lipopolysaccharide or saline. In control animals, interleukin-1 beta messenger RNA was not detectable. In the brains of lipopolysaccharide-injected animals, two temporally and spatially distinct waves of interleukin-1 beta messenger RNA induction were observed. First, cell labelling appeared at 0.5 h, peaked at 2 h, and declined at 4-8 h. The labelled cells were concentrated in circumventricular organs organum vasculosum of the lamina terminalis, subfornical organ, median eminence, and area postrema and in choroid plexus, meninges, and blood vessels. Second, at 8-12 h, scattered small cells became labelled throughout the entire brain parenchyma; the labelling subsided by 24 h. Labelling was not observed in any neurons. In the pituitary, lipopolysaccharide induced strong interleukin-1 beta messenger RNA expression initially in the anterior lobe at 0.5-1 h, and later in the neural lobe at 1-2 h, and subsiding thereafter. The results show that at early rime points, peripheral lipopolysaccharide induces interleukin-1 beta message production at the blood-brain barrier and in circumventricular organs where the blood-brain barrier is leaky. After a time delay of 6-10 h, however, interleukin-1 beta messenger RNA is primarily expressed by non-neuronal cells of the brain in the brain parenchyma. These results suggest that the source of initial brain IL-1 activity after peripheral lipopolysaccharide injection derives from cells of the blood-brain barrier and the circumventricular organs, and the sustained interleukin-1 activity in the central nervous system thereafter is derived from glia . Published by Elsevier Science Ltd. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Quan, N (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Room 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 39 TC 208 Z9 222 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1998 VL 83 IS 1 BP 281 EP 293 DI 10.1016/S0306-4522(97)00350-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA YP379 UT WOS:000071271000024 PM 9466417 ER PT J AU Maurice, T Su, TP Privat, A AF Maurice, T Su, TP Privat, A TI Sigma(1) (sigma(1)) receptor agonists and neurosteroids attenuate B25-35-amyloid peptide-induced amnesia in mice through a common mechanism SO NEUROSCIENCE LA English DT Article DE beta-amyloid peptides; sigma(1) (sigma(1)) receptor ligands; neurosteroids; alternation behavior; passive avoidance; amnesia model ID METHYL-D-ASPARTATE; PREGNENOLONE SULFATE POTENTIATION; EXTRACELLULAR ACETYLCHOLINE LEVEL; INDUCED NEURONAL ACTIVATION; RAT FRONTAL-CORTEX; BINDING-SITES; DEHYDROEPIANDROSTERONE SULFATE; MK-801-INDUCED IMPAIRMENT; HIPPOCAMPAL-NEURONS; MEDIATED INCREASES AB The sigma(1) (sigma(1)) receptor agonists exert potent anti-amnesic effects, as they apparently block the learning impairments either induced by the muscarinic receptor antagonist scopolamine, the N-methyl-D-aspartate receptor antagonist dizocilpine or inherently due to the age-related deficits in senescence-accelerated mice. We recently described the amnesia induced by the beta-amyloid-related peptide beta(25-35), administered centrally in an aggregated form, in mice. The deficits were sensitive to cholinomimetics or to N-methyl-D-aspartate/glycine modulatory site agonists. Herein, we examined the effects of sigma(1) receptor ligands on the beta(25-35) peptide-induced amnesia. The effects of neuro(active) steroids, which interact in vitro and in vivo with sigma(1) receptors were examined in parallel. Mnesic capacity was evaluated seven days after administration of aggregated beta(25-35) peptide (3 nmol), using spontaneous alternation in the Y-maze for spatial short-term memory, or after 14 days, using the step-down type passive avoidance test for long-term memory. The sigma(1) receptor agonists (+)-pentazocine, PRE-084, or SA4503 attenuated, in a dose-dependent and bell-shaped manner, the beta(25-35) peptide-induced deficits on both tests. These effects were antagonized by haloperidol or BMY-14802, confirming the sigma(1) receptor pharmacology. Pregnenolone, dehydroepiandrosterone, and their sulphate esters, but not progesterone, also dose-dependently attenuated the beta(25-35) peptide-induced deficits. Progesterone blocked the beneficial effects of each other neurosteroid, behaving as an antagonist. Furthermore, haloperidol blocked the effects induced by neurosteroids, whereas progesterone antagonized the effects of the non-steroidal sigma(1) receptor agonists, showing a clear crossed pharmacology of different drug classes. These results demonstrate that: (i) the anti-amnesic effect of sigma(1) receptor agonists may be of therapeutic relevance in pathological states affecting the cholinergic and/or glutamatergic systems, such as in pathological aging; (ii) neurosteroids play an important role in learning processes and may collectively constitute a therapeutic target; (iii) the interaction between sigma(1) systems and neurosteroids appears indeed of behavioural relevance. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 INSERM, U336, Unite Dev Plast & Vieillissement Syst Nerveux, F-34296 Montpellier 5, France. NIDA, Unit Pathobiol, Mol Neuropsychiat Sect, Div Intramural Res,NIH, Baltimore, MD 21224 USA. RP Maurice, T (reprint author), INSERM, U336, Unite Dev Plast & Vieillissement Syst Nerveux, 8 Rue Ecole Normale, F-34296 Montpellier 5, France. NR 66 TC 179 Z9 186 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR PY 1998 VL 83 IS 2 BP 413 EP 428 PG 16 WC Neurosciences SC Neurosciences & Neurology GA YQ777 UT WOS:000071422200008 PM 9460750 ER PT J AU Savory, J Garruto, RM AF Savory, J Garruto, RM TI Aluminum, tau protein, and Alzheimer's disease: An important link? SO NUTRITION LA English DT Editorial Material ID ACCUMULATION; MICROPROBE; RABBITS; BRAIN C1 Univ Virginia, Dept Pathol & Biochem, Charlottesville, VA 22903 USA. NIH, Frederick Canc Res & Dev Ctr, Cent Nervous Syst Studies Lab, Frederick, MD USA. RP Savory, J (reprint author), Univ Virginia, Dept Pathol & Biochem, Charlottesville, VA 22903 USA. NR 20 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD MAR PY 1998 VL 14 IS 3 BP 313 EP 314 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZJ593 UT WOS:000073232300010 PM 9583377 ER PT J AU Raghuramulu, N Underwood, B Bhaskaram, P Arunjyothi Chennaiah, S Reddy, V AF Raghuramulu, N Underwood, B Bhaskaram, P Arunjyothi Chennaiah, S Reddy, V TI Vitamin A relative dose response test in undernourished children SO NUTRITION RESEARCH LA English DT Article DE RDR; vitamin A; malnutrition; children; deficiency; retinol binding protein; liver ID A-DEFICIENCY; MALNUTRITION; DIARRHEA; DISEASE; RETINOL; PROTEIN; PLASMA AB The relative dose response (RDR) has been proposed as a method for the estimation of body vitamin A stores and has been tested in children suffering from various grades of malnutrition. RDR was tested before and after 4-6 days of vitamin A administration either as a single massive oral dose of 200,000 i.u. or four smaller doses of 50,000 i.u. each. The results of the study indicated a positive RDR (>14%) reflecting liver stores depletion in children whose serum levels of vitamin A were less than 0.35 mu mol/l. Normal RDR (<14%) was observed in children whose serum levels of vitamin A were above 0.7 mu mol/l indicating normal liver vitamin A reserves. However, the RDR showed variable results in children whose serum vitamin A levels were between 0.35-0.70 mu mol. Eleven out of 49 children continued to show positive RDR even after vitamin A supplementation. Associated malnutrition might be responsible for the variation in the response. These results suggest that RDR test may be of a limited value in populations where malnutrition is prevalent. (C) 1998 Elsevier Science Inc. C1 Indian Council Med Res, Natl Inst Nutr, Hyderabad 500007, Andhra Pradesh, India. NIH, Natl Eye Hosp Inst, Bethesda, MD 20892 USA. RP Raghuramulu, N (reprint author), Indian Council Med Res, Natl Inst Nutr, Jamai Osmania PO, Hyderabad 500007, Andhra Pradesh, India. EM icmrnin@ren.nic.in NR 21 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAR PY 1998 VL 18 IS 3 BP 533 EP 541 DI 10.1016/S0271-5317(98)00040-2 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZD438 UT WOS:000072685600009 ER PT J AU Haque, M Andreola, F De Luca, LM AF Haque, M Andreola, F De Luca, LM TI The cloning and characterization of a novel cytochrome P450 family, CYP26, with specificity toward retinoic acid SO NUTRITION REVIEWS LA English DT Review ID SIGNALING PATHWAY; CELLS AB A new family of cytochrome P45O enzymes, CYP26, has been cloned and characterized in zebra fish, human and mouse tissues. CYP26 displays specificity toward retinoic acid and it may function as an important regulator of differentiation and a possible modulator of disease states by controlling retinoid concentration and homeostasis. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Haque, M (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 16 TC 20 Z9 20 U1 0 U2 2 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAR PY 1998 VL 56 IS 3 BP 84 EP 85 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZF844 UT WOS:000072938900004 PM 9564181 ER PT J AU Kaltenbach, K Berghella, V Finnegan, L AF Kaltenbach, K Berghella, V Finnegan, L TI Opioid dependence during pregnancy - Effects and management SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID METHADONE-MAINTENANCE TREATMENT; IMMUNODEFICIENCY-VIRUS TYPE-1; MATERNAL-INFANT TRANSMISSION; NEONATAL NARCOTIC WITHDRAWAL; ZIDOVUDINE TREATMENT; WOMEN; ADDICTION; PROGRAM; NEWBORN; ABUSE AB This article describes the complex problems associated with opioid dependence during pregnancy. Medical, obstetric, and psychosocial problems are presented. Methadone maintenance for the treatment of opioid dependence is described in this article. Specific issues of appropriate methadone dose during pregnancy medical withdrawal, and the relationship of methadone dose and the severity of neonatal abstinence also are discussed. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Div Maternal Fetal Med, Philadelphia, PA USA. NIH, Womens Hlth Initiat, Bethesda, MD 20892 USA. RP Kaltenbach, K (reprint author), MATER, Dept Pediat, 1201 Chestnut St,9th Floor, Philadelphia, PA 19107 USA. NR 71 TC 146 Z9 146 U1 2 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD MAR PY 1998 VL 25 IS 1 BP 139 EP + DI 10.1016/S0889-8545(05)70362-4 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZD193 UT WOS:000072660700009 PM 9547764 ER PT J AU Blair, A Hartge, P Stewart, PA McAdams, M Lubin, J AF Blair, A Hartge, P Stewart, PA McAdams, M Lubin, J TI Mortality and cancer incidence of aircraft maintenance workers exposed to trichloroethylene and other organic solvents and chemicals: extended follow up SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE trichloroethylene; organic solvents; lymphatic cancer; haematopoietic cancer; breast cancer ID RETROSPECTIVE COHORT MORTALITY; OCCUPATIONAL RISK-FACTORS; NON-HODGKINS-LYMPHOMA; FEMALE BREAST-CANCER; MULTIPLE-MYELOMA; LUNG-FUNCTION; EXPOSURES; INDUSTRY; ASTHMA; PERCHLOROETHYLENE AB Objectives-To extend the follow up of a cohort of 14 457 aircraft maintenance workers to the end of 1990 to evaluate cancer risks from potential exposure to trichloroethylene and other chemicals. Methods-The cohort comprised civilians employed for at least one year between 1952 and 1956, of whom 5727 had died by 31 December 1990. Analyses compared the mortality of the cohort with the general population of Utah and the mortality and cancer incidence of exposed workers with those unexposed to chemicals, while adjusting for age, sex, and calendar time. Results-In the combined follow up period (1952-90), mortality from all causes and all cancer was close to expected (standardised mortality ratios (SMRs) 97 and 96, respectively). Significant excesses occurred for ischaemic heart disease (SMR 108), asthma (SMR 160), and cancer of the bone (SMR 227), whereas significant deficits occurred for cerebrovascular disease (SMR 88), accidents (SMR 70), and cancer of the central nervous system Workers exposed to trichloshowed non-significant excesses for non-Hodgkin's lymphoma (relative risk (RR) 2.0), and cancers of the oesophagus (RR 5.6), colon (RR 1.4), primary liver (RR 1.7), breast (RR 1.8), cervix (RR 1.8), kidney (RR 1.6), and bone (RR 2.1). None of these cancers showed an exposure-response gradient and RRs among workers exposed to other chemicals but not trichlorethylene of ten had RRs as large as workers exposed to trichloroethylene. Workers exposed to solvents other than trichloroethylene had slightly increased mortality from asthma, non-Hodgkin's lymphoma, multiple myeloma, and breast cancer. Conclusion-These findings strongly support a causal trichloroethylene because the associations were not significant, not clearly dose-related, and inconsistent between men and women. Because findings from experimental investigations and other epidemiological studies on solvents other than trichloroethylene provide some biological plausibility, the suggested links between these chemicals and nonHodgkin's lymphoma, multiple myeloma, and breast cancer found here deserve further attention. Although this extended follow up cannot rule out a connection between exposures to solvents and some diseases, it seems clear that these workers have not experienced a major increase in cancer mortality or cancer incidence. C1 NCI, Occupat Epidemiol Unit, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv, Silver Spring, MD 20904 USA. RP Blair, A (reprint author), NCI, Occupat Epidemiol Unit, Div Canc Epidemiol & Genet, Execut Plaza N,Room 418, Bethesda, MD 20892 USA. NR 56 TC 127 Z9 127 U1 0 U2 7 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAR PY 1998 VL 55 IS 3 BP 161 EP 171 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YY055 UT WOS:000072107700004 PM 9624267 ER PT J AU Whitcup, SM Pleyer, U Lai, JC Lutz, S Mochizuki, M Chan, CC AF Whitcup, SM Pleyer, U Lai, JC Lutz, S Mochizuki, M Chan, CC TI Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE uveitis; endotoxin; FK506; liposome; inflammation ID FK-506; INVITRO; DISEASE AB Purpose: Liposome preparations of FK506 improve the penetration of topically administered drug into the aqueous humor. The purpose of the experiment was to compare topically administered high-dose oil-dissolved FK506 (OD-FK506) and low-dose liposome bound FK506 (LB-506) for the treatment of endotoxin-induced uveitis (EIU). Methods: Endotoxin-induced uveitis was produced in female Lewis rats with Salmonella typhimurium endotoxin. Four hours prior to endotoxin injection, one eye received to mu l eyedrops every four hours containing either high-dose OD-FK506 at 3 mg/ml (N=20), low-dose LB-FK506 at 0.16 mg/ml (N=19), prednisolone acetate 1% (N=20), or empty liposomes (N=20). Eyes were enucleated 24 hours after endotoxin injection and inflammatory cells were counted on histologic sections by two II-tasked observers. Results: The mean number of infiltrating inflammatory cells per section +/- S.E.M. was 127.8 +/- 20.1, 76.8 +/- 16.7, 75.0 +/- 19.1, and 3.6 +/- 0.4 for animals treated with empty liposomes, LB-FK506, OD-FK506, and prednisolone acetate, respectively. The difference in inflammation between the empty liposome controls and the LB-FK506- and OD-FK506-treated animals was statistically significant (p=0.03 and p=0.02, respectively). The difference in inflammation between the high-dose OD-FK506- and low-dose LB-FK506-treated animals was not statistically significant (o=0.94). Conclusion: in this study, low-dose LB-FK506 and high-dose (OD-FK506) were both effective in inhibiting EIU. Higher concentrations of LB-FK506 are being developed and should augment the therapeutic effect of topical FK506. C1 National Eye Institute, NIH, Bethesda, MD 20892 USA. Humboldt Univ, Charite, Dept Ophthalmol, Berlin, Germany. Kurume Univ, Sch Med, Dept Ophthalmol, Kurume, Fukuoka 830, Japan. RP Whitcup, SM (reprint author), National Eye Institute, NIH, 10 Ctr Dr,Bldg 10,Rm 105221, Bethesda, MD 20892 USA. NR 11 TC 15 Z9 20 U1 0 U2 1 PU AEOLUS PRESS PI BUREN PA PO BOX 740, 4116 ZJ BUREN, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD MAR PY 1998 VL 6 IS 1 BP 51 EP 56 DI 10.1076/ocii.6.1.51.8079 PG 6 WC Ophthalmology SC Ophthalmology GA ZR167 UT WOS:000073944400007 PM 9798194 ER PT J AU Smith, MA Cheson, BD Nelson, AP AF Smith, MA Cheson, BD Nelson, AP TI Clinical trials referral resource: Children with brain tumors SO ONCOLOGY-NEW YORK LA English DT Article C1 NCI, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 1998 VL 12 IS 3 BP 393 EP + PG 3 WC Oncology SC Oncology GA ZC362 UT WOS:000072570300017 PM 9534189 ER PT J AU Bragg, DG AF Bragg, DG TI Radiologic diagnosis of extrathoracic metastases to the lung - The Woodard/Dehdashti/Putman article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. NCI, Bethesda, MD 20892 USA. RP Bragg, DG (reprint author), Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 1998 VL 12 IS 3 BP 441 EP 442 PG 2 WC Oncology SC Oncology GA ZC362 UT WOS:000072570300029 ER PT J AU Fogt, F Zhuang, ZP Poremba, C Dockhorn-Dworniczak, B Vortmeyer, A AF Fogt, F Zhuang, ZP Poremba, C Dockhorn-Dworniczak, B Vortmeyer, A TI Comparison of p53 immunoexpression with allelic loss of p53 in ulcerative colitis-associated dysplasia and carcinoma SO ONCOLOGY REPORTS LA English DT Article DE ulcerative colitis; p53; loss of heterozygosity ID GENETIC ALTERATIONS; COLORECTAL-CANCER; ASTROCYTIC TUMORS; MUTATIONS; PROTEIN AB We correlated p53 overexpression with allelic deletion of p53 in ulcerative colitis (UC) with high grade dysplasia (HGD, n=12) and carcinoma (CA, n=8). Sections were immunostained against p53 and epithelium was microdissected on consecutive sections with subsequent amplification for LOH of p53 (17p). Staining with anti-p53 was positive in HGD (9 of 12) and CA (7 of 8). Percent positive cells were less in HGD than in CA. LOH of p53 was present in HGD (5 of 12) and CA (5 of 7). Of cases with <10% of positive cells, including negative cases, 50% also showed LOH. These results suggest that most cases with prominent p53 overexpression but also significant numbers of cases with weak or negative expression have associated allelic p53 deletion. We conclude that i) immunohistochemical stains but not LOH for p53 correlate with progression of dysplasia to carcinoma, ii) p53 immunohistochemistry appears to more accurately predict biologic behavior of dysplasia and carcinoma in UC compared to allelic deletion studies alone. Further microdissection studies are necessary to evaluate the possibility of different carcinoma risk in patients with low percentage of p53 overexpression and associated LOH. C1 Univ Penn, Presbyterian Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Munster, Gerhard Domagk Inst Pathol, D-48149 Munster, Germany. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol, 39th & Market St, Philadelphia, PA 19104 USA. NR 20 TC 25 Z9 25 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 1998 VL 5 IS 2 BP 477 EP 480 PG 4 WC Oncology SC Oncology GA YX326 UT WOS:000072029000039 PM 9468583 ER PT J AU Ravi, RK Scott, FM Cuttitta, F Weber, E Kalemkerian, GP Nelkin, BD Mabry, M AF Ravi, RK Scott, FM Cuttitta, F Weber, E Kalemkerian, GP Nelkin, BD Mabry, M TI Induction of gastrin releasing peptide by all-trans retinoic acid in small cell lung cancer cells SO ONCOLOGY REPORTS LA English DT Article DE retinoids; retinoic acid receptors; lung cancer ID BRONCHIAL EPITHELIAL-CELLS; BOMBESIN-LIKE PEPTIDES; GENE-EXPRESSION; MESSENGER-RNA; NUCLEAR RECEPTORS; GROWTH-FACTOR; LINES; DIFFERENTIATION; CARCINOMA; SUPERFAMILY AB All-trans retinoic acid (RA) has been shown to inhibit cell proliferation while increasing neuroendocrine differentiation in small cell lung cancer (SCLC) cells. RA and related compounds are rapidly becoming integrated into clinical trials to prevent lung cancers and other aerodigestive neoplasms. We found that expression of gastrin releasing peptide (GRP), which can promote lung tumorigenesis in model systems, was increased by RA in SCLC cells which have functional retinoid signaling. In SCLC cells that possess functional GRP receptors, ectopic expression of RAR gamma increased GRP expression and augmented cloning efficiency, demonstrating that these maneuvers result in biologically active GRP. SCLC cells with defects in RA pathway signaling did not efficiently induce GRP upon RA exposure. In these cells, transfection of RARs rendered the cells competent to induce GRP upon RA exposure. These data show that activation of intact retinoid signaling by RA can induce GRP, a growth factor that can act as a tumor promoter. Our findings suggest the possibility that retinoids may increase, rather than decrease, lung cancer risks in some individuals. C1 Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21287 USA. NCI, Biomarkers & Prevent Res Branch, Rockville, MD 20850 USA. Wayne State Univ, Div Hematol & Oncol, Detroit, MI 48201 USA. Karmanos Canc Inst, Detroit, MI 48201 USA. RP Mabry, M (reprint author), Matrix Pharmaceut Inc, 34700 Campus Dr, Fremont, CA 94555 USA. FU NCI NIH HHS [CA58184, CA48081, CA 58794] NR 41 TC 8 Z9 8 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 1998 VL 5 IS 2 BP 497 EP 501 PG 5 WC Oncology SC Oncology GA YX326 UT WOS:000072029000044 PM 9468588 ER PT J AU White, EL Ross, LJ Schmid, SM Kelloff, GJ Steele, VE Hill, DL AF White, EL Ross, LJ Schmid, SM Kelloff, GJ Steele, VE Hill, DL TI Screening of potential cancer preventing chemicals for induction of glutathione in rat liver cells SO ONCOLOGY REPORTS LA English DT Article DE glutathione; black tea; trans-charcone; N-ethyl-9-cis-retinoic acid; indole-3-carbinol; dehydroepiandrosterone; curcumin; N-(4-carboxyphenyl)retinamide; chemoprevention ID BUTYLATED HYDROXYTOLUENE TREATMENT; SKIN PAPILLOMA FORMATION; LONG-TERM TREATMENT; BLACK TEA; EXPERIMENTAL CARCINOGENESIS; N-NITROSOMETHYLBENZYLAMINE; DIETARY INDOLE-3-CARBINOL; CHEMOPREVENTIVE AGENTS; MODIFYING INFLUENCE; LUNG TUMORIGENESIS AB With BRL 3A hepatocytes, a series of selected, potentially chemopreventive chemicals was evaluated for their capacity to elevate glutathione (GSH) levels. Since sodium selenite consistently increased GSH levels by similar to 70%, it was selected as a positive control. Of 62 test chemicals, eighteen stimulated GSH levels by >30%, but eleven of these had only a modest effect or displayed considerable toxicity. At non-toxic concentrations, seven compounds had substantial activity: black tea extract (decaffeinated), trans-chalcone, N-ethyl-9-cis-retinamide, indole-3-carbinol, dehydroepiandrosterone (DHEA) curcumin and N-(4-carboxyphenyl)retinamide. These should be considered for further development as cancer preventive agents. C1 So Res Inst, Birmingham, AL 35255 USA. NCI, Chemoprevent Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Hill, DL (reprint author), So Res Inst, Box 55305, Birmingham, AL 35255 USA. FU NCI NIH HHS [N01-CN-45587] NR 48 TC 18 Z9 18 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 1998 VL 5 IS 2 BP 507 EP 512 PG 6 WC Oncology SC Oncology GA YX326 UT WOS:000072029000046 PM 9468590 ER PT J AU Benoliel, R Sharav, Y AF Benoliel, R Sharav, Y TI Paroxysmal hemicrania - Case studies and review of the literature SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Review ID CLUSTER HEADACHE; CPH; INDOMETHACIN; CONTINUA; ATTACKS; CHILD; SUMATRIPTAN; MECHANISM; ENTITY; STAGE AB Paroxysmal hemicrania is a vascular-type headache that is characterized by short bouts of severe unilateral pain in the area of the orbit and temple. A chronic and episodic form that has been described is similar to cluster headache and reflects a distinctive temporal pattern. Signs associated with paroxysmal hemicrania include ipsilateral conjunctival injection and tearing with nasal congestion and rhinorrhea. The condition's absolute response to indomethacin pharmacotherapy differentiates paroxysmal hemicrania from cluster headache. Typical symptoms usually make for a relatively straightforward diagnosis of paroxysmal hemicrania, but it may masquerade as pulpitic or temporomandibular-joint-related pain and may even herald systemic disease or malignancy. Paroxysmal hemicrania is a rare syndrome; ill cases have been reported in the literature thus far. All of these cases have been reported by "headache specialists"; no cases of paroxysmal hemicrania were found in the dental literature. In this review, a relatively large series of seven new cases is reported; all seven were seen in an orofacial pain clinic. C1 Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Oral Diag Oral Med & Oral Radiol, Orofacial Pain Clin, IL-91010 Jerusalem, Israel. RP Benoliel, R (reprint author), NIDR, NIH, Bldg 49,Room 1WW25, Bethesda, MD 20892 USA. NR 58 TC 26 Z9 26 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAR PY 1998 VL 85 IS 3 BP 285 EP 292 DI 10.1016/S1079-2104(98)90010-5 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZC202 UT WOS:000072551800011 PM 9540085 ER PT J AU Gulya, AJ AF Gulya, AJ TI The Clinical Trials Branch at the National Institute on Deafness and Other Communication Disorders SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material C1 NIDCD, Clin Trials Branch, Bethesda, MD 20892 USA. RP Gulya, AJ (reprint author), NIDCD, Clin Trials Branch, EPS 400D-7,6120 Execut Blvd, MSC 7180, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 1998 VL 118 IS 3 BP 289 EP 290 PN 1 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZB914 UT WOS:000072520700001 PM 9527105 ER PT J AU Elmer, GI Pieper, JO Negus, SS Woods, JH AF Elmer, GI Pieper, JO Negus, SS Woods, JH TI Genetic variance in nociception and its relationship to the potency of morphine-induced analgesia in thermal and chemical tests SO PAIN LA English DT Article DE behavior genetics; nociception; analgesia; morphine; inbred strain ID OPIATE RECEPTOR CONCENTRATION; MEDULLARY DORSAL HORN; PERCEIVED INTENSITY; NOXIOUS HEAT; STIMULUS-INTENSITY; STRAIN DIFFERENCES; PAIN HISTORY; MICE; RESPONSES; STIMULATION AB The perceived intensity of a painful stimulus is determined in part by the stimulus intensity and environmental conditions. The purpose of this study was to determine the influence of genetic factors in nociception and its contribution to the potency of morphine to produce antinociception. Eight inbred strains of mice were tested across a range of stimulus intensities in thermal (hot plate) and chemical irritant (acetic acid) nociceptive tests. Stimulus intensities in the thermal test included hot plate temperatures of 51, 53, 55, 57 and 59 degrees C. Stimulus intensities in the chemical irritant test included acetic acid concentrations of 0.1, 0.3 and 0.6%. Linear interpolation of stimulus-effect curves revealed large genotype-dependent differences in the effective temperature resulting in a 10 s latency on the hot-plate (ET10") and the acetic acid concentration resulting in the same number of writhes as determined by the area under the curve (AUC(50)). There was no genetic correlation between sensitivity to thermal versus chemical stimuli. Morphine dose response curves were then determined al a fixed stimulus intensity in each test (55 degrees C and 0.6% acetic acid) to determine analgesic ED50 doses for each inbred strain. A significant effect of genotype on relative sensitivity to morphine-induced analgesia in both the thermal and chemical irritant tests was found, however there was no genetic correlation between the potency of morphine in each test. There was an inverse genetic correlation between sensitivity to thermal and chemical stimuli and morphine ED50 values in each respective test. In both tests, strains less sensitive to the nociceptive stimuli were more sensitive to the antinociceptive effects of morphine. Confirmation studies in a separate genetic population confirmed the inverse relationship between hot-plate sensitivity and antinoceptive potency. In summary, this study demonstrated (i) a large degree of genetically determined variability in sensitivity to painful stimuli, (ii) sensitivity to thermal stimuli (hot-plate) is genetically unrelated to sensitivity to chemical (acetic acid) stimuli, (iii) the mechanism by which morphine produces its antinociceptive effects against thermal stimuli is largely genetically independent of the mechanism by which morphine produces its antinociceptive effects against chemical stimuli, and (iv) inherent differences in sensitivity to painful stimuli may be responsible, in part, for individual differences in the potency of morphine's antinociceptive effects. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 NIDA, Behav Pharmacol & Genet Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. McLean Hosp, Alcohol & Drug Addict Res Ctr, Belmont, MA 02178 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48104 USA. RP Elmer, GI (reprint author), Univ Maryland Baltimore Cty, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat,Neurosci Program, POB 21247,Maple & Locust St, Baltimore, MD 21228 USA. EM gelme001@umabnet.ab.umd.edu NR 50 TC 106 Z9 107 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 1998 VL 75 IS 1 BP 129 EP 140 DI 10.1016/S0304-3959(97)00215-7 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA ZB005 UT WOS:000072425300014 PM 9539682 ER PT J AU Makinen, K Loimas, S Kosma, VM Wahlfors, J Pettengill, OS Longnecker, DS Johansson, R Alhava, E AF Makinen, K Loimas, S Kosma, VM Wahlfors, J Pettengill, OS Longnecker, DS Johansson, R Alhava, E TI Azaserine-induced rat pancreas tumor model with transplantable cultured cells SO PANCREAS LA English DT Article DE azaserine; cancer; cultured cells; pancreas; rat; tumor ID TREATED RATS; CANCER; CARCINOMA; ADENOCARCINOMA; INDUCTION; HAMSTERS AB The purpose of this study was to describe the inoculation technique and patterns of growth as well as to characterize typical histological features of Lewis rat subcutaneous and intrapancreatic tumors, induced by inoculation of cultured pancreatic cancer cells (DSL-BA/Cl), Subcutaneous inoculation of cultured cells produced a solid tumor that was a locally invasive, well-to moderately differentiated ductal adenocarcinoma. Tumor take was 100% in animals 5 weeks of age; tumor growth was consistent and predictable and a tumor volume of similar to 1 cm(3) was reached in 8 weeks. After intrapancreatic transplantation the rumors showed the same histological features as subcutaneous tumors. During inoculation carcinoma cells easily spread around the injected area, and after 2 weeks both pancreatic tumors and superficially infiltrating carcinomas were found in the liver and spleen and around the peritoneum. Tumor take was 60% and tumor growth was somewhat indefinite and unpredictable in the pancreas. However, by reducing the injected carcinoma cell volume and solving the technical problems, 100% tumor take was achieved, The tumor volume reached 2 mm(3) during 2 weeks and larger tumors showed a tendency for invasion. According to our results, subcutaneous as well as intrapancreatic tumor induction with cultured cells offers a model for pancreatic cancer studies. C1 Kuopio Univ Hosp, Dept Surg, SF-70210 Kuopio, Finland. Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland. Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. Univ Kuopio, AI Virtanen Inst, SF-70211 Kuopio, Finland. NCHGR, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. Dartmouth Med Sch, Dept Pathol, Lebanon, NH 03756 USA. RP Makinen, K (reprint author), Kuopio Univ Hosp, Dept Surg, SF-70210 Kuopio, Finland. NR 17 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAR PY 1998 VL 16 IS 2 BP 160 EP 164 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YZ569 UT WOS:000072267200009 PM 9510139 ER PT J AU Trollfors, B Taranger, J Lagergard, T Sundh, V Bryla, DA Schneerson, R Robbins, JB AF Trollfors, B Taranger, J Lagergard, T Sundh, V Bryla, DA Schneerson, R Robbins, JB TI Immunization of children with pertussis toxoid decreases spread of pertussis within the family SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pertussis; vaccine; spread; herd immunity ID CONTROLLED TRIAL; VACCINE AB Objective. In a previously reported double blind placebo-controlled trial it was shown that vaccination with pertussis toroid during infancy reduced the incidence of pertussis in the vaccinees. Parents and siblings of participants in the trial were followed for pertussis to determine whether vaccination provided indirect protection of close contacts in a nonvaccinating country with a high incidence of pertussis. Study design. A group of 3450 infants mere randomized to vaccination with diphtheria, tetanus and pertussis toxoids (DTPtxd) or to diphtheria and tetanus toxoids (DT). Pertussis cases were actively sought and diagnosed by cultures and serology in vaccinees (previously reported) and in family members during 2 years after the third vaccination. Results. Pertussis as defined by the World Health Organization (paroxysmal cough of greater than or equal to 21 days and certain laboratory criteria) was diagnosed in 11 parents of DTPtxd recipients and in 26 parents of DT recipients; indirect protection was 60% (95% confidence intervals, 16 to 82%). In nonvaccinated younger siblings of DTPtxd and DT recipients there were 10 and 18 cases of pertussis, respectively; indirect protection was 43% (95% confidence intervals, -31 to 76%). When all cases of pertussis with cough greater than or equal to 7 days were included, the indirect protection was 44% (95% confidence intervals, 7 to 67%) in parents and 56% (95% confidence intervals, 9 to 81%) in younger siblings. Conclusion. Vaccination of children with pertussis toroid reduces spread of pertussis to close contacts, which suggests that mass vaccination with pertussis toroid would induce herd immunity. C1 Gothenburg Univ, Goteborg Pertussis Vaccine Trial, S-41660 Gothenburg, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. RP Trollfors, B (reprint author), Gothenburg Univ, Goteborg Pertussis Vaccine Trial, St Paulig 6, S-41660 Gothenburg, Sweden. FU NICHD NIH HHS [N01-HD-2905] NR 17 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 1998 VL 17 IS 3 BP 196 EP 199 DI 10.1097/00006454-199803000-00005 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA ZB564 UT WOS:000072485200004 PM 9535245 ER PT J AU Mueller, BU NElson, RP Sleasman, J Zuckerman, J Heath-Chiozzi, M Steinberg, SM Balis, FM Brouwers, P Hsu, A Saulis, R Sei, S Wood, LV Zeichner, S Katz, TTK Higham, C Aker, D Edgerly, M Jarosinski, P Serchuck, L Whitcup, SM Pizzuti, D Pizzo, PA AF Mueller, BU NElson, RP Sleasman, J Zuckerman, J Heath-Chiozzi, M Steinberg, SM Balis, FM Brouwers, P Hsu, A Saulis, R Sei, S Wood, LV Zeichner, S Katz, TTK Higham, C Aker, D Edgerly, M Jarosinski, P Serchuck, L Whitcup, SM Pizzuti, D Pizzo, PA TI A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection SO PEDIATRICS LA English DT Article; Proceedings Paper CT 4th Conference on Retroviruses and Opportunistic Infections CY JAN 22-31, 1997 CL WASHINGTON, D.C. DE protease inhibitor; child; HIV-1; CD4 cells; HIV RNA; pharmacokinetics ID HIV-1 INFECTION; PHARMACOKINETIC PROPERTIES; COMBINATION THERAPY; DIDANOSINE; RESISTANCE; ABT-538; PLASMA; ZIDOVUDINE; LAMIVUDINE; STAVUDINE AB Background. Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. Methods. HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m(2) given every 12 hours) were evaluated in two age groups (less than or equal to 2 years, >2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. Results. A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm(3) after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log(10) copies/ml within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m(2) for the 24-week period. Conclusions. The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine. C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. Univ Florida, Gainesville, FL USA. Abbott Labs, Abbott Pk, IL 60064 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, Dept Pharm, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. RP Mueller, BU (reprint author), Childrens Hosp HU 215, Hunnewell 302,300 Longwood Ave, Boston, MA 02115 USA. NR 32 TC 69 Z9 69 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1998 VL 101 IS 3 BP 335 EP 343 DI 10.1542/peds.101.3.335 PG 9 WC Pediatrics SC Pediatrics GA ZA433 UT WOS:000072362800002 PM 9480994 ER PT J AU Troiano, RP Flegal, KM AF Troiano, RP Flegal, KM TI Overweight children and adolescents: Description, epidemiology, and demographics SO PEDIATRICS LA English DT Article DE body weight; body mass index; health surveys; nutrition surveys; child; adolescence; socioeconomic factors ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEYS; NATIONAL-HEALTH; UNITED-STATES; CHILDHOOD OBESITY; PHYSICAL-ACTIVITY; YOUNG MEN; PREVALENCE; TRENDS; WEIGHT AB We describe prevalence and trends in overweight among children and adolescents (6 to 17 years old) in the US population and variation in the prevalence by sex, age, race-ethnicity, income, and educational level. Height and weight were measured in nationally representative surveys conducted between 1963 and 1994: cycles II (1963 to 1965) and III (1966 to 1970) of the National Health Examination Survey (NHES) and the National Health and Nutrition Examination Surveys (NHANES I, 1971 to 1974; NHANES II, 1976 to 1980; and NHANES III, 1988 to 1994). Overweight was defined by the age-and sex-specific 95th percentile of body mass index (BMI) from NHES II and III. BMI values between the 85th and 95th percentiles were considered an area of concern, because at this level there is increased risk for becoming overweight. Approximately 11% of children and adolescents were overweight in 1988 to 1994, and an additional 14% had a BMI between the 85th and 95th percentiles. The prevalence of overweight did not vary systematically with race-ethnicity, income, or education. overweight prevalence increased over time, with the largest increase between NHANES II and NHANES III. Examination of the entire BMI distribution showed that the heaviest children were markedly heavier in NHANES III than in NHES, but the rest of the distribution of BMI showed little change. Data are limited for assessing the causes of the rapid change in the prevalence of overweight. The increased overweight prevalence in US children and adolescents may be one manifestation of a more general set of societal effects. Childhood overweight should be addressed from a public health perspective. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Troiano, RP (reprint author), NCI, NIH, Bethesda, MD 20892 USA. RI Flegal, Katherine/A-4608-2013; OI Troiano, Richard/0000-0002-6807-989X; Flegal, Katherine/0000-0002-0838-469X NR 63 TC 787 Z9 811 U1 6 U2 52 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1998 VL 101 IS 3 SU S BP 497 EP 504 PG 8 WC Pediatrics SC Pediatrics GA ZA434 UT WOS:000072362900002 PM 12224656 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Donowitz, LG Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B Shira, JE Diamond, J O'Connor, ME Packard, JM Reynolds, M Schaeffer, HA Steinhart, CM English, CS Perkins, MT Maruca, R Wilson, JM Wiener, E VanOstenberg, PR Striker, T Raphaely, RC AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Donowitz, LG Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B Shira, JE Diamond, J O'Connor, ME Packard, JM Reynolds, M Schaeffer, HA Steinhart, CM English, CS Perkins, MT Maruca, R Wilson, JM Wiener, E VanOstenberg, PR Striker, T Raphaely, RC TI The revised CDC guidelines for isolation precautions in hospitals: Implications for pediatrics SO PEDIATRICS LA English DT Article AB The Hospital Infection Control Practices Advisory Committee of the US Centers for Disease Control and Prevention and the National Center for Infectious Diseases have issued new isolation guidelines that replace earlier recommendations. Modifications of these guidelines for the care of hospitalized infants and children should be considered specifically as they relate to glove use for routine diaper changing, private room isolation, and common use areas such as playrooms and schoolrooms. These new guidelines replace those provided in the 1994 Red Book and have been incorporated into the 1997 Red Book. C1 Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. Amer Acad Pediat, Comm Hosp Care, Elk Grove Village, IL 60007 USA. Natl Vaccine Program Off, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY USA. Canadian Paediat Soc, Ottawa, ON, Canada. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIH, Bethesda, MD USA. Amer Acad Family Phys, Kansas City, MO 64114 USA. Amer Hosp Assoc, Chicago, IL USA. Natl Assoc Childrens Hosp & Related Inst, Alexandria, VA USA. Joint Commiss Accreditat Healthcare Org, Chicago, IL USA. Amer Acad Pediat, Sect Anesthesiol, Elk Grove Village, IL USA. RP Halsey, NA (reprint author), Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1998 VL 101 IS 3 BP art. no. EP e13 PG 4 WC Pediatrics SC Pediatrics GA ZA433 UT WOS:000072362800034 ER PT J AU Zhai, J Peoples, RW Li, CY AF Zhai, J Peoples, RW Li, CY TI Proton inhibition of GABA-activated current in rat primary sensory neurons SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE pH; GABA receptor; ion channel; sensory neuron; patch-clamp recording ID ROOT GANGLION NEURONS; RECEPTOR; MODULATION; PH; MECHANISMS; RESPONSES; CHANNEL; CELLS; H+ AB The modulation of the Cl- current activated by gamma-aminobutyric acid (GABA) by changes in extracellular pH in freshly isolated rat dorsal root ganglia (DRG) neurons was studied using the whole-cell patch-clamp technique. In the pH range of 5.0-9.0, increased extracellular pH enhanced, and decreased extracellular pH suppressed, current activated by 10 mu M GABA in a reversible and concentration-dependent manner with an IC50 of pH 7.1 in these neurons. Acidification to pH 6.5 inhibited currents activated by the GABA(A)-selective agonist muscimol in all neurons tested. The antagonism of GABA-activated current by lowering the pH was equivalent at holding potentials between -80 and +40 mV and did not involve a significant alteration in reversal potential. Acidification shifted the GABA concentration/response curve to the right, significantly increasing the EC50 for GABA without appreciably changing the slope or maximal value of the curve. Inhibition of the GABA-activated current by protons was not significantly differ ent when the patch-pipette solution was buffered at pH 7.4 or pH 6.5. These results suggest that extracellular protons inhibit GABA(A) receptor channels in primary sensory neurons by decreasing the apparent affinity of the receptor for GABA. This represents a novel mechanism of inhibition by protons of a neurotransmitter-gated ion channel. Proton inhibition of GABA(A) receptor channels may account in part for the modulation by protons of sensory information transmission under certain pathophysiological conditions. C1 Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA. NIAAA, Cellular & Mol Neurobiol Lab, Bethesda, MD 20892 USA. RP Zhai, J (reprint author), Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, 12-432, New York, NY 10032 USA. NR 28 TC 26 Z9 27 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAR PY 1998 VL 435 IS 4 BP 539 EP 545 DI 10.1007/s004240050550 PG 7 WC Physiology SC Physiology GA YX733 UT WOS:000072071800013 PM 9446702 ER PT J AU Wolff, J AF Wolff, J TI Perchlorate and the thyroid gland SO PHARMACOLOGICAL REVIEWS LA English DT Review ID AMIODARONE-INDUCED THYROTOXICOSIS; IODINE-INDUCED THYROTOXICOSIS; INDUCED HYPOTHYROIDISM; CONGENITAL HYPOTHYROIDISM; DISCHARGE TEST; POTASSIUM PERCHLORATE; PLASMA-MEMBRANE; INDUCED HYPERTHYROIDISM; GRAVES-DISEASE; IN-VITRO C1 NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDKD, Biochem Pharmacol Lab, NIH, Bldg B,Room 2A23, Bethesda, MD 20892 USA. NR 201 TC 375 Z9 393 U1 2 U2 20 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD MAR PY 1998 VL 50 IS 1 BP 89 EP 105 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZD175 UT WOS:000072658900005 PM 9549759 ER PT J AU Manley, HJ Smith, JA Garris, RE AF Manley, HJ Smith, JA Garris, RE TI Subcutaneous enoxaparin for outpatient anticoagulation therapy in a patient with an aortic valve replacement SO PHARMACOTHERAPY LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; INTRAVENOUS UNFRACTIONATED HEPARIN; PROSTHETIC HEART-VALVES; INDUCED THROMBOCYTOPENIA; PREVENTION; THROMBOSIS; DISEASE; HOME AB Low-molecular-weight heparins have been administered for a variety of clinical conditions. A patient with a mechanical aortic valve replacement patient underwent elective transurethral prostatectomy. Anticoagulation was managed with unfractionated heparin immediately preoperatively and postoperatively. Warfarin was begun on postoperative day 1. The patient had a prolonged hospitalization due to subtherapeutic international normalized ratios (INR) despite warfarin administration. Because he intended to leave the hospital against medical advice before therapeutic INR was achieved, enoxaparin 1 mg/kg subcutaneously every 12 hours was prescribed to provide anticoagulation, facilitating discharge and improving the patient's quality of life. Enoxaparin was associated with an approximate saving of $4500 over warfarin. The only adverse event reported was bruising at the injection site. C1 Albany Coll Pharm, Albany, NY 12208 USA. Stratton Vet Affairs Med Ctr, Upstate New York Healthcare Network Albany, Albany, NY 12208 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NIH, Dept Pharm, Bethesda, MD 20892 USA. RP Manley, HJ (reprint author), Albany Coll Pharm, 106 New Scotland Ave, Albany, NY 12208 USA. NR 23 TC 12 Z9 12 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR-APR PY 1998 VL 18 IS 2 BP 408 EP 412 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110RY UT WOS:000075395200024 PM 9545164 ER PT J AU Sicard-Rosenbaum, L Danoff, JV Guthrie, JA Eckhaus, MA AF Sicard-Rosenbaum, L Danoff, JV Guthrie, JA Eckhaus, MA TI Effects of energy-matched pulsed and continuous ultrasound on tumor growth in mice SO PHYSICAL THERAPY LA English DT Article; Proceedings Paper CT World-Confederation-for-Physical-Therapy Congress CY JUN 23-30, 1995 CL WASHINGTON, D.C. SP World Confederat Phys Therapy DE energy-matched ultrasound; metastasis; pulsed ultrasound; rhabdomyosarcoma; tumor ID CELLS; PROLIFERATION; RELIABILITY AB Background and Purpose. A diagnosis of cancer is a contraindication for the use of therapeutic ultrasound (US). Continuous US applied to murine tumors has resulted in larger and heavier tumors compared with controls. We compared tumor growth using low-power continuous US and energy-matched pulsed US. Subjects. Female C57BL/6 mice (N=174) were used. Methods. Animals received subcutaneous injections of methylcholanthrene tumor cells. The mice were randomly divided into three groups: 60 mice that received low-power continuous US for 5 minutes at 0.75 W/cm(2) (LC US group), 63 mice that received pulsed US for 12.5 minutes at 1.5 W/cm(2) (pulsed US group), and 51 mice that served as a control group. The LC and pulsed US groups received equal US energy. Both experimental groups received 10 treatments of 3-MHz US, which was applied directly over the tumor. The control group received identical handling but no US. After treatment, the tumors were excised, weighed, and measured. A one-way analysis of variance, followed by Newman-Keuls Post hoc testing, was used to analyze the data. Results. Mean tumor weights (in grams) and volumes (in cubic millimeters) were 0.563 g and 564 mm(3) for the LC US group, 0.560 g and 525 mm(3) for the pulsed US group, and 0.516 g and 406 mm(3) for the control group. Conclusion and Discussion. Reducing total US energy will result in less growth of murine tumors. When infusing equal energy, continuous and pulsed US will produce similar effects on tumor growth. C1 Univ Florida, Coll Hlth Related Profess, Dept Phys Therapy, Gainesville, FL 32611 USA. NIH, Dept Rehabil Med, Phys Therapy Sect, Bethesda, MD 20892 USA. Howard Univ, Coll Allied Hlth, Dept Phys Therapy, Washington, DC 20059 USA. Washington Hosp Ctr, Natl Rehabil Hosp, Washington, DC 20010 USA. NIH, Natl Ctr Res Resources, Vet Resources Program, Sci Serv Branch,Lab Sci Sect,Pathol Unit, Bethesda, MD 20892 USA. RP Sicard-Rosenbaum, L (reprint author), 1847 Commodore Point, Orange Pk, FL 32073 USA. EM loro123@aol.com NR 17 TC 5 Z9 7 U1 0 U2 0 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAR PY 1998 VL 78 IS 3 BP 271 EP 277 PG 7 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA ZE826 UT WOS:000072835500004 PM 9520972 ER PT J AU Wang, BH Ye, CY Stagg, CA Lin, M Fawcett, T VanderKolk, CA Udelsman, R AF Wang, BH Ye, CY Stagg, CA Lin, M Fawcett, T VanderKolk, CA Udelsman, R TI Improved free musculocutaneous flap survival with induction of heat shock protein SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID WARM ISCHEMIC-INJURY; GENE-RELATED PEPTIDE; SUPEROXIDE-DISMUTASE; SKIN FLAPS; THERMOTOLERANCE; RECOVERY; STRESS; SALVAGE; CELLS; RATS AB The cellular response to a wide variety of stresses results in the synthesis of a family of stress response proteins termed heat shock proteins. Recent studies have demonstrated that heat shock proteins produced in response to an initial stress seem to protect against subsequent unrelated stresses. Importantly, hyperthermia-induced heat shack proteins provided protection from ischemia/reperfusion injury in several organ transplantation models. We hypothesized that flee musculocutaneous flap survival could be improved by enhancing the flap's tolerance to relative ischemia by the prior induction of heat shock proteins. Accordingly, we determined the heat shock protein response in skin and muscle after systemic or local heating and examined the effect on free musculocutaneous flap survival in a rat model. Free musculocutaneous naps incorporating thigh adductor muscles and a 2 x 6-cm(2) skin paddle were transplanted to the ipsilateral groin in three groups of male Wistar rats. Systemically heated rats (n = 6) were anesthetized and incubated for 30 minutes at 42 degrees C 6 hours before free musculocutaneous tissue transfer. Locally heated rats (n = 6) were anesthetized, and their donor site anterior thigh was placed for 90 minutes on a heating block set at 44 degrees C 6 hours before free tissue transfer. Control rats (n = 5) did not have heating pretreatment but underwent identical anesthesia. Animals were sacrificed on postoperative day 3, at which time skin loss (cm(2)) and muscle viability, quantified by nitroblue tetrazolium staining time, were assessed in a blinded fashion. The skin and muscle from the free flap were analyzed for HSP72 mRNA and protein using quantitative Northern and Western blot techniques. All free musculocutaneous flaps were viable. However, the locally and systemically heated rats demonstrated a marked improvement of skin survival, which correlated with increased skin levels of HSP72. There were no differences in nitroblue tetrazolium muscle staining times or muscle levels of HSP72 among the three groups. These findings suggest that prior heat-induced heat shock proteins result in improvement in musculocutaneous flap survival, which may have direct clinical applications especially in high-risk patients. C1 Johns Hopkins Univ, Sch Med, Lab Endocrine Surg, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Plast & Reconstruct Surg, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. RP Udelsman, R (reprint author), Johns Hopkins Med Inst, 600 N Wolfe St,Blalock 688, Baltimore, MD 21287 USA. FU NIDDK NIH HHS [DK 02064-05] NR 29 TC 29 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 1998 VL 101 IS 3 BP 776 EP 784 DI 10.1097/00006534-199803000-00029 PG 9 WC Surgery SC Surgery GA ZA118 UT WOS:000072330700029 PM 9500396 ER PT J AU Kaler, SG Tumer, Z AF Kaler, SG Tumer, Z TI Prenatal diagnosis of Menkes disease SO PRENATAL DIAGNOSIS LA English DT Editorial Material ID COPPER-HISTIDINE TREATMENT; CANDIDATE GENE; MUTATION ANALYSIS; ENCODES; THERAPY C1 NINDS, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. John F Kennedy Inst, DK-2600 Glostrup, Denmark. Univ Copenhagen, Panum Inst, Dept Med Genet, DK-2200 Copenhagen, Denmark. RP Kaler, SG (reprint author), NINDS, NIH, Bldg 10,Room 4D-20,10 Ctr Dr,MSC 1424, Bethesda, MD 20892 USA. NR 16 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAR PY 1998 VL 18 IS 3 BP 287 EP 289 DI 10.1002/(SICI)1097-0223(199803)18:3<287::AID-PD352>3.3.CO;2-Z PG 3 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA ZE612 UT WOS:000072812000012 PM 9556046 ER PT J AU Marcus, AC Morra, M Rimer, BK Stricker, M Heimendinger, J Wolfe, P Darrow, SL Hamilton, L Cox, DS Miller, N Perocchia, RS AF Marcus, AC Morra, M Rimer, BK Stricker, M Heimendinger, J Wolfe, P Darrow, SL Hamilton, L Cox, DS Miller, N Perocchia, RS TI A feasibility test of a brief educational intervention to increase fruit and vegetable consumption among callers to the cancer information service SO PREVENTIVE MEDICINE LA English DT Article DE neoplasms prevention and control; diet; information services; health education ID UNITED-STATES; BASE-LINE; WORKING WELL; HEALTH; PREVENTION; PROGRAM; WOMEN; NUTRITION; SMOKING; MODEL AB Background In this paper, results are reported from a pilot study designed to test the feasibility of a proactive educational intervention delivered to callers of the Cancer Information Service (CIS). Methods. The study used a randomized two-group design (intervention vs control). Callers assigned to the intervention condition received a brief educational intervention at the end of usual service to increase fruit and vegetable consumption. As part of the intervention, key educational messages and materials drawn from the 5 A Day for Better Health program of the National Cancer Institute were provided to CIS callers over the telephone and then reinforced with two follow-up mailings. Results. Results from this pilot study indicated high levels of adherence to protocol by CIS Information Specialists who delivered the intervention to eligible CIS callers. Results obtained from the 4-week telephone follow-up interviews indicated that intervention subjects (n = 142) reported higher consumption of fruits and vegetables, averaging approximately 0.75 servings more per day (P < 0.01) than control subjects (n = 134). Conclusion. Nearly 80% of CIS callers endorsed the strategy of providing 5 A Day information at the end of usual service, even if such information was not specifically requested by the caller (i.e., the information was provided to CIS callers proactively). (C) 1998 American Health Foundation and Academic Press. C1 AMC, Ctr Canc Res, Denver, CO 80214 USA. Yale Univ, Ctr Comprehens Canc, New Haven, CT 06520 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Illinois, Survey Res Lab, Chicago, IL 60607 USA. Johns Hopkins Canc Informat Serv, Baltimore, MD 21205 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53711 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Ctr Comprehens Canc, Durham, NC 27705 USA. RP Marcus, AC (reprint author), AMC, Ctr Canc Res, Denver, CO 80214 USA. FU NCI NIH HHS [P01-CA57586] NR 40 TC 19 Z9 19 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR-APR PY 1998 VL 27 IS 2 BP 250 EP 261 DI 10.1006/pmed.1998.0246 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA ZK404 UT WOS:000073317500019 PM 9579004 ER PT J AU Gallin, JI AF Gallin, JI TI The need for clinical research education in the medical school curriculum SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Editorial Material DE informatics; mentoring; training; National Institutes of Health C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gallin, JI (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAR-APR PY 1998 VL 110 IS 2 BP 93 EP 95 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZU657 UT WOS:000074220000004 PM 9542764 ER PT J AU Ackerman, MJ AF Ackerman, MJ TI The visible human project SO PROCEEDINGS OF THE IEEE LA English DT Article DE biomedical imaging; image data bases AB The Visible Human Project data sets are designed to serve as a common reference point for the study of human anatomy, as a set of common public-domain data for resting medical imaging algorithms, and as a testbed and model for the construction of image libraries that can be accessed through networks. The data sets are being applied to a wide range of educational, diagnostic, treatment planning, virtual reality, artistic, mathematical, and industrial uses by more than 800 licensees in 27 countries. But key issues remain in the development of methods to link such image data to text-based data. Standards do not currently exist for such linkages. Basic research is needed in the description and representation of image-based structures and in the connection of image-based structural-anatomical data to text-based functional-physiological data. This is the larger, longterm goal of the Visible Human Project: To link the print library of functional-physiological knowledge with the image library of structural-anatomical knowledge transparently into one unified resource of health information. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. RP Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. EM ackerman@nlm.nih.gov NR 10 TC 205 Z9 214 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9219 EI 1558-2256 J9 P IEEE JI Proc. IEEE PD MAR PY 1998 VL 86 IS 3 BP 504 EP 511 DI 10.1109/5.662875 PG 8 WC Engineering, Electrical & Electronic SC Engineering GA ZB270 UT WOS:000072454200006 ER PT J AU Mori, T Gustafson, KR Pannell, LK Shoemaker, RH Wu, L McMahon, JB Boyd, MR AF Mori, T Gustafson, KR Pannell, LK Shoemaker, RH Wu, L McMahon, JB Boyd, MR TI Recombinant production of cyanovirin-N, a potent human immunodeficiency virus inactivating protein derived from a cultured Cyanobacterium SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article AB Here we describe the recombinant production and purification of a novel anti-human immunodeficiency virus (HIV) protein, cyanovirin-N (CV-N), in Escherichia coli, Initial attempts to express CV-N using a vector containing an ompA signal peptide sequence resulted in production of an intractable mixture of the full-length (101 amino acid residue) protein and a truncated form lacking the first two N-terminal amino acids, The truncated protein was observed regardless of the host cell line, culture conditions, or induction time. These observations suggested that an as yet unidentified protease or peptidase was responsible for proteolytic cleavage between the second and third N-terminal amino acids of CV-N when presented as an ompA-CV-N fusion protein, When the ompA signal peptide sequence was replaced by a pelB signal peptide sequence, CV-N was produced in high yield as a single, homogeneous protein. This was confirmed by electrospray ionization mass spectrometry and N-terminal sequencing, This expression system provides a basis for large-scale production of clinical grade CV-N for further research and development as an anti-HIV microbicide. (C) 1998 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment Diag & C, Frederick, MD 21702 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment Diag & C, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 8 TC 60 Z9 71 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAR PY 1998 VL 12 IS 2 BP 151 EP 158 DI 10.1006/prep.1997.0838 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA ZC787 UT WOS:000072618000002 PM 9518455 ER PT J AU Xu, D Tsai, CJ Nussinov, R AF Xu, D Tsai, CJ Nussinov, R TI Mechanism and evolution of protein dimerization SO PROTEIN SCIENCE LA English DT Article DE compactness; dimerization; domain swapping; intermediate; kinetics; oligomer evolution ID ESCHERICHIA-COLI; CONFORMATIONAL STABILITY; EQUILIBRIUM DENATURATION; DOMAIN; REPRESSOR; DIMER; DISSOCIATION; INTERMEDIATE; FRAGMENTS; SUBUNIT AB We have investigated the mechanism and the evolutionary pathway of protein dimerization through analysis of experimental structures of dimers. We propose that the evolution of dimers may have multiple pathways, including (1) formation of a functional dimer directly without going through an ancestor monomer, (2) formation of a stable monomer as an intermediate followed by mutations of its surface residues, and (3), a domain swapping mechanism, replacing one segment in a monomer by an equivalent segment from an identical chain in the dimer. Some of the dimers which are governed by a domain swapping mechanism may have evolved at an earlier stage of evolution via the second mechanism. Here, we follow the theory that the kinetic pathway reflects the evolutionary pathway. We analyze the structure-kinetics-evolution relationship for a collection of symmetric homodimers classified into three groups: (1) 14 dimers, which were referred to as domain swapping dimers in the literature; (2) nine 2-state dimers, which have no measurable intermediates in equilibrium denaturation; and (3), eight 3-state dimers, which have stable intermediates in equilibrium denaturation. The analysis consists of the following stages: (i) The dimer is divided into two structural units, which have twofold symmetry. Each unit contains a contiguous segment from one polypeptide chain of the dimer, and its complementary contiguous segment from the other chain. (ii) The division is repeated progressively, with different combinations of the two segments in each unit. (iii) The coefficient of compactness is calculated for the units in all divisions. The coefficients obtained for different cuttings of a dimer form a compactness profile. The profile probes the structural organization of the two chains in a dimer and the stability of the monomeric state. We describe the features of the compactness profiles in each of the three dimer groups. The profiles identify the swapping segments in domain swapping dimers, and can usually predict whether a dimer has domain swapping. The kinetics of dimerization indicates that some dimers which have been assigned in the literature as domain swapping cases, dimerize through the 2-state kinetics, rather than through swapping segments of performed monomers. The compactness profiles indicate a wide spectrum in the kinetics of dimerization: dimers having no intermediate stable monomers; dimers having an intermediate with a stable monomer structure; and dimers having an intermediate with a stable structure in part of the monomer. These correspond to the multiple evolutionary pathways for dimer formation. The evolutionary mechanisms proposed here for dimers are applicable to other oligomers as well. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, IRSP,SAIC Frederick, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, IRSP,SAIC Frederick, Bldg 468,Room 151, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov FU NCI NIH HHS [1-CO-74102] NR 48 TC 90 Z9 90 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAR PY 1998 VL 7 IS 3 BP 533 EP 544 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZC005 UT WOS:000072530000001 PM 9541384 ER PT J AU Garrett, DS Seok, YJ Peterkofsky, A Clore, GM Gronenborn, AM AF Garrett, DS Seok, YJ Peterkofsky, A Clore, GM Gronenborn, AM TI Tautomeric state and pK(alpha) of the phosphorylated active site histidine in the N-terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate: sugar phosphotransferase system SO PROTEIN SCIENCE LA English DT Article DE histidine phosphorylation; N-terminal domain of enzyme I; pK(alpha); tautomeric state ID SALMONELLA-TYPHIMURIUM; TRANSPORT; PROTEIN; NMR; HPR AB The phosphorylated form of the N-terminal domain of enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli has been investigated by one-bond and long-range H-1-N-15 correlation spectroscopy. The active site His 189 is phosphorylated at the N epsilon 2 position and has a pK(a) of 7.3, which is one pH unit higher than that of unphosphorylated His 189. Because the neutral form of unphosphorylated His 189 is in the N delta 1-H tautomer, and its N epsilon 2 atom is solvent inaccessible and accepts a hydrogen bond from the hydroxyl group of Thr 168, both protonation and phosphorylation of His 189 must be accompanied by a change in the side-chain conformation of His 189, specifically from a chi(2) angle in the g(+) conformer in the unphosphorylated state to the g(-) conformer in the phosphorylated state. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Seoul 151742, South Korea. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 18 TC 26 Z9 27 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAR PY 1998 VL 7 IS 3 BP 789 EP 793 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZC005 UT WOS:000072530000029 PM 9541412 ER PT J AU Kaskie, B Niederehe, G AF Kaskie, B Niederehe, G TI Neuropsychological assessment in senile dementia SO PSIKHOLOGICHESKII ZHURNAL LA Russian DT Article ID MINI-MENTAL STATE; ALZHEIMERS-DISEASE; MILD DEMENTIA; KORSAKOFFS SYNDROME; DIVIDED ATTENTION; TEST-PERFORMANCE; MEMORY; IMPAIRMENT; DYSFUNCTION; POPULATION AB Neuropsychological assessment plays an integral role in screening for and diagnosings of senile dementia of the Alzheimer type (SDAT), in particular determining whether elderly individuals manifest global mental deterioration as shown by impairments in multiple areas of cognitive function. Neuropsychological tests distinguish reliably between healthy older adults and those with SDAT. Other clinical objectives served by neuropsychological testing include: profiling strengths and deficits in the individual's cognitive functioning; assessing cognitive changes over time, particularly treatment outcomes; and determining the severity and progression of dementia (staging). Longitudinal studies using such assessments can track the patterns of cognitive decline in SDAT, typically beginning with problems in memory, language production, and/or psychomotor performance, and affecting additional areas of cognitive functioning as the disease progresses. In research on blain-behavior relationships, neuropsychological assessments help to specify the cognitive-dysfunctions associated with SDAT and to identify relations between them and their anatomical correlates, thereby also increasing the understanding of these cognitive functions in general. Illustrative tests and recent reports are described in five areas of cognitive functioning: memory and learning, language functioning, visuospatial functioning, psychomotor performance, and attention. Methodological considerations for future research studies are also discussed. C1 Univ So Calif, Fresno, CA USA. NIMH, Rockville, MD 20857 USA. RP Kaskie, B (reprint author), Univ So Calif, Fresno, CA USA. NR 53 TC 0 Z9 0 U1 0 U2 1 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0205-9592 J9 PSIKHOL ZH JI Psikhologicheskii Zhurnal PD MAR-APR PY 1998 VL 19 IS 2 BP 27 EP + PG 14 WC Psychology, Multidisciplinary SC Psychology GA ZM642 UT WOS:000073560600003 ER PT J AU Weickert, CS Kleinman, JE AF Weickert, CS Kleinman, JE TI The neuroanatomy and neurochemistry of schizophrenia SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; HIPPOCAMPAL PYRAMIDAL CELL; DORSOLATERAL PREFRONTAL CORTEX; D2 DOPAMINE-RECEPTORS; GLUTAMIC-ACID DECARBOXYLASE; DRUG-NAIVE SCHIZOPHRENICS; POST-MORTEM BRAINS; GRAY-MATTER VOLUME AB Substantial progress, in part owing to recent refinements in methodology, has been made in unraveling the anatomic correlates of schizophrenia. Subtle pathomorphologic changes, distinct from those of well-known degenerative brain disorders, have been observed. Neurochemical characterization has illuminated the nature of these morphologic abnormalities and has pointed to complex dysregulation of neurotransmitters and G proteins. New biochemical hypotheses such as the glutamate hypothesis have replaced and revitalized more established concepts in the neurochemistry of schizophrenia. C1 St Elizabeth Hosp, Ctr Neurosci, NIMH,Div Intramural Res Program, Sect Neuropathol,Clin Brain Disorders Branch, Washington, DC 20032 USA. RP Weickert, CS (reprint author), St Elizabeth Hosp, Ctr Neurosci, NIMH,Div Intramural Res Program, Sect Neuropathol,Clin Brain Disorders Branch, 2700 Martin Luther King,Jr,Ave SE, Washington, DC 20032 USA. RI Shannon Weickert, Cynthia/G-3171-2011 NR 179 TC 22 Z9 22 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 1998 VL 21 IS 1 BP 57 EP + DI 10.1016/S0193-953X(05)70361-0 PG 20 WC Psychiatry SC Psychiatry GA ZD612 UT WOS:000072704200005 PM 9551491 ER PT J AU Panlilio, LV Weiss, SJ Schindler, CW AF Panlilio, LV Weiss, SJ Schindler, CW TI Motivational effects of compounding discriminative stimuli associated with food and cocaine SO PSYCHOPHARMACOLOGY LA English DT Article DE self-administration; stimulus control; incentive-motivation; stimulus compounding; cocaine; food; rat ID REINFORCEMENT; OPERANT; RATS; ACQUISITION; BEHAVIOR AB In previous experiments, the compounding of two discriminative stimuli associated with the same reinforcer increased rats' responding approximately threefold, regardless of whether the reinforcer was food, water, cocaine, or shock-avoidance. Compounding a discriminative stimulus associated with food with one associated with water increased responding two-fold. In the present experiment, compounding a discriminative stimulus associated with food with one associated with cocaine increased responding two-fold. These results support the hypothesis that 1) the effects of stimuli associated with reinforcers from the same incentive class (appetitive or aversive) are mutually enhancing, and 2) the combined effects of stimuli associated with two different reinforcers from within the same class are not as strong as those of two stimuli associated with the same reinforcer. These results also suggest that discriminative stimuli associated with non-drug reinforcers may increase the motivation to self-administer cocaine when encountered in combination with drug-related stimuli. C1 NIDA, Preclin Pharmacol Lab, Behav Pharmacol & Genet Sect, Div Intramural Res,NIH, Baltimore, MD 21224 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Lab, Behav Pharmacol & Genet Sect, Div Intramural Res,NIH, POB 5180, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA-08651-01A1] NR 24 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 1998 VL 136 IS 1 BP 70 EP 74 DI 10.1007/s002130050540 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZB009 UT WOS:000072425700009 PM 9537684 ER PT J AU Ginsberg, AM AF Ginsberg, AM TI The tuberculosis epidemic - Scientific challenges and opportunities SO PUBLIC HEALTH REPORTS LA English DT Article ID MYCOBACTERIUM-BOVIS BCG; DRUG-RESISTANT TUBERCULOSIS; TRANSPOSON MUTAGENESIS; CALMETTE-GUERIN; GENE-EXPRESSION; VACCINES; ANTIGEN; DNA; INFECTION; STRAIN AB ONE IN EVERY THREE people on Earth is believed to be infected with Mycobacterium tuberculosis, leading to seven to eight million cases of active tuberculosis (TB) per year and approximately three million deaths annually. This epidemic, like those of most infectious diseases, creates scientific challenges and opportunities as it raises the demand for public health solutions. The currently available weapons for fighting TB are inadequate. The ultimate goal of biomedical TB research is to lessen the public health burden of this disease by developing improved diagnostic, therapeutic, and intervention strategics. Achieving this goal requires a base of knowledge about the biology of M. tuberculosis and related mycobacteria, their interactions with human and animal hosts, and the nature of an effective host-protective immune response. TB researchers are applying this accumulating base of knowledge to developing rapid, easy-to-use diagnostic assays appropriate for low- as well as high-income countries, improving the current complicated therapeutic regimen, identifying potential new drugs to combat multidrug-resistant. TB, and creating more effective vaccines. C1 NIAID, TB Leprosy & Other Mycobacterial Dis, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Ginsberg, AM (reprint author), Solar Bldg,Rm 3806,6003 Execut Blvd,MSC 7630, Bethesda, MD 20892 USA. EM ag73i@nih.gov NR 52 TC 31 Z9 31 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 1998 VL 113 IS 2 BP 128 EP 136 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 161RU UT WOS:000078303500018 PM 9719813 ER PT J AU Segal, DD Crespo, CJ Smit, E AF Segal, DD Crespo, CJ Smit, E TI Active seniors - Protect them, don't neglect them SO PUBLIC HEALTH REPORTS LA English DT Article ID HEALTH C1 NHLBI, Off Prevent Educ & Control, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Segal, DD (reprint author), NIDA, Medicat Dev Div, NIH, Rm 11A55,5600 Fishers Lane, Rockville, MD 20857 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 1998 VL 113 IS 2 BP 137 EP 139 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 161RU UT WOS:000078303500019 PM 9719814 ER PT J AU Fischer, G Holl, AC Volff, JN Vandewiele, D Decaris, B Leblond, P AF Fischer, G Holl, AC Volff, JN Vandewiele, D Decaris, B Leblond, P TI Replication of the linear chromosomal DNA from the centrally located oriC of Streptomyces ambofaciens revealed by PFGE gene dosage analysis SO RESEARCH IN MICROBIOLOGY LA English DT Article DE Streptomyces ambofaciens; oriC; linear chromosome; replication; PFGE ID COELICOLOR A3(2) CHROMOSOME; PHYSICAL MAP; LIVIDANS 66; REGION; ORIGIN; ORGANIZATION; CLONING; STRAINS; GENOME AB From a cosmid clone of Streptomyces ambofaciens containing the dnaA and gyrAB genes, a 2.7-kb self-replicating DNA fragment containing the chromosome replication origin oriC was isolated. This cosmid was previously mapped physically to a region near the middle of the 8-Mb linear chromosomal DNA. A pulsed-field gel electrophoresis time-course analysis revealed that sequences flanking oriC were overrepresented relative to the rest of the chromosomal DNA during rapid growth, indicating that this origin is active. In addition, the terminal regions of the chromosomal DNA showed a slight overrepresentation at the onset of stationary phase. C1 Univ Nancy 1, Fac Sci, Lab Genet & Microbiol, Unite Associee INRA 952, F-54506 Vandoeuvre Nancy, France. Univ Sci & Tech Lille Flandres Artois, Lab Genet & Evolut Populat, F-59655 Villeneuve Dascq, France. Univ Wurzburg, Theodor Boveri Inst Biosci, Bioctr, D-97097 Wurzburg, Germany. NICHD, NIH, Bethesda, MD 20892 USA. RP Leblond, P (reprint author), Univ Nancy 1, Fac Sci, Lab Genet & Microbiol, Unite Associee INRA 952, BP 239, F-54506 Vandoeuvre Nancy, France. RI Fischer, Gilles/G-6654-2016; OI LEBLOND, Pierre/0000-0002-8703-454X; Fischer, Gilles/0000-0001-5732-2682 NR 31 TC 8 Z9 8 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD MAR PY 1998 VL 149 IS 3 BP 203 EP 210 DI 10.1016/S0923-2508(98)80080-6 PG 8 WC Microbiology SC Microbiology GA ZJ148 UT WOS:000073184300005 PM 9766222 ER PT J AU Territo, PR Altimiras, J AF Territo, PR Altimiras, J TI The ontogeny of cardio-respiratory function under chronically altered gas compositions in Xenopus laevis SO RESPIRATION PHYSIOLOGY LA English DT Article DE amphibians; African clawed frog (Xenopus laevis); development, egg; egg, amphibian, O-2 transport; oxygen, transport ID BULLFROGS RANA-CATESBEIANA; OXYGEN-CONSUMPTION; CHRONIC HYPOXIA; LARVAE; HYPEROXIA; RESPONSES; BLOOD AB The importance of diffusion and perfusion in terms of oxygen transport was evaluated by chronically altering environmental O-2 availability (hypoxia or hyperoxia) and blood O-2 content (carbon monoxide) through development in Xenopus Inevis. Oxygen consumption ((M) over dot(O2)), individual wet mass, heart rate (fH), and stroke volume (SV) were measured in animals raised from eggs to pre-metamorphic climax while maintained at 11, 21 and 35 kPa O-2, combined with and without 2 kPa carbon monoxide. Additionally, cardiac output ((Q) over dot), and a recently defined O-2 consumption/transport quotient ((M) over dot(O2).(Q) over dot(O2)(-1)) were calculated. Wet mass, (M) over dot(O2), and fH, were not significantly different between controls and experimental treatments at any developmental stage. However, with hemoglobin oxygen transport blocked by carbon monoxide, the exposed larvae showed an increased SV, (Q) over dot and (M) over dot(O2).(Q) over dot(O2)(-1). Combined, these data suggest that in spite of impaired blood O-2 convection, normal aerobic metabolism was maintained, indicating that direct diffusion of O-2 plays an important role in supplying oxygen during early development. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Nevada, Dept Biol Sci, Las Vegas, NV 89154 USA. RP Territo, PR (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 1,Room B3-07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Altimiras, Jordi/G-4239-2012 NR 28 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD MAR PY 1998 VL 111 IS 3 BP 311 EP 323 DI 10.1016/S0034-5687(97)00117-5 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA ZL031 UT WOS:000073391900008 PM 9628236 ER PT J AU Perng, RP Chen, YM Wu, MF Chou, KC Lin, WC Liu, JM Whang-Peng, J AF Perng, RP Chen, YM Wu, MF Chou, KC Lin, WC Liu, JM Whang-Peng, J TI Phase II trial of intrapleural paclitaxel injection for non-small-cell lung cancer patients with malignant pleural effusions SO RESPIRATORY MEDICINE LA English DT Article ID METASTATIC BREAST-CANCER; INTRACAVITARY BLEOMYCIN; CORYNEBACTERIUM-PARVUM; OVARIAN-CANCER; PLEURODESIS; MANAGEMENT; TETRACYCLINE; TALC; TAXOL; SECONDARY AB A phase II clinical trial of intrapleural paclitaxel injection for malignant effusions of non-small-cell lung cancer (NSCLC) was conducted in order to evaluate the efficacy and toxicity profile of paclitaxel pleurodesis in patients with malignant effusions. From February to May of 1996, 15 NSCLC patients with malignant pleural effusions were enrolled on study. After adequate drainage and assurance of lung re-expansion, paclitaxel 125 mg m(-2) diluted in normal saline was infused through a preinserted pig-tail catheter which was removed 2 h later. Chest radiography and sonography were scheduled 4 days later; depending on whether there remained a significant amount of pleural effusion, further drainage by needle thoracentesis or by a pig-tail catheter was performed. All patients were assessable for toxicity. Ipsilateral chest and/or shoulder pain, fever, facial flushing and nausea were the most frequent side-effects. Grade 4 neutropenia, grade 3 anaemia, and grade 3 renal impairment occurred in one patient each. Fourteen patients were evaluable for response at the end of the fourth week. Overall response rate of pleural effusion in evaluable patients was 92.9%, with a complete response rate of 28.6%. There was one out of 14 evaluable patients whose measurable tumour lesion decreased by more than 50% (partial response). No disease progression was noted among evaluable patients at the end of the fourth week. It is concluded that paclitaxel is a useful agent for the treatment of malignant pleural effusions. Because of its relatively low systemic toxicity, intrapleural paclitaxel injection in combination with systemic chemotherapy or radiotherapy can be considered in treating NSCLC patients with malignant pleural effusions. C1 Vet Gen Hosp, Chest Dept, Taipei, Taiwan. Natl Yang Ming Univ, Sch Med, Taipei, Taiwan. Natl Hlth Res Inst, Canc Clin Res Ctr, Taipei, Taiwan. RP Chen, YM (reprint author), NCI, NIH, Bldg 10,Room 4B49, Bethesda, MD 20892 USA. NR 40 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD MAR PY 1998 VL 92 IS 3 BP 473 EP 479 DI 10.1016/S0954-6111(98)90294-3 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA ZH551 UT WOS:000073122400017 PM 9692108 ER PT J AU Varis, K Taylor, PR Sipponen, P Samloff, IM Heinonen, OP Albanes, D Harkonen, M Huttunen, JK Laxen, F Virtamo, J AF Varis, K Taylor, PR Sipponen, P Samloff, IM Heinonen, OP Albanes, D Harkonen, M Huttunen, JK Laxen, F Virtamo, J CA Helsinki Gastritis Study Grp TI Gastric cancer and premalignant lesions in atrophic gastritis: A controlled trial on the effect of supplementation with alpha-tocopherol and beta-carotene SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE alpha-tocopherol; atrophic gastritis; beta-carotene; cancer prevention; gastric cancer; gastric dysplasia; nutrition ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; VITAMIN-A; DYSPLASIA; LINXIAN; CHINA; VEGETABLES; POPULATION; MUCOSA; FRUIT AB Background: Vitamin E and beta-carotene are considered to decrease the risk of gastric cancer both in humans and in laboratory animals. We studied the effect of dietary supplementation with alpha-tocopherol and beta-carotene on the end-of-trial prevalence of premalignant and malignant lesions of the stomach in older men with atrophic gastritis. Methods: The study was carried out within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC study) in Finland, in which 29,133 male smokers aged 50-69 years were randomly assigned to receive daily 50 mg alpha-tocopherol, 20 mg beta-carotene, both of these agents, or placebo, for 5-8 years. Serum pepsinogen was determined at base line and after 3 years' supplementation to find men with atrophic gastritis. A low serum pepsinogen I level, indicating atrophic gastritis of the the corpus area of the stomach, was found in 2132 men. These men were invited to have upper gastrointestinal endoscopy (gastroscopy), which was performed on 1344 subjects after a median supplementation time of 5.1 years. Results: Neoplastic alterations were found in 63 of the men (4.7%): 42 with definite dysplasias of low grade (moderate dysplasia), 7 with definite dysplasias of high grade (severe dysplasia), 11 with carcinomas (of which 7 were 'early' cancers), and 3 with carcinoid tumors. Neither alpha-tocopherol (relative risk, 0.98; 95% confidence interval, 0.57-1.69) nor beta-carotene (relative risk, 1.13; 95% confidence interval, 0.65-1.95) supplementation had any association with end-of-trial prevalence of gastric neoplasias after adjustment for other possible risk factors. The effect was not modified by base-line serum level or dietary intake of vitamins, prevalence of Helicobacter pylori infection, or other covariates. Conclusions: We thus conclude that supplementation with alpha-tocopherol or beta-carotene for 5 years has no major impact on the occurrence of neoplastic changes of the stomach in older male smokers with atrophic gastritis. C1 Jorvi Hosp, Dept Pathol, FIN-02740 Espoo, Finland. Univ Helsinki, Dept Clin Chem, SF-00100 Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. NCI, Bethesda, MD 20892 USA. VA Med Ctr, Sepulveda, CA USA. RP Sipponen, P (reprint author), Jorvi Hosp, Dept Pathol, FIN-02740 Espoo, Finland. RI Albanes, Demetrius/B-9749-2015 NR 29 TC 60 Z9 61 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD MAR PY 1998 VL 33 IS 3 BP 294 EP 300 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZD642 UT WOS:000072707400015 PM 9548624 ER PT J AU Matsuda, M Ulfgren, AK Lenkei, R Petersson, M Ochoa, AC Lindblad, S Andersson, P Klareskog, L Kiessling, R AF Matsuda, M Ulfgren, AK Lenkei, R Petersson, M Ochoa, AC Lindblad, S Andersson, P Klareskog, L Kiessling, R TI Decreased expression of signal-transducing CD3 zeta chains in T cells from the joints and peripheral blood of rheumatoid arthritis patients SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNOVIAL-FLUID LYMPHOCYTES; NATURAL-KILLER-CELLS; TUMOR-BEARING MICE; ANTIGEN RECEPTOR; NK CELLS; HLA-DR; ACTIVATED MACROPHAGES; MOLECULES; CARCINOMA; RESPONSES AB Although T cells from patients with rheumatoid arthritis (RA) have previously been determined to have poor proliferative responses to a variety of stimuli, the underlying mechanism is not known. We have investigated the expression of the signal-transducing zeta molecule in subsets of T cells and natural killer (NK) cells derived from the peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of RA patients using quantitative flow cytometry, Western blot analysis and immunohistochemistry. A decrease of zeta expression was apparent in all investigated lymphocyte subsets from the PBMC and SFMC of RA patients, as compared to the corresponding subsets from healthy age-and sex-matched controls. A less pronounced reduction of cell surface-located CD3 epsilon, CD4 and CD8 was also located in T cells from SFMC as compared to PBMC from RA patients. Biochemical demonstration of the low or absent CD3 zeta in PBMC from patients with RA was achieved by Western blot analysis. Immunohistochemical staining and image analysis also confirmed the low expression of zeta chains in synovial tissue of RA patients. The possibility that the decreased expression of zeta and of immune functions of T cells from RA patients may be related to the presence of free oxygen radiclals, as we have previously reported in cancer patients, should be considered. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. Karolinska Hosp, Dept Rheumatol, S-10401 Stockholm, Sweden. Calab, Stockholm, Sweden. NCI, Frederick, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Karolinska Hosp, Radiumhemmet, Dept Expt Oncol, S-10401 Stockholm, Sweden. RP Kiessling, R (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. NR 40 TC 43 Z9 43 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAR PY 1998 VL 47 IS 3 BP 254 EP 262 PG 9 WC Immunology SC Immunology GA ZA885 UT WOS:000072411800010 PM 9519864 ER PT J AU Agodoa, L AF Agodoa, L TI NIH research goals and federal funding past and present SO SEMINARS IN DIALYSIS LA English DT Article C1 NIDDKD, End Stage Renal Dis Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Agodoa, L (reprint author), NIDDKD, End Stage Renal Dis Program, Div Kidney Urol & Hematol Dis, NIH, Bldg 45,Room 6AS-13B, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 1998 VL 11 IS 2 BP 71 EP 76 DI 10.1111/j.1525-139X.1998.tb00304.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA ZB797 UT WOS:000072509000002 ER PT J AU Avila, NA Ling, A Metcalfe, DD Worobec, AS AF Avila, NA Ling, A Metcalfe, DD Worobec, AS TI Mastocytosis: Magnetic resonance imaging patterns of marrow disease SO SKELETAL RADIOLOGY LA English DT Article DE mastocytosis; MRI; plain radiographs ID MAST-CELL DISEASE; SYSTEMIC MASTOCYTOSIS AB Objective. To report the bone marrow MRI findings of patients with mastocytosis and correlate them with clinical, pathologic, and radiographic features. Design and patients. Eighteen patients with mastocytosis had T1-weighted spin echo and short tau inversion recovery MRI of the pelvis at 0.5 T. In each patient the MR pattern of marrow disease was classified according to intensity and uniformity and was correlated with the clinical category of mastocytosis, bone marrow biopsy results, and radiographic findings. Results. Two patients had normal MRI scans and normal bone marrow biopsies. One patient had a normal MRI scan and a marrow biopsy consistent with mastocytosis. Fifteen patients had abnormal MRI scans and abnormal marrow biopsies. There were several different MR patterns of marrow involvement; none was specifically associated with any given clinical category of mastocytosis. Fifteen of the 18 patients had radiographs of the pelvis; of those, 13 with abnormal MRI scans and abnormal marrow biopsies had the following radiographic findings: normal (nine); sclerosis (three); diffuse osteopenia (one). Conclusion. While radiographs are very insensitive for the detection of marrow abnormalities in mastocytosis, MRI is very sensitive and may display several different patterns of marrow involvement. C1 Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), Dept Diagnost Radiol, Bldg 10,Room 1C-660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. NR 14 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAR PY 1998 VL 27 IS 3 BP 119 EP 126 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA ZD469 UT WOS:000072689100001 PM 9554001 ER PT J AU Tycko, R AF Tycko, R TI Optical pumping in indium phosphide: P-31 NMR measurements and potential for signal enhancement in biological solid state NMR SO SOLID STATE NUCLEAR MAGNETIC RESONANCE LA English DT Article DE optical pumping; semiconductors; nuclear magnetic resonance ID NUCLEAR-MAGNETIC-RESONANCE; LASER-POLARIZED XENON; PHOTOSYNTHETIC REACTION CENTERS; GAAS QUANTUM-WELLS; HIGH-PURITY GAAS; CROSS-POLARIZATION; GALLIUM-ARSENIDE; ELECTRONIC STATES; SPIN POLARIZATION; PUMPED NMR AB The initial results of optically-pumped, directly-detected NMR experiments on InP are reported. At low temperatures (4.2 K and above) and in a 9.39 T magnetic field, irradiation of a sample of an undoped InP wafer with 835-nm-wavelength light from a diode laser enhances the spin polarization of P-31 nuclei near the sample surface in a manner that depends on the polarization of the light. The nuclear spin polarization is monitored by direct radio-frequency detection of nuclear free induction-decay signals. The maximum nuclear spin polarization [S-zn] generated by optical pumping is approximately -0.004, corresponding to a spin temperature of -0.5 K. The nuclear spin polarization may be limited in these experiments by the use of a high photon energy (1.484 eV) relative to the InP band gap (1.423 eV at low temperatures). It is proposed that optically-pumped InP may be useful as a source of enhanced nuclear spin polarizations for solid state NMR measurements on organic and biological overlayers deposited on InP substrates. Estimates are given for the magnitude of the spin polarization and the efficiency of the polarization transfer from the semiconductor substrate to the overlayer that would be required to permit solid state NMR measurements on sub-nanomole quantities of molecules in the overlayer. These estimates appear well within the range of possibility. (C) 1998 Elsevier Science B.V. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 36 TC 59 Z9 59 U1 4 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-2040 J9 SOLID STATE NUCL MAG JI Solid State Nucl. Magn. Reson. PD MAR PY 1998 VL 11 IS 1-2 SI SI BP 1 EP 9 DI 10.1016/S0926-2040(97)00092-1 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Physics, Condensed Matter; Spectroscopy SC Chemistry; Physics; Spectroscopy GA ZT411 UT WOS:000074083000002 PM 9650786 ER PT J AU Cowley, GS Murthy, AE Parry, DM Schneider, G Korf, B Upadhyaya, M Harper, P MacCollin, M Bernards, A Gusella, JF AF Cowley, GS Murthy, AE Parry, DM Schneider, G Korf, B Upadhyaya, M Harper, P MacCollin, M Bernards, A Gusella, JF TI Genetic variation in the 3 ' untranslated region of the neurofibromatosis 1 gene: Application to unequal allelic expression SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID CDNA SEQUENCE; TYPE-1 GENE; NF1 GENE; MUTATIONS; NEUROBLASTOMA AB Neurofibromatosis type I (NF1) is a common genetic disorder caused by inactivation of neurofibromin, a protein capable of modulating signal transduction by activating Ras-GTPase activity. We have used cDNA cloning and Northern blot analysis to confirm the NF1 gene produces alternatively polyadenylated mRNAs with 3' untranslated regions (3'UTR) that show striking evolutionary conservation. Scanning of the 3'UTRs for genetic variation revealed three common sequence polymorphisms (>30% heterozygosity), one less informative polymorphism (similar to 5% heterozygosity) and one rare variant (1/144 chromosomes). These differences were used to examine relative levels of expression of normal and mutant NF1 alleles in lymphoblast cell lines and in one case, autopsy tissue, from patients with NF1. Unequal allelic expression (up to 4-fold) was observed in a subset of both sporadic and familial NF1 cases. Where linkage phase could be determined the allele segregating with the disorder displayed a relative reduction in expression. However; the magnitude of this effect was variable suggesting the operation of additional, non-genetic factors in determining the degree of relative expression of the mutant allele. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Wales Coll Med, Inst Med Genet, Cardiff CF4 4XN, S Glam, Wales. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Cowley, GS (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS24279, NS22224] NR 23 TC 15 Z9 15 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAR PY 1998 VL 24 IS 2 BP 107 EP 119 DI 10.1023/B:SCAM.0000007113.28381.53 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 158EH UT WOS:000078102700003 PM 9919310 ER PT J AU Williams, KS Susla, G Temeck, BK Piscitelli, SC Pass, HI AF Williams, KS Susla, G Temeck, BK Piscitelli, SC Pass, HI TI Pharmacokinetics of fentanyl during hyperthermic, isolated lung perfusion SO SOUTHERN MEDICAL JOURNAL LA English DT Article; Proceedings Paper CT 90th Annual Scientific Assembly of the Southern-Medical-Association CY NOV 20-24, 1996 CL BALTIMORE, MARYLAND SP So Med Assoc ID ALFENTANIL; PLASMA AB Background. Hyperthermic, isolated pulmonary perfusion with tumor necrosis factor is a surgical procedure that isolates the pulmonary vasculature from the systemic circulation in patients with unresectable primary or metastatic disease confined to the chest. High drug levels are delivered to the perfused organ, avoiding systemic toxicity, and preventing loss of active drug through metabolism. Methods. The pharmacokinetics of fentanyl are evaluated in three patients while the operative lung is hyperthermic, ventilated, and perfused with an asanguineous solution during nonpulsatile bypass. A loading dose of fentanyl, 1.5 mu g/kg to 2.5 mu g/kg, was given during the induction of anesthesia followed by a continuous infusion of 150 mu g/hr. Results. Results showed no difference in mean plasma fentanyl concentrations before, during, or after bypass and was consistent with clearance values previously reported in healthy adult surgical patients in the absence of an extracorporeal circuit. Conclusions. Adjustments in fentanyl dosing are not required before, during, or after hyperthermic, isolated pulmonary perfusion is established and a steady state of fentanyl is achieved. C1 NCI, Dept Anesthesiol, Clin Ctr Pharm, Anesthesia Sect,NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Williams, KS (reprint author), NCI, Dept Anesthesiol, Clin Ctr Pharm, Anesthesia Sect,NIH, Bldg 10,10 Ctr Dr,MSC 1512,Rm 2C624, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAR PY 1998 VL 91 IS 3 BP 261 EP 265 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 170AC UT WOS:000078782100009 PM 9521366 ER PT J AU Chae, K Lindzey, J McLachlan, JA Korach, KS AF Chae, K Lindzey, J McLachlan, JA Korach, KS TI Estrogen-dependent gene regulation by an oxidative metabolite of diethylstilbestrol, diethylstilbestrol-4 ',4 ''-quinone SO STEROIDS LA English DT Article DE estrogen receptor; diethylstilbestrol; DES-quinone; transactivation ID 4',4''-DIETHYLSTILBESTROL QUINONE; RECEPTOR STEREOCHEMISTRY; LIGAND-BINDING; FEMALE MOUSE; RESPONSIVENESS; INTERMEDIATE; ANALOGS; INVIVO AB Diethylstilbestrol (DES) is a well-characterized carcinogen in humans and animals although its mechanisms of carcinogenicity are not yet known. While the estrogenic activity of DES is important, there is evidence that oxidative metabolism also plays an important role for its toxicity. DES is oxidatively metabolized in vivo and in vitro to a number of compounds including diethylstilbestrol-4',4 "-quinone (DQ), an unstable and reactive intermediate, and Z,Z-dienestrol (ZZ-DIEN). Estrogen receptor (ER) binding assays with mouse uterine cytosol indicate that DES, DQ and ZZ-MIEN have relative binding affinities of 286, 3.6 and 0.3, respectively, relative to estradiol as 100. In addition, DQ binds irreversibly and specifically to ER suggesting that DQ may be biologically active despite its rapid metabolism and lower binding affinity compared to DES. To test this, COS-1 cells were transfected with an estrogen responsive reporter construct containing a VitA2 estrogen response element (ERE) with or without an ER expression vector. In the presence of ER, treatments with DES, DQ and ZZ-DIEN resulted in 11, 10, and 2-fold induction of chloramphenicol acetyltransferase (CAT) activity, respectively. This induction was mediated by estrogen receptor since it was suppressed by pretreatment with a 10-fold excess of the pure antiestrogen ICI 182,780. These data indicate that DQ is a biologically active intermediate that is capable of transactivation of estrogen responsive genes through the ER. Furthermore, the data suggest that the ability of DQ to irreversibly bind ER may result in persistent stimulation of ER. This persistent stimulation may be related to the carcinogenicity of DES. (C) 1998 by Elsevier Science Inc. C1 NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. Tulane Xavier Ctr Bioenvironm Res, New Orleans, LA USA. RP Chae, K (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, POB 12233,101 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 24 TC 13 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-128X J9 STEROIDS JI Steroids PD MAR PY 1998 VL 63 IS 3 BP 149 EP 157 DI 10.1016/S0039-128X(97)00158-X PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA ZE860 UT WOS:000072838900006 PM 9558716 ER PT J AU Molteni, M Zulian, C Scrofani, S Della Bella, S Bonara, P Kohn, LD Scorza, R AF Molteni, M Zulian, C Scrofani, S Della Bella, S Bonara, P Kohn, LD Scorza, R TI High frequency of T-cell lines responsive to immunodominant epitopes of thyrotropin receptor in healthy subjects SO THYROID LA English DT Article ID AUTOIMMUNE THYROID-DISEASE; MYELIN BASIC-PROTEIN; RECOMBINANT INTERFERON-ALPHA; EXTRACELLULAR DOMAIN; TSH RECEPTOR; SYNTHETIC PEPTIDES; MYASTHENIA-GRAVIS; EXPRESSION; CLONING; RECOGNITION AB In this study we analyzed the proliferative response to the extracellular domain of thyrotropin receptor (TSHR-ECD) of T-cell lines raised from healthy subjects. We found high frequencies of cell lines reactive to TSHR-ECD, ranging from 12% to 37%. The response of the cell lines to a set of overlapping peptides of TSHR-ECD showed that the most recognized epitopes by T lymphocytes are on the C-terminal portion. In particular, the regions of residues 360-396 and 258-277 are immunodominant in T-lymphocyte reactivity. A group of cell lines specific for the peptides of TSHR-ECD lost the response to the peptides during time in culture. However, these lines were still responsive to TSHR extracellular domain. The cloning of one of these lines showed three types of T-cell clones: (1) CD4(+) clones (it = 4) highly responsive to the TSHR-ECD; (2) CD4(+) clones (n = 4) low responsive to TSHR-ECD; (3) CD8(+) clones (n = 9) not responsive to TSHR-ECD. The first group of clones was stable during time in culture, while the second group was characterized by the loss of the specific response to TSHR-ECD after some weeks from the first analysis. The observation of a spontaneous anergy in the second group of CD4(+) clones suggests that mechanisms of control of the lymphocyte response to TSHR-ECD could be activated in vitro. C1 Univ Milan, Osped Maggiore, IRCCS, Ist Med Interna Malattie Infett & Immunopatol, I-20122 Milan, Italy. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Scorza, R (reprint author), Univ Milan, Osped Maggiore, IRCCS, Ist Med Interna Malattie Infett & Immunopatol, Via F Sforza 35, I-20122 Milan, Italy. OI Della Bella, Silvia/0000-0003-0818-5049; Molteni, Monica/0000-0002-5990-3971 NR 37 TC 7 Z9 7 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAR PY 1998 VL 8 IS 3 BP 241 EP 247 DI 10.1089/thy.1998.8.241 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD648 UT WOS:000072708400007 PM 9545111 ER PT J AU Bondy, CA AF Bondy, CA TI Growth hormone augmentation - A new era? SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material ID FACTOR-I; MAMMARY-GLAND; THERAPY; GH; PROLIFERATION; MEN C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10N262,10 Ctr Dr 1862, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 1998 VL 26 IS 2 BP 213 EP 216 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA ZD156 UT WOS:000072657000004 PM 9547858 ER PT J AU Ward, JM Peters, JM Perella, CM Gonzalez, FJ AF Ward, JM Peters, JM Perella, CM Gonzalez, FJ TI Receptor and nonreceptor-mediated organ-specific toxicity of di(2-ethylhexyl)phthalate (DEHP) in peroxisome proliferator-activated receptor alpha-null mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE knockout mice; peroxisomal proliferator; liver; peroxisomal proliferator activated receptor; di(2-ethylhexyl)phthalate (DEHP); kidney; cystic kidneys ID ENZYME GENE-EXPRESSION; RISK AB The peroxisome proliferator-activated receptor alpha (PPAR alpha) is the mediator of the biological effects of peroxisome proliferators through control of gene transcription. To determine if the toxic effects of di(2-ethylhexyl)phthalate (DEHP) are mediated by PPAR alpha, we examined its effect in PPAR alpha-null mice. Male Sv/129 mice, PPAR alpha-null (-/-) or wild-type (+/+) were fed ad libitum either a control diet or one containing 12,000 ppm DEHP for up to 24 wk. Significant body weight loss and high mortality was observed in (+/+) mice fed DEHP. By 16 wk, all DEHP-fed (+/+) mice had died of cystic renal tubular disease. In contrast, the (-/-) mice fed DEHP had no changes in body weight until later in the study nor increased mortality. Histologically, (+/+) mice fed DEHP had typical toxic lesions in liver, kidney, and testis while (-/-) mice fed DEHP had no toxic liver lesions but did show evidence of toxicity in kidney and testis after 4-8 wk of feeding, which progressed into moderate lesions by 24 wk. Analysis of hepatic and renal mRNAs showed a typical pleiotropic response in gene expression in the DEHP-fed (+/+) mice that was absent in the DEHP-fed (-/-) mice. These results provide evidence that PPAR alpha mediates the subacute-chronic toxicity of DEHP in liver, kidney, and testis. However, because (-/-) mice did develop toxic lesions in kidney and testis, DEHP can also act through PPAR alpha-independent pathways in mediating renal and testicular toxicity. C1 Off Lab Anim Resources, Anim Studies Branch, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. RP Ward, JM (reprint author), NCI, FCRDC, Fairview 201,POB B, Frederick, MD 21702 USA. RI Peters, Jeffrey/D-8847-2011 NR 25 TC 174 Z9 180 U1 2 U2 5 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 1998 VL 26 IS 2 BP 240 EP 246 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA ZD156 UT WOS:000072657000008 PM 9547862 ER PT J AU Bucher, JR Haseman, JK Herbert, RA Hejtmancik, M Ryan, MJ AF Bucher, JR Haseman, JK Herbert, RA Hejtmancik, M Ryan, MJ TI Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat SO TOXICOLOGICAL SCIENCES LA English DT Article ID HEPATOCARCINOGEN OXAZEPAM; B6C3F1 MICE; LIVER; BENZODIAZEPINES; ELIMINATION; METABOLISM; KINETICS; MOUSE; RISK AB Oxazepam and related benzodiazepines are used in the treatment of anxiety, Carcinogenicity studies of oxazepam were performed with the F344 rat because of marked differences in tumor responses observed in NTP studies with B6C3F1 and Swiss-Webster mice compared to the results of Sprague-Dawley rat studies submitted to the FDA by a manufacturer to support registration of the drug. Groups of 50 male and 50 female F344/N rats were fed diets containing 0, 625, 2500, or 5000 ppm oxazepam for up to 105 weeks. A stop-exposure group of 50 males and 50 females received 10,000 ppm oxazepam in diet for 26 weeks, after which animals received control diet. All 5000- and 10,000-ppm stop-exposure males died before the end of the study. Survival of 2500-ppm males and females was lower than that of controls. Body weight gains of 2500- and 5000-ppm males and females were less than those of controls, Male rats exposed to 2500 ppm had an increased incidence of renal tubule adenoma and hyperplasia. In addition, the incidences of renal tubule adenoma and hyperplasia were increased in the 10,000-ppm stop-exposure group. The incidences of nephropathy in exposed females were greater than those in controls, and the severity of nephropathy increased in exposed males. Epithelial hyperplasia and chronic inflammation of the nonglandular stomach were increased in males given 2500 and 5000 ppm and the incidence of ulcers of the nonglandular stomach in 2500-ppm males was also greater than that in controls. In males exposed to 5000 ppm, mineralization of the glandular stomach and erosion of the duodenum were observed. In females exposed to 2500 ppm, the incidences of epithelial hyperplasia, chronic inflammation, and ulcers of the nonglandular stomach and the incidence of erosion in the glandular stomach were increased. The incidences of centrilobular hepatocyte hypertrophy in males and females given 2500 and 5000 ppm were greater than those in controls. In summary, there was equivocal evidence of carcinogenicity in males based on increased renal tubule adenomas in groups which also had significantly enhanced nephropathy. There was no evidence of carcinogenicity of oxazepam in females given a diet containing 625, 2500, or 5000 ppm for 2 years or 10,000 ppm for 6 months, (C) 1998 Society of Toxicology. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Mem Labs, Columbus, OH 43210 USA. RP Bucher, JR (reprint author), POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 1998 VL 42 IS 1 BP 1 EP 12 PG 12 WC Toxicology SC Toxicology GA ZM362 UT WOS:000073530900001 PM 9538042 ER PT J AU Cunningham, ML Bucher, JR AF Cunningham, ML Bucher, JR TI Pharmacodynamic responses of F344 rats to the mouse hepatocarcinogen oxazepam in a 90-day feed study SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID HEPATOCELLULAR PROLIFERATION; MUTAGENIC NONCARCINOGENS; B6C3F1 MICE; LIVER; CARCINOGENS; BIOTRANSFORMATION; ELIMINATION; METABOLISM AB Oxazepam (Serax) is a widely used benzodiazepine anxiolytic agent and a metabolite of other benzodiazepines such as Valium and Librium. Chronic feeding studies indicated that oxazepam is an hepatocarcinogen in B6C3F1 mice but did not increase hepatic tumors in F344 rats. The present study was performed to compare the hepatic responses of rats with our previous findings in mice to explore the reason(s) for the dramatic differences in tumor response between the two species. Male F344 rats (10 per dose-time group) received diets containing oxazepam at 0, 25, 125, 2500, and 5000 ppm. Hepatocyte labeling indices were measured immuno-histochemically by PCNA and BrDU during the last 7 days before sacrifices after 15, 30, 45, and 90 days of dosing. Serum oxazepam was determined by reverse phase HPLC. Results indicated that oxazepam induced significant liver weight increases in a dose-related fashion by 15 days, which remained elevated for the entire study. No important clinical chemistry or pathology changes were noted except those related to hypertrophy. Cell proliferation was significantly increased in a dose-related manner by the 15-and 30-day timepoint in the 2500 and 5000 ppm groups. The most significant finding in the present study of oxazepam was plasma levels of the parent compound. Plasma levels in rats were dramatically lower than in B6C3F1 mice exposed to oxazepam in studies conducted earlier at the same dose levels. These results suggest that the early responses of rats and mice to oxazepam, such as cell proliferation and clinical chemistry parameters, are similar. Our previous studies demonstrated that oxazepam metabolites are excreted in the urine of rats, similar to humans, whereas mice excrete oxazepam metabolites in bile allowing enterohepatic recirculation, which results in high plasma levels of oxazepam. These data indicate that the rat excretes oxazepam kinetically (rate and route) similar to humans, but the mouse produces metabolites similar to humans. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Cunningham, ML (reprint author), NIEHS, Environm Toxicol Program, POB 12233,Mail Drop B3-10, Res Triangle Pk, NC 27709 USA. EM cunning1@niehs.nih.gov RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 NR 25 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR PY 1998 VL 149 IS 1 BP 41 EP 48 DI 10.1006/taap.1997.8330 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZA337 UT WOS:000072353400005 PM 9512725 ER PT J AU Zemel, R Dickman, R Tamary, H Bukh, J Zaizov, R Tur-Kaspa, R AF Zemel, R Dickman, R Tamary, H Bukh, J Zaizov, R Tur-Kaspa, R TI Viremia, genetic heterogeneity, and immunity to hepatitis G GB-C virus in multiply transfused patients with thalassemia SO TRANSFUSION LA English DT Article ID BLOOD-DONORS; DRUG-USERS; INFECTION; SEQUENCES; ALPHABET; ANTIBODY; DISEASE; GENOME AB BACKGROUND: Thalassemia patients are at high risk for posttransfusion hepatitis. Hepatitis G virus (HGV) has been suspected of being responsible for acute and chronic hepatitis. STUDY DESIGN AND METHODS: The prevalence of HGV infection, its possible association to liver disease, the genetic heterogeneity among the various HGV isolates, and immunity to HGV were studied in 36 thalassemia patients with reverse transcriptase-polymerase chain reaction assay and sequence analysis. RESULTS: HGV RNA was detected in seven patients (19.4%) only two of whom had evidence of hepatitis C virus infection as well. Sequence analysis of the NS3 gene from isolates of the five patients infected with HGV alone revealed 84.7 to 90.9 percent homology at the nucleotide level. Prolonged HGV viremia was not associated with significant liver enzyme elevation. All five patients were chronically infected with the same viral strain. E2 antibodies were detected in 57 percent of the HGV-nonviremic patients and in only 1 of 7 viremic patients. CONCLUSION: HGV is associated with persistent viremia but not with significant biochemical evidence of liver damage. There is some genetic heterogeneity among HGV isolates from thalassemia patients in Israel. C1 Tel Aviv Univ, Felsenstein Med Res Ctr, Mol Hepatol Res Lab, IL-49100 Petah Tikva, Israel. Rabin Med Ctr, Dept Med D, Petah Tikva, Israel. Rabin Med Ctr, Liver Inst, Petah Tikva, Israel. Schneider Childrens Med Ctr, Dept Pediat Hematol Oncol, Petah Tikva, Israel. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. RP Zemel, R (reprint author), Tel Aviv Univ, Felsenstein Med Res Ctr, Mol Hepatol Res Lab, Beilinson Campus, IL-49100 Petah Tikva, Israel. NR 26 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 1998 VL 38 IS 3 BP 301 EP 306 DI 10.1046/j.1537-2995.1998.38398222876.x PG 6 WC Hematology SC Hematology GA ZH556 UT WOS:000073123200014 PM 9563412 ER PT J AU Brown, P AF Brown, P TI Donor pool size and the risk of blood-borne Creutzfeldt-Jakob disease SO TRANSFUSION LA English DT Editorial Material ID HUMAN GROWTH-HORMONE; VIRUS; CONTAMINATION; TRANSFUSION C1 NINCDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NINCDS, CNS Studies Lab, NIH, Bldg 36,Room 5B21,MSC 4158, Bethesda, MD 20892 USA. NR 13 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 1998 VL 38 IS 3 BP 312 EP 315 DI 10.1046/j.1537-2995.1998.38398222878.x PG 4 WC Hematology SC Hematology GA ZH556 UT WOS:000073123200016 PM 9563414 ER PT J AU Wawrousek, E AF Wawrousek, E TI IBC conference on engineered animal models: Advances and applications, Washington, DC, USA, 22-23 September 1997 SO TRANSGENIC RESEARCH LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Wawrousek, E (reprint author), NEI, NIH, Bldg 6,Room 2A04,6 Ctr Dr,MSC 2730, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD MAR PY 1998 VL 7 IS 2 BP 141 EP 145 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA ZB092 UT WOS:000072434900009 PM 9643963 ER PT J AU Doyle, JL Stubbs, L AF Doyle, JL Stubbs, L TI Ataxia, arrhythmia and ion-channel gene defects SO TRENDS IN GENETICS LA English DT Review ID LONG QT SYNDROME; MUSCLE CHLORIDE CHANNEL; POTASSIUM CHANNEL; GLYCINE RECEPTOR; CARDIAC-ARRHYTHMIA; PERIODIC PARALYSIS; MISSENSE MUTATION; ALPHA-4 SUBUNIT; MOLECULAR-BASIS; K+ CHANNELS AB Ion channels are essential to a wide range of physiological functions including neuronal signaling, muscle contraction cardiac pacemaking, hormone secretion and cell proliferation The important role that highly regulated ion influx plays In these processes has been underscored by a recent flurry of discovered linking ion-channel gene mutations to inherited disorders. Ion channels of many, different types hare been demonstrated as being causative factors. In genetic disease This review discusses the growing number of disorders associated with genes of the voltage-gated ion channel superfamily with special focus on those characterized by neurological, neuromuscular, or cardiac dysfunction in humans and mice. C1 Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. RP Doyle, JL (reprint author), NIHGR, NIH, Bethesda, MD 20892 USA. EM jdoyle@venus.nhgri.nih.gov; stubbs5@llnl.gov OI Stubbs, Lisa/0000-0002-9556-1972 NR 56 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAR PY 1998 VL 14 IS 3 BP 92 EP 98 DI 10.1016/S0168-9525(97)01370-X PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZB856 UT WOS:000072514900004 PM 9540405 ER PT J AU Groll, AH De Lucca, AJ Walsh, TJ AF Groll, AH De Lucca, AJ Walsh, TJ TI Emerging targets for the development of novel antifungal therapeutics SO TRENDS IN MICROBIOLOGY LA English DT Review ID PROTEIN-KINASE-C; SYRINGAE PV SYRINGAE; CANDIDA-ALBICANS; SACCHAROMYCES-CEREVISIAE; AUREOBASIDIN-A; CELL-WALL; CRYPTOCOCCUS-NEOFORMANS; N-MYRISTOYLTRANSFERASE; BIOLOGICAL-ACTIVITY; SQUALENE SYNTHASE AB Invasive mycoses have become important causes of morbidity and mortality in immunocompromised patients. New approaches for antifungal therapy are required to meet the challenges imposed by these life-threatening infections. Such approaches are being developed through identification of novel biochemical and molecular targets of pathogenic fungi. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. ARS, So Reg Res Ctr, USDA, New Orleans, LA USA. RP Groll, AH (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM twalsh@pbmac.nci.nih.gov NR 69 TC 62 Z9 66 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAR PY 1998 VL 6 IS 3 BP 117 EP 124 DI 10.1016/S0966-842X(97)01206-7 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA ZC100 UT WOS:000072539900020 PM 9582938 ER PT J AU Gorse, GJ McElrath, MJ Matthews, TJ Hsieh, RH Belshe, RB Corey, L Frey, SE Kennedy, DJ Walker, MC Eibl, MM AF Gorse, GJ McElrath, MJ Matthews, TJ Hsieh, RH Belshe, RB Corey, L Frey, SE Kennedy, DJ Walker, MC Eibl, MM CA Natl Inst Allergy Infect Dis AIDS Vaccine Eval TI Modulation of immunologic responses to HIV-1(MN) recombinant gp160 vaccine by dose and schedule of administration SO VACCINE LA English DT Article DE HIV-1(MN) envelope glycoprotein; vaccine; immune response; cytokines; immunoglobulin subclasses; neutralizing antibody ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEINS; LYMPHOCYTE PROLIFERATIVE RESPONSES; SUBUNIT VACCINE; HTLV-III; NEUTRALIZING ANTIBODIES; SERONEGATIVE VOLUNTEERS; BINDING-ANTIBODIES; CANDIDATE VACCINE; HIV VACCINE AB The safety and immunogenicity of HIV-1(MN) recombinant gp160 (MN rgp160) vaccine in healthy, uninfected volunteers was tested in a double-blind study with a factorial design. By random assignment, 20 volunteers received three 200 mu g doses of MN rgp160 and four volunteers received placebo at days 0, 28, and 168 or 0, 56, and 224. Of the 24 volunteers, 16 received 200 mu g or 800 mu g of MN rgp160 and two received placebo at day 532 (month 18). The vaccine was safe. It induced T cell memory measured by Th1 cytokine production and lymphocyte proliferation, and serum anti-MN rgp160 IgG (all subclasses) and IgA antibodies. Fifteen of 20 vaccinees developed neutralizing antibody. The regimen including immunizations on days 0, 28, and 168 followed by the 800 Icg fourth dose was most immunogenic. (C) 1998 Elsevier Science Ltd. All lights reserved. C1 St Louis Univ, Ctr Hlth Sci,Sch Med, Dept Internal Med, Div Infect Dis & Immunol, St Louis, MO 63110 USA. Dept Vet Affairs Med Ctr, St Louis, MO 63110 USA. Univ Washington, Seattle, WA 98104 USA. Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA. EMMES Corp, Potomac, MD 20854 USA. NIAID, Vaccine Res & Dev Branch, Div Aids, Rockville, MD USA. IMMUNO AG, Vienna, Austria. RP Gorse, GJ (reprint author), St Louis Univ, Ctr Hlth Sci,Sch Med, Dept Internal Med, Div Infect Dis & Immunol, 3635 Vista Ave,FDT-8N, St Louis, MO 63110 USA. FU NIAID NIH HHS [N01-AI-15106, N01-AI-05064, N01-AI-45211] NR 63 TC 21 Z9 21 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 MAR PY 1998 VL 16 IS 5 BP 493 EP 506 DI 10.1016/S0264-410X(97)80003-5 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YV082 UT WOS:000071787800007 PM 9491504 ER PT J AU Bugert, JJ Lohmuller, C Damon, I Moss, B Darai, G AF Bugert, JJ Lohmuller, C Damon, I Moss, B Darai, G TI Chemokine homolog of Molluscum contagiosum virus: Sequence conservation and expression SO VIROLOGY LA English DT Article DE Molluscum contagiosum virus; chemokine homolog; DNA nucleotide sequencing; in vitro RNA synthesis; transcription; RT-PCR ID NUCLEOTIDE-SEQUENCE; EARLY GENES; GENOME; DNA; POXVIRUSES; CYTOKINES; TYPE-1; CELLS AB An analysis of the complete Molluscum contagiosum virus (MCV-I) genome sequence revealed a 104-amino-acid open reading frame (MC148R) that is structurally related to the beta (CC) family of chemokines. The predicted MCV chemokine homolog (MCCH) has a deletion in the NH2-terminal activation domain, suggesting the absence of chemoattractant activity. The principal objectives of the present study were to determine whether: (i) MCCH is conserved in independent isolates of MCV-1 and MCV-2; (ii) MCCH mRNA is expressed in vivo; and (iii) the MCCH protein is secreted from mammalian cells. The nucleotide sequence of the MCCH gene focus was determined for 27 isolates of MCV-1 and 2 of MCV-2 obtained from 29 MCV-infected individuals. In each case, the characteristic CC sequence, the NH2-terminal deletion, and the length of the open reading frame were conserved, although there were some, mostly conservative, amino acid substitutions. Since MCV cannot be propagated in cell culture, mRNA was synthesized in vitro by the early transcription apparatus in purified MCV virions. MCCH RNA was amplified by RT-PCR; the sequence included the complete open reading frame and extended 40 to 50 nucleotides past the first poxviral termination signal (TTTTTNT). similar RT-PCR results were obtained using total cellular RNA derived from MCV-infected tissue specimens. Finally, the MCCH open reading frame was expressed in a vaccinia virus Vector and the predicted size polypeptide was secreted into the medium, as determined by Western blotting. Taken together, our data support the prediction that MCV expresses a secreted chemokine homolog that could antagonize the inflammatory response in vivo. (C) 1998 Academic Press. C1 Univ Heidelberg, Inst Med Virol, D-69120 Heidelberg, Germany. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Darai, G (reprint author), Univ Heidelberg, Inst Med Virol, Neuenheimer Feld 324, D-69120 Heidelberg, Germany. RI Bugert, Joachim/D-1705-2012 OI Bugert, Joachim/0000-0002-0556-3211 NR 33 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 1 PY 1998 VL 242 IS 1 BP 51 EP 59 DI 10.1006/viro.1997.9001 PG 9 WC Virology SC Virology GA ZA335 UT WOS:000072353200007 PM 9501046 ER PT J AU Ramsey-Ewing, A Moss, B AF Ramsey-Ewing, A Moss, B TI Apoptosis induced by a postbinding step of vaccinia virus entry into Chinese hamster ovary cells SO VIROLOGY LA English DT Article ID HOST-RANGE RESTRICTION; INTERLEUKIN-1-BETA CONVERTING-ENZYME; ACTIVATION-INDUCED APOPTOSIS; PENETRATION PROTEIN; MEDIATED APOPTOSIS; VIRAL INHIBITION; ENCODED SERPIN; GENE-PRODUCT; COWPOX; DEATH AB Unlike most cell types examined, nonpermissive Chinese hamster ovary (CHO) cells readily underwent apoptosis upon infection with vaccinia virus (VV). Apoptosis was observed as early as 3 h postinfection with an electrophoretic assay of DNA fragmentation and by 8 h using an in situ (TUNEL) assay. The CHO hr gene from cowpox virus, which overcomes host range restriction of VV in CHO cells, merely delayed the onset of apoptosis by approximately 3 h. Intermediate and late viral protein synthesis were not necessary for apoptosis since these events do not proceed under nonpermissive conditions, Apoptosis also occurred in the presence of cytosine arabinoside or cycloheximide, which inhibits DNA or protein synthesis, respectively, and after infection with a mutant virus that is blocked in early transcription. We also demonstrated that viral early transcription was not required for induction of apoptosis by infecting CHO cells with psoralen/UV-inactivated virus. On the other hand, apoptosis was inhibited by a neutralizing antibody to the virion L1R protein added either before or after virus attachment to cells. These results indicate that a postbinding step associated with cell entry is sufficient and required for induction of apoptosis in CHO cells. Recent progress on apoptotic signaling pathways raises the possibility that a cellular receptor for W may be involved in apoptosis. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 53 TC 67 Z9 67 U1 0 U2 2 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 MAR 1 PY 1998 VL 242 IS 1 BP 138 EP 149 DI 10.1006/viro.1997.8985 PG 12 WC Virology SC Virology GA ZA335 UT WOS:000072353200016 PM 9501038 ER PT J AU Wiedemann, B Jensen, RT Mignon, M Modlin, CI Skogseid, B Doherty, G Oberg, K AF Wiedemann, B Jensen, RT Mignon, M Modlin, CI Skogseid, B Doherty, G Oberg, K TI Preoperative diagnosis and surgical management of neuroendocrine gastroenteropancreatic tumors: General recommendations by a consensus workshop SO WORLD JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT Workshop on the Preoperative Diagnosis and Surgical Treatment of Neuroendocrine Tumor Disease CY 1996 CL BERLIN, GERMANY AB In 1996 a consensus workshop on the preoperative diagnosis and surgical treatment of neuroendocrine tumor disease took place in Berlin. Although there was a consensus on the diagnosis and surgical treatment by world experts in neuroendocrine surgery in some areas, it became clear that certain management policies vary among centers. In large part, diverging policies reflect a lack df controlled studies. This paper summarizes the various opinions brought forward during this conference and emphasizes consensus approaches for the diagnosis and therapy of neuroendocrine neoplasms. C1 Free Univ Berlin, Klinikum Benjamin Franklin, Abt Innere Med Gastroenterol & Infektiol, D-12000 Berlin, Germany. NIH, Cell Biol Sect, Bethesda, MD 20892 USA. CHU Bichat, Serv Hepatogastroenterol, F-75877 Paris, France. