FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Shimizu, Y Satoh, S Yano, H Minokoshi, Y Cushman, SW Shimazu, T AF Shimizu, Y Satoh, S Yano, H Minokoshi, Y Cushman, SW Shimazu, T TI Effects of noradrenaline on the cell-surface glucose transporters in cultured brown adipocytes: novel mechanism for selective activation of GLUT1 glucose transporters SO BIOCHEMICAL JOURNAL LA English DT Article ID RAT ADIPOSE-CELLS; INTRINSIC ACTIVITY; 3T3-L1 ADIPOCYTES; PLASMA-MEMBRANE; SUGAR-TRANSPORT; INSULIN; TISSUE; NOREPINEPHRINE; MODULATION; BINDING AB Glucose transport into rat brown adipocytes has been shown to be stimulated directly by the sympathetic neurotransmitter, noradrenaline, without a significant increase in the protein content of either GLUT1 or GLUT4 glucose transporter in the plasma membrane [Shimizu, Kielar, Minokoshi and Shimazu (1996) Biochem. J. 314, 485-490]. In the present study, we labelled the exofacial glucose-binding sites of GLUT1 and GLUT4 with a membrane-impermeant photoaffinity reagent, 2-N-[4-(1 -azitrifluoroethyl)benzoyl]-[2-H-3]1,3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-[H-3]BMPA), to determine which isoform is responsible for the noradrenaline-induced increase in glucose transport into intact brown adipocytes in culture. Insulin stimulated the rate of hexose transport by increasing ATB-[H-3]BMPA-labelled cell-surface GLUT4. In contrast, the noradrenaline-induced increase in glucose transport was not accompanied by an increased ATB-[H-3]BMPA labelling of GLUT4, nor with an increased amount of GLUT4 in the plasma membrane fraction as assessed by Western blotting, indicating that noradrenaline does not promote the translocation of GLUT4. However, noradrenaline induced an increase in photoaffinity labelling of cell-surface GLUT1 without an apparent increase in the immunoreactive GLUT1 protein in the plasma membrane. This is suggestive of an increased affinity of GLUT1 for the ligand. In fact, the K-i value of non-radioactive ATB-BMPA for 2-deoxy-D-glucose uptake was significantly decreased after treatment of the cells with noradrenaline. The increased photoaffinity labelling of GLUT1 and increased glucose transport caused by noradrenaline were inhibited by a cAMP antagonist, cAMP-S Rp-isomer. These results demonstrate that noradrenaline stimulates glucose transport in brown adipocytes by enhancing the functional activity of GLUT1 through a cAMP-dependent mechanism. C1 Ehime Univ, Sch Med, Dept Med Biochem, Shigenobu, Ehime 79102, Japan. Yokohama City Univ, Sch Med, Dept Internal Med 3, Yokohama, Kanagawa 236, Japan. NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Shimazu, T (reprint author), Ehime Univ, Sch Med, Dept Med Biochem, Shigenobu, Ehime 79102, Japan. NR 36 TC 48 Z9 48 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 FEB 15 PY 1998 VL 330 BP 397 EP 403 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB154 UT WOS:000072441800056 PM 9461536 ER PT J AU Biro, T Maurer, M Modarres, S Lewin, NE Brodie, C Acs, G Acs, P Paus, R Blumberg, PM AF Biro, T Maurer, M Modarres, S Lewin, NE Brodie, C Acs, G Acs, P Paus, R Blumberg, PM TI Characterization of functional vanilloid receptors expressed by mast cells SO BLOOD LA English DT Article ID H-3 RESINIFERATOXIN BINDING; ROOT GANGLION MEMBRANES; CAPSAICIN RECEPTORS; SENSORY NEURONS; GENE-EXPRESSION; NERVE-FIBERS; CA-45 UPTAKE; SUBSTANCE-P; RAT; INFLAMMATION AB Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. The C-type receptor is coupled to Ca-45 uptake, whereas the R-type is detectable by [H-3]RTX binding. We describe here specific vanilloid responses in murine mast cells (MCs). In the MC lines and in bone marrow-derived mast cells. capsaicin and RTX induced Ca-45 uptake similarly to that observed for cultured rat dorsal root ganglion neurons (DRGs). This response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of MCs with capsaicin or RTX induced desensitization to subsequent stimulation of Ca-45 uptake. The potency for desensitization by RTX in the MCs corresponded to that for Ca-45 uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high-affinity [H-3]RTX binding site. Consistent with this difference, in MCs we were unable to detect [H-3]RTX binding. Vanilloids were noncytotoxic to the MCs, in contrast to the DRGs. Although vanilloids did not cause degranulation in MCs, in the P815 clone capsaicin evoked selective interleukin-4 release. We conclude that certain MCs possess vanilloid receptors, but only the C-type that functions as a channel. Our finding that MCs can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of inflammation in response to vanilloids. This is a US government work. There are no restrictions on its use. C1 NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Humboldt Univ, Charite, Dept Dermatol, Berlin, Germany. RP Blumberg, PM (reprint author), NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37,Room 3A01,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 52 TC 133 Z9 140 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 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1998 VL 91 IS 4 BP 1332 EP 1340 PG 9 WC Hematology SC Hematology GA YW515 UT WOS:000071943500025 PM 9454764 ER PT J AU Tao, Q Robertson, KD Manns, A Hildesheim, A Ambinder, RF AF Tao, Q Robertson, KD Manns, A Hildesheim, A Ambinder, RF TI Epstein-Barr virus (EBV) in endemic Burkitt's lymphoma: Molecular analysis of primary tumor tissue SO BLOOD LA English DT Article ID T-CELL LYMPHOMAS; LATENT GENE-EXPRESSION; TRANSFORMED B-CELLS; NASOPHARYNGEAL CARCINOMA; HODGKINS-DISEASE; NUCLEAR ANTIGEN-1; LMP1 ONCOGENE; EBNA-1 GENE; LYMPHOPROLIFERATIVE DISORDERS; METHYLATION PATTERNS AB Many aspects of Epstein-Barr virus (EBV) and tumor biology have been studied in Burkitt's lymphoma (BL)-derived cell lines, However, in tissue culture, patterns of gene expression and C promoter-G (CpG) methylation often change and viral strain selection may occur. In this report, 10 cases of snap-frozen endemic BL tumors are characterized in terms of viral gene expression, promoter usage, methylation, and viral strain. EBNA1 and BamHI-A rightward transcripts (BART) were detected in 7 of 7 and LMP2A transcripts in 5 of 7 tumors with well-preserved RNA. Transcripts for the other EBNAs and for LMP1 were not detected in any tumor. These tumors differ from BL cell lines in that they lack a variety of lytic cycle transcripts. This pattern of viral gene expression in endemic BL is similar to that reported in peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive individuals. EBNA1 transcripts originated from the Q promoter (Qp) but not C, W, or F promoters that drive transcription of EBNA1 in other circumstances. Whereas Cp has been previously shown to be entirely CpG methylated in BL, bisulfite genomic sequencing showed virtually no methylation in Qp. Type-A EBV was detected in 6 of 10 and type B in 4 of 10 cases. A previously reported 30bp deletion variant in the carboxyl terminal of LMP1 gene was detected in 5 of 10 cases. The association with both A and B strains contrasts with EBV-associated Hodgkin's disease, nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease, which are much more consistently associated with A strain virus. (C) 1998 by The American Society of Hematology. C1 Johns Hopkins Med Inst, Ctr Oncol, Baltimore, MD 21205 USA. NIH, Rockville, MD USA. RP Ambinder, RF (reprint author), Johns Hopkins Oncol Ctr, 418 N Bond St, Baltimore, MD 21231 USA. FU NCI NIH HHS [R01 CA63532] NR 76 TC 115 Z9 117 U1 0 U2 3 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 FEB 15 PY 1998 VL 91 IS 4 BP 1373 EP 1381 PG 9 WC Hematology SC Hematology GA YW515 UT WOS:000071943500029 PM 9454768 ER PT J AU Chow, WH Blaser, MJ Blot, WJ Gammon, MD Vaughan, TL Risch, HA Perez-Perez, GI Schoenberg, JB Stanford, JL Rotterdam, H West, AB Fraumeni, JF AF Chow, WH Blaser, MJ Blot, WJ Gammon, MD Vaughan, TL Risch, HA Perez-Perez, GI Schoenberg, JB Stanford, JL Rotterdam, H West, AB Fraumeni, JF TI An inverse relation between cagA(+) strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma SO CANCER RESEARCH LA English DT Article ID CANCER; ASSOCIATION; CARCINOMA AB Gastric colonization with Helicobacter pylori, especially cagA(+) strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls, Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA(+) strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8), However, there was little association with cagA(-) strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA(+) strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA. Dept Vet Affairs Med Ctr, Med Serv, Nashville, TN 37212 USA. Int Epidemiol Inst, Rockville, MD USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. New Jersey Dept Hlth & Senior Serv, Appl Canc Epidemiol Program, Trenton, NJ USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. RP Chow, WH (reprint author), NCI, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN 418, Rockville, MD 20852 USA. FU NCI NIH HHS [5U01-CA57923, U01-CA57949, U01-CA57983] NR 37 TC 383 Z9 394 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1998 VL 58 IS 4 BP 588 EP 590 PG 3 WC Oncology SC Oncology GA YX289 UT WOS:000072025300004 PM 9485003 ER PT J AU Hennighausen, L Robinson, GW AF Hennighausen, L Robinson, GW TI Think globally, act locally: the making of a mouse mammary gland SO GENES & DEVELOPMENT LA English DT Review ID CYCLIN D1; PARTURITION; OXYTOCIN; GENE C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RI Robinson, Gertraud/I-2136-2012 NR 40 TC 211 Z9 217 U1 2 U2 12 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 1998 VL 12 IS 4 BP 449 EP 455 DI 10.1101/gad.12.4.449 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YY663 UT WOS:000072171100001 PM 9472013 ER PT J AU Jayaraman, L Moorthy, NC Murthy, KGK Manley, JL Bustin, M Prives, C AF Jayaraman, L Moorthy, NC Murthy, KGK Manley, JL Bustin, M Prives, C TI High mobility group protein-1 (HMG-1) is a unique activator of p53 SO GENES & DEVELOPMENT LA English DT Article DE p53 protein; HMG-1; DNA-binding activation; transcription ID DNA-BINDING FUNCTION; NUCLEOPROTEIN STRUCTURES; TRANSCRIPTION FACTORS; GENE-TRANSCRIPTION; CYCLIN-G; DOMAIN; TARGET; INTERACTS; ELEMENTS; TERMINUS AB The binding of p53 protein to DNA is stimulated by its interaction with covalent as well as noncovalent modifiers. We report the identification of a factor from HeLa nuclear extracts that activates p53 DNA binding. This factor was purified to homogeneity and identified as the high mobility group protein, HMG-1. HMG-1 belongs to a family of highly conserved chromatin-associated nucleoproteins that bend DNA and facilitate the binding of various transcription factors to their cognate DNA sequences. We demonstrate that recombinant His-tagged HMG-1 enhances p53 DNA binding in vitro and also that HMG-1 and p53 can interact directly in vitro. Unexpectedly, HMG-1 also stimulates DNA binding by p53 Delta 30, a carboxy terminally deleted form of the protein that is considered to be constitutively active, suggesting that HMG-1 stimulates p53 by a mechanism that is distinct from other known activators of p53. Finally, using transient transfection assays we show that HMG-1 can increase p53 and p53 Delta 30-mediated transactivation in vivo. HMG-1 promotes the assembly of higher order p53 nucleoprotein structures, and these data, along with the fact that HMG-1 is capable of bending DNA, suggest that HMG-1 may activate p53 DNA binding by a novel mechanism involving a structural change in the target DNA. C1 Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. NIH, Bethesda, MD 20892 USA. RP Prives, C (reprint author), Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RI Bustin, Michael/G-6155-2015 FU NCI NIH HHS [CA58316, R37 CA058316, R01 CA058316]; NIGMS NIH HHS [GM37971, R01 GM037971] NR 57 TC 252 Z9 254 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 1998 VL 12 IS 4 BP 462 EP 472 DI 10.1101/gad.12.4.462 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YY663 UT WOS:000072171100003 PM 9472015 ER PT J AU Pavitt, GD Ramaiah, KVA Kimball, SR Hinnebusch, AG AF Pavitt, GD Ramaiah, KVA Kimball, SR Hinnebusch, AG TI eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange SO GENES & DEVELOPMENT LA English DT Article DE phosphorylation; eIF2; GEF; translation initiation ID INITIATION FACTOR-II; GCN2 PROTEIN-KINASE; AMINO-ACID CONTROL; SACCHAROMYCES-CEREVISIAE; TRANSLATION INITIATION; GAMMA-SUBUNIT; EUKARYOTIC INITIATION-FACTOR-2; NEGATIVE REGULATOR; ALPHA-SUBUNIT; MESSENGER-RNA AB eIF2B is a heteropentameric guanine-nucleotide exchange factor essential for protein synthesis initiation in eukaryotes. Its activity is inhibited in response to starvation or stress by phosphorylation of the alpha subunit of its substrate, translation initiation factor eIF2, resulting in reduced rates of translation and cell growth. We have used an in vitro nucleotide-exchange assay to show that wild-type yeast eIF2B is inhibited by phosphorylated eIF2 [eIF2(alpha P)] and to characterize eIF2B regulatory mutations that render translation initiation insensitive to eIF2 phosphorylation in vivo. Unlike wild-type eIF2B, eIF2B complexes with mutated GCN3 or GCD7 subunits efficiently catalyzed GDP exchange using eIF2(alpha P) as a substrate. Using an affinity-binding assay, we show that an eIF2B subcomplex of the GCN3, GCD7, and GCD2 subunits binds to eIF2 and has a higher affinity for eIF2(alpha P), but it lacks nucleotide-exchange activity. In contrast, the GCD1 and GCD6 subunits form an eIF2B subcomplex that binds equally to eIF2 and eIF2(alpha P). Remarkably, this second subcomplex has higher nucleotide-exchange activity than wild-type eIF2B that is not inhibited by eIF2(alpha P). The identification of regulatory and catalytic eIF2B subcomplexes leads us to propose that binding of eIF2(alpha P) to the regulatory subcomplex prevents a productive interaction with the catalytic subcomplex, thereby inhibiting nucleotide exchange. C1 NICHHD, Eukaryot Mol Genet Lab, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. RP Univ Dundee, Dept Anat & Physiol, Dundee DD1 4HN, Scotland. EM ahinnebusch@nih.gov RI Pavitt, Graham/A-1363-2010 OI Pavitt, Graham/0000-0002-8593-2418 FU NIDDK NIH HHS [DK13499, DK15658, R01 DK013499, R01 DK015658] NR 48 TC 147 Z9 155 U1 0 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 1998 VL 12 IS 4 BP 514 EP 526 DI 10.1101/gad.12.4.514 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YY663 UT WOS:000072171100008 PM 9472020 ER PT J AU Takenoshita, S Mogi, A Nagashima, N Yang, K Yagi, K Hanyu, A Nagamachi, Y Miyazono, K Hagiwara, K AF Takenoshita, S Mogi, A Nagashima, N Yang, K Yagi, K Hanyu, A Nagamachi, Y Miyazono, K Hagiwara, K TI Characterization of the MADH2/Smad2 gene, a human Mad homolog responsible for the transforming growth factor-beta and activin signal transduction pathway SO GENOMICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; IN-VIVO ALTERATIONS; HUMAN LUNG CANCERS; II RECEPTOR GENE; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; DNA METHYLATION; DPC4 GENE; PROTEINS; INACTIVATION AB The transforming growth factor beta (TGF-beta) super-family is a family of multifunctional cytokines that transduce signals via serine/threonine kinase receptors. Recent studies revealed that Mothers against dpp (Mad) in Drosophila and its homologs play important roles in the intracellular signal transduction of the serine/threonine kinase receptors. In mammals, one of the Mad homologs, MADH2 (also termed Smad2), was reported to be a mediator of TGF-beta and activin signaling and was found mutated in some of the colon and lung cancer cases. We describe here the genomic organization of the human MADH2 gene. The gene is composed of 12 exons; 2 exons 1, i.e., exon 1a and 1b, are used separately or in conjunction to form exon 1a-exon 1b-exon 2 alternatively spliced mRNA. The 2 exons 1 are closely located, and the MADH2 mRNAs are transcribed from two promoters in one CpG island. The promoter activity in the 5' upstream sequence was confirmed by the luciferase assay. The 3' end of the mRNA is heterogenous, and we found several polyadenylation signals. Northern blot analysis revealed high expression of the MADH2 mRNA, e.g., in skeletal muscle, heart, and placenta. RT-PCR assay using primers in exons 2 and 4 and direct nucleotide sequencing proved that exon 3 is spliced out in about 10% of MADH2 in human placenta. These data will be valuable for studying the MADH2 function in both normal cells and cancer cells. (C) 1998 Academic Press. C1 Gunma Univ, Sch Med, Dept Surg 1, Maebashi, Gumma 371, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Beijing Med Univ, Sch Oncol, Beijing Inst Canc Res, Beijing 100034, Peoples R China. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 170, Japan. Japan Soc Promot Sci, Res Future Program, Tokyo 170, Japan. RP Takenoshita, S (reprint author), Gunma Univ, Sch Med, Dept Surg 1, 3-39-22,Showa Machi, Maebashi, Gumma 371, Japan. NR 55 TC 46 Z9 47 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 FEB 15 PY 1998 VL 48 IS 1 BP 1 EP 11 DI 10.1006/geno.1997.5149 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YZ891 UT WOS:000072304800001 PM 9503010 ER PT J AU Yamashita, T Agulnick, AD Copeland, NG Gilbert, DJ Jenkins, NA Westphal, H AF Yamashita, T Agulnick, AD Copeland, NG Gilbert, DJ Jenkins, NA Westphal, H TI Genomic structure and chromosomal localization of the mouse LIM domain-binding protein 1 gene, Ldb1 SO GENOMICS LA English DT Article ID DIFFERENTIATION; EXPRESSION; ORGANIZATION; REQUIREMENT; RHOMBOTIN AB The LIM domain is a structural motif that is well conserved throughout evolution in a variety of factors known to play important roles in development and cell regulation. Ldb genes encode LIM domain-binding (Ldb) factors. Here we report on the structural organization and chromosomal localization of the mouse Ldb1 gene. It contains at least 10 exons and spans approximately 4 kb of genomic DNA. The transcription initiation site is located 462 bp upstream of the translation initiation codon ATG: as determined by 5'-RACE. Sequencing analysis of the 5'-flanking region shows TATA and CCAAT motifs as well as potential binding sites for GATA, CF-1, PEA3, HRE, APRRE, RARE, Myc, and c-Jun. Ldb1 maps to the distal region of mouse chromosome 19 that is syntenic with human chromosome 10q. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL,Basic Res Program, Frederick, MD 21702 USA. RP Westphal, H (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bldg 6B,Room 413, Bethesda, MD 20892 USA. NR 23 TC 9 Z9 10 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 FEB 15 PY 1998 VL 48 IS 1 BP 87 EP 92 DI 10.1006/geno.1997.5163 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YZ891 UT WOS:000072304800011 PM 9503020 ER PT J AU McDyer, JF Goletz, TJ Thomas, E June, CH Seder, RA AF McDyer, JF Goletz, TJ Thomas, E June, CH Seder, RA TI CD40 ligand CD40 stimulation regulates the production of IFN-gamma from human peripheral blood mononuclear cells in an IL-12- and/or CD28-dependent manner SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; INTERFERON-GAMMA; COSTIMULATORY ACTIVITY; LEISHMANIA-MAJOR; HUMAN MONOCYTES; INTERLEUKIN-12 PRODUCTION; MEDIATED-IMMUNITY; DENDRITIC CELLS; UP-REGULATION; B-CELLS AB CD40 ligand (CD40L)/CD40 costimulation is an important regulator of Th1 responses. Two mechanisms by which CD40L/CD40 stimulation may enhance IFN-gamma are via direct induction of IL-12 and augmentation of the expression of costimulatory molecules such as B7 from APCs, We examined the ability of CD40L/CD40 stimulation to regulate the production of IFN-gamma through IL-12 and/or CD28 costimulation from human PBMCs stimulated with T cell-specific stimuli. The roles of exogenous and endogenous CD40L/CD40 stimulation were evaluated using a trimeric soluble CD40L agonist (CD40T) and an anti-CD40L Ab, respectively. The presence of CD40T in cultures increased the production of IL-12 and IFN-gamma from PBMCs stimulated with varying amounts of PHA. The mechanism, however, by which CD40T enhanced IFN-gamma varied according to the level of T cell activation. Under maximal stimulatory conditions (PHA, 1/100), an IL-12-dependent pathway was dominant. At relatively low levels of T cell stimulation (PHA, 1/500 and 1/1000), however, an additional IL-12-independent CD28-dependent pathway was elucidated. We further studied the role of exogenous CD28 stimulation in regulating the production of IFN-gamma, The enhancement of IFN-gamma production induced by direct CD28 stimulation was primarily dependent on endogenous IL-12 or CD40L/CD40 stimulation. Together, these data suggest that the production of IFN-gamma involves a complex interaction between two interdependent, yet distinct, costimulatory pathways and provide evidence that CD40T may be an effective adjuvant for the enhancement of responses. C1 NIAID, Clin Invest Lab, Lymphokine Regulat Unit, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Immunex Corp, Seattle, WA 98191 USA. Henry M Jackson Fdn Advancement Mil Med, US Mil HIV Res Program, Bethesda, MD 20899 USA. RP McDyer, JF (reprint author), NIAID, Clin Invest Lab, Lymphokine Regulat Unit, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. NR 40 TC 70 Z9 71 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 FEB 15 PY 1998 VL 160 IS 4 BP 1701 EP 1707 PG 7 WC Immunology SC Immunology GA ZN995 UT WOS:000073704800020 PM 9469427 ER PT J AU Monsour, MJ Mikulski, PW AF Monsour, MJ Mikulski, PW TI On limiting distributions in explosive autoregressive processes SO STATISTICS & PROBABILITY LETTERS LA English DT Article DE purely explosive autorepressive process; characteristic roots; Jordan normal, canonical form ID PARAMETERS; MODELS AB The limiting distribution is obtained for the maximum likelihood estimator in the AR(p) process with a random and nonrandom normalization and all characteristic roots outside the unit circle? purely explosive process. Though these results have been in the literature, proofs have been omitted. A detailed proof of these results will be presented. With a random normalization the limiting distribution is multivariate standard normal. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIDR, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Math, College Pk, MD 20742 USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7152 J9 STAT PROBABIL LETT JI Stat. Probab. Lett. PD FEB 15 PY 1998 VL 37 IS 2 BP 141 EP 147 DI 10.1016/S0167-7152(97)00111-9 PG 7 WC Statistics & Probability SC Mathematics GA YX210 UT WOS:000072017400005 ER PT J AU Li, H Kramer, PM Lubet, RA Steele, VE Kelloff, GJ Pereira, MA AF Li, H Kramer, PM Lubet, RA Steele, VE Kelloff, GJ Pereira, MA TI Effect of calcium on azoxymethane-induced aberrant crypt foci and cell proliferation in the colon of rats SO CANCER LETTERS LA English DT Article DE aberrant crypt foci; calcium; cell proliferation; chemoprevention; colon cancer ID DIETARY CALCIUM; ADENOMATOUS POLYPS; CHEMOPREVENTIVE AGENTS; COLORECTAL-CANCER; LARGE-BOWEL; SUPPLEMENTATION; CARCINOGENESIS; INHIBITION; RISK; EPITHELIUM AB Calcium has been proposed for prevention of colon cancer, The effects of calcium on azoxymethane (AOM)-induced aberrant crypt foci (ACP), a putative precancerous lesion, and cell proliferation were determined in rat colon. Male F344 rats were given AIN-76A diet that contained calcium at concentrations of 0.5, 1.0, 2.5, 5.0, 10.0 and 15.0 g/kg in experiment 1 and 0.2, 2.0 and 6.0 g/kg in experiment 2, One week after the rats received these diets, they were given the first of two weekly 15 mg/kg injections of AOM. The rats were killed after 35 days of exposure to the different diets. In experiment 1, exposure to either low (0.5 and 1.0 g/kg) or high (10.0 and 15.0 g/kg) concentrations of calcium reduced the yield of ACF relative to 5.0 g/kg calcium. In experiment 2, exposure to 0.2 and 2.0 g/kg calcium resulted in a lower yield of ACF than 6.0 g/kg. Cell proliferation in ACF and non-involved crypts was reduced in animals that received 0.5 or 15.0 mg/Kg relative to 5.0 mg/kg diet calcium. Our results indicate that both lower and higher concentrations of calcium relative to its standard concentration in AIN-76A diet can prevent ACF and reduce the extent of cell proliferation in the lesion which would likely lead to the prevention of colon cancer. (C) 1998 Elsevier Science Ireland Ltd. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NCI, Chemoprevent Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Li, H (reprint author), Med Coll Ohio, Dept Pathol, Hlth Educ Bldg,Room 200F,3055 Arlington Ave, Toledo, OH 43614 USA. FU NCI NIH HHS [1-CN-55175] NR 35 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 13 PY 1998 VL 124 IS 1 BP 39 EP 46 DI 10.1016/S0304-3835(97)00453-9 PG 8 WC Oncology SC Oncology GA YX725 UT WOS:000072071000006 PM 9500189 ER PT J AU Leung, LK Do, L Wang, TTY AF Leung, LK Do, L Wang, TTY TI Regulation of death promoter Bak expression by cell density and 17 beta-estradiol in MCF-7 cells SO CANCER LETTERS LA English DT Article DE apoptosis; Bak; Bcl-2; breast cancer; estradiol ID BCL-2 HOMOLOG BAK; APOPTOSIS; ESTROGEN; CANCER; SUPPRESSION; PATHWAYS; LINE AB In the current study we examined the regulation of Bak, a death promoter of an apoptotic pathway, in the human breast cancer cell line MCF-7. We observed a time-dependent increase in both Bak mRNA and protein levels which appeared to correlate well with the increase in cell density. We also found that treatment of cells with 17 beta-estradiol resulted in inhibition of the time-dependent increases in Bak mRNA and protein. The effects of estradiol appeared to be via estrogen receptor as treatment of cells with progesterone did not effect Bak expression. Our study provides additional molecular evidence for (1) a link between apoptosis pathways and cell-cell and/or cell-cell matrix interactions and (2) a role for estradiol in the modulation of signals between apoptosis pathways and cell-cell and/or cell-cell matrix interactions. Published by Elsevier Science Ireland Ltd. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Nutr & Mol Regulat, Div Basic Sci,NIH, Frederick, MD 21702 USA. RP Wang, TTY (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Nutr & Mol Regulat, Div Basic Sci,NIH, Bldg 560-12-05,POB B, Frederick, MD 21702 USA. RI Leung, Lai/C-6511-2013; LEUNG, Lai K./E-6314-2011 OI Leung, Lai/0000-0002-7781-3099; LEUNG, Lai K./0000-0002-7781-3099 NR 18 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 13 PY 1998 VL 124 IS 1 BP 47 EP 52 DI 10.1016/S0304-3835(97)00430-8 PG 6 WC Oncology SC Oncology GA YX725 UT WOS:000072071000007 PM 9500190 ER PT J AU Conaway, CC Jiao, D Kelloff, GJ Steele, VE Rivenson, A Chung, FL AF Conaway, CC Jiao, D Kelloff, GJ Steele, VE Rivenson, A Chung, FL TI Chemopreventive potential of fumaric acid, N-acetylcysteine, N-(4-hydroxyphenyl) retinamide and beta-carotene for tobacco-nitrosamine-induced lung tumors in A/J mice SO CANCER LETTERS LA English DT Article DE chemopreventive agent; fumaric acid; N-acetylcysteine; N-(4-hydroxyphenyl) retinamide; beta-carotene; 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone; lung tumors; strain A/J mice ID ARYLALKYL ISOTHIOCYANATES; CHEMICAL CARCINOGENESIS; CIGARETTE-SMOKE; TUMORIGENESIS; INHIBITION; CANCER; RATS; INDUCTION; RETINOIDS; EXPOSURE AB Four agents, fumaric acid (FA), N-acetylcysteine (NAG), N-(4-hydroxyphenyl) retinamide (4-HPR) and beta-carotene (beta-CT), were evaluated for potential chemopreventive activity using the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor model in female A/J mice. The agents were evaluated in both 16-week and 52-week bioassays at two dose levels corresponding to 0.8 maximum tolerated dose (MTD) and 0.4 MTD administered throughout the bioassay either in the diet (FA, 160 and 80 mmol/kg diet; NAG, 160 and 80 mmol/kg diet; 4-HPR, 4 and 2 mmol/kg diet) or by subcutaneous injection twice a week (beta-CT, 32 and 16 mg/kg b.w.). Mice were treated with a single i.p. dose of 10 mu mol NNK in saline 1 week after administration of test agent. Lung adenomas were evaluated in the 16-week bioassay, whereas both adenomas and adenocarcinomas of the lung were determined in the 52-week bioassay. Both bioassays showed that all four agents did not significantly inhibit the total tumor incidence and multiplicity of the lung. However, the incidence of adenocarcinomas was reduced (P < 0.01) at 52 weeks in NNK groups given either 0.8 MTD NAC or 0.8 MTD beta-CT compared with the NNK control group. The decreases in adenocarcinomas were accompanied by corresponding increases in adenomas in these treatment groups. Thus, this study showed that FA, NAG, 4-HPR and beta-CT did not inhibit the total tumor formation, however, at the higher doses both NAC and beta-CT significantly retarded the malignant progression in the lung of NNK-treated A/J mice. Published by Elsevier Science Ireland Ltd. C1 Amer Hlth Fdn, Div Carcinogenesis & Mol Epidemiol, Valhalla, NY 10595 USA. Nabisco Inc, E Hanover, NJ 07936 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Chung, FL (reprint author), Amer Hlth Fdn, Div Carcinogenesis & Mol Epidemiol, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [1-CN-85095] NR 34 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 13 PY 1998 VL 124 IS 1 BP 85 EP 93 DI 10.1016/S0304-3835(97)00454-0 PG 9 WC Oncology SC Oncology GA YX725 UT WOS:000072071000013 PM 9500196 ER PT J AU Orr, MS Reinhold, W Yu, LJ Schreiber-Agus, N O'Connor, PM AF Orr, MS Reinhold, W Yu, LJ Schreiber-Agus, N O'Connor, PM TI An important role for the retinoblastoma protein in staurosporine-induced G(1) arrest in murine embryonic fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; INHIBITOR STAUROSPORINE; POTENT INHIBITOR; G1 PHASE; 2 POINTS; PROGRESSION; CANCER; P21; PHOSPHORYLATION AB In this study, we investigated the molecular basis of the ability of staurosporine to induce G(1) arrest in murine embryonic fibroblasts (MEFs), We used MEFs from transgenic mice lacking several negative regulators of the G(1)/S phase transition including cells from mice lacking p53, p21, retinoblastoma (Rb), or p16 genes. We found that p53 function was not essential for staurosporine-induced G(1) arrest. In contrast, MEFs from mice lacking Rb genes showed approximately a 70% reduced capacity to arrest in the G(1) phase following staurosporine treatment, In support of a role for Rb in staurosporine-induced G(1) arrest, rat embryonic fibroblasts stably overexpressing cyclin D1/Cdk4(R24C) exhibited approximately a 50% reduced G(1) arrest response to staurosporine. The role of Rb in determining the degree of staurosporine-induced G(1) arrest did not depend on the function of the cyclin-dependent kinase inhibitors p16 or p21 because MEFs lacking either of these genes were still capable of undergoing G(1) arrest following staurosporine exposure. Our studies provide evidence of an important role for the Rb protein in determining the degree of staurosporine-induced G(1) arrest in the first cell cycle. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 11724 USA. RP O'Connor, PM (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 5D09, Bethesda, MD 20892 USA. EM po18c@nih.gov NR 36 TC 18 Z9 19 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 13 PY 1998 VL 273 IS 7 BP 3803 EP 3807 DI 10.1074/jbc.273.7.3803 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YX516 UT WOS:000072048400002 PM 9461560 ER PT J AU Prival, MJ Zeiger, E AF Prival, MJ Zeiger, E TI Chemicals mutagenic in Salmonella typhimurium strain TA1535 but not in TA100 SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Salmonella typhimurium; Ames test; TA1535; TA100; base pair substitution mutation ID MAMMALIAN-MICROSOME ASSAY; AMES TEST; CARCINOGENS; MUTATION; DRUGS AB The standard Salmonella mutagenicity test uses two strains of Salmonella typhimurium (TA1535 and TA100) containing the same base pair substitution mutation (hisG46). These strains differ only in that strain TA100 contains the plasmid pKM101, whose mucAB gene products enhance SOS mutagenesis. This makes strain TA100, in general, the more sensitive of the two for mutagen detection, raising the question as to whether or not to include strain TA1535 in the core battery of strains in routine testing. Out of 659 chemicals judged as mutagens in the S. typhimurium assay when subjected to the National Toxicology Program's screening protocol, 36 (5%) were evaluated as positive in strain TA1535 but not in strain TA100. Of these, 23 were judged as negative and 13 as equivocal in strain TA100, and 5 were positive or equivocal in at least one other strain (TA97 or TA98). In general, the data on these chemicals indicate that the absolute increases in revertants per plate induced in strain TA1535 were too small to have been judged as positive if similar increases occurred in strain TA100. which has a much higher spontaneous background. For three chemicals (acetaldehyde oxime, 6-mercaptopurine, and 1,3-butadiene) the absolute increases in revertants in strain TA1535 greatly exceeded those in strain TA100. Evaluation of the reproducibility of these findings and of the mechanisms and relevance of unique TA1535 positives should be useful when decisions are made as to whether this strain should be kept as a part of the core battery of strains in the S. typhimurium assay. (C) 1998 Elsevier Science B.V. C1 US FDA, Genet Toxicol Branch HFS236, Washington, DC 20204 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Prival, MJ (reprint author), US FDA, Genet Toxicol Branch HFS236, 200 C St SW, Washington, DC 20204 USA. NR 27 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 13 PY 1998 VL 412 IS 3 BP 251 EP 260 DI 10.1016/S1383-5718(97)00196-4 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZL336 UT WOS:000073422700006 PM 9600693 ER PT J AU Malling, HV Weaver, RP AF Malling, HV Weaver, RP TI Mutagenesis of a single AT basepair in mice transgenic for PhiX174 am3 cs70 - I. Spleen and testis SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE PhiX174; transgenic; mice; ENU; spleen; testis ID ESCHERICHIA-COLI; LOCUS TEST; MOUSE SPERMATOGONIA; INDUCED MUTATIONS; PHI-X174 DNA; ETHYLNITROSOUREA; INVITRO; CELLS; NITROSOUREA; SPECTRA AB Mutations induced in a single AT base pair were studied in spleen and testis by using mice transgenic for PhiX174 am3, cs70 and ethylnitrosourea (ENU) as the mutagen. The transgenic mice were produced on the C57BL6/J background. The line (am54), which carries 50 copies of PhiX per haploid genome integrated in a tandem array, was selected for experimental use and was maintained by random breeding. The animals for mutagenesis studies were produced by mating homozygous am54 males to wildtype C57BL6/J females. Hemizygous male offspring (8 to 10 weeks old) from this cross were injected i.p. with 150 mg ENU per kg and were euthanized 3, 10 or 110 days after treatment. The spontaneous revertant frequency in the spleen was 1.42 x 10(-6) per plaque forming unit (pfu) and in the testis it was 1.41 x 10(-6) per pfu. There was no significant difference between the two tissues. In spleen, it was not until 110 days after ENU treatment that the average revertant frequency among treated animals was significantly higher than the revertant frequency among the control animals. In spleen, the induced frequency of basepair substitutions in the center AT basepair in the am3 nonsense codon was 2 x 10(-6). Also at this post-injection interval the variance of revertant frequencies in the spleen was not different from control variance. In testis, the average revertant frequency 110 days post ENU injection was not significantly different from the control. However, two important observations were made regarding the testis data. First, one animal had a significantly increased revertant frequency 110 days after ENU treatment in comparison to the other four animals in the group that had revertant frequencies equal to or lower than the average control frequency. Second, the variance of revertant frequencies in the testis among the treated animals increased as the post injection period increased. Taken together, these observations may indicate that the revertants formed large clusters in one testis sample. (C) 1998 Elsevier Science B.V. C1 NIEHS, Mammalian Genet Grp, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Malling, HV (reprint author), NIEHS, Mammalian Genet Grp, Toxicol Lab, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 13 PY 1998 VL 412 IS 3 BP 271 EP 281 DI 10.1016/S1383-5718(97)00198-8 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZL336 UT WOS:000073422700008 PM 9600695 ER PT J AU Brosgart, CL Louis, TA Hillman, DW Craig, CP Alston, B Fisher, E Abrams, DI Lusken-Hawk, RL Sampson, JH Ward, DJ Thompson, MA Torres, RA AF Brosgart, CL Louis, TA Hillman, DW Craig, CP Alston, B Fisher, E Abrams, DI Lusken-Hawk, RL Sampson, JH Ward, DJ Thompson, MA Torres, RA CA T Beirn Commun Programs Clin Res AIDS TI A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals SO AIDS LA English DT Article; Proceedings Paper CT 35th Interscience Conference on Antimicrobial Agents and Chemotherapy CY JUL, 1996 CL VANCOURVER, CANADA DE cytomegalovirus; oral ganciclovir; prophylaxis; survival; opportunistic infections; disease progression; herpesvirus; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; DOUBLE-BLIND; CONTINUED ZIDOVUDINE; DIDANOSINE; AIDS; MANIFESTATIONS; DEATH AB Objective: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV disease. Design: Double-blind, placebo-controlled, randomized clinical trial in primary care clinics and private practice offices specializing in the care of people with HIV. Interventions were oral GCV (1000 mg three times/day) or placebo. Protocol amendment allowed switch to open-label oral GCV. Main outcome measures were confirmed CMV retinal or gastrointestinal mucosal disease, and death. The study enrolled 994 people co-infected with CMV and HIV, with at least one CD4 count recorded < 100 x 10(6) cells/l. Results: At study completion (15 months median follow-up), CMV event rates in the oral GCV and control groups were 13.1 and 14.6 per 100 person years, respectively, a hazard ratio (HR) of 0.92 [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event rates were 12.7 and 15.0, respectively (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45). At study completion, event rates for death were 26.6 and 32.0 (HR, 0.84; P = 0.09), and at protocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78), respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment effect was associated with baseline use of didanosine (ddI). For patients taking ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was 0.62 (P = 0.04). These HR were statistically different (P = 0.0006). Conclusions: In our study, 3 g/day oral GCV did not significantly reduce CMV disease incidence, but there was a suggestion of a death-rate reduction. Furthermore, results suggest that oral GVC decreased risk of CMV disease in patients not prescribed ddI, and increased risk in those prescribed ddI. For the CMV endpoint, our study differs markedly from the only similar study, although for the death endpoint, a combined analysis of studies indicated significant reduction in death rate. C1 Community Consortium, San Francisco, CA 94705 USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, Stat Ctr,Community Programs Clin Res AIDS, Minneapolis, MN 55455 USA. Mayo Clin, Rochester, MN USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Richmond AIDS Consortium, Richmond, VA USA. AIDS Res Alliance, Chicago, IL USA. Res & Educ Grp, Portland, OR USA. Washington Reg AIDS Program, Washington, DC USA. AIDS Res Consortium Atlanta, Atlanta, GA USA. Clin Directors Network Reg 2, New York, NY USA. RP Brosgart, CL (reprint author), Univ Calif Berkeley, E Bay AIDS Ctr, Community Consortium, 3031 Teleg Ave,Suite 235, Berkeley, CA 94705 USA. NR 29 TC 40 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 12 PY 1998 VL 12 IS 3 BP 269 EP 277 DI 10.1097/00002030-199803000-00004 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YT338 UT WOS:000071591600005 PM 9517989 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI Correspondence - Eukaryotic transcription regulators derive from ancient enzymatic domains SO CURRENT BIOLOGY LA English DT Letter ID SEQUENCE; PROTEIN; CHROMATIN; ALIGNMENT; REGIONS; BINDING; DNA C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 18 TC 22 Z9 22 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD FEB 12 PY 1998 VL 8 IS 4 BP R111 EP R113 DI 10.1016/S0960-9822(98)70982-0 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YX724 UT WOS:000072070900004 PM 9501971 ER PT J AU Moriarty, RM Enache, LA Zhao, L Gilardi, R Mattson, MV Prakash, O AF Moriarty, RM Enache, LA Zhao, L Gilardi, R Mattson, MV Prakash, O TI Rigid phencyclidine analogues. Binding to the phencyclidine and sigma(1) receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID METHYL-D-ASPARTATE; RAT-BRAIN MEMBRANES; INDUCED NEURONAL DAMAGE; CENTRAL NERVOUS-SYSTEM; HIGH-AFFINITY BINDING; GUINEA-PIG BRAIN; ANTICONVULSANT MK-801; NMDA RECEPTOR; GLUTAMATE NEUROTOXICITY; BIOLOGICAL-ACTIVITY AB Three phencyclidine (PCP) analogues possessing a highly rigid carbocyclic structure and an attached piperidine ring which is free to rotate were synthesized. Each analogue has a specific fixed orientation of the ammonium center of the piperidinium ring to the centrum of the phenyl ring. The binding affinities of the rigid analogues 1-piperidino-7,8-benzobicyclo[4.2.0]octene (14), 1-piperidinobenzobicyclo[2.2.1]heptene (16), and 1-piperidinobenzobicyclo[2.2.2]octene (13) for the PCP receptor ([H-3]TCP) and sigma-receptor (NANM) were determined. The three analogues show low to no affinity for the PCP receptor but good affinity for the sigma-receptor and can be considered sigma-receptor selective ligands with PCP/sigma ratios of 13, 293, and 368, respectively. The binding affinities for the sigma-receptor are rationalized in terms of a model for the sigma-pharmacophore. C1 Univ Illinois, Dept Chem, Chicago, IL 60607 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Moriarty, RM (reprint author), Univ Illinois, Dept Chem, Chicago, IL 60607 USA. NR 95 TC 23 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 12 PY 1998 VL 41 IS 4 BP 468 EP 477 DI 10.1021/jm970059p PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA YX340 UT WOS:000072030400007 PM 9484497 ER PT J AU Arnheiter, H AF Arnheiter, H TI Evolutionary biology - Eyes viewed from the skin SO NATURE LA English DT Editorial Material C1 NINDS, Lab Dev Neurogenet, Bethesda, MD 20892 USA. RP Arnheiter, H (reprint author), NINDS, Lab Dev Neurogenet, Bldg 36,Room 5D06,36 Convent Dr, Bethesda, MD 20892 USA. NR 12 TC 29 Z9 29 U1 1 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 12 PY 1998 VL 391 IS 6668 BP 632 EP 633 DI 10.1038/35487 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YW872 UT WOS:000071982500020 PM 9490405 ER PT J AU Ogasawara, K Hida, S Azimi, N Tagaya, Y Sato, T Yokochi-Fukuda, T Waldmann, TA Taniguchi, T Taki, S AF Ogasawara, K Hida, S Azimi, N Tagaya, Y Sato, T Yokochi-Fukuda, T Waldmann, TA Taniguchi, T Taki, S TI Requirement for IRF-1 in the microenvironment supporting development of natural killer cells SO NATURE LA English DT Article ID RECEPTOR-GAMMA CHAIN; REGULATORY FACTOR-I; INTERLEUKIN-2 RECEPTOR; BETA-CHAIN; TRANSCRIPTION FACTOR; IL-2 RECEPTOR; MICE; MARROW; DIFFERENTIATION; SUPPRESSION AB Natural killer (NK) cells are critical for both innate and adaptive immunity(1,2). The development of NK cells requires interactions between their progenitors and the bone-marrow microenvironment(3-6); however, little is known about the molecular nature of such interactions, Mice that do not express the transcription factor interferon-regulatory factor-1 (IRF-1; such mice are IRF-1(-/-) mice) have been shown to exhibit a severe NK-cell deficiency(7,8). Here we demonstrate that the lack of IRF-1 affects the radiation-resistant cells that constitute the microenvironment required for NK-cell development, but not the NK-cell progenitors themselves. We also show that IRF-1(-/-) bone-marrow cells can generate functional NK cells when cultured with the cytokine interleukin-15 (refs 9-12) and that the interleukin-15 gene is transcriptionally regulated by IRF-1. These results reveal, for the first time, a molecular mechanism by which the bone-marrow microenvironment supports NK-cell development. C1 Univ Tokyo, Grad Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 113, Japan. Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 113, Japan. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Taki, S (reprint author), Univ Tokyo, Grad Sch Med, Dept Immunol, Bunkyo Ku, Hongo 7-3-1, Tokyo 113, Japan. EM shin-t@m.u-tokyo.ac.jp RI Ogasawara, Kouetsu/G-9892-2011 NR 30 TC 254 Z9 256 U1 0 U2 5 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 12 PY 1998 VL 391 IS 6668 BP 700 EP 703 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YW872 UT WOS:000071982500054 PM 9490414 ER PT J AU Yin, YX Terauchi, Y Solomon, GG Aizawa, S Rangarajan, PN Yazaki, Y Kadowaki, T Barrett, JC AF Yin, YX Terauchi, Y Solomon, GG Aizawa, S Rangarajan, PN Yazaki, Y Kadowaki, T Barrett, JC TI Involvement of p85 in p53-dependent apoptotic response to oxidative stress SO NATURE LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH-FACTOR; KINASE; P53; PROTEIN; REQUIREMENT; SUPPRESSION; ASSOCIATION; GENERATION; ACTIVATION AB Reactive oxygen species have damaging effects on cellular components and so trigger defensive responses by the cell(1,2) and even programmed cell death(3,4), although the mechanisms by which mammalian cells transmit signals in response to oxidative damage are unknown. We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(S)K. We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress. Because the protein p53 is required for cell death induced by oxidative damage, we examined the relation between p85 and p53. Using a chimaeric p53 fusion protein with the oestrogen receptor (p53ER) to supply p53 (p53 is induced upon binding of p53ER to oestradiol) in a p53-deficient cell line, we found that p85 is upregulated by p53 and that its involvement in p53-mediated apoptosis is independent of PI(3)K. We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Univ Tokyo, Dept Internal Med 3, Tokyo 113, Japan. Kumamoto Univ, Sch Med, Lab Morphogenesis, Kumamoto 860, Japan. Indian Inst Sci, Dept Biochem, Bangalore 560012, Karnataka, India. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RI Rangarajan, Pundi/A-7365-2009 OI Rangarajan, Pundi/0000-0002-6536-9891 NR 27 TC 139 Z9 143 U1 1 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD FEB 12 PY 1998 VL 391 IS 6668 BP 707 EP 710 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YW872 UT WOS:000071982500056 PM 9490416 ER PT J AU Kwon, TK Nordin, AA AF Kwon, TK Nordin, AA TI Identification of cdk2 binding sites on the p27(Kip1) cyclin-dependent kinase inhibitor SO ONCOGENE LA English DT Article DE cell cycle; cdk inhibitors; p27(Kip1); cdk2; cyclin E; point mutations ID CELL-CYCLE; POTENTIAL MEDIATOR; TUMOR SUPPRESSION; ARREST; P21; ACCUMULATION; INDUCTION; CLONING; PCNA; BETA AB A cdk2 binding domain on p27(Kip1) located within the sequence of amino acids 53-85 was further characterized by generating a series of point mutations within amino acid residues 62-75. Two regions, FDF (residues 62-64) and GXY (residues 72 and 74), were identified within the beta hairpin region of p27(Kip1)., Mutations within these regions essentially completely inhibited the binding to in vitro translated cdk2 and cdk2/cyclin E complexes formed in vitro or in vivo., The p27(Kip1) GST-fusion protein of the point mutation that replaces phenylalanine at residue 64 to alanine (F64A) showed approximately twofold less inhibition of cdk2 kinase activity. The cellular response to the introduction of the F64A mutant form of p27(Kip1) was compared to that of p27(Kip1) wild type by transfecting HeLa cells with constructs of full length sense and antisense coding sequences, Overexpression of the F64A mutant form of p27(Kip1) bound significantly lower levels of cdk2 as compared to wild type and did not effect the cdk2 related kinase activity of the transfected HeLa cells. Overexpression of wild type p27(Kip1) resulted in a reduction of the level of cdk2 kinase activity and effectively suppressed the growth of the transfected HeLa cells. C1 NIA, Gerontol Res Ctr, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Nordin, AA (reprint author), NIA, Gerontol Res Ctr, Immunol Lab, NIH, 4940 Eastern Ave,Box 21, Baltimore, MD 21224 USA. NR 34 TC 11 Z9 11 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 12 PY 1998 VL 16 IS 6 BP 755 EP 762 DI 10.1038/sj.onc.1201586 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YW403 UT WOS:000071931800007 PM 9488039 ER PT J AU Zhuang, SM Schippert, A Haugen-Strano, A Wiseman, RW Soderkvist, P AF Zhuang, SM Schippert, A Haugen-Strano, A Wiseman, RW Soderkvist, P TI Inactivations of p16(INK4a)-alpha, p16(INK4a)-beta and p15(INK4b) genes in 2 ',3 '-dideoxycytidine- and 1,3-butadiene-induced murine lymphomas SO ONCOGENE LA English DT Article DE p16(INK4a)-alpha; p16(INK4a)-beta; p15(INK4b); murine lymphomas; 1,3-butadiene; 2 ',3 '-dideoxycytidine ID TUMOR-SUPPRESSOR GENE; DEPENDENT KINASE INHIBITORS; ACUTE LYMPHOCYTIC-LEUKEMIA; CELL-CYCLE INHIBITION; METHYL-N-NITROSOUREA; RETINOBLASTOMA-PROTEIN; PANCREATIC-CANCER; THYMIC LYMPHOMAS; CPG ISLAND; MICE AB The p16(INK4a) (alpha and beta form) and p15(INK4b) genes were analysed for homozygous deletion, hypermethylation and point mutation in B6C3F1 mouse lymphomas induced by 2',3'-dideoxycytidine or 1,3-butadiene, Although the p16(INK4a)-alpha gene appeared normal in DNA from 2',3'-dideoxycytidine-induced lymphomas, Southern analyses revealed homozygous deletions or rearrangements of the p16(INK4a)-beta and/or p15(INK4b) genes in four of 16 tumours, Surprisingly, two of these lymphomas showed exclusive deletions of the p16(INK4a) EI beta exon, The p15(INK4b) promoter region was hypermethylated in two additional 2',3'-dideoxycytidine-induced lymphomas, In contrast, homozygous deletions spanning the p16(INK4a), and p15(INK4b) loci were observed in only two of 31 1,3-butadiene-induced tumours, Thus, these cyclin dependent kinase inhibitor genes may play a significant role in chemically induced mouse lymphomas and support the contention of tumour suppressor activity for the p19(ARF) protein encoded by the p16(INK4a)-beta gene, Different genetic pathways may be involved in the development of these chemically induced tumours since we have previously shown that mutations in p53 and rns genes are common in 1,3-butadiene- but not 2',3'-dideoxycytidine-induced lymphomas,. C1 Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Div Cell Biol, S-58185 Linkoping, Sweden. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Zhuang, SM (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Biomed & Surg, Div Cell Biol, S-58185 Linkoping, Sweden. NR 52 TC 36 Z9 37 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 12 PY 1998 VL 16 IS 6 BP 803 EP 808 DI 10.1038/sj.onc.1201600 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YW403 UT WOS:000071931800013 PM 9488045 ER PT J AU Watson, MA Darrow, C Zimonjic, DB Popescu, NC Fleming, TP AF Watson, MA Darrow, C Zimonjic, DB Popescu, NC Fleming, TP TI Structure and transcriptional regulation of the human mammaglobin gene, a breast cancer associated member of the uteroglobin gene family localized to chromosome 11q13 SO ONCOGENE LA English DT Article DE mammaglobin; breast cancer; genomic organization; promoter ID STEROID-BINDING-PROTEIN; TRANSGENIC MICE; SECRETORY PROTEIN; DNA-SEQUENCE; C-3 GENES; PROMOTER; CELLS; PROSTATE; ANTIGEN; MAP AB The mammaglobin gene encodes a novel secreted protein whose corresponding mRNA is frequently up-regulated in human breast cancer, In non-malignant tissues, expression is also strictly limited to the mammary epithelium. To better understand the mechanisms controlling these patterns of expression, we have isolated the human mammaglobin gene and performed an initial assessment of its promoter activity, Mammaglobin gene architecture is very similar to that of a family of related genes that includes uteroglobin and rat prostatein subunits C1, C2, and C3. However, the mammaglobin gene itself is not well conserved phylogenetically. The human mammaglobin gene is localized by fluorescent in situ hybridization to chromosome 11 band q13, a genomic region frequently amplified in breast neoplasia, The sequence of proximal 1 kb of mammaglobin promoter contains several potential transcriptional control elements and directs high-level expression of a transfected reporter construct in human breast tumor cell lines, However, comparable levels of reporter gene expression are also seen in non-mammary human cell lines, These data suggest that, unlike related gene family members, the striking breast-specific expression and tumor-associated overexpression of mammaglobin is mediated by complex transcriptional control at more distal sequence elements,. C1 Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Watson, MA (reprint author), Washington Univ, Sch Med, Dept Pathol, Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. NR 32 TC 72 Z9 78 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 12 PY 1998 VL 16 IS 6 BP 817 EP 824 DI 10.1038/sj.onc.1201597 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YW403 UT WOS:000071931800015 PM 9488047 ER PT J AU Zhou, Y Aran, J Gottesman, MM Pastan, I AF Zhou, Y Aran, J Gottesman, MM Pastan, I TI Co-expression of human adenosine deaminase and multidrug resistance using a bicistronic retroviral vector SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; MEDIATED GENE-TRANSFER; MURINE BONE-MARROW; HUMAN MDR1 GENE; P-GLYCOPROTEIN; EFFICIENT EXPRESSION; INTERNAL INITIATION; MESSENGER-RNA; MICE; VIRUS AB Current gene therapy protocols designed to treat adenosine deaminase (ADA) deficiency and other metabolic disorders suffer from low-efficiency delivery to target cells and a lack of long-term stability in expression of the therapeutic proteins. These problems may be resolved by use of an in vivo dominant selection. The multidrug transporter (MDR1) has been suggested as a useful selective marker for gene therapy. In this work, we co-expressed ADA and MDR1 cDNA in a retroviral vector using an internal ribosome entry site (IRES) from encephalomyocarditis virus. This system produced a bicistronic mRNA containing both ADA and MDR1, which enables co-expression of ADA and MDR1, and also allows the two proteins to be translated separately. After in vitro selection using a cytotoxic MDR1 substrate, vincristine, we demonstrated that functional ADA was co-expressed with MDR1 in proportion to the expression level of MDR1, whereas MDR1 expression was proportional to the stringency of the vincristine selection. Because the efficiency of IRES-dependent translation was much lower than that of cap-dependent translation in this system, we observed lower expression of the genes positioned after the IRES. This asymmetric expression caused a lower viral titer when MDR1 was placed downstream from the IRES, but it also provided a way of modulating the relative expression of ADA and MDR1. The retroviral system described in this work may serve as a useful tool to evaluate the strategies involving in vivo dominant selection for gene therapy of ADA-deficient patients. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,37 Convent Dr,Room 4E16, Bethesda, MD 20892 USA. NR 33 TC 35 Z9 37 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB 10 PY 1998 VL 9 IS 3 BP 287 EP 293 DI 10.1089/hum.1998.9.3-287 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YX560 UT WOS:000072052800002 PM 9508046 ER PT J AU Kagami, H Atkinson, JC Michalek, SM Handelman, B Yu, S Baum, BJ O'Connell, B AF Kagami, H Atkinson, JC Michalek, SM Handelman, B Yu, S Baum, BJ O'Connell, B TI Repetitive adenovirus administration to the parotid gland: Role of immunological barriers and induction of oral tolerance SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT ADENOVIRUS; IMMUNE-RESPONSE; GENE-TRANSFER; IN-VIVO; TRANSGENE EXPRESSION; BETA-GALACTOSIDASE; PREVENTS FORMATION; IGA ANTIBODIES; VIRAL-ANTIGENS; MOUSE-LIVER AB This study assessed the mucosal and systemic immune responses following repetitive adenoviral vector instillation to the parotid glands, Also, we investigated the feasibility of oral tolerance induction as a rational strategy to overcome the immunological reactions, The replication-deficient recombinant adenovirus vector AdCMVCAT was instilled into rat parotid glands, Chloramphenicol acetyltransferase (CAT) activity in the parotid was observed after a first or second AdCMVCAT infection, but not after a third vector administration, ELISA assays showed increased anti-adenovirus immunoglobulin G (IgG) and IgM in serum, and also anti-adenovirus IgA in gland extracts and saliva after virus administration, The results of in vivo neutralization experiments demonstrated that salivary IgA and IgM prevented reinfection of the parotids with adenoviral vectors, Subsequently, studies were conducted to induce tolerance to adenovirus by peroral feedings of ultraviolet (UV)-inactivated virus before gene administration to the parotid glands, Between 3 and 13 doses of virus were fed to rats, Final parotid gene expression was dependent on the number of viral feedings and the amount fed, Tolerized animals showed prolonged and heightened gene expression in the salivary glands compared to control animals and displayed gene expression even after three administrations of vector, Mononuclear cells from the spleens of these animals showed reduced proliferation following adenovirus stimulation, This same cell population was depleted of CD8(+) T cells and found to produce less interferon-gamma (IFN-gamma) after virus challenge, This profile indicates the down regulation of Th1 cell-mediated responses, These results indicate that oral tolerance induction is a potentially useful adjunct to virus-based gene therapy. C1 NIDR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Nagoya Univ, Sch Med, Dept Oral Surg, Showa Ku, Nagoya, Aichi 466, Japan. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP O'Connell, B (reprint author), NIDR, NIH, Bldg 10-1N113,10 Ctr Dr, Bethesda, MD 20891 USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 42 TC 60 Z9 62 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB 10 PY 1998 VL 9 IS 3 BP 305 EP 313 DI 10.1089/hum.1998.9.3-305 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YX560 UT WOS:000072052800004 PM 9508048 ER PT J AU Wolf, PA Mitchell, JB Baker, CS Kannel, WB D'Agostino, RB AF Wolf, PA Mitchell, JB Baker, CS Kannel, WB D'Agostino, RB TI Impact of atrial fibrillation on mortality, stroke, and medical costs SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FRAMINGHAM; RISK; PREVALENCE AB Background: The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. Methods: We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n=26 753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n=14 267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. Results: Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied (P<.05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF (P<.05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8-to 11.2-fold greater in women with AF (P<.05). Second-and third-year costs were increased as well. Conclusion: Prevention of AF and treatment of patients with Af; and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Math, Boston, MA 02118 USA. Hlth Econ Res Inc, Waltham, MA USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Wolf, PA (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B608, Boston, MA 02118 USA. EM pawolf@bu.edu NR 17 TC 388 Z9 402 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 9 PY 1998 VL 158 IS 3 BP 229 EP 234 DI 10.1001/archinte.158.3.229 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YV982 UT WOS:000071883900004 PM 9472202 ER PT J AU Jensen-Taubman, SM Steinberg, SM Linnoila, RI AF Jensen-Taubman, SM Steinberg, SM Linnoila, RI TI Bronchiolization of the alveoli in lung cancer: Pathology, patterns of differentiation and oncogene expression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID P53 OVEREXPRESSION; EPITHELIAL-CELLS; PROTEIN; HYPERPLASIA; CARCINOMA AB We examined the incidence and association of bronchiolization of the alveoli with non-small cell lung cancer in lung resection specimens from 2 patient groups: those with nonsmall cell lung cancer and those diagnosed with a variety of non-neoplastic lung conditions. We observed marked variation in bronchiolization of the alveoli morphology ranging from normal to severely atypical and developed a classification scheme based on growth pattern, cell number and cytologic criteria, Patterns of differentiation, proliferation and growth factor receptor and oncogene expression were studied using immuno-histochemical and in situ hybridization techniques. While low-grade (0-1) bronchiolization of the alveoli lesions demonstrated markers similar to normal bronchiolar epithelium, a significant decrease in the Clara cell 10 kDa protein and tubulin and an increase in surfactant protein-A expression were observed in high-grade (II-III) lesions. Focal p53 expression was detected in 2 high-grade lesions, while c-myc mRNA and dun protein were observed in all grades. No correlation was observed between bronchiolization of the alveoli incidence and histologic tumor type. A comparison of marker expression in lesions and tumors from the same case revealed a negative correlation between cytokeratin-14 and c-erbB-2 immuno-reactivity. Only one bronchialization of the alveoli lesion was found in the non-neoplastic patient group, We conclude that up to 12% of non-small cell lung cancer resection specimens contain bronchiolization of the alveoli lesions which exhibit altered morphology and patterns of differentiation. (C) 1998 Wiley-Liss, Inc. C1 NCI, Div Clin Sci, Med Branch, Dept Cell & Canc Biol,NIH, Rockville, MD 20850 USA. NCI, Div Clin Sci, Biostat & Data Management Sect, NIH, Rockville, MD 20850 USA. RP Linnoila, RI (reprint author), NCI, Div Clin Sci, Med Branch, Dept Cell & Canc Biol,NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 23 TC 22 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 9 PY 1998 VL 75 IS 4 BP 489 EP 496 DI 10.1002/(SICI)1097-0215(19980209)75:4<489::AID-IJC1>3.0.CO;2-P PG 8 WC Oncology SC Oncology GA YV180 UT WOS:000071797400001 PM 9466646 ER PT J AU Cormier, JN Hijazi, YM Abati, A Fetsch, P Bettinotti, M Steinberg, SM Rosenberg, SA Marincola, FM AF Cormier, JN Hijazi, YM Abati, A Fetsch, P Bettinotti, M Steinberg, SM Rosenberg, SA Marincola, FM TI Heterogeneous expression of melanoma-associated antigens and HLA-A2 in metastatic melanoma in vivo SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CLASS-I ANTIGENS; T-LYMPHOCYTES; CELLS; GP100; IMMUNOTHERAPY; RECOGNITION; RELEVANCE; RESPONSES; PEPTIDES AB MART-1/MelanA and Pme117/gp 100 are melanoma-associated antigens (MAAs) that can be recognized by tumor-infiltrating lymphocytes (TILs) capable of mediating successful adoptive therapy in vivo. Analysis of melanoma cell lines in vitro has demonstrated that heterogeneous antigen expression in the context of class I MHC is a significant co-factor in determining the recognition of melanoma targets by cytotoxic lymphocytes (CTLs). In this study, 217 specimens from 103 patients with metastatic melanoma were examined for the expression of MART-1/MelanA (monoclonal antibody [MAb] M27C10) and Pmel17/gp100 (HMB45 MAb) by immuno-histochemistry. Marked heterogeneity in the expression of both MAAs was confirmed by analysis of the percentage of positively staining tumor cells or the average intensity of tumor staining, We also noted heterogeneity of expression among multiple lesions taken from different anatomic sites within a patient. A dissociation was noted in the detection of MART-1 and gp100 in some lesions, with gp 100 being undetectable in 24% of the lesions and MART-1 being undetectable in 11%. In several cases, loss of one MAA was not associated with lass of the other MAA, suggesting that MART-1 can represent a useful additional marker for the diagnosis of melanoma in gp100 (HMB45)-negative lesions. Of the 217 specimens, 155 were obtained from HLA-A*0201 patients, of which 6% were negative for HLA-AZ, 8% were negative for MART-1/MelanA and 21% were negative for Pmel17/gp100. The potential significance of our findings is illustrated by a case study in which a patient with melanoma experienced rapid tumor progression in association with loss of either MAA or HLA expression in several lesions. (C) 1998 Wiley-Liss, Inc. C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIH, HLA Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 22 TC 131 Z9 133 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 9 PY 1998 VL 75 IS 4 BP 517 EP 524 DI 10.1002/(SICI)1097-0215(19980209)75:4<517::AID-IJC5>3.0.CO;2-W PG 8 WC Oncology SC Oncology GA YV180 UT WOS:000071797400005 PM 9466650 ER PT J AU Dillner, J Knekt, P Boman, J Lehtinen, M Af Geijersstam, V Sapp, M Schiller, J Maatela, J Aromaa, A AF Dillner, J Knekt, P Boman, J Lehtinen, M Af Geijersstam, V Sapp, M Schiller, J Maatela, J Aromaa, A TI Sero-epidemiological association between human-papillomavirus infection and risk of prostate cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; VIRUS-LIKE PARTICLES; SQUAMOUS-CELL CARCINOMA; TYPE-16 INFECTION; HPV DNA; ANTIBODIES; IMMUNIZATION; WOMEN; COHORT; P53 AB Some epidemiological studies of prostate cancer have suggested the existence of a sexually transmitted risk factor, and some studies have reported the presence of human papillomavirus (HPV) DNA in prostate-cancer tissue. To perform a sero-epidemiological evaluation of whether HPV infection is associated with increased risk for prostate cancer, we performed a nested case-control study within a serum bank containing samples from 20,243 healthy Finnish men. We identified 165 cases of prostate cancer that were diagnosed up to 24 years after donation of the serum sample. Two control subjects per case were selected, matched for gender, age and municipality of residence. Serum samples were analyzed for the presence of IgG antibodies against 4 HPV types and against Chlamydia. The presence of antibodies against HPV type 18 was associated with a 2.6-fold increased risk of developing prostate cancer during follow-up (p < 0.005). HPV type 16 tended to be associated with subsequent prostate-cancer occurrence (relative risk: 2.4, p = 0.06), whereas seropositivity for HPV type 11 or type 33 or for Chlamydia was not associated with risk. The results suggest that infection with oncogenic HPV might be involved in the etiology of a minority of prostate cancers. (C) 1998 Wiley-Liss, Inc. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Natl Publ Hlth Inst, Helsinki, Finland. Umea Univ, Dept Virol, Umea, Sweden. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Univ Mainz, Dept Med Microbiol, D-6500 Mainz, Germany. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Finnish Social Insurance Inst, Helsinki, Finland. RP Dillner, J (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, Box 280, S-17177 Stockholm, Sweden. NR 33 TC 74 Z9 79 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 9 PY 1998 VL 75 IS 4 BP 564 EP 567 DI 10.1002/(SICI)1097-0215(19980209)75:4<564::AID-IJC12>3.0.CO;2-9 PG 4 WC Oncology SC Oncology GA YV180 UT WOS:000071797400012 PM 9466657 ER PT J AU Garcia-Borreguero, D Dale, JK Rosenthal, NE Chiara, A O'Fallon, A Bartko, JJ Straus, SE AF Garcia-Borreguero, D Dale, JK Rosenthal, NE Chiara, A O'Fallon, A Bartko, JJ Straus, SE TI Lack of seasonal variation of symptoms in patients with chronic fatigue syndrome SO PSYCHIATRY RESEARCH LA English DT Article DE chronic fatigue syndrome; seasonal affective disorder; seasonality of symptoms; controlled clinical study ID AFFECTIVE-DISORDER; MOOD; DEPRESSION; PHOTOTHERAPY; DEFINITION; POPULATION; BEHAVIOR; LIGHT; WOMEN AB Several of the symptoms involved in chronic fatigue syndrome (CFS) such as fatigue, hypersomnia, hyperphagia, weight gain, and mood show seasonal variations in the general population. The aim of this study was to investigate whether patients with CFS experience seasonal fluctuations in these symptoms as well. Seasonal variation of symptoms was assessed in a group of 41 patients with CFS and 41 controls closely matched for age, gender, and city of residence. Participants were recruited across the US and were asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Profile of Mood States (POMS). CFS patients showed significantly lower scores on multiple SPAQ-derived measures as compared with controls. These included seasonal variation in energy, mood, appetite, weight, and sleep length. Patients also reported a significantly reduced sensitivity toward sunny, dry, and long days than controls. No association was noted between intensity of seasonal changes and severity of depressive symptoms. Patients with CFS exhibit an abnormally reduced seasonal variation in mood and behavior and would not be expected to benefit from light therapy. (C) 1998 Elsevier Science Ireland Ltd. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. NIMH, Div Epidemiol & Serv Res, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N228,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 8 Z9 8 U1 1 U2 2 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 9 PY 1998 VL 77 IS 2 BP 71 EP 77 DI 10.1016/S0165-1781(97)00141-8 PG 7 WC Psychiatry SC Psychiatry GA ZC880 UT WOS:000072628300001 PM 9541142 ER PT J AU New, AS Gelernter, J Yovell, Y Trestman, RL Nielsen, DA Silverman, J Mitropoulou, V Siever, LJ AF New, AS Gelernter, J Yovell, Y Trestman, RL Nielsen, DA Silverman, J Mitropoulou, V Siever, LJ TI Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: A preliminary study SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE serotonin; genetics; personality disorders; polymorphism ID SEROTONIN TRANSPORTER GENE; PERSONALITY-DISORDER; VIOLENT OFFENDERS; FIRE SETTERS; POLYMORPHISM; ALCOHOLISM; RFLP AB To assess the relationship between two phenotypes in an extremely well-characterized population of personality disorder patients-impulsive aggression and prolactin response to fenfluramine-and tryptophan hydroxylase (TPH) genotype, TPH genotype (at an intronic polymorphic site) and prolactin response to fenfluramine were assessed in 40 Caucasian patients with personality disorder. Impulsive aggression was assessed by using the Buss-Durkee Hostility Inventory (BDHI). Twenty-one male patients with the "LL" genotype had higher BDHI scores than men with the "UL" or the "UU" genotype. No relationship between genotype and prolactin response to fenfluramine was found. It was concluded that impulsive-aggressive behavior in male personality disorder patients may be associated with the TPH genotype. (C) 1998 Wiley-Liss, Inc. C1 Bronx Vet Adm Med Ctr, Psychiat Serv 116A, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. W Haven VA Med Ctr, Psychiat Serv 116A, W Haven, CT USA. Yale Univ, Sch Med, Dept Psychiat, Div Mol Psychiat, New Haven, CT USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP New, AS (reprint author), Bronx Vet Adm Med Ctr, Psychiat Serv 116A, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. RI Nielsen, David/B-4655-2009 FU NCRR NIH HHS [5 M01-RR00071]; NIMH NIH HHS [K02-MH01387, R01-MH42827] NR 29 TC 97 Z9 101 U1 4 U2 11 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 7 PY 1998 VL 81 IS 1 BP 13 EP 17 DI 10.1002/(SICI)1096-8628(19980207)81:1<13::AID-AJMG3>3.0.CO;2-O PG 5 WC Genetics & Heredity SC Genetics & Heredity GA YZ567 UT WOS:000072267000003 PM 9514581 ER PT J AU Esterling, LE Yoshikawa, T Turner, G Badner, JA Bengel, D Gershon, ES Berrettini, WH Detera-Wadleigh, SD AF Esterling, LE Yoshikawa, T Turner, G Badner, JA Bengel, D Gershon, ES Berrettini, WH Detera-Wadleigh, SD TI Serotonin transporter (5-HTT) gene and bipolar affective disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE linkage; linkage disequilibrium; chromosome 17q; radiation hybrid; GC-rich PCR ID POLYMORPHISM; SUSCEPTIBILITY; DEPRESSION; LINKAGE; TRAITS; REGION AB Interactions with antidepressants, as well as other biochemical evidence, implicate the serotonin transporter 5-HTT in the etiology of affective disorders, However, genetic studies have produced conflicting results concerning an association of 5-HTT with bipolar disorder, We examined a variable number tandem repeat in the regulatory region of this gene to investigate the possible contribution of 5-HTT to bipolar disorder susceptibility in a 22-pedigree series, By affected-sib-pair analysis and the transmission/disequilibrium test, me found no significant linkage or association of 5-HTT to bipolar disorder, During the course of this study, we adapted a PCR technique designed to amplify long templates to replicating long GC stretches with complex structure, We also refined the location of 5-HTT by radiation hybrid mapping, placing the locus between D17S1294 and SHGC11022 on 17q11.2. (C) 1998 Wiley-Liss, Inc. C1 NIMH, Clin Neurogenet Branch, Unit Gene Mapping & Express, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Bethesda, MD USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. RP Esterling, LE (reprint author), NIMH, Clin Neurogenet Branch, Unit Gene Mapping & Express, NIH, Bldg 10,Room 3N218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 51 Z9 55 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 7 PY 1998 VL 81 IS 1 BP 37 EP 40 DI 10.1002/(SICI)1096-8628(19980207)81:1<37::AID-AJMG7>3.0.CO;2-K PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YZ567 UT WOS:000072267000007 PM 9514585 ER PT J AU Yan, WL Jacobsen, LK Krasnerwich, DM Guan, XY Lenane, MC Paul, SP Dalwadi, HN Zhang, HG Long, RT Kumra, S Martin, BM Scambler, PJ Trent, JM Sidransky, E Ginns, EI Rapoport, JL AF Yan, WL Jacobsen, LK Krasnerwich, DM Guan, XY Lenane, MC Paul, SP Dalwadi, HN Zhang, HG Long, RT Kumra, S Martin, BM Scambler, PJ Trent, JM Sidransky, E Ginns, EI Rapoport, JL TI Chromosome 22q11.2 interstitial deletions among childhood-onset schizophrenics and "multidimensionally impaired" SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE childhood schizophrenia; psychosis; velocardiofacial syndrome; DiGeorge syndrome; chromosome 22; mutation ID CARDIO-FACIAL SYNDROME; VELOCARDIOFACIAL SYNDROME; VARIABILITY; PHENOTYPE AB Since its first description almost a century ago schizophrenia with childhood onset, a rare yet devastating disorder, has been diagnosed in children as young as age 5, Recently, the velocardiofacial syndrome, whose underlying cause is interstitial deletions of 22q11.2, was found in 2 of 100 cases of schizophrenics with adult onset [Karayiorgou et al., Proc Natl Acad Sci USA 92:7612-7616, 1995]. No study has documented the prevalence of velocardiofacial syndrome and the 22q11.2 deletion in a population of schizophrenics with childhood onset, Here we describe the result of such a study in a sample originally selected for a trial of atypical antipsychotic drugs, A separate group of patients was also included in the study; they can best be accounted for as a variant of childhood-onset schizophrenia (COS) and had been provisionally termed "multidimensionally impaired." Fluorescent in situ hybridization screening of 32 COS and 21 multidimensionally impaired patients revealed 1 COS patient with an interstitial deletion spanning at least 2.5 megabases. (C) 1998 Wiley-Liss, Inc. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD USA. Univ London, Hosp Sick Children, London, England. RP Yan, WL (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 49,Room B1EE16, Bethesda, MD 20892 USA. RI Scambler, Peter/C-4998-2008; Guan, Xin-Yuan/A-3639-2009 OI Scambler, Peter/0000-0002-1487-4628; Guan, Xin-Yuan/0000-0002-4485-6017 NR 19 TC 48 Z9 50 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 7 PY 1998 VL 81 IS 1 BP 41 EP 43 DI 10.1002/(SICI)1096-8628(19980207)81:1<41::AID-AJMG8>3.0.CO;2-Q PG 3 WC Genetics & Heredity SC Genetics & Heredity GA YZ567 UT WOS:000072267000008 PM 9514586 ER PT J AU Takeuchi, Y Konishi, M Hori, H Takahashi, T Kometani, T Kirk, KL AF Takeuchi, Y Konishi, M Hori, H Takahashi, T Kometani, T Kirk, KL TI Efficient synthesis of a new, highly versatile chiral derivatizing agent, alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) SO CHEMICAL COMMUNICATIONS LA English DT Article ID ENANTIOMERIC EXCESS DETERMINATION; MULTIFUNCTIONAL CARBON STRUCTURE; CANDIDA-RUGOSA LIPASE; DELTA-DELTA VALUES; MOLECULAR DESIGN; CARBOXYLIC-ACIDS; CHEMICAL-SHIFTS; MOSHER METHOD; ENANTIOSELECTIVITY; CONFIGURATION AB The new and versatile chiral derivatizing agent, alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA), has been efficiently synthesized in optically pure form by Candida rugosa lipase-mediated kinetic resolution of racemic CFTA ethyl ester, the latter being readily prepared by fluorination of ethyl alpha-cyano-p-tolylacetate with FClO3. C1 Toyama Med & Pharmaceut Univ, Toyama 93001, Japan. Toyama Natl Coll Technol, Toyama 939, Japan. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Takeuchi, Y (reprint author), Toyama Med & Pharmaceut Univ, Sugitani 2630, Toyama 93001, Japan. NR 13 TC 36 Z9 36 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PD FEB 7 PY 1998 IS 3 BP 365 EP 366 DI 10.1039/a707755f PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA YW909 UT WOS:000071986900037 ER PT J AU Swanson, JM Sergeant, JA Taylor, E Sonuga-Barke, EJS Jensen, PS Cantwell, DP AF Swanson, JM Sergeant, JA Taylor, E Sonuga-Barke, EJS Jensen, PS Cantwell, DP TI Attention-deficit hyperactivity disorder and hyperkinetic disorder SO LANCET LA English DT Article ID CORPUS-CALLOSUM MORPHOLOGY; ONTARIO CHILD HEALTH; GENERAL-POPULATION; MORPHOMETRIC ANALYSIS; CAUDATE-NUCLEUS; RISK-FACTORS; DSM-III; PREVALENCE; SAMPLE; BOYS C1 Univ Calif Irvine, UCI Child Dev Ctr, Irvine, CA 92715 USA. Univ Amsterdam, Amsterdam, Netherlands. Inst Psychiat, Unit Child Psychiat, London, England. Univ Southampton, Dept Psychol, Southampton SO9 5NH, Hants, England. NIMH, Child & Adolescent Disorders Res Branch, Rockville, MD 20857 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Swanson, JM (reprint author), Univ Calif Irvine, UCI Child Dev Ctr, 19262 Jamboree, Irvine, CA 92715 USA. RI Sonuga-Barke, Edmund/D-9137-2011; OI Jensen, Peter/0000-0003-2387-0650 NR 78 TC 428 Z9 435 U1 8 U2 21 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 7 PY 1998 VL 351 IS 9100 BP 429 EP 433 DI 10.1016/S0140-6736(97)11450-7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YW873 UT WOS:000071982600043 PM 9482319 ER PT J AU Low, SH Roche, PA Anderson, HA van Ijzendoorn, SCD Zhang, M Mostov, KE Weimbs, T AF Low, SH Roche, PA Anderson, HA van Ijzendoorn, SCD Zhang, M Mostov, KE Weimbs, T TI Targeting of SNAP-23 and SNAP-25 in polarized epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANINE KIDNEY-CELLS; SYNAPTOSOMAL-ASSOCIATED PROTEIN; NERVE GROWTH-FACTOR; POLYMERIC IMMUNOGLOBULIN RECEPTOR; SYNTAXIN-BINDING PROTEIN; PRIMARY CILIA; CLOSTRIDIAL NEUROTOXINS; BASOLATERAL TRANSPORT; NONNEURONAL TISSUES; NEURITE OUTGROWTH AB SNAP-23 is the ubiquitously expressed homologue of the neuronal SNAP-25, which functions in synaptic vesicle fusion, We have investigated the subcellular localization of SNAP-23 in polarized epithelial cells, In hepatocyte-derived HepG2 cells and in Madin-Darby canine kidney (MDCK) cells, the majority of SNAP-23 was present at both the basolateral and apical plasma membrane domains with little intracellular localization, This suggests that SNAP-23 does not function in intracellular fusion events but rather as a general plasma membrane t-SNARE, Canine SNAP-23 is efficiently cleaved by the botulinum neurotoxin E, suggesting that it is the toxin-sensitive factor previously found to be involved in plasma membrane fusion in MDCK cells, The localization of SNAP-25 in transfected MDCK cells was studied for comparison and was found to be identical to SNAP-23 with the exception that SNAP-25 was transported to the primary cilia protruding from the apical plasma membrane, which suggests that subtle differences in the targeting signals of both proteins exist. In contrast to its behavior in neurons, the distribution of SNAP-25 in MDCK cells remained unaltered by treatment with dibutyryl cAMP or forskolin, which, however, caused an increased growth of the primary cilia, Finally, we found that SNAP-23/25 and syntaxin 1A, when coexpressed in MDCK cells, do not stably interact with each other but are independently targeted to the plasma membrane and lysosomes, respectively. C1 Univ Calif San Francisco, Dept Anat, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Inst Cardiovasc Res, San Francisco, CA 94143 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Groningen, Dept Physiol Chem, NL-9713 AV Groningen, Netherlands. RP Weimbs, T (reprint author), Univ Calif San Francisco, Dept Anat, Inst Cardiovasc Res, 513 Parnassus Ave, San Francisco, CA 94143 USA. FU NIAID NIH HHS [R01 AI25144, AI39161, AI36953] NR 63 TC 81 Z9 81 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 6 PY 1998 VL 273 IS 6 BP 3422 EP 3430 DI 10.1074/jbc.273.6.3422 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV427 UT WOS:000071822300049 PM 9452464 ER PT J AU Dai, RM Chen, EY Longo, DL Gorbea, CM Li, CCH AF Dai, RM Chen, EY Longo, DL Gorbea, CM Li, CCH TI Involvement of valosin-containing protein, an ATPase co-purified with I kappa B alpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of I kappa B alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOMA CELL-LINES; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; PRECURSOR PROTEIN; ESCHERICHIA-COLI; RAT-LIVER; SIGNAL; PROTEOLYSIS; ACTIVATION; SUBUNIT AB The inactivation of the prototype NF-kappa B inhibitor, I kappa B alpha, occurs through a series of ordered processes including phosphorylation, ubiquitin conjugation, and proteasome-mediated degradation. We identify valosin-containing protein (VCP), an AAA (ATPases associated with a variety of cellular activities) family member, that co-precipitates with I kappa B alpha immune complexes, The ubiquitinated I kappa B alpha conjugates readily associate with VCP both in vivo and in vitro, and this complex appears dissociated from NF-kappa B. In ultracentrifugation analysis, physically associated VCP and ubiquitinated I kappa B alpha complexes sediment in the 19 S fractions, while the unmodified I kappa B alpha sediments in the 4.5 S fractions deficient in VCP, Phosphorylation and ubiquitination of I kappa B alpha are critical for VCP binding, which in turn is necessary but not sufficient for I kappa B alpha degradation; while the N-terminal domain of I kappa B alpha is required in all three reactions, both N- and C-terminal domains are required in degradation, Further, VCP co-purifies with the 26 S proteasome on two-dimensional gels and co-immunoprecipitates with subunits of the 26 S proteasome. Our results suggest that VCP may provide a physical and functional link between I kappa B alpha and the 26 S proteasome and play an important role in the proteasome-mediated degradation of I kappa B alpha. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84132 USA. RP Li, CCH (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 58 TC 245 Z9 249 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 6 PY 1998 VL 273 IS 6 BP 3562 EP 3573 DI 10.1074/jbc.273.6.3562 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV427 UT WOS:000071822300068 PM 9452483 ER PT J AU Noguchi, Y Nakamura, S Yasuda, T Kitagawa, M Kohn, LD Saito, Y Hirai, A AF Noguchi, Y Nakamura, S Yasuda, T Kitagawa, M Kohn, LD Saito, Y Hirai, A TI Newly synthesized Rho A, not Ras, is isoprenylated and translocated to membranes coincident with progression of the G(1) to S phase of growth-stimulated rat FRTL-5 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; GDP DISSOCIATION INHIBITOR; COENZYME-A REDUCTASE; REGULATORY PROTEIN; CYCLE PROGRESSION; C-TERMINUS; THYROTROPIN; TRANSITION; EXPRESSION; FARNESYL AB Ras and Rho are involved in the regulation of signal transduction events governing cell growth and cell proliferation. Protein prenylation is essential for the activation and/or the translocation of these small GTPases; however, protein geranylgeranylation rather than farnesylation is required for G(1)/S transition. We studied prenylation and translocation of Ras and Rho A during G(1)/S progression in growth-stimulated rat thyroid FRTL-5 cells. Immunoblot analysis revealed that both Ras and Rho A were detected in membrane fractions at G(0). Rho A was eliminated from the membrane fraction during G(1) and was not detected on the membrane at mid-G(1). Translocation of Rho A from the cytoplasm back to the membranes was observed during late G(1) phase. In contrast, Ras remains in the membrane fraction through the cell cycle progression from G(1) to S phase. The immunoprecipitation of Rho A from the membrane fraction demonstrated that newly synthesized Rho A, labeled by pulsing cells with [S-35]methionine and [S-35]cysteine, was geranylgeranylated and associated with the membrane in late G(1). These results indicate that Rho A, not Ras, was eliminated from membrane fraction during G(1) progression and that newly synthesized Rho A is geranylgeranylated and translocated to membranes during G(1)/S progression in growth-stimulated FRTL-5 cells. C1 Chiba Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Chiba 260, Japan. Okayama Univ, Sch Med, Inst Cellular & Mol Biol, Dept Cell Chem, Okayama 700, Japan. Kyusyu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Higashi Ku, Fukuoka 81282, Japan. NIDDK, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hirai, A (reprint author), Chiba Univ, Sch Med, Dept Internal Med 2, Chuo Ku, 1-8-1 Inohana Cho, Chiba 260, Japan. EM aizan@med.m.chiba-u.ac.jp NR 31 TC 44 Z9 44 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 6 PY 1998 VL 273 IS 6 BP 3649 EP 3653 DI 10.1074/jbc.273.6.3649 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV427 UT WOS:000071822300079 PM 9452494 ER PT J AU Luo, YQ Umegaki, H Wang, XT Abe, R Roth, GS AF Luo, YQ Umegaki, H Wang, XT Abe, R Roth, GS TI Dopamine induces apoptosis through an oxidation-involved SAPK/JNK activation pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; DOMINANT-NEGATIVE MUTANT; CENTRAL-NERVOUS-SYSTEM; X-RAY-MICROANALYSIS; C-JUN; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; PC12 CELLS; MOLECULAR MECHANISMS; SYMPATHETIC NEURONS AB Dopamine (DA) is a neurotransmitter, but it also exerts a neurotoxic effect under certain pathological conditions, including age-related neurodegeneration such as Parkinson's disease. By using both the 293 cell line and primary neonatal rat postmitotic striatal neuron cultures, we show here that DA induces apoptosis in a time-and concentration-dependent manner. Concomitant with the apoptosis, DA activates the JNK pathway, including increases in JNK activity, phosphorylation of c-Jun, and subsequent increase in c-Jun protein. This DA-induced JNK activation precedes apoptosis and is persistently sustained during the process of apoptosis. Transient expression of a dominant negative mutant SEK1(Lys --> Arg), an upstream kinase of JNK, prevents both DA-induced JNK activation and apoptosis. A dominant negative c-Jun mutant FLAG Delta 169 also reduces DA-induced apoptotic cell death. Anti-oxidants N-acetylcysteine and catalase, which serve as scavengers of reactive oxygen species generated by metabolic DA oxidation, effectively block DA-induced JNK activation and subsequent apoptosis. Thus, our data suggest that DA triggers an apoptotic death program through an oxidative stress-involved JNK activation signaling pathway. Given the fact that the anti-oxidative defense system declines during aging, this molecular event may be implicated in the age-related striatal neuronal cell loss and age-related dopaminergic neurodegenerative disorders, such as Parkinson's and Huntington's diseases. C1 NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Gene Express & Aging Sect, NIH, Baltimore, MD 21224 USA. RP Luo, YQ (reprint author), NIA, Gerontol Res Ctr, Mol Physiol & Genet Sect, NIH, 4940 Eastern Ave,4E02, Baltimore, MD 21224 USA. EM luoyq@helix.nih.gov NR 70 TC 272 Z9 279 U1 0 U2 9 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 6 PY 1998 VL 273 IS 6 BP 3756 EP 3764 DI 10.1074/jbc.273.6.3756 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YV427 UT WOS:000071822300093 PM 9452508 ER PT J AU Husbands, SM Kline, RH Allen, AC Newman, AH AF Husbands, SM Kline, RH Allen, AC Newman, AH TI A diastereospecific synthesis of 2-methyl-5 beta-phenyl-5 alpha-carbethoxy-2-azabicyclo[2.2.1]heptane: A ring-constrained analogue of meperidine SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID COCAINE C1 NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Husbands, Stephen/D-5926-2011; OI Husbands, Stephen/0000-0002-9928-6322 NR 8 TC 4 Z9 4 U1 0 U2 1 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 6 PY 1998 VL 63 IS 3 BP 418 EP 419 DI 10.1021/jo971791z PG 2 WC Chemistry, Organic SC Chemistry GA YY535 UT WOS:000072157700004 ER PT J AU Gonzalez, A Marin, O Sanchez-Camacho, C Pena, JJ Zudaire, E Martinez, A Cuttitta, F Munoz, M AF Gonzalez, A Marin, O Sanchez-Camacho, C Pena, JJ Zudaire, E Martinez, A Cuttitta, F Munoz, M TI Localization of adrenomedullin-like immunoreactivity in the hypothalamo-hypophysial system of amphibians SO NEUROSCIENCE LETTERS LA English DT Article DE adrenomedullin; hypothalamus; hypophysis; immunohistochemistry; Rana perezi; Pleurodeles waltl ID XENOPUS-LAEVIS; BRAIN; RAT; TISSUE; FROG; PHEOCHROMOCYTOMA; PLASMA AB The presence of adrenomedullin-like immunoreactive (AMi) cell bodies and fibers in the hypothalamus and hypophysis of the amphibians Rana perezi (anuran) and Pleurodeles waltl (urodele) was examined by immunohistochemistry. A large population of AMi neurons was found in the suprachiasmatic nucleus of both species. Differently, AMi cells in the magnocellular nucleus of the preoptic area were only found in the urodele, whereas dispersed cells in the caudal infundibular region were exclusively present in the anuran. This different staining pattern is reflected in the hypophysis where the neural lobe is primarily immunoreactive in the urodele while the labeling in the intermediate lobe prevailed in the anuran. The results strongly suggest that, as is mammals, the AM in amphibians may play an important regulatory role in the hypothalamo-hypophysial system. (C) 1998 Elsevier Science Ireland Ltd. C1 Univ Complutense Madrid, Fac Biol, Dept Cell Biol, E-28040 Madrid, Spain. Univ Navarra, Dept Cytol & Histol, E-31080 Pamplona, Spain. NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. RP Gonzalez, A (reprint author), Univ Complutense Madrid, Fac Biol, Dept Cell Biol, E-28040 Madrid, Spain. RI Martinez, Alfredo/A-3077-2013; Marin, Oscar/F-3856-2012; Sanchez-Camacho, Cristina/K-6871-2014; Gonzalez, Agustin/H-2146-2015 OI Martinez, Alfredo/0000-0003-4882-4044; Marin, Oscar/0000-0001-6264-7027; Sanchez-Camacho, Cristina/0000-0001-7756-0426; Gonzalez, Agustin/0000-0002-3052-0694 NR 19 TC 16 Z9 16 U1 1 U2 3 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 6 PY 1998 VL 242 IS 1 BP 13 EP 16 DI 10.1016/S0304-3940(98)00033-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YX102 UT WOS:000072006600004 PM 9580198 ER PT J AU Vinetz, JM Li, J McCutchan, TF Kaslow, DC AF Vinetz, JM Li, J McCutchan, TF Kaslow, DC TI Plasmodium malariae infection in an asymptomatic 74-year-old Greek woman with splenomegaly SO NEW ENGLAND JOURNAL OF MEDICINE 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, CALIFORNIA SP Infect Dis Soc Amer ID FALCIPARUM-MALARIA; IMMUNITY; VACCINE C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. RP Vinetz, JM (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm 126, Bethesda, MD 20892 USA. OI Vinetz, Joseph/0000-0001-8344-2004 NR 23 TC 53 Z9 56 U1 0 U2 2 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 5 PY 1998 VL 338 IS 6 BP 367 EP 371 DI 10.1056/NEJM199802053380605 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YV426 UT WOS:000071822200005 PM 9449730 ER PT J AU Guerrero, C Fernandez-Medarde, A Rojas, JM de Mora, JF Esteban, LM Santos, E AF Guerrero, C Fernandez-Medarde, A Rojas, JM de Mora, JF Esteban, LM Santos, E TI Transformation suppressor activity of C3G is independent of its CDC25-homology domain SO ONCOGENE LA English DT Article DE malignant transformation; focus formation; C3G; Ras; Raf; Sis ID GUANINE-NUCLEOTIDE EXCHANGE; DEPENDENT ACTIVATION; RAS P21; H-RAS; R-RAS; CEREVISIAE CDC25; POINT MUTATIONS; SEVENLESS GENE; SH3 DOMAIN; PH DOMAIN AB The guanine nucleotide releasing protein C3G was initially identified as a Crk SH3-binding protein and recently shown to exhibit exchange activity on Rap1 proteins. Overexpression in NIH3T3 cells of a full-length C3G cDNA isolated from human placenta markedly reduced the focus forming activity of cotransfected, malignantly activated, ras oncogenes (5-7-fold). C3G also had a reverting effect on sis-mediated transformation, decreasing the number of c-sis-induced foci by a factor of 5-10-fold. The observed inhibitory effect of C3G on focus-forming activity of Ras and Sis was always higher than that observed with Rap1A, a known target of C3G. The inhibition of focus formation observed in the presence of C3G was not due to toxic effects on cell viability, since transfected C3G cells exhibited the same survival and growth rates as untransfected NIH3T3 cells or cells transfected with plasmid vector alone. Surprisingly, as opposed to Rap1A, which has no effect on Raf-1 oncogene-mediated transformation, C3G also reduced dramatically (6-8-fold) the number of v-raf-induced foci in transfected NIH3T3 cells. The inhibitory effect on Raf-induced transformation suggests that C3G has other functional targets in addition to Rap1. A C3G mutant (C3G Delta Cat) lacking the catalytic domain (CDC25-H) but retaining the rest of the N-terminal sequences, including the Crk-binding domain, exhibited similar ability than full length C3G to inhibit focus formation. In contrast, a C3G mutant (C3G Cat), containing the catalytic domain only but lacking the rest of the N-terminal sequences, did not have any inhibitory effect on transformation mediated by the oncogenes tested. The C3G-derived gene products overexpressed in our transfected cell lines localized to the cytoplasm and did not change the basal MAPK or JNK activity of those cell lines nor their ability to activate the kinases in response to agonists. Our results suggest that the N-terminal region of C3G, and not its catalytic domain, may be responsible for the inhibitory effects observed. C1 NCI, Cellular & Mol Biol Lab, DBS, NIH, Bethesda, MD 20892 USA. RP Santos, E (reprint author), NCI, Cellular & Mol Biol Lab, DBS, NIH, Bldg 37, Bethesda, MD 20892 USA. RI Guerrero, Carmen/F-1776-2010; Font de Mora, Jaime/H-6304-2015 OI Guerrero, Carmen/0000-0002-8747-6831; Font de Mora, Jaime/0000-0002-6816-2095 NR 53 TC 23 Z9 23 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 5 PY 1998 VL 16 IS 5 BP 613 EP 624 DI 10.1038/sj.onc.1201569 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YV376 UT WOS:000071816600006 PM 9482107 ER PT J AU LaCour, TG Guo, CX Bhandaru, S Boyd, MR Fuchs, PL AF LaCour, TG Guo, CX Bhandaru, S Boyd, MR Fuchs, PL TI Interphylal product splicing: The first total syntheses of cephalostatin 1, the north hemisphere of ritterazine G, and the highly active hybrid analogue, ritterostatin G(N)1(N) SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID BIS-STEROIDAL PYRAZINES; DELTA-HYDROGEN ABSTRACTION; ALKYL PHENYL KETONES; II PHOTOPROCESSES; CONVENIENT PROCEDURE; ALPHA-CLEAVAGE; PHOTOCHEMISTRY; GAMMA; REACTIVITY; ALKALOIDS AB Convergent total syntheses of the extremely potent cell growth inhibitor cephalostatin 1 and two hybrid analogues, ritterostatins G(N)1(N) and G(N)1(S), have been achieved. Ritterostatin G(N)1(N) displays sub-nanomolar activity in the 60 cell line human tumor panel of the National Cancer Institute. The North hemisphere of ritterazine G was efficiently constructed from hecogenin acetate in 15% yield over 13 steps. Extension of a key photolysis/Prins sequence to intermediates 19 and 32 proceeded in excellent yield, leading to installation of the Delta(14) moiety in the-North G-and South I steroidal subunits. Application of a method for directed unsymmetrical coupling furnished the natural and analogue pyrazines in good yield from the cephalostatin and ritterazine components. C1 Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. RP LaCour, TG (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM lacourtg@chem.purdue.edu; pfuchs@chem.purdue.edu NR 69 TC 101 Z9 102 U1 0 U2 6 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 4 PY 1998 VL 120 IS 4 BP 692 EP 707 DI 10.1021/ja972160p PG 16 WC Chemistry, Multidisciplinary SC Chemistry GA YW037 UT WOS:000071889300011 ER PT J AU Zujewski, J Nelson, A Abrams, J AF Zujewski, J Nelson, A Abrams, J TI Much ado about not ... enough data: High-dose chemotherapy with autologous stem cell rescue for breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC PROGENITOR CELLS; PROGRESSION-FREE SURVIVAL; PHASE-I TRIAL; ADJUVANT CHEMOTHERAPY; PERIPHERAL-BLOOD; ALKYLATING-AGENTS; FOLLOW-UP; COMBINATION CHEMOTHERAPY; INTENSIVE CHEMOTHERAPY AB High-dose chemotherapy with autologous bone marrow or stem cell rescue (HDC/ASCR) has been proposed as a promising treatment strategy for breast cancer, Despite the frequency with which this procedure is performed, the role of HDC/ASCR in the treatment of breast cancer remains undefined, The purpose of this review is to examine the rationale for the procedure, the research progress to date, and the limitations of available data. A literature search of Medline from January 1966 through May 1997, CancerLit from January 1983 through May 1997, and Current Contents through May 1997 identified more than 600 English language papers or abstracts on this topic, Our review focuses on the preclinical and clinical data that explore the concept of chemotherapy dose intensity and the role of dose intensity in treating breast cancer. HDC/ASCR is based on the hypothesis that high-dose chemotherapy will. overcome drug resistance, eradicate metastatic disease, and increase the proportion of women with breast cancer who are "cured." To date, results from only one phase 3 trial of HDC/ASCR compared with more conventional therapy have been published, Phase 2 and some phase 3 data on HDC/ASCR in the treatment of high-risk primary breast cancer and metastatic breast cancer are discussed, However, the results are inconclusive, The completion of national and international randomized trials is urgently needed to establish definitively the role of HDC/ASCR in the treatment of breast cancer. C1 NCI, NIH, Bethesda, MD 20892 USA. Emmes Corp, Potomac, MD USA. RP Zujewski, J (reprint author), NCI, NIH, Bldg 10,Rm 12N-226, Bethesda, MD 20892 USA. NR 88 TC 36 Z9 36 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 4 PY 1998 VL 90 IS 3 BP 200 EP 209 DI 10.1093/jnci/90.3.200 PG 10 WC Oncology SC Oncology GA YY182 UT WOS:000072121500007 PM 9462677 ER PT J AU Tao, ML Guo, MD Weiss, R Byrne, J Mills, JL Robison, LL Zeltzer, LK AF Tao, ML Guo, MD Weiss, R Byrne, J Mills, JL Robison, LL Zeltzer, LK TI Smoking in adult survivors of childhood acute lymphoblastic leukemia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 17-21, 1997 CL DENVER, COLORADO SP Amer Soc Clin Oncol ID LONG-TERM SURVIVORS; CIGARETTE-SMOKING; SIBLING ADAPTATION; UNITED-STATES; CANCER; ADJUSTMENT; CHILDREN; TRENDS; EXPERIENCE; BEHAVIORS AB Background: Health-related behaviors are of particular concern in survivors of childhood cancer as they are at increased risk for second cancers and long-term organ dysfunction, The purpose of this study was to compare the smoking behavior and associated factors in young-adult survivors of childhood acute lymphoblastic leukemia (ALL) with those in sibling controls, Methods: A telephone interview that surveyed smoking behavior was conducted with 592 young-adult survivors, treated before age 20 years on Children's Cancer Group ALL protocols, and 409 sibling controls, Using stratified chi-squared analyses and Cox proportional hazards models, we compared the rates of smoking initiation and smoking cessation between survivors and control subjects, Demographic characteristics (age, sex, race, and education) and psychological factors (mood and self-concept) were examined as predictors interacting with survivorship in logistic regression analyses to try to distinguish a subgroup of survivors who may be at greater risk for smoking, Results: Survivors were significantly less likely to have ever smoked (23.0% versus 35.7%; P<.0001) and thus were less likely to ever be regular, daily smokers than sibling controls (19.1% versus 31.3%; P<.0001). Survivors were less likely to quit smoking than sibling controls (26.6% versus 35.2%), although this result was not statistically significant, There were no interactions between survivor status and either demographic or psychological features on smoking behavior, Conclusions: Young-adult survivors of childhood ALL are less likely to experiment with smoking but, once having started, are at similar risk for becoming habitual, persistent smokers as sibling controls. C1 Harvard Univ, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. RP Tao, ML (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, L2,75 Francis St, Boston, MA 02115 USA. NR 42 TC 75 Z9 75 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 4 PY 1998 VL 90 IS 3 BP 219 EP 225 DI 10.1093/jnci/90.3.219 PG 7 WC Oncology SC Oncology GA YY182 UT WOS:000072121500009 PM 9462679 ER PT J AU Potischman, N Weiss, HA Swanson, CA Coates, RJ Gammon, MD Malone, KE Brogan, D Stanford, JL Hoover, RN Brinton, LA AF Potischman, N Weiss, HA Swanson, CA Coates, RJ Gammon, MD Malone, KE Brogan, D Stanford, JL Hoover, RN Brinton, LA TI Diet during adolescence and risk of breast cancer among young women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-SIZE; AMERICAN WOMEN; LIFE; MORTALITY; PATTERNS AB Background: A variety of breast cancer risk factors pertain to a woman's adolescence and may be related to nutritional influences, We assessed risk of early-onset breast cancer related to diet during adolescence in a case-control study, Methods: Study participants were accrued from the following three geographical regions covered by cancer registries: Atlanta, GA; Seattle/Puget Sound, WA; and central New Jersey, Case patients (n = 1647) were newly diagnosed with breast cancer, and control subjects (n = 1501) were identified by random-digit-dialing techniques. In an interview, each subject was asked to recall the frequency of consumption and portion size of 29 key food items at ages 12-13 years, Mothers of a subset of respondents completed questionnaires, and food groups were recalculated after removal of foods with poor agreement between mother and daughter, Logistic regression analyses were used to calculate odds ratios and 95% confidence intervals, Results: When high versus low quartiles of consumption were compared, there was a suggestion of a reduced risk associated with high consumption of fruits and vegetables, although this finding was not statistically significant, Slight increases (of borderline statistical significance) in risk of breast cancer were found for intake of chicken or high-fat meat, Intake of animal fat, high-fat foods, high-fat snacks and desserts, or dairy products during adolescence had no apparent influence on breast cancer risk, Removal of foods suspected to be poorly recalled by the daughters did not change any of the risk estimates, Conclusion: These data do not provide evidence for a strong influence of dietary intakes during adolescence on risk of early-onset breast cancer. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA USA. Fred Hutchinson Canc Res Grp, Seattle, WA USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY 10027 USA. RP Potischman, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 430, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 34 TC 65 Z9 70 U1 1 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 4 PY 1998 VL 90 IS 3 BP 226 EP 233 DI 10.1093/jnci/90.3.226 PG 8 WC Oncology SC Oncology GA YY182 UT WOS:000072121500010 PM 9462680 ER PT J AU Cheng, L Song, SY Pretlow, TG Abdul-Karim, FW Kung, HJ Dawson, DV Park, WS Moon, YW Tsai, ML Linehan, WM Emmert-Buck, MR Liotta, LA Zhuang, ZP AF Cheng, L Song, SY Pretlow, TG Abdul-Karim, FW Kung, HJ Dawson, DV Park, WS Moon, YW Tsai, ML Linehan, WM Emmert-Buck, MR Liotta, LA Zhuang, ZP TI Evidence of independent origin of multiple tumors from patients with prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; ALLELIC LOSS; CHROMOSOME 8P12-21; OVARIAN-CARCINOMA; SUPPRESSOR GENE; UNITED-STATES; IN-SITU; HETEROZYGOSITY; LOCI; FEATURES AB Background: In men with prostate cancer, the gland usually contains two or more widely separate tumors, A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin, Molecular analysis of microsatellite (i,e,, highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently, Methods: Four microsatellite polymorphic markers (D8S133, D8S136, and D8S137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCA1 gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i,e,, located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate), Forty distantly separate tumors were microdissected, DNA samples were prepared from formalin-fixed, paraffin-embedded wholemount prostate tissue section, and the overall frequencies of loss of heterozygosity at the four loci were determined, Results: The pattern of allelic loss was compatible with independent tumor origin in 15 of 18 informative cases, A random discordant pattern of allelic deletion was observed in distantly separate tumors, whereas the same allele was consistently lost in cells from different regions of the same tumor, For three patients, the results were compatible with either intraglandular dissemination or independent origin of prostate cancer, Conclusions: Our data suggest that multiple tumors in some patients with prostate cancer have independent origin. C1 NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA. NCI, Urol Oncol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, Div Clin Sci, NIH, Bldg 20,Rm 2A33, Bethesda, MD 20892 USA. RI Kung, Hsing-Jien/C-7651-2013 FU NCI NIH HHS [CA57179]; NCRR NIH HHS [P41RR03655]; NIDDK NIH HHS [DK51347] NR 38 TC 147 Z9 152 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 4 PY 1998 VL 90 IS 3 BP 233 EP 237 DI 10.1093/jnci/90.3.233 PG 5 WC Oncology SC Oncology GA YY182 UT WOS:000072121500011 PM 9462681 ER PT J AU Brinton, LA Brown, SL AF Brinton, LA Brown, SL TI Re: Breast implants and cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 443, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 4 PY 1998 VL 90 IS 3 BP 248 EP 249 PG 2 WC Oncology SC Oncology GA YY182 UT WOS:000072121500018 ER PT J AU Chow, WH Lindblad, P AF Chow, WH Lindblad, P TI Re: Risk of urinary tract cancers following kidney or ureter stones - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Sundsvall Hosp, Dept Urol, Sundsvall, Sweden. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. RP Chow, WH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Rm 415, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 4 PY 1998 VL 90 IS 3 BP 251 EP 251 PG 1 WC Oncology SC Oncology GA YY182 UT WOS:000072121500021 ER PT J AU Hazelwood, S Bernardini, I Shotelersuk, V Tangerman, A Guo, JR Mudd, H Gahl, WA AF Hazelwood, S Bernardini, I Shotelersuk, V Tangerman, A Guo, JR Mudd, H Gahl, WA TI Normal brain myelination in a patient homozygous for a mutation that encodes a severely truncated methionine adenosyltransferase I/III SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE methionine adenosyltransferase; hypermethioninemia; adenosylmethionine; demyelination ID S-ADENOSYLMETHIONINE SYNTHETASE; RAT-LIVER; DEFICIENCY; HYPERMETHIONINEMIA; PURIFICATION; EXPRESSION; DEMYELINATION; ISOZYMES; CLONING; PATHWAY AB Two isozymes of mammalian methionine adenosyltransferase, MAT I and MAT III, are expressed solely in adult liver. They are, respectively, tetramers and dimers of a single subunit encoded by the gene MAT1A. A third isozyme, MAT II, contains a catalytic subunit encoded by a separate gene, MAT2A, and is expressed in a variety of tissues, including (to a slight extent) adult liver. Based on a recent finding that 2 children with isolated hypermethioninemia and brain demyelination were homozygous for MAT1A mutations predicted to produce severely truncated proteins, and devoid of activity when expressed, it was concluded that complete lack of MAT I/III activity may be associated with neurological symptoms and demyelination, We now report that a 43-year-old man with persistent isolated hypermethioninemia, previously demonstrated to have deficient MAT activity in his liver, has normal brain myelination on MRI and normal neurological function, despite being homozygous for a 539 TG insertion in exon V of MAT1A, so that the gene is predicted to encode a protein of only 184 rather than the normal 395 amino acids. This patient's exon V mutation was demonstrated by SSCP analysis and verified by sequencing, Both parents are heterozygous for the same insertion. This suggests that MAT1A mutations producing severely truncated proteins do not necessarily produce brain demyelination, This finding has relevance to a previously reported 4-year-old girl who was also homozygous for the 539insTG mutation, Finally, our patient's 7% residual hepatic MAT activity, measured at 1 mM methionine, may reflect the hepatic activity of the more ubiquitous enzyme form. (C) 1998 Wiley-Liss, Inc.(1) C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Univ Nijmegen Hosp, Lab Gastroenterol & Hepatol, NL-6500 HB Nijmegen, Netherlands. NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHD, Heritable Disorders Branch, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 37 TC 25 Z9 26 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 3 PY 1998 VL 75 IS 4 BP 395 EP 400 DI 10.1002/(SICI)1096-8628(19980203)75:4<395::AID-AJMG9>3.0.CO;2-P PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YU984 UT WOS:000071776800009 PM 9482646 ER PT J AU Karni, A Meyer, G Rey-Hipolito, C Jezzard, P Adams, MM Turner, R Ungerleider, LG AF Karni, A Meyer, G Rey-Hipolito, C Jezzard, P Adams, MM Turner, R Ungerleider, LG TI The acquisition of skilled motor performance: Fast and slow experience-driven changes in primary motor cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Neuroimaging of Human Brain Function CY MAY 29-31, 1997 CL ARNOLD & MABEL BECKMAN CTR, IRVINE, CALIFORNIA SP Natl Acad Sci HO ARNOLD & MABEL BECKMAN CTR ID POSITRON EMISSION TOMOGRAPHY; ADULT OWL MONKEYS; SOMATOSENSORY CORTEX; FINGER MOVEMENTS; FUNCTIONAL MRI; VISUAL-CORTEX; PLASTICITY; DISCRIMINATION; MEMORY; REORGANIZATION AB Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training, These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice, This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training, The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine, Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session, We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident, We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice, This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Karni, A (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. EM bnkarni@weizmann.weizmann.ac.il RI Turner, Robert/C-1820-2008; OI Jezzard, Peter/0000-0001-7912-2251 NR 67 TC 639 Z9 646 U1 4 U2 51 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 3 PY 1998 VL 95 IS 3 BP 861 EP 868 DI 10.1073/pnas.95.3.861 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500015 PM 9448252 ER PT J AU Ungerleider, LG Courtney, SM Haxby, JV AF Ungerleider, LG Courtney, SM Haxby, JV TI A neural system for human visual working memory SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Neuroimaging of Human Brain Function CY MAY 29-31, 1997 CL ARNOLD & MABEL BECKMAN CTR, IRVINE, CALIFORNIA SP Natl Acad Sci HO ARNOLD & MABEL BECKMAN CTR ID POSITRON EMISSION TOMOGRAPHY; INFERIOR TEMPORAL CORTEX; SELECTIVE PREFRONTAL LESIONS; HUMAN EXTRASTRIATE CORTEX; MONKEYS MACACA-MULATTA; FRONTAL-CORTEX; RHESUS-MONKEY; HUMAN BRAIN; FUNCTIONAL-ORGANIZATION; CORTICAL CONNECTIONS AB Working memory is the process of actively maintaining a representation of information for a brief period of time so that it is available for use, In monkeys, visual working memory involves the concerted activity of a distributed neural system, including posterior areas in visual cortex and anterior areas in prefrontal cortex, Within visual cortex, ventral stream areas are selectively involved in object vision, whereas dorsal stream areas are selectively involved in spatial vision, This domain specificity appears to extend forward into prefrontal cortex, with ventrolateral areas involved mainly in working memory for objects and dorsolateral areas involved mainly in working memory for spatial locations, The organization of this distributed neural system for working memory in monkeys appears to be conserved in humans, though some differences between the two species exist, In humans, as compared with monkeys, areas specialized for object vision in the ventral stream have a more inferior location in temporal cortex, whereas areas specialized for spatial vision in the dorsal stream have a more superior location in parietal cortex, Displacement of both sets of visual areas away from the posterior perisylvian cortex may be related to the emergence of language over the course of brain evolution, Whereas areas specialized for object working memory in humans and monkeys are similarly located in ventrolateral prefrontal cortex, those specialized for spatial working memory occupy a more superior and posterior location within dorsal prefrontal cortex in humans than in monkeys, As in posterior cortex, this displacement in frontal cortex also may be related to the emergence of new areas to serve distinctively human cognitive abilities. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA. EM lgu@ln.nimh.nih.gov NR 87 TC 447 Z9 457 U1 4 U2 19 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 3 PY 1998 VL 95 IS 3 BP 883 EP 890 DI 10.1073/pnas.95.3.883 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500018 PM 9448255 ER PT J AU Neville, HJ Bavelier, D Corina, D Rauschecker, J Karni, A Lalwani, A Braun, A Clark, V Jezzard, P Turner, R AF Neville, HJ Bavelier, D Corina, D Rauschecker, J Karni, A Lalwani, A Braun, A Clark, V Jezzard, P Turner, R TI Cerebral organization for language in deaf and bearing subjects: Biological constraints and effects of experience SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Neuroimaging of Human Brain Function CY MAY 29-31, 1997 CL ARNOLD & MABEL BECKMAN CTR, IRVINE, CALIFORNIA SP Natl Acad Sci HO ARNOLD & MABEL BECKMAN CTR ID SIGN LANGUAGE; MATURATIONAL CONSTRAINTS; FUNCTIONAL MRI; VISUAL-CORTEX; PLASTICITY; POTENTIALS; BRAIN; REPRESENTATION; DISCRIMINATION AB Cerebral organization during sentence processing in English and in American Sign Language (ASL) was characterized by employing functional magnetic resonance imaging (fMRI) at 4 T. Effects of deafness, age of language acquisition, and bilingualism were assessed by comparing results from (i) normally hearing, monolingual, native speakers of English, (ii) congenitally, genetically deaf, native signers of ASL who learned English late and through the visual modality, and (iii) normally hearing bilinguals who were native signers of ASL and speakers of English, All groups, hearing and deaf, processing their native language, English or ASL, displayed strong and repeated activation within classical language areas of the left hemisphere, Deaf subjects reading English did not display activation in these regions, These results suggest that the early acquisition of a natural language is important in the expression of the strong bias for these areas to mediate language, independently of the form of the language, In addition, native signers, hearing and deaf, displayed extensive activation of homologous areas within the right hemisphere, indicating that the specific processing requirements of the language also in part determine the organization of the language systems of the brain. C1 Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Washington, Seattle, WA 98195 USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. NIH, Bethesda, MD 20892 USA. Inst Neurol, London WC1N 3BG, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Neville, HJ (reprint author), Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. RI Turner, Robert/C-1820-2008; Rauschecker, Josef/A-4120-2013; Clark, Vincent/B-3343-2010; OI Clark, Vincent/0000-0002-9151-2102; Jezzard, Peter/0000-0001-7912-2251 NR 48 TC 295 Z9 308 U1 8 U2 28 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 3 PY 1998 VL 95 IS 3 BP 922 EP 929 DI 10.1073/pnas.95.3.922 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500023 PM 9448260 ER PT J AU Lee, JS Lee, CH Chung, JH AF Lee, JS Lee, CH Chung, JH TI Studying the recruitment of Sp1 to the beta-globin promoter an in vivo method: Protein position identification with nuclease tail (PIN*POINT) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; RESTRICTION-ENDONUCLEASE; HYPERSENSITIVE SITE; TARGETED DELETION; ERYTHROID-CELLS; TRANSGENIC MICE; KRUPPEL FAMILY AB Transcription is thought to be regulated by recruitment of transcription factors, adaptors, and certain enzymes to cis-acting elements through protein-DNA interactions and protein-protein interactions, To better understand transcription, a method with the capability to detect in vivo recruitment of these individual proteins will be essential, Toward this end, we use a previously undescribed in vivo method that we term protein position identification with nuclease tail (PIN*POINT). In this method, a fusion protein composed of a chosen protein linked to a nonsequence-specific nuclease is expressed in vivo, and the binding of the protein to DNA is made detectable by the nuclease induced cleavage near the binding site, In this article, we used the technique protein position identification with nuclease tail to study the effect of the beta-globin locus control region (LCR) and promoter elements on the recruitment of transcription factor Spl to the beta-globin promoter, We present evidence that the hypersensitive sites of the LCR synergistically enhance the recruitment of a multimeric Spl complex to the beta-globin promoter and that this may be accomplished by protein-protein interactions with proteins bound to the LCR, the upstream activator region, and, possibly, general transcription factors bound near the "TATA" box. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Chung, JH (reprint author), NHLBI, Mol Hematol Branch, NIH, 10 Ctr Dr,MSC 1654, Bethesda, MD 20892 USA. NR 40 TC 19 Z9 19 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 3 PY 1998 VL 95 IS 3 BP 969 EP 974 DI 10.1073/pnas.95.3.969 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500032 PM 9448269 ER PT J AU Pause, A Lee, S Lonergan, KM Klausner, RD AF Pause, A Lee, S Lonergan, KM Klausner, RD TI The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MYC PROTEIN; P27(KIP1); FIBROBLASTS; G1; TRANSCRIPTION; INACTIVATION; ONCOPROTEIN; TRANSITION; INHIBITORS; MUTATIONS AB The inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes affected individuals to the human VHL cancer syndrome and is associated with sporadic renal cell carcinomas (RCC) and brain hemangioblastomas, VHL-negative 786-0 RCC cells are tumorigenic in nude mice which is suppressed by the reintroduction of VHL. Remarkably, this occurs without affecting the growth rate and cell cycle profile of these cells in culture, The 786-0 cell line, like many cancer cells, fails to exit the cell cycle upon serum withdrawal, Here, it is shown that reintroduction of the wild-type VHL gene restores the ability of VHL-negative RCC cancer cells to exit the cell cycle and enter G(0)/quiescence in low serum, Both VHL-positive and VHL-negative RCC cells exit the cell cycle by contact inhibition, The cyclin-dependent kinase inhibitor, p27, accumulates upon serum withdrawal, only in the presence of VHL, as a result of the stabilization of the protein, We propose that the loss of wild-type VHL gene results in a specific cellular defect in serum-dependent growth control, which may initiate tumor formation, This is corrected by the reintroduction of wild-type VHL, implicating VHL as the first tumor suppressor involved in the regulation of cell cycle exit, which is consistent with its gatekeeper function in the kidney. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Off Director, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pause, A (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,MSC 5340,Bldg 18T Room 101, Bethesda, MD 20892 USA. NR 30 TC 190 Z9 196 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 3 PY 1998 VL 95 IS 3 BP 993 EP 998 DI 10.1073/pnas.95.3.993 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500036 PM 9448273 ER PT J AU Alvarez-Salas, LM Cullinan, AE Siwkowski, A Hampel, A DiPaolo, JA AF Alvarez-Salas, LM Cullinan, AE Siwkowski, A Hampel, A DiPaolo, JA TI Inhibition of HPV-16 E6/E7 immortalization of normal keratinocytes by hairpin ribozymes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; IMMUNODEFICIENCY-VIRUS TYPE-1; TOBACCO RINGSPOT VIRUS; CANCER GENE-THERAPY; IN-VITRO; ANTISENSE OLIGODEOXYNUCLEOTIDES; HAMMERHEAD RIBOZYMES; HIV-1 REPLICATION; HUMAN-FIBROBLASTS; E6 ONCOPROTEIN AB HPV-16 E6 and E7 genes are required to efficiently immortalize a broad spectrum of cell types including cervical keratinocytes, Therefore, the E6/E7 genes can be considered relevant targets for anti cancer therapy, We produced several engineered hairpin (HP) ribozymes to specifically disrupt HPV-16 E6/E7 mRNA, After extensive biochemical characterization, one anti-E6 HP ribozyme (R434) was selected for in vivo testing because of its superior catalytic capabilities, When expressed in cis, R434 efficiently inhibited E6 in vitro translation, Cis-expression of the HP ribozyme with HPV-16 E6/E7 genes in normal human keratinocytes reduced the growth rate and prevented immortalization. RNA analysis by reverse transcription-PCR showed that E6/E7 transcripts were cleaved in post-transfected cells and virtually were eliminated after long term expression, Of interest, an inactive version of the HP also was able to significantly affect the immortalizing ability of E6/E7, probably through passive hybridization. The combination of passive and cleaving antisense RNA therefore is established as an effective inhibitor of HPV-16 E6/E7 immortalization. C1 NCI, Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. RP DiPaolo, JA (reprint author), NCI, Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. EM dipaoloj@dc37a.nci.nih.gov NR 64 TC 66 Z9 69 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 3 PY 1998 VL 95 IS 3 BP 1189 EP 1194 DI 10.1073/pnas.95.3.1189 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500070 PM 9448307 ER PT J AU Schiffmann, R Dwyer, NK Lubensky, IA Tsokos, M Sutliff, VE Latimer, JS Frei, KP Brady, RO Barton, NW Blanchette-Mackie, EJ Goldin, E AF Schiffmann, R Dwyer, NK Lubensky, IA Tsokos, M Sutliff, VE Latimer, JS Frei, KP Brady, RO Barton, NW Blanchette-Mackie, EJ Goldin, E TI Constitutive achlorhydria in mucolipidosis type IV SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CULTURED SKIN FIBROBLASTS; SECRETORY FUNCTION; NATURAL-HISTORY; CHILDREN; BASAL; PAIN AB Mucolipidosis type IV is an autosomal recessive lysosomal storage disease of unknown etiology that causes severe neurological and ophthalmological abnormalities, In an attempt to obtain insight into the nature of the metabolic abnormality in this disorder, we prospectively evaluated 15 consecutive patients, aged 2 to 23 years, over a period of 22 months, The finding of iron deficiency in some of the patients led us to the discovery that all patients but one had markedly elevated blood gastrin levels, None had vitamin B12 deficiency, Gastroscopy in three patients showed normal gross appearance of the mucosa in two patients, 4 and 7 years old, and mucosal atrophy in a 22-year-old. Parietal cells were present in normal numbers and contained large cytoplasmic inclusions that were confirmed immunohistochemically to be lysosomal in nature, Other gastric epithelial cells appeared normal, Parietal cells contained very few tubulovesicular membranes, suggesting cellular activation, whereas apical canaliculi appeared relatively nonactivated, Both subunits of the parietal cell H+/K+-ATPase were present, and both partially colocalized with f-actin at the apical membrane, We conclude that patients with mucolipidosis type IV are constitutively achlorhydric and have partially activated parietal cells, We hypothesize that the defective protein in this disease is closely associated with the final stages of parietal cell activation and is critical for a specific type of cellular vacuolar trafficking between the cytoplasm and the apical membrane domain. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Lipid Cell Biol Sect, Lab Cell & Biol, NIH, Bethesda, MD 20892 USA. NIDDKD, Pathol Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Gastroenterol, Washington, DC 20010 USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,10 Ctr Dr,MSC 1260, Bethesda, MD 20892 USA. NR 34 TC 54 Z9 55 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 3 PY 1998 VL 95 IS 3 BP 1207 EP 1212 DI 10.1073/pnas.95.3.1207 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500073 PM 9448310 ER PT J AU Holland, EC Varmus, HE AF Holland, EC Varmus, HE TI Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID A AVIAN-LEUKOSIS; RETROVIRAL VECTORS; TRANSGENIC MICE; SARCOMA-VIRUSES; IN-VITRO; EXPRESSION; RECEPTOR; SYSTEM; RNA; CARCINOGENESIS AB Basic fibroblast growth factor (bFGF) is overexpressed in most high-grade human gliomas, implying that it is involved in the pathogenesis of these tumors, To assess the biological effect of inappropriate production of bFGF in normal astrocytes, we developed a system for glia specific gene transfer in transgenic mice. A transgene encoding the receptor for subgroup A avian leukosis virus and controlled by the astrocyte-specific glial fibrillary acidic protein promoter permits efficient glia-specific transfer of genes carried by subgroup A avian leukosis virus vectors. With this system, we have demonstrated that bFGF induces proliferation and migration of glial cells in vivo, without the induction of tumors. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Holland, EC (reprint author), NCI, Div Basic Sci, NIH, 49 Convent Dr,Bldg 49,Room 4A56, Bethesda, MD 20892 USA. NR 30 TC 187 Z9 192 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 3 PY 1998 VL 95 IS 3 BP 1218 EP 1223 DI 10.1073/pnas.95.3.1218 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500075 PM 9448312 ER PT J AU Naveilhan, P Baudet, C Mikaels, A Shen, LY Westphal, H Ernfors, P AF Naveilhan, P Baudet, C Mikaels, A Shen, LY Westphal, H Ernfors, P TI Expression and regulation of GFR alpha 3, a glial cell line-derived neurotrophic factor family receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MIDBRAIN DOPAMINERGIC-NEURONS; MUSCLE SENSORY NEURONS; DORSAL-ROOT GANGLIA; MICE LACKING GDNF; REQUIRE NEUROTROPHIN-3; IN-VIVO; MESSENGER-RNA; MOTOR-NEURONS; SURVIVAL; BRAIN AB We report the identification of an additional member of the glial cell line-derived neurotrophic factor (GDNF) family receptor, termed GFR alpha 3, that is homologous to the previously identified GDNF and neurturin ligand binding receptors GFR alpha 1 and GFR alpha 2. GFR alpha 3 is 32 % and 37 % identical to GFR alpha 1 and GFR alpha 2, respectively, RNase protection assays show that whereas gfr alpha 1 and gfr alpha 2 are abundant in both developing and adult brain, gfr alpha 3 is exclusively expressed during development. All receptors are widely present in both the developing and adult peripheral nervous system and in peripheral organs, For instance, in situ hybridization shows that the developing liver, stomach, intestine, kidney, and sympathetic chain, which all contain ret-expressing cells, transcribe unique complementary and overlapping patterns of most or all of the GDNF family receptors and ligands, In sensory neurons of the trigeminal ganglion gfr alpha 2 and gfr alpha 3 are expressed in different subpopulations of neurons, whereas gfr alpha 1 is coexpressed in some gfr alpha 2 and gfr alpha 3-positive neurons, We find that the gfr alpha 1 population of trigeminal neurons is absent in GDNF null mutant mice, suggesting that GDNF signals in vivo by interacting with GFR alpha 1. Thus, our results show that there are at least three members in the GDNF family of ligand binding receptors and that these receptors may be crucial in conferring ligand specificity in vivo, The unique complementary and overlapping expression of gfr alpha 3 implies distinct functions in the developing and adult mouse from that of GFR alpha 1 and GFR alpha 2. C1 Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Lab, S-17177 Stockholm, Sweden. NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Ernfors, P (reprint author), Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Lab, S-17177 Stockholm, Sweden. EM Patrik@Cajal.mbb.ki.se RI Naveilhan, Philippe/K-2377-2015 NR 55 TC 119 Z9 123 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 FEB 3 PY 1998 VL 95 IS 3 BP 1295 EP 1300 DI 10.1073/pnas.95.3.1295 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YV928 UT WOS:000071878500088 PM 9448325 ER PT J AU Pozsgay, V AF Pozsgay, V TI Synthetic Shigella vaccines: A carbohydrate-protein conjugate with totally synthetic hexadecasaccharide haptens SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE antigens; carbohydrates; oligosaccharides; protecting groups; vaccines ID O-SPECIFIC POLYSACCHARIDE; INFLUENZAE TYPE-B; NUCLEAR-MAGNETIC-RESONANCE; DYSENTERIAE TYPE-1; OLIGOSACCHARIDE-PROTEIN; CAPSULAR POLYSACCHARIDES; PROMOTED REACTIONS; NMR-SPECTROSCOPY; GLYCOSIDES; ANTIGENS C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. EM vipo@helix.nih.gov NR 47 TC 43 Z9 43 U1 2 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD FEB 2 PY 1998 VL 37 IS 1-2 BP 138 EP 142 DI 10.1002/(SICI)1521-3773(19980202)37:1/2<138::AID-ANIE138>3.3.CO;2-K PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA YW348 UT WOS:000071925600031 ER PT J AU Combadiere, B Sousa, CRE Germain, RN Lenardo, MJ AF Combadiere, B Sousa, CRE Germain, RN Lenardo, MJ TI Selective induction of apoptosis in mature T lymphocytes by variant T cell receptor ligands SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTAGONIST LIGANDS; PARTIAL AGONISTS; TCR; ACTIVATION; DEATH; OCCURS; ZETA AB Activation anergy, and apoptosis are all possible outcomes of T cell receptor (TCR) engagement. The first leads to proliferation and effector function, whereas the others can lead to partial or complete immunological tolerance. Structural variants of immunizing peptide-major histocompatibility complex molecule ligands that induce selective lymphokine secretion or anergy in mature T cells in association with altered intracellular signaling events have been described. Here we describe altered ligands for mature mouse CD4(+) T helper 1 cells that lead to T cell apoptosis by the selective expression of Fas ligand (Fast) and tumor necrosis factor (TNF) without concomitant IL-2, IL-3, or interferon gamma production. All ligands that stimulated cell death were found to induce FasL and TNF mRNA expression and TCR aggregation ("capping") at the cell surface, but did not elicit a common pattern of tyrosine phosphorylation of the TCR-associated signal transduction chains. Thus, TCR Ligands that uniquely trigger T cell apoptosis without inducing cytokines that are normally associated with activation can be identified. C1 NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. RI Combadiere, Behazine/G-3881-2013 NR 24 TC 61 Z9 62 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 2 PY 1998 VL 187 IS 3 BP 349 EP 355 DI 10.1084/jem.187.3.349 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YV635 UT WOS:000071847500008 PM 9449715 ER PT J AU Kulaeva, OI Koonin, EV Wootton, JC Levine, AS Woodgate, R AF Kulaeva, OI Koonin, EV Wootton, JC Levine, AS Woodgate, R TI Unusual insertion element polymorphisms in the promoter and terminator regions of the mucAB-like genes of R471a and R446b SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE retrotransposon; SOS mutagenesis; IS sequence ID SELF-SPLICING INTRONS; GROUP-II INTRONS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; INCOMPATIBILITY GROUPS; RECA PROTEIN; DNA-REPAIR; REVERSE TRANSCRIPTASES; INDUCED MUTAGENESIS; SEQUENCE DATABASES AB We have previously identified umu-complementing genes on two incL/M plasmids, R471a and R446b (C. Ho et al., J, Bacteriol., 175 (1993) 5411-5419), Molecular analysis of these genes revealed that they are more structurally and functionally related to mucAB from the incN plasmid pKM101 than to other members of the previously identified Umu-like family, As a consequence, we have termed these new homologs mucAB((R471a)) and mucAB((R446b)) respectively, Interestingly, while the location of the mucAB-like genes is essentially the same in both R471a and R446b, the regions immediately flanking the mucAB-like genes are highly polymorphic, For example, 5' to mucAB((R471a)) we found an insert that appears to be a novel retroelement encoding a putative reverse transcriptase (RT). This RT is related to the reverse transcriptases encoded by group II introns but is embedded in a retron-like context, Immediately 3' to the mucAB((R471a)) locus is a putative insertion element of a sparsely-dispersed class not previously reported from enteric bacteria, Both the RT and insertion element are absent in R446b, These observations suggest that the mucAB-like genes from R471a and R446b are located within regions of the R-plasmids that perhaps were once (or still are) mobile genetic elements, Such observations might help explain the distribution of umu-like genes on R-plasmids and bacterial chromosomes, (C) 1998 Elsevier Science B.V. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 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 RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 69 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD FEB 2 PY 1998 VL 397 IS 2 BP 247 EP 262 DI 10.1016/S0027-5107(97)00222-4 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZD024 UT WOS:000072643200014 PM 9541650 ER PT J AU Cadet, JL Brannock, C AF Cadet, JL Brannock, C TI Free radicals and the pathobiology of brain dopamine systems SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review ID DISMUTASE TRANSGENIC MICE; METHAMPHETAMINE-INDUCED NEUROTOXICITY; COMPLEX-I DEFICIENCY; RAT SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; STRIATAL DOPAMINE; HYDROGEN-PEROXIDE; METHYLENEDIOXYMETHAMPHETAMINE MDMA AB Oxygen is an essential element for normal life. However, reactive oxygen species (ROS) can also participate in deleterious reactions that can affect lipid, protein, and nucleic acid. Normal physiological function thus depends on a balance between these ROS and the scavenging systems that aerobic organisms have developed over millennia. Tilting of that balance towards a pro-oxidant state might result from both endogenous and exogenous causes. In the present paper, we elaborate on the thesis that the neurodegenerative effects of two drugs, namely methamphetamine (METH, ICE) and methylenedioxymethamphetamine (MDMA, Ecstasy) are due to ROS overproduction in monoaminergic systems in the brain. We also discuss the role of oxygen-based species in 6-hydroxydopamine (6-OHDA)-induced nigrostriatal dopaminergic degeneration and in Parkinson's disease. Studies are underway to identify specific cellular and molecular mechanisms that are regulated by oxygen species. These studies promise to further clarify the role of oxidative stress in neurodegeneration and in plastic changes that occur during the administration of addictive agents that affect the brain. Published by Elsevier Science Ltd. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 131 TC 350 Z9 363 U1 4 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 EI 1872-9754 J9 NEUROCHEM INT JI Neurochem. Int. PD FEB 2 PY 1998 VL 32 IS 2 BP 117 EP 131 DI 10.1016/S0197-0186(97)00031-4 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZD191 UT WOS:000072660500001 PM 9542724 ER PT J AU Thomas, A AF Thomas, A TI Public support for medical research - How deep, how enduring? SO ACADEMIC MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Thomas, A (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 1998 VL 73 IS 2 BP 178 EP 179 DI 10.1097/00001888-199802000-00016 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA YX199 UT WOS:000072016300023 PM 9484190 ER PT J AU Virta, A Komu, M Lundbom, N Kormano, M AF Virta, A Komu, M Lundbom, N Kormano, M TI T1p MR imaging characteristics of human anterior tibial and gastrocnemius muscles SO ACADEMIC RADIOLOGY LA English DT Article DE magnetic resonance (MR), comparative studies; magnetic resonance (MR), tissue characterization; muscle, MR ID RELAXATION-TIMES; MAGNETIZATION-TRANSFER; SPIN-LOCK; TRANSVERSE RELAXATION; TISSUE; WATER; DISPERSION; CONTRAST; PROTONS; 1/T1 AB Rationale and Objectives. The authors evaluated the value of T1 rho in relation to T1 and T2 in the characterization of human muscles. Materials and Methods. The authors studied the effect of muscle type (anterior tibial [AT] and gastrocnemius [GC]), sex, and age on 1/T1 and 1/T2 at 0.1 T and 1/T1 rho at locking-field B(1)s (spin-locking radio-frequency magnetic induction field) of 10-160 mu T in 38 healthy volunteers. The contrast-to-noise ratio (CNR) between muscle and fat was evaluated with different T1-, T2-, and T1 rho-weighted magnetic resonance (MR) sequences. Results. The 1/T1, 1/T2, and 1/T1 rho were slightly higher in AT than in GC muscles. The 1/T2 and 1/T1 rho of AT muscles showed a sex dependence, whereas no correlation with age was found. The CNR of the T1 rho-weighted images did not markedly differ from that of the T1- and T2-weighted images. Conclusion. T1 rho is as sensitive as T2 to the composition of muscle, whereas T1 is less sensitive. In MR imaging of normal muscle, T1 rho and T2 provide a relatively similar tissue contrast. C1 Univ Turku, Dept Diagnost Radiol, Turku, Finland. RP Virta, A (reprint author), NINDS, Neuroimaging Branch, NIH, Bldg 10,Rm 1C 227,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 12 Z9 12 U1 1 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 1998 VL 5 IS 2 BP 104 EP 110 DI 10.1016/S1076-6332(98)80130-X PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZH426 UT WOS:000073107800007 PM 9484543 ER PT J AU Zhuang, P Dang, N Warzeri, A Gerloff, C Cohen, LG Hallett, M AF Zhuang, P Dang, N Warzeri, A Gerloff, C Cohen, LG Hallett, M TI Implicit and explicit learning in an auditory serial reaction time task SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE auditory stimulus modality; EEG; alpha frequency; event-related desynchronization; implicit learning; explicit learning ID EVENT-RELATED DESYNCHRONIZATION; SUPERIOR TEMPORAL SULCUS; RHESUS-MONKEY; CORTICAL CONNECTIONS; PREFRONTAL CORTEX; MOTOR CORTEX; NEURONS; MEMORY; REORGANIZATION; ORGANIZATION AB Objective - To explore the role of the motor cortex during implicit and explicit learning. Materials and methods - EEG signals were recorded from 30 channels by measuring task-related desynchronization (TRD) when 10 right-handed naive volunteers performed a variation of the serial reaction task. Stimuli, consisting of 4 pure tones of 500, 1000, 1500, and 2000 HZ, lasting 200 ms, were presented binaurally through a pair of tubephones at 60 dB with a 2-s constant interstimulus interval. A series of 10 repetitive tones represented the test sequence; the random sequence was the control. Results - All subjects developed implicit and explicit knowledge reflected by decreased response time, increased accuracy, and the ability to generate the sequence. Six of 10 subjects demonstrated implicit learning without explicit learning during the first 3 blocks. When subjects acquired full explicit learning, 10 Hz TRD at C3 reached a peak amplitude, declining thereafter. Conclusions - Properties of the sensorimotor cortex change during learning and these changes are independent of stimulus modality. 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,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 40 TC 19 Z9 19 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD FEB PY 1998 VL 97 IS 2 BP 131 EP 137 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA YX965 UT WOS:000072098400010 PM 9517864 ER PT J AU Teikari, JM Laatikainen, L Rapola, JM Virtamo, J Haukka, J Liesto, K Taylor, P Heinonen, OP AF Teikari, JM Laatikainen, L Rapola, JM Virtamo, J Haukka, J Liesto, K Taylor, P Heinonen, OP TI Retinal vascular changes following supplementation with alpha-tocopherol or beta-carotene SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE alpha-tocopherol; beta-carotene; antioxidant; retina; vascular; supplementation ID LOW-DENSITY-LIPOPROTEIN; VITAMIN-E CONSUMPTION; ATHEROGENESIS; HYPERTENSION; PLASMA; RISK; POPULATION; DISEASE AB Purpose: To examine if long-term supplementation with alpha-tocopherol (AT) or beta-carotene (BC) was associated with the prevalence of vascular changes in retinal arterioles, Methods: An end-of-trial subsample from a double-blind, placebo-controlled clinical trial designed to study the effects of alpha-tocopherol and beta-carotene on lung cancer incidence (ATBC Study). Setting: Source population of Helsinki and the surrounding province. Participants: 1072 men 50-69 years old and smoking at least 5 cigarettes per day at study entry. Interventions: Random allocation to one of four supplementation regimens: 50 mg per day alpha-tocopherol, 20 mg per day beta-carotene, both alpha-tocopherol and beta-carotene, or placebo, Median follow-up time was 6.6 years (range 5.2-8.0 years). Main outcome measure: Presence of vascular changes in retinal arterioles as determined from end-of-trial retinal color photographs. Results: Retinal vascular changes were most prevalent in the AT (161 men, 62%), and in the BC (163 men, 62%) groups, The prevalence rate was lowest in the AT plus BC group (161 men, 55%), and slightly higher in the placebo group (145 men, 57%). There was no statistically significant association of either AT (OR 0.9, 95% CI 0.7-1.2) or BC (OR 1.0, 95% CI 0.8-1.3) supplementation with the prevalence of retinal vascular changes after adjusting for major risk factors. Conclusions: Supplementation with alpha-tocopherol or beta-carotene for a median of 6.6 Sears does not protect against retinal vascular changes among smoking males. C1 Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. Univ Helsinki, Dept Ophthalmol, Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. Laakso Hosp, Helsinki, Finland. NCI, NIH, Bethesda, MD 20892 USA. RP Teikari, JM (reprint author), Sepankatu 7 A 23, Helsinki 00150, Finland. RI Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 27 TC 11 Z9 11 U1 0 U2 1 PU SCRIPTOR PUBLISHER PI HVIDOVRE PA SOVANGSVEJ 1-5, DK-2650 HVIDOVRE, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD FEB PY 1998 VL 76 IS 1 BP 68 EP 73 DI 10.1034/j.1600-0420.1998.760112.x PG 6 WC Ophthalmology SC Ophthalmology GA ZA388 UT WOS:000072358500011 PM 9541437 ER PT J AU O'Brien, TR Padian, NS Hodge, T Goedert, JJ O'Brien, SJ Carrington, M AF O'Brien, TR Padian, NS Hodge, T Goedert, JJ O'Brien, SJ Carrington, M TI CCR-5 genotype and sexual transmission of HIV-1 SO AIDS LA English DT Letter ID HUMAN IMMUNODEFICIENCY VIRUS C1 NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div AIDS STD & TB Lab Res, Atlanta, GA USA. Publ Hlth Serv, US Dept HHS, NCI, Lab Genome Divers, Bethesda, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. NR 6 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD FEB PY 1998 VL 12 IS 4 BP 444 EP 445 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YX416 UT WOS:000072037800019 PM 9520179 ER PT J AU Newcomer, SF AF Newcomer, SF TI Evaluating HIV prevention interventions, 1997 SO AIDS EDUCATION AND PREVENTION LA English DT Book Review C1 NICHD, Bethesda, MD 20892 USA. RP Newcomer, SF (reprint author), NICHD, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD FEB PY 1998 VL 10 IS 1 BP 98 EP 99 PG 2 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA YX007 UT WOS:000071997000008 ER PT J AU Hirschfeld, S AF Hirschfeld, S TI Pain as a complication of HIV disease SO AIDS PATIENT CARE AND STDS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED CHOLANGITIS; AMINO-ACID RECEPTORS; RHEUMATIC MANIFESTATIONS; PARANASAL SINUSES; INFLAMMATORY MYOPATHIES; GASTROINTESTINAL SYMPTOMS; SCLEROSING CHOLANGITIS; PERIPHERAL NEUROPATHY; SEROPOSITIVE PATIENTS AB Pain as a symptom is common to many pathologic conditions. At its most elementary level, it is a signal from peripheral nerves with specialized receptors that there is a change in the local environment, such as pressure, pH, temperature, or some other noxious stimulus, that can be detrimental to function, Pain is particularly prevalent in patients with HIV infection. The assessment, evaluation, and treatment of pain should be an integral part of comprehensive patient care. C1 NCI, Bethesda, MD 20892 USA. RP Hirschfeld, S (reprint author), NCI, Bldg 10,Room 13N240,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 207 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD FEB PY 1998 VL 12 IS 2 BP 91 EP 108 DI 10.1089/apc.1998.12.91 PG 18 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA ZA593 UT WOS:000072380200003 PM 11361928 ER PT J AU Lands, WEM AF Lands, WEM TI A review of alcohol clearance in humans SO ALCOHOL LA English DT Review DE acetate; adenosine; alcohol clearance; alcohol dehydrogenase; alcohol dependence; binding site; blood alcohol level; catalytic site; enzyme kinetics; millimolar alcohol; orphan genes; withdrawal ID ALDEHYDE DEHYDROGENASE GENOTYPES; CENTRAL-NERVOUS-SYSTEM; FIRST-PASS METABOLISM; HUMAN-LIVER; ENZYMATIC-PROPERTIES; ETHANOL ELIMINATION; KINETIC CHARACTERIZATION; OXIDOREDUCTION INVIVO; POSTMENOPAUSAL WOMEN; HYDROGEN TRANSFER AB The level of blood or brain alcohol is considered to influence alcohol ingestion by causing subjective perceptions or neural activations that are reinforcing or rewarding. Alcohol-dependent people may try to maintain some desired tissue level, drinking to replace the millimolar levels that were cleared from the blood by metabolism. The biomedical literature describes many approaches to understanding the role of blood alcohol levels in human physiology and behavior, and this review examines some of the published results. They include the general kinetics of intake and removal of beverage alcohol as well as the characteristics of many different catalysts that can interact with alcohol. Because ingested alcohol creates blood levels that are a 1000-fold greater than those normally experienced during abstinence, ethanol may impose itself as an alternate substrate for the many oxidoreductases that act physiologically on other endogenous alcohols. Many enzymes that can act on millimolar ethanol have been isolated, and their structural genes are sequenced. Unfortunately, the genetic sequence does not indicate the physiological material upon which the translated gene product may act. In a sense, the set of enzymes with catalytic sites occupied by millimolar ethanol during alcohol drinking might constructively be regarded as "orphan gene products" whose physiological role remains to be clarified. This review is designed to indicate some of what is known, what is not known, and what needs to be known to improve the interpretations regarding adaptations to beverage alcohol and the ability of millimolar levels of alcohol to diminish dysphoria. The dysphoria may be influenced by ethanol, by ethanol metabolites, or by altered metabolism of currently unspecified endogenous substrates. A major challenge is to evaluate the multiple alternative variables within a context that stimulates curiosity and encourages quantitative tests of the relative contribution of each variable to the overall physiology of an individual. Published by Elsevier Science Inc. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Lands, WEM (reprint author), NIAAA, NIH, Willco Bldg,Suite 400,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. EM wlands@willco.niaaa.nih.gov NR 134 TC 53 Z9 55 U1 8 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD FEB PY 1998 VL 15 IS 2 BP 147 EP 160 DI 10.1016/S0741-8329(97)00110-9 PG 14 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA YT983 UT WOS:000071667700007 PM 9476961 ER PT J AU Liu, Y AF Liu, Y TI Satellite Symposium of Society for Neuroscience 26th Annual Meeting, Washington, DC, 1996 - Approaches for studying neural circuits: Application to alcohol research SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 NIAAA, Div Neurosci Res, NIH, Bethesda, MD 20892 USA. RP Liu, Y (reprint author), NIAAA, Div Neurosci Res, NIH, Room 402,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 1998 VL 22 IS 1 BP 1 EP 2 DI 10.1111/j.1530-0277.1998.tb03610.x PG 2 WC Substance Abuse SC Substance Abuse GA ZA165 UT WOS:000072335500001 ER PT J AU Woodward, DJ Janak, PH Chang, JY AF Woodward, DJ Janak, PH Chang, JY TI Ethanol action on neural networks studied with multineuron recording in freely moving animals SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Approaches for Studying Neural Circuits - Application to Alcohol Research at the 26th Annual Meeting of the Society-for-Neuroscience CY NOV 16, 1996 CL WASHINGTON, D.C. SP NIH, Natl Inst Alcohol Abuse & Alcoholism, Neurosci Res Program DE electrophysiology; self-administration; ensemble; recording techniques; addiction ID CENTRAL-NERVOUS-SYSTEM; NUCLEUS-ACCUMBENS; BASAL GANGLIA; ENSEMBLE ACTIVITY; MOTOR CONTROL; RATS; REINFORCEMENT; PERFORMANCE; INTEGRATION; MECHANISMS AB The advent of new chronic multineuron recording techniques for examining neural activity in behaving animals has initiated a new phase in the analysis of the neuronal mechanisms that underlie ethanol and other drug self-administration, The technique allows for the simultaneous recording of groups of individual neurons in one or more brain regions during ongoing behavior; therefore, the spatiotemporal patterns of neuronal activity during specific behavioral events can be determined, We have successfully applied this technique to rat models of cocaine and heroin self-administration, Recently, using rats, we have been able to record from neurons in areas of the mesocorticolimbic circuit during ethanol-reinforced operant responding, In this review, we describe the current and future application of this new behavioral neurophysiology to the investigation of the neurobiology of alcohol addiction. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. NIDA, Intramural Res Program, Baltimore, MD USA. RP Woodward, DJ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NIAAA NIH HHS [AA 07565, AA 10980] NR 42 TC 14 Z9 14 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 1998 VL 22 IS 1 BP 10 EP 22 DI 10.1097/00000374-199802000-00002 PG 13 WC Substance Abuse SC Substance Abuse GA ZA165 UT WOS:000072335500003 PM 9514281 ER PT J AU Katzel, LI Fleg, JL Busby-Whitehead, MJ Sorkin, JD Becker, LC Lakatta, EG Goldberg, AP AF Katzel, LI Fleg, JL Busby-Whitehead, MJ Sorkin, JD Becker, LC Lakatta, EG Goldberg, AP TI Exercise-induced silent myocardial ischemia in master athletes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; APOLIPOPROTEIN-E ALLELES; E POLYMORPHISM; OLDER MEN; RISK; PERFORMANCE; VOLUNTEERS; PREVALENCE; PHENOTYPE AB High-physical activity levels are associated with reduced risk of symptomatic coronary artery disease (CAD). However, there are a number of reports of exercise-related sudden death and myocardial infarction in aerobically trained athletes, This study compared the prevalence of exercise-induced silent myocardial ischemia on maximum graded exercise tests with tomographic thallium scintigraphy in 70 master male athletes (63 +/- 6 years, mean +/- SD) (maximum aerobic capacity, (V) over dot O(2)max >40 ml/kg/min) and in 85 healthy untrained men (61 +/- 7 years) with no history of CAD, The prevalence of silent ischemia (exercise-induced ST-segment depression on electrocardiogram and perfusion abnormalities on thallium scintigraphy) was similar in athletes and untrained men; 16% of the athletes (11 of 70) had silent ischemia compared with 21% of the untrained men (chi-square = 0.81, p = 0.36), No athletes had hyperlipidemia, systemic hypertension, or diabetes mellitus, However, the apolipoprotein E4 allele was present in 9 of the 11 athletes with silent ischemia compared with 2 of 32 athletes with normal exercise tests (chi-square = 24, p = 0.0001), These results suggest that older male athletes with the apolipoprotein E4 allele are at increased risk for the development of exercise-induced silent ischemia. (C) 1998 by Excerpta Medica, Inc. C1 Baltimore VA Med Ctr, GRECC 18, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Clin Invest Lab,Metab Sect, NIH, Baltimore, MD 21224 USA. RP Katzel, LI (reprint author), Baltimore VA Med Ctr, GRECC 18, 10 N Greene St, Baltimore, MD 21201 USA. FU NIA NIH HHS [P01 AG04402-05, 5-KO8-AG00383-02, 5-KO8-AG00497] NR 20 TC 21 Z9 21 U1 0 U2 2 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 1 PY 1998 VL 81 IS 3 BP 261 EP 265 DI 10.1016/S0002-9149(97)00898-9 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YU563 UT WOS:000071730400001 PM 9468064 ER PT J AU Blum, A Vardinon, N Kaplan, G Laniado, S Yust, I Burk, M Miller, H AF Blum, A Vardinon, N Kaplan, G Laniado, S Yust, I Burk, M Miller, H TI Autoimmune and inflammatory responses may have an additive effect in postpercutaneous transluminal coronary angioplasty restenosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID UNSTABLE ANGINA; DISEASE; ARTERY; ANTIBODIES; ACTIVATION; ADHESION; PROTEIN; RISK C1 Tel Aviv Univ, Sackler Sch Med, Tel Aviv Med Ctr, Dept Cardiol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Tel Aviv Med Ctr, Dept Immunol, IL-69978 Tel Aviv, Israel. Chaim Sheba Med Ctr, Hlth Serv, Res Unit, Minist Hlth, IL-52621 Tel Hashomer, Israel. RP Blum, A (reprint author), NHLBI, Bldg 10R 7B15, Bethesda, MD 20892 USA. NR 20 TC 18 Z9 18 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 1 PY 1998 VL 81 IS 3 BP 339 EP 341 DI 10.1016/S0002-9149(97)00914-4 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YU563 UT WOS:000071730400016 PM 9468079 ER PT J AU Simsir, A Tsang, P Greenebaum, E AF Simsir, A Tsang, P Greenebaum, E TI Additional mimics of mucinous mammary carcinoma Fibroepithelial lesions SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Scientific Meeting of the American-Society-of-Cytopathology CY NOV 04-09, 1996 CL DENVER, COLORADO SP Amer Soc Cytopathol ID FINE-NEEDLE ASPIRATION; BREAST; TUMORS AB To determine the origin and nature of mucinlike material in fine-needle aspiration (FNA) smears of the breast in noncancerous breast lesions, we studied breast FNA smears from four patients. All smears contained epithelial cells floating in a mucinlike background, which raised suspicion for mucinous (colloid) carcinoma. Mucicarmine stain was performed on one smear from each case. Subsequent tissue biopsy specimens were studied using mucicarmine, periodic acid-Schiff with and without diastase, and alcian blue stains at pH 2.7 and 0.9 on selected tissue sections. Correlation of the cytologic and histologic findings of each lesion was performed. The mucinlike background in all four FNA smears stained strongly with mucicarmine. Corresponding biopsy specimens revealed pseudoangiomatous hyperplasia in the first case, fibroadenoma and atypical ductal hyperplasia in the second, benign phyllodes tumor in the third, and fibroadenoma in the fourth. Each lesion in cases 1 to 3 was associated closely with fibrocystic changes. In case 4, cystic changes were located within the fibroadenoma. On tissue sections of all four cases, the cyst contents and 10% to 50% of normal lobule and duct contents stained with mucicarmine, indicating that the cyst contents were the most probable source of mucin in the FNA smears. The presence of pools of mucicarmine-positive material in FNA smears of the breast is not an exclusive feature of mucinous carcinoma; mucicarmine-positive mucin can arise from benign cystic changes as well as from normal lobules and ducts. C1 Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Columbia Presbyterian Med Ctr, Dept Pathol, New York, NY 10032 USA. NCI, Dept Cytopathol, NIH, Bethesda, MD 20892 USA. Cornell Univ Med Coll, New York, NY USA. Cornell Univ, Med Ctr, New York Hosp, Dept Pathol, New York, NY 10021 USA. RP Greenebaum, E (reprint author), Columbia Univ Coll Phys & Surg, Dept Pathol, 630 W 168th St, New York, NY 10032 USA. NR 11 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 1998 VL 109 IS 2 BP 169 EP 172 PG 4 WC Pathology SC Pathology GA YU743 UT WOS:000071749800006 PM 9583888 ER PT J AU Gammon, MD Schoenberg, JB Britton, JA Kelsey, JL Coates, RJ Brogan, D Potischman, N Swanson, CA Daling, JR Stanford, JL Brinton, LA AF Gammon, MD Schoenberg, JB Britton, JA Kelsey, JL Coates, RJ Brogan, D Potischman, N Swanson, CA Daling, JR Stanford, JL Brinton, LA TI Recreational physical activity and breast cancer risk among women under age 45 years SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; exercise ID DELAYED MENARCHE; UNITED-STATES; EXERCISE; PREVENTION; AMENORRHEA; PROSPECTS AB To evaluate whether recreational physical activity is associated with breast cancer among young women, the authors analyzed data from a population-based case-control study. Cases (n = 1,668) were women under age 45 years who had been newly diagnosed with breast cancer between 1990 and 1992 in Atlanta, Georgia, central New Jersey, or Seattle, Washington. Controls (n = 1,505) were frequency-matched to cases by 5-year age group and geographic area of residence. Breast cancer was not associated with recreational activity in any of the three time periods assessed (highest quartile of activity vs. lowest: age-and center-adjusted odds ratio (OR) = 0.94 (95% confidence interval (CI) 0.77-1.15) at ages 12-13 years, OR = 1.08 (95% CI 0.88-1.32) at age 20 years, and OR = 1.18 (95% CI 0.97-1.44) during the past year), with the average of the three time periods (OR = 1.02, 95% CI 0.84-1.25), or with daily climbing of at least two flights of stairs (without stopping) during the past year (daily climbing vs. never climbing: OR = 1.03, 95% CI 0.86-1.23). Estimates were not modified or confounded by body mass index, menopausal status, or caloric intake during the past year. These results do not support a protective role for physical activity in the risk of breast cancer among young women. C1 Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY 10027 USA. New Jersey Dept Hlth & Senior Serv, Appl Canc Epidemiol Program, Trenton, NJ USA. Stanford Univ, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. Emory Univ, Dept Biostat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Utah, Div Publ Hlth Sci, Salt Lake City, UT USA. RP Gammon, MD (reprint author), Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY 10027 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 38 TC 80 Z9 81 U1 1 U2 3 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 1 PY 1998 VL 147 IS 3 BP 273 EP 280 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YX150 UT WOS:000072011400013 PM 9482502 ER PT J AU Sorensen, HT Friis, S Olsen, JH Thulstrup, AM Mellemkjaer, L Linet, M Trichopoulos, D Vilstrup, H Olsen, J AF Sorensen, HT Friis, S Olsen, JH Thulstrup, AM Mellemkjaer, L Linet, M Trichopoulos, D Vilstrup, H Olsen, J TI Risk of breast cancer in men with liver cirrhosis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; EPIDEMIOLOGY; CARCINOMA; ESTROGEN; WOMEN AB Objective: Liver cirrhosis is associated with increased levels of estrogens, which may be causally related to breast cancer, Because background estrogen levels are lower in men than in women, an estrogen-mediated link between liver cirrhosis and breast cancer would be easier to detect in men, Methods: Men hospitalized with liver cirrhosis in Denmark from January 1, 1977, to December 31, 1989, were followed up, through record linkage, until the end of December 1993 for the possible occurrence of breast cancer, Results: A total of 11,642 men with liver cirrhosis were identified and were followed for a mean period of 4.3 yr, for a total of 49,687 person-years, Three cases of male breast cancer were observed whereas 0.75 was expected, for a standardized incidence ratio of 4.0, (95% confidence interval, 0.8-11.7). Conclusions: Cirrhosis, possibly via high levels of endogenous estrogens, increases the risk of breast cancer in men, (C) 1998 by Am. Coll, of Gastroenterology. C1 Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark. Danish Canc Soc, Div Canc Epidemiol, Copenhagen, Denmark. Aarhus Univ Hosp, Dept Internal Med 5, DK-8000 Aarhus, Denmark. NCI, Radiat Epidemiol Branch, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. RP Sorensen, HT (reprint author), Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, Hoegh Guldbergsgade 10, DK-8000 Aarhus C, Denmark. FU NCI NIH HHS [MAO NO1-CP-85639-04] NR 23 TC 50 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 1998 VL 93 IS 2 BP 231 EP 233 DI 10.1111/j.1572-0241.1998.00231.x PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZB489 UT WOS:000072477100023 PM 9468249 ER PT J AU Kakuda, TN Struble, KA Piscitelli, SC AF Kakuda, TN Struble, KA Piscitelli, SC TI Protease inhibitors for the treatment of human immunodeficiency virus infection SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE antivirals; compliance; costs; dosage; drug administration; drug interactions; food; HIV infections; human immunodeficiency virus; indinavir sulfate; mechanism of action; nelfinavir mesylate; patient information; pharmacists; pharmacokinetics; resistance; ritonavir; saquinavir mesylate; toxicity ID ORALLY BIOAVAILABLE INHIBITOR; HIV-1 PROTEASE; TYPE-1 PROTEASE; IN-VIVO; PROTEINASE-INHIBITOR; INCREASED RESISTANCE; CRYSTAL-STRUCTURE; RATIONAL DESIGN; DRUG-RESISTANCE; RITONAVIR AB The pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration of protease inhibitors are reviewed. Protease inhibitors are a novel class of drugs used for the treatment of human immunodeficiency virus (HIV) infection. Saquinavir, ritonavir, indinavir, and nelfinavir have been approved in the United States; several other agents are under development. Protease inhibitors selectively block HIV protease, an enzyme involved in the later stages of HIV replication. Various pharmacokinetic differences exist among these agents, including differences in bioavailability, protein binding, and drug interactions. The drugs undergo extensive hepatic metabolism; dosage adjustments should be considered for patients with hepatic dysfunction. Clinical trials have shown protease inhibitors to be effective in reducing HIV RNA levels and increasing CD4+ lymphocyte counts. When protease inhibitors are used in combination with other antiretroviral agents, an additional beneficial effect on these markers occurs. Adverse effects of saquinavir and nelfinavir include mild gastrointestinal disturbances such as diarrhea. Ritonavir is less well tolerated because of gastrointestinal disturbances and circumoral and peripheral paresthesia. Indinavir has been associated with nephrolithiasis and asymptomatic hyperbilirubinemia. The development of resistance to protease inhibitors may be related to suboptimal dosages, noncompliance, or partial compliance. Protease inhibitors are potent and highly selective agents that block a critical step in HIV replication. They are effective and relatively well tolerated, but they are expensive, have extensive drug interaction profiles, and require careful compliance with the prescribed regimen. C1 NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Piscitelli, SC (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, 10 Ctr Dr,Bldg 10,Room 1N-257,MSC 1196, Bethesda, MD 20892 USA. EM spisc@nih.gov NR 125 TC 63 Z9 63 U1 1 U2 2 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 1 PY 1998 VL 55 IS 3 BP 233 EP 254 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YX156 UT WOS:000072012000010 PM 9492254 ER PT J AU Briggs, MD Mortier, GR Cole, WG King, LM Golik, SS Bonaventure, J Nuytinck, L De Paepe, A Leroy, JG Biesecker, L Lipson, M Wilcox, WR Lachman, RS Rimoin, DL Knowlton, RG Cohn, DH AF Briggs, MD Mortier, GR Cole, WG King, LM Golik, SS Bonaventure, J Nuytinck, L De Paepe, A Leroy, JG Biesecker, L Lipson, M Wilcox, WR Lachman, RS Rimoin, DL Knowlton, RG Cohn, DH TI Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia multiple epiphyseal dysplasia disease spectrum SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PERICENTROMERIC REGION; CHROMOSOME-19; COLLAGEN; LINKAGE; BINDING; THROMBOSPONDINS; CANDIDATE; RECEPTOR; DOMAIN; EDM2 AB Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [http://www3.ncbi.nlm.nih.gov:80/ htbin-post/Omim/dispmim?600310]). We report the identification of COMP mutations in an additional 14 families with PSACH or MED phenotypes. Mutations predicted to result in single-amino acid deletions or substitutions, all in the region of the COMP gene encoding the calmodulin-like repeat elements, were identified in patients with moderate to severe PSACH. We also identified within this domain a missense mutation that produced MED Fairbank. In two families, one with mild PSACH and the second with a form of MED, we identified different substitutions for a residue in the carboxyl-terminal globular region of COMP. Both the clinical presentations of these two families and the identification of COMP-gene mutations provide evidence of phenotypic overlap between PSACH and MED. These data also reveal a role for the carboxyl-terminal domain in the structure and/or function of COMP. C1 Univ Calif Los Angeles, Sch Med,Burns & Allen Cedars Sinai Res Inst, Steven Spielberg Pediat Res Ctr, Ahmanson Dept Pediat, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA USA. Univ Gent Hosp, Dept Med Genet, Ghent, Belgium. Univ Gent Hosp, Dept Pediat, Ghent, Belgium. Hosp Sick Children, Div Orthoped, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Necker Hosp, Paris, France. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. So Calif Permanente Med Grp, Sacramento, CA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. RP Cohn, DH (reprint author), Cedars Sinai Med Ctr, SSB-3,8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM dcohn@mailgate.csmc.edu RI Mortier, Geert/D-2542-2012 FU NIAMS NIH HHS [AR43139]; NICHD NIH HHS [HD22657] NR 33 TC 115 Z9 123 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 FEB PY 1998 VL 62 IS 2 BP 311 EP 319 DI 10.1086/301713 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA ZA927 UT WOS:000072416000014 PM 9463320 ER PT J AU Annabi, B Hiraiwa, H Mansfield, BC Lei, KJ Ubagai, T Polymeropoulos, MH Moses, SW Parvari, R Hershkovitz, E Mandel, H Fryman, M Chou, JY AF Annabi, B Hiraiwa, H Mansfield, BC Lei, KJ Ubagai, T Polymeropoulos, MH Moses, SW Parvari, R Hershkovitz, E Mandel, H Fryman, M Chou, JY TI The gene for glycogen-storage disease type 1b maps to chromosome 11q23 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MICROSOMAL GLUCOSE-6-PHOSPHATASE SYSTEM; TRANSPORT-SYSTEM; IB; MUTATIONS; DEFECT; HUMANS; 1A AB Glycogen-storage disease type 1 (GSD-1), also known as "von Gierke disease," is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this autosomal recessive disorder: 1a, 1b, 1c, and 1d. All share the same clinical manifestations, which are caused by abnormalities in the metabolism of glucose-6-phosphate (G6P). However, only GSD-1b patients suffer infectious complications, which are due to both the heritable neutropenia and the functional deficiencies of neutrophils and monocytes. Whereas G6Pase deficiency in GSD-1a patients arises from mutations in the G6Pase gene, this gene is normal in GSD-1b patients, indicating a separate locus for the disorder in the 1b subgroup. We now report the linkage of the GSD-1b locus to genetic markers spanning a 3-cM region on chromosome 11q23. Eventual molecular characterization of this disease will provide new insights into the genetic bases of G6P metabolism and neutrophil-monocyte dysfunction. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Ben Gurion Univ Negev, Div Pediat, IL-84105 Beer Sheva, Israel. Rambam Med Ctr, Dept Pediat, Haifa, Israel. Sackler Sch Med, Chaim Sheba Med Ctr, Tel Aviv, Israel. RP Chou, JY (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. RI Hershkovitz, Eli/F-1922-2012 NR 29 TC 79 Z9 84 U1 1 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 FEB PY 1998 VL 62 IS 2 BP 400 EP 405 DI 10.1086/301727 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZA927 UT WOS:000072416000024 PM 9463334 ER PT J AU Knoppers, BM Strom, C Clayton, EW Murray, T Fibison, W Luther, L Billings, PR Godmilow, L Handelin, B AF Knoppers, BM Strom, C Clayton, EW Murray, T Fibison, W Luther, L Billings, PR Godmilow, L Handelin, B CA Amer Soc Human Genetics Social Issues TI Professional disclosure of familial genetic information SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PRIVACY C1 Univ Montreal, CRDP, Fac Droit, Montreal, PQ H3C 3J7, Canada. Illinois Masonic Med Ctr, Chicago, IL 60657 USA. Vanderbilt Univ, Nashville, TN USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Knoppers, BM (reprint author), Univ Montreal, CRDP, Fac Droit, CP 6128,Succursale A, Montreal, PQ H3C 3J7, Canada. NR 46 TC 158 Z9 158 U1 0 U2 5 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 FEB PY 1998 VL 62 IS 2 BP 474 EP 483 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZA927 UT WOS:000072416000030 ER PT J AU Grandin, CB Mathurin, P Duprez, T Stroobandt, G Hammer, F Goffette, P Cosnard, G AF Grandin, CB Mathurin, P Duprez, T Stroobandt, G Hammer, F Goffette, P Cosnard, G TI Diagnosis of intracranial aneurysms: Accuracy of MR angiography at 0.5 T SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE ANGIOGRAPHY; TIME-OF-FLIGHT; DIGITAL SUBTRACTION ANGIOGRAPHY; MAXIMUM INTENSITY PROJECTION; SUBARACHNOID HEMORRHAGE; CONTRAST; DISEASE; IMAGES AB PURPOSE: Our goal was to determine the accuracy of MR angiography at 0.5 T for the diagnosis of intracranial aneurysms, METHODS: We retrospectively studied 140 patients, 70 with acute subarachnoid hemorrhage,who were either at high or now risk for intracranial aneurysm, Three-dimensional time-of-flight MR angiography was typically performed to cover the circle of Willis, with a volume thickness of 30 mm, Conventional spin-echo MR images and MR angiograms were reviewed together, and the results were compared with those obtained at intraarterial cerebral angiography to determine the sensitivity and specificity of MR angiography. RESULTS: Eighty-nine aneurysms (size range, 2 to 27 mm; 25 aneurysms < 5 mm) were identified at intraarterial cerebral angiography. Six aneurysms were missed by MR angiography and two were doubtful (sensitivity, 91% to 93%; specificity, 100%), Missed aneurysms were located outside the MR angiographic acquisition volume (n = 3) or on the carotid siphon (n = 3; size = 2, 3, and 5 mm), CONCLUSION: Even if MR angiography presents some restrictions in acquisition volume and spatial resolution, the detection rate of intracranial aneurysms is excellent at 0.5 T in both asymptomatic patients and in those with subarachnoid hemorrhage. A midfield system is not a restriction to the detection of intracranial aneurysms by MR examination. C1 St Luc Univ Hosp, Dept Med Imaging, Brussels, Belgium. St Luc Univ Hosp, Neurosurg Unit, Brussels, Belgium. RP Grandin, CB (reprint author), NIH, Vivo NMR Res Ctr, Bldg 10,Room B1D-125, Bethesda, MD 20892 USA. OI Duprez, Thierry/0000-0002-1579-0100 NR 31 TC 36 Z9 39 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD FEB PY 1998 VL 19 IS 2 BP 245 EP 252 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YX191 UT WOS:000072015500009 PM 9504473 ER PT J AU Burns, DN Landesman, S Minkoff, H Wright, DJ Waters, D Mitchell, RM Rubinstein, A Willoughby, A Goedert, JJ AF Burns, DN Landesman, S Minkoff, H Wright, DJ Waters, D Mitchell, RM Rubinstein, A Willoughby, A Goedert, JJ TI The influence of pregnancy on human immunodeficiency virus type 1 infection: Antepartum and postpartum changes in human immunodeficiency virus type 1 viral load SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE pregnancy; acquired immunodeficiency syndrome; human immunodeficiency virus; ribonucleic acid; virus ID HIV-1 RNA; ZIDOVUDINE TREATMENT; WOMEN; TRANSMISSION; DEPRESSION; CYTOKINES; CD4(+); COHORT; RISK AB OBJECTIVE: Our objective was to examine the influence of pregnancy on human immunodeficiency virus type 1 viral load by measuring human immunodeficiency virus type 1 ribonucleic acid levels during pregnancy and post partum. STUDY DESIGN: One or more plasma or serum specimens obtained before and during the third trimester, and at 2, 12, and 24 months post partum were available for 160 human immunodeficiency virus type 1-seropositive women enrolled in the Mothers and Infants Cohort Study between January 1986 and January 1991. All specimens were frozen and stored at -70 degrees C until analyzed in batch for human immunodeficiency virus type 1 ribonucleic acid by polymerase chain reaction. A multivariate longitudinal random effects model was developed to examine changes in human immunodeficiency virus type 1 ribonucleic acid levels over time. RESULTS: Overall, human immunodeficiency virus type 1 ribonucleic acid levels rose significantly during the study period, particularly during the second year post partum (mean, 0.09 log per year; 95% confidence interval, 0.03 to 0.15 logs per year; p = 0.005). However, the mean slope during pregnancy was not significantly different from zero (p = 0.65). CONCLUSION: Pregnancy had little immediate effect on human immunodeficiency virus type 1 viral load in most human immunodeficiency virus type 1-seropositive women. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20892 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Westat Inc, Sunnybrook Hlth Sci Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. SAIC, Frederick, MD USA. RP Burns, DN (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Suite 4B11, Rockville, MD 20892 USA. FU NCI NIH HHS [N0-1-CP-61013]; NICHD NIH HHS [N0-1-HD-8-2913, R0-1-HD-25714] NR 25 TC 21 Z9 22 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 1998 VL 178 IS 2 BP 355 EP 359 DI 10.1016/S0002-9378(98)80025-2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YZ971 UT WOS:000072313500025 PM 9500499 ER PT J AU Cotch, MF Hillier, SL Gibbs, RS Eschenbach, DA AF Cotch, MF Hillier, SL Gibbs, RS Eschenbach, DA CA Vaginal Infections Prematurity Study Grp TI Epidemiology and outcomes associated with moderate to heavy Candida colonization during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE Candida; pregnancy; epidemiology; cohort study ID AMNIOTIC-FLUID INFECTION; BACTERIAL VAGINOSIS; PRETERM LABOR; VAGINAL INFECTIONS; FETAL MEMBRANES; TRICHOMONAS; VAGINITIS; ALBICANS; WOMEN AB OBJECTIVE: Our purpose was to determine the risk factors, physical findings, microflora, and pregnancy outcome among pregnant women with moderate to heavy vaginal growth of Candida albicans and other Candida species. STUDY DESIGN: A multicenter cohort of 13,914 women were enrolled between 23 and 26 weeks' gestation. Women completed a questionnaire, underwent a physical examination, and had genital specimens taken for culture. A subset of 1459 women were reexamined during the third trimester. Pregnancy outcomes were recorded at delivery. RESULTS: The prevalence of moderate to heavy Candida colonization at midgestation was 10%. Colonized women, 83% of whom carried C. albicans, were more likely to be black or Hispanic, unmarried, a previous oral contraceptive user, and to manifest clinical signs indicative of Candida carriage. Candida colonization was positively associated with Trichomonas vaginalis, group B streptococci, and aerobic Lactobacillus and was not associated with adverse pregnancy outcome. CONCLUSION: These results suggest that Candida colonization is not associated with low birth weight or preterm delivery. C1 NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. RP Hillier, SL (reprint author), Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, 300 Halket St, Pittsburgh, PA 15213 USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999]; NIAID NIH HHS [AI-4-2532]; NICHD NIH HHS [HD-3-2832, HD-3-2836] NR 25 TC 73 Z9 81 U1 0 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 1998 VL 178 IS 2 BP 374 EP 380 DI 10.1016/S0002-9378(98)80028-8 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YZ971 UT WOS:000072313500028 PM 9500502 ER PT J AU Ried, T AF Ried, T TI Interphase cytogenetics and its role in molecular diagnostics of solid tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; INSITU HYBRIDIZATION; CHROMOSOME-ABERRATIONS; GENE-EXPRESSION; CELLS; IMMUNOCYTOCHEMISTRY; VISUALIZATION; AMPLIFICATION; PROGRESSION C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Ried, T (reprint author), Natl Human Genome Res Inst, NIH, Bldg 49,Room 4A28,49 Convent Dr, Bethesda, MD 20892 USA. NR 30 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1998 VL 152 IS 2 BP 325 EP 327 PG 3 WC Pathology SC Pathology GA YW170 UT WOS:000071905500001 PM 9466555 ER PT J AU Messing, A Head, MW Galles, K Galbreath, EJ Goldman, JE Brenner, M AF Messing, A Head, MW Galles, K Galbreath, EJ Goldman, JE Brenner, M TI Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; ALPHA-B-CRYSTALLIN; ROSENTHAL FIBERS; ALEXANDERS DISEASE; TRANSCRIPTIONAL REGULATION; MALLORY BODIES; MESSENGER-RNA; STRESS; CELLS; EXPRESSION AB Increased expression of glial fibrillary acidic protein (GFAP) is a hallmark of gliosis, the astrocytic hypertrophy that occurs during a wide variety of diseases of the central nervous system. To determine whether this increase in GFAP expression per se alters astrocyte function, we generated transgenic mice that carry copies of the human GFAP gene driven by its own promoter. Astrocytes of these mice are hypertrophic, up-regulate small heat-shock proteins, and contain inclusion bodies identical histologically and antigenically to the Rosenthal fibers of Alexander's disease. Mice in the highest expressing lines die by the second postnatal week, The results support the notion that Alexander's disease is a disorder of astrocytes, and provide an animal model for studying the causes and consequences of inclusion body disease. C1 Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, Div Neuropathol, New York, NY USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Messing, A (reprint author), Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, 2015 Linden Dr W, Madison, WI 53706 USA. FU NCRR NIH HHS [RR-00094]; NEI NIH HHS [EY-09331]; NINDS NIH HHS [NS-22475] NR 31 TC 145 Z9 148 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1998 VL 152 IS 2 BP 391 EP 398 PG 8 WC Pathology SC Pathology GA YW170 UT WOS:000071905500011 PM 9466565 ER PT J AU Chou, CL Ma, TH Yang, BX Knepper, MA Verkman, S AF Chou, CL Ma, TH Yang, BX Knepper, MA Verkman, S TI Fourfold reduction of water permeability in inner medullary collecting duct of aquaporin-4 knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE kidney; urinary concentration; transgenic mice; vasopressin ID RAT-KIDNEY; MOLECULAR-CLONING; CHANNEL; LOCALIZATION; EXPRESSION; GLYCEROL; MEMBRANE; PROTEIN; TISSUES; CELLS AB Aquaporin (AQP)-3 and AQP4 water channels are expressed at the basolateral membrane of mammalian collecting duct epithelium. To determine the contribution of AQP4 to water permeability in the initial inner medullary collecting duct (IMCD), osmotic water permeability (P-f) was compared in isolated perfused IMCD segments from wild-type and AQP4 knockout mice. The AQP4 knockout mice were previously found to have normal gross appearance, survival, growth, and kidney morphology and a mild urinary concentrating defect (T. Ma, B. Yang, A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman. J. Clin. Invest. 100: 957-962, 1997). Transepithelial Pc was measured in microdissected IMCDs after 18-48 h of water deprivation and in the presence of 0.1 nM arginine vasopressin (to make basolateral P-f rate limiting). P-f values (37 degrees C; means +/- SE in cm/s x 10(-3)) were 56.0 +/- 8.5 for wild-type mice (n = 5) and 13.1 +/- 3.7 for knockout mice (n = 6) (P < 0.001). Northern blot analysis of kidney showed that transcript expression of AQP1, AQP2, AQP3, and AQP6 were not affected by AQP4 deletion. Immunoblot analysis indicated no differences in protein expression of AQP1, AQP2, or AQP3, and immunoperoxidase showed no differences in staining patterns. Coexpression of AQP3 and AQP4 in Xenopus laevis oocytes showed additive water permeabilities, suggesting that AQP4 deletion does not affect AQP3 function. These results indicate that AQP4 is responsible for the majority of basolateral membrane water movement in IMCD but that its deletion is associated with a very mild defect in urinary concentrating ability. C1 Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA 94143 USA. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Verkman, S (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, 1246 Hlth Sci E Tower, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL-42368, HL-51854]; NIDDK NIH HHS [DK-35124] NR 36 TC 117 Z9 124 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 1998 VL 274 IS 2 BP C549 EP C554 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA YV983 UT WOS:000071884000031 PM 9486146 ER PT J AU Bogdanov, KY Spurgeon, HA Vinogradova, TM Lakatta, EG AF Bogdanov, KY Spurgeon, HA Vinogradova, TM Lakatta, EG TI Modulation of the transient outward current in adult rat ventricular myocytes by polyunsaturated fatty acids SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE linoleic acid; eicosapentaenoic acid; fish oil; arachidonic acid; potassium currents ID RECTIFIER K+ CHANNEL; CARDIAC MYOCYTES; ARACHIDONIC-ACID; POTASSIUM CHANNELS; CELLS; FIBRILLATION; PHOSPHOLIPIDS; MYOCARDIUM; BLOCKADE; RABBIT AB With the whole cell patch-clamp technique, we studied the effects of the n-3 and n-6 polyunsaturated fatty acids (PUFAs), linoleic (C18:2n-6), eicosapentaenoic (C20:4n-3), docosahexaenoic (C22:5n-3), and arachidonic (AA; C20:4n-6) acids, on K+ currents in rat ventricular myocytes. At low concentrations (5-10 mu M) all PUFAs except AA inhibited, by similar to 40%, the transient outward current (I-to) without affecting other K+ currents and markedly prolonged the action potential (AP). AA inhibited I-to but also augmented a sustained depolarization-induced outward K+ current (I-sus); the latter effect did not occur in the presence of 4-aminopyridine or with eicosatetraynoic acid, a nonmetabolizable analog of AA. Higher concentrations of PUFAs (20-50 mu M) further inhibited I-to and also inhibited I-sus. Thus, at high concentrations, PUFAs have a nonspecific effect on several K+ channels; at low concentrations, PUFAs preferentially inhibit I-to and prolong the AP. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Cardiol Res Ctr, Inst Expt Cardiol, Lab Heart Electrophysiol, Moscow 121552, Russia. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 32 TC 59 Z9 61 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 1998 VL 274 IS 2 BP H571 EP H579 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA YV839 UT WOS:000071868500025 PM 9486261 ER PT J AU Marples, D Schroer, TA Ahrens, N Taylor, A Knepper, MA Nielsen, S AF Marples, D Schroer, TA Ahrens, N Taylor, A Knepper, MA Nielsen, S TI Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cytoplasmic dynein; vasopressin; regulated exocytosis; membrane trafficking ID CYTOPLASMIC DYNEIN; PERMEABILITY RESPONSE; EPITHELIAL-CELLS; PLASMA-MEMBRANE; URINARY-BLADDER; RAT-KIDNEY; VASOPRESSIN; MICROTUBULES; PROTEIN; ORGANIZATION AB We investigated whether the motor protein cytoplasmic dynein and dynactin, a protein complex thought to link dynein with vesicles, are present in rat renal collecting ducts and associated with aquaporin-2 (AQP2)-bearing vesicles. Immunoblotting demonstrated cytaplasmic dynein heavy and intermediate chains in kidney, with relative expression levels of inner medulla > outer medulla > cortex. In addition to being. present in cytoplasmic fractions, dynein was abundant in membrane fractions enriched for intracellular vesicles. Dynactin was also abundant in membrane fractions enriched far intracellular vesicles. Furthermore, both dynactin and dynein were present in vesicles specifically immunoisolated using anti-AQP2 antibodies. Immunocytochemistry revealed labeling for dynein in the collecting duct principal cells with a pattern consistent with labeling of intracellular vesicles. Moreover, quantitative double immunogold labeling confirmed colocalization of AQP2 and dynein in the same vesicles at the electron microscopic level. Thus the microtubule-associated motor protein dynein and the-associated dynactin complex are present in rat renal collecting duct principal cells and are associated with intracellular vesicles, including those bearing AQP2, consistent with the view that dynein and dynactin are involved in vasopressin-regulated trafficking of A4P2-bearing vesicles. C1 Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Univ Leeds, Dept Physiol, Leeds LS2 9NQ, W Yorkshire, England. Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21215 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. NR 39 TC 65 Z9 67 U1 1 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 FEB PY 1998 VL 274 IS 2 BP F384 EP F394 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA YV963 UT WOS:000071882000017 PM 9486234 ER PT J AU Voorhees, CC Yanek, LR Stillman, FA Becker, DM AF Voorhees, CC Yanek, LR Stillman, FA Becker, DM TI Reducing cigarette sales to miners in an urban setting: Issues and opportunities for merchant intervention SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE cigarettes; sales; minors; advertising; at risk populations; government policy ID YOUTH ACCESS; TOBACCO; MINORS; AGE AB Introduction: Intervention studies to reduce cigarette sales to miners have been conducted primarily in suburban settings. Little is known about sociocultural factors influencing cigarette sales to miners in urban settings, This study sought to determine sociodemographic and cultural factors that may play a role in cigarette sales and in efforts to reduce sales to miners in urban areas. Methods: Merchant education and follow-up surveys were conducted in small local stores in predominantly African-American urban census tracts in Baltimore, The stores had prior evidence of cigarette sales to miners. Results: Merchants reported hostility (66%) and foul language (64%) when they requested youth identification. Youthful-oriented advertising of cigarettes was highly prevalent in all stores and moreso in stores owned and staffed by Asian merchants. Advertising with specific youthful content was predictive (OR = .97; 95% CI = 1.70, 9.23; P = .0014) of higher requests for cigarettes from miners. Conclusions: Youth-oriented cigarette advertising is a prevalent environmental risk for urban youth. Differences between Asian and African-American merchants suggest socioethnic factors may be an influential component of illegal sales and educational campaigns to reduce smoking among miners. C1 Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Ctr Hlth Promot, Baltimore, MD USA. RP Voorhees, CC (reprint author), NHLBI, NIH, Div Epidemiol & Clin Applicat, Prevent & Behav Med SRG, Rockledge 2,Room 8215, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [R01HL43604-0651] NR 22 TC 12 Z9 12 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD FEB PY 1998 VL 14 IS 2 BP 138 EP 142 DI 10.1016/S0749-3797(97)00024-X PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 104AQ UT WOS:000074990400008 PM 9631166 ER PT J AU Swedo, SE Leonard, HL Garvey, M Mittleman, B Allen, AJ Perlmutter, S Dow, S Zamkoff, J Dubbert, BK Lougee, L AF Swedo, SE Leonard, HL Garvey, M Mittleman, B Allen, AJ Perlmutter, S Dow, S Zamkoff, J Dubbert, BK Lougee, L TI Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE-DISORDER; SYDENHAMS CHOREA; TOURETTES DISORDER; TREATMENT RESPONSE; FOLLOW-UP; CHILDREN; ADOLESCENTS; EPIDEMIOLOGY; CHILDHOOD; SYMPTOMS AB Objective: The purpose of this study was to describe the clinical characteristics of a novel group of patients with obsessive-compulsive disorder (OCD) and tic disorders, designated as pediatric autoimmune neuropsychiatric disorders associated with streptococcal (group A beta-hemolytic streptococcal [GABHS] infections (PANDAS). Method: The authors conducted a systematic clinical evaluation of 50 children who met all of the following five working diagnostic criteria: presence of OCD and/or a tic disorder, prepubertal symptom onset, episodic course of symptom severity, association with GABHS infections, and association with neurological abnormalities. Results: The children's symptom onset was acute and dramatic, typically triggered by GABHS infections at a very early age (mean = 6.3 years, SD = 2.7, for ties; mean = 7.4 years, SD = 2.7, for OCD). The PANDAS clinical course tr,as characterized by a relapsing-remitting symptom pattern with significant psychiatric comorbidity accompanying the exacerbations; emotional lability, separation anxiety, nighttime fears and bedtime rituals, cognitive deficits, oppositional behaviors, and motoric hyperactivity were particularly common. Symptom onset was triggered by GABHS infection for 22 (44%) of the children and by pharyngitis (no throat culture obtained) for 14 others (28%). Among the 50 children, there were 144 separate episodes of symptom exacerbation; 45 (31%) were associated with documented GABHS infection, 60 (42%) with symptoms of pharyngitis or upper respiratory infection (no throat culture obtained), and six (4%) with GABHS exposure. Conclusions: The working diagnostic criteria appear to accurately characterize a homogeneous patient group in which symptom exacerbations are triggered by GABHS infections. The identification of such a subgroup will allow for testing of models of pathogenesis, as well as the development of novel treatment and prevention strategies. C1 NIMH, Child Psychiat Branch, Behav Pediat Sect, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), NIMH, Child Psychiat Branch, Behav Pediat Sect, Bldg 10,Rm 4N224,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 664 Z9 694 U1 5 U2 45 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 1998 VL 155 IS 2 BP 264 EP 271 PG 8 WC Psychiatry SC Psychiatry GA YV303 UT WOS:000071809700018 PM 9464208 ER PT J AU Goldenberg, RL Iams, JD Mercer, BM Meis, PJ Moawad, AH Copper, RL Das, A Thom, E Johnson, F McNellis, D Miodovnik, M Van Dorsten, JP Caritis, SN Thurnau, GR Bottoms, SF AF Goldenberg, RL Iams, JD Mercer, BM Meis, PJ Moawad, AH Copper, RL Das, A Thom, E Johnson, F McNellis, D Miodovnik, M Van Dorsten, JP Caritis, SN Thurnau, GR Bottoms, SF CA NICHD MFMU Network TI The preterm prediction study: The value of new vs standard risk factors in predicting early and all spontaneous preterm births SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FETAL FIBRONECTIN; BACTERIAL VAGINOSIS; ETHNIC-GROUPS; DELIVERY; WEIGHT; PREGNANCY; WOMEN; COLONIZATION; POPULATION AB Objective. This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. Methods. From 1992 through 1994, 2929 women were screened at the gestational age of 22 to 24 weeks. Results. The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common-and a stronger predictor of spontaneous preterm birth-in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. Conclusions. Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors. Bacterial vaginosis was found more often in Black than in non-Black women and accounted for 40% of the attributable risk for spontaneous preterm birth at less than 32 weeks. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Ohio State Univ, Columbus, OH 43210 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Univ Tennessee, Memphis, TN USA. Univ Chicago, Chicago, IL 60637 USA. George Washington Univ, Washington, DC 20052 USA. Ctr Biostat, Rockville, MD USA. NICHD, Bethesda, MD USA. Univ Cincinnati, Cincinnati, OH USA. Med Univ S Carolina, Charleston, SC 29425 USA. Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Oklahoma, Oklahoma City, OK USA. Hutzel Hosp, Detroit, MI 48201 USA. RP Goldenberg, RL (reprint author), Univ Alabama, Dept Obstet & Gynecol, 618 S 20th St,Room 560-OHB, Birmingham, AL 35294 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21434, HD21410, HD21414] NR 26 TC 241 Z9 247 U1 1 U2 13 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 FEB PY 1998 VL 88 IS 2 BP 233 EP 238 DI 10.2105/AJPH.88.2.233 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT677 UT WOS:000074113400012 PM 9491013 ER PT J AU Halloran, ME Anderson, RM Azevedo-Neto, RS Bellini, WJ Branch, O Burke, MA Compans, R Day, K Gooding, L Gupta, S Katz, J Kew, O Keyserling, H Krause, R Lal, AA Massad, E McLean, AR Rosa, P Rota, P Wiener, P Wynn, SG Zanetta, DMT AF Halloran, ME Anderson, RM Azevedo-Neto, RS Bellini, WJ Branch, O Burke, MA Compans, R Day, K Gooding, L Gupta, S Katz, J Kew, O Keyserling, H Krause, R Lal, AA Massad, E McLean, AR Rosa, P Rota, P Wiener, P Wynn, SG Zanetta, DMT TI Population biology, evolution, and immunology of vaccination and vaccination programs SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Population Biology, Evolution, and Control of Infectious Diseases CY FEB 22-23, 1995 CL EMORY UNIV, ATLANTA, GEORGIA HO EMORY UNIV DE immunology; modeling; populations; vaccines ID MEASLES-VIRUS; TRANSMISSION DYNAMICS; SEVERE MALARIA; CHOLERA-TOXIN; B-SUBUNIT; SAO-PAULO; WILD-TYPE; INFECTION; IMMUNITY; VACCINES AB The purpose of prophylactic vaccination is to reduce morbidity and mortality in a population. Many questions related to the design of vaccines and vaccination programs require a population standpoint for their sharp formulation and laboratory and field studies to understand their immunologic background. Practical suggestions of the workshop included increased studies of age-specific immunity, better immunoepidemiologic surveillance, better design of efficacy studies, and more systematic sampling of parasite strains to study the evolutionary pressure exerted by vaccines. Theoretical immunology has much to contribute. One of the realizations of the workshop was the value of a strong interdisciplinary approach in vaccine development, utilizing relevant contributions from immunology, population biology, mathematical modeling, epidemiology, molecular biology, and virology. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Oxford, Dept Zool, Oxford OX1 2JD, England. Univ Sao Paulo, Sch Med, Dept Pathol, Discipline Med Informat, BR-05508 Sao Paulo, Brazil. Ctr Dis Control, Atlanta, GA 30333 USA. Fogarty Inst, Bethesda, MD USA. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Halloran, ME (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. RI Massad, Eduardo/H-6143-2011; Massad, Eduardo/B-1169-2012; Zanetta, Dirce/G-4950-2013; Compans, Richard/I-4087-2013; Azevedo, Raymundo/B-7593-2008 OI Massad, Eduardo/0000-0002-7200-2916; Day, Karen/0000-0002-6115-6135; Compans, Richard/0000-0003-2360-335X; Azevedo, Raymundo/0000-0003-0660-2371 FU NIAID NIH HHS [R01-AI32042, R29-AI3105, T32-AI07442] NR 51 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD FEB PY 1998 VL 315 IS 2 BP 76 EP 86 DI 10.1097/00000441-199802000-00003 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA YV976 UT WOS:000071883300003 PM 9472906 ER PT J AU Branch, OH Udhayakumar, V Hightower, AW Oloo, AJ Hawley, WA Nahlen, BL Bloland, PB Kaslow, DC Lal, AA AF Branch, OH Udhayakumar, V Hightower, AW Oloo, AJ Hawley, WA Nahlen, BL Bloland, PB Kaslow, DC Lal, AA TI A longitudinal investigation of IgG and IgM antibody responses to the merozoite surface protein-1 19-kilodalton domain of Plasmodium falciparum in pregnant women and infants: Associations with febrile illness, parasitemia, and anemia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HUMORAL IMMUNE-RESPONSES; MONOCLONAL-ANTIBODIES; MALARIA TRANSMISSION; TERMINAL FRAGMENT; CELL INVASION; ANTIGEN; GROWTH; EPITOPES; INHIBIT; BACULOVIRUS AB This study was aimed at delineating characteristics of naturally acquired immunity against the merozoite surface antigen-1 (MSP-1) of Plasmodium falciparum, a candidate malaria vaccine antigen, A case/control study was performed on 75 case/control pairs of infants with febrile illness at the time of the first detected infection indicating a clinical case. The presence and level of antibodies at one month prior to the first infection and at the time of the first infection in the afebrile group was significantly higher than in the febrile group. Decreased parasite density and decreased infection-related loss of hemoglobin was seen in infants with anti-MSP-1(19kD) IgG antibodies. In addition, mothers who were positive for the presence of these antibodies conferred protection against placental infection and infection in their infants. In this study, development of anti-MSP-1(19kD) antibody responses in 24 infants were studied longitudinally using monthly serum samples collected from birth until approximately one year of age. In addition, umbilical cord blood sera and respective mothers' sera were analyzed. Longitudinal studies of antibody responses revealed several short-lived IgG and IgM peaks throughout an infant's first year that correlated with detection of parasitemia. The protection against parasitemia and febrile illness was observed in infants when anti-MSP1-(19kD) antibodies were present; when infants were negative for IgG, they had a 10-times greater risk of becoming parasitemic. These data from a longitudinal and prospective study of malaria suggest a protective role for anti-MSP-1(19kD) antibodies in infants and pregnant women. C1 Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Kenya Med Res Inst, Vector Biol & Control Res Ctr, Kissian, Kenya. NIAID, Malaria Res Lab, NIH, Bethesda, MD 20892 USA. RP Branch, OH (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Mailstop F-12,4770 Buford Highway, Chamblee, GA 30341 USA. NR 27 TC 135 Z9 135 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 1998 VL 58 IS 2 BP 211 EP 219 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA YZ465 UT WOS:000072256800018 PM 9502606 ER PT J AU Korn, EL Graubard, BI AF Korn, EL Graubard, BI TI Scatterplots with survey data SO AMERICAN STATISTICIAN LA English DT Article DE added variable plot; conditional percentile; graphical methods; imputation; influential points; kernel smoothing; nonparametric regression; partial residual plot; sample weights; survey methods ID REGRESSION; DESIGN; RISK AB We suggest various modifications to make scatterplots more informative when used with data obtained from a sample survey. Aspects of survey data leading to the plot modifications include the sample weights associated with the observations, imputed data for item nonresponse, and large sample sizes. Examples are given using data from the 1988 National Maternal Infant and Health Survey, the second National Health and Nutrition Examination Survey, and the epidemiologic follow-up of the first National Health and Nutrition Examination Survey. C1 NCI, Clin Trials Sect, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Biostat Methodol & Canc Control Epidemiol Sect, Biometry Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Clin Trials Sect, Biometr Res Branch, Bethesda, MD 20892 USA. NR 26 TC 11 Z9 11 U1 2 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD FEB PY 1998 VL 52 IS 1 BP 58 EP 69 DI 10.2307/2685570 PG 12 WC Statistics & Probability SC Mathematics GA ZD569 UT WOS:000072699700014 ER PT J AU Millar, DB AF Millar, DB TI Resuspension-induced ion flux SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID INTRACELLULAR CALCIUM FLUX AB Pelleting and resuspension of Fura 2-labeled c6 glioma cells leads to a large Ca flux characterized by a high initial internal level of Ca which rapidly declines to close to basal levels. The effect has been termed resuspension-induced ion flux (RIIF). The RIIF effect is temperature dependent and requires external calcium, cytoskeletal integrity, and functional calcium and potassium channels. The magnitude of the RIIF effect is dependent upon pelleting speed, suggesting cell contact and reduction in external fluid medium to be important causative parameters. Several other cell species also exhibit the RIIF effect. (C) 1998 Academic Press. C1 New Ideas Co, Rockville, MD 20852 USA. RP Millar, DB (reprint author), NIDDK, Lab Phys Biochem, NIH, 9650 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 1 PY 1998 VL 256 IS 1 BP 122 EP 126 DI 10.1006/abio.1997.2478 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YV740 UT WOS:000071858000015 PM 9466805 ER PT J AU Rifkind, BM Gordon, DJ AF Rifkind, BM Gordon, DJ TI Population trends in HDL-cholesterol levels SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material C1 NHLBI, Vasc Res Program, Bethesda, MD 20892 USA. RP Rifkind, BM (reprint author), NHLBI, Vasc Res Program, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1998 VL 8 IS 2 BP 83 EP 83 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YW173 UT WOS:000071905800002 PM 9491931 ER PT J AU Burchfiel, CM Abbott, RD Curb, JD Sharp, DS Rodriguez, BL Arakaki, R Yano, K AF Burchfiel, CM Abbott, RD Curb, JD Sharp, DS Rodriguez, BL Arakaki, R Yano, K TI Association of insulin levels with lipids and lipoproteins in elderly Japanese-American men SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Asian Americans; insulin; lipoproteins; HDL cholesterol; obesity; triglycerides ID CORONARY HEART-DISEASE; PLASMA-INSULIN; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; DIABETES-MELLITUS; GLUCOSE-TOLERANCE; RISK-FACTORS; HYPERINSULINEMIA; CHOLESTEROL; PROGRAM AB PURPOSE: Elevated insulin levels have been associated with cardiovascular disease, but the relationship of insulin with other risk factors and its position in the atherosclerotic pathway is uncertain, A cross-sectional study was conducted to determine whether insulin concentrations were associated with lipids and lipoproteins independently of adiposity and other cardiovascular rick factors. METHODS: Subjects included 3417 Japanese-American men from the Honolulu Heart Program who completed a follow-up examination between 1991 and 1993 and were 71-93 years of age. Men were categorized by quintiles of fasting and 2-hour insulin concentration. RESULTS: Age-adjusted mean high density lipoprotein (HDL) cholesterol and triglyceride levels varied significantly across quintiles of fasting and 2-hour insulin (P < 0.001, tests for trend), but insulin was not related to total cholesterol and low-density lipoprotein (LDL) cholesterol. HDL cholesterol decreased from 59.3 to 43.7 mg/dL and triglycerides increased from 95.6 to 175.8 mg/dL comparing lowest to highest quintiles of fasting insulin, respectively. These associations were slightly stronger in lean than obese subjects and in nondiabetic versus diabetic individuals particularly for 2-hour insulin levels. Multiple linear regression analysis adjusting for several adiposity measures separately (body mass index (BMI), subscapular skinfold thickness, waist circumference, and waist/hip ratio) and other cardiovascular risk factors attenuated associations slightly but they still remained statistically significant. Estimated differences in HDL cholesterol across extreme quintiles of fasting insulin were reduced slightly from 15.6 mg/dL with adjustment for age to 12.5 mg/dL with adjustment for age and BMI, and to 11.3 mg/dL with adjustment for age, BMI, and cardiovascular risk factors. CONCLUSIONS: Insulin concentration was strongly and independently associated with HDL cholesterol and triglycerides in this cohort of elderly Japanese-American men. Since this study was cross-sectional, further investigation is required to determine whether elevated insulin levels are causally related to dyslipidemia. Published by Elsevier Science Inc. C1 NHLBI, Honolulu Epidemiol Res Unit, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Honolulu, HI USA. Univ Virginia, Sch Med, Div Biostat, Charlottesville, VA 22908 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96817 USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. RP Burchfiel, CM (reprint author), NHLBI, Div Epidemiol & Clin Applicat, NIH, 2 Rockledge Ctr,6701 Rockledge Dr,MSC 7934, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102] NR 43 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1998 VL 8 IS 2 BP 92 EP 98 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YW173 UT WOS:000071905800004 PM 9491933 ER PT J AU Sharp, DS Masaki, K Burchfiel, CM Yano, K Schatz, IJ AF Sharp, DS Masaki, K Burchfiel, CM Yano, K Schatz, IJ TI Prolonged QT(c) interval, impaired pulmonary function, and a very lean body mass jointly predict all-cause mortality in elderly men SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE mortality; aging; body mass index; wasting syndrome; forced expiratory volume; obstructive lung diseases; increased QT interval; autonomic nervous system diseases ID CORONARY HEART-DISEASE; JAPANESE-AMERICAN MEN; CARDIOVASCULAR-DISEASE; NATIONAL COHORT; QT-INTERVAL; ASCERTAINMENT; PROGRAM AB PURPOSE: Assess the joint impact of prolonged QT(c) interval (QT interval corrected for heart rate), impaired lung function, and low body weight on all-cause mortality. METHODS: This is a population-based, prospective study of the Honolulu Heart Program cohort, performed in Oahu Island, Hawaii, during the 1991-1993 fourth examination of cohort survivors. The participants were 3056 Japanese-American men, 71 to 93 years of age. The measurement consisted of: 1) instrument calculated, heart rate corrected QT interval; 2) one second forced expiratory volume (FEV1) as a percentage of age-and height-predicted FEV1; and 3) body mass index (BMI, kg/m(2)). Relations of subsequent 3 1/2 year, on average, mortality rates with high risk states of these variables are determined. High risk states are QT(c) > 440 msec, percent predicted FEV1 less than or equal to 80%, and BMI less than or equal to 21 kg/m(2). RESULTS: Mortality rates synergistically increase among groups with one, two, or three high risk states. Men having all three high risk states are seven times more likely to die in the follow-up period than men with no high risk conditions. Very thin men having one other high risk state, pulmonary impairment or prolonged QT(c), are four times more likely to die. Excluding diabetics, active smokers, or men taking drugs affecting QT interval does not alter findings. Excluding prevalent coronary heart disease decreases mortality rates among joint high risk groups. CONCLUSION: Results are consistent with clinical studies identifying an autonomic neuropathy associated with wasting chronic lung disease, prolonged QT(c), and mortality. Aging populations in developed nations will increase the prevalence of diseases associated with these conditions in decades to come. Published by Elsevier Science Inc. C1 NHLBI, Honolulu Epidemiol Res Unit, Field Studies & Clin Epidemiol Sci Res Grp, Epidemiol & Biometry Program,Div Epidemiol & Clin, Bethesda, MD 20892 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96817 USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. RP Sharp, DS (reprint author), 2 Rockledge Ctr,6701 Rockledge Dr,MSC 7934, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102] NR 21 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1998 VL 8 IS 2 BP 99 EP 106 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YW173 UT WOS:000071905800005 PM 9491934 ER PT J AU Klebanoff, MA Levine, RJ Dersimonian, R Clemens, JD Wilkins, DG AF Klebanoff, MA Levine, RJ Dersimonian, R Clemens, JD Wilkins, DG TI Serum caffeine and paraxanthine as markers for reported caffeine intake in pregnancy SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE caffeine; biological markers; markers; serum; pregnancy ID BIRTH-WEIGHT; CONSUMPTION; WOMEN; RISK AB PURPOSE: Previous studies of maternal caffeine use and pregnancy outcome have relied on self-reported use. Even if these were perfectly accurate, inter-individual differences in caffeine metabolism result in a relatively weak correlation between caffeine intake and serum concentration. The purpose of this study was to determine whether the serum concentration of caffeine or its primary metabolite, paraxanthine, obtained at an unknown time during working hours, is useful to distinguish between pregnant women who report consuming small and large amounts of caffeine. METHODS: We selected from the Birmingham fetal growth study 60 women with normal pregnancy outcomes who reported consuming less than or equal to 0.8 mg/kg/day of caffeine in a 24-hour dietary recall, 60 who consumed 0.81-2.5 mg/kg/day, 60 who consumed 2.51-5.0 mg/kg/day and 59 who consumed greater than or equal to 5.01 mg/kg/day. These women had serum drawn for storage during regular clinic hours on the same day as the recall interview. Caffeine and paraxanthine were measured in the stored serum using high performance liquid chromatography. RESULTS: The weighted kappa coefficient between strata of caffeine intake and quartiles of serum paraxanthine was 0.58 among smokers and 0.53 among nonsmokers, versus 0.44 and 0.51, respectively, for quartiles of serum caffeine. The Pearson correlation coefficient between intake and paraxanthine was 0.50 for smokers and 0.53 for nonsmokers, and 0.37 and 0.51, respectively, for serum caffeine. These values are comparable to the correlation between reported smoking and serum cotinine in pregnancy. CONCLUSIONS: The serum concentrations of paraxanthine, and to a lesser degree, caffeine are useful to distinguish between women with varying levels of caffeine intake. Published by Elsevier Science Inc. C1 NICHD, DESPR, NIH, Bethesda, MD 20892 USA. Univ Utah, Ctr Human Toxicol, Salt Lake City, UT USA. RP Klebanoff, MA (reprint author), NICHD, DESPR, NIH, 6100 Bldg Room 7B03, Bethesda, MD 20892 USA. NR 20 TC 33 Z9 33 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 1998 VL 8 IS 2 BP 107 EP 111 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YW173 UT WOS:000071905800006 PM 9491935 ER PT J AU Corti, MC Guralnik, JM AF Corti, MC Guralnik, JM TI Total cholesterol and death from coronary heart disease in older persons - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID PRAVASTATIN C1 NIA, Bethesda, MD 20892 USA. RP NIA, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 1 PY 1998 VL 128 IS 3 BP 242 EP 243 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YU303 UT WOS:000071703200013 ER PT J AU Boswell, GW Bekersky, I Buell, D Hiles, R Walsh, TJ AF Boswell, GW Bekersky, I Buell, D Hiles, R Walsh, TJ TI Toxicological profile and pharmacokinetics of a unilamellar liposomal vesicle formulation of amphotericin B in rats SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PULMONARY ASPERGILLOSIS; LIPID FORMULATIONS; CANDIDA-ALBICANS; AMBISOME; RABBITS; INFECTION; SAFETY; MICE AB AmBisome (ABLP) is a unilamellar liposomal preparation of amphotericin B that has demonstrated an improved safety profile compared to conventional amphotericin B. Single-and multiple-dose pharmacokinetics were determined by using noncompartmental methods for rats administered ABLP at 1, 3, 9, and 20 mg/kg/day. The toxicological profile was evaluated following 30 consecutive days of intravenous ABLP administration. Mean plasma amphotericin B concentrations reached 500 and 380 mu g/ml (males and females, respectively) following 30 days of ABLP administration at 20 mg/kg. The overall apparent half-life was 11.2 +/- 4.5 h (males) or 8.7 +/- 2.2 h (females), and the overall clearance (CL) was 9.4 +/- 5.5 ml/h/kg (males) or 10.2 +/- 4.1 m/h/kg (females), ABLP appears to undergo saturable disposition, resulting in a non-dose-proportional amphotericin B area under the curve and a lower CL at higher doses. Histopathological examination revealed dose-related transitional-cell hyperplasia in the transitional epithelium of the urinary tract (kidney, ureters, and urinary bladder) and moderate hepatocellular necrosis at the 20-mg/kg/day dose, Administration of ABLP in doses of up to 20 mg/kg/day resulted in 100-fold higher plasma amphotericin B concentrations, with significantly lower toxicity than that reported with conventional amphotericin B therapy. C1 Fujisawa USA Inc, Deerfield, IL 60015 USA. NCI, Bethesda, MD 20892 USA. RP Boswell, GW (reprint author), Fujisawa USA Inc, 3 Pkwy N, Deerfield, IL 60015 USA. NR 17 TC 54 Z9 54 U1 0 U2 3 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 FEB PY 1998 VL 42 IS 2 BP 263 EP 268 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YU748 UT WOS:000071750300010 PM 9527770 ER PT J AU Odds, FC Van Gerven, F Espinel-Ingroff, A Bartlett, MS Ghannoum, MA Lancaster, MV Pfaller, MA Rex, JH Rinaldi, MG Walsh, TJ AF Odds, FC Van Gerven, F Espinel-Ingroff, A Bartlett, MS Ghannoum, MA Lancaster, MV Pfaller, MA Rex, JH Rinaldi, MG Walsh, TJ TI Evaluation of possible correlations between antifungal susceptibilities of filamentous fungi in vitro and antifungal treatment outcomes in animal infection models SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; CRYPTOCOCCAL MENINGITIS; MURINE MODEL; IN-VITRO; THERAPY; HYALOHYPHOMYCOSIS; ASPERGILLOSIS; ITRACONAZOLE; COMBINATION; CANDIDIASIS AB Nine isolates of filamentous fungi previously tested in 11 different laboratories for their susceptibilities to amphotericin B and itraconazole in vitro were injected intravenously into mice and guinea pigs, and responses to treatment with both agents were studied, The experiments were done in a single laboratory, Mean survival times, the percentages of animals surviving 12 days after infection, and culture results for samples of deep organs obtained postmortem were used as markers of antifungal efficacy, Because of variations in organism pathogenicity, interpretable test systems in vivo could not be established for Fusarium spp, in mice or guinea pigs or for Pseudallescheria boydii in mice, even with the use of immunosuppressive pretreatments, Among the infections that could be evaluated, some degree of response to the corresponding treatment in vivo was seen in animals infected with each of two Rhizopus arrhizus isolates susceptible to amphotericin B at < 0.5 mu g/ml and Aspergillus spp, isolates susceptible to itraconazole at < 1.0 mu g/ml. Conversely, no responses were apparent with infecting strains for which MICs were greater than or equal to 2 mu g/ml (amphotericin B) or greater than or equal to 1 mu g/ml (itraconazole). However, the limitations of the intravenous challenge systems studied mean that no firm conclusion relating MICs in vitro to the lowest effective doses in vivo could be drawn. C1 Janssen Res Fdn, Dept Bacteriol & Mycol, B-2340 Beerse, Belgium. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Ctr Med Mycol, Cleveland, OH USA. Ctr Dis Control & Prevent, Antimicrobial Resistance Sect, Atlanta, GA USA. Univ Iowa, Coll Med, Special Microbiol Lab, Iowa City, IA USA. Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. RP Odds, FC (reprint author), Janssen Res Fdn, Dept Bacteriol & Mycol, B-2340 Beerse, Belgium. EM fodds@janbelc1.ssw.jnj.com NR 25 TC 112 Z9 115 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 FEB PY 1998 VL 42 IS 2 BP 282 EP 288 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YU748 UT WOS:000071750300013 PM 9527773 ER PT J AU Boyer, PL Gao, HQ Hughes, SH AF Boyer, PL Gao, HQ Hughes, SH TI A mutation at position 190 of human immunodeficiency virus type 1 reverse transcriptase interacts with mutations at positions 74 and 75 via the template primer SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANGSTROM RESOLUTION; RESISTANCE; HIV-1; SENSITIVITY; REPLICATION; MUTANTS; DNA; INHIBITORS; FINGERS; THERAPY AB We have analyzed amino acid substitutions at position G190 in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). The mutation G190E, which is responsible for resistance to certain nonnucleoside inhibitors, results in RT that has significantly less polymerase activity and that is less processive than wild-type RT. Its kinetic profile with respect to dGTP and poly(rC).oligo(dG) is significantly altered compared to that of wild-type RT. The combination of either of the mutations L74V or V75I with the G190E mutation appears to be compensatory and mitigates many of the deleterious effects of the G190E mutation. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B,Bldg 539, Frederick, MD 21702 USA. NR 31 TC 57 Z9 58 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 FEB PY 1998 VL 42 IS 2 BP 447 EP 452 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YU748 UT WOS:000071750300045 PM 9527805 ER PT J AU Grady, PA AF Grady, PA TI Bringing research to life SO APPLIED NURSING RESEARCH LA English DT Editorial Material C1 Natl Inst Nursing Res, Bethesda, MD USA. RP Grady, PA (reprint author), Natl Inst Nursing Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD FEB PY 1998 VL 11 IS 1 BP 1 EP 1 DI 10.1016/S0897-1897(98)80011-6 PG 1 WC Nursing SC Nursing GA ZB636 UT WOS:000072492400001 PM 9549152 ER PT J AU Lewis, EN AF Lewis, EN TI Image is everything SO APPLIED SPECTROSCOPY LA English DT Editorial Material C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Lewis, EN (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD FEB PY 1998 VL 52 IS 2 BP 91A EP 93A PG 3 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA ZF981 UT WOS:000072952600002 ER PT J AU Regier, DA Kaelber, CT Rae, DS Farmer, ME Knauper, B Kessler, RC Norquist, GS AF Regier, DA Kaelber, CT Rae, DS Farmer, ME Knauper, B Kessler, RC Norquist, GS TI Limitations of diagnostic criteria and assessment instruments for mental disorders - Implications for research and policy SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; COMMUNITY SAMPLE; PREVALENCE; INTERVIEW; VALIDITY; RELIABILITY; LIFETIME AB During the past 2 decades, psychiatric epidemiological studies have contributed a rapidly growing body of scientific knowledge on the scope and risk factors associated with mental disorders in communities. Technological advances in diagnostic criteria specificity and community case-identification interview methods, which made such progress feasible, now face new challenges. Standardized methods are needed to reduce apparent discrepancies in prevalence rates between similar population surveys and to differentiate clinically important disorders in need of treatment from less severe syndromes. Reports of some significant differences in mental disorder rates from 2 large community surveys conducted in the United States-the Epidemiologic Catchment Area study-and the National Comorbidity Survey-provide the basis for examining the stability of methods in this field. We discuss the health policy implications of discrepant and/or high prevalence rates for determining treatment need in the context of managed care definitions of "medical necessity". C1 NIMH, NIH, Bethesda, MD 20892 USA. NIMH, Div Basic & Clin Neurosci Res, NIH, Rockville, MD 20857 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Boston, MA USA. NIMH, Div Intervent & Serv Res, NIH, Rockville, MD 20857 USA. RP Regier, DA (reprint author), NIMH, NIH, Suite 4A52,31 Ctr Dr, Bethesda, MD 20892 USA. RI Knauper, Barbel/G-8405-2012 NR 29 TC 335 Z9 340 U1 4 U2 13 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 FEB PY 1998 VL 55 IS 2 BP 109 EP 115 DI 10.1001/archpsyc.55.2.109 PG 7 WC Psychiatry SC Psychiatry GA YV744 UT WOS:000071858400001 PM 9477922 ER PT J AU Hampel, H Teipel, SJ Alexander, GE Horwitz, B Teichberg, D Schapiro, MB Rapoport, SI AF Hampel, H Teipel, SJ Alexander, GE Horwitz, B Teichberg, D Schapiro, MB Rapoport, SI TI Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease - A magnetic resonance imaging analysis SO ARCHIVES OF NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; MULTIPLE-SCLEROSIS; LAMINAR; MR; DISTRIBUTIONS; PLAQUES; MONKEY AB Background: Pathological studies in Alzheimer disease indicate the specific loss of layer III and V large pyramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and between the cerebral hemispheres. Objective: To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. Method: Using a new imaging technique, we measured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on midsagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age-and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. Results: The total callosal area was significantly reduced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and relative sparing of the callosal body. Regional callosal atrophy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. Conclusions: Callosal atrophy in patients with Alzheimer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in corresponding regions of the cortex. Because these neurons are a subset of corticocortical projecting neurons, region-specific callosal atrophy may serve as a marker of progressive neocortical disconnection in Alzheimer disease. C1 Univ Munich, Sch Med, Dept Psychiat, Geriatr Psychiat Branch, D-80336 Munich, Germany. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Hampel, H (reprint author), Univ Munich, Sch Med, Dept Psychiat, Geriatr Psychiat Branch, Nussbaumstr 7, D-80336 Munich, Germany. EM Hampel@psy.med.uni-muenchen.de NR 41 TC 132 Z9 133 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 1998 VL 55 IS 2 BP 193 EP 198 DI 10.1001/archneur.55.2.193 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA YX019 UT WOS:000071998200007 PM 9482361 ER PT J AU Kuller, L Fisher, L McClelland, R Fried, L Cushman, M Jackson, S Manolio, T AF Kuller, L Fisher, L McClelland, R Fried, L Cushman, M Jackson, S Manolio, T TI Differences in prevalence of and risk factors for subclinical vascular disease among black and white participants in the Cardiovascular Health Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cardiovascular disease; race; risk factors; subclinical disease ID LEFT-VENTRICULAR HYPERTROPHY; CORONARY HEART-DISEASE; BODY-MASS INDEX; OLDER ADULTS; CAROTID-ARTERY; SYSTOLIC HYPERTENSION; FOLLOW-UP; ATHEROSCLEROSIS; MORTALITY; WOMEN AB A composite measure of subclinical vascular disease has been developed in the Cardiovascular Health Study (CHS). In previous reports, we measured the prevalence of subclinical disease among the original 5201 participants in the CHS, the relationship of risk factors to subclinical disease, and the association of subclinical disease to clinical coronary heart disease. In 1992 to 1993 (year 4 of the study), a larger cohort of 424 black women and 248 black men was added to the study. In this study, we have compared the prevalence of subclinical disease among blacks and whites in the CHS and the association with cardiovascular risk factors. The prevalence of subclinical disease for all participants (aged greater than or equal to 65 years) was 41.3% for white women, 39.7% for black women, 41.9% for white men, and 43.7% for black men. The prevalence increased with age. The risk factor associations for subclinical disease were similar among blacks and whites. In multivariate analysis, age, systolic blood pressure, LDL cholesterol, smoking, and family history of myocardial infarction were independently associated with subclinical disease among both black and white women, while for white men, systolic blood pressure, use of antihypertensive medication, smoking, body mass index, and diastolic blood pressure (inverse) were related to subclinical disease. In black men, blood triglyceride level, use of. antihypertensive medications, and family history of myocardial infarction (inverse) were associated with subclinical disease. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Cardiovasc Hlth Study Coordinating Ctr, Seattle, WA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Vermont, Burlington, VT USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NHLBI, Bethesda, MD 20892 USA. RP Kuller, L (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM kuller+@pitt.edu FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85081, N01-HC-85079] NR 35 TC 33 Z9 34 U1 0 U2 0 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 FEB PY 1998 VL 18 IS 2 BP 283 EP 293 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YY243 UT WOS:000072127600019 PM 9484995 ER PT J AU Erlacher, L Ng, CK Ullrich, R Krieger, S Luyten, FP AF Erlacher, L Ng, CK Ullrich, R Krieger, S Luyten, FP TI Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TGF-BETA-SUPERFAMILY; SERINE/THREONINE KINASE RECEPTORS; HUMAN OSTEOGENIC PROTEIN-1; EXPLANT CULTURES; GROWTH-FACTOR; PROTEOGLYCANS; CHONDROCYTES; INVITRO; STIMULATION; PHENOTYPE AB Objective. To investigate the effects of the cartilage-derived morphogenetic proteins (CDMPs) in an in vitro cartilage explant model that mimics the chondrocytic response to matric depletion, and to demonstrate their presence in articular cartilage. Methods. Adult bovine articular cartilage and postmortem specimens from adult human donors with and without osteoarthritic (OA) lesions were stained by immunohistochemistry using polyclonal antibodies specific for CDMP-1 and CDMP-2. Extracts of bovine articular cartilage were analyzed by Western blotting for the presence of the CDMPs. Bovine articular cartilage explants were depleted of their matrix by trypsin digestion, followed by a 7-day culture period in a chemically defined serum-free basal medium (BM), with or without recombinant CDMPs 1 and 2. The metabolic activity of chondrocytes was measured by S-35-sulfate incorporation into macromolecules. Newly synthesized proteoglycans (PGs) were analyzed using Sephacryl S-500 HR gel chromatography. The expression levels of the messenger RNA (mRNA) for chondrogenic markers were investigated by Northern analysis. Results. CDMP-1 and CDMP-2 were detected in both bovine and human healthy and OA articular cartilage. Treatment of matrix-depleted cartilage explants with CDMPs 1 and 2 increased equally the incorporation of S-35-sulfate into PGs compared with tissue maintained in BM. Gel chromatography analysis indicated that aggrecan was the predominant PG species. Northern blot analysis showed that the expression of link protein, type II collagen, and aggrecan mRNA transcripts was not modulated by CDMP treatment. Conclusion. This study shows the presence of CDMP-1 and CDMP-2 in adult bovine and human articular cartilage. In addition, our in vitro data indicate that CDMPs 1 and 2 stimulate the metabolic activity of articular chondrocytes. Therefore, these signaling molecules may be contributing to the maintenance of the integrity of the joint surface. C1 NIDR, NIH, Bethesda, MD 20892 USA. Univ Vienna, Vienna, Austria. RP Erlacher, L (reprint author), Clin Internal Med 3, Dept Rheumatol, Wahringergurtel 18-20, A-1090 Vienna, Austria. NR 29 TC 83 Z9 91 U1 0 U2 0 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 FEB PY 1998 VL 41 IS 2 BP 263 EP 273 DI 10.1002/1529-0131(199802)41:2<263::AID-ART10>3.0.CO;2-5 PG 11 WC Rheumatology SC Rheumatology GA YW210 UT WOS:000071909500009 PM 9485084 ER PT J AU Davis, JC Austin, H Boumpas, D Fleisher, TA Yarboro, C Larson, A Balow, J Klippel, JH Scott, D AF Davis, JC Austin, H Boumpas, D Fleisher, TA Yarboro, C Larson, A Balow, J Klippel, JH Scott, D TI A pilot study of 2-chloro-2 '-deoxyadenosine in the treatment of systemic lupus erythematosus-associated glomerulonephritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PROGRESSIVE MULTIPLE-SCLEROSIS; PULSE CYCLOPHOSPHAMIDE; CONTROLLED TRIAL; DEOXYCYTIDINE KINASE; RHEUMATOID-ARTHRITIS; CLADRIBINE; 2-CHLORODEOXYADENOSINE; THERAPY; NEPHRITIS AB Objective. To determine the safety and tolerability, as well as the clinical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomerulonephritis. Methods. In a phase I study, 12 patients with proliferative lupus nephritis received 2-CdA either in weekly escalating intravenous treatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7). Safety, renal improvement, and immunologic effects were evaluated for 12 months. Results. Patients treated with 2-CdA showed peripheral lymphocyte depletion without a significant reduction in neutrophil, monocyte, or platelet numbers or hematocrit levels. Naive and memory T cells were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with significant decreases in serum immunoglobulin levels. Continuous infusion induced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0%), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinary dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%), Several infections occurred; these responded to standard antibiotic therapy. Conclusion. In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations and may be efficacious in selected patients with lupus nephritis when administered as a continuous infusion. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. RP Davis, JC (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9S205, Bethesda, MD 20892 USA. NR 45 TC 56 Z9 57 U1 0 U2 0 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 FEB PY 1998 VL 41 IS 2 BP 335 EP 343 DI 10.1002/1529-0131(199802)41:2<335::AID-ART18>3.0.CO;2-O PG 9 WC Rheumatology SC Rheumatology GA YW210 UT WOS:000071909500017 PM 9485092 ER PT J AU Hirsch, R Fernandes, RJ Pillemer, SR Hochberg, MC Lane, NE Altman, RD Bloch, DA Knowler, WC Bennett, PH AF Hirsch, R Fernandes, RJ Pillemer, SR Hochberg, MC Lane, NE Altman, RD Bloch, DA Knowler, WC Bennett, PH TI Hip osteoarthritis prevalence estimates by three radiographic scoring systems SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OSTEO-ARTHRITIS; RELIABILITY; POPULATION; HAND; PROGRESSION; INDEXES; WOMEN; JOINT AB Objective. To estimate and compare the age- and sex-specific prevalence of radiographic hip osteoarthritis (RHOA) in a population-based study of the Pima Indians, using 3 atlas-based methods for assessing features of RHOA. Methods. Pelvic radiographs from 755 Pima Indians age greater than or equal to 45 years enrolled in a population-based study were read using the Kellgren/Lawrence (K/L) grading scale (grade 0-4) and 2 validated individual-radiographic-features (IRF) scales (grades 0-3 for narrowing and osteophytes), Results. The age- and sex-specific prevalence of RHOA among Pima Indians assessed using the K/L scale was <10% in all age and sex groups. The prevalence of grade 12 osteophytes assessed using the 2 IRF scales were similar to each other in all age and sex groups. However, differences between the 2 IRF scoring systems were found for the prevalence of grade greater than or equal to 2 joint space narrowing. Conclusion. Pima Indians have an age-and sex-specific prevalence of RHOA similar to that found in the US population. Our finding of different joint space narrowing prevalence by the 2 IRF grading scales supports the use of the same atlas-based case definitions for determining disease prevalence for comparative studies. C1 NIAMSD, Bethesda, MD 20892 USA. NIDDKD, Phoenix, AZ 85016 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Vet Affairs Med Ctr, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Miami, Sch Med, Miami, FL USA. Stanford Univ, Stanford, CA 94305 USA. RP Hirsch, R (reprint author), Natl Arthrit & Musculoskeletal & Skin Dis Informa, 1 AMS Circle, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR-43584] NR 29 TC 27 Z9 27 U1 0 U2 0 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 FEB PY 1998 VL 41 IS 2 BP 361 EP 368 DI 10.1002/1529-0131(199802)41:2<361::AID-ART21>3.0.CO;2-2 PG 8 WC Rheumatology SC Rheumatology GA YW210 UT WOS:000071909500020 PM 9485095 ER PT J AU Torrey, EF Miller, J AF Torrey, EF Miller, J TI Season of birth and schizophrenia in Tasmania SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter C1 Natl Inst Mental Hlth Neurosci Ctr, Washington, DC USA. RP Torrey, EF (reprint author), Natl Inst Mental Hlth Neurosci Ctr, Washington, DC USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD FEB PY 1998 VL 32 IS 1 BP 137 EP 137 PG 1 WC Psychiatry SC Psychiatry GA ZB369 UT WOS:000072465000024 ER PT J AU Kakuta, Y Pedersen, LC Chae, K Song, WC Leblanc, D London, R Carter, CW Negishi, M AF Kakuta, Y Pedersen, LC Chae, K Song, WC Leblanc, D London, R Carter, CW Negishi, M TI Mouse steroid sulfotransferases - Substrate specificity and preliminary x-ray crystallographic analysis SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE steroid sulfotransferase; bacterial expression; substrate specificity; diethylstilbestrol; stereospecificity; crystallization ID ESTROGEN SULFOTRANSFERASE; MOLECULAR-CLONING; LIVER; DIETHYLSTILBESTROL; ENZYMES; MICE; FORM AB Three mouse cytosolic sulfotransferases were expressed in Escherichia coli cells in order to study their substrate specificities toward natural as well as synthetic steroid hormones, The K-m and V-max values confirmed the high substrate specificity of estrogen and hydroxysteroid sulfotransferases toward estradiol and dehydroepiandrosterone, respectively. In sharp contrast, the synthetic estrogen diethylstilbestrol was metabolized efficiently by both enzymes to its disulfate ester. These sulfotransferases display highly stereospecific sulfotransferase activity for sulfating only the trans-isomer of diethylstilbestrol. Crystals suitable for high-resolution structure determination of estrogen sulfotransferase were grown with polyethylene glycol. The crystals belong to the orthorhombic space group P2(1)2(1)2, and diffracted to 2.5 Angstrom. (C) 1998 Elsevier Science Inc. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27541 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 20 TC 24 Z9 27 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 1 PY 1998 VL 55 IS 3 BP 313 EP 317 DI 10.1016/S0006-2952(97)00465-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM223 UT WOS:000071042100010 PM 9484797 ER PT J AU Mitchell, DC Litman, BJ AF Mitchell, DC Litman, BJ TI Molecular order and dynamics in bilayers consisting of highly polyunsaturated phospholipids SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE ANISOTROPY DECAY; CHAIN PHOSPHATIDYLCHOLINE VESICLES; ACYL-CHAIN; ORIENTATIONAL ORDER; POLARIZED FLUORESCENCE; MEMBRANE SUSPENSIONS; ROTATIONAL DIFFUSION; LIPID-MEMBRANES; CHOLESTEROL; DEPOLARIZATION AB The time-resolved fluorescence emission and decay of fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to characterize equilibrium and dynamic bilayer structural properties of symmetrically substituted phosphatidylcholines (PCs) with acyl chains containing no, one, four, or six double bonds and mixed-chain phosphatidylcholines with a saturated sn-l chain and one, four, or six double bonds in the sn-2 chain. Both the Brownian rotational diffusion (BRD) model and the wobble-in-cone model were fit to all differential polarization data, and the descriptions of the data provided by the BRD model were found to be statistically superior. Global analysis of differential polarization data revealed two statistically equivalent solutions. The solution corresponding to a bimodal orientational distribution function, f(theta), was selected based on the effects of temperature on f(theta) and previous measurements on fixed, oriented bilayers. The overall equilibrium acyl chain order in these bilayers was analyzed by comparing the orientational probability distribution for DPH, f(theta) sin theta, with a random orientational distribution. Orientational order decreased and probe dynamics increased in mixed-chain species as the unsaturation of the sn-2 chain was increased. The degree of orientational order dropped dramatically in the dipolyunsaturated species compared with the mixed-chain phosphatidylcholines, which contained a polyunsaturated sn-2 chain. In terms of both orientational order and probe dynamics, the differences between the highly polyunsaturated species and the monounsaturated species were much greater than the differences between the monounsaturated species and a disaturated PC. C1 NIAAA, Sect Fluorescence Studies, Lab Membrane Biophys & Biochem, NIH, Rockville, MD 20852 USA. RP Mitchell, DC (reprint author), NIAAA, Sect Fluorescence Studies, Lab Membrane Biophys & Biochem, NIH, Room 55,Flow Bldg,12501 Washington Ave, Rockville, MD 20852 USA. NR 49 TC 92 Z9 93 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP 879 EP 891 PN 1 PG 13 WC Biophysics SC Biophysics GA ZL047 UT WOS:000073393500019 PM 9533699 ER PT J AU Adachi, M Iwasa, KH AF Adachi, M Iwasa, KH TI Pressure insensitivity of outer hair cell motility SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A86 EP A86 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400490 ER PT J AU Alarcon, JM Rojas, E AF Alarcon, JM Rojas, E TI Alzheimer's disease amyloid beta-peptide [1-40] induces an increase in Na+ and Ca2+ permeabilin in a human astrocytoma cell line SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Chile, Fac Med, Dept Physiol Biophys, Santiago, Chile. NIDDK, NIH, LCBB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A389 EP A389 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402247 ER PT J AU Bahar, I Ptitsyn, OB Erman, B Jernigan, RL AF Bahar, I Ptitsyn, OB Erman, B Jernigan, RL TI Protein dynamics for global motions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Expt & Computat Biol, Mol Struct Sect, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A276 EP A276 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401597 ER PT J AU Balagopalakrishna, C Horsky, J Nagababu, E Manoharan, PT Abugo, OO Rifkind, JM AF Balagopalakrishna, C Horsky, J Nagababu, E Manoharan, PT Abugo, OO Rifkind, JM TI The formation of a thiyl radical during hemoglobin autoxidation: An electron transfer process involving beta-93 cysteine residue. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Cellular & Mol Biol Lab, Mol Dynam Sect, Baltimore, MD 21224 USA. RI Horsky, Jiri/G-3442-2014 NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A251 EP A251 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401450 ER PT J AU Bax, A Tjandra, N Ottiger, M Marquardt, J Cornilescu, G Hu, JS AF Bax, A Tjandra, N Ottiger, M Marquardt, J Cornilescu, G Hu, JS TI A new approach to the study of biomolecular structure by NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Cornilescu, Gabriel/H-3113-2011 OI Cornilescu, Gabriel/0000-0002-1204-8904 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A137 EP A137 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400785 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI From sequence to structure: The role of bioinformatics in biological discovery. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A117 EP A117 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400674 ER PT J AU Beuron, F Belnap, D Booy, FP Maurizi, M Steven, AC AF Beuron, F Belnap, D Booy, FP Maurizi, M Steven, AC TI The energy-dependent ClpAP protease complex: A three-dimensional model derived from cryo-electron microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NIAMS, LSBR, Bethesda, MD 20892 USA. NIH, NCI, LCB, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A254 EP A254 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401467 ER PT J AU Bose, S Hendler, RW AF Bose, S Hendler, RW TI Influence of light energy on proton-pumping by the fast and slow M intermediates of the bacteriorhodopsin (BR) photocycle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A292 EP A292 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401687 ER PT J AU Bradrick, TD Galdzicki, Z Jones, C Ehrenstein, G AF Bradrick, TD Galdzicki, Z Jones, C Ehrenstein, G TI Choline leakage from synaptosomes prepared from post-mortem brains of Alzheimer's disease patients SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Biophys Sect, Bethesda, MD 20892 USA. NIA, NIH, Neurosci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A91 EP A91 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400520 ER PT J AU Chanturiya, A Zimmerberg, J AF Chanturiya, A Zimmerberg, J TI Two dimensional computer simulation of divalent ion induced bilayer fusion. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. AV Palladin Biochem Inst, Dept Neurochem, Kiev, Ukraine. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A141 EP A141 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400808 ER PT J AU Chen, J Zeldin, DC Rosenberg, RL AF Chen, J Zeldin, DC Rosenberg, RL TI Inhibition of cardiac L-type calcium channels by epoxyeicosatrienoic acids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Physiol, Chapel Hill, NC 27599 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A105 EP A105 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400606 ER PT J AU Chen, YD Sen, A Chalovich, JM AF Chen, YD Sen, A Chalovich, JM TI Kinetics of binding of caldesmon and myosin subfragment-1 to actin: Differentiation between the pure competitive and the mosaic multiple binding models SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. E Carolina Univ, Sch Med, Dept Biochem, Greenville, NC 27858 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A151 EP A151 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400861 ER PT J AU Chen-Izu, Y Spangler, RA Nicholson, BJ AF Chen-Izu, Y Spangler, RA Nicholson, BJ TI A two opposing gates model for the asymmetric voltage-gating of gap junction channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. SUNY Buffalo, Dept Biophys, Buffalo, NY 14260 USA. SUNY Buffalo, Dept Biol, Buffalo, NY 14260 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A317 EP A317 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401835 ER PT J AU Cheng, HP Song, LS Lakatta, EG Stern, MD AF Cheng, HP Song, LS Lakatta, EG Stern, MD TI How and how many ryanodine receptors are activated during a calcium spark? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, LCS, GRC, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A118 EP A118 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400680 ER PT J AU Cheng, HP Song, LS Shirokova, N Lakatta, EG Stern, MD Rios, E AF Cheng, HP Song, LS Shirokova, N Lakatta, EG Stern, MD Rios, E TI Automated, objective detection and measurement of Ca2+ sparks in confocal images. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, LCS, NIH, Baltimore, MD 21224 USA. Rush Univ, Chicago, IL 60612 USA. RI Song, Long-Sheng/D-5899-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A269 EP A269 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401557 ER PT J AU Chernomordik, LV Leikina, EA Frolov, V Zimmerberg, J AF Chernomordik, LV Leikina, EA Frolov, V Zimmerberg, J TI Structural intermediates in influenza hemagglutinin-mediated fusion. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A4 EP A4 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400018 ER PT J AU Chik, JK Rau, DC Parsegian, VA AF Chik, JK Rau, DC Parsegian, VA TI The transition between two water associated states of poly-l-proline SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, ODIR, NIH, Bethesda, MD 20892 USA. NICHD, LPSB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A279 EP A279 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401613 ER PT J AU Coorssen, JR Blank, PS Tahara, M Zimmerberg, J AF Coorssen, JR Blank, PS Tahara, M Zimmerberg, J TI SNARE complex dissociation does not initiate membrane fusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A95 EP A95 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400546 ER PT J AU Durell, SR Hao, Y Guy, HR AF Durell, SR Hao, Y Guy, HR TI Structural models of K+ channels: Latest update SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, LECB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A127 EP A127 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400730 ER PT J AU Gawrisch, K Holte, LL Koenig, BW Huster, D AF Gawrisch, K Holte, LL Koenig, BW Huster, D TI Biophysical properties of polyunsaturated membranes with docosahexaenoyl hydrocarbon chains SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A12 EP A12 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400066 ER PT J AU Hager, GL Htun, H Barsony, J Smith, C Fragoso, G AF Hager, GL Htun, H Barsony, J Smith, C Fragoso, G TI Interactions of steroid receptors with the chromatin fiber SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Lab Receptor Biol & Gene Express, DBS, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A33 EP A33 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400179 ER PT J AU Hammer, JA Wu, X Wei, Q Bowers, B Kocher, B AF Hammer, JA Wu, X Wei, Q Bowers, B Kocher, B TI Myosin V function in vivo. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A6 EP A6 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400028 ER PT J AU Hansen, PL Miao, L Ipsen, JH AF Hansen, PL Miao, L Ipsen, JH TI Fluid lipid-bilayers: Intermonolayer coupling and its thermodynamic manifestation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A312 EP A312 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401806 ER PT J AU Hendler, RW Bose, S AF Hendler, RW Bose, S TI Influence of light energy on voltage generation by fast and slow components of the bacteriorhodopsin (BR) photocycle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A292 EP A292 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401690 ER PT J AU Hess, ST Webb, WW AF Hess, ST Webb, WW TI Measurement of fluorescence signal of a voltage-sensitive dye using two-photon excitation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Cornell Univ, NIH Dev Resource Biophys Imaging & Optoelect, Ithaca, NY 14853 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A201 EP A201 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401159 ER PT J AU Hinterdorfer, P Raab, A Badt, D Smith-Gill, SJ Schindler, H AF Hinterdorfer, P Raab, A Badt, D Smith-Gill, SJ Schindler, H TI Force spectroscopy of antibody-antigen recognition measured by scanning force microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, Inst Biophys, A-4040 Linz, Austria. NCI, Genet Lab, NIH, Bethesda, MD 20982 USA. RI Hinterdorfer, Peter/C-4235-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A186 EP A186 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401071 ER PT J AU Hofrichter, J Thompson, PA Munoz, V Eaton, WA AF Hofrichter, J Thompson, PA Munoz, V Eaton, WA TI Folding dynamics of an alpha helix and a beta hairpin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A3 EP A3 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400016 ER PT J AU Holte, LL Koenig, BW Strey, HH Gawrisch, K AF Holte, LL Koenig, BW Strey, HH Gawrisch, K TI Structure and dynamics of the docosahexaenoic acid chain in bilayers studied by NMR and X-ray diffraction. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. NIH, Struct Biol Lab, DCRT, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A371 EP A371 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402141 ER PT J AU Huster, D Arnold, K Gawrisch, K AF Huster, D Arnold, K Gawrisch, K TI Noesy NMR crosspeaks between lipids as a tool to study lateral lipid organization in membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Univ Leipzig, Inst Med Phys & Biophys, D-04103 Leipzig, Germany. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A203 EP A203 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401173 ER PT J AU Iwasa, KH AF Iwasa, KH TI Electromechanical coupling in the outer hair cell: a statistical thermodynamic examination SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A86 EP A86 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400493 ER PT J AU Jin, AJ Mudd, CP Gershfeld, NL AF Jin, AJ Mudd, CP Gershfeld, NL TI Unusual structural transformations in large unilamellar vesicle suspensions of DMPC by Cp lambda-1 calorimetry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A312 EP A312 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401803 ER PT J AU Kinard, TA de Vries, G Sherman, A Satin, LS AF Kinard, TA de Vries, G Sherman, A Satin, LS TI Single B-cells from mouse pancreatic islets exhibit a fast form of bursting which does not require free [Ca] accumulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIDDK, Math Res Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A101 EP A101 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400582 ER PT J AU Kinsella, JL Froehlich, JP AF Kinsella, JL Froehlich, JP TI Na+-H+ exchanger: H+ modifier site activation involves slow conformational changes in an oligomer. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, GRC, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A194 EP A194 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401116 ER PT J AU Koenig, BW Strey, HH Gawrisch, K AF Koenig, BW Strey, HH Gawrisch, K TI Effect of lipid acyl chain length and degree of unsaturation on lateral compressibility of membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A371 EP A371 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402143 ER PT J AU Lane, CJ Yang, H Muller-Borer, BJ Zeldin, DC Cascio, WE AF Lane, CJ Yang, H Muller-Borer, BJ Zeldin, DC Cascio, WE TI Disparate effects of 11,12-epoxyeicosatrienoic acid (11,12-EET) and arachidonic acid (AA) in perfused and ischemic myocardium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, NIH, RTP, Res Triangle Pk, NC USA. NR 0 TC 2 Z9 2 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 FEB PY 1998 VL 74 IS 2 BP A161 EP A161 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400922 ER PT J AU Levin, IW McCarthy, PK Kidder, LH Lewis, EN AF Levin, IW McCarthy, PK Kidder, LH Lewis, EN TI Biomembrane and cellular domains: Infrared spectroscopic and imaging studies SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A7 EP A7 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400035 ER PT J AU Liu, XB Rojas, E Ambudkar, IS AF Liu, XB Rojas, E Ambudkar, IS TI Carbachol-activated K-CA currents are initiated by IP3-induced CA(2+) release and sustained by store-operated Ca2+ influx, in HSG cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A377 EP A377 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402181 ER PT J AU Lockwich, T Arispe, N Chauthaiwale, J Ambudkar, SV Ambudkar, IS AF Lockwich, T Arispe, N Chauthaiwale, J Ambudkar, SV Ambudkar, IS TI Functional reconstitution of a putative CA(2+) channel from salivary gland plasma membrane vesicles. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIDR, NIH, Bethesda, MD 20892 USA. USUHS, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A377 EP A377 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402180 ER PT J AU Luo, G Horowits, R AF Luo, G Horowits, R TI Protein binding properties of N-RAP, a nebulin-related protein of striated muscle SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A47 EP A47 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400257 ER PT J AU Markovic, I Pulyaeva, E Leikina, E Sokoloff, A Chernomordik, LV AF Markovic, I Pulyaeva, E Leikina, E Sokoloff, A Chernomordik, LV TI Oligomeric structure of baculovirus GP64 in membrane fusion mediated by this protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, LCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A94 EP A94 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400541 ER PT J AU McCarthy, PK Huang, CH Levin, IW AF McCarthy, PK Huang, CH Levin, IW TI Microdomain formation in monounsaturated phosphatidylcholine prayers: Vibrational spectroscopic studies SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Dept Biochem, Charlottesville, VA 22908 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A314 EP A314 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401816 ER PT J AU Mears, D Zimliki, C Harper, J Daly, JW Rojas, E Atwater, I AF Mears, D Zimliki, C Harper, J Daly, JW Rojas, E Atwater, I TI Loperamide activates calcium release-activated current in pancreatic B-cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, LCBB, Bethesda, MD 20892 USA. NIDDK, NIH, LBC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A390 EP A390 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402256 ER PT J AU Mejia-Alvarez, R Kettlun, C Rios, E Stern, M Fill, M AF Mejia-Alvarez, R Kettlun, C Rios, E Stern, M Fill, M TI Unitary calcium currents through cardiac ryanodine receptors under physiological conditions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Loyola Univ, Maywood, IL 60153 USA. Univ Chile, Santiago, Chile. Rush Univ, Chicago, IL 60612 USA. NIH, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 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 FEB PY 1998 VL 74 IS 2 BP A58 EP A58 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400328 ER PT J AU Munoz, V Thompson, PA Henry, ER Hofrichter, J Eaton, WA AF Munoz, V Thompson, PA Henry, ER Hofrichter, J Eaton, WA TI Folding dynamics of a beta-hairpin studied by laser temperature jump and kinetic modelling. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A175 EP A175 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401008 ER PT J AU Nossal, R AF Nossal, R TI A thermodynamic model for clathrin basket assembly. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A95 EP A95 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400542 ER PT J AU Nussinov, R AF Nussinov, R TI Structural motifs at protein-protein interfaces. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt Computat Biol, SAIC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Ramat Aviv, Israel. NR 5 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A117 EP A117 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400671 ER PT J AU Podgornik, R Parsegian, VA AF Podgornik, R Parsegian, VA TI Charge fluctuation forces between stiff polyelectrolytes in salt solution: Pairwise summability re-examined SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 3 Z9 3 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 FEB PY 1998 VL 74 IS 2 BP A177 EP A177 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401021 ER PT J AU Rios, E Stern, MD Gonzalez, A Shirokova, N AF Rios, E Stern, MD Gonzalez, A Shirokova, N TI Release flux underlying Ca2+ sparks in frog skeletal muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. NIA, Baltimore, MD 21214 USA. NR 0 TC 3 Z9 3 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 FEB PY 1998 VL 74 IS 2 BP A234 EP A234 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401351 ER PT J AU Rostovtseva, TK Bezrukov, SM AF Rostovtseva, TK Bezrukov, SM TI ATP transport through a single VDAC channel, studied by noise analysis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20982 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A383 EP A383 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402214 ER PT J AU Rostovtseva, TK Colombini, M Bezrukov, SM AF Rostovtseva, TK Colombini, M Bezrukov, SM TI Studies of ATP flow through the mitochondrial channel, VDAC. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20982 USA. Univ Maryland, Dept Zool, College Pk, MD 20742 USA. RI Colombini, Marco/A-1540-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A14 EP A14 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400073 ER PT J AU Rotberg, AV O'Hara, PB Dosemeci, A Albers, RW AF Rotberg, AV O'Hara, PB Dosemeci, A Albers, RW TI Calmodulin trapping and autophosphorylation in calcium/calmodulin dependent protein kinase II. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Amherst Coll, Dept Chem, Amherst, MA 01002 USA. NINDS, Lab Neurobiol & Neurochem, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A379 EP A379 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402192 ER PT J AU Sham, JSK Song, LS Deng, LH Chen-Izu, Y Stern, MD Lakatta, EG Cheng, HP AF Sham, JSK Song, LS Deng, LH Chen-Izu, Y Stern, MD Lakatta, EG Cheng, HP TI Local Ca2+ release is determined by the first openings of ryanodine receptors (RyR). SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. NIA, NIH, GRC, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A247 EP A247 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401429 ER PT J AU She, M Frisbie, S Trimble, DC Yu, LC Chalovich, JM AF She, M Frisbie, S Trimble, DC Yu, LC Chalovich, JM TI Characterization of Tn exchange in myofibrils and solution. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 E Carolina Univ, Sch Med, Greenville, NC 27834 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A346 EP A346 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401998 ER PT J AU Sidorova, NY Rau, DC AF Sidorova, NY Rau, DC TI The number of waters released accompanying specific EcoRI binding is temperature dependent. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A69 EP A69 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400391 ER PT J AU Song, LS Sham, JSK Lakatta, EG Cheng, HP AF Song, LS Sham, JSK Lakatta, EG Cheng, HP TI Spatially and temporally resolved SR calcium release function in cardiac myocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Cardiovasc Sci Lab, GRC, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A247 EP A247 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401426 ER PT J AU Stanley, EF Sheng, ZH Mirotznik, RR AF Stanley, EF Sheng, ZH Mirotznik, RR TI Rapid inactivation of presynaptic calcium channels via a G protein pathway SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, Synapt Mechanisms Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A139 EP A139 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400799 ER PT J AU Strey, HH Rau, DC AF Strey, HH Rau, DC TI Forces between alpha-helices SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, LPSB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A173 EP A173 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400998 ER PT J AU Sudhakar, K Henderson, LE Casas-Finet, JR De Guzman, RN Summers, MF AF Sudhakar, K Henderson, LE Casas-Finet, JR De Guzman, RN Summers, MF TI Thermodynamic study of MMTV nucleocapsid (NC) protein-nucleic acid binding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, AVP, SAIC, Frederick, MD 21702 USA. UMBC, HHMI, Baltimore, MD 21250 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A70 EP A70 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400399 ER PT J AU Thompson, PA Munoz, V Eaton, WA Hofrichter, J AF Thompson, PA Munoz, V Eaton, WA Hofrichter, J TI Dynamics of the helix-coil transition. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A278 EP A278 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401610 ER PT J AU Tozer, K Mirotznik, RR Stanley, EF AF Tozer, K Mirotznik, RR Stanley, EF TI Localization of potassium channel proteins to a presynaptic nerve terminal SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, Synapt Mechanisms Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A109 EP A109 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400627 ER PT J AU Tycko, R Long, HW Weliky, DP Bennett, AE AF Tycko, R Long, HW Weliky, DP Bennett, AE TI Conformational distributions of disordered biopolymers from solid state NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A137 EP A137 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400787 ER PT J AU Urbaneja, MA Kane, BP Henderson, IE Casas-Finet, JR AF Urbaneja, MA Kane, BP Henderson, IE Casas-Finet, JR TI Nucleic acid binding properties of the SIV nucleocapsid (NC) protein p8. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, AVP, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A241 EP A241 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401394 ER PT J AU Wang, Z Jiang, H Yang, ZQ Chacko, S AF Wang, Z Jiang, H Yang, ZQ Chacko, S TI Actin filament velocity over myosin heads in the in vitro motility assay is mediated by tethering of actin to myosin by smooth muscle caldesmon. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Penn, Dept Pathobiol, Philadelphia, PA 19104 USA. Univ Penn, Div Urol, Philadelphia, PA 19104 USA. NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A39 EP A39 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400212 ER PT J AU Xie, L Schoenberg, M AF Xie, L Schoenberg, M TI Is myosin tethered to F-actin with EDC a good model for myosin interacting with actin at very high concentration? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, LPB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A263 EP A263 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401522 ER PT J AU Xu, S Gu, J Frisbie, S Yu, LC AF Xu, S Gu, J Frisbie, S Yu, LC TI Structural changes in rigor (nucleotide-free) cross-bridges induced by the addition of MgADP. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 FEB PY 1998 VL 74 IS 2 BP A363 EP A363 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445402099 ER PT J AU Xu, S Yu, LC AF Xu, S Yu, LC TI Nucleotide dependence for forming helices by myosin heads in rabbit skinned psoas muscle fibers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 74 IS 2 BP A22 EP A22 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400115 ER PT J AU Yau, WM Steinbach, PJ Wimley, WC White, SH Gawrisch, K AF Yau, WM Steinbach, PJ Wimley, WC White, SH Gawrisch, K TI Indole and N-methyl indole orientation in lipid bilayers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NIH, DCRT, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Physiol Biophys, Irvine, CA 92697 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1998 VL 74 IS 2 BP A303 EP A303 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445401752 ER PT J AU Yeager, M Wilson-Kubalek, EM Weiner, SG Brown, PO Rein, A AF Yeager, M Wilson-Kubalek, EM Weiner, SG Brown, PO Rein, A TI Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: Implications for retroviral assembly mechanisms SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Scripps Res Inst, Dept Cell Biol, La Jolla, CA USA. NCI, Frederick Canc Res Facil, ABL Basic Res Program, Frederick, MD USA. Stanford Univ, Med Ctr, Howard Hughes Med Inst, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A72 EP A72 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400406 ER PT J AU Zhang, JQ Weisberg, A Horowits, R AF Zhang, JQ Weisberg, A Horowits, R TI Visualization of nebulin-F-actin complexes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 FEB PY 1998 VL 74 IS 2 BP A46 EP A46 PN 2 PG 1 WC Biophysics SC Biophysics GA ZL549 UT WOS:000073445400256 ER PT J AU Rosenberg, HF AF Rosenberg, HF TI Isolation of recombinant secretory proteins by limited induction and quantitative harvest SO BIOTECHNIQUES LA English DT Article ID EOSINOPHIL-DERIVED NEUROTOXIN; RIBONUCLEASE GENE FAMILY; ESCHERICHIA-COLI; CATIONIC PROTEIN C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N104,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 18 Z9 19 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 1998 VL 24 IS 2 BP 188 EP + PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YW209 UT WOS:000071909400003 PM 9494711 ER PT J AU Leonard, JT Grace, MB Buzard, GS Mullen, MJ Barbagallo, CB AF Leonard, JT Grace, MB Buzard, GS Mullen, MJ Barbagallo, CB TI Preparation of PCR products for DNA sequencing SO BIOTECHNIQUES LA English DT Article ID PURIFICATION AB We demonstrate that routine PCR product analytical agarose gels can also serve as preparative gels for quick DNA template purification before sequencing. The band of interest is excised, placed into a Gel Nebulizer(TM) inside a Micropure(TM) separator and rapidly purified in a single centrifugation step. Gel-purified PCR product, suitable for manual and automated sequencing, is delivered within 10 min. C1 Millipore Corp, Mol Biol Grp, Analyt Prod Div, Danvers, MA 01923 USA. NIMH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Leonard, JT (reprint author), Millipore Corp, Mol Biol Grp, Analyt Prod Div, 17 Cherry Hill Dr, Danvers, MA 01923 USA. NR 5 TC 7 Z9 8 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 1998 VL 24 IS 2 BP 314 EP 317 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YW209 UT WOS:000071909400027 PM 9494735 ER PT J AU Gubina, E Rinaudo, MS Szallasi, Z Blumberg, PM Mufson, RA AF Gubina, E Rinaudo, MS Szallasi, Z Blumberg, PM Mufson, RA TI Overexpression of protein kinase C isoform epsilon but not delta in human interleukin-3-dependent cells suppresses apoptosis and induces bcl-2 expression SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; NIH 3T3 CELLS; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; SIGNAL TRANSDUCTION; MESSENGER-RNA; ACTIVATION; RECEPTOR; INDUCTION; SURVIVAL AB Hematopoietic progenitor cells die by apoptosis after removal of the appropriate colony-stimulating factor (CSF). Recent pharmacologic data have implicated protein kinase C (PKC) in the suppression of apoptosis in interleukin-3 (IL-3) and granulocyte-macrophage (GM)-CSF-dependent human myeloid cells. Because IL-3 and GM-CSF induce increases in diacylglycerol without mobilizing intracellular Ca++, it seemed that one of the novel Ca++ independent isoforms of PKC was involved. We report here that overexpression of PKC epsilon in factor-dependent human TF-1 cells extends cell survival in the absence of cytokine. Overexpression of PKC delta does not have this effect. By 72 to 96 hours after cytokine withdrawal, the PKC epsilon transfectants remain distributed in all phases of the cell cycle, as shown by fluorescence-activated cell sorting (FAGS) analysis, while little intact cellular DNA is detectable in vector or PKC delta transfectants. PKC epsilon induces bcl-2 protein expression fivefold to sixfold over the levels in empty vector transfectants, whereas the levels in PKC delta transfectants are similar to those in vector controls. (C) 1998 by The American Society of Hematology. C1 Amer Red Cross, Jerome H Holland Lab, Dept Immunol, Rockville, MD 20855 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. RP Mufson, RA (reprint author), Amer Red Cross, Jerome H Holland Lab, Dept Immunol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NCI NIH HHS [CA53609-06] NR 40 TC 110 Z9 111 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1998 VL 91 IS 3 BP 823 EP 829 PG 7 WC Hematology SC Hematology GA YT777 UT WOS:000071644000013 PM 9446642 ER PT J AU Weichold, FF Zella, D Barabitskaja, O Maciejewski, JP Dunn, DE Sloand, EM Young, NS AF Weichold, FF Zella, D Barabitskaja, O Maciejewski, JP Dunn, DE Sloand, EM Young, NS TI Neither human immunodeficiency virus-1 (HIV-1) nor HIV-2 infects most-primitive human hematopoietic stem cells as assessed in long-term bone marrow cultures SO BLOOD LA English DT Article ID BLOOD MONONUCLEAR-CELLS; PROGENITOR CELLS; IN-VITRO; ENVELOPE GLYCOPROTEIN; PERIPHERAL-BLOOD; INVITRO GROWTH; TYPE-1 HIV-1; HIV-1-INFECTED SUBJECTS; MAJOR RESERVOIR; REPLICATION AB Attempts to clarify the pathophysiology of human immunodeficiency virus (HIV)-mediated bone marrow (BM) dysfunction have yielded inconsistent results regarding the susceptibility of BM progenitors to the viral infection. To specifically address this question, we exposed highly purified subpopulations of human BM progenitor cells to various HIV-1 and HIV-2 strains and assessed (pro)viral gene presence and expression in more-committed (CD34(+)CD38(+)) as well as most-primitive (CD34(+)CD38(-)) cells in long-term BM cultures. Quantitative analysis of long-term culture-initiating cells (LTCIC) failed to demonstrate adverse effects of exposing hematopoietic stem cells to HIV. Our results show that HIV-2, similar to HIV-1, does not infect hematopoietic stem cells in vitro with any significant frequency and infected cells are not present within LTCICs. Cytofluorometric analysis of CD34(+) cells for surface molecules that facilitate HIV entry was consistent with the functional assay in that expression of virus receptors was predominantly on the more-committed subsets of BM progenitors. The failure to detect productive or latent HIV in the most-primitive human BM progenitor and stem cells has important implications for future therapeutic strategies, including those dealing with transduction of these cells with protective genes as a treatment modality for AIDS. (C) 1998 by The American Society of Hematology. C1 Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Weichold, FF (reprint author), Univ Maryland, Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. NR 57 TC 44 Z9 45 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 FEB 1 PY 1998 VL 91 IS 3 BP 907 EP 915 PG 9 WC Hematology SC Hematology GA YT777 UT WOS:000071644000022 PM 9446651 ER PT J AU Fiorelli, V Gendelman, R Sirianni, MC Chang, HK Colombini, S Markham, PD Monini, P Sonnabend, J Pintus, A Gallo, RC Ensoli, B AF Fiorelli, V Gendelman, R Sirianni, MC Chang, HK Colombini, S Markham, PD Monini, P Sonnabend, J Pintus, A Gallo, RC Ensoli, B TI gamma-interferon produced by CD8(+) T cells infiltrating Kaposi's sarcoma induces spindle cells with angiogenic phenotype and synergy with human immunodeficiency virus-1 tat protein: An immune response to human herpesvirus-8 infection? SO BLOOD LA English DT Review ID FIBROBLAST GROWTH-FACTOR; VASCULAR ENDOTHELIAL-CELLS; BLOOD MONONUCLEAR-CELLS; YOUNG HOMOSEXUAL MEN; PERIPHERAL-BLOOD; DNA-SEQUENCES; GENE-EXPRESSION; LYMPHOCYTES-T; ALVEOLAR MACROPHAGES; ADHESION MOLECULE-1 AB Kaposi's sarcoma (KS) is an angioproliferative disease associated with infection by the human herpesvirus-8 (HHV-8). HHV-8 possesses genes including homologs of interleukin-8 (IL-8) receptor, Bcl-2, and cyclin D, which can potentially transform the host cell. However, the expression of these genes in KS tissues is very low or undetectable and HHV-8 does not seem to transform human cells in vitro. In addition, KS may not be a true cancer at least in the early stage. This indicated that besides its transforming potential, HHV-8 may act in KS pathogenesis also through indirect mechanisms. Evidence suggests that KS may start as an inflammatory-angiogenic lesion mediated by cytokines. However, little is known on the nature of the inflammatory cell infiltration present in KS, on the type of cytokines produced and on their role in KS, and whether this correlates with the presence of HHV-8. Here we show that both acquired immunodeficiency syndrome (AIDS)-KS and classical KS (C-KS) lesions are infiltrated by CD8(+) T cells and CD14(+)/CD68(+) monocytes-macrophages producing high levels of gamma-interferon (gamma IFN) which, in turn, promotes the formation of KS spindle cells with angiogenic phenotype. gamma IFN, in fact, induces endothelial cells to acquire the same features of KS cells, including the spindle morphology and the pattern of cell marker expression. In addition, endothelial cells activated by gamma IFN induce angiogenic lesions in nude mice closely resembling early KS. These KS-like lesions are accompanied by production of basic fibroblast growth factor, an angiogenic factor highly expressed in primary lesions that mediates angiogenesis and spindle cell growth. The formation of KS like lesions is upregulated by the human immunodeficiency virus Tat protein demonstrating its role as a progression factor in AIDS-KS. Finally, gamma IFN and HLA-DR expression correlate with the presence of HHV-8 in lesional and uninvolved tissues from the same patients. As HHV-8 infects both mononuclear cells infiltrating KS lesions and KS spindle cells, these results suggest that HHV-8 may elicit or participate in a local immune response characterized by infiltration of CD8(+) T cells and intense production of gamma IFN which, in turn, plays a key role in KS development. (C) 1998 by The American Society of Hematology. C1 Univ Rome La Sapienza, Dept Allergy & Clin Immunol, I-00185 Rome, Italy. NCI, Tumor Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Adv BioSci Labs Inc, Kensington, MD USA. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. Community Res Initiat AIDS New York, New York, NY USA. Ist Clin Med, Cattedra Genet, Cagliari, Italy. RP Ensoli, B (reprint author), Ist Super Sanita, Virol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. RI Ensoli, Barbara/J-9169-2016; Monini, Paolo/K-1429-2016 OI Ensoli, Barbara/0000-0002-0545-8737; Monini, Paolo/0000-0002-4941-6854 NR 110 TC 113 Z9 116 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 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1998 VL 91 IS 3 BP 956 EP 967 PG 12 WC Hematology SC Hematology GA YT777 UT WOS:000071644000028 PM 9446657 ER PT J AU Moyo, VM Mandishona, E Hasstedt, SJ Gangaidzo, IT Gomo, ZAR Khumalo, H Saungweme, T Kiire, CF Paterson, AC Bloom, P MacPhail, AP Rouault, T Gordeuk, VR AF Moyo, VM Mandishona, E Hasstedt, SJ Gangaidzo, IT Gomo, ZAR Khumalo, H Saungweme, T Kiire, CF Paterson, AC Bloom, P MacPhail, AP Rouault, T Gordeuk, VR TI Evidence of genetic transmission in African iron overload SO BLOOD LA English DT Article ID SERUM FERRITIN; HEREDITARY HEMOCHROMATOSIS; TRANSFERRIN SATURATION; LIVER-DISEASES; METABOLISM; THALASSEMIA; AMERICANS; ALCOHOL AB Iron overload in Africa was previously regarded as purely due to excessive iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated iron binding capacity may be influenced by an interaction between dietary iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated iron binding capacity after supplementation with vitamin C. For each measure of iron status, segregation analysis was consistent with an interaction between a postulated iron-loading gene and dietary iron content (P < .01). In the most likely model, transferrin saturation is 75% and serum ferritin is 985 mu g/L in a 40-year-old male heterozygote with an estimated beer consumption of 10,000 L, whereas the saturation is 36% and serum ferritin is 233 mu g/L in an unaffected individual with identical age, sex, and beer consumption, This segregation analysis provides further evidence for a genetic influence on iron overload in Africans, (C) 1998 by The American Society of Hematology. C1 George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Univ Zimbabwe, Sch Med, Dept Med, Harare, Zimbabwe. Univ Zimbabwe, Sch Med, Dept Chem Pathol, Harare, Zimbabwe. Univ Zimbabwe, Sch Med, Clin Epidemiol Unit, Harare, Zimbabwe. Univ Witwatersrand, Dept Med, ZA-2001 Johannesburg, South Africa. Univ Witwatersrand, Dept Pathol Anat, ZA-2001 Johannesburg, South Africa. Univ Utah, Med Ctr, Dept Human Genet, Salt Lake City, UT USA. Dist Gen Hosp, Ormskirk, Lancs, England. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Gordeuk, VR (reprint author), George Washington Univ, Med Ctr, Dept Med, 2150 Penn Ave NW, Washington, DC 20037 USA. FU NICHD NIH HHS [1-HD 3-3196.] NR 56 TC 69 Z9 69 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD FEB 1 PY 1998 VL 91 IS 3 BP 1076 EP 1082 PG 7 WC Hematology SC Hematology GA YT777 UT WOS:000071644000042 PM 9446671 ER PT J AU Catalan, MJ Honda, M Weeks, RA Cohen, LG Hallett, M AF Catalan, MJ Honda, M Weeks, RA Cohen, LG Hallett, M TI The functional neuroanatomy of simple and complex sequential finger movements: a PET study SO BRAIN LA English DT Article DE sequential movement; simple movement; premotor cortex; parietal cortex; PET ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; SUPPLEMENTARY MOTOR AREA; CORTICAL AREAS; PREMOTOR CORTEX; CORTICOSPINAL PROJECTIONS; MENTAL REPRESENTATION; SUSTAINED ATTENTION; VOLUNTARY MOVEMENTS; HAND MOVEMENTS AB The brain regions activated by simple repetitive and sequential finger movements of different length were localized by measuring regional cerebral blood flow (rCBF) with PET The experimental design consisted of finger movements cued by auditory pacing at 0.5 HZ. In all conditions of different sequence length the contralateral primary sensorimotor and premotor cortex, supplementary motor area and ipsilateral cerebellar cortex were activated. These areas showed a large increase in activation from rest to simple repetitive movement, and a further increase with the shortest sequence, suggesting art executive role in running sequences. The ipsilateral premotor area (Brodmann area 6), bilateral posterior parietal areas (Brodmann area 7) and precuneus showed art increase in rCBF related only to the length of the sequences, without any change from rest to simple repetitive movement. These areas are more selectively related to sequence performance. This finding is consistent with the hypothesis that these areas function in the storage of motor sequences in spatial working memory. Our results suggest that sequential finger movements recruit discrete sets of brain areas with different functions. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Hosp Univ San Carlos, Serv Neurol, Madrid, Spain. 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 58 TC 261 Z9 270 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 1998 VL 121 BP 253 EP 264 DI 10.1093/brain/121.2.253 PN 2 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZB056 UT WOS:000072430500006 PM 9549504 ER PT J AU Ridge, SA Sludden, J Wei, X Sapone, A Brown, O Hardy, S Canney, P Fernandez-Salguero, P Gonzalez, FJ Cassidy, J McLeod, HL AF Ridge, SA Sludden, J Wei, X Sapone, A Brown, O Hardy, S Canney, P Fernandez-Salguero, P Gonzalez, FJ Cassidy, J McLeod, HL TI Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE dihydropyrimidine dehydrogenase; 5-fluorouracil; polymorphism; colorectal cancer ID SEVERE 5-FLUOROURACIL TOXICITY; MONONUCLEAR-CELLS; DEFICIENCY; POPULATION; CHEMOTHERAPY AB Individuals with a deficiency in the enzyme dihydropyrimidine dehydrogenase (DPD) may experience severe life-threatening toxicity when treated with 5-fluorouracil (5-FU). As routine measurement of enzyme activity is not practical in many clinical centres, we have investigated the use of DNA mutation analysis to identify cancer patients with low enzyme levels. We have identified two new mutations at codons 534 and 543 in the DPD cDNA of a patient with low enzyme activity and screened the DNA from 75 colorectal cancer patients for these mutations and the previously reported splice site mutation (Vreken et al, 1996; Wei et al, 1996). In all cases, DPD enzyme activity was also measured. The splice site mutation was detected in a patient (1 out of 72) with low enzyme activity whereas mutations at codons 534 (2 out of 75) and 543 (11 out of 23) were not associated with low enzyme activity. These studies highlight the need to combine DPD genotype and phenotype analysis to identify mutations that result in reduced enzyme activity. C1 Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Western Infirm, Beatson Oncol Ctr, Glasgow G12 6NT, Lanark, Scotland. RP McLeod, HL (reprint author), Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Foresterhill, Aberdeen AB25 2ZD, Scotland. RI Sapone, Andrea/E-6704-2013; OI Sapone, Andrea/0000-0001-8496-6977; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 15 TC 71 Z9 81 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 FEB PY 1998 VL 77 IS 3 BP 497 EP 500 DI 10.1038/bjc.1998.79 PG 4 WC Oncology SC Oncology GA YV199 UT WOS:000071799300023 PM 9472650 ER PT J AU Anolik, JH Giovanna, JJD Gaspari, AA AF Anolik, JH Giovanna, JJD Gaspari, AA TI Effect of isotretinoin therapy on natural killer cell activity in patients with xeroderma pigmentosum SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID RETINOIC ACID; DNA-REPAIR; INTERFERON-PRODUCTION; SKIN-CANCER; TRICHOTHIODYSTROPHY; EXPRESSION; CARCINOMA AB Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP. although its mechanism of action is unknown. We describe a series of eight SP patients, sis of whom were given oral isotretinoin, The NK cell activity was not affected by low-dose isotretinoin, i.e. 0.5 mg/kg per day However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day produced a significant decrease in NK cell function, at the same lime as producing a reduction in the frequency of development of skin cancers, Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation. C1 NIAMSD, Dept Dermatol, NIH, Rochester, NY 14642 USA. NIAMSD, Dermatol Clin Res Unit, NIH, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Ctr Canc, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Strong Childrens Res Ctr, Rochester, NY 14642 USA. RP Gaspari, AA (reprint author), NIAMSD, Dept Dermatol, NIH, 601 Elmwood Ave, Rochester, NY 14642 USA. NR 29 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD FEB PY 1998 VL 138 IS 2 BP 236 EP 241 PG 6 WC Dermatology SC Dermatology GA YY232 UT WOS:000072126500006 PM 9602867 ER PT J AU Ruggieri, M Pavone, V Polizzi, A Smilari, P Magro, G Merino, M Duray, PH AF Ruggieri, M Pavone, V Polizzi, A Smilari, P Magro, G Merino, M Duray, PH TI Familial osteoma of the cranial vault SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID BONES; SKIN AB A case of solitary osteoma of the parietal skull is described in a mother and her 12-year-old son. There were no other craniofacial or dysmorphic features and there was no history of previous cranial trauma or inflammatory process and no radiographic evidence of other skeletal lesions in both patients. Family history was otherwise unremarkable. Gardner syndrome was ruled out by excluding other associated clinical abnormalities and by family history. The clinical and radiological features of the patients' osteomas were different from those of Albright hereditary osteodystrophy, fibrodysplasia ossificans progressiva, progressive osseous heteroplasia and familial ectopic ossification. To the author's knowledge this is the first case of the familial presentation of osteomas. C1 Oxford Radcliffe Hosp NHS Trust, Dept Clin Genet, Oxford OX3 7LJ, England. Univ Catania, Paediat Clin, Div Paediat Neurol, I-95125 Catania, Italy. Univ Catania, Orthopaed Clin, I-95125 Catania, Italy. Univ Catania, Inst Pathol Anat, I-95125 Catania, Italy. NCI, Dept Hlth & Human Serv, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Ruggieri, M (reprint author), Oxford Radcliffe Hosp NHS Trust, Dept Clin Genet, The Churchill, Oxford OX3 7LJ, England. OI Magro, Gaetano Giuseppe/0000-0003-3244-6827 NR 18 TC 3 Z9 3 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD FEB PY 1998 VL 71 IS 842 BP 225 EP 228 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YY056 UT WOS:000072107800015 PM 9579189 ER PT J AU Chen, R AF Chen, R TI Electrophysiological studies in the critical care unit: Investigating polyneuropathies SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID GUILLAIN-BARRE-SYNDROME; MULTIPLE ORGAN FAILURE; ACUTE AXONAL FORM; RESPIRATORY-FAILURE; PARALYSIS; SEPSIS; CHINA AB Polyneuropathies frequently contribute to ventilator dependency and prolonged stay in the intensive care unit, As clinical examination is often limited in critically ill patients, electrophysiological studies are invaluable in establishing the diagnosis of neuropathy, determining its pathophysiology, severity and in following the patients' progression. Guillain-Barre syndrome (GBS) developing before intensive care unit admission and critical illness polyneuropathy (CIP) developing as a complication of sepsis and multiorgan failure are the commonest causes of neuropathy. Electrophysiological findings iii CIP are that of an axonal neuropathy whereas the findings in GBS are usually consistent with a demyelinating neuropathy, Axonal GBS can be distinguished from CIP by the preceding illnesses, slow nerve conduction velocity in some cases, lack of spontaneous activity on the initial needle electromyographic study and cerebrospinal fluid findings. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. RP Chen, R (reprint author), NIH Bldg 10,Room 5N234,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 15 TC 3 Z9 3 U1 0 U2 0 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD FEB PY 1998 VL 25 IS 1 BP S32 EP S35 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA YW720 UT WOS:000071965900023 PM 9532295 ER PT J AU Meredith, R Alvarez, R Partridge, E Khazaeli, MB Grizzle, W Mayo, M Schlom, J LoBuglio, A AF Meredith, R Alvarez, R Partridge, E Khazaeli, MB Grizzle, W Mayo, M Schlom, J LoBuglio, A TI Enhanced intraperitoneal radioimmunotherapy salvage of ovarian cancer with adjuvant Interferon and Taxol. SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 1998 VL 13 IS 1 MA 9 BP 54 EP 54 PG 1 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA ZB239 UT WOS:000072451100015 ER PT J AU Borchardt, PE Vriesendorp, HM Freedman, RS Quadri, SM AF Borchardt, PE Vriesendorp, HM Freedman, RS Quadri, SM TI Intracompartmental administration of radiolabeled human IgM SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 Arlington Canc Ctr, Arlington, TX USA. Univ Texas, Md Anderson Canc Ctr, Houston, TX USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 1998 VL 13 IS 1 MA 24 BP 59 EP 59 PG 1 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA ZB239 UT WOS:000072451100031 ER PT J AU Buchsbaum, DJ Khazaeli, MB Mayo, MS Hand, PH Schlom, J Meredith, RF AF Buchsbaum, DJ Khazaeli, MB Mayo, MS Hand, PH Schlom, J Meredith, RF TI Evaluation of CH2 deleted HuCC49 for intraperitoneal radioimmunotherapy. SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 Univ Alabama, Dept Radiat Oncol, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RI Mayo, Matthew/E-3774-2015 NR 0 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 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 1998 VL 13 IS 1 MA 25 BP 59 EP 59 PG 1 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA ZB239 UT WOS:000072451100033 ER PT J AU Farrow, DC Vaughan, TL Hansten, PD Stanford, JL Risch, HA Gammon, MD Chow, WH Dubrow, R Ahsan, H Mayne, ST Schoenberg, JB West, AB Rotterdam, H Fraumeni, JF Blot, WJ AF Farrow, DC Vaughan, TL Hansten, PD Stanford, JL Risch, HA Gammon, MD Chow, WH Dubrow, R Ahsan, H Mayne, ST Schoenberg, JB West, AB Rotterdam, H Fraumeni, JF Blot, WJ TI Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER; ANTIINFLAMMATORY DRUGS; BREAST-CANCER; REDUCED RISK; COLON CANCER; LARGE-BOWEL; ADENOCARCINOMA; CARCINOMA; TOBACCO; ALCOHOL AB Regular users of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) are at reduced risk of colon cancer, but the evidence for protective effects of NSAIDs elsewhere in the digestive tract is scant. We investigated the association between the use of NSAIDs and risk of esophageal and gastric cancer, using data from a large population-based, case-control study. Cases were individuals, ages 30-79 years, diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or noncardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were selected by random digit dialing and through the rosters of the Health Care Financing Administration. After controlling for the major risk factors, we found that current users of aspirin were at decreased risk of esophageal adenocarcinoma [odds ratio (OR), 0.37; 95% confidence interval (CI), 0.24-0.58], esophageal squamous cell carcinoma (OR, 0.49; 95% CI, 0.28-0.87), and noncardia gastric adenocarcinoma (OR, 0.46; 95% CI, 0.31-0.68), but not of gastric cardia adenocarcinoma (OR, 0.80; 95% CI, 0.54-1.19), when compared to never users. Risk was similarly reduced among current users of nonaspirin NSAIDs. The associations with current NSAID use persisted when we excluded use within 2 or 5 years of reference date, which might have been affected by preclinical disease in cases, and when we restricted analyses to subjects reporting no history of chronic gastrointestinal symptoms. Our findings add to the growing evidence that the risk of cancers of the esophagus and stomach is reduced in users of NSAIDs, although whether the association is causal in nature is not clear. C1 Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Columbia Sch Publ Hlth, Div Epidemiol, New York, NY 10032 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. New Jersey Dept Hlth & Senior Serv, Off Canc Epidemiol, Trenton, NJ 08625 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Int Epidemiol Inst, Rockville, MD 20850 USA. RP Farrow, DC (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,POB 19024,MP-474, Seattle, WA 98104 USA. FU NCI NIH HHS [5U01-CA57923, U01-CA57949, U01-CA57983] NR 31 TC 327 Z9 348 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 FEB PY 1998 VL 7 IS 2 BP 97 EP 102 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA150 UT WOS:000072333900002 PM 9488582 ER PT J AU Nupponen, NN Hyytinen, ER Kallioniemi, AH Visakorpi, T AF Nupponen, NN Hyytinen, ER Kallioniemi, AH Visakorpi, T TI Genetic alterations in prostate cancer cell lines detected by comparative genomic hybridization SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID IN-SITU HYBRIDIZATION; SOLID TUMORS; CARCINOMA; LNCAP; ABNORMALITIES; CHROMOSOME-8; LOSSES; GAINS AB Recent studies have identified several chromosomal regions that are altered in prostate cancer. However, the specific genes affected are, in most of the cases, not known. Cancer cell lines could provide a valuable resource for cloning of genes that are commonly affected in cancer. The first step in the identification of such genes is the detection of chromosomal aberrations. Here, we have used comparative genomic hybridization (CGH) to screen for genetic alterations in four prostate cancer cell lines, LNCaP, DU145, PC-3, and TSU-Pr1. The analysis showed that, except for the LNCaP, these cell lines contained many genetic changes (greater than or equal to 10 per cell line), suggesting that they resemble genetically more closely hormone-refractory or metastatic than primary prostate carcinomas. All the chromosomal regions that have been implicated in prostate cancer were altered in at least one of the cell lines. The most common genetic changes were gain at 11q and losses at 6q, 9p, and 13q, each present in at least three cell lines. Identification of genetic aberrations by CGH in these cell lines should facilitate the choice of individual cell lines for cloning of genes that are involved in the development and progression of prostate cancer. (C) Elsevier Science Inc., 1998. C1 Tampere Univ, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. NIH, NHGRI, Canc Genet Lab, Bethesda, MD 20892 USA. RP Visakorpi, T (reprint author), Tampere Univ, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. OI Kallioniemi, Anne/0000-0003-3552-8158 NR 22 TC 77 Z9 79 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD FEB PY 1998 VL 101 IS 1 BP 53 EP 57 DI 10.1016/S0165-4608(97)00060-5 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YU703 UT WOS:000071745800010 PM 9460501 ER PT J AU Dimond, E Calzone, K Davis, J Jenkins, J AF Dimond, E Calzone, K Davis, J Jenkins, J TI The role of the nurse in cancer genetics SO CANCER NURSING LA English DT Article ID DISCRIMINATION; PERSPECTIVES; JEWISH C1 NCI, Natl Naval Med Ctr, NIH, Bethesda, MD 20892 USA. Univ Penn, Ctr Canc, Breast Canc Risk Evaluat Program, Philadelphia, PA 19104 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Dimond, E (reprint author), NIH, DCS, NMOB, 8901 Wisconsin Ave,Bld 8-5101, Bethesda, MD 20814 USA. NR 23 TC 7 Z9 7 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD FEB PY 1998 VL 21 IS 1 BP 57 EP 70 DI 10.1097/00002820-199802000-00008 PG 14 WC Oncology; Nursing SC Oncology; Nursing GA YY812 UT WOS:000072187900008 PM 9494232 ER PT J AU Lee, JY Dong, SM Park, WS Yoo, NJ Kim, CS Jang, JJ Chi, JG Zbar, B Lubensky, IA Linehan, WM Vortmeyer, AO Zhuang, ZP AF Lee, JY Dong, SM Park, WS Yoo, NJ Kim, CS Jang, JJ Chi, JG Zbar, B Lubensky, IA Linehan, WM Vortmeyer, AO Zhuang, ZP TI Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas SO CANCER RESEARCH LA English DT Article ID VONHIPPEL-LINDAU DISEASE; CENTRAL-NERVOUS-SYSTEM; ENDOTHELIAL GROWTH-FACTOR; CAPILLARY HEMANGIOBLASTOMAS; RENAL-CARCINOMA; CHROMOSOME-3; EXPRESSION; RECEPTORS AB Cerebellar hemangioblastoma is a benign central nervous system neoplasm with characteristic proliferation of vascular and stromal cells. There is increasing evidence that the stromal cell population may represent the neoplastic component of hemangioblastoma, whereas the vascular component may be composed of reactive, nonneoplastic cells. Therefore, successful genetic testing for loss of heterozygosity requires selective analysis of target cell populations. Here, tissue microdissection was used to selectively analyze the stromal cell component of 20 archival sporadic cerebellar hemangioblastomas for loss of heterozygosity at the Von-Hippel Lindau (VHL) gene and somatic VHL gene mutations, Allelic deletions at the VHL gene locus were detected in the stromal cell component with one or more markers (D3S1038, D3S1110, and/or 104/105) in 10 of 19 (52.6%) informative cases, In all cases, heterozygosity at the VHL gene locus was retained in the vascular component. In two cases, aberrant bands in exon 2 of the VHL gene were demonstrated in the stromal cells by PCR-based single-strand conformation polymorphism analysis, and somatic missense mutations were successfully characterized in two of the sporadic hemangioblastomas by direct sequencing. The results suggest that allelic losses and mutations of the VHL tumor suppressor gene play a role in sporadic cerebellar hemangioblastoma tumorigenesis. Furthermore, because the genetic changes were detected in selectively procured stromal cell areas, the data provide strong evidence that the stromal cell represents a neoplastic component of hemangioblastoma. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Catholic Univ, Coll Med, Dept Pathol, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N212,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Chi, Je Geun/G-4989-2011; Seoul National University, Pathology/B-6702-2012; OI Chi, Je-Geun/0000-0002-9950-2072 NR 25 TC 97 Z9 101 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1998 VL 58 IS 3 BP 504 EP 508 PG 5 WC Oncology SC Oncology GA YU374 UT WOS:000071710700025 PM 9458097 ER PT J AU Roschke, V Hausner, P Kopantzev, E Pumphrey, JG Riminucci, M Hilbert, DM Rudikoff, S AF Roschke, V Hausner, P Kopantzev, E Pumphrey, JG Riminucci, M Hilbert, DM Rudikoff, S TI Disseminated growth of murine plasmacytoma: Similarities to multiple myeloma SO CANCER RESEARCH LA English DT Article ID IN-VIVO MODEL; BONE-MARROW; CELL-LINES; SCID MICE; DIFFERENTIATION; DISEASE; INTERLEUKIN-6; PROLIFERATION; ANTIBODIES AB Murine plasma cell tumors share a number of common features with human multiple myeloma, suggesting their possible use as a model for this disease. However, one major difference between the two is the peritoneal localization of murine tumors as opposed to bone marrow residence of malignant plasma cells in early stages of multiple myeloma. We have thus examined the ability of murine plasmacytoma to produce disseminated growth similar to that seen in myeloma or other lymphoid neoplasias, Of four murine cell lines evaluated, all were demonstrated to effect highly metastatic disease involving multiple organs, although variation was observed between lines, A temporal analysis was accordingly performed with the S107 line to assess the pattern of cellular localization, Both light microscopy and PCR analysis revealed that engraftment of plasma cells occurs first in the bone marrow, followed by dissemination to other sites including the spleen, lung, and liver, Cells passaged in vivo through the bone marrow display an entirely different metastatic pattern with no homing preference to bone marrow or any other organ, suggesting the occurrence of a phenotypic change, Microscopic osteolytic lesions were observed adjacent to plasma cell tumor masses in the bone marrow, indicating early stages of bone disease, These findings demonstrate previously unrecognized similarities between the murine and human diseases and suggest the use of this in vivo model for experimental approaches to the treatment of human disease. C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NIDR, Cranifacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Rudikoff, S (reprint author), NCI, Genet Lab, NIH, Bldg 37,Room 2B15,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 30 TC 7 Z9 7 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 FEB 1 PY 1998 VL 58 IS 3 BP 535 EP 541 PG 7 WC Oncology SC Oncology GA YU374 UT WOS:000071710700030 PM 9458102 ER PT J AU Watson, MA Stewart, RK Smith, GBJ Massey, TE Bell, DA AF Watson, MA Stewart, RK Smith, GBJ Massey, TE Bell, DA TI Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution SO CARCINOGENESIS LA English DT Article ID DRUG-METABOLIZING-ENZYMES; CARCINOGEN-METABOLISM; AFRICAN-AMERICANS; TOBACCO SMOKING; CANCER PATIENTS; GENE DELETION; EXPRESSION; TUMORS; RISK; SUSCEPTIBILITY AB The association between glutathione S-transferase (GST) activity as measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung tissue obtained from 34 surgical patients. These samples were genotyped for previously identified polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was significantly lower among individuals with the 105 Val allele. Homozygous Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of 74.9 +/- 3.8 mnol/mg per min; heterozygotes (n = 13) had a mean specific activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had a mean specific activity of 52.5 +/- 4.5 nmol/mg mg per min. The CDNB conjugating activity measured for the Ile/Ile genotype group was significantly different from that observed in the Ile/Val group (P = 0.03), and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST activity values mere consistently lower in individuals with genotypes containing the 105 valine allele, regardless of smoking exposure. Genotypes at codon 114 were also assessed but the mean GST activity was not significantly lower in individuals with the 114 valine allele. A new haplotype, present in two samples who were homozygous 105Ile and had a 114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5 and exon 6 polymorphisms were determined in samples obtained from European-Americans, African-Americans and Taiwanese. The differences observed were highly significant suggesting the possibility of GSTP1 genotype-associated, ethnic differences in cancer susceptibility and chemotherapeutic response. C1 NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. Queens Univ, Dept Pharmacol & Toxicol, Kingston, ON K7L 3N6, Canada. RP Bell, DA (reprint author), NIEHS, Lab Computat Biol & Risk Assessment, POB 12233, Res Triangle Pk, NC 27709 USA. NR 44 TC 499 Z9 545 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1998 VL 19 IS 2 BP 275 EP 280 DI 10.1093/carcin/19.2.275 PG 6 WC Oncology SC Oncology GA YY068 UT WOS:000072109000006 PM 9498276 ER PT J AU Felix, K Lin, S Bornkamm, GW Janz, S AF Felix, K Lin, S Bornkamm, GW Janz, S TI Tetravinyl-tetramethylcyclo-tetrasiloxane (tetravinyl D4) is a mutagen in Rat2 lambda lacI fibroblasts SO CARCINOGENESIS LA English DT Article ID SILICONE GELS; MICE; DNA; PLASMACYTOMAS; INTERLEUKIN-6; INDUCTION; ACCUMULATION; NEUTROPHILS; ETHENOBASES; MIGRATION AB Small fragments of silicone gels injected intraperitoneally have been used to induce plasmacytomas in genetically susceptible mice, Silicone oils, in contrast to silicone gels, are apparently not tumorigenic in the mouse plasmacytoma system. The reason for this difference as well as the mechanism of silicone gel-induced plasmacytoma development is poorly understood. We chose to examine the possibility that low molecular wt silicone compounds such as siloxanes, leaking from the complex silicone gel matrix into the surrounding tissue, may be mutagenic. We postulate that this mutagenicity may be a critical determinant of the plasmacytoma inducing potency of silicone gels. Six siloxane compounds, either linear or cyclic di-, tri-, or tetrasiloxanes substituted with methyl or vinyl moieties, were selected as model compounds to study mutagenicity in Rat2 lambda lacI fibroblasts in vitro. Using phage lambda-derived lacI/lacZ genes as target/reporter genes to quantitate mutagenesis, and gamma-cyclodextrin as vehicle to effectively deliver siloxanes, we found that exposure to 50 mu m of tetravinyl-tetramethyl-cyclo-tetrasiloxane (tetravinyl D4) resulted in a modest 1.7-fold increase of mutant frequencies over controls in Rat2 lambda lacI cells. In related toxicity experiments, tetravinyl D4 was shown to perturb lipid membranes leading to a loss of cytosolic glutathione (GSH), which by itself resulted in a 1.5-fold increased mutant rate in Rat2 lambda lacI cells. We conclude that certain siloxanes may act as direct mutagens in mammalian cells. In addition, siloxane-induced mutagenicity may be enhanced by the depletion of intracellular GSH caused by the interaction of lipophilic siloxanes with cell membranes. C1 NCI, Genet Lab, DBS, NIH, Bethesda, MD 20892 USA. GSF, Res Ctr, Inst Clin Mol Biol & Tumor Genet, D-81377 Munich, Germany. RP Felix, K (reprint author), NCI, Genet Lab, DBS, NIH, Bldg 37,Rm 2B03, Bethesda, MD 20892 USA. NR 30 TC 6 Z9 6 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1998 VL 19 IS 2 BP 315 EP 320 DI 10.1093/carcin/19.2.315 PG 6 WC Oncology SC Oncology GA YY068 UT WOS:000072109000013 PM 9498283 ER PT J AU Koban, MU Moorman, AFM Holtz, J Yacoub, MH Boheler, KR AF Koban, MU Moorman, AFM Holtz, J Yacoub, MH Boheler, KR TI Expressional analysis of the cardiac Na-Ca exchanger in rat development and senescence SO CARDIOVASCULAR RESEARCH LA English DT Article DE Na-Ca exchanger; heart development; rat; RNA; promoter; splicing ID SODIUM-CALCIUM EXCHANGE; TISSUE-SPECIFIC ANTIGENS; DEVELOPING HUMAN HEART; SARCOPLASMIC-RETICULUM CA2+-ATPASE; SARCOLEMMAL NA+-CA2+ EXCHANGER; HEAVY-CHAIN PROMOTER; PROTEIN KINASE-C; IMMUNOHISTOCHEMICAL ANALYSIS; FUNCTIONAL EXPRESSION; SPATIAL-DISTRIBUTION AB The cardiac Na-Ca exchanger (NCX) serves as the main calcium extrusion mechanism in heart muscle and is important in maintaining intracellular calcium homeostasis. The accumulations of NCX RNA and protein are known to be regulated in cardiac hypertrophy, by thyroid hormone and during postnatal development. In this study the temporal and spatial patterns of NCX mRNA and protein accumulations were examined, and nuclear run-on assays performed. NCX is highly expressed in late fetal and neonatal rat hearts, decreasing to adult levels by 20 days after birth for RNA (P < 0.05, fetal and 1 neonatal day old (1 ND) versus 20 day old (20 ND)). Maximal protein expression is seen in 19 embryonic day (ED) old hearts, and reaches adult levels sometime after 20 neonatal days. (P < 0.05, fetal versus adult). Spatially, NCX is homogenously expressed in early embryonic and fetal heart, followed by a decline after birth. The protein levels decline more slowly suggesting a long protein half-life. The lowest level of mRNA accumulation is seen in 6 and 18 month old animals (P < 0.05 for all time points before 10 neonatal days). In the 24 month old senescent rat, NCX transcripts are increased by almost 50% above that seen at 6 and 18 months (P < 0.05) but are not different from those at 15 neonatal days. Perinatal NCX expression is regulated transcriptionally: late fetal and neonatal hearts have high transcriptional activity but by 20 postnatal days, no detectable transcriptional activity can be demonstrated. Throughout development, at least five transcription start sites are used, and no significant difference in the 5' untranslated or 3' coding splice sites could be demonstrated, although several new cardiac splicing variants were identified. We also report the cloning of a 3.7 kb fragment containing the cardiac NCX1 promoter which is transcriptionally active in neonatal cardiomyocytes. (C) 1998 Elsevier Science B.V. C1 Natl Heart & Lung Inst, ICSM, London SW3 6LY, England. Univ Amsterdam, Dept Anat & Embryol, Amsterdam, Netherlands. Univ Halle Wittenberg, Inst Pathophysiol, Halle, Germany. RP Boheler, KR (reprint author), NIA, NIH, GRC, LCS, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM bohelerk@grc.nia.nih.gov NR 70 TC 60 Z9 62 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 1998 VL 37 IS 2 BP 405 EP 423 DI 10.1016/S0008-6363(97)00276-9 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZG794 UT WOS:000073040300013 PM 9614496 ER PT J AU Truckenmiller, ME Tornatore, C Wright, RD Dillon-Carter, O Meiners, S Geller, HM Freed, WJ AF Truckenmiller, ME Tornatore, C Wright, RD Dillon-Carter, O Meiners, S Geller, HM Freed, WJ TI A truncated SV40 large T antigen lacking the p53 binding domain overcomes p53-induced growth arrest and immortalizes primary mesencephalic cells SO CELL AND TISSUE RESEARCH LA English DT Article DE amino-terminal SV40 large T; cell-cycle; CNS; immortalization; mesencephalic cells; p53; transfection ID MOUSE EMBRYO FIBROBLASTS; CELLULAR DNA-SYNTHESIS; PRIMORDIAL GERM-CELLS; SIMIAN VIRUS-40; TRANSGENIC MICE; HYBRID-CELLS; IN-VITRO; SV40-TRANSFORMED CELLS; TUMOR-ANTIGEN; GENE-TRANSFER AB As an alternative to primary fetal tissue, immortalized central nervous system (CNS)-derived cell lines are useful for in vitro CNS model systems and for gene manipulation with potential clinical use in neural transplantation. However, obtaining immortalized cells with a desired phenotype is unpredictable, because the molecular mechanisms of growth and differentiation of CNS cells are poorly understood. The SV40 large T antigen is commonly used to immortalize mammalian cells, but it interferes with multiple cell-cycle components, including p53, p300, and retinoblastoma protein, and usually produces cells with undifferentiated phenotypes. In order to increase the phenotypic repertoire of immortalized CNS cells and to address the molecular mechanisms underlying immortalization and differentiation, we constructed an expression vector containing a truncated SV40 large T gene that encodes only the amino-terminal 155 amino acids (T155), which lacks the p53-binding domain. Constructs were first transfected into a p53-temperature-sensitive cell line, T64-7B. Colonies expressing T155 proliferated at the growth-restrictive temperature. T155 was then transfected into primary cultures from embryonic day-14 rat mesencephalon. Two clonal cell lines were derived, AF-5 and AC-IO, which co-expressed T155 and mature neuronal and astrocytic markers, Thus, the amino-terminal portion of SV40 large T is sufficient to: (1) overcome p53-mediated growth arrest despite the absence of a p53-binding region, and (2) immortalize primary CNS cells expressing mature markers while actively dividing. T155 and T155-transfectants may be useful for further studies of cell-cycle mechanisms and phenotyic expression in CNS cells or for further gene manipulation to produce cells with specific properties. C1 Natl Inst Drug Abuse, IRP, Baltimore, MD 21224 USA. NINDS, Mol Therapeut Sect, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. RP Truckenmiller, ME (reprint author), Natl Inst Drug Abuse, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM etrucken@irp.nida.nih.gov OI Geller, Herbert/0000-0002-7048-6144 NR 89 TC 25 Z9 25 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD FEB PY 1998 VL 291 IS 2 BP 175 EP 189 DI 10.1007/s004410050989 PG 15 WC Cell Biology SC Cell Biology GA YT093 UT WOS:000071563300002 PM 9426306 ER PT J AU Dillon-Carter, O Conejero, C Tornatore, C Poltorak, M Freed, WJ AF Dillon-Carter, O Conejero, C Tornatore, C Poltorak, M Freed, WJ TI N18-RE-105 cells: differentiation and activation of p53 in response to glutamate and adriamycin is blocked by SV40 large T antigen tsA58 SO CELL AND TISSUE RESEARCH LA English DT Article DE N18-RE-105 cells; glutamate; p53; adriamycin; etoposide; differentiation; SV40 large T antigen; mouse; rat ID SIMIAN-VIRUS 40; NONPERMISSIVE TEMPERATURE; TOPOISOMERASE INHIBITORS; SV40-TRANSFORMED CELLS; OXIDATIVE STRESS; CARCINOMA-CELLS; RAT STRIATUM; APOPTOSIS; EXPRESSION; LINE AB Process extension was induced in cells of the N18-RE-105 neuroblastoma-retinal hybrid line by toxic agents, including glutamate and the p53-inducing anticancer agents adriamycin and etoposide. Both adriamycin and glutamate activated p53 as measured by a plasmid transfection assay. It was therefore hypothesized that SV40 large T antigen, which binds p53, would interfere with cellular differentiation. To test this hypothesis, the temperature-sensitive form of SV40 large T was transduced into N18-RE-105 cells by retroviral infection. SV40 large T-infected cells became de-differentiated, grew in tightly-packed colonies, lost expression of neurofilament, and lost the ability to differentiate in response to glutamate and adriamycin. The de-differentiating effect of SV40 large T antigen may be due to binding and inactivation of cellular proteins, such as p53, p107, p130, p300, and retinoblastoma protein, which are important in cellular growth and differentiation. It is suggested that p53 may play a role in cellular differentiation, perhaps under unusual circumstances involving stress or cytotoxicity. C1 NIMH, Neurosci Ctr St Elizabeths, Sect Preclin Neurosci, Neuropsychiat Branch, Washington, DC 20032 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20815 USA. George Washington Univ, Med Ctr, Dept Neurol, Washington, DC 20037 USA. RP Freed, WJ (reprint author), NIMH, Neurosci Ctr St Elizabeths, Sect Preclin Neurosci, Neuropsychiat Branch, 2700 Martin Luther King Ave, Washington, DC 20032 USA. EM freedw@dirpc.nimh.nih.gov NR 46 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD FEB PY 1998 VL 291 IS 2 BP 191 EP 205 DI 10.1007/s004410050990 PG 15 WC Cell Biology SC Cell Biology GA YT093 UT WOS:000071563300003 PM 9426307 ER PT J AU Lester, DS Kidder, LH Levin, IW Lewis, EN AF Lester, DS Kidder, LH Levin, IW Lewis, EN TI Infrared microspectroscopic imaging of the cerebellum of normal and cytarabine treated rats SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE infrared imaging; FT-IR spectroscopy; infrared focal-plane arrays; cerebellum; microscopy; neuropathology; histology ID BRAIN-TISSUE AB Conventionally, the diagnosis of neuropathology in a subject requires the identification of a behavioral modification, which provides direction for appropriate histological analyses. However, since the ultimate diagnosis of the pathology largely depends on the initial choice of histological tests, the opportunity exists for inaccurate or insensitive results. An innovative approach using Fourier transform infrared (FT-IR) spectroscopic imaging to diagnose neuropathology should prove useful. This novel method monitors and visualizes the underlying chemistry of the tissue, based on hundreds of vibrational absorption bands that are intrinsic to the sample, As such, it makes no prior assumptions as to the type or degree of pathology. Using this technique, we have spectroscopically imaged cerebellar tissue slices from rats [control subjects and subjects treated with the antineoplastic drug, cytarabine (Ara-C)], and have been able to correlate lipid and protein distributions within distinct cell types in the cerebellum. A further benefit of the technique is that it simultaneously records tens of thousands of independent spectra from different spatial locations within the sample. Thus, a variety of statistical and multivariate techniques can be exploited to characterize large sample areas and to provide robust classification of individual spectral signatures. In comparison to standard histological protocols, FT-IR spectroscopic imaging simultaneously analyzes cell layers and identifies subtle structural and biochemical changes within the sample. We suggest that FT-IR spectroscopic imaging should provide a highly reliable, complementary tool for standard histological tier testing. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. RP Lester, DS (reprint author), NIDDKD, Chem Phys Lab, NIH, 9000 Rockville Pike,Bldg 5,Room B1-38, Bethesda, MD 20892 USA. NR 19 TC 32 Z9 32 U1 0 U2 1 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD FEB PY 1998 VL 44 IS 1 BP 29 EP 38 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZE327 UT WOS:000072781500005 PM 9551635 ER PT J AU Robyr, D Wolffe, AP AF Robyr, D Wolffe, AP TI Hormone action and chromatin remodelling SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE steroid receptor; nuclear receptor; coactivator; corepressor; transcriptional activation; nucleosome positioning; histone modification; transcriptional repression ID TUMOR VIRUS PROMOTER; GLUCOCORTICOID RESPONSE ELEMENT; MAMMALIAN HISTONE DEACETYLASE; RECEPTOR COACTIVATOR COMPLEX; TRANSCRIPTION FACTOR ACCESS; CHICKEN VITELLOGENIN GENE; ACTIVATION FUNCTION AF-2; NUCLEAR FACTOR-I; THYROID-HORMONE; ESTROGEN-RECEPTOR AB Current attention in transcriptional regulation is focused on the properties of coactivators and corepressors that mediate communication between sequence-specific transcription factors, the basal transcriptional machinery and the chromatin environment. Nuclear and steroid hormone receptors represent the best-understood transcription factors that utilize coactivators and corepressors. This review considers the access of these receptors to chromatin, the modifications of chromatin structure that the receptors instigate and the implications for transcriptional control. Nucleosome positioning and targeted histone modification emerge as central controlling elements for gene expression. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. NR 138 TC 15 Z9 15 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD FEB PY 1998 VL 54 IS 2 BP 113 EP 124 DI 10.1007/s000180050130 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZD507 UT WOS:000072692900001 PM 9539951 ER PT J AU Dietzel, S Jauch, A Kienle, D Qu, GQ Holtgreve-Grez, H Eils, R Munkel, C Bittner, M Meltzer, PS Trent, JM Cremer, T AF Dietzel, S Jauch, A Kienle, D Qu, GQ Holtgreve-Grez, H Eils, R Munkel, C Bittner, M Meltzer, PS Trent, JM Cremer, T TI Separate and variably shaped chromosome arm domains are disclosed by chromosome arm painting in human cell nuclei SO CHROMOSOME RESEARCH LA English DT Article DE chromosome arms; chromosome structure; chromosome territories; confocal microscopy; fluorescence in situ hybridization; nuclear organization; random walk/giant loop model ID FLUORESCENCE INSITU HYBRIDIZATION; ALPHA-SATELLITE DNA; INTERPHASE CHROMOSOMES; IN-SITU; CLONES; PROBES; MICRODISSECTION; TERRITORIES; MICROSCOPY; GENERATION AB Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding. C1 Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. Univ Heidelberg, Interdisciplinary Ctr Sci Comp, Heidelberg, Germany. Deutsch Krebsforschungszentrum, Div Biophys Macromol, D-6900 Heidelberg, Germany. Natl Human Genome Res Inst, Canc Genet Lab, NIH, Bethesda, MD 20892 USA. RP Cremer, T (reprint author), Univ Munich, Inst Anthropol & Human Genet, Richard Wagner Str 10-1, D-80333 Munich, Germany. RI Eils, Roland/B-6121-2009 OI Eils, Roland/0000-0002-0034-4036 NR 42 TC 78 Z9 80 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD FEB PY 1998 VL 6 IS 1 BP 25 EP 33 DI 10.1023/A:1009262223693 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA YU284 UT WOS:000071700900004 PM 9510507 ER PT J AU Baskar, PV Collins, GD Dorsey-Cooper, BA Pyle, RS Nagel, JE Dwyer, D Dunston, G Johnson, CE Kendig, N Israel, E Nalin, DR Adler, WH AF Baskar, PV Collins, GD Dorsey-Cooper, BA Pyle, RS Nagel, JE Dwyer, D Dunston, G Johnson, CE Kendig, N Israel, E Nalin, DR Adler, WH TI Serum antibodies to HIV-1 are produced post-measles virus infection: evidence for cross-reactivity with HLA SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE HIV-1; measles; indeterminate Western blot ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; MLS(F) SYSTEM; AUTOIMMUNITY; PATHOGENESIS; PROTEINS; ADULTS; IDENTIFICATION; INDIVIDUALS; SPECIFICITY AB Convalescent sera obtained from patients who were recently recovered from an acute measles virus infection were tested for the presence of anti-HIV-l antibodies by Western blot analysis. While 16% (17/104) of control sera displayed reactive bands to a variety of HIV proteins, 62% (45/73) of convalescent sera demonstrated immunoreactive bands corresponding to HIV-I Pol and Gag, but not Env antigens. This cross-reactivity appears to be the result of an active measles infection. No HIV-1 immunoblot reactivity (0/10) was observed in sera obtained from young adults several weeks after a combined measles, mumps, and rubella (MMR) vaccination. Interestingly, examination of anti-HLA typing sera specific for either class I and class Il molecules revealed that 46% (19/41) of these sera contained cross-reactive antibodies to HIV-1 proteins. Absorption of measles sera with mixed lymphocyte reaction (MLR)-activated lymphocytes and/or HIV-1 recombinant proteins significantly decreased or removed the presence of these HIV-1-immunoreactive antibodies. Together, these findings suggest that the immune response to a natural measles virus infection results in the production of antibodies to HIV-1 and possibly autoantigens. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Howard Univ, Sch Med, Washington, DC 20059 USA. Maryland State Hlth Dept, Baltimore, MD USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Merck Res Labs, W Point, PA USA. RP Baskar, PV (reprint author), NIA, Immunol Lab, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 41 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD FEB PY 1998 VL 111 IS 2 BP 251 EP 256 PG 6 WC Immunology SC Immunology GA YX719 UT WOS:000072070400003 PM 9486389 ER PT J AU Blaney, SM Needle, MN Gillespie, A Sato, JK Reaman, GH Berg, SL Adamson, PC Krailo, MD Bleyer, WA Poplack, DG Balis, FM AF Blaney, SM Needle, MN Gillespie, A Sato, JK Reaman, GH Berg, SL Adamson, PC Krailo, MD Bleyer, WA Poplack, DG Balis, FM TI Phase II trial of topotecan administered as a 72-hour continuous infusion in children with refractory solid tumors: A Collaborative Pediatric Branch, National Cancer Institute, and Children's Cancer Group Study SO CLINICAL CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-I; DOSE INTENSITY; CHEMOTHERAPY; XENOGRAFTS AB The antitumor activity of topotecan administered as a 72-h continuous i,v, infusion was evaluated in children with refractory neuroblastoma and sarcomas of soft tissue and bone, We also attempted to increase the dose intensity of topotecan by including an intrapatient dose escalation in the trial design, Ninety-three children (85 eligible and evaluable for response) with recurrent or refractory neuroblastoma, osteosarcoma, Ewing's sarcoma/peripheral neuroectodermal tumor, rhabdomyosarcoma, or other soft-tissue sarcomas received topotecan administered as a 72-h i,v, infusion every 21 days, The initial dose was 1.0 mg/m(2)/day, with subsequent intrapatient dose escalation to 1.3 mg/m(2)/day for those patients who did not experience dose-limiting toxicity after their first cycle of topotecan, There was one complete response in a patient with neuroblastoma (n = 26) and one partial response in a patient with Ewing's sarcoma/peripheral neuroectodermal tumor (n = 25), No complete or partial responses were observed in 17 patients with osteosarcoma, 15 patients with rhabdomyosarcoma, or 2 patients with other soft-tissue sarcomas; however, 8 patients had prolonged (15-48 weeks) stable disease while receiving topotecan, Topotecan was well tolerated, The most commonly observed toxicities were myelosuppression (dose-limiting) and nausea and vomiting, Intrapatient dose escalations were performed in 68% of the patients who received more than one cycle of topotecan, and 1.3 mg/m(2)/day was tolerated by 79% of the patients who received the higher dose and were evaluable for hematological toxicity, In conclusion, topotecan administered as a 72-h continuous infusion every 21 days is inactive (objective response rate, <20%) in children with refractory or recurrent neuroblastoma and sarcomas of soft tissue or bone. C1 Childrens Canc Grp, Arcadia, CA USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. RP Blaney, SM (reprint author), Texas Childrens Canc Ctr, 6621 Fannin St,MC 3-3320, Houston, TX 77030 USA. FU PHS HHS [13539] NR 12 TC 43 Z9 44 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 FEB PY 1998 VL 4 IS 2 BP 357 EP 360 PG 4 WC Oncology SC Oncology GA YV861 UT WOS:000071870700015 PM 9516923 ER PT J AU Sharaf, BL Bourassa, MG McMahon, RP Pepine, CJ Chaitiman, BR Williams, DO Davies, RF Proschan, M Conti, CR AF Sharaf, BL Bourassa, MG McMahon, RP Pepine, CJ Chaitiman, BR Williams, DO Davies, RF Proschan, M Conti, CR CA ACIP Investigators TI Clinical and detailed angiographic findings in patients with ambulatory electrocardiographic ischemia without critical coronary narrowing: Results from the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study SO CLINICAL CARDIOLOGY LA English DT Article DE coronary anatomy; ambulatory ischemia; coronary angiography; myocardial ischemia ID SILENT MYOCARDIAL ISCHEMIA; UNSTABLE ANGINA-PECTORIS; ARTERY DISEASE; STABLE ANGINA; FOLLOW-UP; PROGNOSTIC-SIGNIFICANCE; DAILY LIFE; ARTERIOGRAMS; INFARCTION; TRANSIENT AB Background: Patients with ambulatory electrocardiographic (AECG) ST-segment depression and critical coronary narrowing are known to be at increased risk for adverse outcome, but little is known about patients with AECG ST-segment depression without critical coronary narrowing, Hypothesis: The objectives of this study were to characterize the coronary angiographic pathology in patients with AECG ST-segment depression but without critical (< 50% diameter stenosis) coronary narrowing and to compare demographic and clinical findings in these patients with those enrolled in the Asymptomatic Cardiac Ischemia Pilot Study with AECG ST-segment depression and critical (greater than or equal to 50% diameter stenosis) coronary narrowing. Methods: Coronary angiograms from patients with AECG ST-segment depression were reviewed in a central laboratory and quantitative measurement of percent stenosis was performed. Clinical and angiographic comparisons were made between patients with and without critical coronary narrowing. Results: Patients without critical coronary narrowing (n = 64) were younger (p = 0.02), less likely to be male (p < 0.001) or to have risk factors for coronary atherosclerosis or a history of myocardial infarction (p < 0.001), and had fewer ischemic episodes per 24 h on the screening AECG (p = 0.02) than patients with critical coronary narrowing (n = 441). Of patients without critical narrowing, one half had angiographic evidence for coronary artery disease (greater than or equal to 20% stenosis) and 60% had an ejection fraction > 70%. Conclusions: Patients with AECG ST-segment depression without critical coronary narrowing are heterogeneous, with half having measurable coronary artery disease. Demographically and clinically, they appear to be different than patients with AECG ST-segment depression with critical coronary narrowing. C1 Brown Univ, Rhode Isl Hosp, Div Cardiol, Providence, RI 02903 USA. Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. Univ Florida, Div Cardiol, Gainesville, FL USA. St Louis Univ, Med Ctr, Div Cardiol, St Louis, MO USA. Ottawa Heart Inst, Res Ctr, Ottawa, ON, Canada. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RI McMahon, Robert/C-5462-2009; OI Bourassa, Martial G./0000-0002-4439-8650 FU NHLBI NIH HHS [HV-90-07, HV-90-08, HV-91-05] NR 46 TC 2 Z9 2 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD FEB PY 1998 VL 21 IS 2 BP 86 EP 92 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW153 UT WOS:000071903800004 PM 9491946 ER PT J AU Lieberman, R Crowell, JA Hawk, ET Boone, CW Sigman, CC Kelloff, GJ AF Lieberman, R Crowell, JA Hawk, ET Boone, CW Sigman, CC Kelloff, GJ TI Development of new cancer chemoprevention agents: role in pharmacokinetic/pharmacodynamic and intermediate endpoint biomarker monitoring SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT Program on the Role of Therapeutic Drug Monitoring in Disease Management at the Annual Meeting of the AACC CY JUL, 1997 CL ATLANTA, GEORGIA SP AACC, Therapeut Drug Monitoring & Clin Toxicol Div, Natl Acad Clin Biochem, Abbott Lab, Behring Diagnost Inc, Boehringer Mannheim Corp, Chiron Diagnost, Dade Int ID FENRETINIDE; MODEL AB Recently, several promising strategies have been advanced for improving the efficiency of new agent development. These include pharmacokinetic/pharmacodynamic (PK/PD) and intermediate endpoint biomarker (IEB) monitoring. Here, We review their essential role as practical tools for guiding the evaluation of agents for cancer chemoprevention (CP) and provide examples of CP agents that utilize these approaches, Several important categories of IEBs are delineated, including histologically based (intraepithelial neoplasias and nuclear morphometry). The use of select IEBs combined with a Bayesian method for clinical trial monitoring for rapid identification of ineffective or promising agents is discussed. The similarities between IEB and TBM are described. Finally, we present future tools for enhanced monitoring of CP agents that will impact on laboratory medicine and are also applicable to many other drug classes, e.g., laser capture microdissection and cDNA chip microarrays that assess gene expression patterns of precancerous and cancerous lesions. C1 NCI, Chemoprevent Branch, Rockville, MD 20852 USA. RP Lieberman, R (reprint author), NCI, Chemoprevent Branch, 6130 Execut Blvd,Rm EPN 201, Rockville, MD 20852 USA. EM Liebermr@dcpcepn.nci.nih.gov NR 20 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD FEB PY 1998 VL 44 IS 2 BP 420 EP 427 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA YW156 UT WOS:000071904100049 PM 9474054 ER PT J AU Enders, G Dotsch, J Bauer, J Nutzenadel, W Hengel, H Haffner, D Schalasta, G Searle, K Brown, KE AF Enders, G Dotsch, J Bauer, J Nutzenadel, W Hengel, H Haffner, D Schalasta, G Searle, K Brown, KE TI Life-threatening parvovirus B19-associated myocarditis and cardiac transplantation as possible therapy: Two case reports SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID B19 AB Parvovirus B19 infection can cause a wide spectrum of disease syndromes, Two cases of parvovirus B19 infection were identified that resulted in life-threatening myocarditis shortly after acute infection in immunocompetent individuals, The diagnosis was made with serological and polymerase chain reaction techniques, One patient was succesfully treated by heart transplantation. Sequence analysis showed that the parvovirus B19 cloned from the patients' sera had 99% homology with the prototype sequence, Clinicians should be alerted to the possible role of parvovirus B19 in myocarditis presenting in immunocompetent patients. C1 Inst Virol Infektiol & Epidemiol EV, D-70193 Stuttgart, Germany. Univ Giessen, Dept Pediat, D-35390 Giessen, Germany. Univ Heidelberg, Dept Pediat, D-6900 Heidelberg, Germany. Univ Heidelberg, Dept Virol, D-6900 Heidelberg, Germany. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Enders, G (reprint author), Inst Virol Infektiol & Epidemiol EV, Rosenbergstr 85, D-70193 Stuttgart, Germany. NR 10 TC 48 Z9 52 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 FEB PY 1998 VL 26 IS 2 BP 355 EP 358 DI 10.1086/516295 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YW499 UT WOS:000071941900018 PM 9502455 ER PT J AU Komatsu, T Kanatsu, K Kuze, K Iehara, N Takeoka, H Yamada, Y Kita, T Doi, T AF Komatsu, T Kanatsu, K Kuze, K Iehara, N Takeoka, H Yamada, Y Kita, T Doi, T TI Demonstration of DNA replication factor C in human glomerular lesions SO CLINICAL NEPHROLOGY LA English DT Article DE glomerulosclerosis; proliferation; DNA binding protein; type IV collagen ID CELL NUCLEAR ANTIGEN; GROWTH-HORMONE; PROGRESSIVE GLOMERULOSCLEROSIS; MESSENGER-RNA; LARGE SUBUNIT; KIDNEY; GLOMERULONEPHRITIS; COLLAGEN; TURNOVER; MATRIX AB Glomerulosclerosis is a common pathological finding in many human glomerular diseases that ultimately leads to end-stage kidney disease. The regulatory mechanism that controls mesangial proliferation as well as accumulation of mesangial matrix: however, is not known. Recently, a protein factor (MSW) which binds to the specific sequence of the promoter of the alpha(1) and alpha(2) type IV collagen genes was cloned. MSW was found to be identical to a large subunit (Alp145) of DNA replication factor C. These findings suggest that MSW may have important functions in mesangial cell proliferation and type IV collagen synthesis, both of which are prominent findings in glomerulosclerosis. In the present study, we report that augmented expression of MSW protein in human glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy, membranoproliferative glomerulonephritis, and focal glomerulosclerosis). Minimal expression of MSW protein was observed in human glomerular diseases that rarely show glomerulosclerosis (membranous nephropathy, and minimal change nephrotic syndrome). There was a significant correlation between the levels of MSW expression and type IV collagen expression. Elevated expressions of both proliferating cell nuclear antigen and MSW were also observed in most patients with proliferative glomerular diseases. These studies suggest that MSW protein plays a regulatory role in the development of mesangial cell proliferation and matrix expansion during progression of glomerular injuries. C1 Amagasaki Prefectural Hosp, Dept Internal Med, Amagasaki, Hyogo, Japan. Kyoto Univ, Fac Med, Dept Geriatr Med, Div Clin Bioregulatory Sci, Kyoto, Japan. Kyoto Univ, Fac Med, Div Artificial Kidneysf, Kyoto, Japan. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Doi, T (reprint author), Kyoto Univ Hosp, Div Artificial Kidneys, Sakyo Ku, 54 Shogoin Kawahara Cho, Kyoto 606, Japan. NR 15 TC 1 Z9 1 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD FEB PY 1998 VL 49 IS 2 BP 69 EP 73 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA YX726 UT WOS:000072071100001 PM 9524775 ER PT J AU Binks, SW Gold, JM AF Binks, SW Gold, JM TI Differential cognitive deficits in the neuropsychology of schizophrenia SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID MONOZYGOTIC TWINS DISCORDANT; CARD SORTING TEST AB Controversy concerning interpretation of neuropsychological findings in schizophrenia fan partly be attributed to use of tests lacking in accepted factor structure and having widely varying norming populations, sensitivity, and specificity. The Woodcock-Johnson (WJ-R) overcomes many of these psychometric weaknesses by providing seven co-normed cognitive factor scores covering a wide range of cognitive domains, thereby allowing for the rigorous determination of individual strengths/weaknesses. We administered it with traditional neuropsychological batteries to 30 schizophrenic patients. WJ-R data suggest: (1) average premorbid achievement; (2) general decline across factors: (3) differential weaknesses in processing speed and memory; (4) substantial within-subject heterogeneity across cognitive factors; and (5) substantial within-factor homogeneity across subjects. Stepwise regression of the WJ-R factors using traditional test batteries suggests that they have neuropsychological validity and psychometric advantages. C1 NIMH, Neuropsychiat Res Hosp, Clin Res Serv Branch, NIH, Washington, DC 20032 USA. RP Binks, SW (reprint author), 1828 Calvert St,NW, Washington, DC 20009 USA. NR 32 TC 6 Z9 6 U1 1 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD FEB PY 1998 VL 12 IS 1 BP 8 EP 20 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA ZE592 UT WOS:000072810000002 ER PT J AU Ramirez, J Iyer, L Lush, RM Mortell, M Feuer, JA Figg, WD Sausville, EA Ratain, MJ AF Ramirez, J Iyer, L Lush, RM Mortell, M Feuer, JA Figg, WD Sausville, EA Ratain, MJ TI In vitro glucuronidation of flavopiridol (NSC649890) (FLAVO) by human liver microsomes. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Comm Clin Pharmacol, Chicago, IL 60637 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PI50 BP 149 EP 149 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300051 ER PT J AU Gotschall, R Leeder, JS Farrar, H McCubbin, M Johnson, K Kearns, GL AF Gotschall, R Leeder, JS Farrar, H McCubbin, M Johnson, K Kearns, GL TI Caffeine plasma clearance in cystic fibrosis (CF) does not correlate with CYP1A2 activity. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. Univ Missouri, Dept Pharmacol, Kansas City, MO 64110 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. NICHD, PPRU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PII79 BP 192 EP 192 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300221 ER PT J AU Kearns, GL Wells, TW Blowey, DL Jackson, MA Burry, VF AF Kearns, GL Wells, TW Blowey, DL Jackson, MA Burry, VF TI Pharmacokinetics of pleconaril in children. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. Univ Missouri, Dept Pharmacol, Kansas City, MO 64110 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NICHD, Pediat Pharmacol Res Unit Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PII81 BP 193 EP 193 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300223 ER PT J AU George, D Sirocco, K Eckardt, M Linnoila, M AF George, D Sirocco, K Eckardt, M Linnoila, M TI Age of onset for alcoholism and CSF homovanillic acid concentrations predict relapse. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PII124 BP 203 EP 203 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300266 ER PT J AU Preston, KL Cone, EJ Wong, CJ Huestis, MA AF Preston, KL Cone, EJ Wong, CJ Huestis, MA TI Monitoring cocaine use with sweat patches. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PII122 BP 203 EP 203 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300264 ER PT J AU DePetrillo, PB AF DePetrillo, PB TI Calcium-channel blockers prevent ethanol-induced decreases in calpain activity in PC12 cells. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, DICBR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PII125 BP 204 EP 204 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300267 ER PT J AU Umhau, JC George, DT Porges, S Reed, S Graham, S Rawlings, R Linnoila, M AF Umhau, JC George, DT Porges, S Reed, S Graham, S Rawlings, R Linnoila, M TI Parasympathetic dyscontrol in perpetrators of domestic abuse. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. Univ Maryland, Inst Child Study, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PII130 BP 205 EP 205 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300272 ER PT J AU Kieffer, LV Takimoto, CH Morrison, GB Cantilena, LR Allegra, CJ Grem, JL Marino, M AF Kieffer, LV Takimoto, CH Morrison, GB Cantilena, LR Allegra, CJ Grem, JL Marino, M TI Development of a pharmacokinetic and pharmacodynamic population model of paclitaxel administered with 5-fluorouracil. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI, USN, Metab Oncol Branch, NIH, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. WRAIR, Washington, DC USA. USUHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PIII69 BP 224 EP 224 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300348 ER PT J AU Dai, R Wei, X Zhai, S Friedman, FK Vestal, RE AF Dai, R Wei, X Zhai, S Friedman, FK Vestal, RE TI A computer modeling study of P450 1A2 inhibition by class 1B antiarrhythmics. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. VAMC, Boise, ID USA. MSMRI, Boise, ID USA. Idaho State Univ, Pocatello, ID USA. Univ Washington, Seattle, WA 98195 USA. RI Friedman, Fred/D-4208-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PIII74 BP 225 EP 225 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300353 ER PT J AU Zhai, S Dai, R Friedman, FK Vestal, RE AF Zhai, S Dai, R Friedman, FK Vestal, RE TI Differential inhibition by flavonoids of human P450 1A1 and 1A2. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 VAMC, Boise, ID USA. MSMRI, Boise, ID USA. Idaho State Univ, Pocatello, ID 83209 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. RI Friedman, Fred/D-4208-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PIII75 BP 225 EP 225 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300354 ER PT J AU Bergan, R Patel, S Kyle, E Vishnuvajjala, B Lieberman, R AF Bergan, R Patel, S Kyle, E Vishnuvajjala, B Lieberman, R TI PK-PD of perillyl alcohol (PAL) and metabolites (METAB) in a human prostate cancer (PCA) model system: Implications for TDM in cancer SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PIII127 BP 238 EP 238 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300406 ER PT J AU Dionne, RA Gordon, SM Brahim, JS Rowan, J Kent, AA AF Dionne, RA Gordon, SM Brahim, JS Rowan, J Kent, AA TI Peripheral PGE(2) levels following tissue injury and NSAID analgesia. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA OIIIB3 BP 240 EP 240 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300414 ER PT J AU Bigger, JT Parides, MK Rolnitzky, LM Meier, P Levin, B Egan, DA AF Bigger, JT Parides, MK Rolnitzky, LM Meier, P Levin, B Egan, DA TI Changes in sample size and length of follow-up to maintain power in the coronary artery bypass graft (CABG) patch trial SO CONTROLLED CLINICAL TRIALS LA English DT Article DE arrhythmia; clinical trial; coronary artery bypass graft surgery; group sequential monitoring; implantable cardiac defibrillator; sample size; statistical power; survival analysis ID SUDDEN-DEATH SURVIVORS; FIRST-CHOICE THERAPY; IMPLANTABLE DEFIBRILLATOR; CLINICAL-TRIALS; STATISTICS; STRATEGY AB The CABG Patch Trial is testing the hypothesis that prophylactic use of implantable cardiac defibrillators (ICDs) will improve survival in high-risk coronary heart disease patients undergoing CABG surgery. The original design called for 800 patients to be randomized to ICD prophylaxis or to no therapy and followed for 2 to 6.5 years (average, 40 months) to a common termination date. Since the ICD pulse generators used in this trial lasted about 42 months, the original design required ICD replacement in many patients. At its first two meetings in 1993, the Data and Safety Monitoring Board (DSMB) formalized a plan to adjust sample size in October 1994 if the control group mortality rate was lower than expected. In June 1994, an unanticipated and unique event-a subpoena from the Office of the Inspector General (OIG)-made it impossible to replace about half of the ICD generators and threatened to shorten follow-up substantially. If follow-up had been stopped on the date originally planned, but without replacing ICDs, the average follow-up would have fallen from 40 months to about 33 months. Also, in October 1994, the control group mortality rate was found to be somewhat lower than expected. Together, the abbreviated follow-up and lower control group mortality threatened to reduce power substantially. The DSMB reviewed several options for restoring power. Because mortality rates in the first month after CABG surgery were about seven times as high as thereafter and because ICD therapy did not reduce surgical mortality (death during the first 30 days), extending the follow-up benefits power more than does increasing the sample size. However, the limit on extending follow-up was 42 months (the expected battery life of the ICD). Data from the ICD-treated group was not reviewed or considered in making the decision. After reviewing many options for restoring power, the DSMB recommended that the sample size be increased from 800 to 900 patients and that almost all patients be followed for 42 months. This recommendation extended follow-up for 2 years beyond the original termination date planned for the trial and dictated that patients close out after 42 months rather than on a common termination date. (C) Elsevier Science Inc. 1998. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Columbia Univ, Sch Publ Hlth, Div Biostat, New York, NY 10032 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Bigger, JT (reprint author), Columbia Univ, Data Coordinating ctr, CABG Patch Trial, PH 103-D,630 W 168th St, New York, NY 10032 USA. FU NHLBI NIH HHS [HL-48120, HL-48159] NR 11 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1998 VL 19 IS 1 BP 1 EP 14 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA YV669 UT WOS:000071850900001 PM 9492965 ER PT J AU Adams, RJ McKie, VC Brambilla, D Carl, E Gallagher, D Nichols, FT Roach, S Abboud, M Berman, B Driscoll, C Files, B Hsu, L Hurlet, A Miller, S Olivieri, N Pegelow, C Scher, C Vichinsky, E Wang, W Woods, G Kutlar, A Wright, E Hagner, S Tighe, F Lewin, J Cure, J Zimmerman, RA Waclawiw, MA AF Adams, RJ McKie, VC Brambilla, D Carl, E Gallagher, D Nichols, FT Roach, S Abboud, M Berman, B Driscoll, C Files, B Hsu, L Hurlet, A Miller, S Olivieri, N Pegelow, C Scher, C Vichinsky, E Wang, W Woods, G Kutlar, A Wright, E Hagner, S Tighe, F Lewin, J Cure, J Zimmerman, RA Waclawiw, MA TI Stroke prevention trial in sickle cell anemia SO CONTROLLED CLINICAL TRIALS LA English DT Article DE Sickle Cell Disease; stroke; cerebral infarction; cerebral hemorrhage; transcranial Doppler ultrasound; transfusion; Magnetic Resonance Imaging; Magnetic Resonance Angiography; children/pediatric; randomized controlled trial ID TRANSFUSION THERAPY; CNS INFARCTION; DISEASE; CHILDREN AB Stroke occurs in 7-8% of children with Sickle Cell Disease (Hb SS) and is a major cause of morbidity. Rates of recurrence have been reduced from 46-90% to less than 10% through chronic blood transfusions. Prevention of first stroke, however, would be preferable because even one stroke can cause irreversible brain injury. Transcranial Doppler (TCD) ultrasound can detect arterial blood flow rates associated with subsequent stroke risk. By combining TCD screening and a potentially effective treatment, first stroke may be prevented. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) is the first stroke prevention trial in Hb SS and the first randomized, controlled use of transfusion in Hb SS. This multi-center trial is designed to test whether reducing sickle hemoglobin to 30% or less with periodic blood transfusions will reduce first-time stroke by at least 70% compared to standard care. Primary endpoints will be clinically evident symptoms of cerebral infarction with consistent findings on Magnetic Resonance Imaging and Angiography (MRI/MRA) or symptomatic intracranial hemorrhage. Secondary endpoints will be asymptomatic brain lesions detected by MRI in brain areas not involved in primary endpoints. The design calls for a 6-month start-up interval, 18 months of TCD screening and randomization, and observation for stroke from entry through month 54. Key features of the trial are standardized TCD and MRI/MRA protocols interpreted blindly, and blinded adjudication of endpoints. The sample size (60 per treatment group) is based on prospective data relating TCD velocity to risk of stroke. A time-averaged mean velocity of greater than or equal to 200 cm/sec is associated with a 46% risk of cerebral infarction over 39 months. The sample size is sufficient to detect 70% reduction in the primary endpoint at 90% power. This trial will determine if transfusion is effective in the primary prevention of stroke. Secondary aims may further the understanding of the effects of transfusion on the brain and guide future research into cerebrovascular disease in Hb SS. (C) Elsevier Science Inc. 1998. C1 Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Med Univ S Carolina, Charleston, SC 29425 USA. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp Eastern N Carolina, Greenville, NC USA. Emory Univ, Sch Med, Atlanta, GA USA. Columbia Presbyterian Hosp, Atlanta, GA USA. SUNY Hlth Sci Ctr, Brooklyn, NY USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Miami, Miami, FL 33152 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Childrens Hosp Oakland, Oakland, CA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. RP Adams, RJ (reprint author), Med Coll Georgia, Dept Neurol, 1467 Harper St,HB-2060, Augusta, GA 30912 USA. RI Hsu, Lewis/A-3360-2008 FU NHLBI NIH HHS [5-P01 HL 41544, 5-U10 HL 52193] NR 20 TC 109 Z9 109 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1998 VL 19 IS 1 BP 110 EP 129 PG 20 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA YV669 UT WOS:000071850900007 PM 9492971 ER PT J AU Hasinoff, BB Hellmann, K Herman, EH Ferrans, VJ AF Hasinoff, BB Hellmann, K Herman, EH Ferrans, VJ TI Chemical, biological and clinical aspects of dexrazoxane and other bisdioxopiperazines SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID CARDIOPROTECTIVE AGENT ICRF-187; SPONTANEOUSLY HYPERTENSIVE RATS; SYRIAN GOLDEN-HAMSTERS; DNA TOPOISOMERASE-II; DOXORUBICIN-INDUCED CARDIOTOXICITY; HYDROXYL RADICAL PRODUCTION; CHRONIC DAUNORUBICIN CARDIOTOXICITY; PERFORMANCE LIQUID-CHROMATOGRAPHY; HEART SUBMITOCHONDRIAL PARTICLES; IRON-ANTHRACYCLINE COMPLEXES AB The bisdioxopiperazine dexrazoxane (ICRF-187) has proven to be clinically very effective in reducing the cardiotoxicity of doxorubicin and other anthracyclines. Doxorubicin is thought to exert its toxicity through iron-based oxygen free radical-induced oxidative stress on the relatively unprotected cardiac muscle. Upon hydrolysis, dexrazoxane forms a compound similar to ethylenediaminetetraacetic acid (EDTA) which, like EDTA, is a strong chelator of iron. Dexrazoxane presumably exerts its cardioprotective effects by either binding free or loosely bound iron, or iron complexed to doxorubicin, thus preventing or reducing site-specific oxygen radical production that damages cellular components. The chemistry, biochemistry, and cell biology of dexrazoxane and other bisdioxopiperazines are discussed. The pre-clinical studies demonstrating the protective effects of dexrazoxane against toxicities caused by doxorubicin, other anthracyclines, bleomycin, alloxan. acetaminophen, and oxygen are also discussed. in vitro and in vivo studies of the cardioprotective and other effects of other bisdioxopiperazines are also covered. Also discussed are the anti-metastatic and radiosensitization effects of razoxane and dexrazoxane. The current clinical status of dexrazoxane in preventing anthracycline-induced toxicities in both adult and pediatric patients is reviewed. C1 Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. Windleshaw House, Withyham 7N7 4DB, E Sussex, England. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Hasinoff, BB (reprint author), Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. NR 223 TC 111 Z9 112 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD FEB PY 1998 VL 5 IS 1 BP 1 EP 28 PG 28 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA YZ154 UT WOS:000072225700001 PM 9481032 ER PT J AU Gait, MJ Hughes, SH AF Gait, MJ Hughes, SH TI Analytical biotechnology - Overview SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Editorial Material C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Gait, MJ (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 1998 VL 9 IS 1 BP 11 EP 13 DI 10.1016/S0958-1669(98)80077-3 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YY066 UT WOS:000072108800001 ER PT J AU Fivash, M Towler, EM Fisher, RJ AF Fivash, M Towler, EM Fisher, RJ TI BIAcore for macromolecular interaction SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID SURFACE-PLASMON RESONANCE; BINDING; AFFINITY; SELECTION; KINETICS AB Examination of the literature for the period of this review revealed nearly two hundred citations that employed surface plasmon resonance (SPR) spectroscopy using BIAcore technology to evaluate biospecific interactions, demonstrating the increasing popularity of this powerful technique. Among these we noted the development of several new applications/modifications of standard techniques. In general, we find the qualitative aspects of the reported experiments to be excellent but the quantitative descriptions (k(T), k(on), k(off), and K-eq) as well as the binding models still lagging behind. (C) Current Biology Ltd ISSN 0958-1669. C1 NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, SAIC, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Prot Chem Lab, SAIC, Frederick, MD 21702 USA. RP Fisher, RJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, SAIC, POB B, Frederick, MD 21702 USA. RI Fisher, Robert/B-1431-2009 NR 34 TC 154 Z9 157 U1 2 U2 27 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 1998 VL 9 IS 1 BP 97 EP 101 DI 10.1016/S0958-1669(98)80091-8 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YY066 UT WOS:000072108800015 PM 9503595 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, J TI Cytoskeletal proteins and Golgi dynamics SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ACTIN-RELATED PROTEIN; ENDOPLASMIC-RETICULUM; DYNACTIN COMPLEX; MEMBRANE; KINESIN; MICROTUBULES; ORGANIZATION; APPARATUS; CHAINS; IDENTIFICATION AB Association of the Golgi complex with cytoskeletal elements, in particular microtubules, is required for maintenance of the Golgi's characteristic spatial location within cells and for efficient delivery of proteins and lipids to diverse cellular sites. Recent work has suggested the mechanisms underlying this association involve components, such as ankyrin and spectrin, that facilitate Golgi membrane association with motor proteins, including cytoplasmic dynein, kinesin and myosin. Understanding how these associations are regulated and what roles they play in Golgi trafficking and dynamics is fundamental for insight into the spatial and functional integration of secretory membrane traffic. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov NR 59 TC 145 Z9 151 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD FEB PY 1998 VL 10 IS 1 BP 52 EP 59 DI 10.1016/S0955-0674(98)80086-0 PG 8 WC Cell Biology SC Cell Biology GA YW906 UT WOS:000071986600006 PM 9484595 ER PT J AU Auerbach, JD AF Auerbach, JD TI The role of behavioral research in HIV/AIDS prevention SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID METHADONE-MAINTENANCE TREATMENT; RISK-REDUCTION INTERVENTION; INJECTING DRUG-USERS; HIV-INFECTION; SEXUAL-BEHAVIOR; WOMEN; MEN; SEROCONVERSION; HETEROSEXUALS AB Behavioral and social research has been at the core of HIV/AIDS prevention efforts, by identifying the factors that contribute to the risk of transmission and by developing effective behavioral interventions to modify that risk. The historical focus of behavior-change strategies on decision-making processes within the individual has evolved to include more attention to the dynamics of interpersonal relationships and the sociocultural contexts in which HIV-related risk behaviors occur. (C) 1988 Rapid Science Ltd. C1 NIH, Off AIDS Res, Bethesda, MD 20892 USA. RP Auerbach, JD (reprint author), NIH, Off AIDS Res, Bldg 31,Room 4C06,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 44 TC 4 Z9 4 U1 12 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD FEB PY 1998 VL 11 IS 1 BP 3 EP 7 PG 5 WC Infectious Diseases SC Infectious Diseases GA YT332 UT WOS:000071590900002 PM 17033358 ER PT J AU Hackstadt, T AF Hackstadt, T TI The diverse habitats of obligate intracellular parasites SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID ENDOGENOUSLY SYNTHESIZED SPHINGOMYELIN; CHLAMYDIA-TRACHOMATIS INCLUSION; PHOSPHOLIPASE-A ACTIVITY; COXIELLA-BURNETII; GOLGI-APPARATUS; RICKETTSIA-PROWAZEKII; PARASITOPHOROUS VACUOLES; ELECTRON-MICROSCOPY; TOXOPLASMA-GONDII; ENDOCYTIC PATHWAY AB Bacterial obligate intracellular parasites have evolved diverse mechanisms for evasion of host cellular defenses. These mechanisms involve adaptations for survival in distinct intracellular compartments. Intracellular niches inhabited by obligate intracellular parasites include the cytoplasm, arrested early endosomes, lysosomes, and vesicles that do not fuse with the endosomal compartment but intersect with an exocytic pathway. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov NR 60 TC 53 Z9 58 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD FEB PY 1998 VL 1 IS 1 BP 82 EP 87 DI 10.1016/S1369-5274(98)80146-X PG 6 WC Microbiology SC Microbiology GA 117DH UT WOS:000075765000012 PM 10066459 ER PT J AU Raedler, TJ Knable, MB Weinberger, DR AF Raedler, TJ Knable, MB Weinberger, DR TI Schizophrenia as a developmental disorder of the cerebral cortex SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID CHILDHOOD-ONSET SCHIZOPHRENIA; PREFRONTAL WHITE-MATTER; PATHOLOGY; NEURONS; EXPRESSION; EXPOSURE; DENSITY; BRAINS; RISK AB The hypothesis that schizophrenia results from a developmental, as opposed to a degenerative, process affecting the cerebral cortex has become popular in current thinking about the disorder. While many of the data gathered in support of this hypothesis do not in themselves represent conclusive proof, an intriguing picture is emerging from a variety of research approaches. These approaches include the observation of minor physical anomalies, premorbid neuropsychological and social deficits, obstetrical complications, and exposure to adverse intrauterine events. Morphometric brain measurement techniques and neuropathological studies have perhaps provided more substantial support. C1 NIMH, Intramural Res Program, Clin Brain Disorders Branch, Washington, DC 20032 USA. RP Raedler, TJ (reprint author), NIMH, Intramural Res Program, Clin Brain Disorders Branch, 2700 Martin Luther King Jr Ave SE, Washington, DC 20032 USA. EM knablem@kirpc.nimh.nih.gov NR 42 TC 104 Z9 107 U1 5 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD FEB PY 1998 VL 8 IS 1 BP 157 EP 161 DI 10.1016/S0959-4388(98)80019-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZE252 UT WOS:000072773400017 PM 9568403 ER PT J AU Sueoka, N Sueoka, E Miyazaki, Y Okabe, S Kurosumi, M Takayama, S Fujiki, H AF Sueoka, N Sueoka, E Miyazaki, Y Okabe, S Kurosumi, M Takayama, S Fujiki, H TI Molecular pathogenesis of interstitial pneumonitis with TNF-alpha transgenic mice SO CYTOKINE LA English DT Article DE cytokine network; fibrosis; interstitial; pneumonitis; TNF-alpha ID IDIOPATHIC PULMONARY FIBROSIS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; LOWER RESPIRATORY-TRACT; GENE-EXPRESSION; MESSENGER-RNA; ALVEOLAR MACROPHAGES; CELL-PROLIFERATION; ASBESTOS EXPOSURE; EPITHELIAL-CELLS AB Tumour necrosis factor alpha (TNF-alpha)transgenic mice, which overexpress TNF-alpha only in the lungs, develop interstitial pneumonitis resembling idiopathic pulmonary fibrosis (IPF) in humans, Transgenic mice were used to study molecular pathogenesis of interstitial pneumonitis with regard to sequential histological changes and cytokine network induced by TNF-alpha, The authors divided the histological process of interstitial pneumonitis into three stages: early stage with lymphocytic infiltration in alveolar septa, middle stage with recruitment of macrophages, and late stage with hyperplasia of epithelial cells and mild fibrosis, As for cytokine network, prolonged overexpression of TNF-a along with increasing interleukin 6 (IL-6) were associated with the progression of interstitial pneumonitis, Increasing IL-1 was found only in the early stage, the beginning of lymphocyte proliferation, The mRNA level of an anti-inflammatory cytokine, IL-10, was constantly enhanced in the lungs of transgenic mice, However, transforming growth factor beta 1 (TGF-beta 1) protein decreased, which is closely associated with prolonged TNF-alpha synthesis, resulting in development of chronic inflammation and less severe fibrosis in the lungs of this animal model, analogous to inflammatory stage of human IPF, TNF-alpha transgenic mice enabled the analysis of the sequential process of interstitial pneumonitis as a model of IPF pathogenesis in humans, the results of which will give rise to new therapeutic measures for human IPF. (C) 1998 Academic Press Limited. C1 Saitama Canc Ctr, Res Inst, Ina, Saitama 362, Japan. Kyushu Univ, Med Inst Bioregulat, Dept Clin Immunol, Oita 874, Japan. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Fujiki, H (reprint author), Saitama Canc Ctr, Res Inst, Ina, Saitama 362, Japan. NR 37 TC 23 Z9 26 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 1043-4666 J9 CYTOKINE JI Cytokine PD FEB PY 1998 VL 10 IS 2 BP 124 EP 131 DI 10.1006/cyto.1997.0267 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA YY446 UT WOS:000072147400007 PM 9512902 ER PT J AU Xu, XL Weinstein, M Li, CL Naski, M Cohen, RI Ornitz, DM Leder, P Deng, CX AF Xu, XL Weinstein, M Li, CL Naski, M Cohen, RI Ornitz, DM Leder, P Deng, CX TI Fibroblast growth factor receptor 2 (FGFR2)-mediated reciprocal regulation loop between FGF8 and FGF10 is essential for limb induction SO DEVELOPMENT LA English DT Article DE FGFR2; chorioallantoic fusion; placentation; FGF8 induction; Fgf10 expression; limb bud initiation ID APICAL ECTODERMAL RIDGE; TRACHEAL CELL-MIGRATION; SONIC-HEDGEHOG; TARGETED DISRUPTION; VERTEBRATE LIMB; MICE LACKING; MOUSE DEVELOPMENT; LIGAND-BINDING; NERVOUS-SYSTEM; FEEDBACK LOOP AB FGFR2 is a membrane-spanning tyrosine kinase that serves as a high affinity receptor for several members of the fibroblast growth factor (FGF) family, To explore functions of FGF/FGFR2 signals in development, we have mutated FGFR2 by deleting the entire immunoglobin-like domain III of the receptor, We showed that murine FGFR2 is essential for chorioallantoic fusion and placenta trophoblast cell proliferation. Fgfr2(Delta IgIII/Delta IgIII) embryos displayed two distinct defects that resulted in failures in formation of a functional placenta, About one third of the mutants failed to form the chorioallantoic fusion junction and the remaining mutants did not have the labyrinthine portion of the placenta. Consequently, all mutants died at 10-11 days of gestation. Interestingly, Fgfr2(Delta IgIII/Delta IgIII) embryos do not form limb buds, Consistent with this defect, the expression of Fgf8, an apical ectodermal factor, is absent in the mutant presumptive limb ectoderm, and the expression of Fgf10, a mesenchymally expressed limb bud initiator, is down regulated in the underlying mesoderm, These findings provide direct genetic evidence that FGF/FGFR2 signals are absolutely required for vertebrate limb induction and that an FGFR2 signal is essential for the reciprocal regulation loop between FGF8 and FGF10 during limb induction. C1 NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA. NIH, Lab Dev Neurogenet, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. RP Deng, CX (reprint author), NIDDKD, Biochem & Metab Lab, 10-9N105, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016; OI Ornitz, David/0000-0003-1592-7629 FU NCI NIH HHS [CA60673] NR 75 TC 376 Z9 384 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 1998 VL 125 IS 4 BP 753 EP 765 PG 13 WC Developmental Biology SC Developmental Biology GA ZB953 UT WOS:000072524900019 PM 9435295 ER PT J AU Cinti, S Eberbach, S Castellucci, M Accili, D AF Cinti, S Eberbach, S Castellucci, M Accili, D TI Lack of insulin receptors affects the formation of white adipose tissue in mice. A morphometric and ultrastructural analysis SO DIABETOLOGIA LA English DT Article DE diabetes mellitus; adipocyte; genetics; growth; receptors ID GENE; DIFFERENTIATION; RESISTANCE; MECHANISMS; PERIOD AB Lack of insulin receptors in mice is associated with near-normal intrauterine growth, unlike patients with leprechaunism, in whom growth deficiency is a prominent clinical feature. Genetic crosses of insulin receptor-and insulin-like growth-factor-1 (IGF-1) receptor-deficient mice indicate, however, that insulin receptors play an important role in late gestational growth, and that absence of growth retardation in insulin receptor-deficient (IR-/-) mice may be due to a compensatory increase in IGF-1 receptor levels. In human fetuses, insulin has a paramount role in the generation and maintenance of adipose tissue, as demonstrated by changes associated with genetic and maternally caused fetal hyperinsulinaemia. In the present study, we have investigated whether genetic ablation of insulin receptors affects differentiation and trophism of white adipose tissue, the main target organ for the growth-promoting actions of fetal insulin. Histological, immunohistochemical, and ultrastructural analyses of white dermal adipose tissue were performed in newborn IR-/- mice, as well as normal (IR+/+) and heterozygous controls (IR+/-). Stereological measurements revealed a marked decrease of the adipose area in IR-/- mice compared to IR+/+ and IR+/- mice. Fat cell depletion resulted mainly from a reduction of adipocyte volume (similar to 90 %), with a small decrease of adipocyte number. Electron microscopy analysis detected all stages of differentiation of the adipocyte precursor in IR-/- mice, suggesting that lack of insulin receptors is not associated with selective impairment of the adipocyte differentiation process. These data are consistent with a bi-modal action of fetal insulin receptors, one to mediate embryonic growth in response to IGF-2, and one to mediate adipose cell formation in response to insulin. C1 Univ Ancona, Fac Med & Chirurg, Ist Morfol Umana Normale, I-60128 Ancona, Italy. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Accili, D (reprint author), Bldg 10 Room 10D18, Bethesda, MD 20892 USA. NR 31 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 1998 VL 41 IS 2 BP 171 EP 177 DI 10.1007/s001250050886 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YV135 UT WOS:000071792900007 PM 9498650 ER PT J AU Chan, CC Shen, DF Nussenblatt, RB Boni, R Zhuang, ZP AF Chan, CC Shen, DF Nussenblatt, RB Boni, R Zhuang, ZP TI Detection of molecular changes in primary intraocular lymphoma by microdissection and polymerase chain reaction SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Letter C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, Bethesda, MD 20892 USA. NR 4 TC 17 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD FEB PY 1998 VL 7 IS 1 BP 63 EP 64 DI 10.1097/00019606-199802000-00011 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 103EU UT WOS:000075145900010 PM 9646037 ER PT J AU Hahm, KB Lee, KJ Kim, YS Kim, JH Cho, SW Yim, H Joo, HJ AF Hahm, KB Lee, KJ Kim, YS Kim, JH Cho, SW Yim, H Joo, HJ TI Augmented eradication rates of Helicobacter pylori by new combination therapy with lansoprazole, amoxicillin, and rebamipide SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Helicobacter pylori; rebamipide; oxidative stress; cytokine; eradication ID SUPEROXIDE-DISMUTASE; GASTRITIS; DAMAGE; ASSAY AB The aim of the present study was to determine the efficacy of a new combination regimen including an antioxidant, a proton pump inhibitor, and antibiotics against Helicobacter pylori and to document the changes of oxidative stress and cytokines involved in H. pylori-associated gastric inflammation. From 57 patients with endoscopically diagnosed gastric and/or duodenal ulcers associated with H. pylori infection five gastric antral biopsy specimens were taken for the diagnosis of H. pylori and for the experimental measures. The patients were then treated either with lansoprazole 30 mg + amoxicillin 1.5 g (LA group; 21 patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM group; 36 patients) for two weeks, Four weeks after the initiation of treatment, the patients were endoscoped again and biopsy specimens were obtained. Mucosal malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed and secreted) were measured, Using paraffin-embedded tissue sections, in situ terminal deoxyribonucleotide transferase (TdT) mediated dUTP nick end labeling (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide synthase (iNOS) were performed. Two weeks of treatment with the LA regimen resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment with the LAM regimen resulted in 75.0% eradication rates, Eradication rates between these two groups were statistically significantly different (P < 0.05). Mucosal MDA levels and MPO activities were significantly lower in the LAM group than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the treatment of H. pylori, especially so in the LAM group. The apoptotic index and iNOS score were significantly reduced after the eradication of H. pylori. The addition of an antioxidative drug to the eradication regimen against H. pylori has advantages either in augmenting the eradication rates of H. pylori or in decreasing the oxidative stress and cytokines levels generated by H. pylori infection. C1 Ajou Univ, Sch Med, Dept Gastroenterol, Suwon 441749, South Korea. Ajou Univ, Sch Med, Dept Pathol Anat, Suwon 441749, South Korea. RP Hahm, KB (reprint author), NCI, Chemoprevent Lab, Bldg 41,Rm B1111,Lib Dr, Bethesda, MD 20892 USA. NR 22 TC 15 Z9 15 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD FEB PY 1998 VL 43 IS 2 BP 235 EP 240 DI 10.1023/A:1018825532059 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZB223 UT WOS:000072449400003 PM 9512112 ER PT J AU Zhang, LJ Zhan, QM Zhan, SL Kashanchi, F Fornace, AJ Seth, P Helman, LJ AF Zhang, LJ Zhan, QM Zhan, SL Kashanchi, F Fornace, AJ Seth, P Helman, LJ TI p53 regulates human insulin-like growth factor II gene expression through active P4 promoter in rhabdomyosarcoma cells SO DNA AND CELL BIOLOGY LA English DT Article ID WILD-TYPE; IN-VIVO; RECEPTOR; TUMOR; SUPPRESSES; FREQUENCY; PROTEIN; MICE AB The developmentally regulated human insulin-like growth factor II (IGFII) gene is expressed at high levels in many types of tumors and promotes the proliferation of tumor cells with a high incidence of p53 gene defects. We have previously shown that p53 inhibits IGFII P3 promoter activity and decreases endogenous IGFII gene expression derived from the P3 promoter in rhabdomyosarcomas by interfering with TBP binding to the TATA element of the IGFII P3 promoter, In this report, we demonstrate that wild-type p53 expression in rhabdomyosarcoma cell lines containing mutant p53 leads to a decrease in the activity of another active IGFII promoter, P4, and a 5-fold reduction of IGFII mRNA derived from the P4 promoter. This inhibition of P4 activity is associated with direct binding of p53 to the P4 proximal promoter element despite the lack of a p53 consensus binding site, Our results suggest that p53 inhibits IGFII P4 promoter activity by a mechanism different than its effect on the P3 promoter. These data also supply further evidence of cross-talk between the IGF and p53 signaling pathways. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Biochem Lab, Bethesda, MD 20892 USA. NCI, Mol Virol Lab, Bethesda, MD 20892 USA. NCI, Med Breast Canc Sect, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 21 TC 31 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 FEB PY 1998 VL 17 IS 2 BP 125 EP 131 DI 10.1089/dna.1998.17.125 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA YZ753 UT WOS:000072288200003 PM 9502429 ER PT J AU van den Bree, MBM Svikis, DS Pickens, RW AF van den Bree, MBM Svikis, DS Pickens, RW TI Genetic influences in antisocial personality and drug use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE antisocial personality disorder; substance use disorder; comorbidity ID CROSS-FOSTERING ANALYSIS; SUBSTANCE-ABUSE; ENVIRONMENTAL-FACTORS; PSYCHIATRIC-DISORDERS; SEX-DIFFERENCES; ALCOHOL-ABUSE; TWIN PAIRS; FAMILIAL TRANSMISSION; PETTY CRIMINALITY; SWEDISH ADOPTEES AB While an association between antisocial personality disorder (APD) and substance use disorder (SUD) has been frequently observed, the causes of the comorbidity remain unclear. Adoption and twin studies have found evidence of both genetic and environmental influences in APD and SUD. Therefore, comorbidity between APD and SUD may be the result of shared genetic influences, shared environmental influences, or a combination of the two. However. only a limited number of adoption and twin studies have addressed this issue and the results have not been conclusive. In future studies. a distinction should be made between alcohol and drug abuse and between juvenile and adult APD symptoms. Twin samples of adequate size would allow use of structural equation analytical methods for estimation of the relative magnitude of genetic and environmental influences shared between the two conditions, as well as influences contributing to each specifically. Results would be highly relevant for the clinical setting as well as for efforts to identify the genes involved in either trait. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. RP van den Bree, MBM (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI turton, miranda/F-4682-2011 NR 95 TC 44 Z9 44 U1 10 U2 17 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 FEB 1 PY 1998 VL 49 IS 3 BP 177 EP 187 DI 10.1016/S0376-8716(98)00012-X PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZF591 UT WOS:000072869900002 PM 9571383 ER PT J AU Manganotti, P Gerloff, C Toro, C Katsuta, H Sadato, N Zhuang, P Leocani, L Hallett, M AF Manganotti, P Gerloff, C Toro, C Katsuta, H Sadato, N Zhuang, P Leocani, L Hallett, M TI Task-related coherence and task-related spectral power changes during sequential finger movements SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; coherence; motor control ID POSITRON EMISSION TOMOGRAPHY; SUPPLEMENTARY MOTOR AREA; CEREBRAL BLOOD-FLOW; CORTICAL AREAS; HAND MOVEMENT; BETA-RHYTHMS; HUMAN CORTEX; MU-RHYTHM; EEG; OSCILLATIONS AB In order to investigate the activity of cortical regions in the control of complex movements, we studied task-related coherence (TRCoh) and task-related spectral power (TRPow) changes in 8 right-handed subjects during the execution of 4 different finger movement sequences of increasing complexity. Ail sequences were performed with the right hand and were paced by a metronome at 2 Hz. EEG power spectra and coherence values were computed within alpha (8-12 Hz) and beta (13-20 Hz) frequency bands for 29 scalp EEG positions during the execution of the sequences and were compared with values obtained during a rest (control) condition. Movement sequences were associated with TRPow decreases in the alpha and beta frequency bands over bilateral sensorimotor and parietal areas, with a preponderance over the contralateral hemisphere. Increases of TRCoh occurred over bilateral frontocentral regions. TRCoh decreases were present over the temporal and occipital areas. The spatial extent and the magnitude of TRPow decreases and TRCoh increases in both frequency bands were greater for sequential movements of higher complexity than for simpler ones. These results are consistent with previous findings of bilateral activation of sensorimotor areas during sequential finger movements. Moreover, the present results indicate an active intercommunication between bilateral and mesial central and prefrontal regions which becomes more intense with more complex sequential movements. (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. EM hallett@codon.nih.gov NR 62 TC 150 Z9 150 U1 0 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD FEB PY 1998 VL 109 IS 1 BP 50 EP 62 DI 10.1016/S0924-980X(97)00074-X PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA YX442 UT WOS:000072040400007 PM 11003064 ER PT J AU Yarmola, E Chen, N Yi, D Chrambach, A AF Yarmola, E Chen, N Yi, D Chrambach, A TI Enhanced detection sensitivity of "fluorescence reduction" by shifting the analyte absorbance spectrum and use of a fluorescent paper with higher signal/noise ratio SO ELECTROPHORESIS LA English DT Article DE detection sensitivity; fluorescence; fluorescent paper ID GEL-ELECTROPHORESIS; RESOLUTION AB Nonfluorescing protein bands can be detected by the fluorescence optics of the commercial gel electrophoresis apparatus with automated scanning of the migration path (HPGE-1000, LabIntelligence, Belmont CA), taking advantage of the decrease of emission from a fluorescent paper placed below the gel by the absorbance of proteins ("fluorescence reduction"). That decrease of fluorescence gives rise to an inverted protein peak. Nonfluorescent colorless proteins appear to reduce the intensity of light emitted from the fluorescent paper due to absorbance of incident and emitted light. When the absorbance spectrum only slightly overlaps with the excitation and emission spectra of the fluorescent paper, that reduction is weak, and detection sensitivity in that application is consequently only 1/30 of that of fluorescent proteins. By contrast, when the protein is colored so that its absorbance spectrum overlaps widely with the excitation and emission spectra of the fluorescent paper, the sensitivity of "fluorescence reduction" equals 1/4 to 1/5 of that obtained for fluorescent proteins. Bands detected by "fluorescence reduction" provide a quantitative measure of protein load and mobility. The area of the inverted bands is proportional to protein loads up to 16 mu g/lane of the gel tray. A theory of "fluorescence reduction" is presented which accounts for the existence of a linear relationship between band area and load. C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Biopolymer Phys, Moscow, Russia. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 7 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD FEB PY 1998 VL 19 IS 2 BP 206 EP 211 DI 10.1002/elps.1150190211 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZB078 UT WOS:000072433100010 PM 9548280 ER PT J AU Ohlsson, C Bengtsson, BA Isaksson, OGP Andreassen, TT Slootweg, MC AF Ohlsson, C Bengtsson, BA Isaksson, OGP Andreassen, TT Slootweg, MC TI Growth hormone and bone SO ENDOCRINE REVIEWS LA English DT Review ID OSTEOBLAST-LIKE CELLS; MESSENGER-RIBONUCLEIC-ACID; IGF-BINDING PROTEIN-3; PLACEBO-CONTROLLED TRIAL; RAT OSTEOSARCOMA CELLS; VITAMIN-D METABOLISM; GH-DEFICIENT ADULTS; ISOENZYME ALKALINE-PHOSPHATASE; INSULIN-RECEPTOR SUBSTRATE-1; CLINICAL RESEARCH-CENTER C1 Sahlgrens Univ Hosp, Res Ctr Endocrinol & Metab, S-41345 Gothenburg, Sweden. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Aarhus, Inst Anat, Dept Connect Tissue Biol, Aarhus, Denmark. Eli Lilly & Co, Nieuwegein, Netherlands. RP Ohlsson, C (reprint author), Sahlgrenska Hosp, Dept Internal Med, Div Endocrinol, S-41345 Gothenburg, Sweden. EM Claes@SS.GU.SE NR 359 TC 539 Z9 554 U1 4 U2 39 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD FEB PY 1998 VL 19 IS 1 BP 55 EP 79 DI 10.1210/er.19.1.55 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YX480 UT WOS:000072044200003 PM 9494780 ER PT J AU Chrousos, GP AF Chrousos, GP TI Ultradian, circadian, and stress-related hypothalamic-pituitary-adrenal axis activity - A dynamic digital-to-analog modulation SO ENDOCRINOLOGY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; ARGININE-VASOPRESSIN; STIMULATED ADRENOCORTICOTROPIN; IN-VIVO; SECRETION; BASAL; INFLAMMATION; SUPPRESSION; ACTIVATION; RHYTHM C1 NICHHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHHD, Sect Pediat Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 30 TC 45 Z9 45 U1 0 U2 4 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 FEB PY 1998 VL 139 IS 2 BP 437 EP 440 DI 10.1210/en.139.2.437 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YR396 UT WOS:000071491000001 PM 9449607 ER PT J AU Haidan, A Bornstein, SR Glasow, A Uhlmann, K Lubke, C Ehrhart-Bornstein, M AF Haidan, A Bornstein, SR Glasow, A Uhlmann, K Lubke, C Ehrhart-Bornstein, M TI Basal steroidogenic activity of adrenocortical cells is increased 10-fold by coculture with chromaffin cells SO ENDOCRINOLOGY LA English DT Article ID RAT ADRENAL-CORTEX; ZONA GLOMERULOSA INVIVO; SIDE-CHAIN CLEAVAGE; IN-VITRO; CORTISOL SECRETION; FASCICULATA-RETICULARIS; EMBRYO COCULTURE; GENE-EXPRESSION; CORTICAL-CELLS; PROTEIN-KINASE AB Historically, catecholamine-producing chromaffin cells and steroid-producing adrenocortical cells have been regarded as two independent endocrine systems that are united under a common capsule to form the adrenal gland. There is increasing evidence for bidirectional interactions, with regulatory influences of adrenocortical secretory products on adrenomedullary functions and vice versa. However, the direct involvement of chromaffin cells on the regulation and maintenance of cortical function has not yet been demonstrated. Therefore, we analyzed glucocorticoid secretion and P450 messenger RNA (mRNA) expression in bovine adrenocortical cells in cocultures with chromaffin cells compared with those in pure cortical cell cultures. Cortisol release from cortical cells in coculture with chromaffin cells was 10 times as high (mean +/- SEM, 1035 +/- 119%) as that from the same number of isolated cortical cells (100 +/- 11%). By st [H-3]thymidine incorporation assay, it was demonstrated that this effect was not due to a higher proliferation rate. Northern analysis revealed an increasing expression of P450(17 alpha) mRNA in the coculture from days 1-5, whereas in isolated cortical cells, P450(17 alpha) mRNA decreased, leading to a 6-fold difference on day 5. Inhibitors of protein (cycloheximide) or RNA (actinomycin D) synthesis completely annulled the observed increase in cortisol release, indicating that de novo protein synthesis is required for this activation of adrenocortical steroidogenesis. Addition of the cyclooxygenase inhibitor indomethacin reduced the stimulatory effect, suggesting that this stimulation is in part mediated by PGs. Locally produced ACTH, catecholamines, and interleukin-1 accounted for 43% of the effect. Secretory products of chromaffin cells that act in concert are believed to be responsible for the stimulation of steroidogenesis in the coculture. The coculture system is an in vitro model that corresponds to the in vivo situation in the intact adrenal gland, where both endocrine cell systems are in close contact. Our data demonstrate the requirement of intraadrenal cellular communication for the full strength of the adrenocortical hormonal response. C1 Univ Leipzig, Med Klin & Poliklin 3, Dept Internal Med 3, D-04103 Leipzig, Germany. Res Inst Mol Pharmacol, D-10315 Berlin, Germany. NICHHD, NIH, Bethesda, MD 20892 USA. RP Haidan, A (reprint author), Univ Leipzig, Med Klin & Poliklin 3, Dept Internal Med 3, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. NR 49 TC 61 Z9 62 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1998 VL 139 IS 2 BP 772 EP 780 DI 10.1210/en.139.2.772 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YR396 UT WOS:000071491000046 PM 9449652 ER PT J AU Goehl, TJ AF Goehl, TJ TI Reviews of environmental health, 1998 - Introduction SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Goehl, TJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1998 VL 106 SU 1 BP 3 EP 3 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700001 ER PT J AU Eastin, WC AF Eastin, WC TI The US National Toxicology Program evaluation of transgenic mice as predictive models for identifying carcinogens SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE transgenic; Tg.AC; p53(+/-); NTP; model; carcinogen ID BIOASSAYS AB National institute of Environmental Health Sciences researchers have invested considerable effort in exploring the utility of transgenic mice to detect carcinogens and study mechanisms of carcinogenesis. Work has assessed several mouse models genetically altered to enhance their expression of chemically induced tumors. Results with the p53(def) (hemizygous for the tumor-suppressor gene) and the Tg.AC (carrier of an activated H-ras oncogene) mice have been used as a basis for a proposed new strategy for identifying chemical carcinogens and assessing risk. The U.S. National Toxicology Program is conducting a series of studies with these two transgenic strains to further examine their strengths and weaknesses for identification of documented rodent and human carcinogens and to explore their ability to provide information concerning the effective dosimetry for target organ mutation. C1 NIEHS, Expt Toxicol Branch, Res Triangle Pk, NC 27709 USA. RP Eastin, WC (reprint author), NIEHS, Expt Toxicol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 14 TC 26 Z9 26 U1 1 U2 2 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 FEB PY 1998 VL 106 SU 1 BP 81 EP 84 DI 10.2307/3433914 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700006 PM 9539007 ER PT J AU Harry, GJ Billingsley, M Bruinink, A Campbell, IL Classen, W Dorman, DC Galli, C Ray, D Smith, RA Tilson, HA AF Harry, GJ Billingsley, M Bruinink, A Campbell, IL Classen, W Dorman, DC Galli, C Ray, D Smith, RA Tilson, HA TI In vitro techniques for the assessment of neurotoxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE primary cell cultures; cell lines; central nervous system; peripheral nervous system; neuron; astrocyte; glia; oligodendroglia; astrocytomas; glutamate; neuropathy target esterase; organophosphate; reaggregate cell culture; organ culture; tissue slice; glioma cell line; neuroblastoma cell line; PC-12 cells; cytotoxicity; myelin; axonal transport; blood-brain barrier; neurotransmitter; calcium ID BLOOD-BRAIN-BARRIER; MYELIN-ASSOCIATED GLYCOPROTEIN; SCHWANN-CELL PROLIFERATION; NERVE GROWTH-FACTOR; DIFFERENTIATING N1E.115 NEUROBLASTOMA; CEREBELLAR GRANULE CELLS; IN-VITRO; PRIMARY CULTURES; RAT-BRAIN; PHEOCHROMOCYTOMA CELLS AB Risk assessment is a process often divided into the following steps: a) hazard identification, b) dose-response assessment, c) exposure assessment, and d) risk characterization. Regulatory toxicity studies usually are aimed at providing data for the first two steps. Human case reports, environmental research, and in vitro studies may also be used to identify or to further characterize a toxic hazard. In this report the strengths and limitations of in vitro techniques are discussed in light of their usefulness to identify neurotoxic hazards, as well as for the subsequent dose-response assessment. Because of the complexity of the nervous system, multiple functions of individual cells, and our limited knowledge of biochemical processes involved in neurotoxicity, it is not known how well any in vitro system would recapitulate the in vivo system. Thus, it would be difficult to design an in vitro test battery to replace in vivo test systems. in vitro systems are well suited to the study of biological processes in a more isolated context and have been most successfully used to elucidate mechanisms of toxicity, identify target cells of neurotoxicity, and delineate the development and intricate cellular changes induced by neurotoxicants. Both biochemical and morphological end points can be used, but many of the end points used can be altered by pharmacological actions as well as toxicity. Therefore, for many of these end points it is difficult or impossible to set a criterion that allows one to differentiate between a pharmacological and a neurotoxic effect. For the process of risk assessment such a discrimination is central. Therefore, end points used to determine potential neurotoxicity of a compound have to be carefully selected and evaluated with respect to their potential to discriminate between an adverse neurotoxic effect and a pharmacologic effect. It is obvious that for in vitro neurotoxicity studies the primary end points that can be used are those affected through specific mechanisms of neurotoxicity. For example, in vitro systems may be useful for certain structurally defined compounds and mechanisms of toxicity, such as organophosphorus compounds and delayed neuropathy, for which target cells and the biochemical processes involved in the neurotoxicity are well known. For other compounds and the different types of neurotoxicity, a mechanism of toxicity needs to be identified first. Once identified, by either in vivo or in vitro methods, a system can be developed to detect and to evaluate predictive ability for the type of in vivo neurotoxicity produced. Therefore, in vitro tests have their greatest potential in providing information on basic mechanistic processes in order to refine specific experimental questions to be addressed in the whole animal. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov NR 211 TC 63 Z9 66 U1 2 U2 15 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1998 VL 106 SU 1 BP 131 EP 158 DI 10.2307/3433917 PG 28 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700009 PM 9539010 ER PT J AU Kim, SY Smith, MA Post, RM Rosen, JB AF Kim, SY Smith, MA Post, RM Rosen, JB TI Attenuation of kindling-induced decreases in NT-3 mRNA by thyroid hormone depletion SO EPILEPSY RESEARCH LA English DT Article DE kindling; in situ hybridization; thyroid hormone; neurotrophin-3 (NT-3); brain derived neurotrophic factor (BDNF); nerve growth factor (NGF); thyrotropin-releasing hormone (TRH) ID NERVE GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; LIMBIC SEIZURES; PARAVENTRICULAR NUCLEUS; DIFFERENTIAL REGULATION; NEUROTROPHIC FACTOR; RAT FOREBRAIN; BRAIN; HIPPOCAMPUS; TRIIODOTHYRONINE AB The expression of neurotrophins is altered by amygdala kindled seizures. Because thyroid hormone can regulate the transcription of neurotrophins, we asked whether thyroid hormone regulates neurotrophin mRNA expression following amygdala kindling. Rats with electrodes implanted in the basolateral nucleus of the amygdala were either depleted of thyroid hormone or given excess thyroid hormone. The rats were then kindled daily until they had one generalized seizure. The brains were removed 4 h after the seizure and processed for in situ hybridization of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs. In non-kindled rats, thyroid hormone depletion increased the levels of BDNF mRNA in the paraventricular nucleus of the hypothalamus and the pituitary gland. NGF and NT-3 mRNA expression was not altered. In addition, thyroid hormone manipulations had no effect on kindling or on kindling-induced BDNF and NGF mRNA. However, the kindling-induced decrease in NT-3 mRNA expression in the dentate gyrus granule cell layer was significantly attenuated by thyroid hormone depletion. These effects were reversed by thyroid hormone replacement. The results indicate that thyroid hormone plays a modulatory role in the seizure-induced changes of NT-3 mRNA expression found in the dentate gyrus. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Rosen, JB (reprint author), Univ Delaware, Dept Psychol, 220 Wolf Hall, Newark, DE 19716 USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD FEB PY 1998 VL 29 IS 3 BP 211 EP 220 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA ZC783 UT WOS:000072617600005 PM 9551783 ER PT J AU Westergaard, GC Kuhn, HE Suomi, SJ AF Westergaard, GC Kuhn, HE Suomi, SJ TI Laterality of hand function in tufted capuchin monkeys (Cebus apella): Comparison between tool use actions and spontaneous non-tool actions SO ETHOLOGY LA English DT Article ID WILD CHIMPANZEES; PONGO-PYGMAEUS; PREFERENCE; HANDEDNESS; ORANGUTANS; AGE AB This study examined hand preference for tool use and spontaneous non-tool actions in tufted capuchin monkeys (Cebus apella). We noted a lack of lateral bias across measures, and greater strength of hand preference for tool use than for self-directed or feeding activities. Animals that used tools exhibited a population-level right-hand bias for self-touching whereas animals that did not use tools exhibited a lack of lateral bias for this measure. Our findings are consistent with views that hand preference is expressed more strongly for tool use than for non-tool activities, and that lateral bias for self-directed behavior is related to problem-solving skills in primates. C1 NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. RP Westergaard, GC (reprint author), NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. NR 26 TC 11 Z9 11 U1 0 U2 4 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0179-1613 J9 ETHOLOGY JI Ethology PD FEB PY 1998 VL 104 IS 2 BP 119 EP 125 PG 7 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA YY709 UT WOS:000072175900003 ER PT J AU Abrams, JS AF Abrams, JS TI North American adjuvant breast cancer trials SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD FEB PY 1998 VL 34 SU 1 MA S40 BP S10 EP S10 DI 10.1016/S0959-8049(97)89213-1 PG 1 WC Oncology SC Oncology GA ZB329 UT WOS:000072460100032 ER PT J AU Fisher, B AF Fisher, B TI Preoperative therapy (PROP) for breast cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD FEB PY 1998 VL 34 SU 1 MA S21 BP S5 EP S6 DI 10.1016/S0959-8049(97)89195-2 PG 2 WC Oncology SC Oncology GA ZB329 UT WOS:000072460100013 ER PT J AU Snyderwine, EG AF Snyderwine, EG TI Diet and breast cancer: Lessons from experimental studies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD FEB PY 1998 VL 34 SU 1 MA S3 BP S3 EP S3 DI 10.1016/S0959-8049(97)89184-8 PG 1 WC Oncology SC Oncology GA ZB329 UT WOS:000072460100002 ER PT J AU Tani, K Su, SB Utsunomiya, I Oppenheim, JJ Wang, JM AF Tani, K Su, SB Utsunomiya, I Oppenheim, JJ Wang, JM TI Interferon-gamma maintains the binding and functional capacity of receptors for IL-8 on cultured human T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; IL-8; IL-8 receptor; IFN-gamma; chemotaxis ID INTERLEUKIN-8 RECEPTORS; MONOCLONAL-ANTIBODY; LYMPHOCYTES; NEUTROPHILS; EXPRESSION; MONOCYTES; IDENTIFICATION; RECRUITMENT; INHIBITION AB The neutrophil chemotactic cytokine, IL-8, has been reported to also chemoattract T lymphocytes in vitro and in vivo. Previously we showed that freshly isolated T cells migrated in response to IL-8, but incubation of T cells at 37 degrees C resulted in progressively decreased levels of IL-8 binding sites on T cells in association with reduced chemotactic responses. However, this reduced binding and migration of cultured T cells in response to IL-8 can be prevented by the presence of mononuclear cells in the culture. In order to define the factor(s) responsible for the restoration of T cell binding and migration in response to IL-8, we examined the effects of various cytokines. Addition of IFN-gamma in cultured T cells maintained both the CXC chemokine receptor CXCR1 and CXCR2 binding sites for IL-8 on these cells to the level comparable to that expressed on freshly purified T cells accompanied by an almost complete restoration of their chemotactic response to IL-8. The results suggest that Th1 cytokine, IFN-gamma, produced by mononuclear cells stimulated by proinflammatory signals may play an important role in regulating IL-8 receptor expression on T cells and in sustaining the function of these cells in response to IL-8. C1 NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, LMI, DBS, Bldg 560,Room 31-40, Frederick, MD 21702 USA. NR 24 TC 46 Z9 46 U1 1 U2 1 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 FEB PY 1998 VL 28 IS 2 BP 502 EP 507 DI 10.1002/(SICI)1521-4141(199802)28:02<502::AID-IMMU502>3.0.CO;2-5 PG 6 WC Immunology SC Immunology GA YZ917 UT WOS:000072307700013 PM 9521059 ER PT J AU Chougnet, C Thomas, E Landay, AL Kessler, HA Buchbinder, S Scheer, S Shearer, GM AF Chougnet, C Thomas, E Landay, AL Kessler, HA Buchbinder, S Scheer, S Shearer, GM TI CD40 ligand and IFN-gamma synergistically restore IL-12 production in HIV-infected patients SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokine; IL-10; co-stimulatory molecule; AIDS; antigen-presenting cell ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-12 PRODUCTION; DENDRITIC CELLS; T-CELLS; ALVEOLAR MACROPHAGES; CYTOKINE PRODUCTION; MEDIATED-IMMUNITY AB IL-12 production in HIV-infected (HIV+) individuals is severely impaired after stimulation by bacterial products or T cell-dependent stimuli. Because CD40-CD40 ligand (CD40L) interactions are the major mechanism involved in the T cell-dependent activation of antigen-presenting cells, we investigated whether this pathway was functional in HIV+ donors. CD40 expression was increased on freshly isolated monocytes from HIV+ individuals compared to HIV- donors. However, equivalent CD40 expression was obtained in the two groups after cytokine stimulation. Since CD40 expression was intact in HIV+ donors' cells, we determined whether IL-12 production could be restored by providing exogenous T cell-dependent stimuli, CD40L and IFN-gamma, at the time of bacterial stimulation. IL-12 production was not altered by CD40L alone, was increased by IFN-gamma, and was synergistically restored to normal values by IFN-gamma + CD40L. This combination was more efficient for enhancing IL-12 production than granulocyte-macrophage colony-stimulating factor + CD40L or neutralizing anti-IL-10 antibody + CD40L. CD40L did not affect IL-10 production, whereas IFN-gamma significantly decreased it. This study demonstrates that the defect in IL-12 production by leukocytes from HIV+ donors can be overcome in vitro if the interacting cells are provided with the right T cell-dependent co-stimuli. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Immunex Corp, Seattle, WA USA. Rush Med Coll, Chicago, IL 60612 USA. Dept Publ Hlth, AIDS Off, San Francisco, CA USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10 Rm 4B17,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ShearerS@exchange.nih.gov NR 52 TC 40 Z9 40 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 FEB PY 1998 VL 28 IS 2 BP 646 EP 656 DI 10.1002/(SICI)1521-4141(199802)28:02<646::AID-IMMU646>3.0.CO;2-6 PG 11 WC Immunology SC Immunology GA YZ917 UT WOS:000072307700029 PM 9521075 ER PT J AU Persico, AM Reich, S Henningfield, JE Kuhar, MJ Uhl, GR AF Persico, AM Reich, S Henningfield, JE Kuhar, MJ Uhl, GR TI Parkinsonian patients report blunted subjective effects of methylphenidate SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID VENTRAL TEGMENTAL AREA; D-AMPHETAMINE; CEREBRAL-CORTEX; RHESUS-MONKEYS; DOPAMINE; DISEASE; RAT; METHAMPHETAMINE; DEPRESSION; COCAINE AB Mesolimbic-mesocortical dopamine brain circuits important for psychostimulant reward in animals are developed to greater extents in humans. Brains of patients with Parkinson's disease show depletion of ventral tegmental area mesolimbic-mesocortical neurons. The authors assessed psychostimulant responses in parkinsonian patients to test whether intact dopaminergic systems are required for subjective psychostimulant effects. Responses to placebo and 15, 20, 25, and 30 mg of methylphenidate were studied in 12 parkinsonian patients and 12 neurologically intact matched controls. Physiological and subjective mood responses were recorded using the Profile of Mood States, Addiction Research Center Inventory, and Visual Analog Scale. Drug-induced changes in "good" feelings and overall drug responses were attenuated in the parkinsonian patients. These results, in conjunction with animal data, provide support for dopamine hypotheses of psychostimulant reward in humans and suggest possible basis for some of the mood disturbances found in many parkinsonian patients. C1 NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Neurosci Lab, Rome, Italy. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 49 TC 25 Z9 25 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 1998 VL 6 IS 1 BP 54 EP 63 DI 10.1037//1064-1297.6.1.54 PG 10 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA ZC056 UT WOS:000072535100006 PM 9526146 ER PT J AU Liepert, J Classen, J Cohen, LG Hallett, M AF Liepert, J Classen, J Cohen, LG Hallett, M TI Task-dependent changes of intracortical inhibition SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE intracortical inhibition; transcranial magnetic stimulation; motor exercise; human ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; INTRINSIC CONNECTIONS; CORTICOCORTICAL INHIBITION; CORTICAL EXCITABILITY; REPRESENTATION ZONES; REORGANIZATION; MODULATION; MOVEMENT; OUTPUTS AB The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1-6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10-15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APE, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in re sponse to both single and paired TMS showed a trend to increase with the number of exercise sets in both APE and 4DIO. By contrast, more focal, selective thumb movements involving APE with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APE, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1-3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APE and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently. C1 NINDS, Human Cort Physiol Unit, Human Motor Control Sect, Med Neurol Branch,NIH, Bethesda, MD 20892 USA. RP Liepert, J (reprint author), FSU Jena, Neurol Klin, Philosophenweg 3, D-07743 Jena, Germany. NR 24 TC 170 Z9 171 U1 0 U2 8 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 FEB PY 1998 VL 118 IS 3 BP 421 EP 426 DI 10.1007/s002210050296 PG 6 WC Neurosciences SC Neurosciences & Neurology GA YV132 UT WOS:000071792600013 PM 9497149 ER PT J AU Sato, S Mori, K Wyman, M Kador, PF AF Sato, S Mori, K Wyman, M Kador, PF TI Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose reductase inhibitor M79175 SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE cataract; dog; aldose reductase; diabetes; galactosemia ID RETINAL VESSEL CHANGES; RETINOPATHY AB Sugar cataracts rapidly develop in dogs fed a diet containing 30% galactose. While studies on the formation and progression of these sugar cataracts suggest that they are osmotic in nature and are linked to aldose reductase, sugar cataract formation in the dog to date has not been completely prevented by the administration of aldose reductase inhibitors sorbinil and M79175. To demonstrate that the formation and progression of sugar cataracts in galactose-fed dogs can be dose-dependently inhibited by the administration of aldose reductase inhibitors, 9-month old male beagles were placed on diet containing 30% galactose with/without 10 or 16 mg kg(-1) day(-1) of M79175 for up to 39 months. Cataract progression in all dogs was followed by periodic slit lamp examination and documented by retroillumination photography. Although large variations in cataract formation and progression were observed, all dogs fed a 30% galactose diet for 39 months developed cataracts. Lens changes were significantly less in galactose-fed dogs treated with either 10 or 16 mg kg(-1) M79175 and no cataract formation was observed in 3 of 6 galactose-fed dogs treated with 16 mg kg(-1) M79175. These observations confirm that aldose reductase plays a key role in initiating cataract formation in galactose-fed dogs and that cataract formation can be prevented by adequate inhibition of aldose reductase. (C) 1998 Academic Press Limited. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Sato, S (reprint author), NEI, Lab Ocular Therapeut, NIH, 10 Ctr Dr MSC 1850,Bldg 10,Room 10B09, Bethesda, MD 20892 USA. NR 21 TC 25 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 1998 VL 66 IS 2 BP 217 EP 222 DI 10.1006/exer.1997.0412 PG 6 WC Ophthalmology SC Ophthalmology GA YX485 UT WOS:000072044700009 PM 9533847 ER PT J AU Vawter, MP Cannon-Spoor, HE Hemperly, JJ Hyde, TM VanderPutten, DM Kleinman, JE Freed, WJ AF Vawter, MP Cannon-Spoor, HE Hemperly, JJ Hyde, TM VanderPutten, DM Kleinman, JE Freed, WJ TI Abnormal expression of cell recognition molecules in schizophrenia SO EXPERIMENTAL NEUROLOGY LA English DT Article DE schizophrenia; bipolar disorder; suicide; hippocampus; prefrontal cortex; neural cell adhesion molecule; L1, cell recognition molecules ID NCAM MESSENGER-RNA; ADHESION MOLECULE; N-CAM; RAT-BRAIN; L1; HIPPOCAMPUS; MOUSE; CSF; LOCALIZATION; ASTROCYTES AB Schizophrenia is a neuropsychiatric disorder of unknown etiology associated with subtle changes ill brain morphology. The cell recognition molecules (CRMs) neural cell adhesion molecule (N-CAM) and L1 are involved in morphoregulatory events and numerous neurodevelopmental processes. We found a selective increase of 105- to 115-kDa N-CAM in the hippocampus and prefrontal cortex of patients with schizophrenia while other N-CAM isoforms and L1 proteins were not altered. There was also evidence for an abnormality in CRM expression in schizophrenic patients: concentrations of 200-kDa L1 were strongly correlated with expression of N-CAM isoforms and cleaved L1 proteins In controls, whereas these correlations were absent in patients with schizophrenia. The increase of the 105- to 115-kDa N-CAM isoform in the brains of patients with schizophrenia confirms previous cerebrospinal fluid findings. Increased N-CAM in schizophrenia may result from structural brain abnormalities, from glial processing of N-CAM, or from an aberration in the regulation of N-CAM expression. C1 NIMH, St Elizabeths Hosp, Ctr Neurosci, Sect Preclin Neurosci,Neuropsychiat Branch, Washington, DC 20032 USA. Becton Dickinson & Co, Res Ctr, Neurobiol Sect, Res Triangle Pk, NC 27709 USA. RP Vawter, MP (reprint author), NIMH, St Elizabeths Hosp, Ctr Neurosci, Sect Preclin Neurosci,Neuropsychiat Branch, Washington, DC 20032 USA. NR 50 TC 56 Z9 57 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1998 VL 149 IS 2 BP 424 EP 432 DI 10.1006/exnr.1997.6721 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZA117 UT WOS:000072330600013 PM 9500955 ER PT J AU Isaacs, KR Hanbauer, I Jacobwitz, DM AF Isaacs, KR Hanbauer, I Jacobwitz, DM TI A method for the rapid analysis of neuronal proportions and neurite morphology in primary cultures SO EXPERIMENTAL NEUROLOGY LA English DT Article DE tyramide; fluorescence immunohistochemistry; tissue culture; Sholl analysis ID AMPLIFICATION; CELLS AB This article provides basic guidelines for a rapid analysis of subpopulation proportions and neurite morphology in primary cultures. We describe, in E14 mesencephalic primary cultures, an immunohistochemical method for the simultaneous identification of multiple neuronal phenotypes and an estimation of the ratio of subpopulations. In addition, we describe the use of the Renaissance TSA-Direct hit (NEN, DuPont) to enhance the visualization of neurites when the antigen is in low abundance. Finally, a modified SholI analysis is used to rapidly and reliably estimate neurite number and length. C1 NIMH, Sect Histopathol, Clin Sci Lab, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Isaacs, KR (reprint author), NIMH, Sect Histopathol, Clin Sci Lab, Bldg 10,Rm 3D-48,10 Ctr Dr,MSC 1266, Bethesda, MD 20892 USA. NR 10 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1998 VL 149 IS 2 BP 464 EP 467 DI 10.1006/exnr.1997.6727 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZA117 UT WOS:000072330600018 PM 9500959 ER PT J AU Shahabuddin, M Gayle, M Zieler, H Laughinghouse, A AF Shahabuddin, M Gayle, M Zieler, H Laughinghouse, A TI Plasmodium gallinaceum: Fluorescent staining of zygotes and ookinetes to study malaria parasites in mosquito SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE adhesion; insect; PKH26; transmission; vector ID INFECTED ERYTHROCYTES; FALCIPARUM; PROTEIN AB We have developed a fluorescent labeling procedure for staining the mosquito stages of Plasmodium gallinaceum. PKH26, a lipophilic dye, is efficiently and permanently incorporated into the membranes of zygotes and ookinetes. Stained zygotes undergo normal development into ookinetes; the stain does not interfere with ookinete mobility or ability to adhere to the mosquito midgut lumen. Stained zygotes and ookinetes are comparable to untreated parasites in their ability to give rise to oocysts when fed to mosquitoes. This technique can be used to study the development of Plasmodium parasites in the complex cellular environment of the mosquito midgut after a blood meal. It may also be adapted to study other parasite-vector interactions. (C) 1998 Academic Press. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Shahabuddin, M (reprint author), NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD FEB PY 1998 VL 88 IS 2 BP 79 EP 84 DI 10.1006/expr.1998.4198 PG 6 WC Parasitology SC Parasitology GA ZE177 UT WOS:000072765900001 PM 9538861 ER PT J AU Rauhala, P Lin, AMY Chiueh, CC AF Rauhala, P Lin, AMY Chiueh, CC TI Neuroprotection by S-nitrosoglutathione of brain dopamine neurons from oxidative stress SO FASEB JOURNAL LA English DT Article DE hydroxyl radical; lipid peroxidation; nitric oxide; peroxynitrite; Parkinson's disease ID LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE RELEASE; GLUTATHIONE; NITROSOTHIOLS; NEUROTOXICITY; PEROXIDATION; ACTIVATION; SUPEROXIDE; INHIBITION; TOXICITY AB The proposed anti- and prooxidant effects of nitric oxide (NO) derivatives, such as S-nitrosoglutathione (GSNO) and peroxynitrite, were investigated in the rat nigrostriatal dopaminergic system. Intranigal infusion of freshly prepared GSNO (0-16.8 nmol, i.n.) prevented iron-induced (4.2 nmol, i.n.) oxidative stress and nigral injury, reflected by a decrease in striatal dopamine levels. This neuroprotective effect of GSNO was verified by ex vivo imaging of brain dopamine uptake sites using I-125-labeled RTI-55. In addition, in vitro data indicate that GSNO concentration-dependently inhibited iron-evoked hydroxyl radical generation and brain lipid peroxidation. In this iron-induced oxidant stress model, GSNO was approximately 100-fold more potent than the antioxidant glutathione (GSH). Light-exposed, NO-exhausted GSNO produced neither antioxidative nor neuroprotective effects, which indicates that NO may mediate at least part of GSNO's effects. Moreover, GSNO completely (and GSH only partially) inhibited the weak pro-oxidant effect of peroxynitrite, which produced little injury to nigral neurons in vivo. This study provides relevant in vivo evidence suggesting that nanomol GSNO can protect brain dopamine neurons from iron-induced oxidative stress and degeneration. In conclusion, S-nitrosylation of GSH by NO and oxygen may be part of the antioxidative cellular defense system. C1 NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Chiueh, CC (reprint author), NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, NIH, Bldg 10,Rm 3D-41, Bethesda, MD 20892 USA. EM chiueh@helix.nih.gov OI Rauhala, Pekka/0000-0003-2036-3522 FU NIMH NIH HHS [Z01 MH 02648-04LCS] NR 53 TC 136 Z9 137 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 1998 VL 12 IS 2 BP 165 EP 173 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA YV644 UT WOS:000071848400004 PM 9472981 ER PT J AU Gentile, GP Kaufman, SC Helbig, DW AF Gentile, GP Kaufman, SC Helbig, DW TI Is there any evidence for a post-tubal sterilization syndrome? SO FERTILITY AND STERILITY LA English DT Article DE post-tubal ligation syndrome; post-tubal sterilization syndrome; luteal phase defect; menstrual blood loss; laparoscopic tubal sterilization; contraception ID LONG-TERM RISK; PITUITARY-OVARIAN FUNCTION; WOMEN REQUESTING REVERSAL; MENSTRUAL PATTERN CHANGES; LAPAROSCOPIC STERILIZATION; FOLLOW-UP; UNITED-STATES; FALOPE-RINGS; HYSTERECTOMY; LIGATION AB Objective: To review the literature on menstrual and hormonal changes in women who undergo tubal sterilization. Design: A systematic review through MEDLINE and a literature search identified more than 200 articles in the English literature from which the most relevant were selected for this review. Result(s): Many authors have investigated the sequelae of female sterilization. Increased premenstrual distress, heavier and more prolonged menstrual bleeding, and increased dysmenorrhea have been reported. However, failure to control for age, parity, obesity, previous contraceptive use, interval since sterilization, or type of sterilization may have affected study results. Most studies that have controlled for these important variables have not reported significant changes, except in women who undergo sterilization between 20 and 29 years of age. Conclusion(s): Tubal sterilization is not associated with an increased risk of menstrual dysfunction, dysmenorrhea, or increased premenstrual distress in women who undergo the procedure after age 30 years. There may be some increased risk for younger women, although they do not appear to undergo significant hormonal changes. (C) 1998 by American Society for Reproductive Medicine. C1 SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. NICHHD, Contracept Res & Evaluat Branch, Bethesda, MD 20892 USA. RP Gentile, GP (reprint author), SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Box 24,450 Clarkson Ave, Brooklyn, NY 11203 USA. FU NICHD NIH HHS [N01-HD-2908] NR 61 TC 44 Z9 46 U1 0 U2 3 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 1998 VL 69 IS 2 BP 179 EP 186 DI 10.1016/S0015-0282(97)00229-X PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA YY935 UT WOS:000072202700001 PM 9496325 ER PT J AU Sugino, A Ohara, T Sebastian, J Nakashima, N Araki, H AF Sugino, A Ohara, T Sebastian, J Nakashima, N Araki, H TI DNA polymerase epsilon encoded by cdc20(+) is required for chromosomal DNA replication in the fission yeast Schizosaccharomyces pombe SO GENES TO CELLS LA English DT Article ID CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; S-PHASE; FACTOR-C; DELTA; GENE; PURIFICATION; PROGRESSION; CHECKPOINT; INITIATION AB Background: DNA polymerase II (PolII), the homologue of mammalian DNA polymerase epsilon, is essential for chromosomal DNA replication in the budding yeast Saccharomyces cerevisiae and also participates in S-phase checkpoint control. An important issue is whether chromosomal DNA replication in other eukaryotes, including the fission yeast Schizosaccharomyces pombe-in which the characteristics of replication origins are poorly defined-also requires DNA polymerase E. It has been shown that DNA polymerase epsilon is not required for the in vitro replication of SV40 DNA by human cell extracts. Results: We have cloned and sequenced S. pombe pol2(+), which is identical to the cell-cycle gene cdc20(+), encoding the catalytic polypeptide of DNA polymerase epsilon (Pol epsilon). The predicted amino acid sequence of Pol epsilon is highly homologous to that of S. cerevisiae PolII and human Pol epsilon. Consistent with this, the Pol epsilon polypeptide was recognized by polyclonal antibodies against S. cerevisiae PolII holoenzyme (PolII(star)). The terminal morphology of cells containing the disrupted pol2 gene was similar to that of DNA replication mutant cells and cdc20 mutant cells. Furthermore, the Pol epsilon activity from temperature-sensitive S. pombe cdc20 mutant cells was temperature-sensitive, and chromosomal DNA replication in the mutant cells was inhibited at the restrictive temperatures. Conclusion: These data strongly suggest that Pol epsilon is required for normal chromosomal DNA replication in S. pombe, as is PolII in S. cerevisiae. Thus, eukaryotic chromosomal DNA is replicated differently from that of viral SV40 DNA. C1 Osaka Univ, Microbial Dis Res Inst, Dept Biochem & Mol Biol, Suita, Osaka 565, Japan. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM asugino@biken.osaka-u.ac.jp NR 43 TC 16 Z9 17 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-9597 EI 1365-2443 J9 GENES CELLS JI Genes Cells PD FEB PY 1998 VL 3 IS 2 BP 99 EP 110 DI 10.1046/j.1365-2443.1998.00169.x PG 12 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA ZJ624 UT WOS:000073235400003 PM 9605404 ER PT J AU Pruitt, KD AF Pruitt, KD TI WebWise: Guide to the Stanford Human Genome Center and the Whitehead/MIT Genome Center Web sites SO GENOME RESEARCH LA English DT Editorial Material C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 1 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 FEB PY 1998 VL 8 IS 2 BP 86 EP 90 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA ZJ467 UT WOS:000073218600003 PM 9477336 ER PT J AU Cancilla, MR Tainton, KM Barry, AE Larionov, V Kouprina, N Resnick, MA Du Sart, D Choo, KHA AF Cancilla, MR Tainton, KM Barry, AE Larionov, V Kouprina, N Resnick, MA Du Sart, D Choo, KHA TI Direct cloning of human 10q25 neocentromere DNA using transformation-associated recombination (TAR) in yeast SO GENOMICS LA English DT Article ID ARTIFICIAL CHROMOSOMES; CENTROMERE; IDENTIFICATION; CELLS AB The transformation-associated recombination (TAR) procedure allows rapid, site-directed cloning of specific human chromosomal regions as yeast artificial chromosomes (YACs). The procedure requires knowledge of only a single, relatively small genomic sequence that resides adjacent to the chromosomal region of interest. We applied this approach to the cloning of the neocentromere DNA of a marker chromosome that we have previously shown to have originated through the activation of a latent centromere at human chromosome 10q25. Using a unique 1.4-kb DNA fragment as a "hook" in TAR experiments, we achieved single-step isolation of the critical neocentromere DNA region as two stable, 110- and 80-kb circular YACs. For obtaining large quantities of highly purified DNA, these YACs were retrofitted with the yeast-bacteria-mammalian-cells shuttle vector ERVI, electroporated into Escherichia coli DH10B, and isolated as bacterial artificial chromosomes (BACs). Extensive characterization of these YACs and BACs by PCR and restriction analyses revealed that they are identical to the corresponding regions of the normal chromosome 10 and provided further support for the formation of the neocentromere within the marker chromosome through epigenetic activation. (C) 1998 Academic Press. C1 Royal Childrens Hosp, Murdoch Inst Res Birth Defects, Parkville, Vic 3052, Australia. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Choo, KHA (reprint author), Royal Childrens Hosp, Murdoch Inst Res Birth Defects, Flemington Rd, Parkville, Vic 3052, Australia. NR 14 TC 26 Z9 27 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 FEB 1 PY 1998 VL 47 IS 3 BP 399 EP 404 DI 10.1006/geno.1997.5129 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA YZ595 UT WOS:000072269800009 PM 9480754 ER PT J AU Landau, D Domene, H Flyvbjerg, A Gronbaek, H Roberts, CT Argov, S LeRoith, D AF Landau, D Domene, H Flyvbjerg, A Gronbaek, H Roberts, CT Argov, S LeRoith, D TI Differential expression of renal growth hormone receptor and its binding protein in experimental diabetes mellitus SO GROWTH HORMONE & IGF RESEARCH LA English DT Article ID FACTOR-I; GENE-EXPRESSION; RIBONUCLEIC-ACID; TRANSGENIC MICE; MESSENGER-RNA; IGF-I; RAT; KIDNEY; SERUM; SOMATOSTATIN AB Growth hormone (GH) may have a role in the development of diabetic nephropathy. The effect of experimental diabetes on renal expression of the growth hormone receptor gene products, including the receptor itself (GHR) and its binding protein (GHBP) was examined, Adult female rats received i.v. streptozotocin and were killed at 7, 30, 90 and 180 days after the induction of diabetes. Diabetic animals had a pronounced increase in kidney weight and progressive albuminuria. In renal cortex, no change was seen in GHR mRNA levels throughout the observation period of 6 months, while a significant increase in cortical GHBP mRNA levels was observed after 1 month of diabetes and sustained for the rest of the study period. Immunohistochemical analysis of kidney sections revealed a stronger staining for GHBP at the cortical and inner medullary areas in the diabetic animals. These data indicate that although the GHR and GHBP mRNAs originate from the same gene, their renal levels are differentially regulated during the development of experimental diabetic kidney disease, suggesting a functional role for GHBP. (C) 1998 Churchill Livingstone. C1 Soroka Med Ctr, Dept Pediat, IL-84101 Beer Sheva, Israel. Soroka Med Ctr, Dept Pathol, IL-84101 Beer Sheva, Israel. Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. Aarhus Kommune Hosp, Inst Expt Clin Res, Aarhus C, Denmark. Childrens Hosp H Gutierrez, CONICET, CEDIE, Buenos Aires, DF, Argentina. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Landau, D (reprint author), Soroka Med Ctr, Dept Pediat, POB 151, IL-84101 Beer Sheva, Israel. OI Roberts, Charles/0000-0003-1756-5772 NR 44 TC 16 Z9 17 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD FEB PY 1998 VL 8 IS 1 BP 39 EP 45 DI 10.1016/S1096-6374(98)80320-1 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 131MC UT WOS:000076579000006 PM 10990443 ER PT J AU Kurc, M Dodane, V Pinto, DS Kachar, B AF Kurc, M Dodane, V Pinto, DS Kachar, B TI Presynaptic localization of G protein isoforms in the efferent nerve terminals of the mammalian cochlea SO HEARING RESEARCH LA English DT Article DE G protein; SNAP-25; cochlea; nerve terminal; hair cell; efferent system ID CROSSED OLIVOCOCHLEAR BUNDLE; HETEROTRIMERIC-G-PROTEINS; GUINEA-PIG; ACETYLCHOLINE-RELEASE; SYNAPTIC VESICLES; ALPHA-SUBUNITS; RAT COCHLEA; STIMULATION; RECEPTOR; FAMILY AB Heterotrimeric guanine nucleotide binding proteins (G proteins) are known to be involved in receptor-mediated synaptic activity. In order to determine which G protein isoforms, if any, are involved in synaptic regulation in the organ of Corti, we performed an extensive immunocytochemical screening. We localized. a G alpha(q/11) isoform to the efferent nerve terminals using antibodies specific against the a subunit of these proteins. The label was observed in the efferent boutons contacting either the outer hair cells or the afferent fibers at the inner spiral bundle. We compared the localization of this isoform to that of the presynaptic protein SNAP-25 ill double labeling experiments. G alpha(q/11) immunoreactivity was present predominantly in the cytoplasm of the presynaptic boutons in a region of high density of synaptic vesicles, while SNAP-25 was localized predominantly in the plasma membrane of the boutons. No label for these proteins was found al the afferent synapses, including the presynaptic terminals on hair cells. These results suggest that an isoform of the G(q) subfamily of the G proteins might be involved in presynaptic modulation of neurotransmitter release at the cochlear efferents. (C) 1998 Published by Elsevier Science B.V. C1 NIH, Sect Struct Cell Biol, Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Kachar, B (reprint author), NIH, Sect Struct Cell Biol, Natl Inst Deafness & Other Commun Disorders, 9000 Rockville Pk Bldg 36,Room 5D-15, Bethesda, MD 20892 USA. RI Pinto, Decio/B-6041-2011 OI Pinto, Decio/0000-0001-6198-5155 NR 34 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD FEB PY 1998 VL 116 IS 1-2 BP 1 EP 9 DI 10.1016/S0378-5955(97)00183-4 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA YY665 UT WOS:000072171400001 PM 9508023 ER PT J AU Greco, AV Mingrone, G Benedetti, G Capristo, E Tataranni, PA Gasbarrini, G AF Greco, AV Mingrone, G Benedetti, G Capristo, E Tataranni, PA Gasbarrini, G TI Daily energy and substrate metabolism in patients with cirrhosis SO HEPATOLOGY LA English DT Article ID DECREASED INSULIN BINDING; LIVER-CIRRHOSIS; DIABETES-MELLITUS; FATTY-ACIDS; ALCOHOLIC HEPATITIS; 24-HOUR ENERGY; EXPENDITURE; GLUCOSE; DISEASE; RESISTANCE AB Twenty-four-hour energy expenditure (EE) and substrate oxidation (respiratory chamber), and whole-body glucose uptake and oxidation rates (euglycemic hyperinsulinemic clamp [EHC] and indirect calorimetry) were measured in 10 male patients with posthepatitis, Child B cirrhosis, and 8 healthy male controls matched for age, body size, and body composition. Twenty-four-hour EE was higher in cirrhotic patients than in controls (8,567 +/- 764 vs. 6,825 +/- 507 kJ/d; P < .001). Resting energy expenditure (REE) was also higher in cirrhotic patients than in controls (7,881 +/- 1,125 vs. 5,868 +/- 489 kJ/d; P < .01). Twenty-four-hour respiratory quotient (RQ) (trend) and fasting RQ (0.76 +/- 0.05 vs. 0.82 +/- 0.04; P < .05) were lower in cirrhotic patients than in controls, reflecting higher lipid oxidation rates in the former group. Whole-body glucose uptake was markedly reduced in cirrhotic patients when compared with controls (22.4 +/- 3.2 vs. 44.5 +/- 7.6 mmol/kg/min; P < .001). Carbohydrate oxidation rates, computed during the last 40 minutes of the clamp, were 8.5 +/- 1.1 mmol/kg/min in cirrhotic patients and 22.6 +/- 6.1 mmol/kg/min in controls (P < .001). Nonoxidative glucose disposal was 13.9 +/- 2.5 mmol/kg/min in cirrhotic patients and 22.0 +/- 5.5 mmol/kg/min in normal controls (P < .01). In conclusion, our data indicate that patients with Child B cirrhosis who still maintain a nutritional status (i,e., body composition) comparable with healthy controls are characterized by a cluster of metabolic defects that include hypermetabolism increased lipid utilization, and insulin resistance. This suggests that the above metabolic syndrome precedes and probably leads to malnutrition in the natural history of the liver disease. In fact, in spite of the absence of a significant difference in caloric intake between cirrhotic patients and normal controls, the elevated 24-hour EE might allow for a relevant weight loss in cirrhotic patients, because, with time, the differences may be cumulative. However, whether this hypermetabolism can lead to a real weight loss remains to be evaluated in a longitudinal study. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ USA. RP Greco, AV (reprint author), Univ Cattolica Sacro Cuore, Ist Med Interna & Geriatr, Largo A Gemelli 8, I-00168 Rome, Italy. NR 53 TC 55 Z9 57 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1998 VL 27 IS 2 BP 346 EP 350 DI 10.1002/hep.510270205 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YU242 UT WOS:000071696500005 PM 9462629 ER PT J AU Choi, KS Lim, IK Brady, JN Kim, SJ AF Choi, KS Lim, IK Brady, JN Kim, SJ TI ICF-Like protease (caspase) is involved in transforming growth factor beta 1-mediated apoptosis in FaO rat hepatoma cell line SO HEPATOLOGY LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; DEATH GENE CED-3; INTERLEUKIN-1-BETA-CONVERTING ENZYME; CYSTEINE PROTEASE; POLY(ADP-RIBOSE) POLYMERASE; ICE/CED-3 PROTEASE; MOLECULAR-CLONING; COMMON MEDIATOR; CPP32 PROTEASE; FACTOR-BETA AB Transforming growth factor-beta(1) (TGF-beta(1)) arrests growth and/or stimulates apoptosis of a variety of cells. The biochemical pathways involved in the apoptotic processes, however, remain poorly defined. TGF-beta(1) induces DNA fragmentation together with morphological changes, which are characteristic of apoptosis in the FaO rat hepatoma cell line. Histones were remarkably enriched in lysates of these cells during TGF beta(1)-induced apoptosis. We identified U1-70 kd as a death substrate which is cleaved following TGF-beta(1) treatment. The tetrapeptide caspase inhibitor carbobenzoxy-valyl-alanly-aspartyl-(beta-O-methyl)-fluoromethyl ketone (ZVAD-FMK) prevented TGF beta(1)-induced apoptotic DNA fragmentation and cleavage of the U1-70 kd protein, showing that caspase(s) are involved in TGF beta(1)-mediated apoptosis. To identify specific caspases involved in apoptosis induced by TGF-beta(1) in FaO cells, proteolytic activation of several of these caspases and their substrates were studied as a function of time following TGF beta(1)-treatment. TGF beta(1)-treatment induced the progressive proteolytic processing of caspase-2 (ICH-1L/Nedd-2), whereas caspase-1 itself did not show any cleavage from the precursor. Pretreatment with ZVAD-FMK abrogated the maturation of caspase-2 and blocked the apoptotic progress. These results suggest that caspase-2, but not caspase-1, may play a crucial role in TGF beta(1)-induced apoptosis in these cells. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Ajou Univ, Sch Med, Dept Biochem, Suwon 441749, South Korea. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NR 56 TC 46 Z9 46 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1998 VL 27 IS 2 BP 415 EP 421 DI 10.1002/hep.510270215 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YU242 UT WOS:000071696500015 PM 9462639 ER PT J AU Delnomdedieu, M Hedlund, LW Maronpot, RR Johnson, GA AF Delnomdedieu, M Hedlund, LW Maronpot, RR Johnson, GA TI Magnetic resonance microscopy and histopathology: Comparative approach of bromobenzene-induced hepatotoxicity in the rat SO HEPATOLOGY LA English DT Article ID MR MICROSCOPY; HISTOLOGY; MICROANGIOGRAPHY; NECROSIS AB The development of magnetic resonance (MR) microscopy has provided new approaches to histology and histopathology. Recent work has shown the promise of increased sensitivity in animal models of chemically induced hepatotoxicity, However, the field is so new that there is little experience to relate changes seen in MR micrographs to the more traditional optical images stained with hematoxylin and eosin. This work compares the sensitivity and reproducibility of MR microscopy with conventional histopathology in detecting bromobenzene-induced hepatotoxicity in the rat. A time-course study was undertaken to provide a range of histopathologies. Specimens were studied at 24, 48, 72, and 96 hours after exposure to 10% of the median lethal dose of bromobenzene. Using 4 animals per group (a total of 32 rats) added statistical significance to the study and defined a range of interanimal variability over 96 hours. This work shows that MR microscopy, besides being nondestructive and three-dimensional, is at least as sensitive as conventional hematoxylin-eosin staining in detecting bromobenzene-induced centrilobular lesions and recovery of the hepatocellular architecture in the rat. This study further suggests that, as we begin to understand the underlying mechanisms of contrast in MR histology, MR may, in fact, supply even higher specificity than more traditional studies: variations were observed in MR images of treated livers at a given time point that could be not be differentiated based on the grading of necrosis and inflammation on hematoxylin-eosin-stained sections. C1 Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Dept Radiol, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Delnomdedieu, M (reprint author), Duke Univ, Med Ctr, Ctr In Vivo Microscopy, Dept Radiol, Box 3302 DUMC, Durham, NC 27710 USA. OI Hedlund, Laurence/0000-0001-5275-0397; Johnson, G.Allan/0000-0002-7606-5447 FU NCRR NIH HHS [P41 RRO5959] NR 16 TC 9 Z9 9 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1998 VL 27 IS 2 BP 526 EP 532 DI 10.1002/hep.510270229 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YU242 UT WOS:000071696500029 PM 9462653 ER PT J AU Fu, KL Thuss, PC Fujino, T Digweed, M Liu, JM Walsh, CE AF Fu, KL Thuss, PC Fujino, T Digweed, M Liu, JM Walsh, CE TI Retroviral gene transfer for the assignment of Fanconi anemia (FA) patients to a FA complementation group SO HUMAN GENETICS LA English DT Article ID GROUP-C GENE; MUTATION; VECTOR AB Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone marrow failure, cancer susceptibility, and a variety of developmental defects, The disease is clinically heterogeneous eight different complementation groups (FA A-H) and, thus, genetic loci have been discovered. Two genes, FAA and FAC, have been cloned, Disease-associated mutations: have been detected and rapid mutation screening makes possible the assignment of patients without resorting to time-consuming cell fusion and complementation analysis, Amplification of specific cDNAs from RNA followed by direct or indirect sequence analysis is a standard method for mutation detection. During the course of such examinations of the FAC gene, we have noted that frequently only one of the expressed alleles Is successfully amplified. This can lead to false assignment of patients to a complementation group. As we report here, such cases can be rapidly clarified by retroviral gene transfer and complementation analysis. C1 Univ N Carolina, Dept Med, Gene Therapy Ctr, Chapel Hill, NC 27599 USA. Humboldt Univ, Klinikum Rudolf Virchow, Inst Human Genet, Berlin, Germany. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Walsh, CE (reprint author), Univ N Carolina, Dept Med, Gene Therapy Ctr, Chapel Hill, NC 27599 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 1998 VL 102 IS 2 BP 166 EP 169 DI 10.1007/s004390050671 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA ZB303 UT WOS:000072457500007 PM 9521584 ER PT J AU Jalanko, A Tenhunen, K McKinney, CE LaMarca, ME Rapola, J Autti, T Joensuu, R Manninen, T Sipila, I Ikonen, S Riekkinen, P Ginns, EI Peltonen, L AF Jalanko, A Tenhunen, K McKinney, CE LaMarca, ME Rapola, J Autti, T Joensuu, R Manninen, T Sipila, I Ikonen, S Riekkinen, P Ginns, EI Peltonen, L TI Mice with an aspartylglucosaminuria mutation similar to humans replicate the pathophysiology in patients SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN LYSOSOMAL ASPARTYLGLUCOSAMINIDASE; STORAGE DISEASE; TARGETED DISRUPTION; TAY-SACHS; GENE; ASPARTYLGLYCOSAMINURIA; ACTIVATION; METABOLISM; LETHALITY; DELETION AB Aspartyglucosaminurla (AGU) is a lysosomal storage disease with autosomal recessive inheritance that is caused by deficient activity of aspartylglucosaminidase (AGA), a lysosomal enzyme belonging to the newly described enzyme family of N-terminal hydrolases, An AGU mouse model was generated by targeted disruption of the AGA gene designed to mimic closely one human disease mutation, These homozygous mutant mice have no detectable AGA activity and excrete aspartylglucosamine in their urine, Analogously to the human disease, the affected homozygous animals showed storage in lysosomes in all analyzed tissues, including the brain, liver, kidney and skin, and lysosomal storage was already detected in fetuses at 19 days gestation, Electron microscopic studies of brain tissue samples demonstrated lysosomal storage vacuoles in the neurons and glia of the neocortical and cortical regions. Magnetic resonance images (MRI) facilitating monitoring of the brains of living animals indicated cerebral atrophy and hypointensity of the deep gray matter structures of brain-findings similar to those observed in human patients. AGU mice are fertile, and up to 11 months of age their movement and behavior do not differ from their age-matched littermates, However, in the Morris water maze test, a slow worsening of performance could be seen with age, The phenotype mimics well AGU in humans, the patients characteristically showing only slowly progressive mental retardation and relatively mild skeletal abnormalities. C1 Natl Publ Hlth Inst, Dept Human Mol Genet, SF-00300 Helsinki, Finland. NIMH, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Childrens Hosp, FIN-00290 Helsinki, Finland. Univ Helsinki, Dept Radiol, Helsinki, Finland. Univ Kuopio, Dept Neurol & Neurosci, FIN-70211 Kuopio, Finland. RP Peltonen, L (reprint author), Natl Publ Hlth Inst, Dept Human Mol Genet, Mannerheimintie 166, SF-00300 Helsinki, Finland. EM leena.peltonen@ktl.fi NR 30 TC 23 Z9 23 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 FEB PY 1998 VL 7 IS 2 BP 265 EP 272 DI 10.1093/hmg/7.2.265 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA YU940 UT WOS:000071771900014 PM 9425233 ER PT J AU Park, WS Vortmeyer, AO Pack, S Duray, PH Boni, R Ali Guerami, A Emmert-Buck, MR Liotta, LA Zhuang, ZP AF Park, WS Vortmeyer, AO Pack, S Duray, PH Boni, R Ali Guerami, A Emmert-Buck, MR Liotta, LA Zhuang, ZP TI Allelic deletion at chromosome 9p21(p16) and 17p13(p53) in microdissected sporadic dysplastic nevus SO HUMAN PATHOLOGY LA English DT Article DE dysplastic nevus; chromosome 9; chromosome 17; PCR; loss of heterozygosity ID CELL-CYCLE INHIBITION; MALIGNANT-MELANOMA; HOMOZYGOUS DELETION; CUTANEOUS MELANOMA; MELANOCYTIC NEVI; HUMAN CANCERS; TUMOR TYPES; GENE; P16; ASSOCIATION AB A critical area of chromosomal loss at region p16(9p21-22) and p53(17p13) has been implicated in the genesis of malignant melanoma. It is still unclear whether the genetic alterations can be detected in dysplastic nevus, a premalignant lesion of malignant melanoma. We have searched the frequency of p16 and p53 deletion in nine dysplastic nevi and 13 benign intradermal nevi with five microsatellite markers. Hemizygous deletion was detected in seven of nine (78%) dysplastic nevi at one or more loci for p16 and three of seven (43%) for p53, respectively. No loss of heterozygosity (LOH) was detected in any of the benign intradermal nevi. All three dysplastic nevi with LOH for p53 also showed LOH at p16. However, not all dysplastic nevi showing p16 deletion showed P53 gene deletion. Therefore, these data suggest that deletion of p16 may play an important role in the development of dysplastic nevus as an early event and that the changes may represent an early event in the development of malignant melanoma. This is a US government work. There are no restrictions on its use. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Zurich Hosp, Dept Dermatol, Zurich, Switzerland. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2N204,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 35 TC 56 Z9 56 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 1998 VL 29 IS 2 BP 127 EP 130 DI 10.1016/S0046-8177(98)90221-0 PG 4 WC Pathology SC Pathology GA YX336 UT WOS:000072030000005 PM 9490270 ER PT J AU Fogt, F Vortmeyer, AO Goldman, H Giordano, TJ Merino, MJ Zhuang, ZP AF Fogt, F Vortmeyer, AO Goldman, H Giordano, TJ Merino, MJ Zhuang, ZP TI Comparison of genetic alterations in colonic adenoma and ulcerative colitis-associated dysplasia and carcinoma SO HUMAN PATHOLOGY LA English DT Article DE ulcerative colitis; adenomas; loss of heterozygosity ID COLORECTAL ADENOMAS; MUTATIONS; CANCER AB Carcinoma is an important complication of ulcerative colitis (UC) and develops from dysplastic precursor lesions. Genetic changes involved in the malignant transformation have not been fully characterized. We studied 19 cases of UC with high-grade dysplasia (HGD) and eight samples of associated carcinoma (CA). Microdissection of normal epithelium, epithelium at the site of chronic inflammation, HGD, and CA was performed. Polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of the following polymorphic microsatellites of putative tumor suppressor gene loci was done: APC (5q), DCC (18q), p16 (9p), P53 (17p), and 8p12. To compare genetic alterations, 22 typical adenomas of the colon were studied with the markers for APC and p16 gene loci. The results indicated that LOH of p16 and p53 were present in nondysplastic epithelium, HGD, and CA. However, the LOH in nondysplastic epithelium was detected in some associated HGD, but not all. Whereas LOH of p16 was present in 7 of 14 cases of HGD (50%), it was noted in only 1 of 22 adenomas (5.0%). LOH in the APC and DCC gene loci in UC was noted in HGD with associated CA, but LOH of APC was not present either in cases of nondysplastic epithelium or in HGD alone. Conversely, LOH in APC was present in 4 of 19 colonic adenomas. We conclude that LOH of p53 and p16 in nondysplastic epithelium may be associated with chronic reparative processes. These changes may lead to susceptibility to further genetic damage involving the APC and DCC gene loci in the development of dysplasia and progression of CA in UC. The low frequency of LOH in the p16 gene (9p) in adenomas compared with dysplasia in UC combined with infrequent LOH in APC gene loci in cases of pure dysplasia in UC may support this combination of markers as a clinical test for the differentiation of polypoid dysplasia from adenomas in UC. This is a US government work. There are no restrictions on its use. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, 39th & Market St, Philadelphia, PA 19104 USA. OI Giordano, Thomas/0000-0003-0641-8873 NR 21 TC 81 Z9 81 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 1998 VL 29 IS 2 BP 131 EP 136 DI 10.1016/S0046-8177(98)90222-2 PG 6 WC Pathology SC Pathology GA YX336 UT WOS:000072030000006 PM 9490271 ER PT J AU Romero, R AF Romero, R TI Clinical application of nitric oxide donors and blockers SO HUMAN REPRODUCTION LA English DT Article ID UTERINE CERVIX; GLYCERYL TRINITRATE; PREMATURE DELIVERY; PRETERM LABOR; GUINEA-PIG; PARTURITION; EXTRACTION; DILATATION; PREGNANCY C1 Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 39 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 1998 VL 13 IS 2 BP 248 EP 250 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZF722 UT WOS:000072925500002 PM 9557813 ER PT J AU Wilcox, AJ Weinberg, CR Baird, DD AF Wilcox, AJ Weinberg, CR Baird, DD TI Post-ovulatory ageing of the human oocyte and embryo failure SO HUMAN REPRODUCTION LA English DT Article DE embryonic death; human; oocyte; pregnancy ID EARLY-PREGNANCY LOSS; PROGESTERONE METABOLITES; INVITRO FERTILIZATION; SPONTANEOUS-ABORTION; URINARY ESTROGEN; CONCEPTION; INTERCOURSE; PROBABILITY; SURVIVAL; RISK AB We carried out a prospective study of 221 healthy women who were attempting pregnancy. During the study, women collected daily urine samples and kept daily records of intercourse. Ovulation and early pregnancy losses were later identified by immunoassays of urinary human chorionic gonadotrophin and steroid metabolites. We have used these data to examine whether the risk of early pregnancy loss was higher with post-ovulatory ageing of the oocyte, 192 pregnancies were ranked by the probability that the oocyte might have aged before fertilization. There was a statistically significant increase in the risk of early loss as the likelihood of oocyte ageing increased (P < 0.05). No similar risk was observed for clinical miscarriages. Post-ovulatory ageing of the oocyte prior to fertilization may cause early pregnancy failure in humans as it does in several other mammalian species. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 23 TC 104 Z9 106 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 1998 VL 13 IS 2 BP 394 EP 397 DI 10.1093/humrep/13.2.394 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZF722 UT WOS:000072925500034 PM 9557845 ER PT J AU Evans, GA AF Evans, GA TI 3B1 against renaturable kinase pk55 SO HYBRIDOMA LA English DT Article C1 NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Frederick, MD 21702 USA. RP Evans, GA (reprint author), NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Frederick, MD 21702 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD FEB PY 1998 VL 17 IS 1 BP 84 EP 84 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA ZA135 UT WOS:000072332400018 ER PT J AU Pajevic, S Daube-Witherspoon, ME Bacharach, SL Carson, RE AF Pajevic, S Daube-Witherspoon, ME Bacharach, SL Carson, RE TI Noise characteristics of 3-D and 2-D PET images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE correlation; GE advance scanner; noise; 3-D positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; ECAT EXACT; PERFORMANCE; SCANNER; RECONSTRUCTION AB We analyzed the noise characteristics of two-dimensional (2-D) and three-dimensional (3-D) images obtained from the GE Advance positron emission tomography (PET) scanner, Three phantoms were used: a uniform 20-cm phantom, a 3-D Hoffman brain phantom, and a chest phantom with heart and lung inserts. Using gated acquisition, we acquired 20 statistically equivalent scans of each phantom in 2-D and 3-D modes at several activity levels. From these data, we calculated pixel normalized standard deviations (NSD's), scaled to phantom mean, across the replicate scans, which allowed us to characterize the radial and axial distributions of pixel noise. We also performed sequential measurements of the phantoms in 2-D and 3-D modes to measure noise (from interpixel standard deviations) as a function of activity. To compensate for the difference in axial slice width between 2-D and 3-D images (due to the septa and reconstruction effects), we developed a smoothing kernel to apply to the 2-D data, After matching the resolution, the ratio of image-derived NSD values (NSD2D/NSD3D)(2) averaged throughout the uniform phantom was in good agreement with the noise equivalent count (NEC) ratio (NEC3D/NEC2D). By comparing different phantoms, we showed that the attenuation and emission distributions influence the spatial noise distribution. The estimates of pixel noise for 2-D and 3-D images produced here can be applied in the weighting of PET kinetic data and may be useful in the design of optimal dose and scanning requirements for PET studies. The accuracy of these phantom-based noise formulas should be validated for any given imaging situation, particularly in 3-D, if there is significant activity outside the scanner field of view. C1 NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20982 USA. RP Carson, RE (reprint author), NIH, PET Dept, Ctr Clin, Bldg 10,Room 1C401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 34 TC 56 Z9 56 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD FEB PY 1998 VL 17 IS 1 BP 9 EP 23 DI 10.1109/42.668691 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA ZN446 UT WOS:000073646700002 PM 9617904 ER PT J AU Matsumoto, N Ribaudo, RK Abastado, JP Margulies, DH Yokoyama, WM AF Matsumoto, N Ribaudo, RK Abastado, JP Margulies, DH Yokoyama, WM TI The lectin-like NK cell receptor Ly-49A recognizes a carbohydrate-independent epitope on its MHC class I ligand SO IMMUNITY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODIES; KD/DD RECOMBINANTS; ANIMAL LECTINS; BINDING-SITE; T-CELLS; MOLECULES; ANTIGEN; EXPRESSION AB The mouse NK inhibitory Ly-49A receptor specifically interacts with a peptide-induced conformational determinant on its MHC class I ligand, H-2D(d). In addition, it binds the polysaccharide fucoidan, consistent with its C-type lectin homology and the hypothesis that Ly-49A interacts with carbohydrates on D-d. Herein, however, we demonstrate that Ly-49A recognizes D-d mutants lacking N-glycosylation. Fucoidan competes for binding with anti-Ly-49A antibodies that inhibit Ly-49A-D-d interaction, and blocks apparent Ly-49A binding to unglycosylated D-d. We confirm that Ly-49A recognizes the alpha 1 and amino-terminal alpha 2 domains of D-d by analysis of recombinant H-2K(d)-H-2D(d) molecules. These studies indicate that Ly-49A recognizes carbohydrate-independent epitope(s) on D-d and suggest that Ly-49A has two distinct ligands, carbohydrate and MHC class I. C1 Washington Univ, Sch Med, Howard Hughes Med Inst, Div Rheumatol, St Louis, MO 63110 USA. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. Inst Pasteur, Dept Immunol, F-75724 Paris, France. Natl Inst Hlth, Immunol Lab, Bethesda, MD 20892 USA. RP Yokoyama, WM (reprint author), Washington Univ, Sch Med, Howard Hughes Med Inst, Div Rheumatol, St Louis, MO 63110 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 55 TC 71 Z9 71 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1998 VL 8 IS 2 BP 245 EP 254 DI 10.1016/S1074-7613(00)80476-8 PG 10 WC Immunology SC Immunology GA YY926 UT WOS:000072201800011 PM 9492005 ER PT J AU Urban, JF Noben-Trauth, N Donaldson, DD Madden, KB Morris, SC Collins, M Finkelman, FD AF Urban, JF Noben-Trauth, N Donaldson, DD Madden, KB Morris, SC Collins, M Finkelman, FD TI IL-13, IL-4R alpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis SO IMMUNITY LA English DT Article ID RECEPTOR-ALPHA CHAIN; COMMON GAMMA-CHAIN; INTERLEUKIN-4 RECEPTOR; MONOCLONAL-ANTIBODIES; SIGNAL-TRANSDUCTION; TRICHINELLA-SPIRALIS; PROTECTIVE IMMUNITY; RAPID EXPULSION; BINDING SUBUNIT; IGE RESPONSE AB Although IL-4 induces expulsion of the gastrointestinal nematode parasite, Nippostrongylus brasiliensis, from immunodeficient mice, this parasite is expelled normally by IL-4-deficient mice. This apparent paradox is explained by observations that IL-4 receptor alpha chain (IL-4R alpha)-deficient mice and Stat6-deficient mice fail to expel N. brasiliensis, and a specific antagonist for IL-13, another activator of Stat6 through IL-4R alpha, prevents worm expulsion. Thus, N. brasiliensis expulsion requires signaling via IL-4R alpha and State, and IL-13 may be more important than IL-4 as an inducer of the State signaling that leads to worm expulsion. Additional observations made in the course of these experiments demonstrate that State signaling is not required for IL-4 enhancement of IgG1 production and actually inhibits IL-4-induction of mucosal mastocytosis. C1 Univ Cincinnati, Coll Med, Div Immunol, Cincinnati, OH 45267 USA. USDA, Beltsville, MD 20705 USA. NIH, Immunol Lab, Rockville, MD 20852 USA. Genet Inst, Cambridge, MA 02140 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. Vet Adm Med Ctr, Cincinnati, OH 45220 USA. RP Finkelman, FD (reprint author), Univ Cincinnati, Coll Med, Div Immunol, Cincinnati, OH 45267 USA. EM ffinkelman@mem.po.com OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [R01 AI35987, R01 AI37180] NR 56 TC 389 Z9 393 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1998 VL 8 IS 2 BP 255 EP 264 DI 10.1016/S1074-7613(00)80477-X PG 10 WC Immunology SC Immunology GA YY926 UT WOS:000072201800012 PM 9492006 ER PT J AU Cho, KW Youn, HY Okuda, M Satoh, H Cevario, S O'Brien, SJ Watari, T Tsujimoto, H Hasegawa, A AF Cho, KW Youn, HY Okuda, M Satoh, H Cevario, S O'Brien, SJ Watari, T Tsujimoto, H Hasegawa, A TI Cloning and mapping of cat (Felis catus) immunoglobulin and T-cell receptor genes SO IMMUNOGENETICS LA English DT Article DE cat; Ig; TcR; cloning; mapping ID COMPLETE NUCLEOTIDE-SEQUENCE; DELTA-CHAIN GENES; ALPHA-CHAIN; GAMMA-CHAIN; MOLECULAR-CLONING; ANTIGEN RECEPTOR; CHROMOSOMAL TRANSLOCATIONS; MOUSE IMMUNOGLOBULIN; CONSTANT REGIONS; BETA-CHAIN AB Molecular cloning and chromosomal mapping of the cat immunoglobulin (Ig) and T-cell receptor (TcR) genes were carried out to provide basic information for genetic analysis of immunologic diseases including leukemias and lymphomas in cats. We cloned two ii: constant genes, IGHM and IGHG and three Ten constant genes, TRAC, TRGC, and TRDC, by polymerase chain reaction (FCR) amplification of cDNA from cat peripheral blood mononuclear cells. For chromosomal mapping of the ip and TcR loci including the IGK, TC;I, and TRB on the cat genome, we performed PCR screening of DNAs li-om 37 cat x rodent somatic cell hybrids by using specific primers for the given genes. Consequently, three loci for IGH, TRA, and TRD, and two loci for TRB and TRG were found to be syntenic and assigned to cat chromosomes (FCA) B3 and A2, respectively. Further, IGK and IGL loci were mapped on FCA A3 and D3, respectively. These findings support the notion that the genetic linkages between the Ig and TcR genes are extensively conserved between humans and cats. C1 Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Internal Med, Bunkyo Ku, Tokyo 113, Japan. Seoul Natl Univ, Coll Vet Med, Dept Vet Internal Med, Seoul 151742, South Korea. Univ Tokyo, Inst Med Sci, Dept Pathol, Minato Ku, Tokyo 108, Japan. NCI, Lab Genon Divers, Frederick, MD 21702 USA. RP Cho, KW (reprint author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Vet Internal Med, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 113, Japan. NR 41 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 1998 VL 47 IS 3 BP 226 EP 233 DI 10.1007/s002510050352 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA YV181 UT WOS:000071797500006 PM 9435341 ER PT J AU Arepalli, SR Jones, EP Howcroft, TK Carlo, I Wang, CR Lindahl, KF Singer, DS Rudikoff, S AF Arepalli, SR Jones, EP Howcroft, TK Carlo, I Wang, CR Lindahl, KF Singer, DS Rudikoff, S TI Characterization of two class I genes from the H2-M region: evidence for a new subfamily SO IMMUNOGENETICS LA English DT Article DE divergent class Ib gene; H2-M region; M1 subfamily; M10 subfamily; distal Mhc ID MAJOR HISTOCOMPATIBILITY COMPLEX; INTESTINAL EPITHELIAL-CELLS; 3-DIMENSIONAL STRUCTURE; HMT REGION; TLA REGION; MOUSE; EXPRESSION; MHC; ANTIGEN; THYMUS AB We cloned, sequenced, and mapped two divergent major histocompatibility class Ib genes from BALB/c mice, M9(d) and M10(d) both have the potential to encode full-length class I molecules, but transcripts were not readily detectable. M9 is 86% similar to Mt in its nucleotide sequence and maps next to it on YAC clones. M9 is only 64% similar to M10 and 60% to H2-K-k. Probes from M10 define a new subfamily of eight class I genes in C3M mice; five cluster directly distal to H2-T1, and three are located between M9-1-7-8 and M6-4-5 in the H2-M region. C1 Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dept Microbiol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dept Biochem, Dallas, TX 75235 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Lindahl, KF (reprint author), Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dept Microbiol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NIAID NIH HHS [R29 AI040310, AI37818, R29 AI040310-04] NR 30 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 1998 VL 47 IS 3 BP 264 EP 271 DI 10.1007/s002510050356 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA YV181 UT WOS:000071797500010 PM 9435345 ER PT J AU McInnes, IB Liew, FY AF McInnes, IB Liew, FY TI Interleukin 15: a proinflammatory role in rheumatoid arthritis synovitis SO IMMUNOLOGY TODAY LA English DT Editorial Material ID T-CELL PROLIFERATION; BETA-CHAIN; IL-15; CYTOKINE; LYMPHOCYTES; RECEPTOR; EXPRESSION; ACTIVATION; MIGRATION; INDUCTION AB In rheumatoid arthritis (RA), locally produced interleukin 15 (IL-15) can recruit and activate synovial T cells, which then amplify and perpetuate inflammation through induction of monocyte-derived tumour necrosis factor alpha (TNF-alpha) via a cell-contact-dependent mechanism. Thus, IL-15 could play a pivotal role in disease pathogenesis, acting upstream of TNF-alpha in orchestrating the induction of a cascade of inflammatory cytokines. C1 NIH, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Royal Infirm, Ctr Rheumat Dis, Glasgow G31 2ER, Lanark, Scotland. Univ Glasgow, Dept Immunol, Glasgow G12 8QQ, Lanark, Scotland. RP McInnes, IB (reprint author), NIH, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. EM F.Y.Liew@clinmed.gla.ac.uk NR 32 TC 121 Z9 124 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD FEB PY 1998 VL 19 IS 2 BP 75 EP 79 DI 10.1016/S0167-5699(97)01205-X PG 5 WC Immunology SC Immunology GA YY200 UT WOS:000072123300006 PM 9509762 ER PT J AU Del Giudice, RA AF Del Giudice, RA TI M-CRML, a new axenic medium to replace indicator cell cultures for the isolation of all strains of Mycoplasma hyorhinis SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Letter C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Mycoplasma Lab, Frederick, MD 21702 USA. RP Del Giudice, RA (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Mycoplasma Lab, POB B, Frederick, MD 21702 USA. NR 9 TC 2 Z9 2 U1 1 U2 1 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD FEB PY 1998 VL 34 IS 2 BP 88 EP 89 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA ZB963 UT WOS:000072525900002 PM 9542642 ER PT J AU Hinnebusch, BJ Barbour, AG Restrepo, BI Schwan, TG AF Hinnebusch, BJ Barbour, AG Restrepo, BI Schwan, TG TI Population structure of the relapsing fever spirochete Borrelia hermsii as indicated by polymorphism of two multigene families that encode immunogenic outer surface lipoproteins SO INFECTION AND IMMUNITY LA English DT Article ID VARIABLE MAJOR PROTEINS; LATERAL GENE EXCHANGE; LYME-DISEASE; ANTIGENIC VARIATION; PLASMODIUM-FALCIPARUM; IMMUNE-RESPONSE; C OSPC; BURGDORFERI; EXPRESSION; RECOMBINATION AB The tick-borne relapsing fever spirochete Borrelia hermsii evades the mammalian immune system by periodically switching expression among members of two multigene families that encode immunogenic, antigenically distinct outer surface proteins, The type strain, B. hermsii HS1, has at least 40 complete genes and pseudogenes that participate in this multiphasic antigenic variation, Originally termed vmp (for variable major protein) genes, they have been reclassified as vsp (for variable small protein) and vip (for variable large protein) genes, based on size and amino acid sequence similarities, To date, antigenic variation in B. hermsii has been studied only in the type strain, HS1, Nucleotide sequence comparisons of 23 B. hermsii HS1 genes revealed five distinct groups, the vsp gene family and four subfamilies of vip genes, We used PCR with family-and subfamily-specific primers, followed by restriction fragment length polymorphism analysis, to compare the vsp and vip repertoires of HS1 and seven other B. hermsii isolates from Washington, Idaho, and California. This analysis, together with pulsed-field gel electrophoresis genome profiles, revealed that the eight isolates formed three distinct groups, which likely represent clonal lineages, Members of the three groups coexisted in the same geographic area, but they could also be isolated across large geographical distances, This population structure may result from immune selection by the host, as has been proposed for other pathogens with polymorphic antigens. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. Univ Calif Irvine, Coll Med, Dept Med, Irvine, CA 92717 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. RP Hinnebusch, BJ (reprint author), NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 FU NIAID NIH HHS [AI24424, R01 AI024424, R37 AI024424] NR 54 TC 51 Z9 75 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1998 VL 66 IS 2 BP 432 EP 440 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YU693 UT WOS:000071744800005 PM 9453591 ER PT J AU Zea, AH Ochoa, MT Ghosh, P Longo, DL Alvord, WG Valderrama, L Falabella, R Harvey, LK Saravia, N Moreno, LH Ochoa, AC AF Zea, AH Ochoa, MT Ghosh, P Longo, DL Alvord, WG Valderrama, L Falabella, R Harvey, LK Saravia, N Moreno, LH Ochoa, AC TI Changes in expression of signal transduction proteins in T lymphocytes of patients with leprosy SO INFECTION AND IMMUNITY LA English DT Article ID RECEPTOR ZETA-CHAIN; TUMOR-BEARING MICE; CELL RECEPTOR; KAPPA-B; INTERFERON-GAMMA; HELPER SUBSETS; PHENOTYPES; LESIONS; LEISHMANIASIS; CARCINOMA AB Advanced stages of mycobacterial diseases such as leprosy and tuberculosis are characterized by a loss of T-cell function. The basis of this T-cell dysfunction is not well understood. The present report demonstrates major alterations in the expression of signal transduction molecules in T cells of leprosy patients. These alterations were most frequently observed in lepromatous leprosy (LL) patients. Of 29 LL patients, 69% had decreased T-cell receptor zeta-chain expression, 48% had decreased p56(lck) tyrosine kinase, and 63% had a loss of nuclear transcription factor NF-kappa B p65. An electrophoretic mobility shift assay with the gamma interferon core promoter region revealed a loss of the Th1 DNA-binding pattern in LL patients. In contrast, tuberculoid leprosy patients had only minor signal transduction alterations. These novel findings might improve our understanding of the T-cell dysfunction observed in leprosy and other infectious diseases and consequently might lead to better immunologic evaluation of patients. C1 Louisiana State Univ, Ctr Neurosci, Immunotherapy Program, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Hosp Univ Valle, Dermatol Serv, Cali, Colombia. Fdn CIDEIM, Cali, Colombia. Univ Miami, Dept Immunol Microbiol, Miami, FL 33136 USA. NIA, NIH, Baltimore, MD 21224 USA. Frederick Canc Res & Dev Ctr, Data Management Serv Inc, Frederick, MD 21702 USA. RP Zea, AH (reprint author), Louisiana State Univ, Ctr Neurosci, Immunotherapy Program, Stanley S Scott Canc Ctr, 2020 Gravier St,Suite D, New Orleans, LA 70112 USA. EM azea@lsumc.edu; aochoa@lsumc.edu FU NCI NIH HHS [N01-CO-56000]; PHS HHS [P50-A1] NR 33 TC 80 Z9 80 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 FEB PY 1998 VL 66 IS 2 BP 499 EP 504 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YU693 UT WOS:000071744800016 PM 9453602 ER PT J AU George, KM Barker, LP Welty, DM Small, PLC AF George, KM Barker, LP Welty, DM Small, PLC TI Partial purification and characterization of biological effects of a lipid toxin produced by Mycobacterium ulcerans SO INFECTION AND IMMUNITY LA English DT Article ID NECROSIS-FACTOR-ALPHA; MEDIATED ACTIVATION; TUBERCULOSIS; MACROPHAGES; CELLS; LIPOARABINOMANNAN; INHIBITION; SULFATIDE; MONOCYTES; ACTIN AB Organisms in the genus Mycobacterium cause a variety of human diseases, One member of the genus, M. ulcerans, causes a necrotizing skin disease called Buruli ulcer, Buruli ulcer is unique among mycobacterial diseases in that the organisms at the site of infection are extracellular and there is little acute inflammatory response, Previous literature reported the presence of a toxin in the culture supernatant of M. ulcerans which causes a cytopathic effect on the mouse fibroblast cell line L929 in which the adherent cells round up and detach from the tissue culture plate. Here we report partial purification of a lipid toxin from the culture supernatant of M. ulcerans which is capable of causing the cytopathic effect on L929 cells, We also show that this cytopathic effect is a result of cytoskeletal rearrangement. The M. ulcerans toxin does not cause cell death but instead arrests cells in the G(1) phase of the cell cycle. C1 NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. RP George, KM (reprint author), NIAID, Rocky Mt Labs, Microscopy Branch, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM katie_george@nih.gov NR 42 TC 64 Z9 64 U1 0 U2 3 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 FEB PY 1998 VL 66 IS 2 BP 587 EP 593 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YU693 UT WOS:000071744800027 PM 9453613 ER PT J AU Fricker, G Drewe, J Miller, DS AF Fricker, G Drewe, J Miller, DS TI Excretion of a fluorescent rapamycin-derivative in proximal kidney tubules is mediated by P-glycoprotein SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID MECHANISMS; SECRETION C1 Univ Heidelberg, Inst Pharmazeut Technol & Biopharm, D-69120 Heidelberg, Germany. Univ Klin, Basel, Switzerland. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Fricker, G (reprint author), Univ Heidelberg, Inst Pharmazeut Technol & Biopharm, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. NR 9 TC 1 Z9 1 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD FEB PY 1998 VL 36 IS 2 BP 67 EP 69 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YX410 UT WOS:000072037200003 PM 9520145 ER PT J AU Schooler, C AF Schooler, C TI History, social structure and individualism a cross-cultural perspective on Japan SO INTERNATIONAL JOURNAL OF COMPARATIVE SOCIOLOGY LA English DT Article ID UNITED-STATES; BEHAVIOR; VALUES AB This paper explores how history and social structure affect individualism in Japan. It integrates a variety of cross-cultural studies comparing Japan with the West whose methodological approaches vary considerably. Its historical comparisons point to many parallels between Japan and the West and reveal similar links between economic development and individualism. Sociological surveys demonstrate that similar environmental conditions, particularly environmental complexity, have similar effects in the two settings and provide evidence of a growth in individualism in Japan resulting from an increase in such complexity. Anthropological and developmental psychological studies demonstrate how maternal behaviors reproduce cultural norms about appropriate levels of group interdependence and suggest that maternal behavior is becoming more individualistic in Japan, most probably as a result of changing socio-environmental conditions. Reported findings on how the institutionalization of values such as individualism or interdependence lead to such values' continued acceptance provide an indication of why the values embodied in cultures and social structures often seem to change more slowly than do values of individuals. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. NR 57 TC 6 Z9 6 U1 1 U2 2 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0020-7152 J9 INT J COMP SOCIOL JI Int. J. Comp. Sociol. PD FEB PY 1998 VL 39 IS 1 BP 32 EP 51 DI 10.1177/002071529803900104 PG 20 WC Sociology SC Sociology GA ZH749 UT WOS:000073143800004 ER PT J AU Fitzmaurice, JM AF Fitzmaurice, JM TI A new twist in US health care data standards development: adoption of electronic health care transactions standards for administrative simplification SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article; Proceedings Paper CT Meeting on Standardisation in Health Informatics - Towards Global Consensus and Cooperation CY SEP 11-13, 1997 CL HAMILTON, BERMUDA SP Int Med Informat Assoc, Working Grp 16 DE standards; informatics; health care data; HISB; HIPAA; computer-based patient record; AHCPR; privacy AB To reduce the costs of common administrative transactions, health plans, payers and providers encouraged the US Congress to legislate administrative simplification of specific electronic health data transactions. The Health Insurance Portability and Accountability Act (HIPAA) of 1996 created incentives for a public-private partnership to develop and implement standards for the uniformity of health care data used in electronic administrative health transactions and standards for the privacy and security of individually identifiable health information. The standards' requirements of HIPAA and how they have been met by the US government hold promise for accelerating the uniform adoption of standards developed by accredited standards developing organizations. The transactions designated by Congress, the process of choosing the standards in the Department of Health and Human Services, the principles that guided these choices, and the actual choices, are presented here. A successful partnership for administrative health data standards can pave the way for success in clinical health data standards and their application in computer-based patient record systems. Published by Elsevier Science B.V. All rights reserved. C1 US Dept HHS, Agcy Hlth Care Policy & Res, Ctr Informat Technol, Rockville, MD 20852 USA. RP Fitzmaurice, JM (reprint author), US Dept HHS, Agcy Hlth Care Policy & Res, Ctr Informat Technol, 2101 E Jefferson St,Suite 602, Rockville, MD 20852 USA. NR 6 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD FEB PY 1998 VL 48 IS 1-3 BP 19 EP 28 DI 10.1016/S1386-5056(97)00104-4 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA ZG242 UT WOS:000072981400004 PM 9600398 ER PT J AU Song, K Fukushima, P Seth, P Sinha, BK AF Song, K Fukushima, P Seth, P Sinha, BK TI Role of p53 and apoptosis in sensitization of cis-diamminedichloroplatinum antitumor activity by interleukin-1 alpha in ovarian carcinoma cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE p53; apoptosis; IL-1; cisplatin; ovarian tumors; synergy ID HUMAN-MELANOMA CELLS; DNA-DAMAGE; IN-VIVO; C-MYC; LINE NIH-OVCAR-3; ETOPOSIDE; PROLIFERATION; PROTEIN; CANCER; POTENTIATION AB We have previously reported that interleukin-1 alpha (IL-1 alpha) sensitized cisplatin cytotoxicity against human ovarian NIH:OVCAR-3 tumor cells. We have further examined interactions of IL-1 alpha with cisplatin in these ovarian cells. Treatment of cells with either IL-1 alpha or CDDP or combinations resulted in a significant accumulation of cells in G1 phase and a concomitant decrease in the S phase of the cell cycle. IL-1 alpha and CDDP treatment induced p53 protein in NIH:OVCAR-3 tumor cells. CDDP and IL-1 alpha treatment decreased the steady-state expression of c-myc RNA and induced significant degradation of the genomic DNA into internucleosomal sized DNA fragments which was further increased in the presence of both agents in these cells. Taken together, these studies suggest that IL-1 alpha may kill ovarian NIH:OVCAR-3 tumor cells by inducing a blockade at G1/S of the cell cycle, downregulating c-myc gene and inducing p53-dependent apoptosis. The synergistic interactions of IL-1 alpha with CDDP may involve the enhancement of p53-dependent apoptosis. C1 NCI, Dev Therapeut Dept, Med Branch, Bethesda, MD 20892 USA. RP Sinha, BK (reprint author), NCI, Dev Therapeut Dept, Med Branch, Bldg 10,Room 12C-210, Bethesda, MD 20892 USA. NR 37 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 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1998 VL 12 IS 2 BP 299 EP 304 PG 6 WC Oncology SC Oncology GA YT516 UT WOS:000071614900007 PM 9458352 ER PT J AU Wang, H Spillare, EA Wang, QS Sabourin, CLK Stoner, GD AF Wang, H Spillare, EA Wang, QS Sabourin, CLK Stoner, GD TI p53-independent down-regulation of cyclin D1 and p21(Waf1) in the process of immortalization of human esophageal epithelial cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE p53 gene; cyclin D1; p21Waf1 gene; esophageal epithelial cells ID DEPENDENT KINASES; TUMOR SUPPRESSION; HUMAN FIBROBLASTS; MAMMALIAN-CELLS; BREAST-CANCER; EXPRESSION; P53; P21; PROGRESSION; INHIBITOR AB Immortalization is considered to be an initial critical step in the process of multistage cell transformation. However, the molecular mechanisms underlying this event are not well understood. Our laboratory previously established the immortalized human esophageal epithelial cell line, HET-1A, by SV40 T-antigen transfection. In the present study, we investigated the role of G1 cyclins and cyclin dependent kinase inhibitors, in the process of immortalization. By using immunoprecipitation and Western blot analysis, sequential changes in the expression of both cyclin D1 and p21(Waf1) were detected during the conversion of precrisis esophageal epithelial cells to immortalized HET-1A cells. Reduced expression levels of both cyclin D1 and p21(Waf1) were found in early passage and late passage immortalized cells when compared to levels in precrisis cells. In addition, continued subculture of the immortalized cells led to increased expression levels of both cyclin D1 and p21(Waf1). No significant changes in the expression of either cyclin E or p53 were observed in early or late passage immortalized cells when compared to precrisis cells. These results suggest that changes in the expression levels of cyclin D1 and p21(Waf1) but not cyclin E, may be important for immortalization and continued propagation of human esophageal epithelial cells, and these changes are not dependent on regulation by p53. C1 Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Stoner, GD (reprint author), Ohio State Univ, Sch Publ Hlth, Div Environm Hlth Sci, CHRI Suite 1148,300 W 10th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [CA28950] NR 34 TC 5 Z9 5 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1998 VL 12 IS 2 BP 325 EP 328 PG 4 WC Oncology SC Oncology GA YT516 UT WOS:000071614900012 PM 9458357 ER PT J AU Szabo, E Francis, J Birrer, MJ AF Szabo, E Francis, J Birrer, MJ TI Alterations in differentiation and apoptosis induced by bufalin in cJun overexpressing U-937 cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE AP-1; Na+/K+ ATPase; jun and fos oncogenes ID C-JUN EXPRESSION; MYELOID-LEUKEMIA CELLS; MONOCYTIC DIFFERENTIATION; HL-60 CELLS; GENE-EXPRESSION; OKADAIC ACID; PROTEIN; INDUCTION; INVOLVEMENT; GROWTH AB Recent evidence suggests that c-jun plays a pivotal role in macrophage differentiation induced by multiple agents and that cJun overexpression induces partial macrophage differentiation in the leukemic cell line U-937. The novel differentiating agent bufalin, a Na+/K+ ATPase inhibitor, has also been shown to induce macrophage differentiation in U-937. In order to further define the role of c-jun in macrophage differentiation, we examined the function of c-jun/AP-1 during bufalin induced differentiation in both c-jun transfected and parental U-937 cells. In contrast to phorbol esters, bufalin does not significantly stimulate c-jun or c-fos mRNA expression or AP-1 transactivation. However, bufalin treatment leads to markedly greater morphologic and functional changes indicative of more extensive differentiation in the cJun overexpressing cells compared to the non-transfected controls. Furthermore, cJun overexpressing cells maintain greater viability in the presence of bufalin and arrest in a different phase of the cell cycle than do control cell lines (G0/G1 versus S/G2M, respectively), although some apoptosis occurs in all cell lines treated with bufalin. These data suggest that while bufalin can induce some degree of differentiation in U-937 cells independent of c-jun/AP-1 controlled pathways, the involvement of these pathways by enforced cJun expression enhances the extent of differentiation and shifts the balance between differentiation and apoptosis. C1 NCI, Med Branch, Div Clin Sci, Rockville, MD 20850 USA. RP Szabo, E (reprint author), NCI, Med Branch, Div Clin Sci, 9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA. NR 35 TC 8 Z9 10 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1998 VL 12 IS 2 BP 403 EP 409 PG 7 WC Oncology SC Oncology GA YT516 UT WOS:000071614900025 PM 9458368 ER PT J AU Yoshidome, K Shibata, MA Maroulakou, IG Liu, ML Jorcyk, CL Gold, LG Welch, VN Green, JE AF Yoshidome, K Shibata, MA Maroulakou, IG Liu, ML Jorcyk, CL Gold, LG Welch, VN Green, JE TI Genetic alterations in the development of mammary and prostate cancer in the C3(1)/Tag transgenic mouse model SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Review DE prostatic steroid binding protein; C3(1); mammary carcinogenesis; prostate carcinogenesis; transgenic mice ID LARGE T-ANTIGEN; STEROID-BINDING-PROTEIN; LARGE-TUMOR-ANTIGEN; CELL-DEATH; C-3 GENES; MICE; APOPTOSIS; P53; CARCINOMA; SV40 AB We have generated a transgenic mouse model in which female mice develop ductal mammary adenocarcinomas and male mice develop prostatic adenocarcinomas by using a transgene containing the hormone-responsive rat prostatic steroid binding protein 5' flanking region C3(1) fused to the simian virus 40 (SV40) large T antigen. We have identified some genetic alterations during mammary and prostate tumor progression: (i) p53 is functionally inactivated during mammary cancer development without p53 mutations; (ii) Alterations in apoptosis during mammary tumor progression are p53 and bcl-2 independent; (iii) Ha-ms mutations occur early in the development of prostate cancer. This unique animal model offers the opportunity to study multistep tumorigenesis in these organs. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Chemoprevent Lab, NIH, Bldg 41,Room C629,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 10 Z9 10 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1998 VL 12 IS 2 BP 449 EP 453 PG 5 WC Oncology SC Oncology GA YT516 UT WOS:000071614900031 PM 9458374 ER PT J AU Westergaard, GC Kuhn, HE Babitz, MA Suomi, SJ AF Westergaard, GC Kuhn, HE Babitz, MA Suomi, SJ TI Aimed throwing as a means of food transfer between tufted capuchins (Cebus apella) SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE capuchin; Cebus; food-sharing; Homo; throwing ID TOOL USE; MONKEYS; INTELLIGENCE AB We examined aimed throwing as a means of food transfer in tufted capuchins (Cebus apella). We conducted this research in three phases. In Phase 1 we provided food to monkeys in one of two groups housed 1 m apart. We did not provide food to subjects in the second group. An observer recorded each instance in which a subject in the first group threw food toward one in the second group. In Phase 2 we provided a group of capuchins with food and noted each instance in which a subject threw food toward an empty cage. In Phase 3 we provided food simultaneously to two groups of capuchins and noted each instance of food-throwing between them. In Phase 1 subjects in one group threw food toward subjects in a second group, which, when provided the opportunity, did not throw food toward capuchins in the first group. Thrown food was either caught retrieved or lost on the test room floor The rate of throwing decreased significantly when subjects were presented with an empty cage and when both groups of subjects were given food. We propose that psychological processes which underlie aimed throwing and food sharing came into existence through convergent evolution in large-brained, extractive foraging primates. We further speculate that although a well-developed system of exchange, based on contingent reciprocity, may occur among primates only in Homo, simpler transfer systems involving voluntary unidirectional passing of food from one individual to another appear to be more widespread among primates than previously thought and can be expressed in rather unusual circumstances such as those in this experiment. C1 Univ St Andrews, Sch Psychol, St Andrews, Fife, Scotland. NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. RP Westergaard, GC (reprint author), Natl Inst Hlth Anim Ctr, POB 529, Poolesville, MD 20837 USA. NR 24 TC 8 Z9 8 U1 2 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD FEB PY 1998 VL 19 IS 1 BP 123 EP 131 DI 10.1023/A:1020315212310 PG 9 WC Zoology SC Zoology GA ZA849 UT WOS:000072408200008 ER PT J AU Yin, FF Gao, QH Xie, HC Nelson, DF Yu, Y Kwok, WE Totterman, S Schell, MC Rubin, P AF Yin, FF Gao, QH Xie, HC Nelson, DF Yu, Y Kwok, WE Totterman, S Schell, MC Rubin, P TI MR image-guided portal verification for brain treatment field SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 26-30, 1996 CL LOS ANGELES, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE radiation therapy; portal verification; MRI; DRR; treatment planning ID DIGITALLY RECONSTRUCTED RADIOGRAPHS; RADIATION-THERAPY; PATIENT SETUP; RADIOTHERAPY; TOMOGRAPHY; DISTORTION; INSPECTION; ACCURACY; FUSION; CT AB Purpose: To investigate a method for the generation of digitally reconstructed radiographs directly from MR images (DRR-MRI) to guide a computerized portal verification procedure. Methods and Materials: Several major steps were developed to perform an MR image-guided portal verification procedure. Initially, a wavelet-based multiresolution adaptive thresholding method was used to segment the skin slice-by-slice in MR brain axial images. Some selected anatomical structures, such as target volume and critical organs, were then manually identified and were reassigned to relatively higher intensities. Interslice information was interpolated with a directional method to achieve comparable display resolution in three dimensions. Next, a ray-tracing method was used to generate a DRR-MRI image at the planned treatment position, and the ray tracing was simply performed on summation of voxels along the ray. The skin and its relative positions were also projected to the DRR-MRI and were used to guide the search of similar features in the portal image. A Canny edge detector was used to enhance the brain contour in both portal and simulation images. The skin in the brain portal image was then extracted using a knowledge-based searching technique. Finally, a Chamfer matching technique was used to correlate features between DRR-MRI and portal image. Results: The MR image-guided portal verification method was evaluated using a brain phantom case and a clinical patient case. Both DRR-CT and DRR-MRI were generated using CT and MR phantom images with the same beam orientation and then compared. The matching result indicated that the maximum deviation of internal structures was less than 1 mm. The segmented results for brain MR slice images indicated that a wavelet-based image segmentation technique provided a reasonable estimation for the brain skin. For the clinical patient case with a given portal field, the MR image-guided verification method provided an excellent match between features in both DRR-MRI and portal image. Moreover, target volume could be accurately visualized in the DRR-MRI and mapped over to the corresponding portal image for treatment verification. The accuracy of DRR-MRI was also examined by comparing it to the corresponding simulation image. The matching results indicated that the maximum deviation of anatomical features was less than 2.5 mm. Conclusion: A method for MR image-guided portal verification of brain treatment field was developed. Although the radiographic appearance in the DRR-MRI is different from that in the portal image, DRR-MRI provides essential anatomical features (landmarks and target volume) as well as their relative locations to be used as references for computerized portal verification. (C) 1998 Elsevier Science Inc. C1 Univ Rochester, Dept Radiat Oncol, Oncol Imaging Res Lab, New York, NY 14642 USA. Univ Rochester, Dept Radiol, Oncol Imaging Res Lab, New York, NY 14642 USA. NCI, NIH, Radiat Oncol Sect, Bethesda, MD 20892 USA. RP Yin, FF (reprint author), Univ Rochester, Dept Radiat Oncol, Oncol Imaging Res Lab, 601 Elmwood Ave,Box 647, New York, NY 14642 USA. NR 25 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1998 VL 40 IS 3 BP 703 EP 711 DI 10.1016/S0360-3016(97)00763-3 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YX786 UT WOS:000072077700025 PM 9486623 ER PT J AU Davis, MD Fisher, MR Gangnon, RE Barton, F Aiello, LM Chew, EY Ferris, FL Knatterud, GL AF Davis, MD Fisher, MR Gangnon, RE Barton, F Aiello, LM Chew, EY Ferris, FL Knatterud, GL CA Early Treatment Diabet Retinopathy Study Res G TI Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early treatment diabetic retinopathy study report #18 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MICROVASCULAR COMPLICATIONS; 4-YEAR INCIDENCE; GLYCEMIC CONTROL; PLASMA-PROTEINS; BLOOD-PRESSURE; PROGRESSION; MELLITUS; DIAGNOSIS; AGE; ASSOCIATION AB PURPOSE. TO identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS. Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS. The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and, in persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS. These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy. C1 NEI, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. Maryland Med Res Inst, Baltimore, MD USA. Joslin Clin, Boston, MA USA. RP Davis, MD (reprint author), NEI, Div Biometry & Epidemiol, NIH, Bldg 31,Room 6A52,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [EY07119, EY08107, EY10295] NR 60 TC 198 Z9 213 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 1998 VL 39 IS 2 BP 233 EP 252 PG 20 WC Ophthalmology SC Ophthalmology GA YW563 UT WOS:000071948900008 PM 9477980 ER PT J AU Hibbs, ED AF Hibbs, ED TI Improving methodologies for the treatment of child and adolescent disorders: Introduction SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE children; adolescents; treatment methodologies AB This special issue grew out of a workshop sponsored by the National Institute of Mental Health, the MacArthur Foundation, and the Child and Adolescent Psychosocial Interventions Consortium. The goals of the workshop are outlined. The contents of the special issue are then described: definitions of psychotherapy and its mechanisms of action, developmental issues in psychotherapy research, methodologies for the treatment of anxious youth, measurement of change in interventions, predicting the outcome of treatment, and advancing the efficacy and effectiveness of psychosocial treatments. Finally, some areas that need to be addressed in the future are discussed, such as process research, the effects of comorbidity on outcomes, intensity, and duration, and transferability of treatments. C1 NIMH, Psychosocial Treatment Res, Rockville, MD 20857 USA. RP Hibbs, ED (reprint author), NIMH, Psychosocial Treatment Res, 5600 Fishers Lane,Room 10C-09, Rockville, MD 20857 USA. NR 5 TC 9 Z9 9 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 1998 VL 26 IS 1 BP 1 EP 6 DI 10.1023/A:1022638621210 PG 6 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA ZF486 UT WOS:000072902300001 PM 9566541 ER PT J AU Zahn, TP Jacobsen, LK Gordon, CT McKenna, K Frazier, JA Rapoport, JL AF Zahn, TP Jacobsen, LK Gordon, CT McKenna, K Frazier, JA Rapoport, JL TI Attention deficits in childhood-onset schizophrenia: Reaction time studies SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID SENSORY DOMINANCE; VISUAL DOMINANCE; CHILDREN; CLOZAPINE; INTERVIEW; DISORDER; SYMPTOMS AB The hypothesis of continuity between childhood-onset and adult schizophrenia was tested by comparing the performance of 15 patients with childhood-onset schizophrenia and 52 age-matched controls on 2 reaction time paradigms that have been used to study adult schizophrenia. On simple reaction time to tones with regular and irregular preparatory intervals of 2, 4, and 8 s, patients showed greater effects of the length of the preparatory interval in the regular condition and greater effects of the preparatory interval (girls only) and the preceding preparatory interval in the irregular series. On simple reaction time to random lights and tones, patients were faster on ipsimodal sequences than cross-modal sequences compared with controls. Overall, patients were much slower than controls in both paradigms. The results suggest similar attention dysfunction as is found in adult schizophrenia and thus are consistent with the continuity hypothesis. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Zahn, TP (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C110,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. EM ted_zahn@nih.gov NR 58 TC 10 Z9 10 U1 3 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 1998 VL 107 IS 1 BP 97 EP 108 DI 10.1037/0021-843X.107.1.97 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA YX330 UT WOS:000072029400009 PM 9505042 ER PT J AU Maloney, EM Cleghorn, FR Morgan, OS Rodgers-Johnson, P Cranston, B Jack, N Blattner, WA Bartholomew, C Manns, A AF Maloney, EM Cleghorn, FR Morgan, OS Rodgers-Johnson, P Cranston, B Jack, N Blattner, WA Bartholomew, C Manns, A TI Incidence of HTLV-I-associated myelopathy tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HTLV-I; Jamaica; Trinidad; paraparesis, tropical spastic; sexually transmitted diseases ID VIRUS TYPE-I; RISK-FACTORS; LYMPHOMA AB HTLV-I is sexually transmitted more efficiently from men to women than vice versa, and the majority of HTLV-I endemic areas report a female preponderance of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) cases. The objective of this study was to estimate the gender-and age specific incidence rates of HAM/TSP in the general population as well as in the HTLV I-infected population in Jamaica and in Trinidad and Tobago. Incidence rates for HAM/TSP were computed based on all reported incident cases in both countries between 1990 and 1994. Population census reports for 1990 were used to calculate the population at risk, The age-standardized HAM/TSP incidence rate (mean +/- stardard error of the mean) in Jamaica was 1.8 +/- 0.2/100,000 person years (PY). Among individuals of African descent in Trinidad and Tobago, the rate was 1.7 +/- 0.4/100,000 PY. As in HTLV-I seroprevalence, the incidence rate of HAM/TSP increased with age through the fifth decade of life and was three times as high in women than in men. The HAM/TSP incidence rate, calculated as a function of the number of HTLV-I-infected persons in each age stratum, is higher in women (24.7/100,000 PY) than in men (17.3/100,000 PY). With HTLV-I infection, the lifetime risk of developing HAM/TSP was estimated to be 1.9% overall and is slightly higher in women (1.8%) than in men (1.3%). Thus, the higher prevalence of HTLV-I in women in endemic areas does not fully explain the preponderance of female HAM/TSP, suggesting that other cofactors must be present. The higher incidence rate in women between the ages of 40 and 59 years, as well as the increase in HAM/TSP incidence rates with age, are indicative of the importance of adult-acquired HTLV-I infection, presumably through sexual transmission. C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ Maryland, Inst Human Virol, Div Epidemiol & Prevent, Baltimore, MD 21201 USA. Univ W Indies, Dept Med, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. Caribbean Epidemiol Ctr, Med Res Ctr, Port Of Spain, Trinid & Tobago. Univ W Indies, Dept Med, St Augustine, Trinid & Tobago. RP Maloney, EM (reprint author), Viral Epidemiol Branch, Room 434,6130 Execut Blvd, Rockville, MD 20852 USA. NR 15 TC 67 Z9 69 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD FEB 1 PY 1998 VL 17 IS 2 BP 167 EP 170 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YV911 UT WOS:000071876700011 PM 9473019 ER PT J AU Shearer, WT Kalish, LA Zimmerman, PA AF Shearer, WT Kalish, LA Zimmerman, PA CA Women Infants Transmission Study Grp TI CCR5 HIV-1 vertical transmission SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Letter ID INFECTION; INDIVIDUALS; PROGRESSION; RESISTANCE; ALLELE; GENE C1 Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. New England Res Inst, Watertown, MA 02172 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. FU NIAID NIH HHS [UO1 AI 34842, UO1 AI 34840, UO1 AI 34841] NR 12 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD FEB 1 PY 1998 VL 17 IS 2 BP 180 EP 181 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YV911 UT WOS:000071876700014 PM 9473022 ER PT J AU Nasioulas, G Dean, M Koumbarelis, E Paraskevis, D Gialeraki, A Karafoulidou, A Mandalaki, T Hatzakis, A AF Nasioulas, G Dean, M Koumbarelis, E Paraskevis, D Gialeraki, A Karafoulidou, A Mandalaki, T Hatzakis, A TI Allele frequency of the CCR5 mutant chemokine receptor in Greek Caucasians SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Letter ID HIV-1 INFECTION; PROGRESSION; COFACTOR; ENTRY; GENE C1 Univ Athens, Sch Med, Natl Retrovirus Ref Ctr, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Laikon Gen Hosp, Reg Blood Transfus Ctr 2, Haemophilia Ctr, Athens, Greece. RP Nasioulas, G (reprint author), Univ Athens, Sch Med, Natl Retrovirus Ref Ctr, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Paraskevis, Dimitrios/0000-0001-6167-7152 NR 17 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD FEB 1 PY 1998 VL 17 IS 2 BP 181 EP 182 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YV911 UT WOS:000071876700015 PM 9473023 ER PT J AU Rogers, AS Schwarz, D English, A Weissman, G AF Rogers, AS Schwarz, D English, A Weissman, G CA Adolescent Med HIV AIDS Res Network TI Adolescent participation in clinical research: Eleven sites, one common protocol, eleven IRBs SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1998 VL 22 IS 2 BP 133 EP 133 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA YT594 UT WOS:000071622700014 ER PT J AU Rogers, AS Futterman, DK Moscicki, AB Wilson, CM Ellenberg, J Vermund, SH AF Rogers, AS Futterman, DK Moscicki, AB Wilson, CM Ellenberg, J Vermund, SH TI The REACH Project of the Adolescent Medicine HIV/AIDS Research Network: Design, methods, and selected characteristics of participants. SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1998 VL 22 IS 2 BP 159 EP 159 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA YT594 UT WOS:000071622700065 ER PT J AU Rogers, AS Futterman, D Henry-Reid, L Moreno, V AF Rogers, AS Futterman, D Henry-Reid, L Moreno, V TI HIV counseling and testing: Youth report what will work. SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 NICHHD, REACH Project, Community Advisory Board Adolescent Med HIV AIDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1998 VL 22 IS 2 BP 160 EP 160 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA YT594 UT WOS:000071622700066 ER PT J AU Bailey, L Nolan-Polite, E Saunders, P Booth, J Ficker, AH Baylor, MS Holmes, JJ Wood, LV AF Bailey, L Nolan-Polite, E Saunders, P Booth, J Ficker, AH Baylor, MS Holmes, JJ Wood, LV TI Barriers to enrollment of HIV-infected adolescents in clinical research protocols. SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 Hosp Sick Children, NE Pl Adolescent Clin, Washington, DC USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1998 VL 22 IS 2 BP 166 EP 166 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA YT594 UT WOS:000071622700078 ER PT J AU Pfutzner, W Thomas, P Rueff, F Przybilla, B AF Pfutzner, W Thomas, P Rueff, F Przybilla, B TI Anaphylactic reaction elicited by condurango bark in a patient allergic to natural rubber latex SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article C1 Univ Munich, Dermatol Klin, Munich, Germany. RP Pfutzner, W (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238, Bethesda, MD 20992 USA. NR 6 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 1998 VL 101 IS 2 BP 281 EP 282 PN 1 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA YZ342 UT WOS:000072244800019 PM 9500763 ER PT J AU Adrie, C Ichinose, F Holzmann, A Keefer, L Hurford, WE Zapol, WM AF Adrie, C Ichinose, F Holzmann, A Keefer, L Hurford, WE Zapol, WM TI Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE nitric oxide adducts; sodium nitroprusside; sheep ID RESPIRATORY-DISTRESS-SYNDROME; NITROGLYCERIN; NITROPRUSSIDE; DISEASE; THERAPY; VASOCONSTRICTION; HYDRALAZINE; ZAPRINAST; RESPONSES; ADDUCT AB Sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate {DEA/NO; Et2N-[N(O)NO]Na} is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (less than or equal to 10(-2) M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR (-5%), but nonselectively dilated the systemic circulation at larger doses (>10(-2) M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NCI, Frederick, MD 21702 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL-42397] NR 34 TC 30 Z9 31 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 1998 VL 84 IS 2 BP 435 EP 441 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YU964 UT WOS:000071774300007 PM 9475849 ER PT J AU Hu, JS Bax, A AF Hu, JS Bax, A TI Measurement of three-bond, C-13 '-C-13(beta) J couplings in human ubiquitin by a triple resonance, E. COSY-type NMR technique SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE carbon-carbon J coupling; E-COSY; Karplus equation; phi angle; 3D NMR; ubiquitin ID ISOTOPICALLY ENRICHED PROTEINS; BACKBONE; ASSIGNMENT; CONSTANTS; H-1-NMR; PROTON AB A [CO]HN(CA)CB-E.COSY pulse scheme is described for measurement of three-bond couplings, (3)J(C'C beta), between carbonyl and aliphatic CB carbons in ubiquitin, uniformly enriched with C-13 and N-15. A Karplus relation, (3)J(C'C beta) = 1.28 cos(2)(phi - 120 degrees) - 1.02 cos(phi - 120 degrees) +0.30 Hz, is obtained by correlating the (3)J(C'C beta) values measured for human ubiquitin with backbone phi angles from its crystal structure. As predicted, the new Karplus parametrization yields (3)J(C'C beta) values slightly larger than previously obtained by quantitative J correlation [Hu, J.-S. and Bar, A. (1997) J. Am. Chem. Sec., 119, 6360-6368], but considerably smaller than what has been reported on the basis of other E.COSY-type measurements carried out on flavodoxin. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hu, JS (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 20 TC 9 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD FEB PY 1998 VL 11 IS 2 BP 199 EP 203 DI 10.1023/A:1008241904271 PG 5 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 100HR UT WOS:000074811200008 PM 9679294 ER PT J AU Levenberg, S Katz, BZ Yamada, KM Geiger, B AF Levenberg, S Katz, BZ Yamada, KM Geiger, B TI Long-range and selective autoregulation of cell-cell or cell-matrix adhesions by cadherin or integrin ligands SO JOURNAL OF CELL SCIENCE LA English DT Article DE adhesion-mediated signaling; cadherin; cell adhesion; integrin; tyrosine phosphorylation ID ADHERENS-TYPE JUNCTIONS; PROTEIN-KINASE-C; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; FOCAL ADHESIONS; MOLECULAR-BASIS; N-CADHERIN; SRC GENE AB In this study we demonstrate that local stimulation of cell surface cadherins or integrins induces al enhancement of adherens junction or focal assembly, respectively, throughout the cell, IV-cadherin transfected CHO cells (CHO-Ncad) were incubated with different ligands including N-cadherin extracellular domain (NEC), anti-N-cadherin antibodies, fibronectin and concanavalin A (ConA), conjugated to synthetic beads, Electron microscopic examination indicated that both cadherin-and integrin-reactive beads bound tightly to the cell surface and were apparently endocytosed after several hours of incubation, The ConA-beads remained largely at the cell surface, Immunofluorescence labeling of the cells with antibodies to different adhesion-associated molecules indicated that both NEC- and anti-N-cadherin-conjugated beads induced a major increase in the level of junction-associated cadherin and beta-catenin labeling and a modest increase in junctional vinculin labeling, compared to untreated cells or cells bound to ConA-bleads. FN-conjugated beads, on the other hand, significantly enhanced vinculin labeling at focal contacts and suppressed cadherin and beta-catenin staining in cell-cell junctions, The cadherin-reactive beads specifically stimulated tyrosine phosphorylation at cell-cell junctions, while the FN-beads increased the levels of focal contact-associated phosphotyrosine, as shown by immunofluorescence labeling of the cells for phosphotyrosine, Inhibition of this phosphorylation by genistein resulted in a complete suppression of the effects of both types of beads. These findings indicate that specific cadherin- and integrin-mediated surface interactions can trigger positively cooperative long-range signaling events which lead to the selective assembly of cell-cell or cell-matrix adhesions, and that these signals involve tyrosine phosphorylation. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Levenberg, S (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RI Zhou, Feng/E-9510-2011; OI Yamada, Kenneth/0000-0003-1512-6805 NR 66 TC 69 Z9 70 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB PY 1998 VL 111 BP 347 EP 357 PN 3 PG 11 WC Cell Biology SC Cell Biology GA YZ525 UT WOS:000072262800006 PM 9427683 ER PT J AU Coghill, RC Sang, CN Berman, KF Bennett, GJ Iadarola, MJ AF Coghill, RC Sang, CN Berman, KF Bennett, GJ Iadarola, MJ TI Global cerebral blood flow decreases during pain SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE pain; autoregulation; sympathetic nervous system; global blood flow; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; HEAT PAIN; BRAIN; HUMANS; AUTOREGULATION; HYPERALGESIA; STIMULATION; CAPSAICIN; NEURONS AB Positron emission tomography studies have identified a common set of brain regions activated by pain. No studies, however, have quantitatively examined pain-induced CBF changes. To better characterize CBF during pain, 14 subjects received positron emission tomography scans during rest, during capsaicin-evoked pain (250 mu g, intradermal injection), and during innocuous vibration. Using the (H2O)-O-15 intravenous bolus method with arterial blood sampling, global CBF changes were assessed quantitatively. Painful stimulation produced a 22.8% decrease in global CBF from resting levels (P < 0.0005). This decrease was not accounted for by arterial PCO2, or heart rate changes. Although the exact mechanism remains to be determined, this pain-induced global decrease represents a previously unidentified response of CBF. C1 NIDR, Neurobiol & Anesthesiol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Allegheny Univ Hlth Sci, Dept Neurol, Philadelphia, PA 19102 USA. RP Coghill, RC (reprint author), NIDR, Neurobiol & Anesthesiol Branch, NIH, Bldg 49,Room 1A11 NAB,49 Convent Dr, Bethesda, MD 20892 USA. NR 38 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 1998 VL 18 IS 2 BP 141 EP 147 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA YV905 UT WOS:000071876100003 PM 9469155 ER PT J AU Frerichs, KU Hallenbeck, JM AF Frerichs, KU Hallenbeck, JM TI Hibernation in ground squirrels induces state and species-specific tolerance to hypoxia and aglycemia: An in vitro study in hippocampal slices SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ischemia; tolerance; brain slices; hibernation; histology; in vitro ID BRAIN-SLICES; MAMMALIAN HIBERNATION; PREPARATIVE METHODS; HYPOTHERMIA; OXYGEN; DEPENDENCE; ADAPTATION; PROTECTION; STABILITY; INVITRO AB Hibernation in mammals is associated with a regulated depression or global cellular functions accompanied by reductions of cerebral blood flow that would render the brain profoundly ischemic under normal conditions, Homeostatic control is preserved, however, and brain damage does not occur, We investigated the possibility that hibernation not only confers tolerance to profound hypothermia, but also to hypo?iia and aglycemia independent of temperature, Hippocampal slices from ground squirrels Citellus tidecemlineatus in both the active and hibernating states and from rats were subjected to in vitro hypoxia and aglycemia at incubation temperatures of 36 degrees C, 20 degrees C, and 7 degrees C, and evaluated histologically. A binary bioassay was used to determine the duration of hypoxia/aglycemia tolerated in each group. At all temperatures. slices from hibernating animals were most tolerant compared with both active squirrels and rats. Slices from active ground squirrels were more tolerant than rat at 20 degrees C and 7 degrees C but not at 36 degrees C indicating a species-specific difference that becomes manifest at lower temperatures. These results indicate that hibernation is associated not only with tolerance to profound hypothermia but also to deprivation of oxygen and glucose. Because tolerance was already demonstrable at the shortest duration of hibernation studied, rapid therapeutic induction of a similar state mau be possible, Therefore, identification of the regulatory mechanisms underlying this tolerance may lead to novel neuroprotective strategies. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Neurosurg, Boston, MA 02115 USA. RP Frerichs, KU (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4A03,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 34 TC 104 Z9 106 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD FEB PY 1998 VL 18 IS 2 BP 168 EP 175 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA YV905 UT WOS:000071876100007 PM 9469159 ER PT J AU Yanovski, JA Cutler, GB Chrousos, GP Nieman, LK AF Yanovski, JA Cutler, GB Chrousos, GP Nieman, LK TI The dexamethasone-suppressed corticotropin-releasing hormone stimulation test differentiates mild Cushing's disease from normal physiology SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DIAGNOSIS; ADRENOCORTICOTROPIN; CORTISOL; HYPERCORTISOLISM; HORMONOGENESIS; DEPRESSION; CLEARANCE AB The dexamethasone-suppressed CRH test (Dex-CRH test) differentiates patients with Cushing's syndrome (CS) from those with pseudo-Cushing states, who have decreased ACTH responses to CRH because of negative feedback exerted by chronic hypercortisolism. Normal subjects, however, have not been studied with the Dex-GRH test, raising concern that this test might not separate patients with GS from patients with normal adrenal function. To determine whether the criterion that separates CS from pseudo-Cushing states also would differentiate patients with Cushing's disease (CD) from individuals with eucortisolism, we studied 20 healthy volunteers during low-dose (2 mg/day) dexamethasone suppression, and then during the Dex-GRH test (CRH stimulation test performed 2 h after completion of low-dose dexamethasone suppression), and contrasted their results with those of 20 patients with surgically proven mild CD (urine free cortisol (UFC) <1000 nmol/day). Basal UFC was significantly greater in patients with CD (P < 0.001) but within the normal range (55-250 nmol/day) in 4 patients. During low-dose dexamethasone suppression, a UFC less than 100 nmol/day (36 mu g/day) was found in all but 1 volunteer subject, and a urine 17-hydroxycorticosteroid excretion less than 14.6 mu mol/day (5.3 mg/day) was found in all but 2 subjects. During the Dex-CRH test, plasma cortisol less than 38 nmol/L was found in all 20 normal volunteers until 30 min after CRH administration. By contrast, the 15-min CRH-stimulated plasma cortisol exceeded 38 nmol/L in all patients with CD (P < 0.001). Plasma dexamethasone measured just before CRH administration was similar in normal volunteers (13.0 +/- 6.1 mu mol/L) and patients with CD (16.4 +/- 6.4 mu mol/L). We conclude that cortisol measurements obtained during the Dex-CRH test are suppressed in normal volunteers below those found in mild CD. These results suggest that the Dex-CRH test maybe useful in the evaluation of CS in patients without significant hypercortisoluria. However, its value in patients with episodic hormonogenesis has not been tested. C1 NICHHD, Off Director, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Off Director, Warren Grant Magnuson Clin Ctr, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM yanovskj@cc1.nichd.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 NR 25 TC 56 Z9 61 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 FEB PY 1998 VL 83 IS 2 BP 348 EP 352 DI 10.1210/jc.83.2.348 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YV437 UT WOS:000071823900009 PM 9467539 ER PT J AU Nemansky, M Moy, E Lyons, CD Yu, I Blithe, DL AF Nemansky, M Moy, E Lyons, CD Yu, I Blithe, DL TI Human endometrial stromal cells generate uncombined alpha-subunit from human chorionic gonadotropin, which can synergize with progesterone to induce decidualization SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IN-VITRO DECIDUALIZATION; BETA-SUBUNIT; GLYCOPROTEIN HORMONES; LUTEINIZING-HORMONE; HUMAN CHORIOGONADOTROPIN; PROLACTIN PRODUCTION; PREGNANCY; DIFFERENTIATION; PITUITARY; SERUM AB During the secretory phase of the menstrual cycle, endometrial stromal cells differentiate into decidual cells, which play a crucial role in implantation and maintenance of pregnancy. In this and our previous study, we demonstrate that glycoprotein hormone free a-subunit potentiates progesterone-mediated decidualization of human endometrial stromal cells in vitro. Although addition of intact hCG to cultures resulted in stimulatory activity, its potency was 20-fold less than that of alpha-subunit. However, in the present study we show that decidualizing endometrial cells actively generate uncombined alpha-subunit by dissociating hCG. The amount of dissociated alpha-subunit could fully account for the stimulatory activity observed with hCG. Active dissociation of hCG was dependent on the presence of endometrial cells and did not occur in conditioned medium, excluding involvement of a stable secreted factor such as a protease. In addition to dissociated alpha- and beta-subunits, minor amounts of beta-core and alpha-fragments were detected as degradation products during active dissociation. We also observed an increase in beta-immunoreactivity that coeluted with hCG on size-exclusion gel chromatography, indicating that a portion of the still dimeric hCG may have been nicked in the dissociation process. However, using an assay with specificity for nicked hCG, we showed that dissociation of hCG was not produced from a pool of preexisting nicked hCG. These findings more firmly establish the concept that gonadotropin hormone free alpha-subunit plays a role in the regulation of human endometrial cell differentiation. In addition, identification of the various products formed by incubation of hCG with decidualizing cells yielded insight into the mechanism of hCG degradation, and may explain some activity previously ascribed to hCG. C1 NICHHD, Contracept & Reprod Hlth Branch, Unit Glycobiol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. RP Blithe, DL (reprint author), NICHHD, Contracept & Reprod Hlth Branch, Unit Glycobiol, Dev Endocrinol Branch,NIH, Bldg 61E,Room 8B13, Bethesda, MD 20892 USA. EM BlitheD@hd01.nichd.nih.gov NR 58 TC 25 Z9 27 U1 2 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1998 VL 83 IS 2 BP 575 EP 581 DI 10.1210/jc.83.2.575 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YV437 UT WOS:000071823900047 PM 9467577 ER PT J AU Mericq, MV Cutler, GB AF Mericq, MV Cutler, GB TI High fluid intake increases urine free cortisol excretion in normal subjects SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID DIAGNOSIS; PLASMA AB To test the hypothesis that increased fluid intake increases the urine free cortisol, we prescribed 5 liters of fluid intake per day or a normal fluid intake according to a randomized cross-over design in six normal volunteers. Each period lasted 5 days, with a 2-day washout period of normal fluid intake between the two periods. Urine free cortisol, 17-hydroxycorticosteroids, and creatinine were measured daily during each study period, and the average value over each 5-day period was calculated for each subject. High fluid intake caused a significant increase in the mean urine free cortisol [126 +/- 33 (SD) us. 77 +/- 18 mu g/day, P < 0.005]. The frequency of urine free cortisol results that exceeded the upper normal limit of 95 mu g/day was also much higher during high fluid intake (23/30 vs. 6/30, P < 0.005). By contrast, urine 17-hydroxycorticosteroids (high fluid vs. normal fluid: 5.3 +/- 1.5 vs. 5.0 +/- 1.7 mg/day, respectively, P = not significant) and urine creatinine (1.51 +/- 0.48 vs. 1.45 +/- 0.37 g/day, P = not significant) did not differ between the two study periods. We conclude that high fluid intake (5 liters/day) increases free cortisol excretion without an increase in urine 17-hydroxycorticosteroids. Thus, mild to moderate increases in urine cortisol excretion may not indicate hypercortisolism in individuals who have a high fluid intake and urine volume. C1 NICHHD, Dev Endocrinol Branch, SDE, NIH, Bethesda, MD 20892 USA. RP Cutler, GB (reprint author), NICHHD, Dev Endocrinol Branch, SDE, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM mericqV@cc1.NICHD.NIH.gov NR 18 TC 56 Z9 62 U1 1 U2 1 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 FEB PY 1998 VL 83 IS 2 BP 682 EP 684 DI 10.1210/jc.83.2.682 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YV437 UT WOS:000071823900062 PM 9467592 ER PT J AU Pitt, J Goldfarb, J Schluchter, M Kovacs, A Cooper, E Hodes, D McIntosh, K Peavy, H Shearer, W AF Pitt, J Goldfarb, J Schluchter, M Kovacs, A Cooper, E Hodes, D McIntosh, K Peavy, H Shearer, W CA Paediat Pulm Cardiovascular Complications Vert TI HIV vertical transmission rate determinations are subject to differing definitions and therefore different rates SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE HIV; vertical transmission; pediatric AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; TYPE-1; MOTHER; INFECTION; INFANTS; WOMEN AB The HIV infection status of a cohort of 600 prospectively followed children horn to HIV infected mothers was determined using HIV peripheral blood culture tests at 0, 3, and 6 months of age, HIV serology at greater than or equal to 15 months, and CDC AIDS criteria. We estimated transmission rates using five methods which differed in how HIV indeterminates are handled. These methods were applied at two points in time to illustrate effects of length of follow-up of the cohort on results. In January 1997, 30 months after the last birth, transmission rate estimates ranged from 15.5% (known positives/known positives x known negatives) to 18.1% (known positives x those with one positive culture x deaths/entire cohort minus those lacking negative cultures at age greater than or equal to 5 months). Estimates ranged from 14.8% to 20.7% using the subcohort of 284 children followed greater than or equal to 12 months as of May 1993. These results indicate that methods for assigning HIV infection status and for handling HIV indeterminates should be carefully defined when estimating transmission rates. (C) 1998 Elsevier Science Inc. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Div Pediat & Adolescent Med, Cleveland, OH 44195 USA. Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA. USC, Med Ctr, Div Pediat Infect Dis, Los Angeles, CA USA. Boston City Hosp, Dept Pediat Infect Dis, Boston, MA 02118 USA. Mt Sinai Sch Med, Dept Pediat, New York, NY USA. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. Texas Childrens Hosp, Baylor Coll Med, Dept Allergy & Immunol, Houston, TX 77030 USA. Harvard Med Sch, Childrens Hosp, Boston, MA USA. Columbia Univ, Presbyterian Hosp, New York, NY USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Cent Lab Epstein Barr Virus Testing, San Antonio, TX USA. Cleveland Clin Fdn, Clin Coordinating Ctr, Cleveland, OH 44195 USA. Baylor Coll Med, Ctr Clin, Houston, TX 77030 USA. RP Schluchter, M (reprint author), Cleveland Clin Fdn, Dept Biostat, 9500 Euclid Ave,Desk P-88, Cleveland, OH 44195 USA. FU NHLBI NIH HHS [N01-HR-96038, N01-HR-96037, N01-HR-96040] NR 19 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 1998 VL 51 IS 2 BP 159 EP 164 DI 10.1016/S0895-4356(97)00239-4 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YV166 UT WOS:000071796000010 PM 9474076 ER PT J AU Hayden, FG Fritz, RS Lobo, MC Alvord, WG Strober, W Straus, SE AF Hayden, FG Fritz, RS Lobo, MC Alvord, WG Strober, W Straus, SE TI Local and systemic cytokine responses during experimental human influenza A virus infection - Relation to symptom formation and host defense SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE influenza; interleukin-6; tumor necrosis factor-alpha; interferon-alpha; interleukin-8 ID TUMOR-NECROSIS-FACTOR; ALPHA GENE-EXPRESSION; A VIRUS; INTERLEUKIN-6; STIMULATION; MACROPHAGES; PHASE; MICE AB To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1 beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity, We found that IL-6 and IFN-alpha levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores, IL-6 elevations were also found in the circulation at this time point, In contrast, TNF-alpha responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding, Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late, None of IL-1 beta, IL-2, or TGF-beta levels increased significantly, These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Data Management Serv, Frederick, MD 21702 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM ss44z@nih.gov NR 28 TC 419 Z9 442 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB 1 PY 1998 VL 101 IS 3 BP 643 EP 649 DI 10.1172/JCI1355 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YW195 UT WOS:000071908000017 PM 9449698 ER PT J AU Crotchfelt, KA Pare, B Gaydos, C Quinn, TC AF Crotchfelt, KA Pare, B Gaydos, C Quinn, TC TI Detection of Chlamydia trachomatis by the Gen-Probe AMPLIFIED Chlamydia Trachomatis Assay (AMP CT) in urine specimens from men and women and endocervical specimens from women SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; UROGENITAL SPECIMENS; GENITAL SPECIMENS; DIAGNOSIS; INFECTIONS; TEMPERATURE; STORAGE; CULTURE AB Molecular biology-based amplification methods are significantly more sensitive than other methods for the detection of Chlamydia trachomatis. The performance characteristics of the new Gen-Probe AMPLIFIED Chlamydia Trachomatis Assay (AMP CT) with endocervical and urine specimens were compared to those of culture for patients attending two Baltimore City sexually transmitted disease clinics and a clinic for adolescents. AMP CT uses transcription-mediated amplification (TMA) and hybridization protection assay procedures to qualitatively detect C. trachomatis by targeting a 23S rRNA. Discrepant results between culture-negative and AMP CT-positive specimens were resolved by direct fluorescent-antibody staining of sedimented culture transport medium for elementary bodies and by TMA with 16S rRNA as a target. Following discrepant analysis, for 480 female urine specimens AMP CT had a sensitivity of 93.8% and a specificity of 100%. For 464 male urine specimens, the resolved sensitivity and specificity of AMP CT were 95.6 and 98.7%, respectively. For the 479 endocervical swab specimens the sensitivity of AMP CT was 100% and the specificity was 99.5%, Resolved culture sensitivities of AMP CT for female and male swab specimens were 52.3 and 58.9%, respectively. These results demonstrate that AMP CT is highly sensitive for the detection of C. trachomatis in endocervical specimens and in urine specimens from men and women. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Div Infect Dis, 720 Rutland Ave,Ross Res Bldg 1159, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 22 TC 56 Z9 60 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 1998 VL 36 IS 2 BP 391 EP 394 PG 4 WC Microbiology SC Microbiology GA YR636 UT WOS:000071515100012 PM 9466747 ER PT J AU Kacena, KA Quinn, SB Howell, MR Madico, GE Quinn, TC Gaydos, CA AF Kacena, KA Quinn, SB Howell, MR Madico, GE Quinn, TC Gaydos, CA TI Pooling urine samples for ligase chain reaction screening for genital Chlamydia trachomatis infection in asymptomatic women SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REACTION ASSAY; POOLED SERA; MEN; SEROPREVALENCE; TRANSMISSION; DIAGNOSIS AB The accuracy of pooling urine samples for the detection of genital Chlamydia trachomatis infection by ligase chain reaction (LCR) was examined, A model was also developed to determine the number of samples to be pooled for optimal cost savings at various population prevalences, Estimated costs included technician time, laboratory consumables, and assay costs of testing pooled samples and retesting individual specimens from presumptive positive pools: Estimation of population prevalence based on the pooled LCR results was also applied, After individual urine specimens were processed, 568 specimens were pooled by 4 into 142 poets and another 520 specimens were pooled by 10 into 52 pools. For comparison, all 1,088 urine specimens were tested individually. The sample-to-cut-off ratio was lowered from 1.0 to 0.2 for pooled samples, after a pilot study which tested 148 samples pooled by 4 was conducted. The pooling algorithm was 100% (48 of 48) sensitive when samples were pooled by 4 and 98.4% (61 of 62) Sensitive when samples were pooled by 10. Although 2.0% (2 of 99) of the negative pools of 4 and 7.1% (1 of 14) of the negative pools of 10 tested presumptive positive, all samples in these presumptive-positive pools were negative when retested individually, making the pooling algorithm 100% specific. In a population with 8% genital C. trachomatis prevalence, pooling by four would reduce costs by 39%. The model demonstrated that with a lower prevalence of 2%, pooling eight samples would reduce costs by 59%. Pooling urine samples for detection of C. trachomatis by LCR is sensitive, specific, and cost saving compared to testing individual samples. C1 Johns Hopkins Univ, Div Infect Dis, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Peruana Cayetano Heredia, Lima, Peru. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, Sch Hyg & Publ Hlth, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@welchlink.welch.jhu.edu RI Gaydos, Charlotte/E-9937-2010 NR 18 TC 63 Z9 65 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 1998 VL 36 IS 2 BP 481 EP 485 PG 5 WC Microbiology SC Microbiology GA YR636 UT WOS:000071515100028 PM 9466763 ER PT J AU Uckun, FM Sensel, MG Sather, HN Gaynon, PS Arthur, DC Lange, BJ Steinherz, PG Kraft, P Hutchinson, R Nachman, JB Reaman, GH Heerema, NA AF Uckun, FM Sensel, MG Sather, HN Gaynon, PS Arthur, DC Lange, BJ Steinherz, PG Kraft, P Hutchinson, R Nachman, JB Reaman, GH Heerema, NA TI Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: A report from the Children's Cancer Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; B-CELL LEUKEMIA; PRE-B; MOLECULAR ANALYSIS; DNA-BINDING; T(1-19)(Q23-P13); FUSION; PROTEINS; PBX1; BREAKPOINT AB Purpose: The nonrandom translocation t(1;19) has been associated with poor outcome in pediatric B-lineage acute lymphoblastic leukemia (ALL). Because most patients treated by contemporary therapies now achieve improved outcomes, we have reassessed the prognostic significance of t(1;19). Patients and: Cytogenetic data were accepted for 1,322 children (< 21 years old) with newly diagnosed ALL enrolled between 1988 and 1994 on risk-adjusted studies of the Children's Cancer Group (CCG). Forty-seven patients (3.6%) were t(1;19) positive ((+)); 1,275 (96.4%) were t(1;19) negative ((-)). Clinical characteristics and treatment outcome were compared using standard methods. Results: Translocation (1;19)(+) patients were more likely than t(1;19)(-) patients to be 10 years of age or greater (P < .001) or CD10(+)CD19(+)CD34(-) (P < .0001), or nonwhite (P = .02). patients with a balanced t(1;19) were less likely to be hyperdiploid than patients with an unbalanced der(19)t(1;19). Event-free survival (EFS) was similar for the overall group of t(1;19)(+) and t(1;19)(-) patients, with 4-year estimates of 69.5% (SD, 6.8%) and 74.8% (SD, 1.3%; P = .48), respectively. However, patients with unbalanced der(19)t(1;19) had significantly better outcomes than patients with balanced t(1;19): 4-year EFS were 80.6% (SD, 7.1%) and 41.7% (SD, 13.5%), respectively (P = .003). These differences were maintained within the individual studies analyses and after exclusion of t(1;19)(+) patients whose cells were hyperdiploid with more than 50 chromosomes. Conclusion: The overall group of t(1;19)(+) patients, as well as the subgroup with an unbalanced der(19)+ (1;19) had outcomes similar to that of t(1;19)(-) patients, whereas patients with balanced t(1;19) had poorer outcomes. Thus, although the overall prognostic significance of t(1;19) has been obviated by contemporary risk-adjusted protocols, the balanced t(1;19) translocation remains an adverse prognostic factor. (C) 1998 by American Society of Clinical Oncology. C1 Childrens Canc Grp, ALL Biol Reference Lab, St Paul, MN 55113 USA. Wayne Hughes Inst, St Paul, MN 55113 USA. Grp Operat Ctr, Childrens Canc Grp, Arcadia, CA USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ Wisconsin, Dept Pediat Hematol Oncol, Madison, WI USA. NCI, Dept Clin Cytogenet, Pathol Lab, Bethesda, MD USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Univ Michigan, Dept Pediat Hematol Oncol, Ann Arbor, MI 48109 USA. Univ Chicago, Dept Pediat Hematol Oncol, Div Oncol, Chicago, IL 60637 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. George Washington Univ, Washington, DC USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. RP Uckun, FM (reprint author), Childrens Canc Grp, ALL Biol Reference Lab, 2665 Long Lake Rd, St Paul, MN 55113 USA. EM fatih-uckun@mercury.lh.org FU NCI NIH HHS [CA-13539, CA-42633, CA-51425] NR 36 TC 81 Z9 82 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 FEB PY 1998 VL 16 IS 2 BP 527 EP 535 PG 9 WC Oncology SC Oncology GA YU724 UT WOS:000071747900018 PM 9469337 ER PT J AU Little, R Wittes, RE Longo, DL Wilson, WH AF Little, R Wittes, RE Longo, DL Wilson, WH TI Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMBINATION CHEMOTHERAPY; SALVAGE CHEMOTHERAPY; ETOPOSIDE; EXPERIENCE AB Purpose: Bone marrow transplant (BMT) can cure recurrent Hodgkin's disease, but more than half of patients will progress and require additional treatment. When this occurs, there are no curative options and palliative therapy is usually indicated. In such patients, we have routinely used long-term vinblastine therapy because of its relatively low toxicity and high activity. Patients and Methods: We retrospectively reviewed the charts of all patients with Hodgkin's disease who relapsed after autologous BMT since 1991. Of 23 patients, 16 received vinblastine; we also include our index case, who began vinblastine following relapse in 1987. Patients received vinblastine 4 to 6 mg/m(2) every 1 to 2 weeks, and continued until evidence of disease progression. Results: The 17 patients in this report herd a median age of 31 years, performance status of 2, had received a median of three prior regimens, and 12 (71%) patients were advanced stage. Ten (59%) patients had objective responses, of which two (12%) were complete (CR) and eight (47%) were partial (PR). Two additional patients without measurable disease clinically improved for more than 6 months, and 1 patient had stable disease for more than 18 months. With a median follow-up of 20.4 months, the median event-free (EFS) and overall survival were 8.3 and 38.8 months, respectively. The two complete responders remain in remission at 4.6+ and 9+ years. Vinblastine was well tolerated with 3% of cycles associated with fever and neutropenia, and no cumulative or chronic toxicity. Conclusion: Vinblastine provides effective palliation with low toxicity in recurrent Hodgkin's disease following transplant. These results suggest that long-term vinblastine therapy may be potentially curative and should be considered as initial therapy for such patients. (C) 1998 by American Society of Clinical Oncology. C1 NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Div Clin Sci, Med Branch, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@box-w.nih.gov NR 26 TC 35 Z9 36 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 FEB PY 1998 VL 16 IS 2 BP 584 EP 588 PG 5 WC Oncology SC Oncology GA YU724 UT WOS:000071747900026 PM 9469345 ER PT J AU Herscher, LL Hahn, SM Kroog, G Pass, H Temeck, B Goldspiel, B Cook, J Mitchell, JB Liebmann, J AF Herscher, LL Hahn, SM Kroog, G Pass, H Temeck, B Goldspiel, B Cook, J Mitchell, JB Liebmann, J TI Phase I study of paclitaxel as a radiation sensitizer in the treatment of mesothelioma and non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; THERAPY-ONCOLOGY-GROUP; HUMAN TUMOR; TAXOL; CHEMOTHERAPY; TRIAL; RADIOTHERAPY; CARCINOMA; COMBINATION; SURVIVAL AB Purpose: to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities of paclitaxel with concurrent thoracic irradiation in patients with malignant pleural mesothelioma and locally advanced non-small-cell lung cancer (NSCLC) using a 120-hour continuous infusion regimen. A secondary objective was to assess the effect of paclitaxel on the cell cycle through serial tumor biopsies. Patients and Methods: Paclitaxel was administered as a 120-hour (5-day) continuous infusion repeated every 3 weeks during the course of radiation therapy. The starting dose of paclitaxel was 90 mg/m(2). Doses were escalated at 15-mg/m(2) increments in successive cohorts of three patients. In NSCLC patients, radiation was delivered to the primary tumor and regional lymph nodes for a total tumor dose of 6,120 cGy. In mesothelioma patients, hemithoracic irradiation was delivered as the initial treatment field with a conedown to the tumor volume for a total dose of 5,760 to 6,300 cGy. Tumor biopsies were obtained, if possible, before and during paclitaxel treatment. Results: Thirty patients were entered onto this study through three dose levels (from 90 mg/m(2) to 120 mg/m(2)). The MTD was determined to be 105 mg/m(2). The dose-limiting toxicity was grade 4 neutropenia (two patients). Grade 2 gastrointestinal (GI) toxicity (nausea and vomiting) was also observed at 120 mg/m(2). Three of 30 patients developed a hypersensitivity reaction. Six patients had grade 2 lung injury manifested by a persistent cough that required antitussives. Five patients underwent tumor biopsies. None of the patients showed a significant block of cells in mitosis (G2/M) after paclitaxel infusion. Conclusion: The MTD of paclitaxel, when administered as a 120-hour continuous infusion with concurrent radiotherapy, was determined to be 105 mg/m(2). The dose-limiting toxicity was neutropenia. Continuous infusion paclitaxel administered with large field irradiation of the lung is well tolerated and deserves continued evaluation. This is a US government work. There are no restrictions on its use. C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Div Canc Treatment, Bethesda, MD 20892 USA. RP Herscher, LL (reprint author), NCI, Radiat Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm B3B69, Bethesda, MD 20892 USA. NR 38 TC 32 Z9 33 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 FEB PY 1998 VL 16 IS 2 BP 635 EP 641 PG 7 WC Oncology SC Oncology GA YU724 UT WOS:000071747900033 PM 9469352 ER PT J AU Lebowitz, BD Rudorfer, MV AF Lebowitz, BD Rudorfer, MV TI Treatment research at the millennium: From efficacy to effectiveness SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 NIMH, Adult & Geriatr Treatment & Prevent Intervent Res, Rockville, MD 20857 USA. RP Lebowitz, BD (reprint author), NIMH, Adult & Geriatr Treatment & Prevent Intervent Res, Rockville, MD 20857 USA. NR 0 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1998 VL 18 IS 1 BP 1 EP 1 DI 10.1097/00004714-199802000-00001 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YR848 UT WOS:000071537000001 PM 9472835 ER PT J AU Rissanen, A Naukkarinen, H Virkkunen, M Rawlings, RR Linnoila, M AF Rissanen, A Naukkarinen, H Virkkunen, M Rawlings, RR Linnoila, M TI Fluoxetine normalizes increased cardiac vagal tone in bulimia nervosa SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; RESPIRATORY SINUS ARRHYTHMIA; SEROTONIN; HUMANS AB Patients with bulimia nervosa have been reported to respond to treatment with the serotonin uptake inhibitor fluoxetine. In a preliminary study, which had a small sample size, women with bulimia nervosa were reported to have elevated cardiac vagal tone. We investigated cardiac vagal tone in women with bulimia nervosa before and after treatment with fluoxetine. At baseline, resting cardiac vagal tone, deduced from the respiratory component of heart rate variability, was quantified in 41 healthy volunteer women and in 25 women with bulimia nervosa. The bulimic women received in a parallel-group design, double blind, either placebo or fluoxetine 60 mg/24 hr for 8 weeks. All patients participated in behavioral therapy. Resting cardiac vagal tone was measured again at the end of the treatment. Women with bulimia nervosa had higher cardiac vagal tone than age-matched healthy volunteer women. Placebo had no effect on cardiac vagal tone. Fluoxetine reduced cardiac vagal tone among the women with bulimia nervosa to a level similar to the healthy volunteer women. Women with bulimia nervosa have elevated resting cardiac vagal tone. Fluoxetine normalized the elevated resting cardiac vagal tone among the women with bulimia nervosa. At both the central and peripheral levels, vagal neurons are endowed with serotonin-3 receptors. In vitro, fluoxetine desensitizes or blocks serotonin-3 receptors. A controlled trial of serotonin-3 receptor blockers is warranted in bulimia nervosa. C1 NIAAA, Clin Studies Lab, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Linnoila, M (reprint author), NIAAA, Off Sci Director, NIH, Bldg 10,Room 3C103,10 Ctr Dr,MSC 1256, Bethesda, MD 20892 USA. NR 39 TC 27 Z9 27 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1998 VL 18 IS 1 BP 26 EP 32 DI 10.1097/00004714-199802000-00005 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YR848 UT WOS:000071537000005 PM 9472839 ER PT J AU Grothe, DR Piscitelli, SC Dukoff, R Fullerton, T Sunderland, T Molchan, SE AF Grothe, DR Piscitelli, SC Dukoff, R Fullerton, T Sunderland, T Molchan, SE TI Penetration of tacrine into cerebrospinal fluid in patients with Alzheimer's disease SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DOUBLE-BLIND; MULTICENTER; BRAIN AB Tacrine is widely used for the treatment of Alzheimer's disease, but data are limited regarding cerebrospinal fluid (CSF) concentrations at steady state. To evaluate CSF penetration, seven patients with Alzheimer's disease who were receiving tacrine at doses of 40 to 140 mg/day as a part of a double-blind trial were studied. After 6 weeks of tacrine therapy, concomitant plasma and CSF samples were collected 30 minutes after the morning dose of tacrine. Although this time point is before the peak oral absorption in most patients, the critical issue for this study is that the plasma and CSF samples were collected concomitantly so that a percentage of tacrine penetration could be derived. The morning dose of tacrine ranged from 10 to 40 mg, which was given in the fasting state. Mean (+/-SD) plasma levels of tacrine were 8.01 +/- 7.07 ng/mL, whereas mean (+/-SD) CSF levels of tacrine were 5.21 +/- 6.00 ng/mL. The mean (+/-SD) ratio of CSF to plasma tacrine concentration was 0.50 +/- 0.45, with wide interindividual variability. No relationship between dose and percentage of penetration was observed. Plasma concentrations ranged from 0.99 to 22.6 ng/mL and were unrelated to dose, suggesting erratic oral absorption and/or rapid metabolism. CSF concentrations ranged from not detectable to 15.92 ng/mL. The authors support that penetration of tacrine into CSF is highly variable in patients with Alzheimer's disease and that disparity in tacrine concentrations at the site of action may be one reason for conflicting results from studies of the efficacy of tacrine in Alzheimer's disease. C1 NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Sect Geriatr Psychiat, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Sch Pharm, Buffalo, NY 14260 USA. Millard Fillmore Hosp, Dept Neuropharmacol, Dent Neurol Inst, Buffalo, NY USA. RP Grothe, DR (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Pharm, 10 Ctr Dr,MSC 1196, Bethesda, MD 20892 USA. NR 14 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1998 VL 18 IS 1 BP 78 EP 81 DI 10.1097/00004714-199802000-00013 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YR848 UT WOS:000071537000013 PM 9472847 ER PT J AU Moss, H Bose, S Wolters, P Brouwers, P AF Moss, H Bose, S Wolters, P Brouwers, P TI A preliminary study of factors associated with psychological adjustment and disease course in school-age children infected with the human immunodeficiency virus SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE adjustment; disease course; pediatric HIV; stress ID SELF-ESTEEM; LIFE-EVENTS; COMMON COLD; STRESS; PSYCHONEUROIMMUNOLOGY; ADOLESCENTS; SUSCEPTIBILITY; PREDICTORS; HEMOPHILIA; ILLNESS AB This study consisted of a longitudinal examination (baseline and approximately 2-yr follow-up) of factors associated with psychological adjustment in a sample of 24 school-age children infected with the human immunodeficiency virus (HIV). Measures of depression, anxiety, and self-concept were administered to the children, and measures of behavioral problems, social functioning, and negative life events were administered to the parents. Generally, psychological adjustment seemed stable, though a decrease in positive social self-concept over time was observed. Negative life events were significantly associated with greater adverse psychological and behavioral outcomes at both baseline and follow-up. An additional component to the study investigated factors associated with survival. Examination of an additional five children who died within 12 months of baseline indicated that they experienced significantly more adverse life events, were less resilient, and had greater disease progression. The sample size was small and requires that these findings be considered as preliminary and suggestive rather than conclusive. C1 NCI, HIV AIDS Malignancy Branch, Med Illness Counseling Ctr, Bethesda, MD 20892 USA. RP Moss, H (reprint author), NCI, HIV AIDS Malignancy Branch, Med Illness Counseling Ctr, Bldg 10,13N240, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-SC-47002] NR 34 TC 25 Z9 25 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD FEB PY 1998 VL 19 IS 1 BP 18 EP 25 DI 10.1097/00004703-199802000-00003 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA YZ900 UT WOS:000072305700003 PM 9524301 ER PT J AU Weiss, BD Coyne, C Michielutte, R Davis, TC Meade, CD Doak, LG Doak, CC Brown, P Askov, E Mettger, W Songer, T Friedell, GH Smith, T Furnas, S AF Weiss, BD Coyne, C Michielutte, R Davis, TC Meade, CD Doak, LG Doak, CC Brown, P Askov, E Mettger, W Songer, T Friedell, GH Smith, T Furnas, S CA Natl Work Grp Literacy Hlth TI Communicating with patients who have limited literacy skills - Report of the National Work Group on Literacy and Health SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE literacy; illiteracy; health status; patient education; communication ID DEVELOPING-COUNTRIES; EDUCATION MATERIALS; INFORMED CONSENT; RANDOMIZED TRIAL; READABILITY; EMERGENCY; INFORMATION; SMOKING; COMPREHENSION; PAMPHLETS AB Between 40 and 44 million persons in the United States have rudimentary literacy skills, and are unable to understand written materials that require only basic reading proficiency. The purpose of this report is to characterize the current status of illiteracy in the United States, describe the relationship between poor literacy and poor health, and make recommendations on how to deal with patients who have poor reading skills. Data collected by the National Work Group on Literacy and Health indicate that one quarter of the US population has rudimentary reading skills, and another 25% has limited reading skills. This makes it difficult to have written communication with much of the US population. Poor reading skills are associated with poor health and greater use of health services, but the basis for this association is unclear. Instruments are available to measure patients' reading skills in clinical settings, and information can be transmitted to patients in ways that make it understandable to poor readers. However, it is not known if using special low-literacy education materials with these patients improves health outcomes. When written communication with low-literacy patients is essential, materials should be at the 5th-grade revel or lower, supplemented by nonwritten communication. Simple and nonwritten materials are appropriate for persons with limited literacy, and also for those with well-developed literacy. Research is needed to clarify the mechanisms through which illiteracy influences health status and health services utilization, and to determine if using low-literacy health education materials improves health outcomes. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Louisiana State Univ, Med Ctr, Shreveport, LA USA. H Lee Moffitt Canc Res Ctr & Inst, Tampa, FL USA. Patient Learnig Associates, Potomac, MD USA. W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. Inst Study Adult Literacy, University Pk, PA USA. Mettger Commun, Takoma Pk, MD USA. Interact Knowledge Inc, Charlotte, NC USA. Univ Kentucky, Lucille Parker Markey Canc Ctr, Lexington, KY USA. Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. Hlth Promot Council SE Penn, Philadelphia, PA USA. NCI, Off Canc Commun, Bethesda, MD 20892 USA. MPH, Baltimore, MD USA. Literacy Volunteers Amer, Manlius, NY USA. Louisiana State Univ, Med Ctr, Shreveport, LA 71105 USA. Patient Learning Associates, Potomac, MD USA. Natl Inst Literacy, Washington, DC USA. US Dept HHS, Washington, DC 20201 USA. Project Literacy US, Pittsburgh, PA USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ N Carolina, Sch Educ, Chapel Hill, NC 27599 USA. Laubach Literacy Act, Syracuse, NY USA. Program Appropriate Technol Hlth, Washington, DC USA. NCI, NIH, Bethesda, MD 20892 USA. Univ New England, AHEC Hlth Literacy Program, Biddeford, ME USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis, Atlanta, GA 30333 USA. Hlth Educ & Literacy Program, Boston, MA USA. AMC Canc Res Ctr, Denver, CO USA. Media Educ Surveys, San Francisco, CA USA. RP Weiss, BD (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM bdweiss@uthscsa.edu NR 75 TC 112 Z9 114 U1 1 U2 13 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD FEB PY 1998 VL 46 IS 2 BP 168 EP 176 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA YX398 UT WOS:000072036000014 ER PT J AU Stoica, B DeBell, KE Graham, L Rellahan, BL Alava, MA Laborda, J Bonvini, E AF Stoica, B DeBell, KE Graham, L Rellahan, BL Alava, MA Laborda, J Bonvini, E TI The amino-terminal Src homology 2 domain of phospholipase C gamma 1 is essential for TCR-induced tyrosine phosphorylation of phospholipase C gamma 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; GROWTH-FACTOR RECEPTOR; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; SH2 DOMAIN; C-GAMMA; PHOSPHATIDYLINOSITOL 3-KINASE; CD2 STIMULATION; EGF RECEPTOR; BINDING-SITE AB TCR engagement activates phospholipase C gamma 1 (PLC gamma 1) via a tyrosine phosphorylation-dependent mechanism. PLC gamma 1 contains a pair of Src homology 2 (SH2) domains whose function is that of promoting protein interactions by binding phosphorylated tyrosine and adjacent amino acids, The role of the PLC gamma 1 SH2 domains in PLC gamma 1 phosphorylation was explored by mutational analysis of an epitope-tagged protein transiently expressed in Jurkat T cells. Mutation of the amino-terminal SH2 domain (SH2(N) domain) resulted in defective tyrosine phosphorylation of PLC gamma 1 in response to TCR/CD3 perturbation. In addition, the PLC gamma 1 SH2(N) domain mutant failed to associate with Grb2 and a 36- to 38-kDa phosphoprotein (p36-38), which has previously been recognized to interact with PLC gamma 1, Grb2, and other molecules involved in TCR signal transduction. Conversely, mutation of the carboxyl-terminal SH2 domain (SH2(C) domain) did not affect TCR-induced tyrosine phosphorylation of PLC gamma 1. Furthermore, binding of p36-38 to PLC gamma 1 was not abrogated by mutations of the SH2(C) domain. In contrast to TCR/CD3 Ligation, treatment of cells with pervanadate induced tyrosine phosphorylation of either PLC gamma 1 SH2(N) or SH2(C) domain mutants to a level comparable with that of the mild-type protein, indicating that pervanadate treatment induces an alternate mechanism of PLC gamma 1 phosphorylation, These data indicate that the SH2(N) domain is required for TCR-induced PLC gamma 1 phosphorylation, presumably by participating in the formation of a complex that promotes the association of PLC gamma 1 with a tyrosine kinase. C1 Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, OTRR, Bethesda, MD 20892 USA. RP Bonvini, E (reprint author), Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, OTRR, HFM-564,Natl Inst Hlth Campus,Bldg 29B,Room 3NN10, Bethesda, MD 20892 USA. RI STOICA, BOGDAN/H-9782-2013; Laborda, Jorge/L-5726-2014 OI STOICA, BOGDAN/0000-0002-2501-6434; Laborda, Jorge/0000-0002-9210-838X NR 50 TC 49 Z9 50 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 FEB 1 PY 1998 VL 160 IS 3 BP 1059 EP 1066 PG 8 WC Immunology SC Immunology GA YW269 UT WOS:000071915400002 PM 9570517 ER PT J AU Ortaldo, JR Winkler-Pickett, R Mason, AT Mason, LH AF Ortaldo, JR Winkler-Pickett, R Mason, AT Mason, LH TI The Ly-49 family: Regulation of cytotoxicity and cytokine production in murine CD3(+) cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MULTIGENE FAMILY; RECEPTOR-ALPHA/BETA(+) CELLS; RECOGNITION; MOLECULES; MOUSE; SPECIFICITY; POPULATION; ADHESION; RECEPTOR AB The Ly-49 gene families are class I-recognizing receptors on murine NK cells. Most Ly-49 receptors inhibit NK cell lysis upon recognizing their target class I ligands, In this report ne have examined the ability of Ly-49A and Ly-49G2 to regulate T cell functions on CD3(+) cells, primarily the subset that also expresses NK-1.1 and/or DX5. The majority (>50%) of T cells that express Ly-49 molecules also coexpress NK-1.1 and/or DX5, although some NK-1.1(-) and/or DX5(-)/CD3(+) cells express Ly-49 molecules, Lysis of target cells bg IL-2-cultured T cells expressing Ly-49A and G2 was enhanced by Abs specific for Ly-49A and G2 as well as by Abs to class I (H-2D(d) alpha 1/alpha 2). Murine T cells also were cultured in the presence of targets that express (H-2D(d)) which is inhibiting for the Ly-49A and GZ receptors, These cells were examined for a coincident increase in cytokine production (IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF). Abs to Ly-49A and G2 or their respective class I ligands blocked the negative signals mediated via the Ly-49 receptors and increased IFN-gamma and granulocyte-macrophage CSF production after interaction of these T cells with H-2D(d)-expressing tumor targets, Furthermore, an EL-4 T cell line expressing both Ly-49A and G2, when treated with mAb YE148 and 4D11, demonstrated reduced cytokine production and calcium mobilization, These results demonstrate for the first time that Ly-49 class I binding receptors, previously thought to be restricted to mouse NK cells, can mediate important physiological functions of T cell subsets. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA. RP Ortaldo, JR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Bldg 560,Room 31-93, Frederick, MD 21702 USA. NR 30 TC 121 Z9 121 U1 2 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 FEB 1 PY 1998 VL 160 IS 3 BP 1158 EP 1165 PG 8 WC Immunology SC Immunology GA YW269 UT WOS:000071915400014 PM 9570529 ER PT J AU Suri-Payer, E Amar, AZ Thornton, AM Shevach, EM AF Suri-Payer, E Amar, AZ Thornton, AM Shevach, EM TI CD4(+)CD25(+) T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AUTOIMMUNE-DISEASE; SELF-TOLERANCE; NEONATAL THYMECTOMY; INTRATHYMIC INJECTION; MOLECULAR TARGETS; TRANSGENIC MICE; PARIETAL-CELLS; BASIC-PROTEIN; GASTRITIS; OOPHORITIS AB Thymectomy of susceptible strains of mice on day 3 of life results in a spectrum of organ-specific autoimmunity that can be prevented by reconstitution of the thymectomized animals early in life with normal adult lymphocytes. The effectors and suppressors of autoimmunity in this model have been convincingly shown to be CD4(+) T cells, It has been demonstrated recently that the regulatory CD4(+) T cells that prevent disease coexpress CD25. We have further characterized the population of CD4(+)CD25(+) immunoregulator cells and demonstrated that they can suppress not only the induction of disease post-thymectomy but can also efficiently suppress disease induced by cloned autoantigen-specific effecter cells. Furthermore, the CD4(+)CD25(+) T cells appear to be members of a unique lineage of regulatory T cells, as the induction of CD25 expression on a monospecific population of T cells derived from TCR transgenic SCID mice did not result in suppression of post-thymectomy autoimmunity. In addition, the TCR transgenic SCID mice were highly susceptible to autoimmune disease induced by the cloned line of autoantigen-specific effecters, while normal mice were relatively resistant. The capacity; of the cloned line to transfer disease to nulnu recipients could be inhibited by normal spleen cell populations containing CD4(+)CD25(+) cells and by purified CD4(+)CD25(+) cells. Although the target Ag(s) and mechanism of action of the CD4(+)CD25(+) T cells remain to be determined, it is likely that they also play an important role in modulating other autoimmune diseases that are mediated by activation of "ignorant" self-reactive T cells present in the normal peripheral lymphocyte pool. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 40 TC 691 Z9 709 U1 2 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1998 VL 160 IS 3 BP 1212 EP 1218 PG 7 WC Immunology SC Immunology GA YW269 UT WOS:000071915400021 PM 9570536 ER PT J AU Sehgal, D Mage, RG Schiaffella, E AF Sehgal, D Mage, RG Schiaffella, E TI V-H mutant rabbits lacking the V(H)1a2 gene develop a2(+) B cells in the appendix by gene conversion-like alteration of a rearranged V(H)4 gene SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMORAL IMMUNE-SYSTEM; REGION SEQUENCES; ALICIA RABBITS; VHA ALLOTYPE; VDJ GENES; DIVERSIFICATION; EXPRESSION; HYPERCONVERSION; ONTOGENY; GERMLINE AB We investigated the molecular basis for the appearance of V(H)a2 allotype-bearing B cells in mutant Alicia rabbits. The mutation arose in an a2 rabbit; mutants exhibit altered expression of V-H, genes because of a small deletion encompassing V(H)1a2, the 3'-most gene in the V-H locus, The V(H)1 gene is the major source of V(H)a allotype because this gene is preferentially. rearranged in normal rabbits, In young homozygous ali/ali animals, the levels of a2 molecules found in the serum increase with age, In adult ali/ali rabbits, 20 to 50% of serum Igs and B cells bear a2 allotypic determinants. Precious studies suggested that positive selection results in expansion of a2 allotype-bearing B cells in the appendix of young mutant ali/ali rabbits, We separated appendix cells from a 6-wk-old Alicia rabbit by FAGS based on the expression of surface IgM and a2 allotype. The VDJ portion of the expressed Ig mRNA was amplified from the IgM(+) a2(+) and IgM(+) a2(-) populations by reverse transcriptase-PCR, The cDNAs from both populations were cloned and sequenced. Analysis of these sequences suggested that, in a2(+) B cells, the first D proximal functional gene in Alicia rabbits, V(H)4a2, rearranged and was altered further by a gene conversion-like mechanism, Upstream V-H genes were identified as potential gene sequence donors: V(H)9 was found to be the most frequently used gene donor, Among the a2(-) B cells, y33 was the most frequently rearranged gene. C1 NIAID, Mol Immunogenet Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Mol Immunogenet Sect, Immunol Lab, NIH, Bldg 10 Room 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. NR 36 TC 17 Z9 17 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 FEB 1 PY 1998 VL 160 IS 3 BP 1246 EP 1255 PG 10 WC Immunology SC Immunology GA YW269 UT WOS:000071915400026 PM 9570541 ER PT J AU Yap, GS Scharton-Kersten, T Charest, H Sher, A AF Yap, GS Scharton-Kersten, T Charest, H Sher, A TI Decreased resistance of TNF receptor p55- and p75-deficient mice to chronic toxoplasmosis despite normal activation of inducible nitric oxide synthase in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENDOGENOUS IFN-GAMMA; NATURAL-KILLER-CELLS; FACTOR-ALPHA; L-ARGININE; GONDII INFECTION; INTERFERON-GAMMA; IMMUNE-RESPONSE; NITROGEN-OXIDES; IN-VIVO AB The importance of TNF-alpha in host defense to the intracellular parasite, Toxoplasma gondii, was investigated in mice lacking both the p55 and p75 receptors for this cytokine. Upon i.p. infection with the avirulent ME49 strain, knockout mice were capable of limiting acute i.p. infection, but succumbed within 3 to 4 wk to a fulminant necrotizing encephalitis, Receptor deficient mice harbored higher cyst burdens and exhibited uncontrolled tachyzoite replication in the brain, The luck of TNF receptors did not adversely affect the development of a type 1 IFN-gamma response. In vitro studies with peritoneal macrophages stimulated with IFN-gamma and tachyzoites indicated that under limiting concentrations of IFN-gamma, nitric oxide-mediated toxoplasmastatic activity is TNF-alpha dependent, However, this requirement is overcome by increasing the dose of IFN-gamma, Furthermore, both es vivo and in vivo studies demonstrated that inducible nitric oxide synthase induction in the peritoneal cavity and brain is unimpaired in receptor-deficient mice, Thus, TNF-dependent immune control of T. gondii expansion in the brain involves an effector function distinct from inducible nitric oxide synthase activation. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. RP Yap, GS (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bldg 4,Rm 126,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 32 TC 101 Z9 105 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 FEB 1 PY 1998 VL 160 IS 3 BP 1340 EP 1345 PG 6 WC Immunology SC Immunology GA YW269 UT WOS:000071915400037 PM 9570552 ER PT J AU Zhou, P Miller, G Seder, RA AF Zhou, P Miller, G Seder, RA TI Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-alpha plays a critical role in maintaining secondary immunity in the absence of IFN-gamma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; RECEPTOR-DEFICIENT MICE; NITRIC-OXIDE; INTRACELLULAR GROWTH; INTERFERON-GAMMA; LISTERIA-MONOCYTOGENES; MONOCLONAL-ANTIBODIES; FUNGISTATIC ACTIVITY; DEPENDENT MECHANISM; TOXOPLASMA-GONDII AB Primary infection to Histoplasma capsulatum often results in a self-limited upper respiratory infection in humans; however, in immunocompromised hosts, disseminated infection can occur through reactivation of a previous infection, Since disseminated histoplasmosis has emerged as a difficult clinical entity to treat in individuals infected with HIV, it was of interest to study the mechanisms involved in maintaining an effective memory immune response, It has been previously shown in a murine model of disseminated histoplasmosis that IL-12, IFN-gamma, and TNF-alpha were important factors in mediating primary protection, To study whether these and other factors were involved in maintaining a protective immune response following secondary infection, normal C57BL/6 mice were first infected with a sublethal dose of Ei, capsulatum (1 x 10(5)) and then reinfected 3 wk later with a lethal dose of H. capsulatum (6 x 10(5)), Under these conditions, all mice developed an effective immune response with sterilizing immunity, Moreover, normal C57BL/6 mice treated with neutralizing Abs against either IL-12, TNF-alpha, or IFN-gamma, depleted of neutrophils or treated with aminoguanidine al the time of reinfection, maintained an effective immune response, The ability of animals to survive a secondary infection in the absence of IFN-gamma was verified by showing that IFN-gamma(-/-) mice previously immunized with H. capsulatum and treated with amphotericin B at the time of primary infection had prolonged survival following reinfection with a normally lethal dose, It was further shown that enhancement of TNP-alpha production in IFN-gamma(-/-) mice was the major mechanism by which these mice were effective in controlling secondary infection. C1 NIAID, Clin Invest Lab, Lymphokine Regulat Unit, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Vet Resources Program, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Clin Invest Lab, Lymphokine Regulat Unit, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 47 TC 90 Z9 91 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 FEB 1 PY 1998 VL 160 IS 3 BP 1359 EP 1368 PG 10 WC Immunology SC Immunology GA YW269 UT WOS:000071915400040 PM 9570555 ER PT J AU Tiffany, HL Alkhatib, G Combadiere, C Berger, EA Murphy, PM AF Tiffany, HL Alkhatib, G Combadiere, C Berger, EA Murphy, PM TI CC chemokine receptors 1 and 3 are differentially regulated by IL-5 during maturation of eosinophilic HL-60 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; ENVELOPE GLYCOPROTEIN; PRIMARY MACROPHAGES; EOTAXIN RECEPTOR; FUSION COFACTORS; TYPE-1 TROPISM; HIV-1 ENTRY; RANTES AB CC chemokine receptors I and 3 (CCR1 and CCR3) are expressed by eosinophils; however, factors regulating their expression and function have not previously been defined, Here we analyze chemokine receptor expression and function during eosinophil differentiation, using the eosinophilic cell line HL-60 clone 15 as a model system, RNA for CCR1, -3, -4, and -5 was not detectable in the parental cells, and the cells did not specifically bind CC chemokines, Cells treated with butyric acid acquired eosinophil characteristics; expressed mRNA for CCR1 and CCR3, but not for CCR4 or CCR5; acquired specific binding sites for macrophage-inflammatory protein-1 alpha and eotaxin (the selective ligands for CCR1 and CCR3, respectively); and exhibited specific calcium flux and chemotaxis responses to macrophage-inflammatory protein-1 alpha; eotaxin, and other known CCR1 and CCR3 agonists, CCR3 was expressed later and at lower levels than CCR1 and could be further induced by IL-5, whereas IL-5 had little or no effect on CCR1 expression, Consistent with the HIV-I coreceptor activity of CCR3, HL-60 clone 15 cells induced with butyric acid and IL-5 fused with HeLa cells expressing CCR3-tropic HIV-1 envelope glycoproteins, and fusion was blocked specifically by eotaxin or an anti-CCR3 mAb. These data suggest that CCR1 and CCR3 are markers of late eosinophil differentiation that are differentially regulated by IL-5 in this model. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 43 TC 51 Z9 52 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1998 VL 160 IS 3 BP 1385 EP 1392 PG 8 WC Immunology SC Immunology GA YW269 UT WOS:000071915400043 PM 9570558 ER PT J AU Zhou, P Goldstein, S Devadas, K Tewari, D Notkins, AL AF Zhou, P Goldstein, S Devadas, K Tewari, D Notkins, AL TI Cells transfected with a non-neutralizing antibody gene are resistant to HIV infection: Targeting the endoplasmic reticulum and trans-golgi network SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SINGLE-CHAIN ANTIBODY; HTLV-III/LAV ENVELOPE; INTRACELLULAR EXPRESSION; REVERSE-TRANSCRIPTASE; PROTEIN; TYPE-1; FRAGMENTS; RECEPTOR; GLYCOPROTEIN AB Plasmids containing single chain Fv (scFv) non-neutralizing human anti-HIV-l gp41 Ab cDNA, with or without endoplasmic reticulum (ER) or trans-Golgi network (TGN) retention signals, were constructed, Stable transfectants expressing these scFvs then were generated from COS-7 cells and HIV-l-susceptible CD4(+) human T cells (Jurkat), scFv without a retention signal was secreted from cells, whereas scFv with an ER or TGN retention signal remained primarily within targeted intracellular compartments, The expression of scFv, scFv-ER, and scFv-TGN did not adversely affect the appearance of uninfected cells, as measured by growth rate or CD4 expression, Pulse-chase experiments revealed that the t(1/2) of scFv-ER and scFv-TGN within cells was greater than 24 h and less than 9 h, respectively, The scFv-ER and scFv-TGN bound HIV gp160, and the scFv-ER-gp160 and the scFv-TGN-gp160 complexes were stable within HIV-infected transfectants, Further studies revealed that the maturation processing of gp160 into gp120 and gp41 was blocked in the scFv-ER transfectants, but not in the scFv-TGN transfectants, Moreover, HIV replication, as measured by p24, was inhibited by up to 99% in cells transfected with scFv-ER or scFv-TGN, but was not inhibited in cells transfected with the secretory form of scFv. It is concluded that the targeting of non-neutralizing anti-HN-l Abs to specific intracellular compartments blocks HIV replication and represents a potential therapeutic strategy for protecting uninfected lymphopoietic stem cells from HIV-l-infected patients. C1 NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunodeficiency Virus Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, P (reprint author), NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 114, Bethesda, MD 20892 USA. NR 45 TC 31 Z9 33 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1998 VL 160 IS 3 BP 1489 EP 1496 PG 8 WC Immunology SC Immunology GA YW269 UT WOS:000071915400056 PM 9570571 ER PT J AU Cohen, JI Wang, Y Nussenblatt, R Straus, SE Hooks, JJ AF Cohen, JI Wang, Y Nussenblatt, R Straus, SE Hooks, JJ TI Chronic uveitis in guinea pigs infected with varicella-zoster virus expressing Escherichia coli beta-galactosidase SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 21st International Herpesvirus Workshop CY JUL 26-AUG 02, 1996 CL DE KALB, ILLINOIS ID ACUTE RETINAL NECROSIS; PIGMENT EPITHELIAL-CELLS; TRIGEMINAL GANGLIA; INVIVO MODEL; REPLICATION; LATENCY; RETINITIS; SEQUENCE; TROPISM; DNA AB There is no small animal model that replicates chickenpox and herpes tester, which are caused by varicella-zoster virus (VZV). Therefore, to detect VZV in tissues of infected animals, the Escherichia coli beta-galactosidase gene was inserted into the viral genome. Intravitreal inoculation of guinea pigs with virus-infected cells resulted in a chronic uveitis, with mononuclear cells in the vitreous cavity of the eye of nearly all animals. Staining with X-gal demonstrated the presence of VZV in the ciliary body or iris of similar to 40% of the animals and in retinal pigmented epithelial cells in 4 animals. X-gal staining showed VZV in the eye of 1 animal 140 days after inoculation. These experiments indicate that VZV expressing beta-galactosidase is useful for detecting virus in tissues and that VZV can cause a chronic uveitis in which virus can be detected in some animals for up to 4 months. C1 NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, Immunol & Virol Sect, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bldg 10,Room 11N214, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 7 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 FEB PY 1998 VL 177 IS 2 BP 293 EP 300 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YV221 UT WOS:000071801500004 PM 9466514 ER PT J AU Corey, L McElrath, MJ Weinhold, K Matthews, T Stablein, D Graham, B Keefer, M Schwartz, D Gorse, G AF Corey, L McElrath, MJ Weinhold, K Matthews, T Stablein, D Graham, B Keefer, M Schwartz, D Gorse, G CA AIDS Vaccine Evaluation Grp TI Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GP160 RECOMBINANT VACCINIA; EXPRESSING HIV ENVELOPE; SUBUNIT VACCINE; LYMPHOCYTE RESPONSES; SERONEGATIVE VOLUNTEERS; NAIVE ADULTS; INFECTION; INDUCTION; SAFETY; IMMUNOGENICITY AB Effective human immunodeficiency virus (HIV) vaccination may require induction of neutralizing antibodies (NAs) and CD8(+) cytotoxic T lymphocytes (CTL) to prevent transmission and control early infection, Recombinant envelope proteins induce NAs but rarely CD8(+) CTL responses, and vaccinia vectors containing HIV-1 envelope elicit CD8(+) cytotoxicity but few NAs, To benefit from both approaches, 56 vaccinia-naive subjects were randomized to a regimen of priming with recombinant vaccinia gp160(LAI) and boosting with recombinant gp120(SF-2), gp120(LAI), gp120(MN), or gp160(MN) Of 51 persons for whom assays were done, 26 demonstrated envelope-specific CTL, Boosting with gp120, compared with gp160, elicited significantly more NAs and CD4-blocking antibodies, Neutralization of the homologous and heterologous HIV-1 laboratory strains occurred in all subjects receiving vac/env and gp120 and was detectable in 91% of the subjects for >6 months, Thus, vaccine regimens in which one component elicits primarily CTL and the other NAs offer promise for the development of an effective HIV-1 vaccine strategy. C1 Univ Washington, Sch Med, Program Infect Dis, Seattle, WA USA. Duke Univ, Med Ctr, Ctr AIDS Res, Durham, NC USA. Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. EMMES Corp, Potomac, WV USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. St Louis Univ, Sch Med, Div Infect Dis, St Louis, MO USA. RP Corey, L (reprint author), 1124 Columbia St M-115, Seattle, WA 98104 USA. FU NIAID NIH HHS [AI-45211, AI-45210, AI-45206] NR 34 TC 67 Z9 68 U1 1 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 FEB PY 1998 VL 177 IS 2 BP 301 EP 309 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YV221 UT WOS:000071801500005 PM 9466515 ER PT J AU Graham, BS McElrath, MJ Connor, RI Schwartz, DH Gorse, GJ Keefer, MC Mulligan, MJ Matthews, TJ Wolinsky, SM Montefiori, DC Vermund, SH Lambert, JS Corey, L Belshe, RB Dolin, R Wright, PF Korber, BT Wolff, MC Fast, PE AF Graham, BS McElrath, MJ Connor, RI Schwartz, DH Gorse, GJ Keefer, MC Mulligan, MJ Matthews, TJ Wolinsky, SM Montefiori, DC Vermund, SH Lambert, JS Corey, L Belshe, RB Dolin, R Wright, PF Korber, BT Wolff, MC Fast, PE CA AIDS Vaccine Evaluation Grp HIV Immune Protection Grp TI Analysis of intercurrent human immunodeficiency virus type 1 infections in phase I and II trials of candidate AIDS vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1995 Annual Meeting on AIDS CY SEP, 1995 CL BETHESDA, MARYLAND SP Lab Tumor Cell Biol ID PRIMARY HIV-INFECTION; SUBSEQUENT COURSE; IMMUNE-RESPONSE; CLINICAL COURSE; PLASMA; VIREMIA; BLOOD; PROGRESSION; PHENOTYPE; ANTIBODY AB Among 2099 uninfected subjects in phase I and II trials of candidate AIDS vaccines, 23 were diagnosed with intercurrent human immunodeficiency virus type 1 (HIV-1) infection, High-risk sexual exposures accounted for 17 infections, and intravenous drug use accounted for 6, Four subjects received placebo, 13 received a complete immunization schedule (greater than or equal to 3 injections), and 6 were partially immunized (less than or equal to 2 injections), There was no significant difference between vaccine recipients and control groups in incidence of HIV-1 infection, virus load, CD4 lymphocyte count, or V3 loop amino acid sequence, In summary, 19 vaccinated subjects acquired HIV 1 infection during phase I and II trials, indicating that immunization with the products described is < 100% effective in preventing or rapidly clearing infection, Laboratory analysis suggested that vaccine-induced immune responses did not significantly affect the genotypic or phenotypic characteristics of transmitted virus or the early clinical course of HIV-1 infection. C1 Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA. Univ Washington, Sch Med, Seattle, WA USA. Aaron Diamond AIDS Res Ctr, New York, NY USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. St Louis Univ, Sch Med, St Louis, MO USA. Univ Alabama, Sch Med, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Durham, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Sch Med, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. EMMES Corp, Potomac, WV USA. RP Graham, BS (reprint author), Vanderbilt Univ, Sch Med, A-4103 MCN, Nashville, TN 37232 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697; Korber, Bette/0000-0002-2026-5757; Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [AI-45206, AI-45207, AI-45208] NR 56 TC 81 Z9 82 U1 0 U2 2 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 FEB PY 1998 VL 177 IS 2 BP 310 EP 319 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YV221 UT WOS:000071801500006 PM 9466516 ER PT J AU Konadu, EY Parke, JC Tran, HT Bryla, DA Robbins, JB Szu, SC AF Konadu, EY Parke, JC Tran, HT Bryla, DA Robbins, JB Szu, SC TI Investigational vaccine for Escherichia coli O157: Phase I study of O157 O-specific polysaccharide Pseudomonas aeruginosa recombinant exoprotein A conjugates in adults SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; SHIGELLA INFECTIONS; SERUM ANTIBODIES; LIPOPOLYSACCHARIDE; CHILDREN; IMMUNOGENICITY; DYSENTERY; SEROTYPE; DIARRHEA; TOXIN AB Escherichia coli O157 causes severe enteritis and the extraintestinal complication hemolytic-uremic syndrome. Serum IgG against the surface polysaccharide antigen, the 0-specific polysaccharide of lipopolysaccharide (LPS), may confer protective immunity by lysing the inocula. In a phase 1 clinical study, three investigational vaccines were studied in 87 healthy adults. The vaccines were prepared by covalently binding E. coli O157 0-specific polysaccharide with Pseudomonas aeruginosa recombinant exoprotein A. No significant reactions were reported. Most volunteers (81%) responded with a >4-fold increase in IgG LPS antibodies 1 week after vaccination; all volunteers responded with a >4-fold rise at 4 weeks and this level was sustained for 26 weeks after injection. All three vaccines elicited high titers of serum bactericidal activity that roughly correlated with the serum IgG and IgM LPS antibody levels. A phase 2 study in young children is planned. C1 NIH, Bethesda, MD 20892 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. RP Szu, SC (reprint author), NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. EM SCSZU@HELIX.NIH.GOV FU NICHD NIH HHS [HD-4-3212] NR 32 TC 44 Z9 52 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1998 VL 177 IS 2 BP 383 EP 387 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YV221 UT WOS:000071801500015 PM 9466525 ER PT J AU Gaydos, CA Crotchfelt, KA Howell, MR Kralian, S Hauptman, P Quinn, TC AF Gaydos, CA Crotchfelt, KA Howell, MR Kralian, S Hauptman, P Quinn, TC TI Molecular amplification assays to detect chlamydial infections in urine specimens from high school female students and to monitor the persistence of chlamydial DNA after therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 36th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 15-18, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Soc Microbiol ID LIGASE CHAIN-REACTION; PELVIC INFLAMMATORY DISEASE; FIRST-VOID URINE; TRACHOMATIS INFECTION; ANTIMICROBIAL THERAPY; ENZYME-IMMUNOASSAY; ASYMPTOMATIC MEN; FOLLOW-UP; DIAGNOSIS; WOMEN AB Polymerase chain reaction (PCR) and ligase chain reaction (LCR) were compared for the diagnosis of Chlamydia trachomatis infections by testing urine specimens from 408 high school female students. After therapy, sequential urine specimens were tested to determine persistence of chlamydial DNA in urine. Baseline PCR of cervical specimens was positive in 53 (13.0%) students, and PCR and LCR of urine specimens were positive in 63 (15.4%) and 60 (14.7%), respectively. After discrepant analysis, 64 (15.7%) patients could be confirmed as truly infected. Follow-up urine specimens from 33 infected patients demonstrated that at 1-3 days after therapy, PCR and LCR were positive for 40% and 73.3%, respectively. Only at 15 days after therapy did all specimens test negative. Urine tests for Chlamydia organisms should not be used as a test of cure within 3 weeks after treatment. Use of urine assays for screening sexually active adolescents has the potential to significantly improve control of chlamydial infections. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. Baltimore City Hltl Dept, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Gaydos, CA (reprint author), 1159 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@welchlink.welch.jhu.edu RI Gaydos, Charlotte/E-9937-2010 NR 45 TC 83 Z9 88 U1 1 U2 2 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 FEB PY 1998 VL 177 IS 2 BP 417 EP 424 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YV221 UT WOS:000071801500020 PM 9466530 ER PT J AU Waisbren, SE Chang, P Levy, HL Shifrin, H Allred, E Azen, C de la Cruz, F Hanley, W Koch, R Matalon, R Rouse, B AF Waisbren, SE Chang, P Levy, HL Shifrin, H Allred, E Azen, C de la Cruz, F Hanley, W Koch, R Matalon, R Rouse, B TI Neonatal neurological assessment of offspring in maternal phenylketonuria SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID INTERNATIONAL SURVEY; PRETERM INFANTS; GESTATIONAL-AGE; NEWBORN-INFANT; UNITED-STATES; HYPERPHENYLALANINEMIA; PREGNANCIES; BIRTH; PKU; IQ AB This study assesses the impact of prenatal and postnatal factors in maternal phenylketonuria (PKU). The Dubowitz Neurological Assessment of the Preterm and Full-term Newborn Infant was administered within the first 8 days of life to 56 offspring of women with PKU and 45 controls. Follow-up testing of the maternal PKU offspring at age 1 year consisted of the Bayley Scales of Infant Development and the Receptive-Expressive Emergent Language Scale (REEL). In addition, the Home Observation for Measurement of the Environment (HOME Scale) was given. Birth weight was lower (z = 2.0, p = 0.045), birth length was lower (z = 2.1, p = 0.03) and birth head circumference was smaller (z = 3.5, p = 0.0005) in the maternal PKU offspring than in the control infants. Examiners rated 29% of the maternal PKU offspring and 9% of the control infants abnormal (Fisher's exact test, p = 0.01). At 1 year of age, 19% of the maternal PKU offspring attained a Bayley Developmental Quotient (DQ) and a score on the Bayley Motor Scale below 85, 19% had receptive language delay; and 26% had expressive language delay. The gestational age at which the mother attained metabolic control was an important factor associated with birth measurements, the Dubowitz Rating and subsequent developmental scores. The Dubowitz Neurological Assessment score did not predict developmental outcome (chi-square = 1.3, p = 0.53), while the HOME score correlated with the DQ (r = 0.36, p = 0.02). In logistic regression analyses, the home environment was a greater determinant of risk for a low DQ than whether or not the mother attained metabolic control prior to pregnancy (OR = 0.85, p = 0.02). These results suggest that treatment strategies addressing both prenatal and postnatal factors will most effectively reduce risks in maternal PKU. C1 Childrens Hosp, Boston, MA 02115 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Childrens Hosp, Minneapolis, MN USA. Childrens Hosp Los Angeles, Div Med Genet, PKU Program, Los Angeles, CA 90027 USA. NICHHD, Mental Retardat & Dev Disabil Branch, Rockville, MD USA. Hosp Sick Children, PKU Programme, Toronto, ON M5G 1X8, Canada. Univ Texas, Med Branch, Dept Pediat, Child Dev Div, Galveston, TX 77550 USA. RP Waisbren, SE (reprint author), Childrens Hosp, 300 Longwood Ave,IC Smith 107, Boston, MA 02115 USA. FU NICHD NIH HHS [N01-HD-2-3148] NR 31 TC 15 Z9 18 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD FEB PY 1998 VL 21 IS 1 BP 39 EP 48 DI 10.1023/A:1005359313883 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA YX049 UT WOS:000072001300006 PM 9501268 ER PT J AU Bowden, PE Hainey, SD Parker, G Jones, DO Zimonjic, D Popescu, N Hodgins, MB AF Bowden, PE Hainey, SD Parker, G Jones, DO Zimonjic, D Popescu, N Hodgins, MB TI Characterization and chromosomal localization of human hair-specific keratin genes and comparative expression during the hair growth cycle SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE chromosome 12; DNA sequencing; FISH; hair growth cycle; intermediate filaments ID IN-SITU HYBRIDIZATION; EVOLUTIONARY CONSERVATION; FOLLICLE DIFFERENTIATION; EPITHELIAL CYTOKERATINS; SOFT KERATINS; STEM-CELLS; SEQUENCE; PATTERNS; CLUSTER; FAMILY AB During anagen, cell proliferation in the germinative matrix of the hair follicle gives rise to the fiber and inner root sheath. The hair fiber is constructed from structural proteins belonging to four multigene families: keratin intermediate filaments, high-sulfur matrix proteins, ultra high-sulfur matrix proteins, and high glycine-tyrosine proteins, Several hair-specific keratin intermediate filament proteins have been characterized, and all have relatively cysteine-rich N- and C-terminal domains, a specialization that allows extensive disulfide cross-linking to matrix proteins, We have cloned two complete type II hair-specific keratin genes (ghHb1 and ghHb6). Both genes have nine exons and eight introns spanning about 7 kb and lying about 10 kb apart, The structure of both genes is highly conserved in the regions that encode the central rod domain but differs considerably in the C-terminal coding and noncoding sequences, although some conservation of introns does exist, These genes have been localized to the type II keratin cluster on chromosome 12q13 by fluorescence in situ hybridization, They, and their type I partner ghHa1, are expressed in differentiating hair cortical cells during anagen, In cultured follicles, ghHa1 expression declined in cortical cells and was no longer visible after 6 d, whereas the basal epidermal keratin hK14 appeared in the regressing matrix, The transition from anagen to telogen is marked by downregulation of hair cortical specific keratins and the appearance of hK14 in the epithelial sac to which the telogen hair fiber is anchored, Further studies of the regulation of these genes will improve our understanding of the cyclical molecular changes that occur as the hair follicle grows, regresses, and rests. C1 Univ Wales Coll Med, Dept Dermatol, Cardiff CF4 4XN, S Glam, Wales. Univ Dundee, Dept Sci Biol, Dundee, Scotland. Univ Glasgow, Dept Dermatol, Glasgow G12 8QQ, Lanark, Scotland. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Bowden, PE (reprint author), Univ Wales Coll Med, Dept Dermatol, Heath Pk, Cardiff CF4 4XN, S Glam, Wales. NR 38 TC 32 Z9 36 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1998 VL 110 IS 2 BP 158 EP 164 DI 10.1046/j.1523-1747.1998.00097.x PG 7 WC Dermatology SC Dermatology GA YT480 UT WOS:000071608100011 PM 9457912 ER PT J AU Darling, TN Yee, C Koh, B McGrath, JA Bauer, JW Uitto, J Hintner, H Yancey, KB AF Darling, TN Yee, C Koh, B McGrath, JA Bauer, JW Uitto, J Hintner, H Yancey, KB TI Cycloheximide facilitates the identification of aberrant transcripts resulting from a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collagen; epidermal basement membrane; premature termination codon; RNA splicing ID PEMPHIGOID ANTIGEN BPAG2 AB Patients with generalized atrophic benign epidermolysis bullosa often show decreased expression of type XVII collagen, a transmembrane hemidesmosomal protein encoded by COL17A1. This report documents a novel splice-site mutation in COL17A1 in a patient with generalized atrophic benign epidermolysis bullosa, and applies a new methodology to define and characterize the resulting mRNA splice variants. Mutational analysis of COL17A1 identified a maternally inherited G-to-T transversion at the -1 position of exon 32. This acceptor splice-site mutation led to the formation of aberrant transcripts present at extremely low levels, Based on our recent finding that cycloheximide stabilized mutant COL17A1 transcripts in keratinocytes homozygous for a frameshift mutation, the effects of the splice-site mutation on splicing of COL17A1 transcripts were determined using reverse transcriptase polymerase chain reaction of total RNA from keratinocytes incubated for 2.5 h in the presence or absence of 10 mu g cycloheximide per ml. Using this approach, an abnormally spliced transcript was identified that contains an extra 264 bases upstream from exon 32, resulting in a premature termination codon 27 bp downstream from the cryptic splice site. Three other splice variants, including one derived from the skipping of exon 32, were also identified. These results indicate the usefulness of cycloheximide treatment in evaluating the abnormal processing of mRNA due to splice-site mutations, because: (i) aberrant splicing often generates a premature termination codon, (ii) transcripts with premature termination codons can occur at low or undetectable levels due to nonsense-mediated mRNA decay, and (iii) the levels of these transcripts can be increased by cycloheximide. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA. St Thomas Hosp, St Johns Inst Dermatol, London, England. Gen Hosp, Dept Dermatol, Salzburg, Austria. RP Darling, TN (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. RI McGrath, John/D-6824-2012; OI McGrath, John/0000-0002-3708-9964; Darling, Thomas/0000-0002-5161-1974 FU NIAMS NIH HHS [P01AR38923] NR 17 TC 19 Z9 19 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 FEB PY 1998 VL 110 IS 2 BP 165 EP 169 DI 10.1046/j.1523-1747.1998.00103.x PG 5 WC Dermatology SC Dermatology GA YT480 UT WOS:000071608100012 PM 9457913 ER PT J AU Darling, TN Koh, BB Bale, SJ Compton, JG Bauer, WJ Hintner, H Yancey, KB AF Darling, TN Koh, BB Bale, SJ Compton, JG Bauer, WJ Hintner, H Yancey, KB TI A deletion mutation in COL17A1 in five Austrian families with generalized atrophic benign epidermolysis bullosa represents propagation of an ancestral allele SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE inherited blistering disease; polymorphism; type XVII collagen ID PEMPHIGOID ANTIGEN BPAG2; GENE AB Patients with generalized atrophic benign epidermolysis bullosa, a usually nonlethal form of junctional epidermolysis bullosa, have generalized blistering, nail dystrophy, patchy alopecia, and dental abnormalities, Skin fragility in most cases is due to mutations in the gene encoding type XVII collagen (COL17A1), Recently, we reported five Austrian families with generalized atrophic benign epidermolysis bullosa who share the same COL17A1 mutation, Affected individuals in three families are homozygous for 4003delTC, whereas those in two others are compound heterozygotes, To determine if the occurrence of 4003delTC in these unrelated families signifies propagation of an ancestral allele or a mutational hot spat, haplotypes were determined for polymorphisms both within and flanking COL17A1, Fire intragenic polymorphisms were chosen based on their informativeness, One of these, not previously reported, was 2988 A or C that introduces a new restriction site for Eco0109 I. All the 4003delTC alleles showed the same haplotype for these five polymorphic markers, Fourteen microsatellite polymorphisms were selected based on their high heterozygosity and their location within 10q23-q25 near COL17A1. Three families shared microsatellite polymorphisms covering at most 19 cM, whereas the others shared smaller regions consistent with cross-over events during passage of this mutation through several generations, These results indicate that 4003delTC occurs on a single ancestral allele. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Gen Hosp, Dept Dermatol, Salzburg, Austria. RP Darling, TN (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. OI Darling, Thomas/0000-0002-5161-1974 NR 24 TC 12 Z9 12 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 FEB PY 1998 VL 110 IS 2 BP 170 EP 173 DI 10.1046/j.1523-1747.1998.00101.x PG 4 WC Dermatology SC Dermatology GA YT480 UT WOS:000071608100013 PM 9457914 ER PT J AU Feuer, JA Lush, RM Venzon, D Duray, P Tompkins, A Sartor, O Figg, WD AF Feuer, JA Lush, RM Venzon, D Duray, P Tompkins, A Sartor, O Figg, WD TI Elevated carcinoembryonic antigen in patients with androgen-independent prostate cancer SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE CEA; prostate cancer; PSA; androgen-independent; survival ID SERUM; DIAGNOSIS; CARCINOMA AB Background: Extraordinarily high serum carcinoembryonic antigen (CEA) values have been reported to be associated with many malignant disorders, including carcinoma with primary sites in the colon, pancreas, stomach, bile duct, lung, and breast, This study was undertaken to determine if a marked elevation of serum CEA levels in androgen-independent prostate cancer patients exists, and to evaluate the potential of using CEA monitoring as a marker for disease progression. Methods: Records from 141 patients with progressive androgen-independent prostate cancer who were treated at the National Cancer Institute from 1990 to 1996 were analyzed, Serum CEA concentrations were measured using a micro-particle enzyme immunoassay. Results: Among these cases of prostatic carcinoma, 69 (48.9%) had abnormally elevated plasma CEA values (greater than the normal upper limit of 2.5 ng/mL) at some time during their treatment on a clinical investigation protocol, No correlation was found between the elevated CEA concentrations and prostate specific antigen (PSA), In comparison, 32.5% of patients with elevated CEAs had disease that had metastasized to soft tissue (adenopathy, etc) versus 22.2% with normal CEA who had soft tissue involvement (p = 0.3 (2)(chi)) We examined the CEA values with respect to survival time, defined as the interval from the date of the earliest CEA level to the date of death and found no association (p > 0.3). Conclusions: Based on these observations, it appears that in the context of androgen-independent prostate cancer, CEA can be elevated but is an inviable surrogate marker of disease progression with minimal prognostic value. C1 NCI, Med Branch, Clin Pharmacokinet Unit, Clin & Cellular Pharmacol Sect, Bethesda, MD 20892 USA. NCI, Med Branch, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Med Branch, Dev Therapeut Dept, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. Louisiana State Univ, Sch Med, Dept Hematol Oncol, Shreveport, LA USA. RP Figg, WD (reprint author), NCI, Med Branch, Clin Pharmacokinet Unit, Clin & Cellular Pharmacol Sect, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 17 TC 14 Z9 14 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 FEB PY 1998 VL 46 IS 2 BP 66 EP 72 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZC174 UT WOS:000072548200007 PM 9549229 ER PT J AU Miller, JL AF Miller, JL TI Release and extracellular transit of glycosylphosphatidylinositol proteins SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Review ID MEMBRANE-ATTACK-COMPLEX; CELL-ADHESION MOLECULE; GPI-ANCHORED PROTEINS; PHOSPHATIDYLINOSITOL-LINKED PROTEINS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; DETERGENT-RESISTANT COMPLEXES; OUTGROWTH-PROMOTING ACTIVITY; PHOSPHOLIPASE-C; PLASMA-MEMBRANE; ALKALINE-PHOSPHATASE C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Room 9N308, Bethesda, MD 20892 USA. NR 123 TC 11 Z9 14 U1 0 U2 1 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 FEB PY 1998 VL 131 IS 2 BP 115 EP 123 DI 10.1016/S0022-2143(98)90152-4 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA YY181 UT WOS:000072121400001 PM 9488493 ER PT J AU Foletta, VC Segal, DH Cohen, DR AF Foletta, VC Segal, DH Cohen, DR TI Transcriptional regulation in the immune system: all roads lead to AP-1 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE Fos; Jun; lymphocyte; apoptosis; cytokine; anergy ID ACTIVATED T-CELLS; C-FOS EXPRESSION; INTERLEUKIN-2 GENE-EXPRESSION; INTERFERON-GAMMA PROMOTER; DNA-BINDING ACTIVITY; DISTINCT SIGNALING PATHWAYS; STIMULATING FACTOR PROMOTER; LEUCINE ZIPPER PROTEINS; ACCESSORY MOLECULE CD28; OSTEO-SARCOMA VIRUS AB The mechanisms regulating the development and function of the immune system are diverse and complicated. The signaling pathways and target genes that become activated upon cell-surface stimulation are currently being defined, and transcription factor activator protein 1 (AP-1) is proving to be an important regulator of nuclear gene expression in leukocytes. In vitro and in vivo studies have demonstrated that AP-1 expression is induced after a diverse range of stimuli and that AP-I contributes to the regulation of a large number of genes. In this review we will examine the role of AP-1 during leukocyte activation and differentiation in the immune system. C1 NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Australian Natl Univ, John Curtin Sch Med Res, Div Cell Biol & Immunol, Canberra, ACT 2601, Australia. RP Foletta, VC (reprint author), NIMH, Lab Cellular & Mol Regulat, NIH, Bldg 36,Room 2D10,36 Convent Dr,MSC 4068, Bethesda, MD 20892 USA. EM torie@codon.nih.gov NR 213 TC 233 Z9 236 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 FEB PY 1998 VL 63 IS 2 BP 139 EP 152 PG 14 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YW271 UT WOS:000071915600001 PM 9468273 ER PT J AU Fisher, WR Zech, LA Stacpoole, PW AF Fisher, WR Zech, LA Stacpoole, PW TI Apolipoprotein B metabolism in hypertriglyceridemic diabetic patients administered either a fish oil- or vegetable oil-enriched diet SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoprotein B (apoB); fish oil; SAAM; compartmental modeling; [H-3]-leucine; tracer kinetics; hypertriglyceridemia; diabetes ID LOW-DENSITY-LIPOPROTEIN; POLYUNSATURATED FATTY-ACIDS; FAMILIAL HYPERCHOLESTEROLEMIA; TRIGLYCERIDE-RICH; HYPERLIPOPROTEINEMIC SUBJECTS; SAFFLOWER OIL; RAT-LIVER; PLASMA; MELLITUS; KINETICS AB The effect on apolipoprotein B kinetics of a diet enriched in either fish oil or safflower oil was investigated in five hypertriglyceridemic (HTG), non-insulin-dependent diabetic subjects. The fish oil diet decreased plasma triglycerides and VLDL-apoB but increased LDL-apoB and LDL-cholesterol. Total plasma apoB concentration did not change, nor did the increased VLDL-apoB secretion present in these HTG subjects, which, accompanied by impaired lipolysis, accounted for their elevated VLDL. The fish oil-induced fall in VLDL resulted from a decrease in secretion without a change in residence time. The IDL fraction, which also contained small VLDL, was the primary site for the secretion of apoB particles in the HTG subjects. On the fish oil diet there was a further, compensatory increase in the secretion of these lipoproteins such that the transport of apoB in IDL remained the same, as did its mass. In the HTG subjects the major portion of IDL lipoproteins was catabolized, with LDL-apoB production comprising the lesser quantity. On the fish oil diet, a shift in the channeling of the lipoprotein output from IDL resulted in a decrease in the catabolic pathway and an increase in conversion to LDL. As the residence time of LDL did not change, this increased input gave rise to the larger mass of LDL-apoB seen in these hypertriglyceridemic subjects when receiving a fish oil diet. C1 Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Biochem, Gainesville, FL 32610 USA. NCI, Math Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fisher, WR (reprint author), Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA. FU NCRR NIH HHS [RR-00082]; NHLBI NIH HHS [HL-23994]; NIDDK NIH HHS [DK-40439] NR 47 TC 27 Z9 27 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 1998 VL 39 IS 2 BP 388 EP 401 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YX524 UT WOS:000072049200016 PM 9507999 ER PT J AU Tardif, SD Jaquish, CE Toal, RL Layne, DG Power, RA AF Tardif, SD Jaquish, CE Toal, RL Layne, DG Power, RA TI Estimation of gestational ages in the common marmoset (Callithrix jacchus) from published prenatal growth curves SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE gestational age; ultrasonography; callitrichid primate ID FETAL GROWTH; ULTRASOUND AB This report compares estimated gestational ages from published cubic spline curves to gestational ages estimated retrospectively from delivery dates in 28 pregnancies from ten common marmosets (Callithrix jacchus). Both CRL- and BPD-based estimates of gestational age were closely correlated with delivery-based gestational age estimates. Of the three ultrasound machines used, the one with 16 shades of gray and a sequential linear array overestimated gestational age during early pregnancy, based on CRL measures. Measures from the other two machines (64 or 264 shades of gray; linear sector and annular array or electronic phase array) were similar and resulted in a correlation of the two estimates of gestational age of 0.94 and a mean difference between the two estimates of 0.16 days with 80% of CRL-based gestational age estimates being within +/- 5 days of the delivery-based estimate. The reliability of BPD-based estimates of gestational age was strongly related to pregnancy outcome. BPD-based estimates underestimated gestational age in poor outcome pregnancies (i.e., those in which infants died within 7 days of birth) but not in good outcome pregnancies. The combined CRL- and BPD-based estimates on poor outcome pregnancies suggest that there was less growth in BPD in late gestation for those pregnancies that resulted in nonviable offspring. For good outcome pregnancies, the correlation between BPD-based and delivery-based estimates of gestational age was 0.871 and the mean difference between the two estimates was -0.06 days with 83.3% of BPD-based estimates falling within +/- 5 days of delivery-based estimates. C1 Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Coll Vet Med, Dept Large Anim Clin Sci, Knoxville, TN USA. RP Tardif, SD (reprint author), Kent State Univ, Dept Biol Sci, Cunningham Hall, Kent, OH 44242 USA. NR 11 TC 11 Z9 11 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB PY 1998 VL 27 IS 1 BP 28 EP 32 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA ZJ925 UT WOS:000073267500005 PM 9606040 ER PT J AU Chen, HS Miller, RH Hornbuckle, WE Tennant, BC Cote, PJ Gerin, JL Purcell, RH AF Chen, HS Miller, RH Hornbuckle, WE Tennant, BC Cote, PJ Gerin, JL Purcell, RH TI Titration of recombinant woodchuck hepatitis virus DNA in adult woodchucks SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE woodchuck hepatitis virus infections; DNA; titration transfection; in vivo ID B VIRUS; HEPATOCELLULAR-CARCINOMA; NUCLEOTIDE-SEQUENCE; NATURAL HOST; GENOME; INFECTION; LIVER; ESTABLISHMENT; GENE AB In vivo transfection of Eastern woodchucks (Marmota monax) with recombinant woodchuck hepatitis virus (WHV) DNA is effective in inducing virus infection for the study of replication, pathogenicity, and oncogenicity of wild-type and mutated WHV. The one drawback to this procedure is the need for preparation of large amounts of WHV DNA. Reduction of the amount of WHV DNA in the transfection protocol necessary to induce infection would save considerable time and resources. Therefore, we conducted a titration of WHV DNA, ranging from 50 mu g to 50 pg of DNA, in adult woodchucks to determine the minimum infectious dose of recombinant WHV DNA. As little as 50 ng of transfected WHV DNA induced productive infection in adult woodchucks. Thus, transfection with large amounts of recombinant WHV DNA appears to be unnecessary. (C) 1998 Wiley-Liss, Inc. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA. Georgetown Univ, Div Mol Virol & Immunol, Rockville, MD USA. RP Purcell, RH (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. FU NIAID NIH HHS [N01-AI-82698, N01-AI-72623] NR 21 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1998 VL 54 IS 2 BP 92 EP 94 DI 10.1002/(SICI)1096-9071(199802)54:2<92::AID-JMV4>3.0.CO;2-J PG 3 WC Virology SC Virology GA YV169 UT WOS:000071796300004 PM 9496365 ER PT J AU Sadaie, MR Zamani, M Whang, S Sistron, N Arya, SK AF Sadaie, MR Zamani, M Whang, S Sistron, N Arya, SK TI Towards developing HIV-2 lentivirus-based retroviral vectors for gene therapy: Dual gene expression in the context of HIV-2 LTR and Tat SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE gene transfer; promoter/cell specificity; regulatory loops; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; RIBOSOME ENTRY SITE; REGULATORY ELEMENTS; HEMATOPOIETIC-CELLS; TYPE-2 HIV-2; 2 GENES; IN-VIVO; TRANSLATION; INITIATION AB Because of the distinct ability of retroviruses to integrate into the target cell genome and thus achieve long-term expression, retrovirus vectors hold great promise for stable gene transfer. Such vectors derived from human immunodeficiency retroviruses (HIVs) and other lentiviruses are envisioned to possess several advantages, especially for in vivo gene therapy of HIV infection and acquired immunodeficiency syndrome (AIDS) where targeting CD4+ T cells/macrophages and pluripotent non-dividing stem cells would be required. Among these is the ability of HIVs to transduce nondividing cells in contrast to the murine retroviruses which require target cell mitosis. The advantages of the lentivirus vectors will be further enhanced by the development of multigenic vectors carrying more than one gene in a dependent or independent transcriptional unit. Separate from the issue of transduction efficiency, information is needed about the impact of the configuration of the genes in a multigenic vector on their expression. Towards this end, we investigated the expression of genes specifically directed by the HIV-2 LTR and Tat in a prototypic minimal transfer vector. We found that the expression of a gene in a dual gene configuration depended upon its position in the transcriptional unit and that the insertion of an internal translational initiation mechanism improved the expression of the downstream gene. Apparently not sufficiently appreciated previously, these effects were promoter and cell-type dependent. Our data also suggest that the commonly used cellular or viral promoters may be orders of magnitude less effective than HIV-2 LTR in the presence of Tat, and thus may not be useful as internal promoters in the context of the HIV-2 LTR:Tat regulatory loop. (C) 1998 Wiley-Liss, Inc.dagger. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. US FDA, Lab Immunochem, Div Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. RP Arya, SK (reprint author), NCI, Basic Res Lab, Div Basic Sci, NIH, 37 Convent Dr,Bldg 37,Room 6C24, Bethesda, MD 20892 USA. NR 40 TC 19 Z9 19 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1998 VL 54 IS 2 BP 118 EP 128 PG 11 WC Virology SC Virology GA YV169 UT WOS:000071796300009 PM 9496370 ER PT J AU Cubitt, WD Green, KY Payment, P AF Cubitt, WD Green, KY Payment, P TI Prevalence of antibodies to the Hawaii strain of human calicivirus as measured by a recombinant protein based immunoassay SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE Hawaii virus; Mexico virus; Norwalk virus; calicivirus; epidemiology; transplant; Canada ID ROUND-STRUCTURED VIRUSES; SNOW MOUNTAIN; MOLECULAR CHARACTERIZATION; ENZYME-IMMUNOASSAY; CAPSID PROTEIN; NORWALK; AGENT; GASTROENTERITIS; SEROPREVALENCE; EXPRESSION AB The evaluation of an enzyme immunoassay using recombinant Hawaii virus-like particles (rHVLPs) with a panel of sera which had been screened previously for antibodies to Norwalk virus (NV) and Mexico virus (MxV) is described. The assay was also applied to study the epidemiology of Hawaii virus. Adult volunteers challenged with the prototype (genogroup II, human calicivirus) HV developed significant IgG responses (16-32 fold rises) following challenge whereas adults challenged or naturally infected with NV (genogroup I) did not. Lesser antibody responses (4-8 fold rises) were demonstrated in volunteers challenged with Snow Mountain agent (SMA) and patients infected by SRSV 'UK3' and 'UK4' strains, indicating a degree of antigenic relatedness among viruses within genogroup II. Comparison of the seroprevalence of Ig G antibodies to rHV, rMxV and rNV in 338 children in London showed that infections with genogroup II viruses are prevalent and occur earlier in life than NV. Many young children had antibodies to MxV but not HV indicating that genogroup II viruses have both conserved and antigenically distinct epitopes. A serological study on 566 Canadians aged between 9 and 79 years showed that the prevalence of antibodies to rHV rose with age from 65-100% and from 53-100% for NV. Measurement of antibody response in a heart transplant patient infected with an MxV-like virus showed significant responses to both rMxV and rHV. Continuous monitoring of the patient over two years showed that antibody levels declined rapidly to prechallenge levels after a year. (C) 1998 Wiley-Liss, Inc. C1 Hosp Sick Children, Camelia Botnar Labs, Dept Virol, London WC1N 3JH, England. NIH, Bethesda, MD 20892 USA. Univ Quebec, Inst Armand Frappier, Laval, PQ, Canada. RP Cubitt, WD (reprint author), Hosp Sick Children, Camelia Botnar Labs, Dept Virol, Great Ormond St, London WC1N 3JH, England. EM d.cubitt@ich.ucl.ac.uk NR 24 TC 31 Z9 32 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1998 VL 54 IS 2 BP 135 EP 139 PG 5 WC Virology SC Virology GA YV169 UT WOS:000071796300011 PM 9496372 ER PT J AU Sonnhammer, ELL Wootton, JC AF Sonnhammer, ELL Wootton, JC TI Dynamic contact maps of protein structures SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article ID FOLD RECOGNITION; PAIR POTENTIALS; SEQUENCE AB The two-dimensional contact map of interresidue distances is a visual analysis technique for protein structures. We present two standalone software tools designed to be used in combination to increase the versatility of this simple yet powerful technique. First, the program Structer calculates contact maps for three-dimensional molecular structural data. the contact map matrix can then be viewed in the graphical matrix-visualization program Dotter. Instead of using a predefined distance cutoff, we exloit Dotter's dynamic rendering control, allowing interactive exploration at varying distance cutoffs after calculating the matrix once. Structer can use a number of distance measures, can incorporate multiple chains in one contact map, and allows masking of user-defined residue sets. It works either directly with PDB files, or can use the MMDB network API for reading structures. (C) 1998 by Elsevier Science Inc. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. RP Sonnhammer, ELL (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bldg 38A,Room 8N805, Bethesda, MD 20894 USA. NR 12 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD FEB PY 1998 VL 16 IS 1 BP 1 EP + DI 10.1016/S1093-3263(98)00009-6 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 123EF UT WOS:000076112300001 PM 9783253 ER PT J AU Bonafe, N Sellers, JR AF Bonafe, N Sellers, JR TI Molecular characterization of myosin V from Drosophila melanogaster SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID BRUSH-BORDER CYTOSKELETON; UNCONVENTIONAL MYOSIN; SACCHAROMYCES-CEREVISIAE; GENE ENCODES; ACTIVE-SITE; BRAIN; LOCALIZATION; PROTEINS; FAMILY; CELLS AB Recent studies have revealed unconventional myosin V to be an important actin-based molecular motor involved in vesicular movement. In this paper we report the molecular characterization of the Drosophila myosin V, identified by reverse genetics. The gene encodes a 1792-residue, 207 kDa heavy chain polypeptide which possesses a typical head or motor domain of 771 residues, a region of six IQ motifs (139 residues) which serve as potential calmodulin/light chain binding sites at the head/ tail junction, and a tail domain of 882 residues containing sequences of putative alpha-helical coiled-coils required for dimerization of the molecule and sequences of non-helical structure at the C-terminal end. Based on Southern blot analyses and chromosomal localization, evidence is presented for a single Drosophila myosin V gene. RNA analyses revealed a doublet of transcripts of about 6 kb, expressed throughout the lifetime of a fly but particularly abundant in the early stages of embryonic development (maternally contributed), in the ectodermic tissue of the hindgut starting at stage 16, and in the adult head. These results suggest that myosin V may be involved in processes required in a variety of cell types in Drosophila. We have also mapped the Drosophila myosin V locus to chromosome 2 at the position 43C-D, and we are currently searching for known mutations in this region. Finally, phylogenetic analysis of the head domain reveals that Drosophila myosin V is more closely related to mammalian myosin Va and Vb than to other invertebrate class-V myosins; nevertheless, it is not significantly more related to myosin Va than to myosin Vb. While vertebrates would need two different myosin V isoforms to accomplish specific functions, we speculate that Drosophila myosin V might provide the equivalent functions by itself. (C) Chapman & Hall Ltd. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, NIH, Bldg 10,Rm 8N202, Bethesda, MD 20892 USA. NR 49 TC 16 Z9 16 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1998 VL 19 IS 2 BP 129 EP 141 DI 10.1023/A:1005356511634 PG 13 WC Cell Biology SC Cell Biology GA YX370 UT WOS:000072033400003 PM 9536440 ER PT J AU Rall, JE AF Rall, JE TI The scientific revolution SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 1998 VL 186 IS 2 BP 127 EP 128 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YX387 UT WOS:000072034900011 ER PT J AU Hampson, AJ Bornheim, LM Scanziani, M Yost, CS Gray, AT Hansen, BM Leonoudakis, DJ Bickler, PE AF Hampson, AJ Bornheim, LM Scanziani, M Yost, CS Gray, AT Hansen, BM Leonoudakis, DJ Bickler, PE TI Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE anandamide; cannabinoid; NMDA; glutamate; calcium channel ischemia ID CANNABINOID RECEPTOR; RAT-BRAIN; CALCIUM CHANNELS; ENZYMATIC-SYNTHESIS; XENOPUS OOCYTES; BINDING; ASTROCYTES; EXPRESSION; AGONIST; POTENTIATION AB Anandamide is an endogenous ligand of cannabinoid receptors that induces pharmacological responses in animals similar to those of cannabinoids such as Delta(9)-tetrahydrocannabinol (THC). Typical pharmacological effects of cannabinoids include disruption of pain, memory formation, and motor coordination, systems that all depend on NMDA receptor mediated neurotransmission, We investigated whether anandamide can influence NMDA receptor activity by examining NMDA-induced calcium flux (Delta Ca-NMDA(2+)) in rat brain slices, The presence of anandamide reduced Delta Ca-NMDA(2+) and the inhibition was disrupted by cannabinoid receptor antagonist, pertussis toxin treatment, and agatoxin (a calcium channel inhibitor), Whereas these treatments prevented anandamide inhibiting Delta Ca-NMDA(2+), they also revealed another, underlying mechanism by which anandamide influences Delta Ca-NMDA(2+). In the presence of cannabinoid receptor antagonist, anandamide potentiated Delta Ca-NMDA(2+) in cortical, cerebellar, and hippocampal slices, Anandamide (but not THC) also augmented NMDA-stimulated currents in Xenopus oocytes expressing cloned NMDA receptors, suggesting a capacity to directly modulate NMDA receptor activity, In a similar manner, anandamide enhanced neurotransmission across NMDA receptor-dependent synapses in hippocampus in a manner that was not mimicked by THC and was unaffected by cannabinoid receptor antagonist, These data demonstrate that anandamide can modulate NMDA receptor activity in addition to its role as a cannabinoid receptor ligand. C1 Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. RP Hampson, AJ (reprint author), NIMH, Lab Cellular & Mol Regulat, NIH, LCMR Bldg 36A15,Convent Dr, Bethesda, MD 20892 USA. NR 36 TC 147 Z9 154 U1 0 U2 2 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 FEB PY 1998 VL 70 IS 2 BP 671 EP 676 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YT381 UT WOS:000071596800025 PM 9453561 ER PT J AU Sinha, D Bonner, TI Bhat, NR Matsuda, LA AF Sinha, D Bonner, TI Bhat, NR Matsuda, LA TI Expression of the CB1 cannabinoid receptor in macrophage-like cells from brain tissue: immunochemical characterization by fusion protein antibodies SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Marijuana; Cannabis; microglial G protein coupled receptors ID ACTIVATED MICROGLIA; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; INHIBITION; DELTA(9)-TETRAHYDROCANNABINOL; OLIGODENDROCYTES; PHARMACOLOGY; ANANDAMIDE; MECHANISM; STIMULATE AB Antibodies designed to recognize a 74 amino acid sequence of the N- or C-terminal domain of the rat CBI cannabinoid receptor detected a 58 kDa protein in immunoblots of brain and various cells known to express the CB1 cannabinoid receptor. A human B-lymphoblastoid cell line and macrophage-like cells from neonatal rat brain were also positive for CB1 receptor-like immunoreactivity. Immunocytochemical analysis performed with isolated Fab fragments showed surface staining in NG108-15 cells and brain macrophage like cells which also express MHC class II antigens. The data suggest a plausible role for CB1 receptors in the immune function of brain. (C) 1998 Elsevier Science B.V. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. RP Sinha, D (reprint author), NEI, Sect Mol Struct & Funct, NIH, Bldg 6,Room 218, Bethesda, MD 20892 USA. FU NIDA NIH HHS [DA 08104] NR 35 TC 45 Z9 47 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 1998 VL 82 IS 1 BP 13 EP 21 DI 10.1016/S0165-5728(97)00181-1 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZB175 UT WOS:000072443900003 PM 9526841 ER PT J AU Mazzanti, B Vergelli, M Riccio, P Martin, R McFarland, HF Liuzzi, GM Amaducci, L Massacesi, L AF Mazzanti, B Vergelli, M Riccio, P Martin, R McFarland, HF Liuzzi, GM Amaducci, L Massacesi, L TI T-cell response to myelin basic protein and lipid-bound myelin basic protein in patients with multiple sclerosis and healthy donors SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE myelin basic protein; lipids; T-cells; multiple sclerosis ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DEMYELINATING DISEASES; COSTIMULATORY SIGNALS; FINE SPECIFICITY; RECEPTOR USAGE; RECOGNITION; FORM; LYMPHOCYTES; INDIVIDUALS; CITRULLINE AB An autoimmune T-cell response to myelin proteins is thought to be involved in the pathogenesis of multiple sclerosis (MS) and myelin basic protein (MBP) is the most widely studied potential target antigen. We investigated the T-cell response to MBP in MS patients and controls using two different molecular forms of the protein: the classical hydrophilic MBP (lipid-free MBP, LF-MBP) and a lipid-bound. native-like preparation of MBP isolated in a molecular form retaining the binding to all myelin lipids (lipid-bound-MBP, LB-MBP), Short term T-cell lines (TCL) were generated using either LF-or LB-MBP and tested for their reactivity to the in vitro stimulating antigen. No differences were detected between MS patients and healthy donors in the percentage of T-cell cultures responsive to the LF-MBP. In contrast, the number of LB-MBP reactive cultures was higher in MS patients than in controls. This difference was almost entirely due to the presence of high numbers of LB-MBP-specific TCL in MS patients which did not cross-react with LF-MBP and were not present in healthy subjects. LB-MBP may represent a novel antigen worth to be investigated in MS. (C) 1998 Elsevier Science B.V. C1 Univ Florence, Dept Neurol & Psychiat Sci, I-50134 Florence, Italy. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Basilicata, Dept Biol, DBAF, I-85100 Potenza, Italy. CNR, CSMME, Dept Biochem & Mol Biol, I-70126 Bari, Italy. RP Massacesi, L (reprint author), Univ Florence, Dept Neurol & Psychiat Sci, Viale Morgagni 85, I-50134 Florence, Italy. EM massacesi@cesit1.unifi.it OI Massacesi, Luca/0000-0001-5083-372X; Liuzzi, Grazia Maria/0000-0001-5692-9335 NR 29 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 1998 VL 82 IS 1 BP 96 EP 100 DI 10.1016/S0165-5728(97)00194-X PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZB175 UT WOS:000072443900013 PM 9526851 ER PT J AU Wenning, GK Litvan, I Jankovic, J Granata, R Mangone, CA McKee, A Poewe, W Jellinger, K Chaudhuri, KR D'Olhaberriague, L Pearce, RKB AF Wenning, GK Litvan, I Jankovic, J Granata, R Mangone, CA McKee, A Poewe, W Jellinger, K Chaudhuri, KR D'Olhaberriague, L Pearce, RKB TI Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE corticobasal degeneration; atypical parkinsonism; survival; natural history; clinicopathological study ID PROGRESSIVE SUPRANUCLEAR PALSY; RICHARDSON-OLSZEWSKI-SYNDROME; CRITERIA; PATTERN; SPECT AB Objective-To analyse the natural history and survival of corticobasal degeneration bg investigating the clinical features of 14 cases confirmed by postmortem examination. Methods-Patients with definite corticobasal degeneration were selected from the research and clinical files of seven tertiary medical centres in Austria, the United Kingdom, and the United States, Clinical features were analysed in detail. Results-The sample consisted of eight female and six male patients; mean age at symptom onset was 63 (SD 7.7) years, and mean disease duration was 7.9 (SD 2.6) years. The mast commonly reported symptom at onset included asymmetric limb clumsiness with or without rigidity (50%) or tremor (21%). At the first neurological visit, on average 3.0 (SD 1.9) years after symptom onset, the most often encountered extrapyramidal features included unilateral limb rigidity (79%) or bradykinesia (71%), postural imbalance (45%), and unilateral limb dystonia (43%). Ideomotor apraxia. (64%), and to a lesser extent cortical dementia (36%), were the most common cortical signs present at the first visit. During the course of the disease, virtually all patients developed asymmetric or unilateral akinetic rigid parkinsonism and a gait disorder. No patient had a dramatic response to levodopa therapy Median. survival time after onset of symptoms was 7.9 (SD 0.7) (range, 2.5-12.5) years, and, after the first clinic visit, 4.9 (SD 0.7) (range, 0.8-10) years. Early bilateral bradykinesia, frontal syndrome, or two out of tremor, rigidity, and bradykinesia, predicted a shorter survival. Conclusion-The results confirm that unilateral parkinsonism unresponsive to levodopa and limb ideomotor apraxia are the clinical hallmarks of corticobasal degeneration, and only a minority of patients with corticobasal degeneration present with dementia. The study also suggests that a focal cognitive and extrapyramidal motor syndrome is indicative of corticobasal degeneration. Survival in corticobasal degeneration was shortened by the early presence of (more) widespread parkinsonian features or frontal lobe syndrome. C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Innsbruck Hosp, Dept Neurol, A-6020 Innsbruck, Austria. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Parkinsons Dis Soc, Brain Bank Res Ctr, London, England. RP Litvan, I (reprint author), NINDS, Neuroepidemiol Branch, NIH, Fed Bldg,Room 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 25 TC 194 Z9 199 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 FEB PY 1998 VL 64 IS 2 BP 184 EP 189 DI 10.1136/jnnp.64.2.184 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA YW972 UT WOS:000071993200011 PM 9489528 ER PT J AU Furuya, K Sano, K Segawa, H Ide, K Yoneyama, H AF Furuya, K Sano, K Segawa, H Ide, K Yoneyama, H TI Symptomatic tonsillar ectopia SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE Chiari type I malformation; magnetic resonance image; neurotological examination; tonsillar ectopia ID CHIARI-I MALFORMATION; CEREBELLAR TONSILS; POSITION; EXPERIENCE; ADULTS; MR AB Objective-To determine if slight descent of the cerebellar tonsils (< 5 mm below the foramen magnum; tonsillar ectopia) may cause surgically treatable symptomatology. Methods-A consecutive series of nine symptomatic patients with tonsillar ectopia seen between December 1990 and March 1993 are reported on. The same number of age and sex matched controls were selected at random from outpatients. Twelve asymptomatic subjects with tonsillar ectopia were found among 5000 people between January 1991 and March 1996. Diagnosis of tonsillar ectopia was based on midsagittal MRI. Results-Patients presented mainly with chronic intractable occipital dull pain, vertigo, and dysequilibrium. In all patients MRI showed normal brain structure except for tonsillar ectopia (-2.9 (SD 0.8) mm), which has historically been thought to be of no clinical relevance. In the control group the tonsillar position was +2.1 (SD 2.8) mm (p<0.01). Neurotologically abnormal findings were detected with a monaural speech integration test (100%), eye tracking test (56%), optokinetic nystagmus test (89%), and visual suppression test (67%) which strongly suggested a CNS lesion. In accordance with the results of MRI and precise neurotological examination, posterior fossa decompression surgery was carried out, followed by improvement of preoperative symptoms and less severity of neurotological abnormalities in all patients. Conclusion-Tonsillar ectopia could cause neurological symptoms in small populations, which were surgically treatable. Neurotological assessment was necessary to verify the aetiological relation between tonsillar ectopia and various symptoms. C1 Fuji Brain Inst & Hosp, Dept Neurosurg, Fujinomiya, Shizuoka 418, Japan. Fuji Brain Inst & Hosp, Dept Neurotol, Fujinomiya, Shizuoka 418, Japan. RP Furuya, K (reprint author), NINDS, Stroke Branch, Bldg 36,Room 4A03, Bethesda, MD 20892 USA. NR 37 TC 12 Z9 14 U1 0 U2 1 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 FEB PY 1998 VL 64 IS 2 BP 221 EP 226 DI 10.1136/jnnp.64.2.221 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA YW972 UT WOS:000071993200018 PM 9489535 ER PT J AU Classen, J Liepert, J Wise, SP Hallett, M Cohen, LG AF Classen, J Liepert, J Wise, SP Hallett, M Cohen, LG TI Rapid plasticity of human cortical movement representation induced by practice SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; MODULATION; SKILL; FORCE; REORGANIZATION; ACQUISITION; DIRECTION; PATHWAYS; NEURONS AB The process of acquiring motor skills through the sustained performance of complex movements is associated with neural plasticity. However, it is unknown whether even simple movements, repeated over a short period of time, are effective in inducing cortical representational changes. Whether the motor cortex can retain specific kinematic aspects of a recently practiced movement is also unknown. We used focal transcranial magnetic stimulation (TMS) of the motor cortex to evoke isolated and directionally consistent thumb movements. Thumb movements then were practiced in a different direction. Subsequently, TMS came to evoke movements in or near the recently practiced direction for several minutes before returning to the original direction. To initiate a change of the TMS-evoked movement direction, 15 or 30 min of continuous training were required in most cf the subjects and, on two occasions, as little as 5 or 10 min. Substantially smaller effects followed more direct stimulation of corticofugal axons with transcranial electrical stimulation, pointing to cortex as che site of plasticity. These findings suggest that the training rapidly, and transiently, established a change in the cortical network representing the thumb, which encoded kinematic details of the practiced movement. This phenomenon may be regarded as a short-term memory for movement and be the first step of skill acquisition. C1 NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, Poolesville, MD 20837 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Unit, NIH, Bldg 10,Room 54234-1430, Bethesda, MD 20892 USA. NR 38 TC 629 Z9 638 U1 2 U2 29 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1998 VL 79 IS 2 BP 1117 EP 1123 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YY123 UT WOS:000072115600053 PM 9463469 ER PT J AU Davenport, RW Thies, E Zhou, RP Nelson, PG AF Davenport, RW Thies, E Zhou, RP Nelson, PG TI Cellular localization of ephrin-A2, ephrin-A5, and other functional guidance cues underlies retinotopic development across species SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retinocollicular; topographic projection; growth cone; neuronal development; filopodia; repulsion; retraction; retinotopic; retinotectal; Eph receptor tyrosine kinase; ephrin; guidance cues ID CHICK OPTIC TECTUM; ADULT AVIAN BRAIN; MONOCLONAL-ANTIBODIES; SUPERIOR COLLICULUS; RETINAL AXONS; RADIAL GLIA; IN-VITRO; RETINOTECTAL PROJECTION; NEURITE OUTGROWTH; VISUAL-SYSTEM AB Avian retinotectal and rodent retinocollicular systems are general model systems used to examine developmental processes that underpin topographically organized neuronal circuits. The two systems rely on guidance components to establish their precise retinotopic maps, but many cellular events differ during their development. For example, compared with the chick, a generally less restricted outgrowth pattern is observed when retinae innervate their targets in rodents. Cellular or molecular distributions of guidance components may account for such differences in retinotopic development across species. Candidate repellent molecules, such as ephrin-A2 and ephrin-A5, have been cloned in both chick and rodents; however, it has not yet been shown in rodents that living cells express sufficient amounts of any repellent components to deter outgrowth. We used a coculture assay that gives cellular resolution of retino-target interactions and demonstrate that living, caudal superior colliculus cells selectively prevent extension of axons from temporal regions of the retinae. Time-lapse video microscopy revealed the cellular localization of permissive and repulsive guidance components in rodents, which differed from that in chick. To analyze the potential molecular basis for these differences, we investigated the function and localization of ephrin-A2 and -A5. Cells transfected with ephrin-A2 and -A5 selectively repelled retinal axons. Ephrin-A2 and -A5 RNA expression patterns differed across cell populations and between species, suggesting molecular mechanisms and key cellular interactions that may underlie fundamental differences in the development of retinotectal and retinocollicular maps. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Coll Pharm, Canc Res Lab, Piscataway, NJ 08855 USA. RP Davenport, RW (reprint author), NICHHD, Dev Neurobiol Lab, NIH, 49 Convent Dr,MSC4480,Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 63 TC 33 Z9 33 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB 1 PY 1998 VL 18 IS 3 BP 975 EP 986 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YT570 UT WOS:000071620300018 PM 9437019 ER PT J AU Ziemann, U Corwell, B Cohen, LG AF Ziemann, U Corwell, B Cohen, LG TI Modulation of plasticity in human motor cortex after forearm ischemic nerve block SO JOURNAL OF NEUROSCIENCE LA English DT Article DE motor cortical excitability; cortical reorganization; transient forearm deafferentation; ischemic nerve block; human; transcranial magnetic stimulation; modulation of plasticity ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM POTENTIATION; MASSIVE CORTICAL REORGANIZATION; ADULT-RATS; HORIZONTAL CONNECTIONS; INTRACORTICAL MICROSTIMULATION; CORTICOCORTICAL INHIBITION; VOLUNTARY CONTRACTION; DYNAMIC ORGANIZATION; RAPID REORGANIZATION AB Deafferentation leads to cortical reorganization that may be functionally beneficial or maladaptive. Therefore, we were interested in learning whether it is possible to purposely modulate deafferentation-induced reorganization. Transient forearm deafferentation was induced by ischemic nerve block (INB) in healthy volunteers. The following five interventions were tested: INB alone; INB plus low-frequency (0.1 Hz) repetitive transcranial magnetic stimulation of the motor cortex ipsilateral to INB (INB+rTMS(i)); rTMS(i) alone; INB plus rTMS of the motor cortex contralateral to INB (INB+rTMS(c)); and rTMS(c) alone. Plastic changes in the motor cortex contralateral to deafferentation were probed with TMS, measuring motor threshold (MT), motor evoked-potential (MEP) size, and intracortical inhibition (ICI) and facilitation (ICF) to the biceps brachii muscle proximal to the level of deafferentation. INB alone induced a moderate increase in MEP size, which was significantly enhanced by INB+rTMS, but blocked by INB+rTMS(i). INB alone had no effect on ICI or ICF, whereas INB+rTMS(c) reduced ICI and increased ICF, and conversely, INB+rTMS(i) deepened ICI and suppressed ICF. rTMS(i) and rTMS(c) alone were ineffective in changing any of these parameters. These findings indicate that the deafferented motor cortex becomes modifiable by inputs that are normally subthreshold for inducing changes in excitability. The deafferentation-induced plastic changes can be up-regulated by direct stimulation of the "plastic" cortex and likely via inhibitory projections down-regulated by stimulation of the opposite cortex. This modulation of cortical plasticity by noninvasive means might be used to facilitate plasticity when it is primarily beneficial or to suppress it when it is predominately maladaptive. C1 NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Ziemann, U (reprint author), NINDS, Human Cort Physiol Unit, NIH, Bldg 36,Rm 5N234,10 Ctr Dr,MSC-1430, Bethesda, MD 20892 USA. NR 68 TC 249 Z9 254 U1 1 U2 11 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 FEB 1 PY 1998 VL 18 IS 3 BP 1115 EP 1123 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YT570 UT WOS:000071620300030 PM 9437031 ER PT J AU Wang, YX Wenthold, RJ Ottersen, OP Petralia, RS AF Wang, YX Wenthold, RJ Ottersen, OP Petralia, RS TI Endbulb synapses in the anteroventral cochlear nucleus express a specific subset of AMPA-type glutamate receptor subunits SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlear nucleus; auditory; AMPA; glutamate receptors; spherical bushy cell; endbulb ID CA2+ PERMEABILITY; GUINEA-PIG; RAT-BRAIN; ULTRASTRUCTURAL-LOCALIZATION; IMMUNOGOLD LOCALIZATION; DIFFERENTIAL EXPRESSION; SYNAPTIC TRANSMISSION; ELECTRON-MICROSCOPE; GLIAL LOCALIZATIONS; ANTERIOR DIVISION AB The anteroventral cochlear nucleus (AVCN) acts as the first relay center in the conduction of auditory information from the ear to the brain, and it probably performs a crucial role in sound localization. Auditory nerve input to the principal neurons of the AVCN, the spherical bushy cells, appears to be mediated by an excitatory amino acid such as glutamate, which acts at a specialized, large synaptic ending called an endbulb of Held. Presumably, endbulb synapses contain some specific combination of glutamate receptors to facilitate rapid neurotransmission of auditory signals. AMPA glutamate receptor composition at the endbulb synapses was examined with both light and electron microscope immunocytochemistry. Electron microscope localization of AMPA receptors was examined with two techniques, preembedding immunoperoxidase and postembedding immunogold, which provide maximum sensitivity and greatest accuracy, respectively. Dense and frequent labeling was seen with the AMPA receptor subunit antibodies GluR2/3 and GluR4, which were colocalized at the endbulb synapses. In contrast, immunolabeling with antibody to GluR2 was low. These data indicate that the major glutamate receptor at this synapse is an AMPA receptor made up mainly of GluR3 and GluR4 subunits. Receptors composed of these subunits dis; play properties, such as calcium permeability and rapid desensitization, that facilitate their specialized functions in auditory information processing. C1 NIDOCD, NIH, Bethesda, MD 20892 USA. Univ Oslo, N-0317 Oslo, Norway. RP Petralia, RS (reprint author), NIDOCD, NIH, 36-5D08,36 Convent Dr,MSC 4162, Bethesda, MD 20892 USA. NR 74 TC 84 Z9 84 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 FEB 1 PY 1998 VL 18 IS 3 BP 1148 EP 1160 PG 13 WC Neurosciences SC Neurosciences & Neurology GA YT570 UT WOS:000071620300034 PM 9437035 ER PT J AU Horky, LL Pluta, RM Boock, RJ Oldfield, EH AF Horky, LL Pluta, RM Boock, RJ Oldfield, EH TI Role of ferrous iron chelator 2,2 '-dipyridyl in preventing delayed vasospasm in a primate model of subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE vasospasm; subarachnoid hemorrhage; ferrous iron chelator; dipyridyl; cynomolgus monkey ID CEREBRAL VASOSPASM; NITRIC-OXIDE; AGENT DEFEROXAMINE; HEME OXYGENASE; BRAIN; OXYHEMOGLOBIN; RAT; ENDOTHELIUM; DAMAGE; CELLS AB Object. Oxyhemoglobin (HbO(2)) causes vasospasm after subarachnoid hemorrhage (SAH). The most likely spasmogenic component of HbO(2) is iron. Various iron chelators, such as deferoxamine, have prevented vasospasm in vivo with limited success. However, only chelators of iron in the ferric state have been studied in animal models of vasospasm after SAH. Because free radical formation requires the ferrous (Fe++) moiety and Fe++ is a potent binder of the vasodilator nitric oxide, the authors hypothesized that iron in the ferrous state causes vasospasm and that chelators of Fe++, such as 2,2'-dipyridyl, may prevent vasospasm. This study was undertaken to investigate the influence of 2,2'-dipyridyl on vasospasm after induction of SAH in a primate model. Methods. Twelve cynomolgus monkeys were randomly divided into two groups and then both groups underwent placement of an arterial autologous blood clot in the subarachnoid space around the right middle cerebral artery (MCA). The five animals in the control group received intravenously administered saline and the seven treated animals received intravenously administered chelator (2,2'-dipyridyl) for 14 days. Sequential arteriography for assessment of MCA diameter was performed before and on the 7th day after SAH. Conclusions. Prevention of cerebral vasospasm by means of treatment with continuous intravenous administration of 2,2'-dipyridyl is reported in a primate model of SAH. This result provides insight into the possible mechanism of delayed vasospasm after aneurysmal SAH and provides a potential preventive therapy for it. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D-37, Bethesda, MD 20892 USA. NR 51 TC 57 Z9 60 U1 1 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 1998 VL 88 IS 2 BP 298 EP 303 DI 10.3171/jns.1998.88.2.0298 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YT578 UT WOS:000071621100015 PM 9452239 ER PT J AU Lekstrom-Himes, JA Wang, KN Pesnicak, L Krause, PR Straus, SE AF Lekstrom-Himes, JA Wang, KN Pesnicak, L Krause, PR Straus, SE TI The comparative biology of latent herpes simplex virus type 1 and type 2 infections: latency-associated transcript promoter activity and expression in vitro and in infected mice SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE animal models; herpes simplex virus; latency-associated transcripts; virus latency; viral pathogenesis ID HUMAN TRIGEMINAL GANGLIA; NERVE GROWTH-FACTOR; GENITAL HERPES; MESSENGER-RNA; IN-VIVO; INDUCED REACTIVATION; SODIUM-BUTYRATE; PC12 CELLS; GENE; IDENTIFICATION AB HSV-1 and HSV-2 express abundant latency-associated transcripts (LATs) without which these viruses reactivate in animals inefficiently. To further characterize the importance of LATs to the comparative biology of latent HSV-1 and -2 infections, we assessed the relative activities of the viral LAT promoters in vitro using transient transfection assays? and the accumulation of LATs in vivo using a mouse ocular infection model. In vitro, the HSV-2 LAT promoter proved to be six to tenfold more potent than the HSV-1 promoter in driving reporter gene expression. In mice HSV-1 and -2 achieved comparable levels of virus replication in the eye, but HSV-2, grew to higher titers than HSV-1 in trigeminal ganglia and brain. Quantitative-competitive DNA and RNA (RT) PCR and in situ hybridization showed that ganglia latently infected with HSV-2 contained sixfold more copies of DNA (P=0.003), eightfold more LATS (P=0.01), and ninefold more LAT in situ-positive neurons. However, the numbers of LATs per latent genome were equivalent for both viruses. Although the HSV-2 LAT promoter is more potent than the HSV-1 promoter in transient expression assays, the accumulation of HSV-1 and 2 LATs in mouse trigeminal ganglia is comparable. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Virol, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10 Room 11N-228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 52 TC 6 Z9 6 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 1998 VL 4 IS 1 BP 27 EP 37 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA YZ339 UT WOS:000072244500002 PM 9531009 ER PT J AU Chen, CC Czerwiec, FS Feuillan, PP AF Chen, CC Czerwiec, FS Feuillan, PP TI Visualization of fibrous dysplasia during somatostatin receptor scintigraphy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE indium-111-pentetreotide; fibrous dysplasia; McCune-Albright syndrome; somatostatin ID MCCUNE-ALBRIGHT SYNDROME; IN-111 OCTREOTIDE SCINTIGRAPHY; GROWTH; BONE; ANALOG; CHONDROSARCOMA; PROTEIN; TUMORS; CELLS AB Somatostatin receptor scintigraphy was performed on a patient with McCune-Albright syndrome and acromegaly. No evidence of pituitary disease was found, but uptake of In-111-pentetreotide ws noted in areas of fibrous dysplasia This uptake was not changed after 6 mo of octreotide therapy. The patient's bone disease also remained stable. The possible implications of these findings are discussed. C1 NICHHD, Warren G Magnuson Clin Ctr, Dept Nucl Med, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chen, CC (reprint author), NICHHD, Warren G Magnuson Clin Ctr, Dept Nucl Med, NIH, Bldg 10-1C401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. NR 21 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 FEB PY 1998 VL 39 IS 2 BP 238 EP 240 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YX068 UT WOS:000072003200014 PM 9476926 ER PT J AU Underwood, BA AF Underwood, BA TI From research to global reality: The micronutrient story SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LOUISIANA DE vitamin A; iron; iodine; micronutrients; nutrition history ID VITAMIN-A; IODINE DEFICIENCY; IRON-DEFICIENCY; SUPPLEMENTATION; MORTALITY AB The professional life history of E. V. McCollum exemplifies how sound nutrition-related laboratory research was translated into practical realities that influenced individual and national nutrition-related decisions. Public health and educational programs emerging in the first third of this century improved health and nutritional well-being in the United Slates. Characteristics that surrounded pioneering efforts early in the century are similar to those that have reinvigorated global micronutrient concerns in the last third of the century. Sound community-oriented scientific research revealed the true consequences of iodine, vitamin A and iron micronutrient malnutrition. Repositioning the image of these three micronutrients from that of a clinical problem affecting relatively few to one with consequences for individual, national and global development affecting many more, and disseminating these facts through high-level political forums incited attention, commitment and actions. As in the early days of McCollum and his contemporaries, current nutrition scientists played a significant role, interacting with politically oriented counterparts, in laking micronutrient research to reality for improving health and quality of life globally. Lessons learned from the process, both past and present, should guide future nutrition-oriented endeavours in moving research to reality for betterment of global community health. C1 NEI, NIH, Bethesda, MD 20814 USA. RP Underwood, BA (reprint author), NEI, NIH, Bethesda, MD 20814 USA. NR 44 TC 16 Z9 18 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 1998 VL 128 IS 2 BP 145 EP 151 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YW531 UT WOS:000071945700001 PM 9446835 ER PT J AU Diamond, FB Shulman, DI Lacson, A Casadonte, J Favara, B AF Diamond, FB Shulman, DI Lacson, A Casadonte, J Favara, B TI Atypical dendritic cell-related histiocytosis with goiter and primary hypothyroidism SO JOURNAL OF PEDIATRICS LA English DT Article ID INVOLVEMENT AB Langerhans cell histiocytosis may be seen with goiter and histiocytic infiltration of the thyroid. We report a 21/2-year-old boy who had goiter and primary hypothyroidism develop, later had pulmonary disease, and died of neurologic involvement. Autopsy lesions suggested a transitional dendritic cell precursor of the epidermal Langerhans cell. Of the reported cases of Langerhans cell histiocytosis with goiter in children and adolescents, 82% were male when the relative incidence of Langerhans cell histiocytosis is two males to one female. C1 Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. NIH, Rocky Mt Labs, Hamilton, MT USA. Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Pathol, Tampa, FL 33612 USA. RP Diamond, FB (reprint author), Univ S Florida, All Childrens Hosp, 801 6th St S, St Petersburg, FL 33701 USA. NR 14 TC 11 Z9 11 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 FEB PY 1998 VL 132 IS 2 BP 357 EP 360 DI 10.1016/S0022-3476(98)70462-7 PG 4 WC Pediatrics SC Pediatrics GA ZA254 UT WOS:000072344800037 PM 9506658 ER PT J AU Darden, PM Reigart, JR Goyer, RA AF Darden, PM Reigart, JR Goyer, RA TI Lead: Let's be careful - Reply SO JOURNAL OF PEDIATRICS LA English DT Letter C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Darden, PM (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 1998 VL 132 IS 2 BP 376 EP 376 PG 1 WC Pediatrics SC Pediatrics GA ZA254 UT WOS:000072344800046 ER PT J AU Archer, RP Fontaine, J McCrae, RR AF Archer, RP Fontaine, J McCrae, RR TI Effects of two MMPI-2 validity scales on basic scale relations to external criteria SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID SOCIAL DESIRABILITY SCALES; K-CORRECTION AB Many clinicians have come to rely on the broad array of validity scales available on the MMPI and the MMPI-2. In this study, we evaluated the utility of 2 MMPI-2 validity scales, the K scale and VRIN scale, in a sample of 692 psychiatric inpatients. Specifically, the effects of the K-correction procedure and the exclusion of protocols based on VRIN scale elevations were examined on the relation between MMPI-2 basic clinical scales and external criteria including both self-report and clinician ratings of psychopathology. Results indicated that the K-correction procedure commonly used with the MMPI and MMPI-2 did not result in higher correlations with external criteria in comparison to non-K-corrected scores. In contrast, MMPI-2 protocols that produced VRIN T-score values greater than or equal to 80 generally produced lower correlations with patient self-reports and clinician ratings of psychopathology in comparison to protocols judged to be valid based on VRIN scale results. C1 Eastern Virginia Med Sch, Dept Psychiat, Norfolk, VA 23507 USA. NIA, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA. RP Archer, RP (reprint author), Eastern Virginia Med Sch, Dept Psychiat, 825 Fairfax Ave, Norfolk, VA 23507 USA. NR 39 TC 14 Z9 14 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 1998 VL 70 IS 1 BP 87 EP 102 DI 10.1207/s15327752jpa7001_6 PG 16 WC Psychology, Clinical; Psychology, Social SC Psychology GA ZP569 UT WOS:000073766600006 PM 9615425 ER PT J AU Li, P Vishnuvajjala, R Tabibi, SE Yalkowsky, SH AF Li, P Vishnuvajjala, R Tabibi, SE Yalkowsky, SH TI Evaluation of in vitro precipitation methods SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID INJECTION; DILUTION AB Four in vitro precipitation methods were tested and evaluated using flavopiridol and diazepam formulations. The methods include static serial dilution, dynamic injection, and dropwise addition with and without stirring. The results generated from these methods are comparable and complementary. The static serial dilution method is most effective in quantifying the amount of precipitation and more descriptive of the formation and redissolution of the precipitate than the others. The dynamic injection method, however, has its merit in more realistically simulating the physiological environment of drug-blood interaction near the injection sites. C1 Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NCI, Bethesda, MD 20892 USA. RP Yalkowsky, SH (reprint author), Univ Arizona, Coll Pharm, Dept Pharmaceut Sci, Tucson, AZ 85721 USA. NR 9 TC 19 Z9 19 U1 1 U2 3 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 FEB PY 1998 VL 87 IS 2 BP 196 EP 199 DI 10.1021/js970266c PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA YV917 UT WOS:000071877300011 PM 9519153 ER PT J AU Jeglitsch, G Rein, K Baden, DG Adams, DJ AF Jeglitsch, G Rein, K Baden, DG Adams, DJ TI Brevetoxin-3 (PbTx-3) and its derivatives modulate single tetrodotoxin-sensitive sodium channels in rat sensory neurons SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BRAIN SYNAPTOSOMES; CELLS; TOXINS; NA+; CURRENTS; RECEPTOR; BINDING AB Brevetoxin-3 (PbTx-3), produced by marine dinoflagellates (Ptychodiscus brevis), is a lipophilic 11-ring polyether molecule that binds with high affinity to site 5 of the voltage-sensitive sodium (Na+) channel. The effects of PbTx-3 and its derivatives were studied in cell-attached membrane patches on neurons dissociated from neonatal rat nodose ganglia by the path clamp technique, PbTx-3 (30-500 nM) produced a shift in activation to more negative membrane potentials whereby single-channel activity was observed under steady-state conditions (maintained depolarization at -50 mV). The unitary current-voltage relationship is linear, which exhibits a reversal potential of approximately +60 mV, Two unitary current amplitudes could be observed in the presence of PbTx-3, with slope conductances of 10.7 pS and 21.2 pS. PbTx-3 inhibits the inactivation of Na+ channels and prolongs the mean open time of these channels, Unitary Na+ currents could be blocked by 1 mu M tetrodotoxin (TXX) added to the pipette solution, which indicates that the single-channel currents are caused by the opening of TTX-sensitive Na+ channels. The PbTx-3 molecule is proposed to have multiple active centers (A-ring lactone, C-42 of R side chain) interacting with the Na+ channel binding site, Modification of the molecular structure of PbTx-3 at these centers produced derivatives (PbTx-6, 2,3,41,43-tetrahydro-PbTx-3, 2,3,27,28,41,43-hexahydro-PbTx-3 and 2,3-dihydro-PbTx-3 A-ring diol), which were less potent than PbTx-3 in producing similar effects on Na+ channel kinetics. PbTx-3 and its derivatives may provide insight into the mechanics of voltage-sensitive Na+ channel gating. C1 Univ Queensland, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia. Univ Miami, Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33101 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Adams, DJ (reprint author), Univ Queensland, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia. RI Adams, David/J-9125-2014 OI Adams, David/0000-0002-7030-2288 FU NIEHS NIH HHS [ES05705, ES05853] NR 25 TC 75 Z9 80 U1 3 U2 9 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 FEB PY 1998 VL 284 IS 2 BP 516 EP 525 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YW378 UT WOS:000071929100012 PM 9454792 ER PT J AU Dai, RK Pincus, MR Friedman, FK AF Dai, RK Pincus, MR Friedman, FK TI Molecular modeling of cytochrome P450 2B1: Mode of membrane insertion and substrate specificity SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE cytochrome P450; molecular modeling; membrane; substrate specificity ID PROTEIN SECONDARY STRUCTURE; SITE-DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURES; MICROSOMAL P450S; ACTIVE-SITE; AMINO-ACID; RAT; SEQUENCE; LIVER; 2D6 AB A molecular model of a mammalian membrane-bound cytochrome P450, rat P450 2B1, was constructed in order to elucidate its mode of attachment to the endoplasmic reticulum and the structural basis of substrate specificity. The model was primarily derived from the structure of P450BM-3, which as a class II P450 is the most functionally similar P450 of known structure. However, model development was also guided by the conserved core regions of P450cam and P450terp. To optimally align the P450 2B1 and P450BM-3 sequences, multiple alignment was performed using sequences of five P450s in the II family, followed by minor adjustments on the basis of secondary structure predictions. The resulting P450 2B1 homology model structure was refined by molecular dynamics heating, equilibration, simulation, and energy minimization. The model suggests that the F-G loop serves as both a hydrophobic membrane anchor and entrance channel for hydrophobic substrates from the membrane to the P450 active site. To assess the mode of substrate binding, benzphetamine, testosterone, and benzo[a]pyrene were docked into the active site. The hydrophobic substrate-binding pocket is consistent with the preferences of this P450 toward hydrophobic substrates, while the presence of an acidic Glu-105 in this pocket is consistent with the preference of this P450 for the cationic substrate benzphetamine. This model is thus consistent with several known experimental properties of this P450, such as membrane attachment and substrate selectivity. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. SUNY Hlth Sci Ctr, Dept Pathol, New York, NY 11239 USA. RP Friedman, FK (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. RI Friedman, Fred/D-4208-2016 NR 42 TC 30 Z9 31 U1 0 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD FEB PY 1998 VL 17 IS 2 BP 121 EP 129 DI 10.1023/A:1022527432229 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB357 UT WOS:000072463600006 PM 9535274 ER PT J AU Selbie, WS Zhang, L Levine, WS Ludlow, CL AF Selbie, WS Zhang, L Levine, WS Ludlow, CL TI Using joint geometry to determine the motion of the cricoarytenoid joint SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article AB Facet surfaces of the cricoarytenoid joints from two cadaver larynges were digitized. The data were used to compute the optimal axis of rotation for each of the joints in the sense that the computed axis minimized the variance of the joint gap over the full range of joint motion. The optimal axis corresponded to a rocking motion of the arytenoid on the corresponding cricoid. This motion was consistent with experimental data from digitized recordings of vocal fold movement. Using the rigid laryngoscopic view, a similarity in vocal process movement, over the range in motion, between the rocking axis and the vertical axis described in the literature was found, resolving the controversy between two conflicting views of motion of the vocal processes. (C) 1998 Acoustical Society of America. [S0001-4966(98)04902-9]. C1 Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, Bethesda, MD 20892 USA. Univ Maryland, Dept Elect Engn, College Pk, MD 20742 USA. RP Selbie, WS (reprint author), Natl Inst Deafness & Other Commun Disorders, Voice & Speech Sect, 10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 FU NIDCD NIH HHS [N01-DC-1-2116] NR 23 TC 20 Z9 20 U1 0 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 1998 VL 103 IS 2 BP 1115 EP 1127 DI 10.1121/1.421223 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA YX461 UT WOS:000072042300050 PM 9479765 ER PT J AU Giedd, JN Swedo, SE Lowe, CH Rosenthal, NE AF Giedd, JN Swedo, SE Lowe, CH Rosenthal, NE TI Case series: Pediatric seasonal affective disorder. A follow-up report SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE seasonal affective disorder; pediatric disorders ID CHILDREN; ADOLESCENTS AB Six subjects who as children had received a diagnosis of seasonal affective disorder consented to participate in a 7-year follow-up study. Structured and semistructured interviews were conducted to assess the course of illness, response to treatment, and current clinical state. Seasonal patterns of symptoms and response to light therapy remained relatively stable over a 7-year period. Two subjects were using adjunctive fluoxetine. Seasonal affective disorder can occur in children and adolescents, responds to light therapy, and should be considered in the differential diagnosis of pediatric affective symptoms or cyclic school performance. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr MSC 1600, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 9 TC 4 Z9 5 U1 2 U2 2 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 FEB PY 1998 VL 37 IS 2 BP 218 EP 220 DI 10.1097/00004583-199802000-00015 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YW320 UT WOS:000071922100015 PM 9473919 ER PT J AU Kumra, S Jacobsen, LK Lenane, M Smith, A Lee, P Malanga, CJ Karp, BI Hamburger, S Rapoport, JL AF Kumra, S Jacobsen, LK Lenane, M Smith, A Lee, P Malanga, CJ Karp, BI Hamburger, S Rapoport, JL TI Case series: Spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE childhood-onset schizophrenia; tardive dyskinesia; withdrawal dyskinesia; extrapyramidal side effects; neuroleptics ID TARDIVE-DYSKINESIA; CLOZAPINE; HALOPERIDOL; ADOLESCENTS; CHILDREN; RISK AB Objective: Neuroleptic-treated pediatric patients with childhood-onset schizophrenia (COS) are at risk for developing extrapyramidal side effects and involuntary movement disorders. A preliminary examination of the incidence of withdrawal dyskinesias (WD), tardive dyskinesia (TD), and extrapyramidal side effects in these patients is presented. Method: Thirty-four COS patients (mean age +/- SD, 14.2 +/- 2.1 years) were examined for TD using the Abnormal Involuntary Movements Scale and for extrapyramidal side effects using the Simpson-Angus Neurologic Rating Scale, after a 14- to 28-day drug-free period (n = 33), at week 6 of treatment and 2 to 4 years after completion of the study (n = 14). The mean (+/- SD) number of months of prior neuroleptic exposure for the group was 22.4 (15.0) months. Results: Seventeen (50%) of 34 patients were noted to have either WD or TD at some point during their participation in the studies. The majority of patients experienced WD that were mainly in the orofacial region, transient in nature, and diminished with haloperidol and clozapine. Patients with TD/WD had greater levels of premorbid impairment (p = .02), increased severity of positive symptoms of schizophrenia (p < .01), and a trend toward more months of neuroleptic exposure (p = .10, one-tailed). Conclusions: A high proportion of COS patients were found to have TD/WD. The majority of these abnormal movements were not severe and generally improved over time. TD/WD in COS appears to be associated with greater premorbid impairment, severity of illness, and duration of neuroleptic exposure. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 6N240,10 Ctr Dr MSC1600, Bethesda, MD 20892 USA. OI Malanga, C.J./0000-0003-4808-3995 NR 43 TC 33 Z9 33 U1 4 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 FEB PY 1998 VL 37 IS 2 BP 221 EP 227 DI 10.1097/00004583-199802000-00016 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YW320 UT WOS:000071922100016 PM 9473920 ER PT J AU Thirumurti, V Shou, M Hodge, E Goncalves, L Epstein, SE Lazarous, DF Unger, EF AF Thirumurti, V Shou, M Hodge, E Goncalves, L Epstein, SE Lazarous, DF Unger, EF TI Lack of efficacy of intravenous basic fibroblast growth factor in promoting myocardial angiogenesis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 54A EP 54A DI 10.1016/S0735-1097(97)83941-1 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600210 ER PT J AU Shirani, J Lee, J Kitsiou, AN Srinivasan, G Quigg, RJ Pick, R Bacharach, SL Ohler, L Miller-Davis, C Dilsizian, V AF Shirani, J Lee, J Kitsiou, AN Srinivasan, G Quigg, RJ Pick, R Bacharach, SL Ohler, L Miller-Davis, C Dilsizian, V TI Histomorphologic profile myocardial segments with normal thallium activity in chronic ischemic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 31 IS 2 SU A BP 84A EP 84A DI 10.1016/S0735-1097(97)84074-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600343 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Interaction between nitric oxide and endothelin in the regulation of vascular tone in the human forearm SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 86A EP 86A DI 10.1016/S0735-1097(97)84081-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600350 ER PT J AU Thirumurti, V Shou, M Hodge, EA Goncalves, L Epstein, SE Unger, EF AF Thirumurti, V Shou, M Hodge, EA Goncalves, L Epstein, SE Unger, EF TI Effect of digitalis glycosides on collateral development in ischemic myocardium SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 105A EP 105A DI 10.1016/S0735-1097(97)84164-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600433 ER PT J AU Baek, SH Stoll, HP Szabo, A Keefer, LK Hrabie, J March, KL AF Baek, SH Stoll, HP Szabo, A Keefer, LK Hrabie, J March, KL TI Pharmacokinetics of agent distribution from the pericardial space: Effects of agent size and validation of a mathematical model for epicardial penetration SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. NIH, Frederick, MD USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 108A EP 109A DI 10.1016/S0735-1097(97)84178-2 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600447 ER PT J AU Philbin, EF Hunsberger, S Garg, R Kouz, S Lader, E Thadani, U Weeks, A McSherry, F Silver, MA AF Philbin, EF Hunsberger, S Garg, R Kouz, S Lader, E Thadani, U Weeks, A McSherry, F Silver, MA TI Did clinical features distinguish low from normal ejection fraction in chronic heart failure in the DIG trial? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Henry Ford Hosp, Detroit, MI 48202 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 116A EP 117A DI 10.1016/S0735-1097(97)84212-X PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600481 ER PT J AU Freed, LA Benjamin, EJ Levy, D Larson, MG Evans, JC Fuller, DL Lehman, B Levine, RA AF Freed, LA Benjamin, EJ Levy, D Larson, MG Evans, JC Fuller, DL Lehman, B Levine, RA TI Is mitral valve prolapse more benign in a general population? Reevaluation of echo features in the framingham heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 122A EP 122A DI 10.1016/S0735-1097(97)84235-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600504 ER PT J AU Rywik, TM Vaitkevicius, P Nussbacher, A O'Connor, FC Lakatta, EG Fleg, JL AF Rywik, TM Vaitkevicius, P Nussbacher, A O'Connor, FC Lakatta, EG Fleg, JL TI Are there differences in arterial stiffness between normotensive whites and African Americans? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 FEB PY 1998 VL 31 IS 2 SU A BP 129A EP 129A DI 10.1016/S0735-1097(97)84262-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600531 ER PT J AU Dries, DL Domanski, MJ Stevenson, LW AF Dries, DL Domanski, MJ Stevenson, LW TI Frequency and adverse impact of mild renal dysfunction in stable heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 154A EP 154A DI 10.1016/S0735-1097(97)84376-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600645 ER PT J AU Singh, J Larson, MG O'Donnell, CJ Tsuji, H Levy, D AF Singh, J Larson, MG O'Donnell, CJ Tsuji, H Levy, D TI Heritability of heart rate variability: The framingham heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Framingham Heart Dis Epidemiol Study, Boston, MA 02118 USA. NHLBI, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 169A EP 169A DI 10.1016/S0735-1097(97)84446-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600710 ER PT J AU Lauer, MS Larson, MG Evans, JC Levy, D AF Lauer, MS Larson, MG Evans, JC Levy, D TI Association of left ventricular dilatation and hypertrophy with chronotropic incompetence: The framingham heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 170A EP 170A DI 10.1016/S0735-1097(97)84449-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600713 ER PT J AU Prasad, A Zalos, G Schenke, WH Amegashie, E Kitsiou, AN Quyyumi, AA AF Prasad, A Zalos, G Schenke, WH Amegashie, E Kitsiou, AN Quyyumi, AA TI Coronary vascular effects of physical exercise and dobutamine: Comparison of physiologic and pharmacologic stressors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 179A EP 179A DI 10.1016/S0735-1097(97)84483-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600747 ER PT J AU Koh, KK Bui, MN Hathaway, L Cannon, RO AF Koh, KK Bui, MN Hathaway, L Cannon, RO TI Beneficial effect of estrogen therapy on fibrinolysis is independent of changes in low-density lipoprotein levels SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 194A EP 194A DI 10.1016/S0735-1097(97)84550-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600814 ER PT J AU Mathew, J Hunsberger, S Fleg, J McSherry, F Williford, W Yusuf, S AF Mathew, J Hunsberger, S Fleg, J McSherry, F Williford, W Yusuf, S TI Incidence, predictive factors and prognostic significance of supraventricular tachyarrhythmias in congestive heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Cook Cty Hosp, Digitalis Investigat Grp, Chicago, IL 60612 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 218A EP 218A DI 10.1016/S0735-1097(97)84654-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600918 ER PT J AU Dries, DL Gersh, BJ Domanski, MJ Stevenson, LW AF Dries, DL Gersh, BJ Domanski, MJ Stevenson, LW TI Atrial fibrillation in mild to moderate heart failure is independently associated with progressive pump failure death SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 FEB PY 1998 VL 31 IS 2 SU A BP 219A EP 219A DI 10.1016/S0735-1097(97)84656-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920600920 ER PT J AU Fananapazir, L McAreavey, D AF Fananapazir, L McAreavey, D TI Therapeutic options in patients with obstructive hypertrophic cardiomyopathy and severe drug-refractory symptoms SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID MITRAL-VALVE REPLACEMENT; NONSURGICAL MYOCARDIAL REDUCTION; OPERATIVE TREATMENT; MYOTOMY-MYOMECTOMY; MYECTOMY; RELIEF; IMPROVEMENT; PROGNOSIS C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Fananapazir, L (reprint author), NHLBI, NIH, 10 Ctr Dr MSC 1650,Room 7B-14,Bldg 10, Bethesda, MD 20892 USA. EM fananapa@gwgate.nhlbi.nih.gov NR 48 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 BP 259 EP 264 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YV175 UT WOS:000071796900003 PM 9462564 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Improved endothelium-dependent vasodilation after blockade of endothelin receptors in patients with essential hypertension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 262A EP 262A DI 10.1016/S0735-1097(97)84849-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601113 ER PT J AU Atiga, WL Fananapazir, L McAreavey, D Calkins, H Berger, RD AF Atiga, WL Fananapazir, L McAreavey, D Calkins, H Berger, RD TI A new index of repolarization lability detects mutation-specific differences in hypertrophic cardiomyopathy patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 292A EP 292A DI 10.1016/S0735-1097(97)84982-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601246 ER PT J AU Li, XK Jones, M Shiota, T Delabays, A Sahn, DJ AF Li, XK Jones, M Shiota, T Delabays, A Sahn, DJ TI Lack of dynamic change in effective aortic regurgitant orifice area measured by direct flow convergence surface area from 3D flow images: A chronic animal study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 298A EP 298A DI 10.1016/S0735-1097(97)85004-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601268 ER PT J AU Freed, LA Levy, D Levine, RA Larson, MG Evans, JC Fuller, DL Lehman, B Benjamin, AJ AF Freed, LA Levy, D Levine, RA Larson, MG Evans, JC Fuller, DL Lehman, B Benjamin, AJ TI Mitral valve prolapse reconsidered: Prevalence and epidemiology in the framingham heart study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 303A EP 303A DI 10.1016/S0735-1097(97)85026-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601290 ER PT J AU Doanes, AM Irani, K Goldschmidt-Clermont, PJ Finkel, T AF Doanes, AM Irani, K Goldschmidt-Clermont, PJ Finkel, T TI A requirement for rac1 in platelet-derived growth factor stimulated migration SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 357A EP 357A DI 10.1016/S0735-1097(97)85260-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601522 ER PT J AU Zhu, J Shearer, GM Pinto, LA Marincola, FM Quyyumi, AA Prasad, A Mincemoyer, R Epstein, SE AF Zhu, J Shearer, GM Pinto, LA Marincola, FM Quyyumi, AA Prasad, A Mincemoyer, R Epstein, SE TI Immunodominant cellular versus humoral responses to cytomegalovirus: Relation to high levels of C-reactive protein and susceptibility to coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 1998 VL 31 IS 2 SU A BP 390A EP 390A DI 10.1016/S0735-1097(97)85399-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601661 ER PT J AU Hees, PS Fleg, JL Weiss, JL Bosley, SL Lakatta, EG Shapiro, EP AF Hees, PS Fleg, JL Weiss, JL Bosley, SL Lakatta, EG Shapiro, EP TI Age-associated LV remodeling in normal men and women detected by 3D MRI SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, NIA, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 FEB PY 1998 VL 31 IS 2 SU A BP 406A EP 406A DI 10.1016/S0735-1097(97)85466-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601728 ER PT J AU Kolodgie, FD Luna, RE Burke, AP Horiba, K Ferrans, VJ Stetler-Stevenson, WG Virmani, R AF Kolodgie, FD Luna, RE Burke, AP Horiba, K Ferrans, VJ Stetler-Stevenson, WG Virmani, R TI Differential expression of matrix metalloproteinases in coronary thrombosis: Plaque rupture and erosion SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 31 IS 2 SU A BP 419A EP 419A DI 10.1016/S0735-1097(97)85524-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601786 ER PT J AU Koh, KK Horne, MK Cannon, RO AF Koh, KK Horne, MK Cannon, RO TI Fibrinolytic potentiation by estrogen therapy at conventional dosage in postmenopausal women is independent of coagulation pathway activation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 442A EP 442A DI 10.1016/S0735-1097(97)87917-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601884 ER PT J AU Prasad, A Zalos, G Mincemoyer, R Schenke, WH Quyyumi, AA AF Prasad, A Zalos, G Mincemoyer, R Schenke, WH Quyyumi, AA TI Nitric oxide activity in arterial and venous bypass grafts SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 460A EP 460A DI 10.1016/S0735-1097(97)88003-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601970 ER PT J AU Cardillo, C Nambi, SS Kilcoyne, CM Quon, MJ Panza, JA AF Cardillo, C Nambi, SS Kilcoyne, CM Quon, MJ Panza, JA TI Local hyperinsulinemia increases endothelin activity in the human forearm circulation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 1 Z9 1 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 FEB PY 1998 VL 31 IS 2 SU A BP 507A EP 507A DI 10.1016/S0735-1097(97)88209-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602176 ER PT J AU Devereux, RB Roman, MJ Lee, ET Welty, TK Fabsitz, RR Rhoades, ER Crawford, A Howard, BV AF Devereux, RB Roman, MJ Lee, ET Welty, TK Fabsitz, RR Rhoades, ER Crawford, A Howard, BV TI Differences in echocardiographic findings and systemic hemodynamics among non-diabetic American Indians in different regions: The Strong Heart Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Cornell Univ, Med Ctr, New York, NY 10021 USA. Univ Oklahoma, Oklahoma City, OK USA. Aberdeen Area Indian Hlth Serv, Rapid City, SD USA. NHLBI, Bethesda, MD 20892 USA. Medlant Res Inst, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 526A EP 526A DI 10.1016/S0735-1097(97)88291-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602258 ER PT J AU Narayan, KMV Hanson, RL Smith, CJ Nelson, RG Gyenizse, SB Pettitt, DJ Knowler, WC AF Narayan, KMV Hanson, RL Smith, CJ Nelson, RG Gyenizse, SB Pettitt, DJ Knowler, WC TI Dietary calcium and blood pressure in a native American population SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Epidemiologic-Research CY JUN, 1994 CL MIAMI, FLORIDA SP Soc Epidemiol Res DE blood pressure; hypertension; calcium; dietary; diabetes mellitus; Pima Indians ID PIMA-INDIANS; DIABETES-MELLITUS; UNITED-STATES; ORAL CALCIUM; HYPERTENSION; ASSOCIATION; POTASSIUM; WOMEN; SUPPLEMENTATION; METAANALYSIS AB Objective: To assess the relationship between dietary calcium and blood pressure. Methods: Cross-sectional study of 404 adult Pima Indians of Arizona. Dietary variables were assessed by the 24-hour recall. Hypertension (HTN) was defined as systolic blood pressure (SEP) greater than or equal to 140 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg or drug treatment. Results: Controlled for age and sex, dietary calcium intake was higher in subjects with HTN than in those without (p<0.01), and higher dietary calcium was associated with a higher prevalence of HTN (odds ratio comparing highest with lowest tertile group of calcium=2.6, 95% CI 1.4-4.8). Age-sex-adjusted mean DBP in low, middle and high tertiles of calcium was 74, 76, and 79 mmHg, respectively (p<0.001). SEP was not significantly different in the three tertiles (p=0.07). Multiple regression analyses that controlled for age, sex, body mass index, sodium, potassium and alcohol also suggested a positive association between DBP and dietary calcium (p<0.01), an association which was stronger at higher glucose concentrations (p<0.01 for the calcium-glucose interaction). Conclusion: In Pima Indians, a population with a high incidence of diabetes, the inverse association between dietary calcium and blood pressure reported in other populations was not found. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, Diabet & Arthit Epidemiol Sect, Phoenix, AZ USA. RP Narayan, KMV (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, Diabet & Arthit Epidemiol Sect, Phoenix, AZ USA. RI Nelson, Robert/B-1470-2012; Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [N01-DK-6-2285] NR 43 TC 5 Z9 5 U1 1 U2 1 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD FEB PY 1998 VL 17 IS 1 BP 59 EP 64 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YV639 UT WOS:000071847900011 PM 9477391 ER PT J AU Dionne, RA Gordon, SM McCullagh, LM Phero, JC AF Dionne, RA Gordon, SM McCullagh, LM Phero, JC TI Assessing the need for anesthesia and sedation in the general population SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DENTAL FEAR; OLDER ADULTS; CONSEQUENCES; PREVALENCE; AVOIDANCE AB The authors used a national telephone survey to examine the relationship between dental anxiety and the use of pain and anxiety control measures in the general population, Nearly 30 percent of respondents reported being somewhat nervous, very nervous or terrified about going to the dentist. There was a threefold difference between the reported use of anesthesia and sedation and respondents' preference for these treatment modalities. These data suggest that fear of dentistry is still prevalent and that patients who are fearful would seek oral health care more regularly if general anesthesia or conscious sedation were more readily available. C1 NIDR, Clin Pharmacol Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Anesthesia, Cincinnati, OH 45221 USA. RP Dionne, RA (reprint author), NIDR, Clin Pharmacol Unit, Pain & Neurosensory Mechanisms Branch, NIH, 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. NR 20 TC 35 Z9 36 U1 1 U2 5 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 FEB PY 1998 VL 129 IS 2 BP 167 EP 173 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YW277 UT WOS:000071916200011 PM 9495047 ER PT J AU Slavkin, HC AF Slavkin, HC TI Biomimicry, dental implants and clinical trials SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2280,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 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 FEB PY 1998 VL 129 IS 2 BP 226 EP 230 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YW277 UT WOS:000071916200021 PM 9495057 ER PT J AU Kim, SK AF Kim, SK TI Dietetics professionals and women's health research at the National Institutes of Health SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID DISEASE C1 NIH, Nutr & Metab Sci Initial Review Grp, Ctr Sci Review, Bethesda, MD 20892 USA. NIH, Endocrinol & Reprod Sci Initial Review Grp, Ctr Sci Review, Bethesda, MD 20892 USA. NIH, Nutr Study Sect, Ctr Sci Review, Bethesda, MD 20892 USA. RP Kim, SK (reprint author), NIH, Nutr & Metab Sci Initial Review Grp, Ctr Sci Review, Rockledge 2,Room 6158,MSC 7892, Bethesda, MD 20892 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 1998 VL 98 IS 2 BP 133 EP 136 DI 10.1016/S0002-8223(98)00035-2 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA YU947 UT WOS:000071772600007 PM 12515411 ER PT J AU Maggi, S Langlois, JA Minicuci, N Grigoletto, F Pavan, M Foley, DJ Enzi, G AF Maggi, S Langlois, JA Minicuci, N Grigoletto, F Pavan, M Foley, DJ Enzi, G TI Sleep complaints in community-dwelling older persons: Prevalence, associated factors, and reported causes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID GENERAL-PRACTICE ATTENDERS; MINI-MENTAL-STATE; ELDERLY PERSONS; RISK-FACTORS; SELF-REPORT; INSOMNIA; MORTALITY; AGE; POPULATION; DISORDERS AB OBJECTIVES: To determine the prevalence rates of self-reported sleep complaints and their association with health-related factors. DESIGN: A cross-sectional study. SETTING: People living in the community. PARTICIPANTS: A total of 2398 noninstitutionalized individuals, aged 65 years and older, residing in the Veneto region, northeast Italy. MEASUREMENTS: Odds ratios for the association of sleep complaints with potential risk factors. RESULTS: The prevalence of insomnia was 36% in men and 54% in women, with increased risks for women (odds ratio (OR) = 1.69, 95% CI: 1.3-2.1), depression (OR = 1.93, 95% CI, 1.5-2.5), and regular users of sleep medications (OR = 5.58, 95% CI, 4.3-7.3). About 26% of men and 21% of women reported no sleep complaints. Night awakening, reported by about two-thirds of the participants, was the most common sleep disturbance. Women and regular users of sleep medications had significantly increased odds for insomnia and for not feeling rested upon awakening in the morning. Depressive symptomatology was more strongly associated with insomnia and night awakening than with awakening not rested, whereas physical disability was more strongly associated with awakening not rested than with the other two sleep disturbances. CONCLUSION: Our findings show that sleep complaints, highly common among older Italians, are associated with a wide range of medical conditions and with the use of sleep medications. Further longitudinal studies are needed to investigate the causes and the negative health consequences of sleep disturbances to improve both the diagnosis and treatment. C1 Univ Padua, Inst Hyg, I-35131 Padua, Italy. Univ Padua, Inst Internal Med, I-35131 Padua, Italy. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Natl Res Council, Project Aging, Florence, Italy. RP Maggi, S (reprint author), Univ Padua, Inst Hyg, Via Loredan 18, I-35131 Padua, Italy. RI MINICUCI, NADIA/D-5237-2016 OI MINICUCI, NADIA/0000-0002-0970-6531 NR 40 TC 131 Z9 139 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 1998 VL 46 IS 2 BP 161 EP 168 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YW198 UT WOS:000071908300006 PM 9475443 ER PT J AU Lasser, RA Sunderland, T AF Lasser, RA Sunderland, T TI Newer psychotropic medication use in nursing home residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ANTIPSYCHOTIC DRUG-USE; PHARMACOLOGICAL TREATMENT; PSYCHOACTIVE MEDICATION; NEUROLEPTIC TREATMENT; RANDOMIZED TRIAL; ELDERLY PATIENTS; CARE SETTINGS; DEPRESSION; DEMENTIA; PRESCRIPTIONS AB OBJECTIVE: To evaluate the use of newer psychotropic agents in nursing home residents in the era of new Health Care Financing Administration (HCFA) guidelines. DESIGN: Retrospective chart review of referrals to an on-site geriatric psychiatry service in seven Eastern Massachusetts facilities during 1995-1996. SUBJECTS: The 298 patients examined included 226 women and 72 men with a mean (SD) age of 81.9 (9.4) years. MEASUREMENTS: Patient demographics, psychiatric history and medical diagnoses, prescribed medication information, and mental status examination results were recorded systematically, Descriptive statistics of demographics, medication use, and dosing were generated, and comparative analyses were performed by chi-square, ANOVA, and Tukey's tests RESULTS: Overall, 69% of subjects were taking at least one psychotropic medication. Although benzodiazepines (32%) were used by a large portion of subjects, antidepressants (42%) were the most commonly prescribed psychotropic, with 53% taking serotonin reuptake inhibitors, The atypical antipsychotic, risperidone, accounted for more than 30% of antipsychotic prescriptions, Low rates of anticholinergic use and low doses and rates of tricyclic antidepressant use were found in Alzheimer's disease patients. Mean dosing of the psychotropic agents fell within HCFA guidelines. CONCLUSIONS: Newer-generation psychotropics have had a significant impact on the prescribing practices of primary physicians in treating nursing home residents. Of clinical importance is the high rate of antidepressant use in a population that has traditionally received inadequate pharmacotherapy for depression. More studies are needed to examine a shift to the use of other psychotropic drugs in this population in the post-HCFA area. C1 NIMH, Ctr Clin, NIH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Lasser, RA (reprint author), NIMH, Ctr Clin, NIH, Geriatr Psychiat Branch, Bldg 10,Rm 3D41,10 Ctr Dr,MSC 1264, Bethesda, MD 20892 USA. NR 72 TC 45 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 1998 VL 46 IS 2 BP 202 EP 207 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YW198 UT WOS:000071908300013 PM 9475450 ER PT J AU Simons-Morton, DG AF Simons-Morton, DG TI Dose-response relationship of physical activity and cardiovascular disease risk SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID HEALTH; EXERCISE; PROGRAMS; WALKING C1 NHLBI, Bethesda, MD 20892 USA. RP Simons-Morton, DG (reprint author), NHLBI, Bethesda, MD 20892 USA. NR 12 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 1998 VL 46 IS 2 BP 238 EP 240 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YW198 UT WOS:000071908300019 PM 9475456 ER PT J AU Khan, KS Locatis, C AF Khan, KS Locatis, C TI Searching through cyberspace: The effects of link display and link density on information retrieval from hypertext on the World Wide Web SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article ID HYPERMEDIA; ENVIRONMENT; KNOWLEDGE AB This study investigated information retrieval from hypertext on Internet's World Wide Web (WWW), Significant main and interaction effects were found for both link density (number of links per display) and display format (in paragraphs or lists) on search performance, Low link densities displayed in list format produced the best overall results, in terms of search accuracy, search time, number of links explored, and search task prioritization. Lowell densities affected user ability to prioritize search tasks:and produced more accurate searches, while list displays positively affected all aspects of searching except task prioritization. The performance of novices and experts, in terms of their previous experience browsing hypertext on the WWW, was compared. Experts performed better, mostly because of their superior task prioritization. C1 Natl Lib Med, Cognit Sci Branch, Bethesda, MD 20894 USA. RP Khan, KS (reprint author), Natl Lib Med, Cognit Sci Branch, Mail Stop 43,8600 Rockville Pike, Bethesda, MD 20894 USA. EM kkhan@uiuc.edu; locatis@nlm.nih.gov NR 30 TC 35 Z9 34 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD FEB PY 1998 VL 49 IS 2 BP 176 EP 182 DI 10.1002/(SICI)1097-4571(1998)49:2<176::AID-ASI7>3.0.CO;2-W PG 7 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA YT565 UT WOS:000071619800007 ER PT J AU Jeyarajah, S Parker, CE Sumner, MT Tomer, KB AF Jeyarajah, S Parker, CE Sumner, MT Tomer, KB TI Matrix-assisted laser desorption ionization mass spectrometry mapping of human immunodeficiency virus-gp120 epitopes recognized by a limited polyclonal antibody SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID VIRUS TYPE-1 GP120; ENVELOPE GLYCOPROTEIN GP120; MONOCLONAL-ANTIBODY; HTLV-III; NUCLEOTIDE-SEQUENCE; CD4 RECEPTOR; AIDS VIRUS; PROTEIN; HIV-1; IDENTIFICATION AB In this study we have applied epitope excision and epitope extraction strategies, combined with matrix assisted laser desorption/ionization mass spectrometry, to determine the fine structure of epitopes recognized by a polyclonal antibody to human immunodeficiency virus envelope glycoprotein gp120. This is the first application of this approach to epitope mapping on a large, heavily glycosylated protein. Ln the epitope excision method, gp120 in the native form is first bound to the antibody immobilized on sepharose beads and cleaved with endoproteinase enzymes. In the epitope extraction method, the gp120 was first proteolytically cleaved and then allowed to react with the immobilized antibody. The fragments that remain bound to the antibody, after repeated washing to remove the unbound peptides, contain the antigenic region that is recognized by the antibody, and the bound peptides in both methods can be characterized by direct analysis of the immobilized antibody by matrix assisted laser desorption ionization/mass spectrometry. In this study we have carried out epitope excision and extraction experiments with three different enzymes and have identified residues 472-478 as a major epitope. In addition, antigenic regions containing minor epitopes have also been identified. 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. EM tomer@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 41 TC 34 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD FEB PY 1998 VL 9 IS 2 BP 157 EP 165 DI 10.1016/S1044-0305(97)00247-X PG 9 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA YT841 UT WOS:000071650400007 PM 9679595 ER PT J AU Pass, HI Temeck, BK Kranda, K Steinberg, SM Feuerstein, IR AF Pass, HI Temeck, BK Kranda, K Steinberg, SM Feuerstein, IR TI Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-08, 1997 CL WASHINGTON, D.C. SP Amer Assoc Thorac Surg AB Objectives: Our objective was to analyze the impact of preoperative and postresection solid tumor volumes on outcomes in 47 of 48 consecutive patients undergoing resection for malignant pleural mesothelioma who were treated prospectively and randomized to photodynamic therapy or no photodynamic therapy. Methods: From July 1993 to June 1996, 48 patients with malignant pleural mesothelioma had cytoreductive debulking to 5 mm or less residual tumor by extrapleural pneumonectomy (n = 25) or pleurectomy/decortication (n = 23). Three-dimensional computed tomographic reconstructions of preresection and postresection solid tumor were prospectively performed and the disease was staged postoperatively according to the new International Mesothelioma Interest Group staging. Results: Median survival for all patients is 14.4 months (extrapleural pneumonectomy, 11 months; pleurectomy/decortication, 22 months; p(2) = 0.07), Median survival for preoperative volume less than 100 was 22 months versus 11 months if more than 100 cc, p(2) = 0.03, Median survival for postoperative volume less than 9 cc was 25 months versus 9 months if more than 9 cc, p(2) = 0.0002. Thirty-two of forty-seven (68%) had positive N1 or N2 nodes. Tumor volumes associated with negative nodes were significantly smaller (median 51 cc) than those with positive nodes (median 166 cc, p(2) = 0.01), Progressively higher stage was associated with higher median preoperative volume: stage I, 4 cc; stage II, 94 cc; stage III, 143 cc; stage IV, 505 cc; p(2) = 0.007 for stage I versus II versus III versus IV. Patients with preoperative tumor volumes greater than 52 cc had shorter progression-free intervals (8 months) than those 51 cc or less (11 months; p(2) = 0.02). Conclusions: Preresection tumor volume is representative of T status in malignant pleural mesothelioma and can predict overall and progression-free survival, as well as postoperative stage. Large volumes are associated, with nodal spread, and postresection residual tumor burden may predict outcome. C1 NCI, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Pass, HI (reprint author), Harper Grace Hosp, 3990 John R,Suite 2102, Detroit, MI 48201 USA. NR 11 TC 86 Z9 90 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 1998 VL 115 IS 2 BP 310 EP 317 DI 10.1016/S0022-5223(98)70274-0 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA YW395 UT WOS:000071931000011 PM 9475525 ER PT J AU Muszynski, KW Ohashi, T Hanson, C Ruscetti, SK AF Muszynski, KW Ohashi, T Hanson, C Ruscetti, SK TI Both the polycythemia- and anemia-inducing strains of friend spleen focus-forming virus induce constitutive activation of the Raf-1/mitogen-activated protein kinase signal transduction pathway SO JOURNAL OF VIROLOGY LA English DT Article ID ERYTHROPOIETIN RECEPTOR; C-MYC; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC PRECURSORS; CELL-PROLIFERATION; ERYTHROID-CELLS; GENE-EXPRESSION; ENVELOPE GENE; MAP KINASES; IN-VIVO AB The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). In an attempt to understand how the virus causes Epo independence, we have been studying signal transduction pathways activated by Epo to determine if SFFV exerts its biological effects by constitutively activating any of these pathways in the absence of Epo. We previously demonstrated that Stat proteins, the downstream components of the Epo-induced Jak-Stat pathway, are constitutively activated in SFFV-infected cells. In this study, we demonstrate that SFFV also activates Raf-1, MEK and mitogen-activated protein (MAP) kinase, the downstream components of the Raf-1/MAP kinase pathway. This pathway was activated in cells infected with the polycythemia-inducing strain of SFFV, which induces both proliferation and differentiation of erythroid cells in the absence of Epo, as well as in cells infected,vith the anemia-inducing strain of the virus, which still require Epo for differentiation. Inhibition of Raf-l by using antisense oligonucleotides led to a partial inhibition of the Epo-independent proliferation of SFFV-infected cells. Expression of the transcription factors c-Jun and JunB, but not c-Fos, was induced in SFFV-infected cells in the absence of Epo, suggesting that constitutive activation of the Raf-1/MAP kinase pathway by the virus may result in deregulation of AP-1 activity. We conclude from our studies that infection of erythroid cells with SFFV leads to the constitutive activation of signal transduction molecules in both the Jak-Stat and Raf-1/MAP kinase pathways and that both of these pathways must be activated to achieve maximum proliferation and differentiation of erythroid cells in the absence of Epo. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, DBS, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Ruscetti, SK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, DBS, POB B, Frederick, MD 21702 USA. RI Ohashi, Takashi/C-4671-2012 OI Ohashi, Takashi/0000-0002-3769-4224 NR 71 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 919 EP 925 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200004 PM 9444983 ER PT J AU Zolla-Pazner, S Lubeck, M Xu, S Burda, S Natuk, RJ Sinangil, F Steimer, K Gallo, RC Eichberg, JW Matthews, T Robert-Guroff, M AF Zolla-Pazner, S Lubeck, M Xu, S Burda, S Natuk, RJ Sinangil, F Steimer, K Gallo, RC Eichberg, JW Matthews, T Robert-Guroff, M TI Induction of neutralizing antibodies to T-cell line-adapted and primary human immunodeficiency virus type 1 isolates with a prime-boost vaccine regimen in chimpanzees SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; GLYCOPROTEIN GP120; HIV-INFECTION; PROTECTION; CHALLENGE; IMMUNIZATION; RESISTANCE; PREVENTION; SUBTYPE; COMPLEX AB Five chimpanzees were immunized by administration of one or more intranasal priming doses ofone to three recombinant adenoviruses containing a gp160 insert from human immunodeficiency virus type 1 (HIV-1) MN (HIV-1(MN)) followed by one or more boosts of recombinant HIV-1(SF2) gp120 delivered intramuscularly with MF59 adjuvant, This regimen resulted in humoral immune responses in three of five animals, Humoral responses included immunochemically active anti-HIV-1 antibodies (Abs) directed to recombinant gpl20 and neutralizing Abs reactive with T-cell-line-adapted HIV-1(MN) and HIV-1(SF2). In addition, neutralizing activity was detected to the two homologous primary isolates and to two of three heterologous primary isolates which, like the immunizing strains, can use CXCR4 as a coreceptor for infection, The three animals with detectable neutralizing Abs and a fourth exhibiting the best cytotoxic T-lymphocyte response were protected from a low-dose intravenous challenge with a cell-free HIV-1(SF2) primary isolate administered 4 weeks after the last boost. Animals were rested for 46 weeks and then rechallenged, without a boost, with an eightfold higher challenge dose of HIV-1(SF2). The three animals with persistent neutralizing Abs were again protected, These data show that a strong, long-lived protective Ab response can be induced with a prime-boost regimen in chimpanzees, The data suggest that in chimpanzees, the presence of neutralizing Abs correlates with protection for animals challenged intravenously with a high dose of a homologous strain of HIV-1, and they demonstrate for the first time the induction of neutralizing Abs to homologous and heterologous primary isolates. C1 Vet Affairs Med Ctr, New York, NY 10010 USA. NYU, Med Ctr, New York, NY 10016 USA. Wyeth Ayerst Res, Radnor, PA USA. Wyeth Lederle Vaccines & Pediat, Pearl River, NY USA. Chiron Corp, Emeryville, CA 94608 USA. NCI, Bethesda, MD 20892 USA. Dutch Primate Ctr, Rijswijk, Netherlands. Duke Univ, Med Ctr, Durham, NC USA. RP Zolla-Pazner, S (reprint author), Vet Affairs Med Ctr, Room 1812NO,423 E 23rd St, New York, NY 10010 USA. FU NIAID NIH HHS [AI32424, R01 AI036085, AI36085] NR 45 TC 60 Z9 61 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 FEB PY 1998 VL 72 IS 2 BP 1052 EP 1059 PG 8 WC Virology SC Virology GA YQ942 UT WOS:000071440200020 PM 9444999 ER PT J AU Yedavalli, VRK Chappey, C Matala, E Ahmad, N AF Yedavalli, VRK Chappey, C Matala, E Ahmad, N TI Conservation of an intact vif gene of human immunodeficiency virus type 1 during maternal-fetal transmission SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; HIV-1 INFECTION; DNA-SYNTHESIS; SOR GENE; PERINATAL TRANSMISSION; 1-INFECTED INDIVIDUALS; SEQUENCE HETEROGENEITY; PHYLOGENETIC ANALYSIS; T-LYMPHOCYTES; INFANTS BORN AB The human immunodeficiency virus type 1 (HIV-1) vif gene is conserved among most lentiviruses, suggesting that vif is important for natural infection. To determine whether an intact vif gene is positively selected during mother-to-infant transmission, we analyzed vif sequences from five infected mother-infant pairs following perinatal transmission. The coding potential of the vif open reading frame directly derived from uncultured peripheral blood mononuclear cell DNA was maintained in most of the 78,912 bp sequenced. We found that 123 of the 137 clones analyzed showed an 89.8% frequency of intact vif open reading frames. There was a low degree of heterogeneity of vif genes within mothers, within infants, and between epidemiologically linked mother-infant pairs. The distances between vif sequences were greater in epidemiologically unlinked individuals than in epidemiologically. linked mother-infant pairs, Furthermore, the epidemiologically linked mother-infant pair vif sequences displayed similar patterns that were not seen in vif sequences from epidemiologically unlinked individuals, The functional domains, including the two cysteines at positions 114 and 133, a serine phosphorylation site at position 144, and the C-terminal basic amino acids essential for vif protein function, were highly conserved in most of the sequences. Phylogenetic analyses of 137 mother-infant pair vif sequences and 187 other available vif sequences from HIV-1 databases revealed distinct clusters for vif sequences from each mother-infant pair and for other vif sequences, Taken together, these findings suggest that vif plays an important role in HIV-1 infection and replication in mothers and their perinatally infected infants. C1 Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Ahmad, N (reprint author), Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Microbiol & Immunol, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM nafees@u.arizona.edu FU NIAID NIH HHS [R21 AI040378, AI 40378] NR 73 TC 26 Z9 26 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 FEB PY 1998 VL 72 IS 2 BP 1092 EP 1102 PG 11 WC Virology SC Virology GA YQ942 UT WOS:000071440200025 PM 9445004 ER PT J AU Pise-Masison, CA Choi, KS Radonovich, M Dittmer, J Kim, SJ Brady, JN AF Pise-Masison, CA Choi, KS Radonovich, M Dittmer, J Kim, SJ Brady, JN TI Inhibition of p53 transactivation function by the human T-Cell lymphotropic virus type 1 Tax protein SO JOURNAL OF VIROLOGY LA English DT Article ID WILD-TYPE P53; TUMOR-SUPPRESSOR P53; CYCLE CHECKPOINT PATHWAY; LEUKEMIA-VIRUS; HTLV-I; TRANSCRIPTIONAL REPRESSION; IONIZING-RADIATION; RESPONSE ELEMENT; BAX GENE; EXPRESSION AB Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia. HTLV-1 transforms lymphocytes, and there is increasing evidence that the virus-encoded protein, Tax, plays a primary role in viral transformation, We have shown that wild-type p53 in HTLV-1-transformed cells is stabilized. This study,vas initiated to directly analyze whether the p53 in HTLV-1-transformed cell lines,vas transcriptionally active and to identify the viral gene product responsible for stabilization and inactivation. Transfection experiments using a p53-responsive reporter plasmid and gamma-irradiation studies demonstrate that the wild-type p53 in HTLV-1-transformed cell lines is not fully active. Further, we demonstrate that the HTLV-1-transforming protein, Tax, stabilizes and inactivates p53 function. Cotransfection of Tax with p53 results in a greater than 10-fold reduction in p53 transcription activity. Using Gal4-p53 fusion proteins, we demonstrate that Tax inhibition of p53 transactivation function is independent of sequence-specific DNA binding. Moreover, Tax inhibits p53 function by interfering with the activity of the N-terminal activation domain (amino acids 1 to 52). We conclude that Tax is involved in the inactivation of p53 function and stabilization of p53 in HTLV-1-infected cells. The functional interference of p53 function by Tax may be important for transformation and leukemogenesis. C1 NCI, Lab Receptor Biol & Gene Express, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Chemoprevent Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Lab Receptor Biol & Gene Express, Div Basic Sci, 41 Lib Dr,41-B403, Bethesda, MD 20892 USA. EM bradyj@dce41.nci.nih.gov RI Dittmer, Juergen/G-1160-2011 NR 63 TC 147 Z9 147 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 FEB PY 1998 VL 72 IS 2 BP 1165 EP 1170 PG 6 WC Virology SC Virology GA YQ942 UT WOS:000071440200035 PM 9445014 ER PT J AU Barrera, I Bloom, D Challberg, M AF Barrera, I Bloom, D Challberg, M TI An intertypic herpes simplex virus helicase-primase complex associated with a defect in neurovirulence has reduced primase activity SO JOURNAL OF VIROLOGY LA English DT Article ID UL5 GENE-PRODUCT; DNA HELICASE; PRIMER SYNTHESIS; PUTATIVE HELICASES; TYPE-1 ORIGIN; RECOMBINANTS; REPLICATION; EXPRESSION; PROTEIN; SEQUENCE AB R13-1 is an intertypic recombinant virus in which the left-hand 18% of the herpes simplex virus type 1 (HSV-1) genome is replaced by homologous sequences from HSV-2. R13-1 is nonneurovirulent and defective in DNA replication in neurons. The defect was localized to the UL5 open reading frame by using marker rescue analysis (D. C. Bloom and J. G. Stevens, J. Virol. 68:3761-3772, 1994). To provide conclusive evidence that UL5 is the only HSV-2 gene involved in the restricted replication phenotype of R13-1, we have characterized the phenotype of a recombinant virus (IB1) in which only the UL5 gene of HSV-1 was replaced by HSV-2 UL5. Data from 50% lethal dose determinations and the in vivo yields of virus suggested that IB1 has the same phenotypic characteristics as R13-1. UL5 is the helicase component of a complex with helicase and primase activities, All three subunits of this complex (UL5, UL8, and UL52) are required for viral DNA replication in all cell types, The intertypic complex HSV-2 UL5-HSV-1 UL8-HSV-1 UL52 was purified and biochemically characterized. The primase activity of the intertypic complex was 10-fold lower than that of HSV-1 UL5-HSV-1 UL8-HSV-1 UL52. The ATPase activity was comparable to that of the HSV-1 enzyme complex, and although the helicase activity aas threefold lower, this did not interfere with the synthesis of leading strands by. the HSV polymerase. One explanation for these findings is that the interactions between the subunits of the helicase-primase intertypic complex that are important for the full function of each subunit are inappropriate or weak. C1 NIH, Viral Dis Lab, Bethesda, MD 20892 USA. Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. RP Challberg, M (reprint author), NIH, Viral Dis Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mchllberg@atlas.niid.nih.gov NR 51 TC 9 Z9 9 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 FEB PY 1998 VL 72 IS 2 BP 1203 EP 1209 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200040 PM 9445019 ER PT J AU Atwood, A Choi, J Levin, HL AF Atwood, A Choi, J Levin, HL TI The application of a homologous recombination assay revealed amino acid residues in an LTR-retrotransposon that were critical for integration SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRIMED REVERSE TRANSCRIPTION; DNA-BINDING; SCHIZOSACCHAROMYCES-POMBE; HIV-1 INTEGRASE; RETROVIRAL DNA; FISSION YEAST; ESCHERICHIA-COLI; GENETIC-ANALYSIS; PROTEIN INVITRO AB Retroviruses and their relatives, the LTR-retrotransposons, possess an integrase protein (IN) that is required for the insertion of reverse transcripts into the genome of host cells. Schizosaccharomyces pombe is the host of Tf1, an LTR-retrotransposon with integration activity that can be studied by using techniques of yeast genetics, In this study, we sought to identify amino acid substitutions in Tn that specifically affected the integration step of transposition, In addition to seeking amino acid substitutions in IN, we also explored the possibility that other Tf1 proteins contributed to integration, By comparing the results of genetic assays that monitored both transposition and reverse transcription, we were able to seek point mutations throughout Tf1 that blocked transposition but not the synthesis of reverse transcripts, These mutant versions of Tf1 were candidates of elements that possessed defects in the integration step of transposition. Five mutations in Tf1 that resulted in low levels of integration were found to be located in the IN protein: two substitutions in the N-terminal Zn domain, two in the catalytic core, and one in the C-terminal domain, These results suggested that each of the three IN domains was required for Tf1 transposition, The potential role of these five amino acid residues in the function of IN is discussed, Two of the mutations that reduced integration mapped to the RNase H (RH) domain of Tf1 reverse transcriptase, The Tf1 elements with the RN mutations produced high levels of reverse transcripts, as determined by recombination and DNA blot analysis. These results indicated that the RH of Tf1 possesses a function critical for transposition that is independent of the accumulation of reverse transcripts. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. EM Henry_Levin@nih.gov NR 56 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1324 EP 1333 PG 10 WC Virology SC Virology GA YQ942 UT WOS:000071440200054 PM 9445033 ER PT J AU von Laer, D Thomsen, S Vogt, B Donath, M Kruppa, J Rein, A Ostertag, W Stocking, C AF von Laer, D Thomsen, S Vogt, B Donath, M Kruppa, J Rein, A Ostertag, W Stocking, C TI Entry of amphotropic and 10A1 pseudotyped murine retroviruses is restricted in hematopoietic stem cell lines SO JOURNAL OF VIROLOGY LA English DT Article ID BONE-MARROW CELLS; VESICULAR STOMATITIS-VIRUS; MEDIATED GENE-TRANSFER; PROGENITOR CELLS; LEUKEMIA-VIRUS; EFFICIENT EXPRESSION; MULTIDRUG-RESISTANCE; ADENOSINE-DEAMINASE; CD34(+) CELLS; SELF-RENEWAL AB Although transduction with amphotropic murine leukemia virus (MLV) vectors has been optimized successfully for hematopoietic differentiated progenitors, gene transfer to early hematopoietic cells (stem cells) is still highly restricted. A similar restriction to gene transfer,vas observed in the mouse stern cell line FDC-Pmix compared with transfer in the more mature myeloid precursor cell line FDC-P1 and the human erythroleukemia cell line K562, Gene transfer was not improved when the vector was pseudotyped with gp70(SU) of the 10A1 strain of MLV, which uses the receptor of the gibbon ape leukemia, virus (Pit1), in addition to the amphotropic receptor (Pit2). Although 10A1 and amphotropic gp70(SU) bound to FDC-P1, K562, and fibroblasts, no binding to FDC-Pmix cells was detected. This indicates that FDC-Pmix cells lack functional Pit2 and Pit1 receptors, Pseudotyping with the vesicular stomatitis virus G protein improved transduction efficiency in FDC-Pmix stem cells by 2 orders of magnitude, to fibroblast levels, confirming a block to retroviral infection at the receptor level. C1 Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany. Univ Hamburg, Inst Physiol Chem, D-20146 Hamburg, Germany. NCI, Lab Mol Virol & Carcinogenesis, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP von Laer, D (reprint author), Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, Martinistr 52, D-20251 Hamburg, Germany. EM laer@hpi-uni-hamburg.de NR 40 TC 21 Z9 21 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 FEB PY 1998 VL 72 IS 2 BP 1424 EP 1430 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200065 PM 9445044 ER PT J AU Desrosiers, RC Lifson, JD Gibbs, JS Czajak, SC Howe, AYM Arthur, LO Johnson, RP AF Desrosiers, RC Lifson, JD Gibbs, JS Czajak, SC Howe, AYM Arthur, LO Johnson, RP TI Identification of highly attenuated mutants of simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID UPSTREAM U3 SEQUENCES; RHESUS MACAQUES; NEF GENE; T-CELL; INFECTION; SIV; CHALLENGE; MONKEYS; VACCINE; ABSENCE AB Deletion mutants of the pathogenic clone of simian immunodeficiency virus isolate 239 (SIVmac239) were derived that are missing nef, vpr, and upstream sequences (US) in the U3 region of the LTR (SIVmac239 Delta 3), nef, vpx, and US (SIVmac239 Delta 3x), and nef, vpr, vpx, and US (SIVmac239 Delta 4). These multiply deleted derivatives replicated well in the continuously growing CEMx174 cell line and were infectious for rhesus monkeys. However, on the basis of virus load measurements, strength of antibody responses, and lack of disease progression, these mutants were highly attenuated. Measurements of cell-associated viral load agreed well with assays of plasma viral RNA load and with the strengths of the antibody responses; thus, these measurements likely reflected the extent of viral replication in vivo. A derivative of SIVmac239 lacking vif sequences (SIVmac239 Delta vif) could be consistently grown only in a vif-complementing cell line. This Delta vif virus appeared to be very weakly infectious for rhesus monkeys on the basis of sensitive antibody tests only. The weak antibody responses elicited by SIVmac239 Delta vif were apparently in response to low levels of replicating virus since they were not elicited by heat-inactivated virus and the anti-SIV antibody responses persisted for greater than 1 year. These results, and the results of previous studies, allow a rank ordering of the relative virulence of nine mutant strains of SIVmac according to the following order: Delta vpr > Delta vpx > Delta vpr Delta vpx congruent to Delta nef > Delta 3 > Delta 3x greater than or equal to Delta 4 > Delta vif > Delta 5. The results also demonstrate that almost any desired level of attenuation can be achieved, ranging from still pathogenic in a significant proportion of animals (Delta vpr and Delta vpx) to not detectably infectious (Delta 5), simply by varying the number and location of deletions in these five loci. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Desrosiers, RC (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, 1 Pine Hill Dr,Box 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR 00168]; NIAID NIH HHS [AI 35365, AI 25328, P01 AI035365, R01 AI025328, R37 AI025328, U01 AI035365] NR 36 TC 194 Z9 195 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 FEB PY 1998 VL 72 IS 2 BP 1431 EP 1437 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200066 PM 9445045 ER PT J AU Atreya, PL Peeples, ME Collins, PL AF Atreya, PL Peeples, ME Collins, PL TI The NS1 protein of human respiratory syncytial virus is a potent inhibitor of minigenome transcription and RNA replication SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; EXPRESSION SYSTEM; ELONGATION-FACTOR; VACCINIA VIRUS; NP PROTEIN; GENOME; GENE; NUCLEOTIDE; CELLS; RSV AB The NS1 protein (139 amino acids) is one of the two nonstructural proteins of human respiratory syncytial virus (RSV) and is encoded by a very abundant mRNA transcribed from the promoter-proximal RSV gene, The function of NS1 was unknown and was investigated here by using a reconstituted transcription and RNA replication system that involves a minireplicon and viral proteins (N, P, L and M2-1) expressed from separate cotransfected plasmids, Coexpression of the NS1 cDNA strongly inhibited transcription and RNA replication mediated by the RSV polymerase, even when the level of expressed NS1 protein was substantially below that observed in RSV-infected cells, The effect depended on synthesis of NS1 protein rather than NS1 RNA alone, Transcription and both steps of RNA replication, namely, synthesis of the antigenome and the genome, appeared to be equally sensitive to inhibition, The efficiency of encapsidation of the plasmid-derived minigenome was not altered by coexpression of NS1, indicating that the inhibition occurs at a later step, In two different dicistronic minigenomes, transcription of each gene vt as equally sensitive to inhibition by NS1. This suggested that the gradient of transcriptional polarity was unaffected and that the effect of NS1 instead probably involves an early event such as polymerase entry on the genome, NS1-mediated inhibition of transcription and RNA replication was not affected by eoexpression of the M2 mRNA which has two open reading frames encoding the transcriptional elongation factor M2-1 and the putative negative regulatory factor M2-2. The potent nature of the NS1-mediated inhibition suggests that negative regulation is an authentic function of the NS1 protein, albeit not necessarily the only one. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Dept Microbiol & Immunol, Chicago, IL 60612 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. EM pcollins@atlas.niaid.nih.gov NR 31 TC 72 Z9 76 U1 1 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 FEB PY 1998 VL 72 IS 2 BP 1452 EP 1461 PG 10 WC Virology SC Virology GA YQ942 UT WOS:000071440200069 PM 9445048 ER PT J AU Fu, TM Mylin, LM Schell, TD Bacik, I Russ, G Yewdell, JW Bennink, JR Tevethia, SS AF Fu, TM Mylin, LM Schell, TD Bacik, I Russ, G Yewdell, JW Bennink, JR Tevethia, SS TI An endoplasmic reticulum-targeting signal sequence enhances the immunogenicity of an immunorecessive simian virus 40 large T antigen cytotoxic T-lymphocyte epitope SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; ENDOGENOUSLY SYNTHESIZED PEPTIDE; SIMIAN-VIRUS-40 TUMOR-ANTIGEN; CELL RECEPTOR REPERTOIRE; AMINO-ACID-RESIDUES; VACCINIA VIRUS; VIRAL PEPTIDES; RECOGNITION EPITOPES; BETA-GALACTOSIDASE AB An immunological hierarchy among three H-2D(b)-restricted cytotoxic T lymphocyte (CTL) determinants in simian virus 40 (SV40) large T antigen (Tag) was described previously: determinants I and II/III are immunodominant, whereas determinant V is immunorecessive. To assess the immunogenicity of each determinant individually and define mechanisms that contribute to the immunorecessive nature of determinant V, we constructed a panel of recombinant vaccinia viruses (rVVs) expressing minigenes encoding these determinants in various polypeptide contests. We found the following. (i) Immunization of mice with an rVV encoding full-length SV40 Tag resulted in priming for CTL responses to determinants I and II/III but not determinant V. (ii) rVVs encoding peptide I or II/III in the cytosol or targeted to the endoplasmic reticulum (ER) were highly antigenic and immunogenic. (iii) rVVs encoding peptide V minigenes were antigenic and immunogenic if the peptide was targeted to the ER, expressed in the cytosol with short flanking sequences, or expressed from within a self-protein, murine dihydrofolate reductase. (iv) Presentation of the nonflanked peptide V (preceded by a Met codon only) could be enhanced by using a potent inhibitor of the proteasome. (v) H-2D(b)-epitope V peptide complexes decayed more rapidly than complexes containing epitope I or II/III peptides. In brefeldin A blocking experiments, functional epitope V complexes were detected longer on targets expressing ER-targeted epitope V than on targets expressing forms of epitope V dependent on the transporter associated with antigen processing. Therefore, limited formation of relatively unstable cell surface H-2D(b) complexes most likely contributes to the immunorecessive nature of epitope V within SV40 Tag. Increasing the delivery of epitope V peptide to the major histocompatibility complex class I presentation pathway by ER targeting dramatically enhanced the immunogenicity of epitope V. C1 Penn State Univ, Coll Med, Dept Microbiol & Immunol H107, Hershey, PA 17033 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Tevethia, SS (reprint author), Penn State Univ, Coll Med, Dept Microbiol & Immunol H107, POB 850,500 Univ Dr, Hershey, PA 17033 USA. EM sst1@psu.edu RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NCI NIH HHS [R37 CA025000, CA25000, R01 CA025000] NR 89 TC 64 Z9 64 U1 2 U2 5 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 FEB PY 1998 VL 72 IS 2 BP 1469 EP 1481 PG 13 WC Virology SC Virology GA YQ942 UT WOS:000071440200071 PM 9445050 ER PT J AU Bray, M Men, R Tokimatsu, I Lai, CJ AF Bray, M Men, R Tokimatsu, I Lai, CJ TI Genetic determinants responsible for acquisition of dengue type 2 virus mouse neurovirulence SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; NS1 PROTEIN; MICE; IMMUNIZATION; FLAVIVIRUSES; CONSTRUCTION; REPLICATION; PRM AB Studies conducted some 50 years ago showed that serial intracerebral passage of dengue viruses in mice selected for neurovirulent mutants that also exhibited significant attenuation for humans. We investigated the genetic basis of mouse neurovirulence of dengue virus because it might be directly or indirectly associated with attenuation for humans, Analysis of the sequence in the C-PreM-E-NS1 region of the parental dengue type 2 virus (DEN2) New Guinea C (NGC) strain and its mouse-adapted, neurovirulent mutant revealed that 10 nucleotide changes occurred during serial passage in mice. Seven of these changes resulted in amino acid substitutions, i.e., Leu(55)-Phe and Arg(57)-Lys in PreM, Glu(71)-Asp, Glu(126)-Lys, Phe(402)-Ile, and Thr(454)-IIe in E, and Arg(105)-Gln in NS1. The sequence of C was fully conserved between the parental and mutant DEN2. We constructed intertypic chimeric dengue viruses that contained the PreM-E genes or only the NS1 gene of neurovirulent DEN2 NGC substituting for the corresponding genes of DEN4. The DEN2 (PreM-E)/DEN4 chimera was neurovirulent for mice, whereas DEN2 (NS1)/DEN4 was not, The mutations present in the neurovirulent DEN2 PreM-E genes were then substituted singly or in Combination into the sequence of the nonneurovirulent, parental DEN2. Intracerebral titration of the various mutant chimeras so produced identified two amino acid changes, namely, Glu(71)-Asp and Glu(126)-Lys, in DEN2 E as being responsible for mouse neurovirulence. The conservative amino acid change of Glu(71)-Asp probably had a minor effect, if any. The Glu(126)-Lys substitution in DEN2 E, representing a change from a negatively charged amino acid to a positively charged amino acid, most likely plays an important role in conferring mouse neurovirulence. C1 NIAID, Mol Virol Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lai, CJ (reprint author), NIAID, Mol Virol Biol Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 55 Z9 67 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 FEB PY 1998 VL 72 IS 2 BP 1647 EP 1651 PG 5 WC Virology SC Virology GA YQ942 UT WOS:000071440200092 PM 9445071 ER PT J AU Goelz, MF Mahler, J Harry, J Mayers, P Clark, J Thigpen, JE Forsythe, DB AF Goelz, MF Mahler, J Harry, J Mayers, P Clark, J Thigpen, JE Forsythe, DB TI Neuropathologic findings asociated with seizures in FVB mice SO LABORATORY ANIMAL SCIENCE LA English DT Article ID EPILEPSY; MOUSE; MODELS AB The FVB mouse is used extensively in transgenic research because of its defined inbred background, superior reproductive performance, and prominent pronuclei, which facilitate microinjection of genomic material, Seizures associated with a known mutation and seizure-susceptible inbred strains are men documented in mice; however, to the authors' knowledge, seizures in the FVB strain have not been evaluated, Affected nonmanipulated FVB/N (n = 5) and transgenic FVB/N mice generated, using eight unrelated transgenic constructs (n = 63), we?re submitted for pathologic examination, Most cases were detected during routine observations in animal rooms; however, seizure induction by tail tattooing, fur clipping, and fire alarms has been observed, The majority of mice were female (62 of 68), with mean age of 5.8 months (range, 2 to IB months), Observations made during seizure presentation in 12 of 68 mice included facial grimace, chewing automatism, ptyalism with matting of the fur of the ventral aspect of the neck and/or forelimbs, and clonic convulsions that frequently progressed to tonic convulsions and death, Four mice were dead at presentation, with matting of the fur of the neck and forelimbs, The remainder of the mice had nonspecific signs of disease, such as lethargy moribundity, or malting of the fur, Vendor and in-house animal health surveillance reports indicated that mice were seronegative to all murine pathogens. Results of gross pathologic examination were unremarkable, Microscopic findings were limited to the brain and liver, In all mice, neuronal necrosis was present in the cerebral cortex, hippocampus, and thalamus, Concurrent astrocyte hypertrophy, as evidenced by an increase in glial fibrillary acidic protein staining, was detected, Acute coagulative necrosis of centrilobular hepatocytes was present in the liver of some cases (19 of 68),]reflective agents were not detected in selected brain specimens submitted for electron microscopy or in brain and liver specimens evaluated by use of special stains, Cytopathologic effect was not observed in 3T3, Vero, and BHK-21 cell lines inoculated with brain and liver specimens, The ischemic neuronal necrosis observed in these mice is consistent with lesions associated with status epilepticus in humans. The hepatocellular changes are interpreted to be agonal and associated with terminal hypoxia in seizuring animals, These results provide evidence of a previously unrecognized, often lethal epileptic syndrome in FVB mice that may have a major impact on transgenic research and ether disciplines using this mouse strain. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Goelz, MF (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 18 TC 37 Z9 38 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1998 VL 48 IS 1 BP 34 EP 37 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA YY876 UT WOS:000072196000007 PM 9517887 ER PT J AU Schreurs, BG AF Schreurs, BG TI Long-term memory and extinction of rabbit nictitating membrane trace conditioning SO LEARNING AND MOTIVATION LA English DT Article ID RETENTION; EXCITABILITY; RETRIEVAL; TRANSIENT; SYSTEMS; MODEL; TIME AB Long-term memory for and extinction of trace conditioning were examined using the rabbit nictitating membrane response (NMR) preparation. Rabbits were trained on four consecutive days with 80 trials of a 100-ms tone followed 500 ms later by a 100-ms periorbital electrical pulse. After a period of 1, 2, 3, or 6 months in their home cages, rabbits were given four consecutive days of 80 tone-alone extinction trials followed by a single day of 80 reacquisition trials. The results showed the following: (1) rabbit NMR conditioned responses following trace conditioning were reduced to approximately 55% of acquisition levels after an interval as short as a month between acquisition and extinction. All but one rabbit responded at baseline levels (<2%, CRs) 6 months following trace conditioning. In other words, there was a significant amount of forgetting of the association acquired during trace conditioning. (2) Conditioned responses that occurred 1, 2, or 3 months following acquisition were extinguished whereas responses that were absent following an interval of 6 months tended to reemerge over the course of extinction trials. (3) Reacquisition of the classically conditioned NMR in rabbits that had returned to baseline after extinction was significantly faster than initial acquisition levels in all groups and suggested a substantial level of savings. (C) 1998 Academic Press. C1 NINDS, BNU, LAS, NIH, Bethesda, MD 20892 USA. RP Schreurs, BG (reprint author), NINDS, BNU, LAS, NIH, Bldg 36,Room B205, Bethesda, MD 20892 USA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 43 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0023-9690 J9 LEARN MOTIV JI Learn. Motiv. PD FEB PY 1998 VL 29 IS 1 BP 68 EP 82 DI 10.1006/lmot.1997.0990 PG 15 WC Psychology, Biological; Psychology, Experimental SC Psychology GA ZE704 UT WOS:000072822200004 ER PT J AU Nagata, H Worobec, AS Semere, T Metcalfe, DD AF Nagata, H Worobec, AS Semere, T Metcalfe, DD TI Elevated expression of the proto-oncogene c-kit in patients with mastocytosis SO LEUKEMIA LA English DT Article DE c-kit; mastocytosis; stem cell factor; mast cells ID CELL GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; HEMATOPOIETIC PROGENITOR CELLS; MAST-CELLS; PERIPHERAL-BLOOD; W-LOCUS; HUMAN PIEBALDISM; BONE-MARROW; PROTOONCOGENE; LEUKEMIA AB The stem cell factor (SCF)c-kit receptor interaction plays a critical role in the development and survival of mast cells, Several studies have also associated c-kit receptor mutations with the human diseases, mastocytosis and piebaldism. Overexpression of c-kit has been reported to be associated with myeloproliferative disorders and myelodysplastic syndromes. Using peripheral blood mononuclear cells (PBMCs) from II patients with indolent mastocytosis (category I), mastocytosis with an associated hematologic disorder (category II), or aggressive mastocytosis (category III); a patient with CMML unassociated with mastocytosis, and PBMCs from 13 normal subjects, we examined the level of expression of c-kit mRNA along with other c-kit isoforms to determine if overexpression of the c-kit receptor was associated with mastocytosis. Using quantitative competitive PCR, c-kif mRNA levels on average were found to be statistically elevated in the five patients with mastocytosis with an associated hematologic disorder and in the patient with aggressive mastocytosis as compared with controls, but not elevated in patients with indolent mastocytosis, The relative mRNA expression for the two c-kit isoforms was not significantly different in the mastocytosis patients compared with controls. This demonstration of the overexpression of c-kit mRNA in mastocytosis, and particularly those patients with clinical evidence of myelodysplastic syndrome, adds evidence to support the conclusion that mastocytosis, at least in some patients, is a feature of myelodysplasia; and suggests that determination of c-kit mRNA expression in PBMCs may provide an additional approach to assessing prognosis. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 37 TC 23 Z9 24 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1998 VL 12 IS 2 BP 175 EP 181 DI 10.1038/sj.leu.2400906 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA ZB085 UT WOS:000072434200012 PM 9519779 ER PT J AU Boayue, KB Gu, L Yeager, AM Kreitman, RJ Findley, HW AF Boayue, KB Gu, L Yeager, AM Kreitman, RJ Findley, HW TI Pediatric acute myelogenous leukemia cells express IL-6 receptors and are sensitive to a recombinant IL6-Pseudomonas exotoxin SO LEUKEMIA LA English DT Article DE interleukin-6 receptor; AML; IL6-Pseudomonas exotoxin ID BONE-MARROW TRANSPLANTATION; MONOCLONAL-ANTIBODIES; GROWTH-FACTORS; BLAST CELLS; TUMOR-CELLS; INTERLEUKIN-6; PROLIFERATION; PROTEIN; TOXINS; MICE AB We have studied IL-6 receptor (IL-6R) expression on AML cells from 15 pediatric patients by immunocytochemistry/flow cytometry, reverse-transcription polymerase chain reaction, and Scatchard analysis, High-affinity IL-SR were detected on leukemic cells from 12 (80%) patients. Binding sites per cell ranged from 140 to 3580 (median 920; mean 1240), with dissociation constants of 0.26 to 0.71 nM, We therefore assessed the in vitro sensitivity of IL-6R(+) AML cells to treatment with a recombinant IL6-Pseudomonas exotoxin fusion protein (IL6-PE4E), using the XTT cytotoxicity assay. Leukemic cells from eight patients had ID50 values (concentration of IL6-PE4E producing a 50% decrease in cell viability) of < 1000 ng/ml (median, 87 ng/ml; mean, 282 ng/ml), Sensitivity to IL6-PE4E correlated significantly with receptor number. Normal bone marrow mononuclear cells had undetectable IL6-R expression (<20 receptors/cell) and were relatively resistant 10 IL6-PE4E. To test the efficacy of IL6-PE4E for ex vivo purging in an autologous stem cell transplantation setting, we incubated primary IL-6R(+) AML cells with 10(3) ng/ml 1L6-PE4E for 24 h, followed by Inoculation into SCID mice. Mice receiving treated cells showed no leukemic engraftment, while all mice receiving untreated or control-treated cells developed leukemia with a median presymptomatic interval of 55 days. In recipients of IL6-PE4E treated cells, no evidence of occult leukemia was detected by PCR analysis of blood and bone marrow cells at 185 days post-inoculation. These data suggest that IL-6R are expressed on leukemic cells from a substantial percentage of pediatric AML patients, Furthermore, leukemic cells expressing high numbers of IL6-R may he sensitive to IL6-PE4E in an ex vivo purging protocol. C1 Emory Univ, Sch Med, Div Hematol Oncol Bone Marrow Transplantat, BMT, Atlanta, GA 30322 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Findley, HW (reprint author), Emory Univ, Sch Med, Div Pediat Hematol Oncol, BMT, 2040 Ridgewood Dr NE, Atlanta, GA 30322 USA. FU NCI NIH HHS [R29 CA72020-01] NR 42 TC 4 Z9 6 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1998 VL 12 IS 2 BP 182 EP 191 DI 10.1038/sj.leu.2400914 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA ZB085 UT WOS:000072434200013 PM 9519780 ER PT J AU Rivera, M Vaquero, JJ Santos, A Ruiz-Cabello, J del Pozo, F AF Rivera, M Vaquero, JJ Santos, A Ruiz-Cabello, J del Pozo, F TI MRI visualization of small structures using improved surface coils SO MAGNETIC RESONANCE IMAGING LA English DT Article DE surface coil; high resolution MRI; inductively coupled coils; low noise images AB In this paper we present the spatial resolution enhancement and noise reduction level achieved with an optimized inductively coupled surface coil specifically designed for our experiments, The technique of designing and implementing customized coils for magnetic resonance imaging of very small structures is described, We have designed a low cost prototype of an inductively coupled circular surface coil, tuned for H-1 magnetic resonance imaging at 200 MHz, The coil is mounted on a customized teflon support, The inductive coupling used in this coil improves the signal-to-noise ratio by reducing various loss mechanisms (specially the dielectric losses), Test images have been acquired to determine the evolution of induced articular lesions in a rabbit animal model, as well as brain tumors in rats, The images show high spatial resolution, excellent B-1 field homogeneity and no "hot spots", Comparing these images with those acquired with conventional coils, one finds better spatial resolution and signal-to-noise ratio, as well as larger field of view with less intense illumination artifact. The methodology can be used in any application that requires high quality imaging of small structures. (C) 1998 Elsevier Science Inc. C1 Univ Politecn Madrid, Grp Bioingn & Telemed, Madrid, Spain. RP Vaquero, JJ (reprint author), NIH, Dept Nucl Med, Bldg 10,Room 1C401, Bethesda, MD 20892 USA. RI Vaquero, Juan Jose/D-3033-2009; Santos, Andres/C-4012-2009; DEL POZO GUERRERO, FRANCISCO/H-6668-2015; Ruiz-Cabello, Jesus/A-9570-2012 OI Vaquero, Juan Jose/0000-0001-9200-361X; Santos, Andres/0000-0001-7423-9135; DEL POZO GUERRERO, FRANCISCO/0000-0001-9919-9125; Ruiz-Cabello, Jesus/0000-0001-8681-5056 NR 14 TC 14 Z9 14 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD FEB PY 1998 VL 16 IS 2 BP 157 EP 166 DI 10.1016/S0730-725X(97)00273-7 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YX662 UT WOS:000072063800007 PM 9508272 ER PT J AU Filie, JD Buckler, CE Kozak, CA AF Filie, JD Buckler, CE Kozak, CA TI Genetic mapping of the mouse ferritin light chain gene and 11 pseudogenes on 11 mouse chromosomes SO MAMMALIAN GENOME LA English DT Article ID SUBUNIT GENE; H-SUBUNIT; CLONING; EXPRESSION; IDENTIFICATION; CONSERVATION; SEQUENCES; FAMILY; MAP AB We typed the progeny of two sets of genetic crosses to determine the map locations for loci containing sequences related to the ferritin light chain (Ft11) gene. Twelve loci were positioned on 11 different chromosomes, One of these genes mapped to a position on Chr 7 predicted to contain the expressed gene on the basis of the previously determined position of the human homolog on 19q13.3-q13.4. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 329, Bethesda, MD 20892 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 FEB PY 1998 VL 9 IS 2 BP 111 EP 113 DI 10.1007/s003359900699 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YT468 UT WOS:000071606600004 PM 9457670 ER PT J AU Cancilla, MR Graves, J Matesic, LE Reeves, RH Tainton, KM Choo, KHA Resnick, MA Larionov, VL Kouprina, NY AF Cancilla, MR Graves, J Matesic, LE Reeves, RH Tainton, KM Choo, KHA Resnick, MA Larionov, VL Kouprina, NY TI Rapid cloning of mouse DNA as yeast artificial chromosomes by transformation-associated recombination (TAR) SO MAMMALIAN GENOME LA English DT Article ID CONSTRUCTION; LIBRARY; HYBRIDS; GENOME; CELLS C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Royal Childrens Hosp, Murdoch Inst Res Birth Defects, Parkville, Vic 3052, Australia. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. RP Kouprina, NY (reprint author), NIEHS, Genet Mol Lab, Box 12233, Res Triangle Pk, NC 27709 USA. FU NICHD NIH HHS [HD24605] NR 23 TC 6 Z9 7 U1 0 U2 1 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 FEB PY 1998 VL 9 IS 2 BP 157 EP 159 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YT468 UT WOS:000071606600013 PM 9457679 ER PT J AU Jenkins, NA Gilbert, DJ Copeland, NG Gruzglin, E Bieker, JJ AF Jenkins, NA Gilbert, DJ Copeland, NG Gruzglin, E Bieker, JJ TI Erythroid Kruppel-like transcription factor (Eklf) maps to a region of mouse Chromosome 8 syntenic with human Chromosome 19 SO MAMMALIAN GENOME LA English DT Article ID BETA-THALASSEMIA; GENE; EXPRESSION C1 CUNY Mt Sinai Sch Med, Brookdale Ctr Mol Biol, New York, NY 10029 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. CUNY Mt Sinai Sch Med, Dept Biochem, New York, NY 10029 USA. RP Bieker, JJ (reprint author), CUNY Mt Sinai Sch Med, Brookdale Ctr Mol Biol, Box 1126,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIDDK NIH HHS [DK46865, DK48721] NR 11 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1998 VL 9 IS 2 BP 174 EP 176 DI 10.1007/s003359900716 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YT468 UT WOS:000071606600021 PM 9457687 ER PT J AU Huang, S Sato, S AF Huang, S Sato, S TI Progenitor cells in the adult zebrafish nervous system express a Brn-1-related POU gene, tai-ji SO MECHANISMS OF DEVELOPMENT LA English DT Article DE tai-ji; zebrafish; Brn-1 ID DOMAIN TRANSCRIPTION FACTORS; OPTIC TECTUM; STEM-CELL; XENOPUS EMBRYOS; GOLDFISH RETINA; FACTOR BRN-2; BRAIN; DIFFERENTIATION; REGENERATION; PROTEINS AB The adult fish brain undergoes continuous neurogenesis and retains the capacity to regenerate. However, the cellular and molecular basis of this process is not well understood. We report on the cloning and characterization of a Brain-1-related, class III POU domain gene, tai-ji, in the developing and adult zebrafish, as well as in a human cell line, hNT2. During development, as differentiation occurs, the expression of tai-ji is downregulated in the notochord, muscle, nervous system and dorsal fin. Similarly, tai-ji is expressed in the human neuronal precursor cell, hNT2, but is downregulated upon differentiation with retinoic acid. In the adult zebrafish nervous system, tail-ji persists in germinal zones, including cells in the germinal zone of the retina, the basal cells of the olfactory epithelium and cells of the subependymal zones in the optic tectum and telencephalon. Subsets of the tai-ji-expressing cells in these regions incorporate BrdU. Most of the tai-ji-expressing cells within these regions of the zebrafish brain are not differentiated and do not express a marker for post-mitotic neurons, acetylated tubulin nor do they express a marker of glial cells, glial acidic fibrillary protein (GFAP). We propose that the majority of the tai-ji-expressing cells are neural stem or progenitor cell populations that may represent the cellular basis for continuous growth in the adult nervous system. (C) 1998 Elsevier Science Ireland Ltd. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NR 70 TC 22 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 EI 1872-6356 J9 MECH DEVELOP JI Mech. Dev. PD FEB PY 1998 VL 71 IS 1-2 BP 23 EP 35 DI 10.1016/S0925-4773(97)00199-8 PG 13 WC Developmental Biology SC Developmental Biology GA ZE059 UT WOS:000072753500002 PM 9507055 ER PT J AU Toyama, R Kobayashi, M Tomita, T Dawid, IB AF Toyama, R Kobayashi, M Tomita, T Dawid, IB TI Expression of LIM-domain binding protein (ldb) genes during zebrafish embryogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE zebrafish; LIM domain binding protein; protein-protein interaction ID HOMEODOMAIN; XENOPUS AB LIM homeodomain proteins are developmental regulators whose functions depend on synergism with LIM domain binding proteins (Ldb proteins). We have isolated four members of the [db gene family from the zebrafish, Danio rerio. Ldb1, Ldb2 and Ldb3 share 95%, 73% and 62% amino acid identity with mouse Ldb1, respectively. In overlay assays, Ldb proteins bind LIM homeodomain proteins and LMO1, but not zyxin or MLP. Whole mount in situ hybridization showed that zebrafish ldb1 is expressed ubiquitously from gastrulation onward. Ldb2 is ubiquitous at gastrulation, and later is found in many but not all tissues, especially the anterior central nervous system (CNS) and vasculature. Ldb3 mRNA was expressed primarily in the anterior CNS. (C) 1998 Published by Elsevier Science ireland Ltd. C1 NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RI Kobayashi, Makoto/B-2537-2008 NR 14 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD FEB PY 1998 VL 71 IS 1-2 BP 197 EP 200 DI 10.1016/S0925-4773(97)00202-5 PG 4 WC Developmental Biology SC Developmental Biology GA ZE059 UT WOS:000072753500018 PM 9507128 ER PT J AU Ping, YJ Nakatsu, Y Goldstein, AM Tucker, MA Kraemer, KH Tanaka, K AF Ping, YJ Nakatsu, Y Goldstein, AM Tucker, MA Kraemer, KH Tanaka, K TI RPA2, a gene for the 32 kDa subunit of replication protein A on chromosome 1p35-36, is not mutated in patients with familial melanoma linked to chromosome 1p36 SO MELANOMA RESEARCH LA English DT Article DE chromosome linkage; DNA sequencing; melanoma; Northern blotting; Southern blotting; Western blotting ID DYSPLASTIC NEVUS SYNDROME; CUTANEOUS MALIGNANT-MELANOMA; SUSCEPTIBILITY LOCUS MLM; SINGLE-STRANDED-DNA; ULTRAVIOLET HYPERMUTABILITY; LINKAGE ANALYSIS; PRONE FAMILIES; RECOMBINATION; MUTATIONS; PLASMID AB Although some cases of dysplastic naevi (DN) and familial melanoma have been linked to anonymous markers on chromosome 1p36, the gene has not been identified. A candidate gene, RPA2, which codes for the 32 kDa subunit of replication protein A, is located in the 1p35-36 region. We examined the RPA2 gene in seven lymphoblastoid cell lines from members of melanoma-prone families linked to chromosome 1p36. Southern and Northern blot analyses showed the DNA and RNA bands were of normal size and intensity. DNA sequencing demonstrated no nucleotide alterations in the RPA2 cDNA. Western blot analysis exhibited normal electrophoretic migration and intensity of the RPA2 protein. These results indicate that alterations do not occur in the RPA2 gene in these DN/familial melanoma families linked to chromosome 1p36. (C) 1998 Rapid Science Ltd. C1 Osaka Univ, Inst Mol & Cellular Biol, Osaka 565, Japan. NCI, Genet Epidemiol Branch, Bethesda, MD 20205 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20205 USA. RP Tanaka, K (reprint author), Osaka Univ, Inst Mol & Cellular Biol, 1-3 Yamadaoka, Osaka 565, Japan. RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS [Z01 BC004517-31] NR 41 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD FEB PY 1998 VL 8 IS 1 BP 47 EP 52 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA YX783 UT WOS:000072077400007 PM 9508376 ER PT J AU Jouravleva, EA McDonald, GA Garon, CF Boesman-Finkelstein, M Finkelstein, RA AF Jouravleva, EA McDonald, GA Garon, CF Boesman-Finkelstein, M Finkelstein, RA TI Characterization and possible functions of a new filamentous bacteriophage from Vibrio cholerae O139 SO MICROBIOLOGY-UK LA English DT Article DE Vibrio cholerae O139; filamentous bacteriophage; choleraphage host range; cholera vibrio territoriality; horizontal gene transfer ID VIRULENCE; POLYSACCHARIDE; STRAINS; BENGAL; PROTEINS; GENESIS; CAPSULE; BIOTYPE; TOXIN; DNA AB The emergence and rapid rise to dominance of Vibrio cholerae O139 in India and Bangladesh in 1992 led to the consideration that choleraphage might serve as both a selective mechanism and a means for horizontal transmission of genetic information. A filamentous phage '493' from O139 strain AJ27-493 has been purified and partially characterized. The phage was inactive on classical biotype V. cholerae O1 but it was active on El Tor biotype strains isolated prior to 1994 when El Tor re-emerged in Bangladesh. More recent El Tor isolates were all resistant to the phage. The phage was also active on O139 strains. Unlike the filamentous ctx phi, the receptor for 493 is not TcpA. The phage genome was a 9.3 kb closed circular single-stranded molecule containing a 0.4 kb double-stranded stem supporting a 2 kb single-stranded loop. A 283 bp fragment was cloned and used as a probe in Southern hybridization, in parallel with total phage 493 DNA. These probes hybridized both chromosomally and extrachromosomally with most O139 strains, but not with O1 strains. Infection of hybridization-negative El Tor or O139 strains resulted in the presence of hybridizing loci (both plasmid and chromosomal), in the appearance of an 18 kDa protein, and in marked alterations in colonial morphology. Phage 493 is clearly distinct from other O139 choleraphages which have been described. Phage 493 DNA hybridized with an encapsulated non-O1 (O31) strain (NRT36S) which was isolated before O139 was recognized. NRT36S also produces a phage which can infect Fl Tor strains with low efficiency. Further studies may reveal whether bacteriophage play a role in the emergence and the territoriality of new choleragenic vibrios. C1 Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Finkelstein, RA (reprint author), Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA. FU NIAID NIH HHS [AI17312] NR 39 TC 19 Z9 20 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD FEB PY 1998 VL 144 BP 315 EP 324 PN 2 PG 10 WC Microbiology SC Microbiology GA YW937 UT WOS:000071989700010 PM 9493369 ER PT J AU Quintanilla-Martinez, L Lome-Maldonado, C Schwarzmann, F Gredler, E Reyes, E Angeles-Angeles, A Fend, F AF Quintanilla-Martinez, L Lome-Maldonado, C Schwarzmann, F Gredler, E Reyes, E Angeles-Angeles, A Fend, F TI Post-transplantation lymphoproliferative disorders in Mexico: An aggressive clonal disease associated with Epstein-Barr virus type A SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the US-and-Canadian-Academy-of-Pathology CY MAR 01-07, 1997 CL ORLANDO, FL SP US & Canadian Acad Pathol DE Epstein-Barr virus; immunoglobulin gene rearrangement; LMP-1 deletion; posttransplantation lymphoproliferative disorders ID POLYMERASE CHAIN-REACTION; LATENT MEMBRANE-PROTEIN; MOLECULAR-GENETIC-ANALYSIS; REED-STERNBERG CELLS; HODGKINS-DISEASE; NASOPHARYNGEAL CARCINOMA; ORGAN-TRANSPLANTATION; MALIGNANT-LYMPHOMAS; HIGH PREVALENCE; LMP1 ONCOGENE AB Post-transplantation lymphoproliferative disorders (PT-LPDs) are a complication of immunosuppression with variable clinical behavior and frequent Epstein-Barr virus (EBV) association, There is geographic variation in the association of EBV with certain tumors and a lack of studies of PT-LPDs from developing countries, so we decided to study in detail a series of PT-LPDs from Mexico to identify similarities and differences between populations in Mexico and those in Europe and the United States. We used paraffin-embedded tissue from eight PT-LPDs (six from men, two from women) that arose after renal transplantation. Clinical data, morphologic features, and clonality on the basis of immunoglobulin (Ig) light chain restriction, as well as polymerase chain reaction (PCR) for Ig heavy chain genes, were studied. The presence of EBV was investigated with PCR, immunohistochemical analysis for latent membrane protein (LMP)-1, and in situ hybridization for EBV early RNA transcripts, In addition, the subtype of EBV based on the EBNA 2A and 2B genes and the presence of a 30-bp deletion in the LMP-1 gene were investigated by PCR, Seven (87.5%) of eight cases presented with gastrointestinal involvement; five patients died. Three cases were polymorphic PT-LPDs, four were monomorphic large cell lymphomas (one diffuse large cell, three immunoblastic), and one was unclassifiable, All showed a B-cell phenotype, with a clonal population demonstrated in seven of the eight cases. Tumor cells expressed EBERs in all of the cases and LMP-1 in six of seven evaluable cases. Seven of seven cases showed EBV subtype A. Two (25%) of eight cases had the 30-bp LMP-1 deletion, This study shows that PT-LPDs in Mexico are clonal disorders associated with EBV subtype A. In contrast to series from Europe and the United States, our cases showed a significantly higher incidence of gastrointestinal tract involvement (P < .001), and a lower incidence of the 30-bp LMP-1 deletion, although this was not statistically significant (P < .28). C1 Inst Nacl Nutr, Dept Pathol, Mexico City, DF, Mexico. Univ Innsbruck, Dept Pathol, A-6020 Innsbruck, Austria. Univ Regensburg, Dept Microbiol, D-8400 Regensburg, Germany. RP Quintanilla-Martinez, L (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N110, Bethesda, MD 20892 USA. EM leticiaq@box-1.nih.gov NR 52 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 1998 VL 11 IS 2 BP 200 EP 208 PG 9 WC Pathology SC Pathology GA YX661 UT WOS:000072063700012 PM 9504692 ER PT J AU Qian, XL Vass, WC Papageorge, AG Anborgh, PH Lowy, DR AF Qian, XL Vass, WC Papageorge, AG Anborgh, PH Lowy, DR TI N terminus of Sos1 Ras exchange factor: Critical roles for the Dbl and pleckstrin homology domains SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; SIGNAL-TRANSDUCTION; TYROSINE KINASE; SEVENLESS PROTEIN; ONCOGENE PRODUCT; STRUCTURAL BASIS; FACTOR SON; ACTIVATION; GRB2; RECEPTOR AB We have studied the functional importance of the N terminus of mouse Sos1 (mSos1), a ubiquitously expressed Pas-specific guanine nucleotide exchange factor whose C-terminal sequences bind Grb-2, Consistent with previous reports, addition of a myristoylation signal to mSos1 (MyrSos1) rendered it transforming for NIH 3T3 cells and deletion of the mSos C terminus (MyrSos1-Delta C) did not interfere with this activity. However, an N-terminally deleted myristoylated mSos1 protein (MyrSos1-Delta N) was transformation defective, although the protein was stable and localized to the membrane. Site-directed mutagenesis was used to examine the role of the Dbl and pleckstrin homology (PH) domains located in the N terminus, When mutations in the PH domain were introduced into two conserved amino acids either singly or together in MyrSos1 or MyrSos1-Delta C, the transforming activity was severely impaired, An analogous reduction in biological activity,vas seen when a cluster of point mutations was engineered into the Dbl domain, The mitogen-activation protein (MAP) kinase activities induced by the various Dbl and PH mutants of MyrSos1 correlated with their biological activities, When NIH 3T3 cells were transfected with a myristoylated Sos N terminus, their growth response to epidermal growth factor (EGF), platelet-derived growth factor, lysophosphatidic acid or serum was greatly impaired, The dominant inhibitory biological activity of the N terminus correlated with its ability to impair EGF-dependent activation of GTP-Ras and of MAP kinase, as well with the ability of endogenous Sos to form a stable complex with activated EGF receptors, The N terminus with mutations in the Dbl and PH domains was much less inhibitory in these biological and biochemical assays, In contrast to wild-type Sos1, nonmyristoylated versions of Sos1-Delta N and Sos1-Delta C did not form a stable complex with activated EGF receptors, We conclude that the Dbl and PH domains are critical for Sos function and that stable association of Sos with activated EGF receptors requires both the Sos N and C termini. C1 NCI, Div Basic Sci, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Lowy, DR (reprint author), NCI, Div Basic Sci, Cellular Oncol Lab, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. EM drl@helix.nih.gov NR 43 TC 49 Z9 51 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 FEB PY 1998 VL 18 IS 2 BP 771 EP 778 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000012 PM 9447973 ER PT J AU Gale, M Blakely, CM Hopkins, DA Melville, MW Wambach, M Romano, PR Katze, MG AF Gale, M Blakely, CM Hopkins, DA Melville, MW Wambach, M Romano, PR Katze, MG TI Regulation of interferon-induced protein kinase PKR: Modulation of p58(IPK) inhibitory function by a novel protein, P52(rIPK) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEAT-SHOCK PROTEIN; 58,000-DALTON CELLULAR INHIBITOR; STRANDED-RNA BINDING; INITIATION-FACTOR 4E; MALIGNANT TRANSFORMATION; TRANSLATION INITIATION; EIF-2-ALPHA KINASE; GLUCOCORTICOSTEROID RECEPTOR; MOLECULAR CHAPERONES; BACTERIAL DNAJ AB The cellular response to environmental signals is largely dependent upon the induction of responsive protein kinase signaling pathways, Within these pathways, distinct protein-protein interactions play a role in determining the specificity of the response through regulation of kinase function, The interferon-induced serine/threonine protein kinase, PKR, is activated in response to various environmental stimuli, Like many protein kinases, PKR is regulated through direct interactions with activator and inhibitory molecules, including P58(IPK), a cellular PKR inhibitor. P58(IPK) functions to represses PKR-mediated phosphorylation of the eukaryotic initiation factor 2 alpha subunit (eIF-2 alpha) through a direct interaction, thereby relieving the PKR-imposed block on mRNA translation and cell growth. To further define the molecular mechanism underlying regulation of PKR, we have utilized an interaction cloning strategy to identify a novel cDNA encoding a P58(IPK)-interacting protein. This protein, designated P52(rIPK), possesses limited homology to the charged domain of Hsp90 and is expressed in a wide range of cell lines, p52(rIPK) and P58(IPK) interacted in a yeast two-hybrid assay and were recovered as a complex from mammalian cell extracts, When coexpressed with PKR in yeast, p58(IPK) repressed PKR-mediated eIF-2 alpha phosphorylation, inhibiting the normally toxic and growth-suppressive effects associated with PKR function, Conversely, introduction of P52(rIPK) into these strains resulted in restoration of both PKR activity and eIF-2 alpha phosphorylation, concomitant with growth suppression due to inhibition of P58(IPK) function. Furthermore, P52(rIPK) inhibited p58(IPK) function in a reconstituted in vitro PKR-regulatory assay, Our results demonstrate that p58(IPK) is inhibited through a direct interaction with p52(rIPK) Which, in turn, results in upregulation of PKR activity, Taken together, our data describe a novel protein kinase-regulatory system which encompasses an intersection of interferon-, stress-, and growth-regulatory pathways. C1 Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Katze, MG (reprint author), Univ Washington, Sch Med, Dept Microbiol, Box 357242, Seattle, WA 98195 USA. EM honey@u.washington.edu OI Gale, Michael/0000-0002-6332-7436 FU NCRR NIH HHS [P51 RR000166, RR00166]; NIAID NIH HHS [AI22646, R01 AI022646]; NIGMS NIH HHS [32 GM07270, T32 GM007270] NR 92 TC 69 Z9 73 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 FEB PY 1998 VL 18 IS 2 BP 859 EP 871 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000021 PM 9447982 ER PT J AU Ahn, S Olive, M Aggarwal, S Krylov, D Ginty, DD Vinson, C AF Ahn, S Olive, M Aggarwal, S Krylov, D Ginty, DD Vinson, C TI A dominant-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CAMP-RESPONSIVE ELEMENT; LEUCINE-ZIPPER PROTEINS; NERVE GROWTH-FACTOR; CYCLIC-AMP; BINDING PROTEIN; TARGETED MUTATION; COILED-COIL; LATE-PHASE; PHOSPHORYLATION; EXPRESSION AB Several studies have characterized the upstream regulatory region of c-fos, and identified cis-acting elements termed the cyclic AMP (cAMP) response elements (CREs) that are critical for c-fos transcription in response to a variety of extracellular stimuli, Although several transcription factors can bind to CREs in vitro, the identity of the transcription factor(s) that activates the c-fos promoter via the CRE in vivo remains unclear. To help identify the trans-acting factors that regulate stimulus-dependent transcription of c-fos via the CREs, dominant-negative (D-N) inhibitor proteins that function by preventing DNA binding of B-ZIP proteins in a dimerization domain-dependent fashion were developed, A D-N inhibitor of CREB, termed A-CREB, was constructed by fusing a designed acidic amphipathic extension onto the N terminus of the CREB leucine zipper domain, The acidic extension of A-CREB interacts with the basic region of CREB forming a coiled-coil extension of the leucine zipper and thus prevents the basic region of wild-type CREB from binding to DNA, Other D-N inhibitors generated in a similar manner with the dimerization domains of Fos, Jun, C/EBP, ATF-2, or VBP did not block CREB DNA binding activity, nor did they inhibit transcriptional activation of a minimal promoter containing a single CRE in PC12 cells, A-CREB inhibited activation of CRE-mediated transcription evoked by three distinct stimuli: forskolin, which increases intracellular cAMP; membrane depolarization, which promotes Ca2+ influx; and nerve growth factor (NGF), A-CREB completely inhibited cAMP-mediated, but only partially inhibited Ca2+ and NGF-mediated, transcription of a reporter gene containing 750 bp of the native c-fos promoter, Moreover, glutamate induction of c-fos expression in primary cortical neurons was dependent on CREB, In contrast, induction of c-fos transcription by UV light was not inhibited by A-CREB, Lastly, A-CREB attenuated NGF induction of morphological differentiation in PC12 cells, These results suggest that CREB or its closely related family members are general mediators of stimulus-dependent transcription of c-fos and are required for at least some of the long-term actions of NGF. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St, Baltimore, MD 21205 USA. EM VinsonC@dc37a.nci.nih.gov FU PHS HHS [N534814] NR 64 TC 391 Z9 399 U1 0 U2 5 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 FEB PY 1998 VL 18 IS 2 BP 967 EP 977 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000033 PM 9447994 ER PT J AU Tavner, FJ Simpson, R Tashiro, S Favier, D Jenkins, NA Gilbert, DJ Copeland, NG Macmillan, EM Lutwyche, J Keough, RA Ishii, S Gonda, TJ AF Tavner, FJ Simpson, R Tashiro, S Favier, D Jenkins, NA Gilbert, DJ Copeland, NG Macmillan, EM Lutwyche, J Keough, RA Ishii, S Gonda, TJ TI Molecular cloning reveals that the p160 myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE HEMATOPOIETIC-CELLS; NEGATIVE REGULATORY DOMAIN; TRANSCRIPTION FACTOR UBF; C-MYB; DNA-BINDING; LEUCINE-ZIPPER; CONSTITUTIVE EXPRESSION; MYELOID-LEUKEMIA; TRUNCATED FORMS; GENE-EXPRESSION AB We have previously detected two related murine nuclear proteins, p160 and p67, that can bind to the leucine zipper motif within the negative regulatory domain of the Myb transcription factor. We now describe the molecular cloning of cDNA corresponding to murine p160. The P160 gene is located on mouse chromosome 11, and related sequences are found on chromosomes 1 and 12. The predicted p160 protein is novel, and in agreement with previous studies, we find that the corresponding 4.5-kb mRNA is ubiquitously expressed. We showed that p67 is an N-terminal fragment of p160 which is generated by proteolytic cleavage in certain cell types. The protein encoded by the cloned p160 cDNA and an engineered protein (p67*) comprising the amino-terminal region of p160 exhibit binding specificities for the Myb and Jun leucine zipper regions identical to those of endogenous p160 and p67, respectively. This implies that the Myb-binding site of p160 lies within the N-terminal 580 residues and that the Jun-binding site is C-terminal to this position. Moreover, we show that p67* but not p160 can inhibit transactivation by Myb. Unexpectedly, immunofluorescence studies show that p160 is localized predominantly in the nucleolus. The implications of these results for possible functions of p160 are discussed. C1 Inst Med & Vet Sci, Hanson Ctr Canc Res, Adelaide, SA 5000, Australia. Ludwig Inst Canc Res, Joint Prot Struct Lab, Parkville, Vic 3052, Australia. Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia. RIKEN, Inst Phys & Chem Res, Tsukuba Life Sci Ctr, Mol Genet Lab, Ibaraki, Osaka 305, Japan. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. RP Gonda, TJ (reprint author), Inst Med & Vet Sci, Hanson Ctr Canc Res, Frome Rd, Adelaide, SA 5000, Australia. RI Simpson, Richard/A-6947-2012; Ishii, Shunsuke/A-5271-2016 NR 75 TC 66 Z9 69 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 FEB PY 1998 VL 18 IS 2 BP 989 EP 1002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000035 PM 9447996 ER PT J AU Kokubo, T Swanson, MJ Nishikawa, JI Hinnebusch, AG Nakatani, Y AF Kokubo, T Swanson, MJ Nishikawa, JI Hinnebusch, AG Nakatani, Y TI The yeast TAF145 inhibitory domain and TFIIA competitively bind to TATA-binding protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR-TFIIB; ACTIVATORS IN-VIVO; MOLECULAR-CLONING; BOX-BINDING; CRYSTAL-STRUCTURE; SHUTTLE VECTORS; SACCHAROMYCES-CEREVISIAE; PREINITIATION COMPLEX; TFIIA/TBP/DNA COMPLEX AB The Drosophila 230-kDa TFIID subunit (dTAF230) interacts with the DNA binding domain of TATA box-binding protein (TBP) which exists in the same complex. Here, we characterize the inhibitory domain in the yeast TAF145 (yTAF145), which is homologous to dTAF230. Mutation studies show that the N-terminal inhibitory region (residues 10 to 71) can be divided into two subdomains, I (residues 10 to 37) and LI (residues 36 to 71). Mutations in either subdomain significantly impair function. Acidic residues in subdomain II are important for the interaction with TBP. In addition, yTAF145 interaction is impaired by mutating the basic residues on the convex surface of TBP, which are crucial for interaction with TFIIA. Consistently, TFIIA and yTAF145 hind competitively to TBP. A deletion of the inhibitory domain of yTAF145 leads to a temperature-sensitive growth phenotype. Importantly, this phenotype is suppressed by overexpression of the TFIIA subunits, indicating that the yTAF145 inhibitory domain is involved in TFIIA function. C1 Nara Inst Sci & Technol, Div Gene Funct Anim, Nara 63001, Japan. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Nara Inst Sci & Technol, Div Gene Funct Anim, Nara 63001, Japan. RP Kokubo, T (reprint author), Nara Inst Sci & Technol, Div Gene Funct Anim, 8916-5 Takayama, Nara 63001, Japan. NR 75 TC 93 Z9 94 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1998 VL 18 IS 2 BP 1003 EP 1012 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000036 PM 9447997 ER PT J AU Moore, SP Rinckel, LA Garfinkel, DJ AF Moore, SP Rinckel, LA Garfinkel, DJ TI A Ty1 integrase nuclear localization signal required for retrotransposition SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; SACCHAROMYCES-CEREVISIAE; ELEMENT TRANSPOSITION; REVERSE-TRANSCRIPTASE; HIV-1 INTEGRASE; MATRIX PROTEIN; TYPE-1; INFECTION; CELLS AB Ty1 retrotransposition in Saccharomyces cerevisiae requires integrase (IN)-mediated insertion of Ty1 cDNA into the host genome. The transposition components are assembled in the cytoplasm and must cross the nuclear envelope to reach the genomic target, since, unlike animal cell nuclear membranes, the yeast cell nuclear membrane remains intact throughout the cell cycle. We have identified a bipartite nuclear localization signal (NLS) in IN required for Ty1 transposition (Ty1 IN) that directs IN to the nucleus. Mutations in the NLS that specifically abolish nuclear localization inactivate transpositional integration but do not affect reverse transcription, protein processing, or catalytic activity in vitro, No additional Ty1-encoded proteins are required for IN nuclear localization, Intragenic complementation experiments suggest that Ty1 IN functions as a multimer and contains two distinct domains, one required for integration and the other for nuclear localization. Nuclear targeting of the preintegration complex by an IN NLS may prove to be a general strategy used by retrotransposons and retroviruses that infect nondividing cells. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. EM garfinke@ncifcrf.gov NR 56 TC 59 Z9 60 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1998 VL 18 IS 2 BP 1105 EP 1114 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000047 PM 9448008 ER PT J AU Wrobel, B Murphy, H Cashel, M Wegrzyn, G AF Wrobel, B Murphy, H Cashel, M Wegrzyn, G TI Guanosine tetraphosphate (ppGpp)-mediated inhibition of the activity of the bacteriophage lambda p(R) promoter in Escherichia coli SO MOLECULAR AND GENERAL GENETICS LA English DT Article DE stringent/relaxed response; bacteriophage lambda p(R) promoter; replication of lambda plasmids; dnaA; guanosine 5 '-diphosphate-3 '-diphosphate ID DNA-REPLICATION; COLIPHAGE-LAMBDA; PLASMID REPLICATION; PROTEIN-SYNTHESIS; STRINGENT CONTROL; PPGPP SYNTHESIS; GROWTH-RATE; SPOT; DEGRADATION; EXPRESSION AB It was previously demonstrated that the activity of bacteriophage lambda promoter p(R) is decreased in wild-type Escherichia coli cells starved for amino acids (during the stringent response). Since p(R) activity is necessary for the transcriptional activation of ori lambda, this leads to inhibition of the replication of plasmids derived from phage lambda. These results led to the proposal that the p(R) promoter is susceptible to control by the stringent response. However, subsequent studies demonstrated that this promoter is activated by the host dnaA gene product and since the dnaA promoter was reported to be controlled by the stringent response, it is possible that the inhibition of p(R) activity in amino acid-starved cells is indirect, and results from the impairment of DnaA-mediated transcriptional activation. Here we present evidence that p(R) is negatively regulated by ppGpp, even when DnaA protein is provided in excess as well as in cells devoid of DnaA function. We have checked that the level of ppGpp is increased during prolonged (up to 4 h) starvation for isoleucine in relA(+) cells but not in the relA(-) mutant. At the same time we observed inhibition of lambda plasmid replication during the stringent, but not relaxed, response, even when DnaA was overproduced. Finally, we found that the activity of a p(R)-lacZ fusion is inhibited after gratuitously induced overproduction of ppGpp in unstarved cells, irrespective of the status of the dnaA gene product. We conclude that the activity of the p(R) promoter is inhibited directly by ppGpp. C1 Univ Gdansk, Dept Biol Mol, PL-80822 Gdansk, Poland. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Wegrzyn, G (reprint author), Univ Gdansk, Dept Biol Mol, Kladki 24, PL-80822 Gdansk, Poland. EM wegrzyn@biotech.univ.gda.pl RI Wrobel, Borys/F-3471-2013 OI Wrobel, Borys/0000-0002-4759-725X NR 30 TC 15 Z9 15 U1 2 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD FEB PY 1998 VL 257 IS 4 BP 490 EP 495 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA ZB234 UT WOS:000072450600013 PM 9529531 ER PT J AU Donohue, PJ Shapira, H Mantey, SA Hampton, LL Jensen, RT Battey, JF AF Donohue, PJ Shapira, H Mantey, SA Hampton, LL Jensen, RT Battey, JF TI A human gene encodes a putative G protein-coupled receptor highly expressed in the central nervous system SO MOLECULAR BRAIN RESEARCH LA English DT Article DE G protein-coupled receptor; orphan receptor; substantia nigra; corpus callosum ID GASTRIN-RELEASING PEPTIDE; BOMBESIN RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; DISTINCT; CELLS; CDNA AB The mammalian bombesin (Bn)-like neuropeptide receptors gastrin-releasing peptide receptor (GRP-R) and neuromedin B receptor (NMB-R) transduce a variety of physiological signals that regulate secretion, growth, muscle contraction, chemotaxis and neuromodulation. We have used reverse transcription-polymerase chain reaction (PCR) to isolate a cDNA from human brain mRNA, GPCR/CNS, that encodes a putative G protein-coupled receptor (GPCR) based upon the presence of the paradigmatic seven heptahelical transmembrane domains in its predicted amino acid sequence. Analysis of the deduced protein sequence of GPCR/CNS reveals this putative receptor to be 98% identical to the deduced amino acid sequence of a recently reported gene product and minimally identical (similar to 23%) to both murine GRP-R and human endothelin-B (ET-B) receptor. Our deduced protein sequence differs at 12 positions, scattered throughout the open reading frame, relative to the original sequence. A 3.7 kb GPCR/CNS mRNA species is expressed in vivo in a tissue-specific manner, with highest levels detected in brain and spinal cord, lower levels found in testis, placenta and liver, but no detectable expression observed in any other tissue. Analysis of GPCR/CNS genomic clones reveals that the human gene contains one intron that is about 21 kb in length that divides the coding region into two exons and maps to human chromosome 7q31. No specific binding is observed with either a newly identified ligand (DTyr(6),beta Ala(11),Phe(13),Nle(14)]Bn-(6-14)) having high affinity for all Bn receptor subtypes or Bn after GPCR/CNS is stably expressed in fibroblasts. No elevation in inositol trisphosphate is observed after the application of micromolar levels of either DPhe(6),beta Ala(11),Phe(13),Nle(14)]Bn-(6-14) or Bn, a concentration of agonist known to activate all four known Bn receptor subtypes. When GPCR/CNS is expressed in Xenopus oocytes, no activation of the calcium-dependent chloride channel is detected despite the addition of micromolar levels of Bn peptide agonists. We conclude that the natural ligand for this receptor is none of the known naturally occurring Bn-like peptides and the true agonist for GPCR/CNS remains to be elucidated. (C) 1998 Elsevier Science B.V. C1 Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Ramat Aviv, Israel. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. NR 16 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1998 VL 54 IS 1 BP 152 EP 160 DI 10.1016/S0169-328X(97)00336-7 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZC567 UT WOS:000072593600017 ER PT J AU Phillips, KK White, AE Hicks, DJ Welch, DR Barrett, JC Wei, LL Weissman, BE AF Phillips, KK White, AE Hicks, DJ Welch, DR Barrett, JC Wei, LL Weissman, BE TI Correlation between reduction of metastasis in the MDA-MB-435 model system and increased expression of the Kai-1 protein SO MOLECULAR CARCINOGENESIS LA English DT Article DE metastasis; suppressor gene; breast cancer; human chromosome 11; microcell hybrid ID TUMOR-SUPPRESSOR GENE; CELL LUNG-CANCER; BREAST-CARCINOMA; TRANSMEMBRANE-4 SUPERFAMILY; CHROMOSOMAL LOCALIZATION; SYNCYTIUM FORMATION; HETEROZYGOSITY; DELETION; ANTIGEN; REGION AB Using microcell-mediated transfer of a normal chromosome 11 into the highly metastatic MDA-MB-435 human breast carcinoma cell line, we previously showed that human chromosome 11 contains a metastasis-suppressor gene for breast cancer. A known metastasis-suppressor gene, kai-1, and a related family member, tapa-1, have been mapped to chromosome 11p11.2 and 11p15.5, respectively. To determine if these genes are responsible for the metastasis suppression seen in our microcell hybrids, we examined their expression by western blot analysis. Although tapa-l expression did not significantly correlate with metastasis suppression, kai-1 production was dramatically increased in the metastasis-suppressed chromosome 11 microcell hybrids and unchanged in the metastatic chromosome 6 controls. Transfection of full-length kai-1 cDNA into MDA-MB-435 cells resulted in clones that did not have a significantly decreased in vivo incidence of lung metastases. However, western blot analysis showed that the primary tumors and the metastatic lesions of the transfectants had decreased levels of kai-1 protein compared with the inoculated cells. Furthermore, several of the transfectant clones expressed heavily modified kai-1 protein compared with that of the microcell hybrids. Our data indicate that protein modification may affect the normal function of kai-1 in vivo and that a threshold level of kai-1 protein expression may be necessary for suppression of the metastatic phenotype. (C) 1998 Wiley-Liss, Inc. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Expt Pathol, Hershey, PA 17033 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Weissman, BE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. RI Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 FU NCI NIH HHS [CA 62168, CA 40011]; PHS HHS [44470] NR 33 TC 40 Z9 40 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 FEB PY 1998 VL 21 IS 2 BP 111 EP 120 DI 10.1002/(SICI)1098-2744(199802)21:2<111::AID-MC5>3.0.CO;2-Q PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA ZA167 UT WOS:000072335700005 PM 9496911 ER PT J AU Clark, JA Bonner, TI Kim, AS Usdin, TB AF Clark, JA Bonner, TI Kim, AS Usdin, TB TI Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; N-TERMINAL DOMAIN; TRANSMEMBRANE REGION; SECRETIN RECEPTOR; PLASMA-MEMBRANE; VIP RECEPTOR; SUBSTANCE-P; CYCLIC-AMP; BINDING; RESIDUES AB PTH and PTH-related peptide (PTHrP) bind to the PTH/PTHrP receptor and stimulate cAMP accumulation with similar efficacy. Only PTH activates the PTH2 receptor. To examine the structural basis for this selectivity, we analyzed receptor chimeras in which the amino terminus and third extracellular domains of the two receptors were interchanged. All chimeric receptors bound radiolabeled PTH with high affinity. Transfer of the PTH2 receptor amino terminus to the PTH/PTHrP receptor eliminated high-affinity PTHrP binding and significantly decreased activation by PTHrP. A PTH/PTHrP receptor N terminus modified by deletion of the nonhomologous E2 domain transferred weak PTHrP interaction to the PTH2 receptor. Introduction of the PTH2 receptor third extracellular loop into the PTH/PTHrP receptor increased the EC50 for PTH and PTHrP, while preserving high-affinity PTH binding and eliminating high-affinity PTHrP binding. Similarly, transfer of the PTH/PTHrP receptor third extracellular loop preserved high-affinity PTH binding by the PTH2 receptor but decreased its activation. Return of Gln440 and Arg394, corresponding residues in the PTH/PTHrP and PTH2 receptor third extracellular loops, to the parent residue restored function of these receptors. Simultaneous interchange of wild-type amino termini and third extracellular loops eliminated agonist activation but not binding for both receptors. Function was restored by elimination of the E2 domain in the receptor with a PTH/PTHrP receptor N terminus and return of Gln440/Arg394 to the parent sequence in both receptors. These data suggest that the amino terminus and third extracellular loop of the PTH2 and PTH/PTHrP receptors interact similarly with PTH, and that both domains contribute to differential interaction with PTHrP. C1 NIMH, Genet Sect, Bethesda, MD 20892 USA. RP Clark, JA (reprint author), NIMH, Genet Sect, Bldg 36,Room 3B-12,36 Convent Dr,MSC 4090, Bethesda, MD 20892 USA. EM janet@codon.nih.gov NR 45 TC 30 Z9 30 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1998 VL 12 IS 2 BP 193 EP 206 DI 10.1210/me.12.2.193 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YU587 UT WOS:000071732800004 PM 9482662 ER PT J AU Emmert-Buck, MR Debelenko, LV Agarwal, S Kester, MB Manickam, P Zhuang, ZP Guru, SC Olufemi, SE Burns, AL Chandrasekharappa, SC Lubensky, IA Liotta, LA Skarulis, MC Spiegel, AM Marx, SJ Collins, FS AF Emmert-Buck, MR Debelenko, LV Agarwal, S Kester, MB Manickam, P Zhuang, ZP Guru, SC Olufemi, SE Burns, AL Chandrasekharappa, SC Lubensky, IA Liotta, LA Skarulis, MC Spiegel, AM Marx, SJ Collins, FS TI 11q13 allelotype analysis in 27 Northern American MEN1 kindreds identifies two distinct founder chromosomes SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE MEN1; chromosome 11q13; haplotype ID MULTIPLE ENDOCRINE NEOPLASIA; LINKAGE ANALYSIS; INTEGRATED MAP; TYPE-1; MARKERS; FAMILIES; GENE AB We analyzed constitutional and tumor DNA from 27 MEN1 kindreds not known to be related to each other. Disease allele haplotypes were constructed for each pedigree based on shared alleles from two or more affected members and from determination of allelic loss patterns in their tumors. Analysis of disease allele haplotypes showed unexpected linkage disequilibrium at marker PYGM. Further haplotype analysis indicated this could be explained by the presence of two founder chromosomes, one in four families, the other in three. A shared disease haplotype was not observed among two MEN1 kindreds with the prolactinoma phenotype of MEN1. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 9C101,10 Ctr Dr MSC 1802, Bethesda, MD 20892 USA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD FEB PY 1998 VL 63 IS 2 BP 151 EP 155 DI 10.1006/mgme.1997.2649 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA ZR387 UT WOS:000073969900011 PM 9562970 ER PT J AU Schroeder, HW Zhu, ZB March, RE Campbell, RD Berney, SM Nedospasov, SA Turetskaya, RL Atkinson, TP Go, RCP Cooper, MD Volanakis, JE AF Schroeder, HW Zhu, ZB March, RE Campbell, RD Berney, SM Nedospasov, SA Turetskaya, RL Atkinson, TP Go, RCP Cooper, MD Volanakis, JE TI Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes SO MOLECULAR MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NECROSIS-FACTOR-ALPHA; PERIPHERAL LYMPHOID ORGANS; TNF-ALPHA; PROMOTER REGION; POLYMORPHIC MARKERS; LYMPHOTOXIN-ALPHA; HLA SEGREGATION; CELL-SURFACE; B-CELLS AB Background: A common genetic basis for IgA deficiency (IgAD) and common variable immunodeficiency (CVID) is suggested by their occurrence in members of the same family and the similarity of the underlying B cell differentiation defects. An association between IgAD/CVID and HLA alleles DR3, B8, and Al has also been documented. In a search for the gene(s) in the major histocompatibility complex (MHC) that predispose to IgAD/CVID, we analyzed the extended MHC haplotypes present in a large family with 8 affected members. Materials and Methods: We examined the CVID proband, 72 immediate relatives, and 21 spouses; and determined their serum immunoglobulin concentrations. The MHC haplotype analysis of individual family members employed 21 allelic DNA and protein markers, including seven newly available micsrosatellite markers. Results: Forty-one (56%) of the 73 relatives by common descent were heterozygous and nine (12%) were homozygous for a fragment or the entire extended MHC haplotype designated haplotype 1 that included HLA-DR3, -C4A-0, -B8, and -Al. The remarkable prevalence of haplotype 1 was due in part to marital introduction into the family of 11 different copies of the haplotype, eight sharing 20 identical genotype markers between HLA-DR3 and HLA-B8, and three that contained fragments of haplotype 1. Conclusion: Crossover events within the MHC indicated a susceptibility locus for IgAD/CVID between the class III markers D821/D823 and HLA-Bg, a region populated by 21 genes that include tumor necrosis factor alpha and lymphotoxins alpha and beta. Inheritance of at least this fragment of haplotype 1 appears to be necessary for the development of IgAD/CVID in this family. C1 Univ Alabama, Wallace Tumor Inst 364, Div Dev & Clin Immunol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Dept Publ Hlth, Birmingham, AL 35294 USA. Univ Alabama, Howard Hughes Med Inst, Birmingham, AL 35294 USA. Univ Oxford, Dept Biochem, MRC, Immunochem Unit, Oxford OX1 3QU, England. NCI, Mol Immunoregulat Lab, DBS & Intramural Res Support Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Belozersky Inst Physicochem Biol, Moscow, Russia. RP Schroeder, HW (reprint author), Univ Alabama, Wallace Tumor Inst 364, Div Dev & Clin Immunol, UAB Stn, Birmingham, AL 35294 USA. EM Harry.Schroeder@ccc.uab.edu RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU NIAID NIH HHS [AI07051, AI30879, AI33621, R21 AI033621, T32 AI007051] NR 75 TC 89 Z9 93 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD FEB PY 1998 VL 4 IS 2 BP 72 EP 86 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZC168 UT WOS:000072547600002 PM 9508785 ER PT J AU Varughese, M Chi, A Teixeira, AV Nicholls, PJ Keith, JM Leppla, SH AF Varughese, M Chi, A Teixeira, AV Nicholls, PJ Keith, JM Leppla, SH TI Internalization of a Bacillus anthracis protective antigen c-Myc fusion protein mediated by cell surface anti-c-Myc antibodies SO MOLECULAR MEDICINE LA English DT Article ID TOXIN LETHAL FACTOR; MONOCLONAL-ANTIBODIES; MAMMALIAN-CELLS; PSEUDOMONAS EXOTOXIN; RECEPTOR; SEQUENCE; BINDING; DOMAINS; GROWTH; ENTRY AB Background: Anthrax toxin, secreted by Bacillus anthracis, consists of protective antigen (PA) and either lethal factor (LF) or edema factor (EF). PA, the receptor-binding component of the toxin, translocates LF or EF into the cytosol, where the latter proteins exert their toxic effects. We hypothesized that anthrax toxin fusion proteins could be used to kill virus-infected cells and tumor cells, if PA could be redirected to unique receptors found only on these cells. Materials And Methods: To test this hypothesis in a model system, amino acids 410-419 of the human p62(c-myc) epitope were fused to the C-terminus of PA to redirect PA to the c-Myc-specific hybridoma cell line 9E10. Results: The PA-c-Myc fusion protein killed both mouse macrophages and 9E10 hybridoma cells when administered with LF or an LF fusion protein (FP59), respectively. Similar results were obtained with PA, which suggests that PA-c-Myc used the endogenous PA receptor to enter the cells. By blocking the endogenous PA receptors on 9E10 cells with the competitive inhibitor PA SNKE Delta FF, the PA-c-Myc was directed to an alternate receptor, i.e., the anti-c-Myc antibodies presented on the cell surface. The c-Myc IgG were proven to act as receptors because the addition of a synthetic peptide containing the c-Myc epitope along with PA SNFK Delta FF further reduced the toxicity of PA-c-Myc + FP59. Conclusion: This study shows that PA can be redirected to alternate receptors by adding novel epitopes to the C-terminus of PA, enabling the creation of cell-directed toxins for therapeutic purposes. C1 NIDR, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP NIDR, Oral Infect & Immun Branch, Bldg 30,Room 316,30 Convent Dr MSC 4350, Bethesda, MD 20892 USA. EM leppla@nih.gov NR 41 TC 51 Z9 52 U1 0 U2 0 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD FEB PY 1998 VL 4 IS 2 BP 87 EP 95 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZC168 UT WOS:000072547600003 PM 9508786 ER PT J AU Joshi, PB Sacks, DL Modi, G McMaster, WR AF Joshi, PB Sacks, DL Modi, G McMaster, WR TI Targeted gene deletion of Leishmania major genes encoding developmental stage-specific leishmanolysin (GP63) SO MOLECULAR MICROBIOLOGY LA English DT Article ID PROMASTIGOTE SURFACE PROTEASE; GLYCOPROTEIN GP63; CRITHIDIA-FASCICULATA; PHLEBOTOMUS-PAPATASI; ESCHERICHIA-COLI; CELL-ADHESION; NULL MUTANTS; LIPOPHOSPHOGLYCAN; EXPRESSION; METALLOPROTEINASE AB The major surface glycoprotein of Leishmania major is a zinc metalloproteinase of 63 kDa referred to as leishmanolysin or GP63, which is encoded by a family of seven genes, Targeted gene replacement was used to delete gp63 genes 1-6 encoding the highly expressed promastigote and constitutively expressed GP63, In the L. major homozygous mutants deficient in gp63 genes 1-6, there was no expression of GP63 as detected by reverse transcription-polymerase chain reaction (RT-PCR) or fluorescent staining in promastigotes from the procyclic stage (logarithmic growth phase), The remaining L. major gP63 gene 7 was shown to be developmentally regulated, as it was expressed exclusively in infectious metacyclic stage (late stationary growth phase) promastigotes and in lesion amastigotes, The gp63 genes 1-6-deficient mutants showed increased sensitivity to complement-mediated lysis, The sensitivity to lysis was greater in procyclics than in metacyclics when compared with the equivalent wild-type stages, Increased resistance of the mutant metacyclic promastigotes correlated with the expression of gp63 gene 7 and was restored to the same levels as wild-type promastigotes by transfection with gp63 gene 1, Thus, expression of GP63 is clearly involved in conferring resistance to complement-mediated lysis, The L. major GP63 1-6 mutants were capable of infecting mouse macrophages and differentiating into amastigotes, Similar levels of infection and subsequent intracellular survival were observed when mouse macrophages were infected in vitro with wild type, GP63 1-6 mutants and mutants transfected with gp63 gene 1,The GP63 1-6 mutants were capable of lesion formation in BALB/c mice and, thus, gp63 genes 1-6 do not play a role in the survival of the parasite within mouse macrophages. The role of gp63 genes 1-6 in parasite development within the sandfly vector was studied. GP63 1-6 mutants grew normally in the blood-engorged midgut of both Phlebotomus argentipes and P. papatasi, However, both wild-type and mutant promastigotes were lost after 2 days' growth in P. papatasi. The complete developmental pathway in P. argentipes was observed for wild-type promastigotes, GP63 1-6 mutants and mutants transfected with gp63 gene 1, Normal stage differentiation from amastigotes to procyclics, to nectomonads, to haptomonads and to infectious metacyclics was observed, Thus, the highly expressed promastigote forms of GP63, encoded by gp63 genes 1-6, do not appear to be required for nutrient utilization in the bloodmeal during the early stages of development in the sandfly or for midgut attachment and further development, gp63 1-6 genes do, however, play a major protective role against complement-mediated lysis when promastigotes are introduced into the mammalian host. C1 Univ British Columbia, Dept Med Genet, Jack Bell Res Ctr, Vancouver, BC V6H 3Z6, Canada. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP McMaster, WR (reprint author), Univ British Columbia, Dept Med Genet, Jack Bell Res Ctr, 2660 Oak St, Vancouver, BC V6H 3Z6, Canada. EM robm@unixg.ubc.ca NR 44 TC 80 Z9 83 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1998 VL 27 IS 3 BP 519 EP 530 DI 10.1046/j.1365-2958.1998.00689.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YX027 UT WOS:000071999000002 PM 9489664 ER PT J AU Britton, RA Powell, BS Dasgupta, S Sun, Q Margolin, W Lupski, JR Court, DL AF Britton, RA Powell, BS Dasgupta, S Sun, Q Margolin, W Lupski, JR Court, DL TI Cell cycle arrest in era GTPase mutants: a potential growth rate-regulated checkpoint in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID DIVISION PROTEIN FTSZ; BINDING PROTEIN; RNASE-III; GENETIC-ANALYSIS; RNC OPERON; RAS AB Era is a low-molecular-weight GTPase essential for Escherichia coli viability. The gene encoding Era is found in the me operon, and the synthesis of both RNase ill and Era increases with growth rate. Mutants that are partially defective in Era GTPase activity or that are reduced in the synthesis of wild-type Era become arrested in the cell cycle at the predivisional two-cell stage. The partially defective Era GTPase mutation (era1) suppresses several temperature-sensitive lethal alleles that affect chromosome replication and chromosome partitioning but not cell division. Our results suggest that Era plays an important role in cell cycle progression at a specific point in the cycle, after chromosome partitioning but before cytokinesis. Possible functions for Era in cell cycle progression and the initiation of cell division are discussed. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Lab Gene Regulat & Chromosome Biol, Frederick, MD 21702 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Cell & Mol Biol Program, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Court, DL (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Lab Gene Regulat & Chromosome Biol, Frederick, MD 21702 USA. EM court@ncifcrf.gov NR 46 TC 98 Z9 110 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1998 VL 27 IS 4 BP 739 EP 750 DI 10.1046/j.1365-2958.1998.00719.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA YY283 UT WOS:000072131600007 PM 9515700 ER PT J AU Shi, LM Myers, TG Fan, Y O'Connor, PM Paull, KD Friend, SH Weinstein, JN AF Shi, LM Myers, TG Fan, Y O'Connor, PM Paull, KD Friend, SH Weinstein, JN TI Mining the National Cancer Institute anticancer drug discovery database: Cluster analysis of ellipticine analogs with p53-inverse and central nervous system-selective patterns of activity SO MOLECULAR PHARMACOLOGY LA English DT Article ID TUMOR-CELL-LINES; HUMAN BRAIN; IN-VITRO; TOPOISOMERASE-II; DESIGN; AGENTS; SCREEN; DNA; CYTOTOXICITY; SENSITIVITY AB The United States National Cancer Institute conducts an anticancer 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. To date, similar to 62,000 compounds have been tested in the program, and a large amount of information on their activity patterns has been accumulated. For the current study, anticancer activity patterns of 112 ellipticine analogs were analyzed with the use of a hierarchical clustering algorithm. A dramatic coherence between molecular structures and their activity patterns could be seen from the cluster tree: the first subgroup (compounds 1-66) consisted principally of normal ellipticines, whereas the second subgroup (compounds 67-112) consisted principally of N-2-alkyl-substituted ellipticiniums. Almost all apparent discrepancies in this clustering were explainable on the basis of chemical transformation to active forms under cell culture conditions. Correlations of activity with p53 status and selective activity against cells of central nervous system origin made this data set of special interest to us. The ellipticiniums, but not the ellipticines, were more potent on average against p53 mutant cells than against p53 wild-type ones (i.e., they seemed to be "p53-inverse") in this short term assay. This study strongly supports the hypothesis that "fingerprint" patterns of activity in the National Cancer Institute in vitro cell screening program encode incisive information on the mechanisms of action and other biological behaviors of tested compounds. Insights gained by mining the activity patterns could contribute to our understanding of anticancer drugs and the molecular pharmacology of cancer. C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Informat Technol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment Diag & Ctr, NIH, Bethesda, MD 20892 USA. NCI, Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Weinstein, JN (reprint author), NCI, Mol Pharmacol Lab, NIH, Bldg 37,Room 5D05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 70 Z9 70 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1998 VL 53 IS 2 BP 241 EP 251 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YX664 UT WOS:000072064000010 PM 9463482 ER PT J AU Ismail, ASA van Groeningen, CJ Hardcastle, A Ren, QF Aherne, GW Geoffroy, F Allegra, CJ Grem, JL AF Ismail, ASA van Groeningen, CJ Hardcastle, A Ren, QF Aherne, GW Geoffroy, F Allegra, CJ Grem, JL TI Modulation of fluorouracil cytotoxicity by interferon-alpha and -gamma SO MOLECULAR PHARMACOLOGY LA English DT Article ID COLON-CARCINOMA-CELLS; BETA-SER-INTERFERON; THYMIDYLATE SYNTHASE; CANCER-CELLS; THYMIDINE PHOSPHORYLASE; DNA-POLYMERASES; STRAND BREAKS; TUMOR-CELLS; DAUDI CELLS; 5-FLUOROURACIL AB Because interferons (IFN)-alpha and -gamma individually have increased fluorouracil (FUra) cytotoxicity in several in vitro models, we studied the effects of FUra combined with IFN-alpha + gamma in HT29 colon cancer cells. A 96-hr exposure to IFN-alpha (500 units/ml) plus IFN-gamma (10 units/ml) and a 72-hr exposure to 0.25-1 mu M FUra (hr 24-96) inhibited cell growth and colony formation in an additive or more-than-additive fashion. When cells were exposed to IFN-alpha + gamma and FUra, free FdUMP levels became detectable, whereas [H-3]FUra-RNA incorporation decreased. Exposure to IFN-alpha + gamma, FUra, or the combination decreased dTTP pools to 58%, 43%, and 17% of control, respectively. A marked increase in the dATP to dTTP ratio was seen with FUra with or without IFN-alpha + gamma. Thymidylate synthase catalytic activity was reduced to 28% and 24% of control with FUra with or without IFN-alpha + gamma, suggesting that the enhanced dTTP depletion must be due to another mechanism. FUra-mediated thymidylate synthase inhibition was accompanied by a 124-fold increase in total deoxyuridylate immunoreactivity and a 31-fold increase in dUTP pools, but the addition of IFN-alpha + gamma attenuated the accumulation. Treatment with IFN-alpha + gamma and FUra individually interfered with nascent DNA chain elongation, whereas the three-drug combination produced the most striking effects. IFN-alpha + gamma plus FUra produced the greatest amount of single-strand breaks in nascent DNA and dramatically decreased net DNA synthesis. IFN-alpha + gamma with or without FUra produced double-strand breaks in parental DNA. These results suggest that dTTP depletion, dATP/dTTP imbalance, pronounced inhibition of DNA synthesis, and damage to nascent and parental DNA contribute to the enhanced cytotoxicity with the triple combination. C1 NCI, Natl Naval Med Ctr, NMOB, Bethesda, MD 20889 USA. CRC, Ctr Canc Therapeut, Inst Canc Res, Surrey SM2 5NG, England. RP Grem, JL (reprint author), NCI, Natl Naval Med Ctr, NMOB, Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM jgrem@helix.nih.gov NR 40 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1998 VL 53 IS 2 BP 252 EP 261 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YX664 UT WOS:000072064000011 PM 9463483 ER PT J AU Drayna, D AF Drayna, D TI Genetics tunes in SO NATURE GENETICS LA English DT Editorial Material C1 Natl Inst Deafness & Commun Disorders, NIH, Rockville, MD USA. RP Drayna, D (reprint author), Natl Inst Deafness & Commun Disorders, NIH, 5 Res Court, Rockville, MD USA. EM ddrayna@pop.nidcd.nih.gov NR 8 TC 3 Z9 3 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1998 VL 18 IS 2 BP 96 EP 97 DI 10.1038/ng0298-96 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YV010 UT WOS:000071779500004 PM 9462730 ER PT J AU Perry, WL Hustad, CM Swing, DA O'Sullivan, TN Jenkins, NA Copeland, NG AF Perry, WL Hustad, CM Swing, DA O'Sullivan, TN Jenkins, NA Copeland, NG TI The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a(18H) mice SO NATURE GENETICS LA English DT Article ID MOTH-EATEN; RECEPTOR; MOUSE; GENE; POLYUBIQUITINATION; DEGRADATION; PATHOLOGY; MUTATIONS; PATHWAY; DOMAIN AB Non-agouti-lethal 18H (a(18H)) mice are dark agouti with black pinna hairs. What makes these mice unique is that they develop a spectrum of immunological diseases not seen in other agouti mutant mice(1). On the JU/Ct background, a(18H) mice develop an inflammatory disease of the large intestine, On the C57BL/6J background, they develop a fatal disease characterized by pulmonary chronic interstitial inflammation and alveolar proteinosis, inflammation of the glandular stomach and skin resulting in scarring due to constant itching, and hyperplasia of lymphoid cells, haematopoietic cells and the forestomach epithelium. Previous studies suggested that the a(18H) mutation results from a paracentric inversion that affects two loci: agouti and another, as yet unidentified locus designated itchy (the provisional gene symbol is Itch), that is responsible for the immunological phenotype of a(18H) mice(1). Here we confirm that a(18H) results from an inversion and show that Itch encodes a novel E3 ubiquitin protein ligase, a protein involved in ubiquitin-mediated protein degradation. Our results indicate that ubiquitin-dependent proteolysis is an important mediator of the immune response in vivo and provide evidence for itch's role in inflammation and the regulation of epithelial and haematopoietic cell growth. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. EM copeland@ncifcrf.gov NR 25 TC 211 Z9 216 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1998 VL 18 IS 2 BP 143 EP 146 DI 10.1038/ng0298-143 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YV010 UT WOS:000071779500021 PM 9462742 ER PT J AU Hacia, JG Makalowski, W Edgemon, K Erdos, MR Robbins, CM Fodor, SPA Brody, LC Collins, FS AF Hacia, JG Makalowski, W Edgemon, K Erdos, MR Robbins, CM Fodor, SPA Brody, LC Collins, FS TI Evolutionary sequence comparisons using high-density oligonucleotide arrays SO NATURE GENETICS LA English DT Article ID HYBRIDIZATION; BRCA1; STRATEGY; GENES AB We explored the utility of high-density oligonucleotide arrays (DNA chips) for obtaining sequence information from homologous genes in closely related species. Orthologues of the human BRCA1 exon 11, all approximately 3.4 kb in length and ranging from 98.2% to 83.5% nucleotide identity, were subjected to hybridization-based and conventional dideoxysequencing analysis. Retrospective guidelines for identifying high-fidelity hybridization-based sequence calls were formulated based upon dideoxysequencing results. Prospective application of these rules yielded base-calling with at least 98.8% accuracy over orthologous sequence tracts shown to have approximately 99% identity. For higher primate sequences with greater than 97% nucleotide identity, base-calling was made with at least 99.91% accuracy covering a minimum of 97% of the sequence. Using a second-tier confirmatory hybridization chip strategy, shown in several cases to confirm the identity of predicted sequence changes, the complete sequence of the chimpanzee. gorilla and orangutan orthologues should be deducible solely through hybridization-based methodologies. Analysis of less highly conserved orthologues can still identify conserved nucleotide tracts of at least 15 nucleotides and can provide useful information for designing primers. DNA-chip based assays can be a valuable new technology for obtaining high-throughput cost-effective sequence information from related genomes. C1 Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Affymetrix, Santa Clara, CA 95051 USA. RP Collins, FS (reprint author), Natl Human Genome Res Inst, NIH, Bldg 49-3A14, Bethesda, MD 20892 USA. RI Makalowski, Wojciech/I-2843-2016 FU NHGRI NIH HHS [5POLHGO1323-03] NR 19 TC 83 Z9 98 U1 0 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 FEB PY 1998 VL 18 IS 2 BP 155 EP 158 DI 10.1038/ng0298-155 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YV010 UT WOS:000071779500024 PM 9462745 ER PT J AU Wang, G Chopra, RK Royal, RE Yang, JC Rosenberg, SA Hwu, P AF Wang, G Chopra, RK Royal, RE Yang, JC Rosenberg, SA Hwu, P TI A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen SO NATURE MEDICINE LA English DT Article ID TUMOR-CELLS; ZETA-CHAIN; LYMPHOCYTES; SPECIFICITY; EXPRESSION; VECTORS; LONG AB In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Hwu, P (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. NR 32 TC 46 Z9 47 U1 0 U2 2 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 FEB PY 1998 VL 4 IS 2 BP 168 EP 172 DI 10.1038/nm0298-168 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ392 UT WOS:000072249800031 PM 9461189 ER PT J AU Donahue, RE Bunnell, BA Zink, MC Metzger, ME Westro, RP Kirby, MR Unangst, T Clements, JE Morgan, RA AF Donahue, RE Bunnell, BA Zink, MC Metzger, ME Westro, RP Kirby, MR Unangst, T Clements, JE Morgan, RA TI Reduction in SIV replication in rhesus macaques infused with autologous lymphocytes engineered with antiviral genes SO NATURE MEDICINE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELLS; IMMUNIZATION; EXPRESSION; THERAPY; MUTANTS; MODELS; VIVO AB Simian immunodeficiency virus (SIV) infection of nonhuman primates is one of the most relevant animals models of HIV infection in humans. To test a potential anti-HIV gene therapy strategy in this model, CD4-enriched lymphocytes from three rhesus macaques were subjected to retrovirally mediated gene transfer with a vector expressing an antisense tat/rev gene. This group of animals and three control macaques were subsequently infected with SIVmac239. Blood and lymph nodes from all macaques were sampled for more than a year to monitor the progress of infection. Although all animals became infected, the animals that received the lymphocytes engineered with the antisense vector demonstrated a significant reduction in viral load in both peripheral blood and lymph nodes, had sustained numbers of CD4(+) cells, and exhibited little disruption of lymph node architecture. C1 NIH, Natl Human Genome Res Inst, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Rockville, MD 20901 USA. Johns Hopkins Univ, Sch Med, Div Comparat Med, Baltimore, MD 21205 USA. RP Morgan, RA (reprint author), NIH, Natl Human Genome Res Inst, Clin Gene Therapy Branch, Bldg 10,Room 10C103,10 Ctr Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL 53248]; NINDS NIH HHS [NS 35751, NS 32208] NR 22 TC 35 Z9 36 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 FEB PY 1998 VL 4 IS 2 BP 181 EP 186 DI 10.1038/nm0298-181 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ392 UT WOS:000072249800033 PM 9461191 ER PT J AU Kunkel, TA Wilson, SH AF Kunkel, TA Wilson, SH TI DNA polymerases on the move SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID I KLENOW FRAGMENT; REPLICATION FIDELITY; BETA; MECHANISM; PROTEIN AB Recent crystal structures of DNA polymerases provide new insights into conformational dynamics and DNA minor groove interactions that are critical for efficient and accurate DNA synthesis. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 27 TC 58 Z9 58 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD FEB PY 1998 VL 5 IS 2 BP 95 EP 99 DI 10.1038/nsb0298-95 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YV007 UT WOS:000071779200005 PM 9461069 ER PT J AU Lubkowski, J Hennecke, F Pluckthun, A Wlodawer, A AF Lubkowski, J Hennecke, F Pluckthun, A Wlodawer, A TI The structural basis of phage display elucidated by the crystal structure of the N-terminal domains of g3p SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID FILAMENTOUS BACTERIOPHAGES; 3-DIMENSIONAL STRUCTURE; NUCLEOTIDE-SEQUENCE; ADSORPTION PROTEIN; ESCHERICHIA-COLI; GENE-III; FD; PROGRAM; CRYSTALLOGRAPHY; DIFFRACTION AB The structure of the two N-terminal domains of the gene 3 protein of filamentous phages (residues 1-217) has been solved by multiwavelength anomalous diffraction and refined at 1.46 A resolution. Each domain consists of either five or eight beta-strands and a single alpha-helix. Despite missing sequence homology, their cores superimposed with a root-mean-square deviation of 2 Angstrom. The domains are engaged in extensive interactions, resulting in a horseshoe shape with aliphatic amino acids and threonines lining the inside, delineating the likely binding site for the F-pilus. The glycine-rich linker connecting the domains is invisible in the otherwise highly ordered structure and may confer flexibility between the domains required during the infection process. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, POB B, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI Pluckthun, Andreas/C-2746-2009 OI Pluckthun, Andreas/0000-0003-4191-5306 NR 51 TC 84 Z9 88 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD FEB PY 1998 VL 5 IS 2 BP 140 EP 147 DI 10.1038/nsb0298-140 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YV007 UT WOS:000071779200016 PM 9461080 ER PT J AU Blackwell, KT Vogl, TP Alkon, DL AF Blackwell, KT Vogl, TP Alkon, DL TI Pattern matching in a model of dendritic spines SO NETWORK-COMPUTATION IN NEURAL SYSTEMS LA English DT Article ID HIPPOCAMPAL PYRAMIDAL NEURONS; CALCIUM-CONCENTRATION; K+ CURRENTS; MEMORY; RECOGNITION; CELLS; BRAIN; REDUCTION; CHANNELS; SOMATA AB Pattern matching, the ability to recognize and maximally respond to an input pattern that is similar to a previously learned pattern, is an essential step in any learning process. To investigate the properties of pattern matching in biological neurons, and in particular the role of a calcium-dependent potassium conductance, a circuit model of a small area of dendritic membrane with a number of dendritic spines is developed. Circuit model simulations show that dendritic membrane depolarization is greater in response to a previously learned pattern of synaptic inputs than in response to a novel pattern of synaptic inputs. These simulations, in combination with an analysis of the circuit model equations, reveal that when a synaptic input pattern is similar to the learned pattern of synaptic inputs, the total dendritic depolarization is a linear combination of dendritic depolarization contributed by individual spines. When at least one synaptic input differs markedly from the learned value, dendritic depolarization is at nonlinear combination of individual spine depolarizations. These principles of spine interactions are captured in a computationally simple set of 'similarity measure' equations which are shown to reproduce the response surface of the circuit model output. Thus, these similarity measure equations not only describe a biologically plausible model of pattern matching, they also satisfy computational requirements for use in artificial neural networks. C1 Environm Res Inst Michigan, Arlington, VA 22209 USA. NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Blackwell, KT (reprint author), George Mason Univ, MS 5C3, Fairfax, VA 22030 USA. OI Blackwell, Kim/0000-0003-4711-2344 FU NIMH NIH HHS [K21 MH001141]; NINDS NIH HHS [N01NS02389, N01NS32304] NR 38 TC 6 Z9 6 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0954-898X J9 NETWORK-COMP NEURAL JI Netw.-Comput. Neural Syst. PD FEB PY 1998 VL 9 IS 1 BP 107 EP 121 DI 10.1088/0954-898X/9/1/006 PG 15 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Neurosciences SC Computer Science; Engineering; Neurosciences & Neurology GA ZE593 UT WOS:000072810100006 PM 9861981 ER PT J AU Jacobson, JD Crofford, LJ Sun, LH Wilder, RL AF Jacobson, JD Crofford, LJ Sun, LH Wilder, RL TI Cyclical expression of GnRH and GnRH receptor mRNA in lymphoid organs SO NEUROENDOCRINOLOGY LA English DT Article DE gonadotropin-releasing hormone; gonadotropin-releasing hormone receptor; gonadal steroids; thymus; neuroimmune interactions; molecular neuroendocrinology ID HORMONE-RELEASING HORMONE; MESSENGER-RNA LEVELS; GENE-EXPRESSION; LHRH RECEPTORS; IN-VIVO; RAT; ESTRADIOL; LYMPHOCYTES; RESPONSES; THYMUS AB Gonadotropin-releasing hormone (GnRH) is known to possess dirct immunomodulatory effects, We have previously demonstrated that the administration of GnRH analogues modulates the expression of murine lupus independently of effects on gonadal steroids, We speculate that GnRH exerts direct actions at the level of the immune cells, GnRH receptors have been identified on lymphocytes, Because GnRH and GnRH receptor (GnRH-R) expression varies with the estrous cycle at the levels of the hypothalamus and pituitary, we speculated that similar cyclicity might be demonstrable in lymphoid tissue, In this report, we used competitive reverse transcription PCR to quantitate the expression of GnRH and GnRH-R mRNA in lymphoid organs throughout the estrous cycle in mice. We demonstrate that the pattern of expression of GnRH-R mRNA in spleen agrees closely with the pattern in the pituitaries of the same mice and the pattern previously reported in the rat pituitary, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus, A similar pattern is seen with GnRH-R mRNA expression in the thymus, Furthermore, we show that the expression of GnRH mRNA in both thymus and spleen agrees closely with the pattern of expression of its receptor, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus, Additional in vitro studies demonstrate that both GnRH and estradiol significantly increase the expression of GnRH-R mRNA in immune cells, These findings support an active role for GnRH in the immune system. C1 Univ Missouri, Childrens Mercy Hosp, Sch Med, Dept Pediat,Sect Endocrinol, Kansas City, MO 64108 USA. Univ Michigan, Sch Med, Div Rheumatol, Ann Arbor, MI USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD USA. RP Jacobson, JD (reprint author), Univ Missouri, Childrens Mercy Hosp, Sch Med, Dept Pediat,Sect Endocrinol, 2401 Gillham Rd, Kansas City, MO 64108 USA. EM jjacobson@CMH.edu RI Crofford, Leslie/J-8010-2013 NR 25 TC 38 Z9 39 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD FEB PY 1998 VL 67 IS 2 BP 117 EP 125 DI 10.1159/000054306 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA YW889 UT WOS:000071984200006 PM 9508042 ER PT J AU Deiber, MP Ibanez, V Honda, M Sadato, N Raman, R Hallett, M AF Deiber, MP Ibanez, V Honda, M Sadato, N Raman, R Hallett, M TI Cerebral processes related to visuomotor imagery and generation of simple finger movements studied with positron emission tomography SO NEUROIMAGE LA English DT Article DE human; motor imagery; pre-SMA; cerebellum; motor cortex ID SUPPLEMENTARY MOTOR AREA; FUNCTIONAL-ANATOMY; PREFRONTAL CORTEX; NEURONAL-ACTIVITY; EPISODIC MEMORY; CORTICAL AREAS; BRAIN; REPRESENTATIONS; IMAGINATION; ACTIVATION AB Positron emission tomography was used to compare the functional anatomy of visual imagination and generation of movement. Subjects were asked to generate visual images of their finger movement in response to a preparatory signal. Four conditions were tested: in two, no actual movement was required; in the other two, a second signal prompted the subjects to execute the imagined movement. Which movement to imagine was either specified by the preparatory stimulus or freely selected by the subjects. Compared with a rest condition, tasks involving only imagination activated several cortical regions (inferoparietal cortex, pre-supplementary motor area, anterior cingulate cortex, premotor cortex, dorsolateral prefrontal cortex) contralateral to the imagined movement. Tasks involving both imagination and movement additionally increased activity in the ipsilateral cerebellum, thalamus, contralateral anteroparietal, and motor cortex and decreased activity in the inferior frontal cortex. These results support the hypothesis that distinct functional systems are involved in visuomotor imagination and generation of simple finger movements: associative parietofrontal areas are primarily related to visuomotor imagination, with inferior frontal cortex Likely engaged in active motor suppression, and primary motor structures contribute mainly to movement execution. (C) 1998 Academic Press. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. INSERM, CERMEP, F-69003 Lyon, France. Fukui Med Sch, Dept Radiol, Matsuoka, Fukui, Japan. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, 10 Ctr Dr MSC 1428,Bldg 10,Room 5N226, Bethesda, MD 20892 USA. EM hallett@codon.nih.gov RI Deiber, Marie-Pierre/M-5949-2014 NR 54 TC 190 Z9 198 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1998 VL 7 IS 2 BP 73 EP 85 DI 10.1006/nimg.1997.0314 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZF549 UT WOS:000072908600001 PM 9571132 ER PT J AU Van Horn, JD Ellmore, TM Esposito, G Berman, KF AF Van Horn, JD Ellmore, TM Esposito, G Berman, KF TI Mapping voxel-based statistical power on parametric images SO NEUROIMAGE LA English DT Article ID ACTIVATION MAPS; SAMPLE-SIZE; PET IMAGES; SIGNAL; TOMOGRAPHY; SCALE AB Using a classic technique based on the noncentral F-distribution method for computing statistical power, we developed a general approach to the estimation of voxel-based power in functional brain image data analysis. We applied this method to PET data from a large sample (N = 40) of subjects performing the Wisconsin Card Sorting (WCST) paradigm analyzed with SPM95, produced statistical power maps for a range of sample sizes and smoothing filter widths, and examined the effects of sample size and image smoothing on the expected reliability of activation findings. At an uncorrected alpha of 0.01, a fixed filter size of 10 mm(3), and a range of power thresholds, maps revealed that the power to reject the null hypothesis in brain regions implicated in the task at Ns of 5 and 10 may not be sufficient to ensure reliable replication of significant findings and so should be interpreted with caution. At sample sizes approaching 20 subjects, sufficient power was found in the right dorsolateral prefrontal cortex (BA 46/9), right and left inferior parietal lobule (BA 40), and left inferior temporal lobe (BA 37), comprising the cortical network typically observed during the WCST. Filter size needed to maximize power varied widely, but systematically. across the brain, tending to follow known neuroanatomical landmarks. Statistical power considerations in brain imaging studies are critical for controlling the rate of false negatives and assuring reliable detection of cognitive activation. The variation of filter size for maximizing power across the brain suggests that the underlying neuroanatomy of functional units is an important consideration in the a priori selection of filter size. (C) 1998 Academic Press. C1 NIMH, CBDB, Unit PET, Bethesda, MD 20892 USA. RP Van Horn, JD (reprint author), NIMH, CBDB, Unit PET, Bldg 10,Room 4C-108,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ellmore, Timothy/0000-0001-6125-0044 NR 47 TC 32 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 1998 VL 7 IS 2 BP 97 EP 107 DI 10.1006/nimg.1997.0317 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZF549 UT WOS:000072908600003 PM 9558642 ER PT J AU Hott, JS Dalakas, MC Sung, C Hallett, M Youle, RJ AF Hott, JS Dalakas, MC Sung, C Hallett, M Youle, RJ TI Skeletal muscle-specific immunotoxin for the treatment of focal muscle spasm SO NEUROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; ACETYLCHOLINE-RECEPTOR; BOTULINUM TOXIN; MOUSE MUSCLE; CELL-LINE; RICIN; SELECTIVITY; TRANSFERRIN; MECHANISM; LECTINS AB Intramuscular injection of botulinum toxin type A (BTX) is used to treat many disorders characterized by muscular spasms. The utility of BTX, however, is limited by its short duration of action, the development of resistance after repeated injections, and cross-reactivity with autonomic neurons. To overcome these limitations, we engineered an immunotoxin (ITX) to damage skeletal muscle fibers selectively by chemically linking a monoclonal antibody against the nicotinic acetylcholine receptor to the toxin ricin. In vitro, the ITX was 20,000-fold more toxic to myotubes than myoblasts, consistent with the degree of acetylcholine receptor expression. The gastrocnemius muscles of 30 rats were unilaterally injected with a series of protein toxins at various concentrations and examined histopathologically 7 and 30 days later. ITX produced destructive myopathic changes at a dose 300-fold less than the maximum tolerated dose. Assessment of rat muscle strength after unilateral gastrocnemius injections showed that ITX was more effective and had a longer duration of action than BTX. ITXs may have potential for the treatment of involuntary muscle spasms. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. NIH, Biomed Engn & Instrumentat Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 10,Rm 5D-37, Bethesda, MD 20892 USA. NR 32 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1998 VL 50 IS 2 BP 485 EP 491 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA YX557 UT WOS:000072052500038 PM 9484377 ER PT J AU Harden, RN Rogers, D Fink, K Gracely, RH AF Harden, RN Rogers, D Fink, K Gracely, RH TI Controlled trial of ketorolac in tension-type headache SO NEUROLOGY LA English DT Article ID MANAGEMENT; EMERGENCY AB Intramuscular ketorolac 60 mg, meperidine 50 mg plus promethazine 25 mg, and normal saline were compared in acute exacerbations of tension-type headache. Forty-one subjects (30 females and 11 males) were randomized into three groups and evaluated by the McGill Short-Form Pain Questionnaire before treatment, and 0.5, 1, 2, 3, 4, 5, and 6 hours after treatment. All three groups showed a significant treatment effect that persisted for the 6 hours of evaluation. Ketorolac treatment was significantly better than placebo at 0.5 and 1 hour by the Visual Analog Scale (VAS) and Pain Rating Index, and better than meperidine at 2 hours (by the VAS). Meperidine and placebo did not differ at any time point. Ketorolac is effective in short-term treatment of tension-type headache. C1 Rehabil Inst Chicago, Chicago, IL 60611 USA. Med Univ S Carolina, Dept Phys Med & Rehabil, Charleston, SC 29425 USA. Northwestern Univ, Sch Med, Inst Rehabil, Chicago, IL USA. NIDR, NIH, Bethesda, MD 20892 USA. RP Harden, RN (reprint author), Rehabil Inst Chicago, 345 E Super,Room 407, Chicago, IL 60611 USA. NR 8 TC 14 Z9 14 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 FEB PY 1998 VL 50 IS 2 BP 507 EP 509 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA YX557 UT WOS:000072052500043 PM 9484382 ER PT J AU Caudle, RM Dubner, R AF Caudle, RM Dubner, R TI Ifenprodil blocks the excitatory effects of the opioid peptide dynorphin 1-17 on NMDA receptor mediated currents in the CA3 region of the guinea pig hippocampus SO NEUROPEPTIDES LA English DT Article ID LONG-TERM POTENTIATION; SPINAL-CORD INJURY; TAIL-FLICK REFLEX; D-ASPARTATE NMDA; DENTATE GYRUS; RAT-BRAIN; PYRAMIDAL CELLS; MODULATORY SITE; MECHANISMS; INDUCTION AB This study found that dynorphin had a biphasic concentration response relationship on N-methyl-D-aspartate (NMDA) receptor-mediated currents in the CA3 region of the guinea pig hippocampal slice. A previous study demonstrated that the inhibitory effect was mediated by a kappa(2) opioid receptor. In the present study, the polyamine site antagonist ifenprodil converted dynorphin's biphasic concentration response relationship to a monophasic inhibitory curve. The polyamine diethylenetriamine also blocked dynorphin's excitatory actions. The combination of dynorphin 1-17 and naloxone produced neurotoxicity, presumably as a result of dynorphin's excitatory actions on NMDA receptors. In addition, the release of endogenous dynorphin from mossy fibers in the presence of naloxone injured the cells. Ifenprodil prevented the neurotoxicity of both applied and released dynorphin. These findings suggest that dynorphin acts at a polyamine site to produce its excitatory effects and, further, suggest that dynorphin may mediate some neuropathologies through its interaction at this site. C1 NIDR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Oral & Craniofacial Biol Sci, Baltimore, MD 21201 USA. RP Caudle, RM (reprint author), NIDR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. NR 31 TC 33 Z9 33 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 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 1998 VL 32 IS 1 BP 87 EP 95 DI 10.1016/S0143-4179(98)90022-1 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA ZG936 UT WOS:000073054900008 PM 9571650 ER PT J AU Persico, AM Schindler, CW Davis, SC Ambrosio, E Uhl, GR AF Persico, AM Schindler, CW Davis, SC Ambrosio, E Uhl, GR TI Medial prefrontal cortical injections of c-fos antisense oligonucleotides transiently lower c-fos protein and mimic amphetamine withdrawal behaviours SO NEUROSCIENCE LA English DT Article ID ADHESION MOLECULE-1 EXPRESSION; MESSENGER-RNA; GENE-EXPRESSION; RAT-BRAIN; GLUCOCORTICOID RECEPTOR; GLUCOSE-METABOLISM; NUCLEUS-ACCUMBENS; DEPRESSION; COCAINE; INHIBITION AB Prefrontal cerebral cortical areas display decreased expression of several transcription factor/ immediate-early genes, including c-fos, during amphetamine withdrawal.(52) Antisense strategies can help to test possible roles for this prefrontal c-fos down-regulation in the behavioural correlates of amphetamine withdrawal. Medial prefrontal cortical injections delivering 1.7 nmoles of anti c-fas oligonucleotides revealed an approximately 3 h half-life for phosphothioate and a 15 min half-life for phosphodiester oligonucleotides. Antisense phosphothioates complementary to the c-fos translational start site reduced levels of c-Fos protein, while exerting modest and variable effects on c-fos messenger RNA levels. Neither missense phosphorothioate nor antisense phosphodiester oligonucleotides significantly reduced levels of either c-fos messenger RNA or protein. Animals injected with anti c-fos phosphothioate oligonucleotides into the medial prefrontal cortex displayed marked reductions in linear locomotor activity and repetitive movements measured in a novel environment, effects not seen when missense oligonucleotides were used or when animals were accustomed to the activity monitor prior to antisense oligonucleotide injection. Behavioural changes produced by prefrontal cortical injections of c-fos antisense oligonucleotides closely mimic alterations recorded during amphetamine withdrawal. Prefrontal c-fos could thus conceivably play roles in the neurobiological underpinnings of psychostimulant withdrawal and of responses to stressors such as exposure to novel environments. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 NIDA, MOL NEUROBIOL BRANCH, INTRAMURAL RES PROGRAM, NIH, BALTIMORE, MD 21224 USA. NIDA, BEHAV PHARMACOL & GENET BRANCH, INTRAMURAL RES PROGRAM, NIH, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. LIBERO IST UNIV, NEUROSCI LAB, ROME, ITALY. UNIV LOUISVILLE, DIV NEPHROL, LOUISVILLE, KY 40292 USA. Univ Nacl Educ Distancia, DEPT PSYCHOBIOL, MADRID, SPAIN. NR 81 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1998 VL 82 IS 4 BP 1115 EP 1129 PG 15 WC Neurosciences SC Neurosciences & Neurology GA YH164 UT WOS:A1998YH16400016 PM 9466435 ER PT J AU Buckley, NE Hansson, S Harta, G Mezey, E AF Buckley, NE Hansson, S Harta, G Mezey, E TI Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat SO NEUROSCIENCE LA English DT Article DE cannabinoid receptors; embryogenesis; uterus; brain; liver ID PREIMPLANTATION MOUSE EMBRYO; PIG SMALL-INTESTINE; CANNABINOID RECEPTOR; INTRAOCULAR-PRESSURE; GUINEA-PIG; NORMOTENSIVE RABBITS; PERINATAL EXPOSURE; PRENATAL EXPOSURE; MATERNAL EXPOSURE; DOPAMINE RELEASE AB We mapped the distribution of CB1 and CB2 receptor messenger RNAs in the developing rat to gain insight into how cannabinoids may affect embryogenesis. In situ hybridization histochemistry studies were done using riboprobes specific for CB1 or CB2 receptor messenger RNAs. We found that CB1 and CB2 receptor messenger RNAs are expressed in the placental cone and in the smooth muscle of the maternal uterus at the earliest gestational periods studied [from eight days of gestation (E8) through E12]. In the embryo, as early as E11, CB1 receptor messenger RNA is expressed in some cells of the neural tube and, at later embryological stages (from E15 to E21), in several distinct structures within the central nervous system. In addition, high levels of CB1 receptor messenger RNA were also found in areas of the peripheral nervous system such as the sympathetic and parasympathetic ganglia, in the retina and in the enteric ganglia of the gastrointestinal tract. In addition to neural structures, high levels of the CB1 receptor messenger RNA were also present in two endocrine organs, the thyroid gland and the adrenal gland. On the other hand, CB2 receptor messenger RNA is expressed exclusively in the liver of the embryo as early as E13. The region-specific expression of CB1 and CB2 receptor messenger RNAs suggests that these receptors have a functional role during embryogenesis. (C) 1997 IBRO. Published by Elsevier Science. C1 NIMH,NIH,BETHESDA,MD 20892. RP Buckley, NE (reprint author), NINCDS,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 53 TC 150 Z9 156 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1998 VL 82 IS 4 BP 1131 EP 1149 PG 19 WC Neurosciences SC Neurosciences & Neurology GA YH164 UT WOS:A1998YH16400017 PM 9466436 ER PT J AU Ko, DY Kufta, C Scaffidi, D Sato, S AF Ko, DY Kufta, C Scaffidi, D Sato, S TI Source localization determined by magnetoencephalography and electroencephalography in temporal lobe epilepsy: Comparison with electrocorticography: Technical case report SO NEUROSURGERY LA English DT Article DE brain mapping; electrocorticography; electroencephalography; epilepsy; epilepsy surgery; magnetoencephalography; seizure ID POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN; DIPOLES; MEG; EEG AB OBJECTIVE AND IMPORTANCE: Source modeling by magnetoencephalography (MEG) and electroencephalography (EEG) may be useful techniques for noninvasive localization of epileptogenic zones for surgery in patients with partial seizures. CLINICAL PRESENTATION: Simultaneous recordings of MEG and EEC, obtained in two patients, were coregistered on each patient's magnetic resonance image for direct comparison of these two methods with intracranial electrocorticography, TECHNIQUE: The average difference between MEG and EEG for localization of the same interictal spikes was approximately 2 cm in one patient and 3.8 cm in the other patient. One patient experienced a complex partial seizure during testing, which permitted comparison between interictal and ictal source localization by both MEG and EEG, The EEG ictal localization differed from the interictal one, whereas the MEG ictal and interictal localizations were more similar. In this patient, the MEG interictal source seemed to localize close to the ictal source, whereas EEG did not. The patients underwent temporal lobectomy after electrocorticography, and the results were compared with the findings of MEG and EEG. Although the results of both techniques agreed with the findings of electrocorticography, in one patient the MEG localization seemed to be more accurate. Both patients experienced good surgical outcomes. CONCLUSION: Both MEG and EEC source localization can add useful and complementary information for epilepsy surgery evaluation, MEG seemed to be more accurate than EEG, especially when comparing interictal versus ictal localization. Further study is needed to evaluate the validity of source localization as useful noninvasive techniques to localize the epileptogenic zone. C1 NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Ko, DY (reprint author), Univ So Calif, Gen Hosp, Dept Neurol, 1200 N State St,Room 5641, Los Angeles, CA 90033 USA. NR 22 TC 37 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 1998 VL 42 IS 2 BP 414 EP 421 DI 10.1097/00006123-199802000-00142 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YV348 UT WOS:000071814200055 PM 9482198 ER PT J AU Sills, RC Morgan, DL Harry, GJ AF Sills, RC Morgan, DL Harry, GJ TI Carbon disulfide neurotoxicity in rats: I. Introduction and study design SO NEUROTOXICOLOGY LA English DT Article ID NERVOUS-SYSTEM; NEUROPATHY; TOXICITY; PATTERN C1 NIEHS, Environm Toxicol Program MD B3 08, Res Triangle Pk, NC 27709 USA. RP Sills, RC (reprint author), NIEHS, Environm Toxicol Program MD B3 08, POB 12233, Res Triangle Pk, NC 27709 USA. NR 35 TC 5 Z9 5 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 83 EP 87 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000012 PM 9498224 ER PT J AU Moorman, MP Sills, RC Collins, BJ Morgan, DL AF Moorman, MP Sills, RC Collins, BJ Morgan, DL TI Carbon disulfide neurotoxicity in rats: II. Toxicokinetics SO NEUROTOXICOLOGY LA English DT Article DE carbon disulfide; toxicokinetics; rats; inhalation exposure ID 2-THIOTHIAZOLIDINE-4-CARBOXYLIC ACID; METABOLISM; EXPOSURE; BLOOD; PHARMACOKINETICS; TOXICITY; WORKERS; URINE AB Carbon disulfide (CS2) is an important industrial chemical widely used in the production of rayon, cellophane, fungicides and biocides. The uptake and elimination kinetics of CS2 was characterized for a single iv dose and for a single inhalation exposure. The uptake of CS2 into the blood was rapid with hall times of 6 to 9 minutes. Elimination was relatively quick with terminal elimination half times of 41 to 77 minutes. The plateau CS2 blood concentration was lower in females than in males and lower in the male 50 ppm treatment group than would be predicted by linear dose proportionality compared to the 500 ppm and 800 ppm treatments. The CS2 blood concentration for the female 50 ppm group was below the limit of detection. The total and central compartment apparent volumes of distribution, 4.2 l/kg and .9 l/kg, were estimated from a single 50 mg/kg iv dose. The concentration of CS2 in blood resulting from repeated exposure, was investigated in a 13 week inhalation study. Blood samples were taken in rats previously exposed to 0, 50, 500, and 800 ppm CS2 for 2, 4, 8, or 13 weeks. The concentration of CS2 in the blood of male rats remained relatively constant throughout study. However the female 500 and 800 ppm groups showed a marked decrease over the course of the 13 week study. The concentration of CS2 in the blood from the 500 and 800 ppm groups of both sexes at all time points was higher compared to the 50 ppm group, than would be predicted by linear dose proportionality. The concentration of 2-thiothiazolidine-4-carboxylic acid in urine collected from the same animals lacked dose proportionality between the treatment groups at all time points. CS2 exposure caused dose-related decreases in body weight gain in both male and female rats. (C) Intox Press, Inc. 1998. C1 NIEHS, Resp Toxicol Grp, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Moorman, MP (reprint author), NIEHS, Resp Toxicol Grp, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 25 TC 7 Z9 7 U1 1 U2 3 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 89 EP 97 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000013 PM 9498225 ER PT J AU Valentine, WM Amarnath, V Amarnath, K Erve, JCL Graham, DG Morgan, DL Sills, RC AF Valentine, WM Amarnath, V Amarnath, K Erve, JCL Graham, DG Morgan, DL Sills, RC TI Covalent modification of hemoglobin by carbon disulfide: III. A potential biomarker of effect SO NEUROTOXICOLOGY LA English DT Article DE carbon disulfide; hemoglobin; cross-linking; biomarker ID PROTEIN CROSS-LINKING; POLYNEUROPATHY; EXPOSURE; BINDING; DRUGS; CS2 AB Although the neurotoxicity of CS2 has been recognized for over a century, presently there is no accepted biomarker of effect for CS2 exposure. Previous investigations ha ve supported covalent crosslinking of erythrocyte spectrin as a potential preneurotoxic marker reflective of the biochemical changes occurring within the axon. In the present investigation, the potential of using CS2 promoted modification of hemoglobin as a dosimeter for quantifying exposure to CS2 was evaluated. Liquid chromatography was used to isolate and measure alpha and beta chains of globin in blood obtained from rats exposed to CS2 by inhalation as a function of exposure level and duration. The degree of globin modification was compared to light microscopic and ultrastructural changes in the central and peripheral nervous systems to determine the temporal relationship of globin modification to the structural changes in the axon. Samples obtained from rats exposed to CS2 contained a globin chain not present in control samples. Analysis of the peak corresponding to the new chain using electrospray mass spectrometry was consistent with the generation of a single dithiocarbamate ester or thiourea intramolecular cross-link in the alpha(1) major chain. This altered globin chain was detectable both at the subneurotoxic level of exposure and prior to axonal structural changes at the neurotoxic levels of exposure used. The extent of modification was positively correlated to the exposure level and duration for all conditions examined. These findings support hemoglobin as a potential preneurotoxic biomarker of effect for CS2 possessing several practical advantages relative to the use of CS2 mediated spectrin cross-linking. (C) 1998 Intox Press, Inc. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Valentine, WM (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, B-3318 MCN, Nashville, TN 37232 USA. FU NIEHS NIH HHS [ES02611, ES06387]; PHS HHS [P30 E500267] NR 29 TC 15 Z9 15 U1 0 U2 3 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 99 EP 107 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000014 PM 9498226 ER PT J AU Toews, AD Harry, GJ Lowrey, KB Morgan, DL Sills, RC AF Toews, AD Harry, GJ Lowrey, KB Morgan, DL Sills, RC TI Carbon disulfide neurotoxicity in rats: IV. Increased mRNA expression of low-affinity nerve growth factor receptor - A sensitive and early indicator of PNS damage SO NEUROTOXICOLOGY LA English DT Article DE axonopathy; gene expression; peripheral neuropathy ID SCIATIC-NERVE; GENE-EXPRESSION; SCHWANN-CELLS; NGF RECEPTOR; RNA; DEMYELINATION; MYELIN; EXPOSURE; AXOTOMY; BINDING AB Expression of the low-affinity nerve growth factor receptor (NGF-R) in the peripheral nervous system is regulated by Schwann cell-axonal contact. Steady-state mRNA levels for NGF-R are very low in the mature peripheral nervous system, but are markedly upregulated in sciatic nerve during both primary demyelination (tellurium exposure) and secondary demyelination (Wallerian degeneration). Upregulation also occurs in various subdegenerative axonopathy models where there is axonal atrophy, suggesting its usefulness as a marker for subtle perturbations in normal axon-Schwann cell interactions (Roberson et al., Mol Brain Res 1995; 28:231-238). To further test this hypothesis, we examined NGF-R mRNA expression in sciatic nerves of rats exposed to carbon disulfide (CS2), a toxicant known to cause a distal axonopathy. Adult rats were exposed to CS2 gas (50, 500, or 800 ppm, 6 hr/day, 5 days/wk) for 2-13 weeks. RNA was isolated from sciatic nerves and levels of mRNA for NGF-R determined by Northern blot analysis. NGF-R mRNA expression increased in a dose-and time-dependent manner. Message levels were already increased alter 2 wks of exposure to 800 ppm CS2, and increased further with continued exposure. Morphological alterations were not apparent in the sciatic nerve, even at the highest dosage levels with the longest exposure times. Upregulation of NGF-R mRNA is thus an indicator of subtle alterations in the normal axon-Schwann cell relationship and provides a sensitive measure of CS2 neurotoxicity. Assay of this marker may also be useful as a rapid and very sensitive general screen for other compounds which are potentially toxic to the peripheral nervous system. (C) 1998 Intox Press, Inc. C1 Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Toews, AD (reprint author), Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. FU NICHD NIH HHS [HD-03110]; NIEHS NIH HHS [ES-01104]; NINDS NIH HHS [NS 11615] NR 33 TC 6 Z9 6 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 109 EP 116 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000015 PM 9498227 ER PT J AU Sills, RC Harry, GJ Morgan, DL Valentine, WM Graham, DG AF Sills, RC Harry, GJ Morgan, DL Valentine, WM Graham, DG TI Carbon disulfide neurotoxicity in rats: V. Morphology of axonal swelling in the muscular branch of the posterior tibial nerve and spinal cord SO NEUROTOXICOLOGY LA English DT Article DE carbon disulfide; morphology; light microscopy; electron microscopy; axonal swelling; inhalation exposure; rats ID COVALENT CROSS-LINKING; DEGENERATION; PROTEINS; HEXANE AB The study objectives were to examine the morphological progression and dose response of carbon disulfide (CS2) distal axonopathy in the muscular branch of the posterior tibial nerve (MBPTN) and spinal cord. Male and female F344 rats were exposed to 0, 50, 500 or 800 ppm CS2 by inhalation, 6 hours/day, 5 days per week, for 2, 4, 8 or 13 weeks. At 8 weeks, in the MBPTN, single fascicles contained individual swollen axons. By 13 weeks, multiple fascicles had giant swollen axons with thin myelin sheaths and occasional degenerated and regenerated axons. At 8 weeks, in the spinal cord, white matter changes in cervical segments 1 and 2 consisted of prominent multifocal axonal swelling in the fasciculus gracilis nerve tracts. In lumbar segments 1 and 2, multifocal axonal swelling was first present at 8 weeks in the lateral and ventro-medial funiculus. By 13 weeks, axonal swelling was diffuse in the fasciculus gracilis nerve tracts of the cervical spinal cord and the lateral and ventral funiculus nerve tracts in the lumbar spinal cord. Compared to the spinal cord, where axonal swelling was present in rats exposed to 800 and 500 ppm, in the muscular branch of the posterior tibial nerve, axonal swelling was only present at 800 ppm at both 8 and 13 weeks. Electron microscopic examination demonstrated marked accumulations of neurofilaments in swollen axons in the spinal cord and MBPTN. Axonal swelling was not present in the spinal cord at 50 ppm, or in the MBPT at 50 and 500 ppm. Axonal swelling was not present at earlier time points of 2 and 4 weeks in either the spinal cord or MBPTN. (C) 1998 Intox Press, Inc. C1 NIEHS, Environm Toxicol Program MD B3 08, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. RP Sills, RC (reprint author), NIEHS, Environm Toxicol Program MD B3 08, POB 12233, Res Triangle Pk, NC 27709 USA. NR 17 TC 23 Z9 24 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 117 EP 127 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000016 PM 9498228 ER PT J AU Herr, DW Vo, KT Morgan, DL Sills, RC AF Herr, DW Vo, KT Morgan, DL Sills, RC TI Carbon disulfide neurotoxicity in rats: VI. Electrophysiological examination of caudal tail nerve compound action potentials and nerve conduction velocity SO NEUROTOXICOLOGY LA English DT Article DE carbon disulfide; CS2; compound nerve action potentials; CNAPs; nerve conduction velocity; NCV ID SENSORY-EVOKED POTENTIALS; HUMAN PERIPHERAL-NERVE; PSYCHOPHYSIOLOGICAL RESEARCH; NEUROPATHY; TOXICITY; EXPOSURE; AMPLITUDE; SYSTEM; FIBER; AREA AB The effects of subchronic exposure to carbon disulfide (CS2) on ventral caudal tail nerve compound nerve action potential (CNAP) amplitudes and latencies, and nerve conduction velocity (NCV) in rats were examined. Male and female Fischer 344 rats were exposed to 0, 50, 500, or 800 ppm CS2 for 6 hrs/day, 5 days/week. Using separate groups, exposure duration was 2, 4, 8, or 13 weeks. Exposure to 500 or 800 ppm CS2 for 13 weeks decreased NCV compared to the 50 ppm CS2 group. CNAP amplitudes were increased, and peak P1P2 interpeak latency decreased, after exposure to 500 or 800 ppm CS2 for 13 weeks. Most of the changes in NCV and CNAPs were not attributable to differences in tail or colonic temperature. However, the increases in peak P-1 amplitude may relate to the proximity of the electrodes to the rail nerves. Assessment of tail nerve morphology after 13 weeks exposure to 800 ppm CS2 revealed only minor changes compared to the extent of axonal swelling and degeneration observed in the muscular branch of the tibial nerve and axonal swelling in the spinal cord. As anticipated, in older animals the NCV increased, the CNAP amplitudes increased, and the CNAP latencies decreased. The biological basis for the changes in CNAPs produced by CS2 is under investigation. Future studies will focus on electrophysiological evaluation of spinal nerve function, to allow better correlation with pathological and behavioral endpoints. (C) 1998 Intox Press, Inc. C1 US EPA, Natl Hlth & Environm Effects Res Lab, NTD, NPTB, Res Triangle Pk, NC 27711 USA. Mantech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Herr, DW (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, NTD, NPTB, MD-74B, Res Triangle Pk, NC 27711 USA. FU PHS HHS [N01-EF-05296] NR 55 TC 15 Z9 15 U1 0 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 129 EP 146 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000017 PM 9498229 ER PT J AU Moser, VC Phillips, PM Morgan, DL Sills, RC AF Moser, VC Phillips, PM Morgan, DL Sills, RC TI Carbon disulfide neurotoxicity in rats: VII. Behavioral evaluations using a functional observational battery SO NEUROTOXICOLOGY LA English DT Article DE carbon disulfide; functional observational battery; neurobehavioral; inhalation exposure; rats ID TOXICITY; ACRYLAMIDE; IDPN AB The neurobehavioral consequences of inhalational exposure to carbon disulfide (CS2) were evaluated as part of a joint project between the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. Behavioral changes in rats were measured using a functional observational battery (FOB), which is a series of observations and manipulations designed to assess the neuronal integrity of autonomic, motor, sensory, and integrative functions. Young adult male and female Fischer-344 rats were exposed to one of four CS2 concentrations (0, 50, 500, or 800 ppm, six hours/day, five days/week) and tested at the end of one of several exposure durations (two, four, eight, or 13 weeks). All rats were also tested before exposure began to obtain baseline values. Neuromuscular deficits which were more pronounced in the hindlimbs, e.g., decreased strength and gait alterations, were detected in rats of both sexes. These changes were closely related to CS2 concentration and exposure duration, with mild gait changes evident after only two weeks of exposure. Other effects, mostly observed at 13 weeks, included decreased responsiveness to a visual stimulus and mild tremors. Reactivity in response to handling was generally increased, and excitability in the open field was decreased, in rats tested after the shorter exposures (two and four weeks). Thus, the exposure-concentration and -duration characteristics of the neuromotor syndrome produced by CS2 were detected and defined using the FOB. These studies provide a more complete evaluation of rats under these CS2 exposure conditions, which can then be used to compare with other mechanistic-related endpoints from this collaborative study. (C) 1998 Intox Press, Inc. C1 US EPA, NTD MD74B, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Moser, VC (reprint author), US EPA, NTD MD74B, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. FU NIEHS NIH HHS [N0-ES-05296] NR 30 TC 22 Z9 24 U1 0 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 147 EP 157 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000018 PM 9498230 ER PT J AU Harry, GJ Graham, DG Valentine, WM Morgan, DL Sills, RC AF Harry, GJ Graham, DG Valentine, WM Morgan, DL Sills, RC TI Carbon disulfide neurotoxicity in rats: VIII. Summary SO NEUROTOXICOLOGY LA English DT Editorial Material C1 NIEHS, Environm Toxicol Program MD C1 04, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. RP Harry, GJ (reprint author), NIEHS, Environm Toxicol Program MD C1 04, POB 12233, Res Triangle Pk, NC 27709 USA. NR 7 TC 7 Z9 7 U1 1 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 159 EP 161 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000019 PM 9498231 ER PT J AU Sriram, K Boyd, MR Vistica, DT Ravindranath, V AF Sriram, K Boyd, MR Vistica, DT Ravindranath, V TI In vitro neurotoxicity of the antitumor agent 9-methoxy-N-2-methylellipticinium acetate (MMEA): Role of brain cytochrome P-450 (vol 18, pg 97, 1997) SO NEUROTOXICOLOGY LA English DT Correction DE 9-methoxy-N-2-methylellipticinium acetate; ellipticines; brain; cytochrome p-450; neurotoxicity; brain slices AB 9-Methoxy-N-2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticine derivatives that are selectively cytotoxic to human brain tumor cell lines derived from non-neuronal (glial) cells (Acton et al, 1994). In an attempt to determine whether MMEA may exhibit toxicity to normal brain cells, we have examined the effect of the drug, in vitro, using sagittal slices of rat brain. Incubation of rat brain slices in an artificial cerebrospinal fluid medium containing MMEA resulted in dose-dependent leakage of lactate dehydrogenase (LDH) into the surrounding medium. However, other subcellular marker enzymes such as Na+-K(+)ATPase (plasma membrane), cytochrome c oxidase, isocitrate dehydrogenase, NADH-dehydrogenase (mitochondrial), N-acetylglucosaminidase, acid phosphatase (lysosomal), glyceraldehyde-3-phosphate dehydrogenase and enolase (glycolytic enzymes) were unaffected even at the highest tested concentrations of MMEA (10 and 100 mu M). Preincubation of slices with reserpine (1 nM) or, dopamine or serotonin-specific reuptake inhibitors abolished MMEA-induced toxicity in brain slices. Pretreatment of slices with piperonyl butoxide and metyrapone, inhibitors of cytochrome P-450, also prevented the toxicity of MMEA. Further, brain slices prepared from phenobarbital-treated rats showed enhanced sensitivity to MMEA; significant leakage of LDH was observed at MMEA concentrations as low as 1 nM. The present studies demonstrate the toxicity of MMEA in rat brain slices, in vitro, and suggest a role for brain cytochrome P-450 in the neurotoxicity of MMEA. (C) 1997 Intox Press, Inc. C1 Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. NCI, Lab Drug Discovery, Res & Dev,Dev Therapeut Program, NIH, Frederick, MD 21701 USA. RP Ravindranath, V (reprint author), Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. NR 1 TC 0 Z9 0 U1 1 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD FEB PY 1998 VL 19 IS 1 BP 167 EP 167 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA YZ607 UT WOS:000072271000021 ER PT J AU Danis, M AF Danis, M TI Improving end-of-life care in the intensive care unit: What's to be learned from outcomes research? SO NEW HORIZONS-THE SCIENCE AND PRACTICE OF ACUTE MEDICINE LA English DT Review DE terminal care; ICU; outcomes assessment (health care); review literature ID HOPELESSLY ILL PATIENTS; NOT-RESUSCITATE ORDERS; ADVANCE DIRECTIVES; SUSTAINING TREATMENT; CRITICALLY ILL; PHYSICIANS RESPONSIBILITY; HOSPITALIZED ADULTS; FAMILY MEMBERS; MORTALITY; PREFERENCES AB Current recommendations about the care of dying patients advise that healthcare professionals understand and respect the goals, priorities, needs, and suffering of each dying patient and have command of the skills and resources required to address these concerns. Studies of important features of terminal illness, current use and outcome of intensive care for the terminally ill, and interventions designed to improve the outcome of care for patients who die in ICUs are reviewed to examine discrepancies between recommendations and the reality of ICU care for dying patients. Evidence indicates that it is difficult to predict the time of death or determine patient preferences about treatment prior to death. The utilization of intensive care prior to death varies widely across the United States and is a function of available resources more than individual patient need or choice. The pattern of withdrawal of Life-sustaining treatment also varies widely and does not seem to follow guidelines. Families of deceased patients report that care could be improved by increased attention to analgesia and communication The largest interventional study, the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment (SUPPORT), which provided physicians with information about patient prognosis and preferences for care, did not alter outcomes of end-of-life care. Smaller but successful interventional studies have included examination of an alternative team that provides care tailored to the needs of dying patients, a service tailored to promote family contact with the dying patient, and proactive consultation to facilitate care planning and communication with families. Research suggests that clinicians should be cognizant of the difficulty of predicting death and anticipate the need to change the goals of care as therapeutic trials fail; anticipate and treat bothersome symptoms of dying patients; recognize that family support and contact between the dying patient and family facilitate decision-making and acceptance of death; and facilitate the coordination of care and the development of alternative care teams in order to optimize end-of-life care. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Danis, M (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. NR 51 TC 26 Z9 26 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1063-7389 J9 NEW HORIZ-SCI PRACT JI New Horiz.-Sci. Pract. Acute Med. PD FEB PY 1998 VL 6 IS 1 BP 110 EP 118 PG 9 WC Emergency Medicine SC Emergency Medicine GA 122NQ UT WOS:000076078700015 PM 9508265 ER PT J AU Schwarz, UP Plascjak, P Beitzel, MP Gansow, OA Eckelman, WC Waldmann, TA AF Schwarz, UP Plascjak, P Beitzel, MP Gansow, OA Eckelman, WC Waldmann, TA TI Preparation of At-211-labeled humanized anti-Tac using At-211 produced in disposable internal and external bismuth targets SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT XIIth International Symposium on Radiopharmaceutical Chemistry CY JUN 15-19, 1997 CL UPPSALA, SWEDEN DE At-211; antibody fragments; cyclotron production ID MULTICHAIN INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODIES; RADIOIMMUNOTHERAPY; IMMUNOTHERAPY; LYMPHOMA; MICE AB These studies describe the production and purification of At-211 as well as the procedure for labeling humanized anti Tac, the antibody to the alpha-chain of the IL-2 receptor (IL-2R alpha), which has been shown to be a useful target for immunotherapy. The optimized protocol combines the advantages of the two stage dry distillation procedure with the astatination of trialkylstannyl substances as labeling compounds for proteins. The At-211 was produced by bombarding either an external or a recently developed disposable internal bismuth target with alpha-particles from a Cyclotron Corporation CS-30 cyclotron. The At-211 was found to contain less than 0.01% At-210. The production rate for the external target was 0.15 mCi +/- 0.056 mu A(-1) h(-1) (n = 9) (5.55 MBq mu A(-1) h(-1)). The production rate for the internal target was 0.44 +/- 0.14 mCi mu A(-1) h(-1) (n = 16) (16.28 MBq mu A(-1) h(-1)). Published by Elsevier Science Inc. C1 NCI, PET Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Eckelman, WC (reprint author), NCI, PET Dept, Ctr Clin, NIH, Bldg 10,Rm 1C495,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. NR 12 TC 31 Z9 32 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 1998 VL 25 IS 2 BP 89 EP 93 DI 10.1016/S0969-8051(97)00165-0 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YN130 UT WOS:000071136100002 PM 9468021 ER PT J AU Rossouw, JE AF Rossouw, JE TI Does estrogen have a role in the prevention of cardiovascular disease SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Editorial Material ID CORONARY HEART-DISEASE; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; MYOCARDIAL-INFARCTION; SERUM-CHOLESTEROL; BETA-CAROTENE; RISK; PROGESTINS; REDUCTION; STROKE C1 NHLBI, Womens Hlth Initiat, NIH, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD FEB PY 1998 VL 8 IS 1 BP 62 EP 67 PG 6 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA ZH580 UT WOS:000073125700008 ER PT J AU Whitcup, SM AF Whitcup, SM TI Problems in lymphoma management: Special sites of presentation - The Connors article Reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Whitcup, SM (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 7 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 FEB PY 1998 VL 12 IS 2 BP 192 EP 193 PG 2 WC Oncology SC Oncology GA ZB436 UT WOS:000072461100007 ER PT J AU Cheson, BD Nelson, AP AF Cheson, BD Nelson, AP TI Clinical trials in adult acute myelogenous leukemia SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Cheson, BD (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 FEB PY 1998 VL 12 IS 2 BP 224 EP + PG 2 WC Oncology SC Oncology GA ZB436 UT WOS:000072461100013 PM 9507522 ER PT J AU Glynn, TJ AF Glynn, TJ TI The Cinciripini/McClure article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID PRIMARY CARE C1 NCI, Extramural Res Branch, Bethesda, MD 20892 USA. RP Glynn, TJ (reprint author), NCI, Extramural Res Branch, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 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 FEB PY 1998 VL 12 IS 2 BP 260 EP + PG 2 WC Oncology SC Oncology GA ZB436 UT WOS:000072461100020 ER EF