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. Univ Uppsala Hosp, Dept Internal Med, Endocrine Unit, S-75185 Uppsala, Sweden. Washington Univ, Sch Med, Sect Endocrine & Oncol Surg, St Louis, MO 63110 USA. RP Wiedemann, B (reprint author), Humboldt Univ, Fak Med, Klinikum Charite, Med Klin Schwerpunkt, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. NR 0 TC 99 Z9 101 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD MAR PY 1998 VL 22 IS 3 BP 309 EP 318 PG 10 WC Surgery SC Surgery GA YW591 UT WOS:000071951700015 PM 9494425 ER PT J AU Schoder, H Knight, RJ Kofoed, KF Schelbert, HR Buxton, DB AF Schoder, H Knight, RJ Kofoed, KF Schelbert, HR Buxton, DB TI Regulation of pyruvate dehydrogenase activity and glucose metabolism in post-ischaemic myocardium SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE pyruvate dehydrogenase; ischaemia; reperfusion; dichloroacetate; glucose metabolism ID ISCHEMIC RAT HEARTS; FATTY-ACIDS; CORONARY-ARTERY; KETONE-BODIES; COENZYME-A; OXIDATION; DICHLOROACETATE; REPERFUSION; MECHANISM; RECOVERY AB Pyruvate dehydrogenase (PDH) is regulated both by covalent modification and through modulation of the active enzyme by metabolites. In the isolated heart, post-ischaemic inhibition of PDH, leading to uncoupling of glycolysis and glucose oxidation and a decrease in cardiac efficiency, has been described. In vivo, post-ischaemic reperfusion leads to metabolic abnormalities consistent with PDH inhibition. but the effects of ischaemia/reperfusion on PDH are not well characterized. We therefore investigated PDH regulation following transient ischaemia in vivo. In 33 open-chest dogs, the left anterior descending (LAD) was occluded for 20 min followed by 4 h I reperfusion. In 17 dogs, dichloroacetate (DCA) was injected prior to reperfusion, while 16 dogs served as controls, In dogs without DCA, glucose oxidation and lactate uptake were lower in reperfused than in remote tissue, suggesting reduced flux through PDH, However, percent active and total PDH measured in myocardial biopsies were similar in both territories, excluding covalent enzyme modification or loss of functional enzyme, DCA activated PDH activity similarly in both regions and abolished differences in glucose oxidation and lactate uptake. Thus, decreased PDH flux in reperfused myocardium does not result from covalent modification or loss of total enzyme activity, but more likely from metabolite inhibition of the active enzyme. DCA leads to essentially complete activation of PDH, increases overall glucose utilization and abolishes post-ischaemic inhibition of glucose oxidation. (C) 1998 Elsevier Science B.V. C1 Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lab Struct Biol & Mol Med, Los Angeles, CA 90095 USA. RP Buxton, DB (reprint author), NIH, Mol Cardiol Lab, 10 Ctr Dr,Room 8N202,Bldg 10, Bethesda, MD 20892 USA. OI Buxton, Denis/0000-0003-3077-6435 FU NHLBI NIH HHS [HL 29858] NR 39 TC 38 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD FEB 27 PY 1998 VL 1406 IS 1 BP 62 EP 72 DI 10.1016/S0925-4439(97)00088-4 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZE880 UT WOS:000072840900007 PM 9545535 ER PT J AU Inman, MV Levy, S Mock, BA Owens, GC AF Inman, MV Levy, S Mock, BA Owens, GC TI Gene organization and chromosome location of the neural-specific RNA binding protein Elavl4 SO GENE LA English DT Article DE Hu antigen; sex lethal; homology modeling; alternative mRNA splicing; chromosome 4 ID PARANEOPLASTIC ENCEPHALOMYELITIS ANTIGEN; MESSENGER-RNA; SEX-LETHAL; DROSOPHILA-MELANOGASTER; MOUSE CHROMOSOME-4; CONSERVED FAMILY; HEL-N1; CLONING; HUD; RECOGNITION AB We have isolated the gene that encodes the neural-specific RNA binding protein HuD in the mouse (Elavl4), and have mapped its location to the mid-distal region of chromosome 4, close to the neurological mutant clasper. The coding region of the Elavl4 gene covers approximately 44 kb; the first two RNA binding domains (RBDs) that are homologous to the two RBDs found in the Drosophila sex-lethal gene are each encoded in two exons, whereas the third RED is encoded in a single exon. Elavl4 mRNAs are alternatively spliced in the region between RBDs 2 and 3 due to the variable use of two micro-exons, and RNase protection analysis indicates that two of four possible splice variants are the predominant isoforms expressed in the central nervous system. The high degree of sequence conservation between the Hu proteins suggests that the exon organization of all the Hu protein genes will be similar, if not identical, to the Elavl4 gene. (C) 1998 Elsevier Science B.V. C1 Univ Colorado, Hlth Sci Ctr, Ctr Neurosci, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Univ Colorado, Dept Mol Cellular & Dev Biol, Denver, CO 80202 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Neurosci Training Program, Denver, CO USA. RP Owens, GC (reprint author), Univ Colorado, Hlth Sci Ctr, Ctr Neurosci, Dept Biochem & Mol Genet, B138,4200,E 9th Ave, Denver, CO 80262 USA. NR 43 TC 15 Z9 16 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 FEB 27 PY 1998 VL 208 IS 2 BP 139 EP 145 DI 10.1016/S0378-1119(97)00615-X PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZD054 UT WOS:000072646200005 PM 9524251 ER PT J AU Shakarian, AM Dwyer, DM AF Shakarian, AM Dwyer, DM TI The Ld Cht1 gene encodes the secretory chitinase of the human pathogen Leishmania donovani SO GENE LA English DT Article DE beta-1,4-N-acetylglucosaminohydrolase; human parasite; trypanosomatid; kinetoplastid; leishmaniasis; gene structure ID PARASITE CHITINASE; PROMASTIGOTES; TRANSMISSION; CLONING; SEQUENCE; PROTEIN AB Leishmania donovani promastigotes were shown to release chitinase activity during their growth in vitro. A PCR-based strategy identified a single copy ORF capable of encoding the L. donovani chitinase (Ld Cht1, 1374 bp). Ld Cht1 was shown to be actively transcribed by L. donovani promastigotes using reverse transcription and PCR amplification. The deduced aa sequence of Id Cht1 showed high conservation to known chitinases including the putative active and two substrate binding sites. Antiserum generated against four peptides derived from its deduced aa sequence immunoprecipitated; an approx. 50-kDa in vitro transcription/translation product of Ld Cht1. Further, this antiserum also immunoprecipitated both the native L. donovani 50-kDa Cht1 protein and the native chitinase activity synthesized and released by these parasites. Cumulatively, these data demonstrated that Ld Chtl encoded the chitinase of this important human pathogen. (C) 1998 Elsevier Science B.V. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, 9000 Rockville Pike,Bldg 4,Room 126, Bethesda, MD 20892 USA. EM dennis_dwyer@nih.gov NR 28 TC 28 Z9 28 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 FEB 27 PY 1998 VL 208 IS 2 BP 315 EP 322 DI 10.1016/S0378-1119(98)00011-0 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZD054 UT WOS:000072646200026 PM 9524285 ER PT J AU Wang, TH Wang, HS Ichijo, H Giannakakou, P Foster, JS Fojo, T Wimalasena, J AF Wang, TH Wang, HS Ichijo, H Giannakakou, P Foster, JS Fojo, T Wimalasena, J TI Microtubule-interfering agents activate c-Jun N-terminal kinase stress-activated protein kinase through both ras and apoptosis signal-regulating kinase pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; OVARIAN-CANCER; GROWTH-INHIBITION; GAMMA-RADIATION; JNK ACTIVATION; TAXOL; P53; PHOSPHORYLATION; PHOSPHATASE; BINDING AB The essential cellular functions associated with microtubules have led to a wide use of microtubule-interfering agents in cancer chemotherapy with promising results. Although the most well studied action of microtubule-interfering agents is an arrest of cells at the G(2)/M phase of the cell cycle, other effects may also exist. We have observed that paclitaxel (Taxol), docetaxel (Taxotere), vinblastine, vincristine, nocodazole, and colchicine activate the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway in a variety of human cells. Activation of JNK/SAPK by microtubule-interfering agents is dose-dependent and time-dependent and requires interactions with microtubules. Functional activation of the JNKK/SEK1-JNK/SAPK-c-Jun cascade (where JNKK/SEK1 is JNK kinase/SAPK kinase) was demonstrated by activation of a 12-O-tetradecanoylphorbol-13-acetate response element (TRE) reporter construct in a c-Jun dependent fashion. Microtubule-interfering agents also activated both Ras and apoptosis signal-regulating kinase (ASK1) and coexpression of dominant negative Ras and dominant negative apoptosis signal-regulating kinase exerted individual and additive inhibition of JNK/SAPK activation by microtubule-interfering agents. These findings suggest that multiple signal transduction pathways are involved with cellular detection of microtubular disarray and subsequent activation of JNK/SAPK. C1 Univ Tennessee, Med Ctr, Dept Obstet & Gynecol, Grad Sch Med, Knoxville, TN 37920 USA. Chang Gung Mem Hosp, Chang Gung Med Sch, Dept Obstet & Gynecol, Taipei 10591, Taiwan. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 170, Japan. NCI, NIH, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. RP Wimalasena, J (reprint author), Univ Tennessee, Med Ctr, Dept Obstet & Gynecol, Grad Sch Med, 1924 Alcoa Hwy, Knoxville, TN 37920 USA. FU NCI NIH HHS [CA-68538]; NIAAA NIH HHS [AA-08328] NR 67 TC 328 Z9 339 U1 0 U2 7 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 FEB 27 PY 1998 VL 273 IS 9 BP 4928 EP 4936 DI 10.1074/jbc.273.9.4928 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YZ939 UT WOS:000072310400021 PM 9478937 ER PT J AU Suga, S Nowak, TS AF Suga, S Nowak, TS TI Postischemic hyperthermia increases expression of hsp72 mRNA after brief ischemia in the gerbil SO NEUROSCIENCE LETTERS LA English DT Article DE ischemia; gerbil; heat shock; stress protein; hsp72; hyperthermia ID GLOBAL FOREBRAIN ISCHEMIA; HEAT-SHOCK; CEREBRAL-ISCHEMIA; MESSENGER-RNA; BRAIN; HYPOTHERMIA; STRESS; RAT; TEMPERATURE; HIPPOCAMPUS AB Brain temperature during ischemia critically determines insult severity, and temperature changes during recirculation may also affect subsequent injury. We have examined the impact of postischemic temperature on induction of the 70 kDa stress protein, hsp72, after brief ischemia in the gerbil. Animals were subjected to 2 min ischemia after which they were maintained under continuous halothane anesthesia during 3 h recirculation, and were either kept normothermic or subjected to hyperthermia comparable to that which occurs spontaneously in gerbils released from anesthesia immediately after the occlusion. Quantitative in situ hybridization showed striking dependence of hsp72 induction on postischemic hyperthermia, This result establishes that delayed temperature-sensitive signals mediate this injury-associated transcriptional response, and demonstrates that postischemic temperature must be carefully monitored in studies of gene expression and induced tolerance employing brief ischemic insults. (C) 1998 Elsevier Science Ireland Ltd. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Nowak, TS (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, 855 Monroe Ave,Link Bldg,Room 415, Memphis, TN 38163 USA. NR 22 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 27 PY 1998 VL 243 IS 1-3 BP 57 EP 60 DI 10.1016/S0304-3940(98)00096-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZA352 UT WOS:000072354900015 PM 9535112 ER PT J AU Pesonen, U Koulu, M Bergen, A Eggert, M Naukkarinen, H Virkkunen, M Linnoila, M Goldman, D AF Pesonen, U Koulu, M Bergen, A Eggert, M Naukkarinen, H Virkkunen, M Linnoila, M Goldman, D TI Mutation screening of the 5-hydroxytryptamine(7) receptor gene among Finnish alcoholics and controls SO PSYCHIATRY RESEARCH LA English DT Article DE human; receptors; serotonin/genetics; polymorphism; impulsivity; point mutation ID CEREBROSPINAL-FLUID MONOAMINE; VIOLENT OFFENDERS; FIRE SETTERS; HEALTHY-VOLUNTEERS; RHESUS-MONKEYS; PERSONALITY; CYCLASE; METABOLITES; CLONING; RHYTHMS AB Impaired central serotonin neurotransmission has been associated with increased aggression, impaired impulse control and diurnal activity rhythm disturbances among humans. Neuroanatomic distribution and pharmacological properties of the serotonin 5-HT7 receptor suggest that it may play a role in psychiatric disorders and in circadian rhythm regulation. In this study a point mutation causing proline(279) --> leucine amino acid substitution in the 5-hydroxytryptamine(7) (5-HT7) receptor gene was discovered. This 5-HT7Leu279 variant was observed in six of 825 individuals, all of whom are heterozygous for the substitution. Three of them are alcoholic offenders (3/255), two are relatives of an offender without the 5-HT7Leu279 allele (2/255) and one is a healthy control without any psychiatric diagnosis (1/248). The allele frequency of the 5-HT7Leu279 variant is 0.004 (6/758) among Finns. Although the 5-HT7Leu279 variant is approximately three times more common among alcoholic offenders than among healthy controls, it is not significantly associated with alcoholism or impulsivity in the present study. The 5-HT7Leu279 allele may, however, be a predisposing allele in a subgroup of alcoholic offenders with multiple behavioral problems. (C) 1998 Elsevier Science Ireland Ltd. C1 Univ Turku, MediCity Res Lab, Dept Pharmacol & Clin Pharmacol, FIN-20520 Turku, Finland. NIAAA, Neurogenet Lab, Div Intramural Clin & Biol Res, Rockville, MD 20852 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NIAAA, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. RP Pesonen, U (reprint author), Univ Turku, MediCity Res Lab, Dept Pharmacol & Clin Pharmacol, Tykistokatu 6A, FIN-20520 Turku, Finland. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 22 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB 27 PY 1998 VL 77 IS 3 BP 139 EP 145 DI 10.1016/S0165-1781(98)00005-5 PG 7 WC Psychiatry SC Psychiatry GA ZE602 UT WOS:000072811000001 PM 9707296 ER PT J AU Brebion, G Amador, X Smith, MJ Gorman, JM AF Brebion, G Amador, X Smith, MJ Gorman, JM TI Memory impairment and schizophrenia: the role of processing speed SO SCHIZOPHRENIA RESEARCH LA English DT Article DE memory impairment; processing speed; schizophrenia ID SPATIAL WORKING-MEMORY; PSYCHOMOTOR RETARDATION; DYSFUNCTION; PERFORMANCE; AGE; BRADYPHRENIA; DEPRESSION; COGNITION AB A link between slowing of processing speed and cognitive disorders, including memory, has repeatedly been found in research on aging, and suggested in other cognitively impaired populations. We tested the hypothesis that a link between memory impairment and slowing of processing speed would also be observed in schizophrenia. Forty-four schizophrenic patients and 40 normal controls were administered a memory task involving free recall and recognition. Processing speed was assessed by the Digit Symbol Substitution Test, Working memory span was assessed as well. The measure of processing speed was consistently correlated with the various memory measures in patients, including efficiency of encoding. These correlations remained significant, or tended to be significant, when working memory span was partialled out. Memory deficits observed in schizophrenia mag thus be partly accounted for by a slowing of processing speed. It is suggested that research on cognitive deficits in this and other mental diseases focus more on processing speed. (C) 1998 Elsevier Science B.V. C1 Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Unit 2, New York, NY 10032 USA. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Brebion, G (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Unit 2, 722 W 168th St, New York, NY 10032 USA. FU NIMH NIH HHS [5P20MH50727] NR 43 TC 52 Z9 52 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB 27 PY 1998 VL 30 IS 1 BP 31 EP 39 DI 10.1016/S0920-9964(97)00123-0 PG 9 WC Psychiatry SC Psychiatry GA YZ142 UT WOS:000072224500003 PM 9542786 ER PT J AU Courtney, SM Petit, L Maisog, JM Ungerleider, LG Haxby, JV AF Courtney, SM Petit, L Maisog, JM Ungerleider, LG Haxby, JV TI An area specialized for spatial working memory in human frontal cortex SO SCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN PREFRONTAL CORTEX; EYE-MOVEMENTS; FUNCTIONAL-ANATOMY; NEURAL SYSTEMS; PET; OBJECT; FIELDS; ACTIVATION; LOCATION AB Working memory is the proc!ss of maintaining an active representation of information so that it is available for use. In monkeys, a prefrontal cortical region important for spatial working memory lies in and around the principal sulcus, but in humans the location, and even the existence, of a region for spatial working memory is in dispute. By using functional magnetic resonance imaging in humans, an area in the superior frontal sulcus was identified that is specialized for spatial working memory. This area is located more superiorly and posteriorly in the human than in the monkey brain, which may explain why it was not recognized previously. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Courtney, SM (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA. RI GINSPAN, All/B-8714-2008; Petit, Laurent/D-6583-2011 OI Petit, Laurent/0000-0003-2499-5367 NR 37 TC 624 Z9 640 U1 1 U2 27 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 FEB 27 PY 1998 VL 279 IS 5355 BP 1347 EP 1351 DI 10.1126/science.279.5355.1347 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YZ412 UT WOS:000072251800049 PM 9478894 ER PT J AU Rinzel, J Terman, D Wang, XJ Ermentrout, B AF Rinzel, J Terman, D Wang, XJ Ermentrout, B TI Propagating activity patterns in large-scale inhibitory neuronal networks SO SCIENCE LA English DT Article ID SYNCHRONIZED OSCILLATIONS; IONIC MECHANISMS; SPINDLE WAVES; IN-VITRO; MODEL; NUCLEUS; GENERATION; NEOCORTEX; THALAMUS; CIRCUITS AB The propagation of activity is studied in a spatially structured network model of gamma-aminobutyric acid-containing (GABAergic) neurons exhibiting postinhibitory rebound. In contrast to excitatory-coupled networks, recruitment spreads very slowly because cells fire only after the postsynaptic conductance decays, and with two possible propagation modes. If the connection strength decreases monotonically with distance (on-center), then propagation occurs in a discontinuous manner. If the self-and nearby connections are absent (off-center), propagation can proceed smoothly. Modest changes in the synaptic reversal potential can result in depolarization-mediated waves that are 25 times faster. Functional and developmental roles for these behaviors and implications for thalamic circuitry are suggested. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Math, Columbus, OH 43210 USA. Brandeis Univ, Ctr Complex Syst, Waltham, MA 02254 USA. Brandeis Univ, Dept Phys, Waltham, MA 02254 USA. Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. RP Rinzel, J (reprint author), NYU, Ctr Neural Sci, 4 Washington Pl,Room 809, New York, NY 10003 USA. EM rinzel@cns.nyu.edu RI Wang, Xiao-Jing/D-2722-2009 FU NIMH NIH HHS [MH 47150, MH53717-01] NR 33 TC 95 Z9 97 U1 1 U2 12 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 FEB 27 PY 1998 VL 279 IS 5355 BP 1351 EP 1355 DI 10.1126/science.279.5355.1351 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YZ412 UT WOS:000072251800050 PM 9478895 ER PT J AU Gastel, JA Roseboom, PH Rinaldi, PA Weller, JL Klein, DC AF Gastel, JA Roseboom, PH Rinaldi, PA Weller, JL Klein, DC TI Melatonin production: Proteasomal proteolysis in serotonin N-acetyltransferase regulation SO SCIENCE LA English DT Article ID LIGHT-INDUCED DECREASE; PINEAL-GLAND; PROTEIN; UBIQUITIN; SECRETION; PATHWAY; TURNOVER; RHYTHM; ORGAN AB The nocturnal increase in circulating melatonin in vertebrates is regulated bg, 10- to 100-fold increases in pineal serotonin N-acetyltransferase (AA-NAT) activity. Changes in the amount of AA-NAT protein were shown to parallel changes in AA-NAT activity. When neural stimulation was switched off by either light exposure or L-propranalol-induced beta-adrenergic blockade, both AA-NAT activity and protein decreased rapidly. Effects of L-propranolol were blocked in vitro by dibutyryl adenosine 3',5'-monophasphate (cAMP) or inhibitors of proteasomal proteolysis. This result indicates that adrenergic-cAMP regulation of AA-NAT is mediated by rapid reversible control af selective proteasomal proteolysis. Similar proteasome-based mechanisms may function widely as selective molecular switches in vertebrate neural systems. C1 NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM klein@helix.nih.gov NR 43 TC 214 Z9 218 U1 2 U2 9 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 FEB 27 PY 1998 VL 279 IS 5355 BP 1358 EP 1360 DI 10.1126/science.279.5355.1358 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YZ412 UT WOS:000072251800052 PM 9478897 ER PT J AU Maccaferri, G Toth, K McBain, CJ AF Maccaferri, G Toth, K McBain, CJ TI Target-specific expression of presynaptic mossy fiber plasticity SO SCIENCE LA English DT Article ID LONG-TERM POTENTIATION; METABOTROPIC GLUTAMATE-RECEPTOR; RAT HIPPOCAMPUS; SYNAPSES; CELLS AB Mossy fiber synaptic transmission at hippocampal CA3 pyramidal cells and interneurons was compared in rat brain slices to determine whether mossy terminals are functionally equivalent, Tetanic stimulation of mossy fibers induced long-term potentiation in pyramidal neurons but was either without effect or it induced depression at synapses onto interneurons. Unlike transmission onto pyramidal neurons, transmission onto interneurons was not potentiated after adenosine 3',5'-monophosphate (cAMP) activation. Furthermore, metabotropic glutamate receptor depression of transmission onto interneurons did not involve cAMP-dependent pathways, Thus, synaptic terminals arising from a common afferent pathway do not function as a single compartment but are specialized, depending on their postsynaptic target. C1 NICHHD, Lab Cellular & Mol Neurophysiol, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Room 5A72,Bldg 49,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 149 Z9 152 U1 0 U2 1 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 FEB 27 PY 1998 VL 279 IS 5355 BP 1368 EP 1370 DI 10.1126/science.279.5355.1368 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YZ412 UT WOS:000072251800055 PM 9478900 ER PT J AU Miller, RW AF Miller, RW TI Living history autobiography: Clinical genetics: Key to cancer etiology SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article ID RUBINSTEIN-TAYBI SYNDROME; WILMS-TUMOR; TRILATERAL RETINOBLASTOMA; ATAXIA TELANGIECTASIA; CHILDHOOD LEUKEMIA; UNITED-STATES; NEUROFIBROMATOSIS; MUTATIONS; CARCINOMA; NEOPLASMS C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Miller, RW (reprint author), NCI, Genet Epidemiol Branch, BPN-400, Bethesda, MD 20892 USA. NR 78 TC 1 Z9 1 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 26 PY 1998 VL 76 IS 1 BP 9 EP 20 DI 10.1002/(SICI)1096-8628(19980226)76:1<9::AID-AJMG2>3.0.CO;2-O PG 12 WC Genetics & Heredity SC Genetics & Heredity GA YY344 UT WOS:000072137700002 PM 9508058 ER PT J AU Bowman, ED Bromeke, B Lensing, W Shields, PG AF Bowman, ED Bromeke, B Lensing, W Shields, PG TI Apolipoprotein E allelic frequency in elderly smokers SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE apolipoprotein E; genetic polymorphisms; elderly smokers; lung cancer risk; longevity; race ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; ALZHEIMERS-DISEASE; E POLYMORPHISM; GENETIC-VARIATION; POPULATION; EPSILON-4; RISK; METABOLISM; LONGEVITY AB Susceptibility genes for human diseases (e.g., cancer and atherosclerosis) increase disease risk by altering the metabolic activation of exogenous (e.g., carcinogens) and endogenous (e.g., cholesterol) compounds. The function of these genes, and subsequent risk, can be adversely affected by polymorphisms. This study tests the hypothesis that if specific genetic polymorphisms are related to mortality, then in elderly heavy smokers, there should be a decreased frequency of "at risk" alleles and an increased frequency of "protective" alleles, i.e., a survival effect, One such potential polymorphism is in the apolipoprotein E (apoE) gene, which is involved in cholesterol metabolism, where the epsilon 4 allele is associated with an increased risk of coronary artery disease and is under represented in elderly populations. In this study, ApoE variant alleles were determined in 81 living, elderly current smokers (mean age: 72.5; range: 65-94; mean pack-years: 78; range: 13-192) and in 82 younger autopsy donors (mean age: 33; range: 1-58). There was a borderline difference in the apoE 4 allelic frequencies among the groups (11% in the elderly and 18% in the comparable younger group [df = 1; chi(2) = 4.02; P = 0.051]). A significant difference was found for age when stratified as a continuous variable by genotype in the elderly smokers (P = 0.03; mean age for persons with and without epsilon 4 was 69.9 and 73.2, respectively). Pack-years of cigarette smokers did not differ by genotype, indicating no selective effect. These results confirm earlier associations for differences in the apoE allelic frequencies in the elderly and extend it to smokers, who generally have increased mortality at younger ages. (C) 1998 Wiley-Liss, Inc. C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. US Soldiers & Airmens Home, Washington, DC USA. RP Shields, PG (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37,Rm 2C16,37 Convent Dr, Bethesda, MD 20892 USA. EM Peter_G_Shields@NIH.GOV RI Shields, Peter/I-1644-2012 NR 34 TC 1 Z9 1 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 26 PY 1998 VL 76 IS 1 BP 32 EP 36 DI 10.1002/(SICI)1096-8628(19980226)76:1<32::AID-AJMG5>3.3.CO;2-3 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA YY344 UT WOS:000072137700005 PM 9508061 ER PT J AU Alexander, CB Ellmore, TM Kokate, TG Kirkby, RD AF Alexander, CB Ellmore, TM Kokate, TG Kirkby, RD TI Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide synthase in rodents SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE N-omega-nitro-L-arginine methyl ester; N-G-nitro-L-arginine; GABA(A) receptor; NMDA (N-methyl-D-aspartate); seizure; strain difference; ontogeny ID ACID-INDUCED SEIZURES; ARGININE METHYL-ESTER; PILOCARPINE-INDUCED SEIZURES; DEEP PREPIRIFORM CORTEX; 7-NITRO INDAZOLE; KAINIC ACID; NO SYNTHASE; ENDOGENOUS ANTICONVULSANT; MESSENGER-RNA; TREATED RATS AB We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as N-omega-nitro-L-arginine methyl ester and N-G-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. N-omega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., N-omega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. N-omega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both N-omega-nitro-L-arginine methyl ester and N-G-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and N-omega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, N-omega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs. (C) 1998 Elsevier Science B.V. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. Sensor Syst Inc, Sterling, VA 20164 USA. RP Kokate, TG (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, 10-5N250,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kokate@helix.nih.gov OI Ellmore, Timothy/0000-0001-6125-0044 NR 51 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD FEB 26 PY 1998 VL 344 IS 1 BP 15 EP 25 DI 10.1016/S0014-2999(97)01551-3 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZE995 UT WOS:000072852300002 PM 9570442 ER PT J AU Glaab, WE Risinger, JI Umar, A Barrett, JC Kunkel, TA Tindall, KR AF Glaab, WE Risinger, JI Umar, A Barrett, JC Kunkel, TA Tindall, KR TI Cellular resistance and hypermutability in mismatch repair-deficient human cancer cell lines following treatment with methyl methanesulfonate SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE mismatch repair; HPRT; methyl methanesulfonate; cytotoxicity; induced mutant frequency ID DNA-DAMAGE TOLERANCE; ESCHERICHIA-COLI; MICROSATELLITE INSTABILITY; TUMOR-CELLS; INDUCED MUTAGENESIS; GENOME INSTABILITY; ENDOMETRIAL CANCER; MUTATOR PHENOTYPES; ALKYLATING-AGENTS; BINDING AB Resistance to the cytotoxic effects of S(N)1 alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) is well established in mismatch repair-defective cells, however, little is known about the cellular response to S(N)2 alkylating agents in these cells. Here we describe the cytotoxic response and the mutagenic response at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus to the S(N)2 alkylating agent methyl methanesulfonate (MMS) in human cancer cell lines defective in mismatch repair (MMR), Our findings suggest that cytotoxicity to MMS is mediated through MMR, as indicated by an increased resistance to MMS in MMR-deficient cells. Cells in which specific MMR-gene defects were complemented by chromosome transfer were generally more sensitive to the cytotoxic effects of MMS, Additionally, the induced mutant frequency at HPRT following exposure to MMS is significantly increased in MMR-deficient lines. These findings suggest that resistance to S(N)2 alkylation damage is mediated by MMR genes, and that resistance to such damage in MMR-defective cells correlates with an increase in genomic mutations. The results are consistent with the hypothesis that abasic sites may be substrates for repair involving MMR-gene products inhuman cells. (C) 1998 Elsevier Science B.V. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. RP Tindall, KR (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. EM tindall@niehs.nih.gov NR 49 TC 23 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD FEB 26 PY 1998 VL 398 IS 1-2 BP 197 EP 207 DI 10.1016/S0027-5107(98)00004-9 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZP187 UT WOS:000073726200021 PM 9626980 ER PT J AU Kohn, KW AF Kohn, KW TI Functional capabilities of molecular network components controlling the mammalian G1/S cell cycle phase transition SO ONCOGENE LA English DT Article DE molecular reaction network modeling; molecular reaction diagrams; computer simulation of reaction networks; cell cycle models; G1/S phase transition; E2F; retinoblastoma protein ID UBIQUITIN-PROTEASOME PATHWAY; SPINDLE-ASSEMBLY CHECKPOINT; TRANSCRIPTION FACTOR E2F-1; S-PHASE; NITROGEN-MUSTARD; DNA-SYNTHESIS; RETINOBLASTOMA PROTEIN; INCREASED EXPRESSION; MITOTIC OSCILLATOR; INHIBITS GROWTH AB The molecular interactions implicated in the mammalian G1/S cell cycle phase transition comprise a highly nonlinear network which can produce seemingly paradoxical results and make intuitive interpretations unreliable, A new approach to this problem is presented, consisting of (1) a convention of unambiguous reaction diagrams, (2) a convenient computer simulation method, and (3) a quasi-evolutionary method of probing the functional capabilities of simplified components of the network, Simulations were carried out for a sequence of hypothetical primordial systems, beginning with the simplest plausibly functional system, The complexity of the system was then increased in small steps, such that functionality was added at each step, The results suggested new functional concepts: (1) Rb-family proteins could store E2F in a manner analogous to the way a condenser stores electric charge, and, upon phosphorylation, release a large wave of active E2F; (2) excessive or premature cyclin-dependent kinase activities could paradoxically impair E2F activity during the G1/S transition period, The results show how network simulations, carried out by means of the methods described, can assist in the design and interpretation of experiments probing the control of the G1/S phase transition. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 66 TC 46 Z9 47 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 26 PY 1998 VL 16 IS 8 BP 1065 EP 1075 DI 10.1038/sj.onc.1201608 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZA169 UT WOS:000072335900012 PM 9519880 ER PT J AU Fried, LP Kronmal, RA Newman, AB Bild, DE Mittelmark, MB Polak, JF Robbins, JA Gardin, JM AF Fried, LP Kronmal, RA Newman, AB Bild, DE Mittelmark, MB Polak, JF Robbins, JA Gardin, JM CA Cardiovasc Hlth Stud Collabor Res Grp TI Risk factors for 5-year mortality in older adults - The cardiovascular health study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALL-CAUSE MORTALITY; PHYSICAL-DISABILITY; NATIONAL COHORT; LONG-TERM; FOLLOW-UP; MEN; DISEASE; ASSOCIATION; ATHEROSCLEROSIS; CORONARY AB Context.-Multiple factors contribute to mortality in older adults, but the extent to which subclinical disease and other factors contribute independently to mortality risk is not known. Objective.-To determine the disease, functional, and personal characteristics that jointly predict mortality in community-dwelling men and women aged 65 years or older. Design.-Prospective population-based cohort study with 5 years of follow-up and a validation cohort of African Americans with 4.25-year follow-up. Setting.-Four US communities. Participants.-A total of 5201 and 685 men and women aged 65 years or older in the original and African American cohorts, respectively. Main Outcome Measures.-Five-year mortality. Results.-In the main cohort, 646 deaths (12%) occurred within 5 years. Using Cox proportional hazards models, 20 characteristics (of 78 assessed) were each significantly (P<.05) and independently associated with mortality: increasing age, male sex, income less than $50 000 per year, low weight, lack of moderate or vigorous exercise, smoking for more than 50 pack-years, high brachial (>169 mm Hg) and low tibial (less than or equal to 127 mm Hg) systolic blood pressure, diuretic use by those without hypertension or congestive heart failure, elevated fasting glucose level (>7.2 mmol/L [130 mg/dL]), low albumin level (less than or equal to 37 g/L), elevated creatinine level (greater than or equal to 106 mu mol/L [1.2 mg/dL]), low forced vital capacity (12.06 mL), aortic stenosis (moderate or severe) and abnormal left ventricular ejection fraction (by echocardiography), major electrocardiographic abnormality, stenosis of internal carotid artery (by ultrasound), congestive heart failure, difficulty in any instrumental activity of daily living, and low cognitive function by Digit Symbol Substitution test score. Neither high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol was associated with mortality. After adjustment for other factors, the association between age and mortality diminished, but the reduction in mortality with female sex persisted. Finally, the risk of mortality was validated in the second cohort; quintiles of risk ranged from 2% to 39% and 0% to 26% for the 2 cohorts. Conclusions.-Objective measures of subclinical disease and disease severity were independent and joint predictors of 5-year mortality in older adults, along with male sex, relative poverty, physical activity, smoking, indicators of frailty, and disability. Except for history of congestive heart failure, objective, quantitative measures of disease were better predictors of mortality than was clinical history of disease. C1 Cardiovasc Hlth Study Collaborat Res Grp, Coordinating Ctr, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Bergen, Sch Psychol, Bergen, Norway. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. Univ Calif Irvine, Dept Med, Div Cardiol, Irvine, CA 92717 USA. CHS Coordinating Ctr, Seattle, WA 98101 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. RP Fried, LP (reprint author), Cardiovasc Hlth Study Collaborat Res Grp, Coordinating Ctr, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2600, Baltimore, MD 21205 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-87079, N01-HC-87080, N01-HC-87081] NR 37 TC 697 Z9 706 U1 6 U2 29 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 FEB 25 PY 1998 VL 279 IS 8 BP 585 EP 592 DI 10.1001/jama.279.8.585 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA YX457 UT WOS:000072041900033 PM 9486752 ER PT J AU Odetti, P Angelini, G Dapino, D Zaccheo, D Garibaldi, S Dagna-Bricarelli, F Piombo, G Perry, G Smith, M Traverso, N Tabaton, M AF Odetti, P Angelini, G Dapino, D Zaccheo, D Garibaldi, S Dagna-Bricarelli, F Piombo, G Perry, G Smith, M Traverso, N Tabaton, M TI Early glycoxidation damage in brains from Down's syndrome SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MAILLARD REACTION; MALONDIALDEHYDE; PEROXIDATION; PRODUCTS; PROTEINS; DISEASE AB In Down's syndrome, the presence of three copies of chromosome 21 is associated with premature aging and progressive mental retardation sharing the pathological features of Alzheimer disease, Early cortical dysgenesis and late neuronal degeneration are probably caused by an overproduction of amyloid beta-peptide, followed by an increased cellular oxidation. Interestingly, chromosome 21 codes for superoxide-dismutase and amyloid beta precursor resulting, in Down's syndrome, in an overflow of these gene products and metabolites. We studied Down's fetal brain cortex to evaluate the presence and amount of lipid and protein oxidation markers; moreover, we quantified two forms of glycation end products that are known to be involved in the process of cellular oxidation. All these parameters are significantly increased in Down's fetal brains in comparison to controls, providing the evidence that accelerated brain glycoxidation occurs very early in the life of Down's syndrome subjects. (C) 1998 Academic Press. C1 Univ Genoa, DIMI, Dept Internal Med, I-16132 Genoa, Italy. Natl Canc Inst, Adv Biotechnol Ctr, I-16132 Genoa, Italy. Univ Genoa, Inst Human Anat, I-16132 Genoa, Italy. Galliera Hosp, Ctr Human Genet, I-16128 Genoa, Italy. Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. Univ Genoa, Inst Gen Pathol, Genoa, Italy. Univ Genoa, Dept Neurosci, Genoa, Italy. RP Odetti, P (reprint author), Univ Genoa, DIMI, Dept Internal Med, Viale Benedetto XV 6, I-16132 Genoa, Italy. RI Smith, Mark/A-9053-2009; Perry, George/A-8611-2009; Angelini, Giovanna/C-8476-2013; OI Perry, George/0000-0002-6547-0172; ANGELINI, giovanna/0000-0003-1474-5452; ODETTI, PATRIZIO/0000-0001-9559-7273 FU Telethon [E.0579] NR 17 TC 91 Z9 94 U1 0 U2 6 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 FEB 24 PY 1998 VL 243 IS 3 BP 849 EP 851 DI 10.1006/bbrc.1998.8186 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YZ887 UT WOS:000072304300041 PM 9501012 ER PT J AU Louis, JM Dyda, F Nashed, NT Kimmel, AR Davies, DR AF Louis, JM Dyda, F Nashed, NT Kimmel, AR Davies, DR TI Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEINS; PRECURSOR; POLYPROTEIN; EXPRESSION; SEQUENCES; PEPSTATIN; KINETICS; ANALOG; SALT AB The HIV-1 transframe region (TFR) is between the structural and functional domains of the Gag-Pol polyprotein, flanked by the nucleocapsid and the protease domains at its N and C termini, respectively, Transframe octapeptide (TFP) Phe-Leu-Arg-Glu-Asp-Leu-Ala-Phe, the N terminus of TFR, and its analogues are competitive inhibitors of the action of the mature HIV-1 protease. The smallest, most potent analogues are tripeptides: Glu-Asp-Leu and Glu-Asp-Phe with K-i values of similar to 50 and similar to 20 mu M, respectively, Substitution of the acidic amino acids in the TFP by neutral amino acids and D or retro-D configurations of Glu-Asp-Leu results in an >40-fold increase in K-i, Protease inhibition by Glu-Asp-Leu is dependent on a protonated form of a group with a pK(a), of 3.8; unlike other inhibitors of HIV-I protease which are highly hydrophobic, Glu-Asp-Leu is extremely soluble in water, and its binding affinity decreases with increasing NaCl concentration. However, Glu-Asp-Leu is a poor inhibitor (K-1 similar to 7.5 mM) of the mammalian;aspartic acid protease pepsin. X-ray crystallographic studies at pH 4.2 show that the interactions of Glu at P2 and Leu at P1 of Glu-Asp-Leu with residues of the active site of HIV-1 protease are similar to those of other product-enzyme complexes, It was not feasible to understand the interaction of intact TFP with HIV-1 protease under conditions of crystal growth due to its hydrolysis giving rise to two products. The sequence-specific, selective inhibition of the HIV-1 protease by the viral TFP suggests a role for TFP in regulating protease function during HIV-I replication. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Louis, JM (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5,Room 411, Bethesda, MD 20892 USA. EM jmlouis@helix.nih.gov NR 32 TC 74 Z9 77 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 FEB 24 PY 1998 VL 37 IS 8 BP 2105 EP 2110 DI 10.1021/bi972059x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YZ846 UT WOS:000072299900005 PM 9485357 ER PT J AU Michniak, BB Player, MR Godwin, DA Lockhart, CC Sowell, JW AF Michniak, BB Player, MR Godwin, DA Lockhart, CC Sowell, JW TI In vitro evaluation of azone analogs as dermal penetration enhancers - V. Miscellaneous compounds SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE percutaneous absorption; enhancers; hairless mouse skin; hydrocortisone; steroids ID HAIRLESS MOUSE SKIN; IN-VITRO; PERCUTANEOUS PENETRATION; SERIES; HYDROCORTISONE; INDOMETHACIN; AMIDES AB Dermal penetration enhancers were evaluated (14) using diffusion cell techniques, hairless mouse skin and hydrocortisone as the model drug. The following were synthesized: 1-dodecanoylpiperidine (1), 1-dodecanoylpyrrolidine (2), 1-dodecanoyl-2-piperidinone (3), 1-dodecanoyl-2-pyrrolidinone (4), 2-decylcyclohexanone (5), 2-decylcyclopentanone (6), 4-(dodecanoyl)-thiomorpholine (7), N,N-didodecylacetamide (8) and N-dodecyltricyclo [3.3.1.1(3,7)]decane-1-carboxamide (11). N-Acetylcaprolactam (9), 4-acetylmorpholine (10) and N-dodecylpyrrolidinone (13) were purchased. The syntheses of Azone, N-(1-oxododecyl)morpholine (12) and N-dodecyl-2-piperidinone (14) have been reported previously. Enhancers were applied at 0.4 M in propylene glycol (PG) (or as a suspension) to mouse skin. Hydrocortisone (0.03 M in PG) was applied 1 h following enhancer treatment. Controls (no pretreatment) yielded 24 h diffusion cell receptor concentrations (Q(24)) of 9.93 +/- 3.15 mu M and model drug skin retention of 26.1 +/- 5.6 mu g g(-1). Compound 7 yielded a high Q(24) of 208.18 +/- 39.52 mu M. The highest skin retention was observed with 6 of 566.7 +/- 39.7 mu g g(-1). Azone gave values of 218.96 +/- 47.84 mu M for Q(24) and 294.9 +/- 66.7 mu g g(-1) for skin retention. Compounds 13 and 14 gave Q(24) values of 274.44 +/- 50.90 and 220.21 +/- 59.63 mu M and skin retention values of 226.5 +/- 51.8 and 259.0 +/- 62.2 mu g g(-1), respectively. (C) 1998 Elsevier Science B.V. C1 Univ S Carolina, Coll Pharm, Dept Basic Pharmaceut Sci, Columbia, SC 29208 USA. NIDDK, Med Chem Lab, Sect Biomed Chem, NIH, Bethesda, MD 20892 USA. Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. RP Michniak, BB (reprint author), Univ S Carolina, Coll Pharm, Dept Basic Pharmaceut Sci, Columbia, SC 29208 USA. NR 28 TC 13 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD FEB 23 PY 1998 VL 161 IS 2 BP 169 EP 178 DI 10.1016/S0378-5173(97)00349-9 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZB812 UT WOS:000072510500005 ER PT J AU Marshall, AD Derbyshire, JF McPhie, P Jakoby, WB AF Marshall, AD Derbyshire, JF McPhie, P Jakoby, WB TI A review of the effects of manipulation of the cysteine residues of rat aryl sulfotransferase IV SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 3rd International Sulfation Workshop CY SEP 22-25, 1996 CL DRYMEN, SCOTLAND DE phenol sulfotransferase; aryl sulfotransferase; PAPS hydrolysis; oxidative stress; cysteine oxidation effects ID TYROSINE-ESTER SULFOTRANSFERASE; PHENOL SULFOTRANSFERASE; IDENTIFICATION; LIVER AB Aryl sulfotransferase IV from rat liver has the broad substrate range that is characteristic of the enzymes of detoxication. With the standard assay substrates, 4-nitrophenol and 3'-phosphoadenosine 5'-phosphosulfate (PAPS), sulfation is optimum at pH 5.4 whereas the reaction is minimal in the physiological pH range. These properties preclude a physiological function for this cytosolic enzyme. Partial oxidation of the enzyme, however, results not only in an increase in the rate of sulfation but also in a shift of the pH optimum to the physiological pH range. The mechanism for this dependence on the redox environment involves oxidation at Cys(66), the cysteine residue that is conserved throughout the phenol sulfotransferase family. As documented by mass spectroscopic methods, oxidation by GSSG leads to the formation of an internal disulfide between Cys(66) and Cys(232); for mutants at Cys(232), the oxidation product is a mixed disulfide of Cys(66) and glutathione. Both of these disulfide species activate the enzyme and allow it to function at a pH optimum in the physiological range. The activated enzyme differs from the reduced form by a more circumscribed substrate spectrum. All hue mutants, in which each of the cysteines of the sulfotransferase subunit have been changed to serine, are catalytically active. Only Cys(66) is required for the redox response. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Med Chem, Seattle, WA USA. NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Jakoby, WB (reprint author), NIDDKD, Biochem & Metab Lab, NIH, Bldg 10,9N119, Bethesda, MD 20892 USA. EM wb-jakoby@helix.nih.gov NR 21 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD FEB 20 PY 1998 VL 109 IS 1-3 BP 107 EP 116 DI 10.1016/S0009-2797(97)00124-5 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA ZE613 UT WOS:000072812100009 PM 9566737 ER PT J AU Gong, WH Howard, OMZ Turpin, JA Grimm, MC Ueda, H Gray, PW Raport, CJ Oppenheim, JJ Wang, JM AF Gong, WH Howard, OMZ Turpin, JA Grimm, MC Ueda, H Gray, PW Raport, CJ Oppenheim, JJ Wang, JM TI Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MULTIPLE LEUKOCYTE RECEPTORS; CHEMOKINE RECEPTORS; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; UNIQUE RECEPTORS; MCP3 INTERACTS; RANTES; MIP-1-ALPHA; MIP-1-BETA AB Human immunodeficiency virus, type I (HIV-1) cell-type tropism is dictated by chemokine receptor usage: T-cell line tropic viruses use CXCR4, whereas monocyte tropic viruses primarily use CCR5 as fusion coreceptors. CC chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES (regulated on activation normal T cell expressed and secreted) inhibit CD4/CCR5-mediated HIV-1 cell fusion, MCP-2 is also a member of the CC chemokine subfamily and has the capacity to interact with at least two receptors including CCR-1 and CCR2B. In an effort to further characterize the binding properties of MCP-2 on leukocytes, we observed that MCP-2, but not MCP-1, effectively competed with MIP-1 beta for binding to monocytes, suggesting that MCP-2 may interact with CCR5, As predicted, MCP-2 competitively inhibited MIP-1 beta binding to HEK293 cells stably transfected with CCR5 (CCR5/293 cells). MCP-2 also bound to and induced chemotaxis of CCR5/293 cells with a potency comparable with that of MIP-1 beta. Confocal microscopy indicates that MCP-2 caused remarkable and dose-dependent internalization of CCR5 in CCR5/ 293 cells. Furthermore, MCP-2 inhibited the entry/replication of HIV-1ADA in CCR5/293 cells coexpressing CD4. These results indicated that MCP-2 uses CCR5 as one of its functional receptors and is an additional potent natural inhibitor of HIV-1. C1 NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Frederick, MD 21702 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. SAIC, Intramural Res Support Program, Frederick, MD USA. SAIC, Dev Therapeut Program, Frederick, MD USA. ICOS Corp, Bothell, WA 98021 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Bldg 560,Rm 31-19, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 31 TC 89 Z9 97 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 FEB 20 PY 1998 VL 273 IS 8 BP 4289 EP 4292 DI 10.1074/jbc.273.8.4289 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YY117 UT WOS:000072115000001 PM 9468473 ER PT J AU Martin, DA Siegel, RM Zheng, LX Lenardo, MJ AF Martin, DA Siegel, RM Zheng, LX Lenardo, MJ TI Membrane oligomerization and cleavage activates the caspase-8 (FLICE/MACH alpha 1) death signal SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; INDUCED APOPTOSIS; CRYSTAL-STRUCTURE; CD95 FAS/APO-1; T-CELLS; PROTEASE; RECEPTOR; FAS; PROTEINS; DOMAIN AB Many forms of apoptosis, including that caused by the death receptor CD95/Fas/APO-1, depend on the activation of caspases, which are proteases that cleave specific intracellular proteins to cause orderly cellular disintegration. The requirements for activating these. crucial enzymatic mediators of death are not well understood. Using molecular chimeras with either CD8 or Tac, we find that oligomerization at the cell membrane powerfully induces caspase-8 autoactivation and apoptosis. Death induction was abrogated by the z-VAD-fmk, z-IETD-fmk, or p35 enzyme inhibitors or by a mutation in the active site cysteine but was surprisingly unaffected by death inhibitor Bcl-2, Amino acid substitutions that prevent the proteolytic separation of the caspase from its membrane-associated domain completely blocked apoptosis. Thus, oligomerization at the membrane is sufficient for caspase-8 autoactivation, but apoptosis could involve a death signal conveyed by the proteolytic release of the enzyme into the cytoplasm. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Rm 11N311,Bldg 10,10 Ctr Dr,MSC1892, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 32 TC 296 Z9 313 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 FEB 20 PY 1998 VL 273 IS 8 BP 4345 EP 4349 DI 10.1074/jbc.273.8.4345 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YY117 UT WOS:000072115000011 PM 9468483 ER PT J AU Kim, A Kim, J Martin, BM Dunaway-Mariano, D AF Kim, A Kim, J Martin, BM Dunaway-Mariano, D TI Isolation and characterization of the carbon-phosphorus bond-forming enzyme phosphoenolpyruvate mutase from the mollusk Mytilus edulis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P-C BOND; TRYPANOSOMA-CRUZI; STREPTOMYCES-HYGROSCOPICUS; TETRAHYMENA-PYRIFORMIS; NUCLEOTIDE-SEQUENCE; EPIMASTIGOTE FORMS; BIOSYNTHETIC GENES; BIALAPHOS SF-1293; APLYSIA-KURODAI; PHOSPHOMUTASE AB The enzyme phosphoenolpyruvate mutase was purified to homogeneity from the mollusk Mytilus edulis. The subunit size of the native homotetramer was determined to be 34,000 Da, The steady state kinetic constants for catalysis of the conversion of phosphonopyruvate to phosphoenolpyruvate at pH 7.5 and 25 degrees C were measured at k(cat) = 34 s(-1), phosphonopyruvate K-m = 3 mu M, and Mg2+ K-m = 4 mu M. The enzyme displayed a broad specificity for divalent metal ion activation; Co2+, Mn2+, Zn2+, and Ni2+ are activators, whereas Ca2+ is not. Analysis of the pH dependence of the Mg2+-activated mutase-catalyzed reaction of phosphonopyruvate revealed one residue that must be protonated (apparent pK(a) = 8.3) and a second residue that must be unprotonated (apparent pK(a) = 7.7) for maximal catalytic activity. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. NIMH, Mol Neurogenet Unit, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Dunaway-Mariano, D (reprint author), Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. FU NIGMS NIH HHS [GM 28688] NR 33 TC 26 Z9 26 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 FEB 20 PY 1998 VL 273 IS 8 BP 4443 EP 4448 DI 10.1074/jbc.273.8.4443 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YY117 UT WOS:000072115000024 PM 9468496 ER PT J AU Bae, YS Cantley, LG Chen, CS Kim, SR Kwon, KS Rhee, SG AF Bae, YS Cantley, LG Chen, CS Kim, SR Kwon, KS Rhee, SG TI Activation of phospholipase C-gamma by phosphatidylinositol 3,4,5-trisphosphate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PHOSPHOINOSITIDE-3 KINASE; 3-KINASE; SYSTEM; PHOSPHATIDYLINOSITOL(3,4,5)-TRISPHOSPHATE; PHOSPHATES; WORTMANNIN; RECEPTOR; DOMAINS; CLONING AB Signal transduction across cell membranes often involves the activation of both phosphatidylinositol (PI)-specific phospholipase C (PLC) and phosphoinositide 3-kinase (PI 3-kinase). Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2), a substrate for both enzymes, is converted to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P-3) by the action of PI 3-kinase. Here, we show that PI(3,4,5)P-3 activates purified PLC-gamma isozymes by interacting with their Src homology 2 domains, Furthermore, the expression of an activated catalytic subunit of PI 3-kinase in COS-7 cells resulted in an increase in inositol phosphate formation, whereas platelet-derived growth factor-induced PLC activation in NIH 3T3 cells was markedly inhibited by the specific PI 3-kinase inhibitor LY294002. These results suggest that receptors coupled to PI 3-kinase may activate PLC-gamma isozymes indirectly, in the absence of PLC-gamma tyrosine phosphorylation, through the generation of PI(3,4,5)P-3. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Dept Med, Boston, MA 02115 USA. Univ Kentucky, Coll Pharm, Div Med Chem & Pharmaceut, Lexington, KY 40506 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 3,Rm 122,3 Ctr Dr,MSC 0320, Bethesda, MD 20892 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK48871]; NIGMS NIH HHS [GM53448] NR 34 TC 273 Z9 277 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 FEB 20 PY 1998 VL 273 IS 8 BP 4465 EP 4469 DI 10.1074/jbc.273.8.4465 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YY117 UT WOS:000072115000027 PM 9468499 ER PT J AU Kuniyasu, A Itagaki, K Shibano, T Iino, M Kraft, G Schwartz, A Nakayama, H AF Kuniyasu, A Itagaki, K Shibano, T Iino, M Kraft, G Schwartz, A Nakayama, H TI Photochemical identification of transmembrane segment IVS6 as the binding region of semotiadil, a new modulator for the L-type voltage-dependent Ca2+ channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BI CALCIUM CHANNELS; SKELETAL-MUSCLE; ALPHA-1 SUBUNIT; 1,4-DIHYDROPYRIDINE SENSITIVITY; PHARMACOLOGICAL PROFILE; MOLECULAR DETERMINANTS; ANTAGONIST; BENZOTHIAZINE; SD-3211; FUMARATE AB To identify the binding domain of a new Ca2+ antagonist semotiadil on L-type Ca2+ channels from skeletal muscle, photolabeling was carried out by using an azi dophenyl derivative of [H-3]semotiadil, Photoincorporation was observed in several polypeptides of membrane triad preparations; the only specific photoincorporation was in the alpha 1 subunit of the Ca2+ channel, After solubilization and purification, the photolabeled alpha(1) subunit was subjected to proteolytic and CNBr cleavage followed by antibody mapping, Specific labeling was associated solely with the region of transmembrane segment S6 in repeat IV. Quantitative immunoprecipitation was found in the tryptic and the Lys-C/Glu-C fragments of 6.6 and 6.1 kDa, respectively, Further CNBr cleavage of the Lys-C digests produced two smaller fragments of 3.4 and 1.8 kDa that were included in the tryptic and Lys-C/Glu-C fragments. The smallest labeled fragments were: Tyr(1350)-Met(1366) and Leu(1367)-Met(1381) containing IVS6, a possible pore forming region, The data suggest that semotiadil binds to a region that is overlapped with but not identical to those for phenylalkylamines, dihydropyridines and benzothiazepines. The present study also provides evidence that region IV represents an important component of a binding pocket for Ca2+ antagonists. C1 Kumamoto Univ, Fac Pharmaceut Sci, Kumamoto 862, Japan. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Daiichi Pharmaceut Co Ltd, New Prod Res Labs 2, Edogawa Ku, Tokyo 134, Japan. Univ Cincinnati, Coll Med, Inst Mol Pharmacol & Biophys, Cincinnati, OH 45267 USA. RP Kumamoto Univ, Fac Pharmaceut Sci, 5-1 Oe Honmachi, Kumamoto 862, Japan. EM jin@gpo.kumamoto-u.ac.jp FU NHLBI NIH HHS [P01 HL22619] NR 34 TC 10 Z9 10 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 FEB 20 PY 1998 VL 273 IS 8 BP 4635 EP 4641 DI 10.1074/jbc.273.8.4635 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YY117 UT WOS:000072115000050 PM 9468522 ER PT J AU Breen, JJ Agulnick, AD Westphal, S Dawid, IB AF Breen, JJ Agulnick, AD Westphal, S Dawid, IB TI Interactions between LIM domains and the LIM domain-binding protein Ldb1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOMEOBOX GENE; SYNERGISTIC ACTIVATION; ORGANIZER; XENOPUS; HOMEODOMAIN; DIFFERENTIATION; TRANSCRIPTION; REQUIREMENT; SPECIFICITY; ELEGANS AB LIM domains mediate protein-protein interactions and, within LIM-homeodomain proteins, act as negative regulators of the transcriptional activation function of the protein, The recently described protein Ldb1 (also known as NLI; LIM domain-binding protein) binds LIM domains in vitro and synergizes with the LIM-homeodomain protein Xlim-1 in frog embryo microinjection experiments. Hn this study we localized the transcriptional activation domain of Xlim-1 to its carboxyl-terminal region, and characterized the interactions of the amino-terminally located LIM domains with Ldb1. Ldb1 binds LIM domains through its carboxyl-terminal region, and can form homodimers via its amino-terminal region. Optimal binding to Ldb1 required tandem LIM domains, while single domains could bind at lower but clearly reasonable efficiency. In animal explant experiments, synergism of Ldb1 with Xlim-1 in the activation of downstream genes required both the region containing the dimerization domain of Ldb1 and time region containing the LIM-binding domain. The role of Ldb1 may be to recruit other transcriptional activators depending on the promoter context and LIM-homeodomain partner involved. C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6B,Rm 413, Bethesda, MD 20892 USA. NR 33 TC 75 Z9 81 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 FEB 20 PY 1998 VL 273 IS 8 BP 4712 EP 4717 DI 10.1074/jbc.273.8.4712 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YY117 UT WOS:000072115000061 PM 9468533 ER PT J AU Johnston, NL Cerevnak, J Shore, AD Torrey, EF Yolken, RH AF Johnston, NL Cerevnak, J Shore, AD Torrey, EF Yolken, RH CA Stanley Neuropathology Consortium TI Multivariate analysis of RNA levels from postmortem human brains as measured by three different methods of RT-PCR (vol 77, pg 83, 1997) SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Correction C1 Johns Hopkins Univ, Dept Pediat, Stanley Fdn, Neurovirol Lab, Baltimore, MD 21287 USA. NIMH, St Elizabeths Hosp, Washington, DC 20032 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Hlth Serv Res & Dev Ctr, Baltimore, MD 21287 USA. RP Johnston, NL (reprint author), Johns Hopkins Univ, Dept Pediat, Stanley Fdn, Neurovirol Lab, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD FEB 20 PY 1998 VL 79 IS 2 BP 233 EP 233 PG 1 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZD543 UT WOS:000072697100012 ER PT J AU Bringmann, G Gotz, R Keller, PA Walter, R Boyd, MR Lang, FR Garcia, A Walsh, JJ Tellitu, I Bhaskar, KV Kelly, TR AF Bringmann, G Gotz, R Keller, PA Walter, R Boyd, MR Lang, FR Garcia, A Walsh, JJ Tellitu, I Bhaskar, KV Kelly, TR TI A convergent total synthesis of the michellamines SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ACETOGENIC ISOQUINOLINE ALKALOIDS; CROSS-COUPLING REACTION; ANCISTROCLADUS-KORUPENSIS; A-C; ACIDS; HALOARENES; BIARYLS; ESTERS AB A convergent total synthesis of the anti-HIV michellamines (1) is described. The tetraaryl skeleton of the michellamines mas constructed by formation first of the inner (nonstereogenic) biaryl axis and subsequently of the two other (stereogenic) axes in a highly convergent manner. The key transformation features a double Suzuki-type cross-coupling reaction between binaphthalene ditriflate 26 and isoquinolineboronic acid 35. Ditriflate 26 is synthesized in six steps starting from diene 6 and 2,6-dibromobenzoquinone (9) in 21% overall yield. For large scale production of 26, a substantially shortened version of an existing procedure for the preparation of bisnaphthoquinone 13 was also developed, which allows far the preparation of 13 from benzoquinone and diene 6 in five steps and 67% overall yield. Binaphthoquinone 13 was subsequently converted into ditriflate 26 in three steps and 67% overall yield, By the described synthetic strategy, michellamines A (1a) and B (1b) are produced (1a:1b = 1:2.5) in 24.6% overall yield from diene 6. Curiously, none of the nonnaturally occurring atropoisomer 1c is formed. C1 Univ Wurzburg, Inst Organ Chem, D-97074 Wurzburg, Germany. NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. Boston Coll, Dept Chem, Eugene F Merkert Chem Ctr, Chestnut Hill, MA 02167 USA. RP Bringmann, G (reprint author), Univ Wurzburg, Inst Organ Chem, Am Hubland, D-97074 Wurzburg, Germany. NR 47 TC 73 Z9 73 U1 0 U2 6 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 FEB 20 PY 1998 VL 63 IS 4 BP 1090 EP 1097 DI 10.1021/jo971495m PG 8 WC Chemistry, Organic SC Chemistry GA YZ052 UT WOS:000072215400031 ER PT J AU Segovia, J Vergara, P Brenner, M AF Segovia, J Vergara, P Brenner, M TI Differentiation-dependent expression of transgenes in engineered astrocyte cell lines SO NEUROSCIENCE LETTERS LA English DT Article DE tyrosine hydroxylase; glial fibrillary acidic protein; C6 cells; transgenes; transfection ID FIBRILLARY ACIDIC PROTEIN; IN-VITRO CHARACTERIZATION; TYROSINE-HYDROXYLASE; C6 CELLS; GENE; GFAP; INCREASES; GAD(67); RODENT AB The utility of transgenes for both basic and applied studies has been augmented by the recent advent of versions that can be regulated by the addition of suitable activators. However, still more convenient would be transgenes whose expression responded appropriately to endogenous signals. The promoter of the glial fibrillary acidic protein (GFAP) gene is a candidate for this role in the central nervous system (CNS) since the GFAP gene is specifically expressed in astrocytes in the CNS and its activity is upregulated in response to almost any CNS injury. As a feasibility study, we isolated a C6 rat glioma cell line stably transfected with a lacZ reporter gene driven by the gfa2 human GFAP promoter fragment. We find that the activity of the transgene indeed responds to an environmental signal, forskolin, that induces astrocyte-like differentiation of C6 cells. We also isolated a C6 line carrying a transgene in which the gfa2 promoter directs expression of a cDNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for catecholamine synthesis. This transgene should be of considerable interest for gene therapy for Parkinson's disease. We show that in this cell line both TH mRNA and protein are upregulated by forskolin. Finally, we note that the growth rate of C6 cells is severely depressed by forskolin, suggesting that predifferentiation of these cells prior to implant may retard their tumor forming capacity, prolonging the time that they can be used in animal models in vivo. Published by Elsevier Science Ireland Ltd. C1 Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & Neurociencias, Mexico City 07300, DF, Mexico. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Segovia, J (reprint author), Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & Neurociencias, 2508, Mexico City 07300, DF, Mexico. EM jsegovia@fisio.cinvestav.mx RI Segovia, Jose/C-9277-2011 OI Segovia, Jose/0000-0001-8215-4772 NR 19 TC 29 Z9 29 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 FEB 20 PY 1998 VL 242 IS 3 BP 172 EP 176 DI 10.1016/S0304-3940(98)00042-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA YZ600 UT WOS:000072270300013 PM 9530933 ER PT J AU Pradhan, TK Katsuno, T Taylor, JE Kim, SH Ryan, RR Mantey, SA Donohue, PJ Weber, HC Sainz, E Battey, JF Coy, DH Jensen, RT AF Pradhan, TK Katsuno, T Taylor, JE Kim, SH Ryan, RR Mantey, SA Donohue, PJ Weber, HC Sainz, E Battey, JF Coy, DH Jensen, RT TI Identification of a unique ligand which has high affinity for all four bombesin receptor subtypes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE bombesin; neuromedin B; gastrin-releasing peptide receptor; neuropeptide ID RAT PANCREATIC ACINI; GASTRIN-RELEASING PEPTIDE; LUNG-CARCINOMA CELLS; GUINEA-PIG PANCREAS; NEUROMEDIN-B; INOSITOL PHOSPHATES; GUANINE-NUCLEOTIDES; MOLECULAR-CLONING; DISPERSED ACINI; BINDING AB Four subtypes of bombesin receptors are identified (gastrin-releasing peptide receptor, neuromedin B receptor, the orphan receptor bombesin receptor subtype 3 (BB3 or BRS-3) and bombesin receptor subtype 4 (BB4)), however, only the pharmacology of the gastrin-releasing peptide receptor has been well studied. This lack of data is due in part to the absence of a general ligand. Recently we have discovered a ligand, I-125-[D-Tyr(6),beta Ala(11),Phe(13),Nle(14)]bombesin-(6-14) that binds to BRS-3 receptors. In this study we investigate its ability to interact with all four bombesin receptor subtypes. In rat pancreatic acini containing only gastrin-releasing peptide receptor and in BB4 transfected BALB cells, this ligand and I-125-[Tyr(4)]bombesin, the conventional gastrin-releasing peptide receptor ligand, gave similar results for receptor number, affinity for bombesin and affinity for the unlabeled ligand. In neuromedin B receptor transfected BALB cells, this ligand and I-125-[D-Tyr(0)]neuromedin B, the generally used neuromedin B receptor ligand, gave similar results for receptor number, neuromedin B affinity or the unlabeled ligand affinity. Lastly, in BRS-3 transfected BALB cells, only this ligand had high affinity. For all four bombesin receptors this ligand had an affinity of 1-8 nM and was equal or greater in affinity than any other specific ligands for any receptor. The unlabeled ligand is specific for gastrin-releasing peptide receptors on rat pancreatic acini and did not inhibit binding of I-125-cholecystokinin octapeptide (I-125-CCK-8), I-125-vasoactive intestinal peptide (I-125-VIP) or I-125-endothelin to their receptors. The unlabeled ligand was an agonist only at the gastrin-releasing peptide receptor in rat acini and did not interact with CCKA receptors or muscarinic M-3 acetylcholine receptors to increase [H-3]inositol phosphates. These results demonstrate I-125-[D-Tyr(6),beta Ala(11),Phe(13),Nle(14)]bombesin-(6-14) is a unique ligand with high affinity for all subtypes of bombesin receptors. Because of the specificity for bombesin receptors, this ligand will be a valuable addition for such pharmacological studies as screening for bombesin receptor agonists or antagonists and, in particular, for investigating BRS-3 cell biology, a receptor for which no ligand currently exists. Published by Elsevier Science B.V. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Biomeasure Inc, Milford, MA 01757 USA. NIDOCD, NIH, Rockville, MD 20850 USA. Tulane Univ, Peptide Res Labs, New Orleans, LA 70112 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Room 9C-103,Bldg 10,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 45 TC 72 Z9 74 U1 0 U2 2 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 FEB 19 PY 1998 VL 343 IS 2-3 BP 275 EP 287 DI 10.1016/S0014-2999(97)01527-6 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZE179 UT WOS:000072766100021 PM 9570477 ER PT J AU Long, EO AF Long, EO TI Immunology - Signal sequences stop killer cells SO NATURE LA English DT Editorial Material C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 6 TC 27 Z9 27 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 19 PY 1998 VL 391 IS 6669 BP 740 EP + DI 10.1038/35739 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YX884 UT WOS:000072089500023 PM 9486638 ER PT J AU Mayeux, R Saunders, AM Shea, S Mirra, S Evans, D Roses, AD Hyman, BT Crain, B Tang, MX Phelps, CH AF Mayeux, R Saunders, AM Shea, S Mirra, S Evans, D Roses, AD Hyman, BT Crain, B Tang, MX Phelps, CH CA Alzheimer's Dis Ctr Consortium Apolipoprotein TI Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID E ALLELE EPSILON-4; CLINICAL-DIAGNOSIS; DIFFERENTIAL-DIAGNOSIS; VASCULAR DEMENTIA; CRITERIA; ACCURACY; RELIABILITY AB Background The epsilon 4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. Methods We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon 4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard, The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to gene rare receiver-operating-characteristic curves plotting sensitivity against the false positive rate. Result's Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and The diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon 4 allele, The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon E4 allele were 65 and 68 percent, respectively. The addition of: information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased, The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. Conclusions APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test ibr Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis, (C) 1998, Massachusetts Medical Society. C1 Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Taub Alzheimers Dis Res Ctr, Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY 10032 USA. Duke Univ, Med Ctr, Bryan Alzheimers Dis Res Ctr, Durham, NC USA. Emory Univ, Emory Alzheimers Dis Res Ctr, Atlanta, GA 30322 USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. Rush Presbyterian St Lukes Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NIA, Bethesda, MD 20892 USA. RP Mayeux, R (reprint author), Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. FU NIA NIH HHS [AG05128, AG10963, AG8702] NR 43 TC 338 Z9 345 U1 0 U2 6 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 19 PY 1998 VL 338 IS 8 BP 506 EP 511 DI 10.1056/NEJM199802193380804 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YX639 UT WOS:000072061400004 PM 9468467 ER PT J AU Gemma, A Hagiwara, K Vincent, F Ke, Y Hancock, AR Nagashima, M Bennett, WP Harris, CC AF Gemma, A Hagiwara, K Vincent, F Ke, Y Hancock, AR Nagashima, M Bennett, WP Harris, CC TI hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors SO ONCOGENE LA English DT Article DE transforming growth factor-beta; cDNA; genomic structure; PCR-SSCP ID GROWTH-FACTOR-BETA; MAD-RELATED PROTEIN; II RECEPTOR GENE; TGF-BETA; SIGNALING PATHWAYS; CELL-GROWTH; CLONING; CANCER; INHIBITION; KINASE AB hSmad (mothers against decapentaplegic)-related proteins are important messengers within the Transforming Growth Factor-beta(1) (TGF-beta(1)) superfamily signal transduction pathways. To further characterize a member of this family, we obtained a full length cDNA of the human hSmad5 (hSmad5) gene by rapid amplification of cDNA ends (RACE) and then determined the genomic structure of the gene. There are eight exons and two alternative transcripts; the shorter transcript lacks exon 2. We identified the hSmad5 promoter region from a human genomic YAC clone by obtaining the nucleotide sequence extending 1235 base pairs upstream of the 5' end of the cDNA. We found a CpG island consistent with a promoter region, and we demonstrated promoter activity in a 1232 bp fragment located upstream of the transcription initiation site. To investigate the frequency of somatic hSmad5 mutations in human cancers, we designed intron-based primers to examine coding regions by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Neither homozygous deletions or point mutations were found in 40 primary gastric tumors and 51 cell lines derived from diverse types of human cancer including 20 cell lines resistant to the growth inhibitory effects of TGF-beta(1). These results suggest that the hSmad5 gene is not commonly mutated and that other genetic alterations mediate the loss of TGF-beta(1) responsiveness in human cancers. C1 NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. IFREMER, Lab Ecotoxicol, F-44311 Nantes 03, France. Beijing Med Univ, Sch Oncol, Beijing 100034, Peoples R China. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 30 TC 35 Z9 36 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 19 PY 1998 VL 16 IS 7 BP 951 EP 956 DI 10.1038/sj.onc.1201614 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YX564 UT WOS:000072053200015 PM 9484787 ER PT J AU Walther, MM AF Walther, MM TI Prostate cancer potentially linked to the HPC1 gene SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 4 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 FEB 18 PY 1998 VL 279 IS 7 BP 507 EP 508 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YW470 UT WOS:000071938900019 PM 9480354 ER PT J AU Naficy, A Rao, MR Paquet, C Antona, D Sorkin, A Clemens, JD AF Naficy, A Rao, MR Paquet, C Antona, D Sorkin, A Clemens, JD TI Treatment and vaccination strategies to control cholera in sub-Saharan refugee settings - A cost-effectiveness analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FIELD TRIAL; DEVELOPING-COUNTRIES; EPIDEMIC CHOLERA; PUBLIC-HEALTH; LATIN-AMERICA; FOLLOW-UP; BANGLADESH; VACCINES; MORTALITY; TRANSMISSION AB Context.-There is significant controversy about how best to control cholera epidemics in refugee settings. Specifically, there is marked disagreement about whether to use oral cholera vaccines in these settings, despite the improved safety and effectiveness profiles of these vaccines. Objective.-To determine the cost-effectiveness of alternative intervention strategies, including vaccination, to control cholera outbreaks in sub-Saharan refugee camps. Design.-A cost-effectiveness analysis based on probabilities of cholera outcomes derived from epidemiologic data compiled for refugee settings in Malawi from 1987 through 1993; data for costs were obtained from a large relief agency that provides medical care in such settings. Setting and Participants.-A hypothetical refugee camp with 50 000 persons in sub-Saharan Africa evaluated for a 2-year period. Interventions.-We compared the costs and outcomes of alternative strategies in which appropriate rehydration therapy for cholera is introduced preemptively (at the establishment of a camp) or reactively (once an epidemic is recognized) and in which mass immunization with oral B subunit killed whole-cell (BS-WC) cholera vaccine is added to a rehydration program either preemptively or reactively. Main Outcome Measures.-Cost per cholera case prevented and cost per cholera death averted. Results.-In a situation with no available rehydration therapy suitable for the management of severe cholera, a strategy of preemptive therapy ($320 per death averted) costs less and is more effective than a strategy of reactive therapy ($586 per death averted). Adding vaccination to preemptive therapy is expensive: $1745 per additional death averted for preemptive vaccination and $3833 per additional death averted for reactive vaccination. However, if the cost of vaccine falls below $0.22 per dose, strategies combining vaccination and preemptive therapy become more cost-effective than therapy alone. Conclusions.-Provision for managing cholera outbreaks at the inception of a refugee camp (preemptive therapy) is the most cost-effective strategy for controlling cholera outbreaks in sub-Saharan refugee settings. Should the price of BS-WC cholera vaccine fall below $0.22 per dose, however, supplementation of preemptive therapy with mass vaccination will become a cost-effective option. C1 NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. Epicentre, Paris, France. Med Sans Frontieres, Paris, France. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Univ Maryland Baltimore Cty, Dept Econ, Catonsville, MD USA. RP Naficy, A (reprint author), NICHHD, Epidemiol Branch, Room 7B03,6100 Execut Blvd, Bethesda, MD 20892 USA. NR 31 TC 44 Z9 44 U1 1 U2 11 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 FEB 18 PY 1998 VL 279 IS 7 BP 521 EP 525 DI 10.1001/jama.279.7.521 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YW470 UT WOS:000071938900033 PM 9480362 ER PT J AU George, GN Colangelo, CM Dong, J Scott, RA Khangulov, SV Gladyshev, VN Stadtman, TC AF George, GN Colangelo, CM Dong, J Scott, RA Khangulov, SV Gladyshev, VN Stadtman, TC TI X-ray absorption spectroscopy of the molybdenum site of Escherichia coli formate dehydrogenase SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DIMETHYL-SULFOXIDE REDUCTASE; BOND-VALENCE PARAMETERS; XANTHINE-OXIDASE; CRYSTAL-STRUCTURE; RHODOBACTER-SPHAEROIDES; NUCLEOTIDE-SEQUENCE; SULFITE OXIDASE; HYDROGEN-LYASE; FINE-STRUCTURE; COMPLEXES AB X-ray absorption spectroscopy at the molybdenum and selenium K-edges has been used to probe the active site structure of Escherichia coli formate dehydrogenase H. The active sites of both oxidized and reduced wild-type protein, and of a variant containing cysteine instead of selenocysteine, were studied. The oxidized and reduced enzymes were found to be very similar, both containing a novel des-oxo molybdenum site, with four Mo-S ligands at 2.35 Angstrom, (probably) one Mo-O at 2.1 Angstrom, and one Mo-Se ligand at 2.62 Angstrom being indicated from the Mo K-edge data. The selenium K-edge EXAFS not only is in good agreement with the Mo K-edge data but also indicates the unexpected presence of Se-S ligation, with a bond length of 2.19 Angstrom. We suggest that the active site of Escherichia coli formate dehydrogenase H contains a novel selenosulfide ligand to molybdenum, where the selenium and sulfur originate from selenocysteine and one of the pterin-cofactor dithiolenes, respectively. C1 Stanford Univ, SLAC, Stanford Synchrotron Radiat Lab, Stanford, CA 94309 USA. Univ Georgia, Ctr Metalloenzyme Studies, Athens, GA 30602 USA. Univ Georgia, Dept Chem, Athens, GA 30602 USA. NIH, Bethesda, MD 20892 USA. RP George, GN (reprint author), Stanford Univ, SLAC, Stanford Synchrotron Radiat Lab, POB 4349,MS 69, Stanford, CA 94309 USA. RI Gladyshev, Vadim/A-9894-2013; George, Graham/E-3290-2013; OI Colangelo, Christopher/0000-0002-0438-1395 NR 50 TC 59 Z9 59 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 18 PY 1998 VL 120 IS 6 BP 1267 EP 1273 DI 10.1021/ja973004l PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA YY185 UT WOS:000072121800020 ER PT J AU Lubin, JH Linet, MS Boie, JD Buckley, J Conrath, SM Hatch, EE Kleinerman, RA Tarone, RE Wacholder, S Robison, LL AF Lubin, JH Linet, MS Boie, JD Buckley, J Conrath, SM Hatch, EE Kleinerman, RA Tarone, RE Wacholder, S Robison, LL TI Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RED BONE-MARROW; NATURAL RADIATION; MAGNETIC-FIELDS; LUNG-CANCER; CHILDREN; MINERS; BIASES; STATES; HOUSES; RISKS AB Background: Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]), As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure, Methods: Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer, Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects, Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects, Results: Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)), For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis, There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. Conclusions: In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. US EPA, Washington, DC 20460 USA. Univ Minnesota, Sch Med, Div Pediat Epidemiol & Clin Res, Minneapolis, MN 55455 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 403, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [CA20320, CA02971, CA13539] NR 47 TC 50 Z9 54 U1 1 U2 2 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 FEB 18 PY 1998 VL 90 IS 4 BP 294 EP 300 PG 7 WC Oncology SC Oncology GA YY184 UT WOS:000072121700010 PM 9486815 ER PT J AU McDonald, JP Frank, EG Levine, AS Woodgate, R AF McDonald, JP Frank, EG Levine, AS Woodgate, R TI Intermolecular cleavage by UmuD-like mutagenesis proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MucA; self-processing reactions; protein-protein interactions ID RECA-MEDIATED CLEAVAGE; ESCHERICHIA-COLI; SOS MUTAGENESIS; CONSTITUTIVE EXPRESSION; DEPENDENT CLEAVAGE; MUCA PROTEIN; LEXA; DNA; REPRESSORS; MUTANTS AB The activity of a number of proteins is regulated by self-processing reactions, Elegant examples are the cleavage of the prokaryotic LexA and lambda Cl transcriptional repressors and the UmuD-like mutagenesis proteins. Various studies support the hypothesis that LexA and lambda Cl cleavage reactions are predominantly intramolecular in nature, The recently described crystal structure of the Escherichia coli UmuD' protein (the posttranslational cleavage product of the UmuD protein) suggests, however, that the region of the protein corresponding to the cleavage site is at least 50 Angstrom away from the catalytic active site, We considered the possibility, therefore, that the UmuD-like proteins might undergo self-processing that, in contrast to LexA and lambda Cl, occurs via an intermolecular rather than intramolecular reaction, To test this hypothesis, we introduced into E. coli compatible plasmids with mutations at either the cleavage or the catalytic site of three UmuD-like proteins, Cleavage of these proteins only occurs in the presence of both plasmids, indicating that the reaction is indeed intermolecular in nature, Furthermore, this intermolecular reaction is completely dependent upon the multifunctional RecA protein and leads to the restoration of cellular mutagenesis in nonmutable E. coli strains, Intermolecular cleavage of a biotinylated UmuD active site mutant was also observed in vitro in the presence of the wild-type UmuD' protein, indicating that in addition to the intact UmuD protein, the normal cleavage product (UmuD') can also act as a classical enzyme. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. EM woodgate@helix.nih.gov NR 31 TC 42 Z9 42 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 17 PY 1998 VL 95 IS 4 BP 1478 EP 1483 DI 10.1073/pnas.95.4.1478 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900023 PM 9465040 ER PT J AU Lei, XD Kaufman, S AF Lei, XD Kaufman, S TI Identification of hepatic nuclear factor 1 binding sites in the 5 ' flanking region of the human phenylalanine hydroxylase gene: Implication of a dual function of phenylalanine hydroxylase stimulator in the phenylalanine hydroxylation system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 4A-CARBINOLAMINE DEHYDRATASE; HOMEODOMAIN PROTEINS; 7-SUBSTITUTED PTERINS; COFACTOR; PROMOTER; LIVER; DCOH; RAT; 7-TETRAHYDROBIOPTERIN; MUTATIONS AB Phenylalanine hydroxylase stimulator (PHS) is a component of the phenylalanine hydroxylation system that is involved in the regeneration of the cofactor tetrahydrobiopterin. It is also identical to the dimerization cofactor of hepatocyte nuclear factor 1 (HNF1) (DCoH) that is able to enhance the transcriptional activity of HNF1. Moreover, it has the structural potential for binding macromolecules such as proteins and nucleic acids, consistent with its involvement in gene expression. We investigated whether PHS/DCoH could enhance the expression of phenylalanine hydroxylase (PAH). Cotransfection assays showed that DCoH itself could not transactivate the 9-kb human PAH 5' flanking fragment. However, this 9-kb fragment was transactivated by HNF1 in a dose-dependent manner with a maximum of nearly 8-fold activation; DCoH potentiated this transactivation by another 1.6-fold. The HNF1 binding sites were located at -3.5 kb in a region that is 77.5% identical to the mouse liver-specific hormone-inducible PAH gene enhancer. This study suggests a possible dual function of PBS in vivo in the human phenylalanine hydroxylation system: it is involved in the regeneration of the cofactor tetrahydrobiopterin and can also enhance the expression of the human PAH gene. C1 NIMH, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Kaufman, S (reprint author), NIMH, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 29 TC 23 Z9 25 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 FEB 17 PY 1998 VL 95 IS 4 BP 1500 EP 1504 DI 10.1073/pnas.95.4.1500 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900027 PM 9465044 ER PT J AU Lee, MS Craigie, R AF Lee, MS Craigie, R TI A previously unidentified host protein protects retroviral DNA from autointegration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE retrovirus; integration; nucleoprotein complexes ID MURINE LEUKEMIA-VIRUS; INTEGRATION INVITRO; VIRAL-DNA; POL GENE; PRODUCT AB Integration of a DNA copy of the viral genome into a host chromosome is an essential step in the retrovirus life cycle. The machinery that carries out the integration reaction is a nucleoprotein complex derived from the core of the infecting virion. To successfully integrate into host DNA the viral DNA within this complex must avoid self-destructive integration into itself, a reaction termed autointegration. We have previously shown [Lee, M. S. and Craigie, R. (1994) Proc. Natl. Acad. Sci. USA 91, 9823-9827] that viral nucleoprotein complexes isolated from Moloney murine leukemia virus-infected cells exhibit a barrier to autointegration. This autointegration barrier could be destroyed by stripping factors from the complexes and subsequently restored by incubation with a host cell extract, but not by incubation with an extract of disrupted virions. We have now used this autointegration barrier reconstitution assay to purify the host factor from uninfected NIH 3T3 fibroblasts. It is a single polypeptide of 89 aa that does not match any previously identified protein. The identity of the protein was confirmed by expressing it in Escherichia coli and demonstrating the activity of the heterologously expressed protein in the reconstitution assay. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Room 301,5 Ctr Dr MSC 0560, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov NR 27 TC 181 Z9 185 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 17 PY 1998 VL 95 IS 4 BP 1528 EP 1533 DI 10.1073/pnas.95.4.1528 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900032 PM 9465049 ER PT J AU Guru, SC Goldsmith, PK Burns, AL Marx, SJ Spiegel, AM Collins, FS Chandrasekharappa, SC AF Guru, SC Goldsmith, PK Burns, AL Marx, SJ Spiegel, AM Collins, FS Chandrasekharappa, SC TI Menin, the product of the MEN1 gene, is a nuclear protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOCALIZATION AB The MEN1 gene, mutations in which are responsible for multiple endocrine neoplasia type 1 (MEN1), encodes a 610-amino acid protein, denoted menin. The amino acid sequence of this putative tumor suppressor offers no clue to the function or subcellular location of the protein. We report herein, based on immunofluorescence, Western blotting of subcellular fractions, and epitope tagging with enhanced green fluorescent protein, that menin is located primarily in the nucleus. Enhanced green fluorescent protein-tagged menin deletion constructs identify at least two independent nuclear localization signals (NLS), both located in the C-terminal fourth of the protein. Among the 68 known independent disease-associated mutations, none of the 22 missense and 3 in-frame deletions affect either of the putative NLS sequences. However, if expressed, none of the truncated menin proteins resulting from the 43 known frameshift/nonsense mutations would retain both the NLSs. The precise role(s) of menin in the nucleus remain to be understood. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chandrasekharappa, SC (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bldg 49,Room 3E-13,49 Convent Dr, Bethesda, MD 20892 USA. EM chandra@nhgri.nih.gov NR 16 TC 295 Z9 297 U1 3 U2 11 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 FEB 17 PY 1998 VL 95 IS 4 BP 1630 EP 1634 DI 10.1073/pnas.95.4.1630 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900050 PM 9465067 ER PT J AU Belyakov, IM Derby, MA Ahlers, JD Kelsall, BL Earl, P Moss, B Strober, W Berzofsky, JA AF Belyakov, IM Derby, MA Ahlers, JD Kelsall, BL Earl, P Moss, B Strober, W Berzofsky, JA TI Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mucosal immune system ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPH-NODE IMMUNIZATION; CLASS-I; INFECTION INVITRO; INTERFERON-GAMMA; NEUTRALIZING ANTIBODY; RESPONSES; ENVELOPE; PROTEIN; CELLS AB Mucosal tissues are major sites of HIV entry and initial infection, Thus, the induction of a mucosal cytotoxic T lymphocyte (CTL) response is an important feature fbr an effective HIV vaccine, However, little is known about approaches to induce such a protective CTL response in the mucosa, Here for the first time we show that intrarectal immunization with a synthetic, multideterminant HIV peptide plus cholera toxin adjuvant induced long-lasting, antigen-specific CTL memory in both the inductive (Peyer's patch) and effector (lamina propria) mucosal sites, as well as in systemic sites (spleen), whereas systemic immunization induced specific CTL only in the spleen, Cholera toxin adjuvant, while enhancing the response, was not essential, The CTL recognized target cells either pulsed with HIV peptide or expressing endogenous whole envelope glycoprotein of M-r 160,000 (gp160), Exploring the requirements for CTL induction, we show that mucosal CTL responses are both interleukin 12 and interferon-gamma dependent by using antibody-treated and knockout mice, Finally, to determine whether a mucosal response is actually protective against local mucosal challenge with virus, we show that intrarectal immunization with the synthetic HIV peptide vaccine protected mice against infection via mucosal challenge with a recombinant vaccinia virus expressing HIV-1IIIB gp160, These studies provide an approach to development of an HIV vaccine that induces CTL immunity in the mucosal and systemic immune systems and protects against mucosal infection with a virus expressing HIV-1 gp160. C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Belyakov, IM (reprint author), NCI, Metab Branch, Bethesda, MD 20892 USA. NR 47 TC 234 Z9 235 U1 2 U2 7 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 FEB 17 PY 1998 VL 95 IS 4 BP 1709 EP 1714 DI 10.1073/pnas.95.4.1709 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900064 PM 9465081 ER PT J AU Pletnev, AG Men, R AF Pletnev, AG Men, R TI Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE viral chimeras; neurovirulence; neuroinvasiveness; protective immunity ID ENVELOPE PROTEIN-E; ENCEPHALITIS-VIRUS; STRUCTURAL PROTEINS; SEQUENCE; GENOME; GENES; MICE; CONSTRUCTION; SUBSTITUTION; STRAINS AB Langat virus (LGT) strain TP21 is the most attenuated of the tick-borne flaviviruses for humans, Even though LGT has low level neurovirulence for humans, it, and its more attenuated egg-passage derivative, strain E5, exhibit significant neurovirulence and neuroinvasiveness in normal mice, albeit less than that associated with tick-borne encephalitis virus (TBEV), the most virulent of the tick-borne flaviviruses. We sought to reduce or ablate these viral phenotypes of TP21 and E5 by using a strategy that had been used successfully in the past to reduce neurovirulence and abolish neuroinvasiveness of TBEV, namely substitution of structural protein genes of the tick-borne flavivirus for the corresponding genes of dengue type 4 virus (DEN4). In pursuit of these objectives different combinations of LGT genes were substituted into the DEN4 genome but only chimeras containing LGT structural proteins premembrane (preM) and envelope glycoprotein (E) were viable. The infectious LGT(preM-E)/DEN4 chimeras were restricted in replication in simian cell cultures but grew to moderately high titer in mosquito cell culture, Also, the chimeras were at least 5,000 times less neurovirulent than their parental LGT virus in suckling mice, Significantly, the chimeras lacked detectable evidence of neuroinvasiveness after i.p. inoculation of Swiss mice or the more permissive SCID mice with 10(5) or 10(7) plaque-forming units (PFU), respectively, Nonetheless, i.p. inoculation of Swiss mice with 10 or 10(3) PFU of either chimeric virus induced LGT neutralizing antibodies and resistance to fatal encephalitis caused by i.p. challenge with LGT TP21, The implications of these observations for development of a live attenuated TBEV vaccine are discussed. C1 NIAID, NIH, Mol Viral Biol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, NIH, Mol Viral Biol Sect, Infect Dis Lab, Bldg 7,Room 236,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. NR 28 TC 81 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 FEB 17 PY 1998 VL 95 IS 4 BP 1746 EP 1751 DI 10.1073/pnas.95.4.1746 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900071 PM 9465088 ER PT J AU Junghans, RP Carrasquillo, JA Waldmann, TA AF Junghans, RP Carrasquillo, JA Waldmann, TA TI Impact of antigenemia on the bioactivity of infused anti-Tac antibody: Implications for dose selection in antibody immunotherapies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL LEUKEMIA; INTERLEUKIN-2 RECEPTOR; RADIOIMMUNOTHERAPY; CATABOLISM; CARCINOMA; AFFINITY; TARGET; SERUM AB In patients with malignancies and immune disorders expressing Tac (alpha chain of the interleukin 2 receptor; CD25), physiologic shedding of this receptor may lead to high blood levels of the soluble form (sTac). This system was used to model the interaction of soluble antigen with antibody in therapeutic settings and to develop rational principles to optimize the delivery of antibody to tumor target cells. First, we confirmed that sTac in vivo can block anti-Tac binding sites and diminish antibody binding to Tac+ cells. Second, the bioactivity of antibody in vivo correlated directly with the amount of antibody infused and inversely with the sTac concentration. Third, bindability of antibody declined in the hours and days after anti-Tac infusion in patients. Finally, tumor targeting was achieved even in the presence of excess sTac, demonstrating a partition of antibody between soluble and cell-bound antigen. A role is proposed for the Brambell receptor (FcRB) to delay saturation of human or chimeric antibodies via differential catabolism of antigen-antibody complexes. Principles are developed for predicting activity of administered antibody in the presence of soluble antigen to assist in dose selection in passive, radioimmuno and immunotoxin therapies. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol,Biotherapeut Dev Lab, Boston, MA 02115 USA. Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Junghans, RP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol,Biotherapeut Dev Lab, HIM 403, Boston, MA 02115 USA. EM junghans@warren.med.harvard.edu RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 22 TC 16 Z9 16 U1 1 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 FEB 17 PY 1998 VL 95 IS 4 BP 1752 EP 1757 DI 10.1073/pnas.95.4.1752 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900072 PM 9465089 ER PT J AU Mahana, W Zhao, TM Teller, R Robinson, MA Kindt, TJ AF Mahana, W Zhao, TM Teller, R Robinson, MA Kindt, TJ TI Genes in the pX region of human T cell leukemia virus I influence Vav phosphorylation in T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; HTLV-I; HEMATOPOIETIC DEVELOPMENT; SIGNALING PROTEINS; EXCHANGE FACTOR; SH2 DOMAIN; RAS; ACTIVATION; PATHWAY AB Human T cell leukemia virus I (HTLV-I) causes acute leukemic disease in a low percentage of infected individuals through obscure mechanisms. Our studies compare two rabbit HTLV-I-infected T cell lines: one, RH/K34, causes lethal experimental leukemia and the other, RH/K30, mediates asymptomatic infection. We show herein that the product of the protooncogene vav is constitutively Tyrphosphorylated in RH/K34 but not in RH/K30. A role for the retrovirus in phosphorylation of Vav was assigned by transfection experiments with molecular clones of HTLV-I derived from the two lines. The HTLV-I molecular clone from RH/K30, but not that from RH/K34, down-regulates Vav phosphorylation in a Herpesvirus ateles-transformed T cell line, Use of recombinant virus clones revealed that a pX region sequence differing by two nucleotides between the two clones mediates this down-regulation, Because Vav is involved in T cell signaling and Vav phosphorylation occurs upon activation of T cells, control of the activation state of Vav by viral proteins may relate to the leukemogenic potential of certain HTLV-I-infected cells. C1 NIAID, Immunogenet Lab, Twinbrook Facil 2, Rockville, MD 20852 USA. RP Kindt, TJ (reprint author), NIAID, Immunogenet Lab, Twinbrook Facil 2, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM tk9c@nih.gov NR 54 TC 11 Z9 11 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 FEB 17 PY 1998 VL 95 IS 4 BP 1782 EP 1787 DI 10.1073/pnas.95.4.1782 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900077 PM 9465094 ER PT J AU Greenstone, HL Nieland, JD de Visser, KE De Bruijn, MLH Kirnbauer, R Roden, RBS Lowy, DR Kast, WM Schiller, JT AF Greenstone, HL Nieland, JD de Visser, KE De Bruijn, MLH Kirnbauer, R Roden, RBS Lowy, DR Kast, WM Schiller, JT TI Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CLASS-I PRESENTATION; BOVINE PAPILLOMAVIRUS; PEPTIDE VACCINATION; DEFICIENT MICE; CELLS; L1; PROTEIN; TYPE-16; IMMUNIZATION AB Papillomavirus-like particles (VLPs) are a promising prophylactic vaccine candidate to prevent human papillomavirus (HPV) infections and associated epithelial neoplasia, However, they are unlikely to have therapeutic effects because the virion capsid proteins are not detected in the proliferating cells of the infected epithelia or in cervical carcinomas, To increase the number of viral antigen targets for cell-mediated immune responses in VLP-based vaccine,,ve have generated stable chimeric VLPs consisting of the L1 major capsid protein plus the entire E7 (11 kDa) or E2 (43 kDa) nonstructural papillomavirus protein fused to the L2 minor capsid protein. The chimeric VLPs are indistinguishable from the parental VLPs in their morphology and in their ability to agglutinate erythrocytes and elicit high titers of neutralizing antibodies, Protection from tumor challenge was tested in C57BL/6 mice by using the tumor cell line TC-1, which expresses HPV16 E7, but not the virion structural proteins, Injection of HPV16 L1/L2-HPV16 E7 chimeric VLPs, but not HPV16 L1/L2 VLPs, protected the mice from tumor challenge, even in the absence of adjuvant. The chimeric VLPs also induced protection against tumor challenge in major histocompatibility class II-deficient mice, but not in beta(2)-microglobulin or perforin knockout mice implying that protection was mediated by class I-restricted cytotoxic lymphocytes, These findings raise the possibility that VLPs may generally be efficient vehicles for generating cell-mediated immune responses and that, specifically, chimeric VLPs containing papillomavirus nonstructural proteins may increase the therapeutic potential of VLP-based prophylactic vaccines in humans. C1 NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Univ Leiden Hosp, Dept Immunohematol, NL-2300 RC Leiden, Netherlands. Univ Leiden Hosp, Bloodbank, NL-2300 RC Leiden, Netherlands. Univ Vienna, Sch Med, Dept Dermatol, A-1090 Vienna, Austria. RP Schiller, JT (reprint author), NIH, Cellular Oncol Lab, 36 Convent Dr,MSC 4040, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov FU NCI NIH HHS [P01CA74182, R01 CA074397, R01 CA74397] NR 44 TC 251 Z9 262 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 FEB 17 PY 1998 VL 95 IS 4 BP 1800 EP 1805 DI 10.1073/pnas.95.4.1800 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900080 PM 9465097 ER PT J AU Hanss, B Leal-Pinto, E Bruggeman, LA Copeland, TD Klotman, PE AF Hanss, B Leal-Pinto, E Bruggeman, LA Copeland, TD Klotman, PE TI Identification and characterization of a cell membrane nucleic acid channel SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOSPHOROTHIOATE OLIGONUCLEOTIDES; ANTISENSE RNA; PORE COMPLEX; DNA-BINDING; OLIGODEOXYNUCLEOTIDE; INHIBITION; INTERNALIZATION; STIMULATION; REPLICATION; EXPRESSION AB We have identified a 45-kDa protein purified from rat renal brush border membrane that binds short single-stranded nucleic acid sequences. This activity was purified, reconstituted in proteoliposomes, and then fused with model planar lipid bilayers, In voltage-clamp experiments, the reconstituted 45-kDa protein functioned as a gated channel that allows the passage of nucleic acids, Channel activity was observed immediately after addition of oligonucleotide. Channel activity was not observed in the absence of purified protein or of oligonucleotide or when protein was heat-inactivated prior to forming proteoliposomes. In the presence of symmetrical buffered solution and oligonucleotide, current passed linearly over the range of holding potentials tested, Conductance was 10.4 +/- 0.4 picosiemens (pS) and reversal potential was 0.2 +/- 1.7 mV. There was no difference in channel conductance or reversal potential between phosphodiester and phosphorothioate oligonucleotides. Ion-substitution experiments documented a shift in reversal potential only when a concentration gradient for oligonucleotide was established, indicating that movement of oligonucleotide alone was responsible for current, Movement of oligonucleotide across the bilayer was confirmed by using P-32-labeled oligonucleotides, Channel open probability decreased significantly in the presence of heparan sulfate, These studies provide evidence for a cell surface channel that conducts nucleic acids. C1 Mt Sinai Sch Med, Div Nephrol, New York, NY 10029 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Adv Biosci Labs, Frederick, MD 21702 USA. RP Hanss, B (reprint author), Mt Sinai Sch Med, Div Nephrol, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIDDK NIH HHS [1PO1DK50795-02, P01 DK050795] NR 36 TC 103 Z9 107 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 FEB 17 PY 1998 VL 95 IS 4 BP 1921 EP 1926 DI 10.1073/pnas.95.4.1921 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YY126 UT WOS:000072115900101 PM 9465118 ER PT J AU Berger, A Cultaro, CM Segal, S Spiegel, S AF Berger, A Cultaro, CM Segal, S Spiegel, S TI The potent lipid mitogen sphingosylphosphocholine activates the DNA binding activity of upstream stimulating factor (USF), a basic helix-loop-helix-zipper protein SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article; Proceedings Paper CT Experimental Biology 95 Meeting CY APR 09-13, 1995 CL ATLANTA, GEORGIA SP Federat Amer Soc Exptl Biol DE E-box; Max; Myc; sphingolipid; sphingosylphosphocholine; USF ID TRANSCRIPTION FACTOR USF; C-MYC; GENE; MAX; PROMOTER; CELLS; GROWTH; DIFFERENTIATION; EXPRESSION; MEMBERS AB We previously demonstrated that the sphingolipid, sphingosylphosphocholine (SPC) increased DNA binding activity of AP-1 proteins accompanying cellular proliferation. Herein, the effects of SPC on DNA binding activity and transcription of the basic, helix-loop-helix, leucine zipper (bHLH-ZIP) proteins Myc: Max, and USF were investigated because they regulate genes involved in mitogenesis. E-box (CACGTG) DNA binding proteins were detected by electrophoretic mobility shift assays in nuclear extracts from Swiss 3T3 fibroblasts. The slowest migrating complex (complex I) increased within 1-3min after treatment with SPC, remained elevated for 10min, and increased again after 12h. Complexes I and II contained USF-I and USF-2 proteins, and complex I migrated similarly to recombinant USF-1 protein/DNA complex. Treatment of nuclear extracts with all;aline phosphatase decreased these complexes suggesting USF might be a phosphoprotein, post-translationally modified by SPC. max and usf-l mRNA levels were unaffected by SPC treatment. In contrast, c-myc mRNA was rapidly elevated, reached maximum levels at 0.5-1h, and showed an additional increase after 12h, just preceding S phase. Thus, certain bHLH-ZIP transcription factors may be involved in cell growth regulation by SPC. (C) 1998 Elsevier Science B.V. C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NCI, Navy Med Oncol Branch, NIH, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20889 USA. RP Spiegel, S (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. FU NCI NIH HHS [R01 CA61774, F32CA09249] NR 52 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD FEB 16 PY 1998 VL 1390 IS 2 BP 225 EP 236 DI 10.1016/S0005-2760(97)00180-X PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZD557 UT WOS:000072698500010 PM 9507145 ER PT J AU Kodjabachian, L Delaage, M Maurel, C Miassod, R Jacq, B Rosset, R AF Kodjabachian, L Delaage, M Maurel, C Miassod, R Jacq, B Rosset, R TI Mutations in ccf, a novel Drosophila gene encoding a chromosomal factor, affect progression through mitosis and interact with Pc-G mutations SO EMBO JOURNAL LA English DT Article DE centrosome; chromosome condensation; Drosophila; homeotic transformation; mitosis ID POLYCOMB GROUP GENE; CELL-CYCLE GENES; HISTONE H1; TOPOISOMERASE-II; GROUP PROTEINS; BINDING-SITES; GAGA FACTOR; SMC FAMILY; MELANOGASTER; CONDENSATION AB We report herein the isolation of ccf, a new gene located in region 82E and essential for Drosophila development. This gene, expressed throughout development, encodes a novel product of 68 kDa which is found in the nucleus during interphase and labels, in a novel pattern, centrosomes and chromosome arms during mitosis. Mutations in ccf give rise to late larvae with small imaginal discs and to adults showing appendages of reduced size, consistent with CCP involvement in cell proliferation. Neuroblast squash analyses show that CCF is required for proper condensation of mitotic chromosomes and, therefore, for progression through mitosis. Furthermore, we observe that adult ccf mutants as well as animals overexpressing CCF during larval stages exhibit homeotic transformations. We also find that mutations in the Pc-G genes Polycomb, polyhomeotic and Enhancer of zeste are enhanced by ccf mutations. Finally, we show that the CCF protein binds to specific sites on polytene chromosomes, many of which are shared with the Posterior sex combs Pc-G protein. Together, these results suggest a role for the CCP protein in the maintenance of chromosome structure during mitosis and interphase. C1 Inst Biol Dev Marseille, CNRS, Lab Genet & Physiol Dev, F-13288 Marseille 9, France. RP Kodjabachian, L (reprint author), NICHHD, NIH, Bldg 6B,Room 420, Bethesda, MD 20892 USA. EM kodja@nih.gov NR 63 TC 32 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 16 PY 1998 VL 17 IS 4 BP 1063 EP 1075 DI 10.1093/emboj/17.4.1063 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YZ690 UT WOS:000072281000022 PM 9463384 ER PT J AU Segal, BM Dwyer, BK Shevach, EM AF Segal, BM Dwyer, BK Shevach, EM TI An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD4(+) T-CELLS; MESSENGER-RNA EXPRESSION; NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY TREATMENT; CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; IFN-GAMMA; INTERFERON-GAMMA AB Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon gamma. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4(+) T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. OI Segal, Benjamin/0000-0002-0906-6319 NR 83 TC 359 Z9 365 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 FEB 16 PY 1998 VL 187 IS 4 BP 537 EP 546 DI 10.1084/jem.187.4.537 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YY558 UT WOS:000072160200010 PM 9463404 ER PT J AU Jankovic, D Cheever, AW Kullberg, MC Wynn, TA Yap, G Caspar, P Lewis, FA Clynes, R Ravetch, JV Sher, A AF Jankovic, D Cheever, AW Kullberg, MC Wynn, TA Yap, G Caspar, P Lewis, FA Clynes, R Ravetch, JV Sher, A TI CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MANSONI-INFECTED MICE; DEFICIENT MICE; LYMPHOCYTES-T; IN-VIVO; CUTANEOUS LEISHMANIASIS; MURINE SCHISTOSOMIASIS; ADOPTIVE SUPPRESSION; TARGETED DISRUPTION; TOLERANCE INDUCTION; PROTECTIVE IMMUNITY AB The effector functions of CD4(+) T lymphocytes are generally thought to be controlled by distinct populations of regulatory T cells and their soluble products. The role of B cells in the regulation of CD4-dependent host responses is less well understood. Hepatic egg granuloma formation and fibrosis in murine schistosomiasis are dependent on CD4(+) lymphocytes, and previous studies have implicated CD8(+) T cells or cross-regulatory cytokines produced by T helper (Th) lymphocytes as controlling elements of this pathologic process. In this report, we demonstrate that B cell-deficient (mu MT) mice exposed to Schistosoma mansoni develop augmented tissue pathology and, more importantly, fail to undergo the spontaneous downmodulation in disease normally observed during late stages of infection. Unexpectedly, B cell deficiency did not significantly alter T cell proliferative response or cause a shift in the Th1/Th2 balance. Since schistosome-infected Fc receptor-deficient (FcR gamma chain knockout) mice display the same exacerbated egg pathology as that observed in infected mu MT mice, the B cell-dependent regulatory mechanism revealed by these experiments appears to require receptor-mediated cell triggering. Together, the data demonstrate that humoral immune response/FcR interactions can play a major role in negatively controlling inflammatory disease induced by CD4(+) T cells. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Rockefeller Univ, New York, NY 10021 USA. RP Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM djankovic@atlas.ninid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 53 TC 131 Z9 139 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 FEB 16 PY 1998 VL 187 IS 4 BP 619 EP 629 DI 10.1084/jem.187.4.619 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YY558 UT WOS:000072160200018 PM 9463412 ER PT J AU Podgornik, R Parsegian, VA AF Podgornik, R Parsegian, VA TI Charge-fluctuation forces between rodlike polyelectrolytes: Pairwise summability reexamined SO PHYSICAL REVIEW LETTERS LA English DT Article ID DNA; CONDENSATION; LONG AB We formulate low-frequency charge-fluctuation forces between charged cylinders, parallel or skewed. in salt solution. At high-salt concentrations. forces are exponentially screened. In low-salt solutions, dipolar fluctuation energies go as R-5 or R-4; monopolar energies vary as R-1 or lnR, where R is the minimal separation between cylinder axes. The most important result is not the derivation of long-sought pair potentials but rather the demonstration that pairwise summability of rod-rod ion-fluctuation forces is easily violated under low-salt conditions. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Podgornik, R (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 21 TC 122 Z9 123 U1 2 U2 14 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD FEB 16 PY 1998 VL 80 IS 7 BP 1560 EP 1563 DI 10.1103/PhysRevLett.80.1560 PG 4 WC Physics, Multidisciplinary SC Physics GA YX202 UT WOS:000072016600052 ER PT J AU Olden, K AF Olden, K TI The complex interaction of poverty, pollution, health status SO SCIENTIST LA English DT Editorial Material AB SEEKING environmental justice: Researchers are amassing data on the role of the environment in the overall health of poor, largely minority populations in the United States, but the impact of these efforts will depend on the extent to which they lead to change in national environmental and public health policies, contends Kenneth Olden, director of the National Institute of Environmental Health Sciences. C1 NIEHS, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Olden, K (reprint author), NIEHS, Natl Inst Hlth, POB 12233, Res Triangle Pk, NC 27709 USA. NR 9 TC 12 Z9 12 U1 0 U2 2 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD FEB 16 PY 1998 VL 12 IS 4 BP 7 EP 7 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA YX148 UT WOS:000072011200007 ER PT J AU Sutton-Tyrrell, K Rihal, C Sellers, MA Burek, K Trudel, J Roubin, G Brooks, MM Grogan, M Sopko, G Keller, N Jandova, R AF Sutton-Tyrrell, K Rihal, C Sellers, MA Burek, K Trudel, J Roubin, G Brooks, MM Grogan, M Sopko, G Keller, N Jandova, R CA BARI Invest TI Long-term prognostic value of clinically evident noncoronary vascular disease in patients undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID POPULATION; SURVIVAL AB In the general population, peripheral atherosclerosis is a strong predictor of cardiovascular disease and death. In patients with known coronary artery disease, it is unclear whether the presence of additional noncoronary atherosclerosis is of further prognostic valve. In the Bypass Angioplasty Revascularization Investigation, 5-year outcome was compared between patients with and without clinically evident noncoronary atherosclerosis. Within the subgroup with noncoronary atherosclerosis, surgery, and angioplasty treatment strategies were compared. Noncoronary atherosclerosis was defined as claudication, peripheral vascular surgery, abdominal aortic aneurysm, history of cerebral ischemia, or carotid disease. Among 1,816 patients, 303 (17%) had noncoronary atherosclerosis. These patients were more likely to have a history of congestive heart failure, diabetes, and hypertension, and were more likely: smoke. Coronary angiographic variables were similar between the 2 groups. Five-year survival was 75.8% for patients with noncoronary atherosclerosis and 90.2% for those without (p <0.001). The adjusted relative risk of death was 1.7 for any noncoronary atherosclerosis, 1.5 for lower extremity disease alone, 1.7 for cerebral disease alone, and 2.3 for both conditions. Among the 303 patients with noncoronary atherosclerosis, the adjusted relative risk of death for surgery versus angioplasty was 0.87 (p = 0.40). However, the study has limited power to detect a treatment effect in this small subgroup. Thus, patients with combined coronary and clinically evident noncoronary atherosclerosis are a high-risk group with significantly worse long-term outcome compared patients with isolated coronary disease. (C) 1997 by Excerpta Medica, Inc. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Duke Univ, Durham, NC USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Univ Alabama, Birmingham, AL USA. Brown Univ, Providence, RI 02912 USA. NHLBI, Bethesda, MD 20892 USA. Inst Clin & Expt Med, Prague, Czech Republic. RP Sutton-Tyrrell, K (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. OI Brooks, Maria/0000-0002-2030-7873 FU NHLBI NIH HHS [HL38504, HL38509, HL38493] NR 14 TC 47 Z9 48 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 FEB 15 PY 1998 VL 81 IS 4 BP 375 EP 381 DI 10.1016/S0002-9149(97)00934-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YX444 UT WOS:000072040600001 PM 9485122 ER PT J AU Fleg, JL Kitzman, DW Aronow, WS Rich, MW Gardin, JM Slone, SA AF Fleg, JL Kitzman, DW Aronow, WS Rich, MW Gardin, JM Slone, SA TI Physician management of patients with heart failure and normal versus decreased left ventricular systolic function SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID EJECTION FRACTION; ELDERLY PATIENTS; PREVALENCE; PROGNOSIS AB A questionnaire was administered to a random sample of family practitioners, internists, cardiologists, and geriatricians to examine the current management of heart failure patients with preserved versus reduced left ventricular systolic function. In patients with preserved systolic function, electrocardiogram at rest, chest x-ray, echocardiography, digitalis, angiotensin-converting enzyme inhibitors, and restriction of dietary sodium and physical activity are used less often, whereas calcium channel blockers and beta blockers are given more often than to patients with reduced systolic function. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. Wake Forest Univ, Bowman Gray Sch Med, Div Cardiol & Publ Hlth Sci, Winston Salem, NC USA. Mt Sinai Sch Med, New York, NY USA. Washington Univ, Med Ctr, Barnes Jewish Hosp, Div Cardiol, St Louis, MO USA. RP Fleg, JL (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 18 TC 8 Z9 8 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 FEB 15 PY 1998 VL 81 IS 4 BP 506 EP + DI 10.1016/S0002-9149(97)00941-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YX444 UT WOS:000072040600026 PM 9485147 ER PT J AU Galanis, DJ Harris, T Sharp, DS Petrovitch, H AF Galanis, DJ Harris, T Sharp, DS Petrovitch, H TI Relative weight, weight change, and risk of coronary heart disease in the Honolulu Heart Program SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; coronary disease; weight gain; weight loss ID BODY-WEIGHT; DIABETES-MELLITUS; FOLLOW-UP; MEN; OBESITY; FRAMINGHAM; STROKE; HEALTH; HAWAII; WOMEN AB Risk of coronary heart disease (CHD) among the Honolulu Heart Program participants was examined in relation to body mass index (BMI) at age 25 and two subsequent periods of weight change: age 25 to examination 1 (1965-1968) and examination I to examination III (1971-1974), During a maximum follow-up period of 17 years after examination III, there were 479 incident cases of CHD among the study sample of 6,176 Japanese-American men. Levels of BMI at age 25 were positively related to CHD incidence after statistical control for age, smoking, and subsequent weight change, Relative risk between the lowest and highest BMI categories was 2.44 (95% confidence interval (CI) 1.61-3.69), Compared with a weight change of less than 2.5 kg between age 25 and examination I, relative risks were 1.41 (95% CI 1.00-1.97) for a weight gain between 2.6 and 5 kg, 1.60 (95% CI 1.22-2.11) for a weight gain between 5.1 and 10 kg, and 1.75 (95% CI 1.32-2.33) for a weight gain of more than 10 kg. During the examination I-III period, in contrast, the highest risk of CHD was found in men who lost the greatest amount of weight; the relative risk of CHD for men who lost more than 2.5 kg was 1.25 (95% CI 0.98-1.60). The authors conclude that levels of relative weight in early adulthood were positively related to risk of CHD occurring much later in the lives of these men. The association between CHD incidence and weight change appeared to be modified by age, with higher risks for earlier weight gain and later weight loss in the lives of these men. C1 Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. NHLBI, Honolulu Epidemiol Res Unit, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Div Clin Epidemiol, Honolulu, HI 96822 USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Div Geriatr Med, Honolulu, HI 96822 USA. RP Galanis, DJ (reprint author), State Dept Hlth, Injury Prevent & Control Program, 1250 Punchbowl St,Room 214, Honolulu, HI 96813 USA. NR 41 TC 44 Z9 44 U1 0 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 FEB 15 PY 1998 VL 147 IS 4 BP 379 EP 386 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZA168 UT WOS:000072335800008 PM 9508105 ER PT J AU Pau, AK AF Pau, AK TI New issues in the management of cytomegalovirus retinitis in AIDS patients SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID GANCICLOVIR IMPLANT; CIDOFOVIR C1 NIAID, Dept Pharm, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Pau, AK (reprint author), NIAID, Dept Pharm, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1N257,10 Ctr Dr,MSC 1196, Bethesda, MD 20892 USA. EM apau@nih.gov NR 29 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD FEB 15 PY 1998 VL 55 IS 4 BP 392 EP 395 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YY358 UT WOS:000072139100016 PM 9504201 ER PT J AU Howell, MR Quinn, TC Gaydos, CA AF Howell, MR Quinn, TC Gaydos, CA TI Screening for Chlamydia trachomatis in asymptomatic women attending family planning clinics - A cost-effectiveness analysis of three strategies SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE cost-benefit analysis; Chlamydia trachomatis; mass screening; adnexitis ID POLYMERASE CHAIN-REACTION; PELVIC INFLAMMATORY DISEASE; AMPLICOR-PCR; ENDOCERVICAL SPECIMENS; INCREMENTAL COST; REACTION ASSAY; LOW-PREVALENCE; INFECTION; URINE; DIAGNOSIS AB Background: Screening women for Chlamydia trachomatis in family planning clinics is associated with a reduced incidence of chlamydial sequelae. However, the question of whom to screen to maintain efficient use of resources remains controversial. Objective: To assess the cost-effectiveness of chlamydial screening done according to three sets of criteria in asymptomatic women attending family planning clinics. Design: Cost-effectiveness analysis done by using a decision model with the perspective of a health care system. Model estimates were based on analysis of cohort data, clinic costs, laboratory costs, and published data. Setting: Two family planning clinics in Baltimore, Mary land. Patients: 7699 asymptomatic women who presented between April 1994 and August 1996. Intervention: Three screening strategies-screening according to the criteria of the Centers for Disease Control and Prevention (CDC), screening all women younger than 30 years of age, and universal screening-were retrospectively applied and compared. All women were tested with polymerase chain reaction. Measurements: Medical outcomes included sequelae prevented in women, men, and infants. Total costs included screening program costs and future medical costs of all sequelae. The incremental cost-effectiveness ratios of each strategy were calculated. Results: Without screening, 152 cases of pelvic inflammatory disease would occur at a cost of $676 000. Screening done by using the CDC criteria would prevent 64 cases of pelvic inflammatory disease at a cost savings of $231 000. Screening all women younger than 30 years of age would prevent an additional 21 cases of pelvic inflammatory disease and save $74 000. Universal screening would prevent an additional 6 cases of pelvic inflammatory disease but would cost $19 000 more than age-based screening, or approximately $3000 more per case of pelvic inflammatory disease prevented. If the prevalence of C. trachomatis is more than 10.2% or if less than 88.5% of infections occur in women younger than 30 years of age, universal screening provides the greatest cost savings. Conclusions: These results suggest that age-based screening provides the greatest cost savings of the three strategies examined. However, universal screening is desirable in some situations. In general, screening done by using any criteria and a highly sensitive diagnostic assay should be part of any chlamydial prevention and control program or health plan. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Howell, MR (reprint author), Johns Hopkins Univ, Div Infect Dis, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 34 TC 104 Z9 105 U1 2 U2 5 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 FEB 15 PY 1998 VL 128 IS 4 BP 277 EP + PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA YX170 UT WOS:000072013400004 PM 9471930 ER PT J AU Kopp, JB Miller, KD Falloon, J AF Kopp, JB Miller, KD Falloon, J TI Indinavir and interstitial nephritis - In response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 1 TC 6 Z9 6 U1 0 U2 0 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 FEB 15 PY 1998 VL 128 IS 4 BP 320 EP 321 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YX170 UT WOS:000072013400016 ER PT J AU Del Corso, A Dal Monte, M Vilardo, PG Cecconi, I Moschini, R Banditelli, S Cappiello, M Tsai, L Mura, U AF Del Corso, A Dal Monte, M Vilardo, PG Cecconi, I Moschini, R Banditelli, S Cappiello, M Tsai, L Mura, U TI Site-specific inactivation of aldose reductase by 4-hydroxynonenal SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE aldose reductase; 4-hydroxynonenal; S-thiolation ID LIPID-PEROXIDATION PRODUCT; LOW-DENSITY-LIPOPROTEIN; BOVINE LENS; INHIBITORS; OXIDATION; PROTEINS; BINDING; THIOL AB Bovine lens aldose reductase (ALR2), which catalyzes the NADPH-dependent reduction of 4-hydroxy-2-nonenal (HNE), is readily inactivated by its own substrate in a time- and concentration-dependent manner. Both DTT and NADP(+) can prevent enzyme inactivation but neither extensive dialysis nor thiol-reducing treatment were able to restore enzyme activity once inactivation had occurred. Unlike the native enzyme, S-glutathionyl-modified ALR2 is unaffected by HNE, and can be easily reverted to the native form under thiol-reducing conditions. Evidence is presented of the involvement of Cys298 in the inactivation process, Zofenoprilat, an antioxidant thiol compound, mimics the effect of GSH. The possibility is raised that enzyme thiolation may function as a protection mechanism against the irreversible modification of ALR2. (C) 1998 Academic Press. C1 Univ Pisa, Dipartimento Fisiol & Biochim, I-56100 Pisa, Italy. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Modena, Dipartimento Sci Biomed, I-41100 Modena, Italy. RP Mura, U (reprint author), Univ Pisa, Dipartimento Fisiol & Biochim, Via S Maria 55, I-56100 Pisa, Italy. EM cmario@dfb.unipi.it NR 24 TC 46 Z9 47 U1 1 U2 4 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 FEB 15 PY 1998 VL 350 IS 2 BP 245 EP 248 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZB037 UT WOS:000072428500012 PM 9473298 ER EF