FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tuaillon, N AF Tuaillon, N TI Repertoire analysis in human immunoglobulin heavy chain minilocus transgenic, mu MT/mu MT mice SO MOLECULAR IMMUNOLOGY LA English DT Article DE transgene; immunoglobulin; generation of diversity; minilocus ID TARGETED DISRUPTION; V(D)J RECOMBINATION; MEMBRANE EXON; GENE SEGMENTS; DIVERSITY; MOUSE; REARRANGEMENTS; HYPERMUTATION; ORGANIZATION; REGIONS AB Mice transgenic for the human immunoglobulin heavy chain minilocus pHCl were developed several years ago to help better understand the mechanisms of VDJ recombination and antibody response. Interestingly, these minilocus transgenic mice develop a polyclonal, extremely diverse mu human immunoglobulin heavy chain repertoire, but when immunized, they exclusively use murine immunoglobulin heavy chains. Here, the data shows that when the minilocus is transferred by cross-breeding onto the mu MT background, the resulting mice (HCl-mu MT/mu MT mice) develop polyclonal, extremely diverse mu and gamma 1 human immunoglobulin heavy chain repertoires. Our data indicates that if no antigen specific antibodies are detected in pHCl transgenic mice, it is essentially due to competition with endogenous immunoglobulin heavy chain gene segments. Moreover, the data shows that despite the presence of only one functional V-H gene segment and despite mu and gamma 1 repertoires similar to the early pre-immune human repertoire, HCl-mu MT/mu MT mice, can develop immune responses against proteins and haptens. Finally, the data shows that in aged HCl-mu MT/mu MT mice, the generation of new B-cells may be impaired and old mice may mainly rely on B-cell generated earlier in life to mount immune responses. Published by Elsevier Science Ltd. C1 NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Tuaillon, N (reprint author), NEI, NIH, Immunol Lab, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR PY 2000 VL 37 IS 5 BP 221 EP 231 DI 10.1016/S0161-5890(00)00044-4 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 342RY UT WOS:000088660000004 PM 10930629 ER PT J AU Jafarian-Tehrani, M Listwak, S Barrientos, RM Michaud, A Corvol, P Sternberg, EM AF Jafarian-Tehrani, M Listwak, S Barrientos, RM Michaud, A Corvol, P Sternberg, EM TI Exclusion of angiotensin I-converting enzyme as a candidate gene involved in exudative inflammatory resistance in F344/N rats SO MOLECULAR MEDICINE LA English DT Article ID CORTICOTROPIN-RELEASING-HORMONE; 2 ACTIVE-SITES; SUSCEPTIBLE LEWIS RATS; INDUCED ARTHRITIS; KININASE-II; DELETION POLYMORPHISM; HOMOLOGOUS DOMAINS; MOLECULAR-CLONING; CELL-SURFACE; ACE AB Background: Inbred LEW/N and F344/N rats respectively, are susceptible and relatively resistant to a broad range of inflammatory/autoimmune diseases. we recently identified a quantitative trait locus (QTL) on chromosome 10 that protects the F344/N rat from carrageenan-induced exudation in a dominant fashion. Angiotensin I-converting enzyme (ACE) is one of the candidate genes located in this QTL region that plays an important role in inflammation. Materials and Methods: RNA was extracted from both LEW/N and F344/N rat strains and used to produce full length cDNA by reverse transcription polymerase chain reaction (RT-PCR). Both strands of the PCR products were entirely sequenced to determine nucleotide differences between strains. ACE activity was measured using the synthetic substrate H-3-hippuryl-glycylglycine. ACE protein levels were determined by Western blot using a specific ACE antibody. ACE kinetic and inhibition studies were performed using specific substrates (Hip-His-Leu and Acetyl-Seryl-Aspartyl-Acetyl-Lysyl-Proline) and inhibitors (lisinopril, captopril and quinaprilat) for each C- and N-terminal active site. Finally, the dose-effects of lisinopril treatment on carrageenen-induced exudate volume and ACE activity was studied. Results: In this study, we report for the first time a missense mutation in the coding region of ACE cDNA at 5' 1021 from C to T, resulting in a Leu-341 to Phe substitution, close to the N-domain active site in the F344/N rats. Full characterization of soluble and tissue ACE in both LEW/N and F344/N rat strains showed that soluble ACE levels in serum and exudate were 1.5 fold higher in the F344/N rats than those in LEW/N rats. In addition, the soluble ACE level was inversely correlated with the exudate volume. However, the specific ACE activity and its catalytic properties were identical in both strains. Furthermore, the chronic inhibition of serum and exudate ACE levels by lisinopril treatment did not affect the exudate volume in F344/N rats, indicating that several factors besides ACE were involved in the control of carrageenan-induced exudation. Conclusions: This report describes a complete molecular, biochemical, enzymatic and pharmacologic study of a missense mutation in the ACE cDNA in F344/N rats, that taken together, excludes ACE as a candidate gene involved with resistance to carrageenan-induced exudation in F344/N rats. C1 NIMH, Sect Neuroendocrine Immunol & Behav, CNE, NIH, Bethesda, MD 20892 USA. Coll France, INSERM, U36, F-75231 Paris, France. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, CNE, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. RI Barrientos, Ruth/E-3244-2013 OI Barrientos, Ruth/0000-0001-7224-4109 NR 61 TC 7 Z9 7 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD APR PY 2000 VL 6 IS 4 BP 319 EP 331 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 334LM UT WOS:000088188000006 PM 10949912 ER PT J AU Templeton, TJ Kaslow, DC Fidock, DA AF Templeton, TJ Kaslow, DC Fidock, DA TI Developmental arrest of the human malaria parasite Plasmodium falciparum within the mosquito midgut via CTRP gene disruption SO MOLECULAR MICROBIOLOGY LA English DT Article ID SPOROZOITE SURFACE PROTEIN-2; CIRCUMSPOROZOITE PROTEIN; GLIDING MOTILITY; TRANSFORMATION; THROMBOSPONDIN; HEPATOCYTES; INVASION; SEQUENCE; CELLS; TRAP AB Apicomplexan protozoa possess a family of micronemal and cell surface-associated proteins, each comprised a combination of cell-adhesive vertebrate von Willebrand factor (vWF)-like A domains and thrombospondin (TSP) type 1-like domains. The human malaria parasite Plasmodium falciparum has in the extracellular portion of the CS protein TRAP-related protein (CTRP) six tandemly arrayed A domains followed by seven TSP type 1-like domains, whereas a second member of this family, thrombospondin-related anonymous protein (TRAP), contains a single vWF-like A domain and a single TSP type 1-like domain. Here we show that CTRP transcripts are present within the infected mosquito midgut and that CTRP protein is expressed with a punctate distribution and a predominance at the apical end of mosquito midgut-stage ookinetes. This expression pattern is analogous to micronemal expression of TRAP in Plasmodium sporozoites. Disruption of the CTRP gene by homologous recombination in cultures of the human malaria parasite P. falciparum demonstrates that CTRP is essential for mosquito midgut development. Oocyst formation was never observed following membrane feeds of CTRP disruptant lines to Anopheline mosquitoes, despite the development of mature ookinetes. We propose that CTRP is involved in essential recognition or motility processes at the ookinete cell surface within the mosquito midgut. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Templeton, TJ (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. OI Fidock, David/0000-0001-6753-8938 NR 42 TC 76 Z9 77 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 APR PY 2000 VL 36 IS 1 BP 1 EP 9 DI 10.1046/j.1365-2958.2000.01821.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 301YM UT WOS:000086338200001 PM 10760158 ER PT J AU Bayewitch, ML Nevo, I Avidor-Reiss, T Levy, R Simonds, WF Vogel, Z AF Bayewitch, ML Nevo, I Avidor-Reiss, T Levy, R Simonds, WF Vogel, Z TI Alterations in detergent solubility of heterotrimeric G proteins after chronic activation of G(i/o)-coupled receptors: Changes in detergent solubility are in correlation with onset of adenylyl cyclase superactivation SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-GAMMA-SUBUNITS; CHRONIC OPIOID TREATMENT; GTP-BINDING PROTEINS; INHIBITORY RECEPTORS; MODULATION; DEPENDENCE; REDUCTION; EXPOSURE; MEMBRANE; ISOFORM AB Prolonged G(i/o) protein-coupled receptor activation has been shown to lead to receptor internalization and receptor desensitization. In addition, it is well established that although acute activation of these receptors leads to inhibition of adenylyl cyclase (AC), long-term activation results in increased AC activity (especially evident on removal of the inhibitory agonist), a phenomenon defined as AC superactivation or sensitization. Herein, we show that chronic exposure to agonists of G(i)-coupled receptors also leads to a decrease in cholate detergent solubility of G protein subunits, and that antagonist treatment after such chronic agonist exposure leads to a time-dependent reversal of the cholate insolubility. With Chinese hamster ovary and COS cells transfected with several G(i/o)-coupled receptors (i.e., mu- and kappa-opioid, and m(4)-muscarinic), we observed that although no overall change occurred in total content of G(alpha i)- and beta(1)-subunits, chronic agonist treatment led to a marked reduction in the ability of 1% cholate to solubilize G(beta gamma) as well as G(alpha i). This solubility shift is exclusively observed with G(alpha i), and was not seen with G(alpha s). The disappearance and reappearance of G(alpha i) and G(beta gamma) subunits from and to the detergent-soluble fractions occur with similar time courses as observed for the onset and disappearance of AC superactivation. Lastly, pertussis toxin, which blocks acute and chronic agonist-induced AC inhibition and superactivation, also blocks the shift in detergent solubility. These results suggest a correlation between the solubility shift of the heterotrimeric G(i) protein and the generation of AC superactivation. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Vogel, Z (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. FU NIDA NIH HHS [DA06265] NR 38 TC 34 Z9 35 U1 0 U2 1 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 APR PY 2000 VL 57 IS 4 BP 820 EP 825 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 297DM UT WOS:000086066500024 PM 10727531 ER PT J AU Barrette, S Douglas, J Orlic, D Anderson, SM Seidel, NE Miller, AD Bodine, DM AF Barrette, S Douglas, J Orlic, D Anderson, SM Seidel, NE Miller, AD Bodine, DM TI Superior transduction of mouse hematopoietic stem cells with 10A1 and VSV-G pseudotyped retrovirus vectors SO MOLECULAR THERAPY LA English DT Article DE retrovirus; transduction; Pit-1; Pit-2; amphotropic; 10A1; hematopoietic stem cells; murine ID APE LEUKEMIA-VIRUS; BONE-MARROW CELLS; MEDIATED GENE-TRANSFER; CHRONIC GRANULOMATOUS-DISEASE; HUMAN ADENOSINE-DEAMINASE; RHESUS PERIPHERAL-BLOOD; EXPRESSING HIGH-LEVELS; LONG-TERM ENGRAFTMENT; C-KIT; REPOPULATING CELLS AB The inefficient transduction of human hematopoietic stem cells (HSC) with amphotropic retroviral vectors has been an obstacle to gene therapy for hematopoietic diseases. We have previously reported low levels of amphotropic retrovirus receptor (Pit-2) mRNA and higher levels of gibbon ape leukemia virus (GALV) or 10A1 retrovirus receptor (Pit-1) mRNA in mouse and human HSC. The vesicular stomatitis virus (VSV-C) uses an abundant membrane phospholipid as a receptor. We hypothesized that transduction of HSC requires relatively high levels of retrovirus receptor molecules. Because mouse HSC can be efficiently transduced by ecotropic virus through the abundant ecotropic receptor, the mouse is an ideal model to compare receptor levels and transduction. We have developed a cotransduction assay where ecotropic retrovirus transduction is a positive internal control for downstream steps in retrovirus transduction. A comparison of mouse HSC transduction with amphotropic, 10A1, and VSV-C envelopes showed that the level of amphotropic and 10A1 receptor mRNA in HSC correlated with the frequency of transduction. Transduction with VSV-C vectors was similar to that with 10A1 vectors. We conclude that the level of retrovirus receptor on HSC is critical for HSC transduction and that GALV or VSV-G vectors would be better for human HSC transduction. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Systemix Inc, Palo Alto, CA 94304 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Bodine, DM (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 3A14-MSC 4442, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov OI Miller, Dusty/0000-0002-3736-3660 NR 61 TC 30 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD APR PY 2000 VL 1 IS 4 BP 330 EP 338 DI 10.1006/mthe.2000.0052 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 366RV UT WOS:000090019100006 PM 10933951 ER PT J AU Richert, ND Zierak, MC Bash, CN Lewis, BK McFarland, HF Frank, JA AF Richert, ND Zierak, MC Bash, CN Lewis, BK McFarland, HF Frank, JA TI MRI and clinical activity in MS patients after terminating treatment with interferon beta-1b SO MULTIPLE SCLEROSIS LA English DT Article DE multiple sclerosis; magnetic resonance imaging; interferon beta-1b ID REMITTING MULTIPLE-SCLEROSIS; T-CELL ACTIVATION; IN-VITRO; BRAIN; MECHANISMS; MIGRATION; DECREASES; CONTRAST; LESIONS AB Monthly MRI activity and clinical disability were evaluated in two relapsing-remitting multiple sclerosis (RRMS) patients for 4 years during a crossover treatment trial with IFN beta-1b and for a mean of 21 months after terminating treatment with IFN beta-1b Post-treatment MRI activity was compared to baseline activity in these patients. Although contrast enhancing lesions (CEL) and the bulk white matter lesion load (BWMLL) on T2-weighted images eventually returned to baseline values, there was a refractory period of 6-10 months after terminating treatment, before baseline MRI activity was restored. Although the mechanism for a sustained effect of IFN beta-1b is unclear at this time, these results have important implications for enrollment of such patients into new treatment protocols that rely on contrast enhancing lesion frequency as on outcome measure. C1 NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20010 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. RP Richert, ND (reprint author), NIH, Lab Diagnost Radiol Res, Ctr Clin, Bldg 10,B1N256, Bethesda, MD 20892 USA. NR 27 TC 30 Z9 31 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD APR PY 2000 VL 6 IS 2 BP 86 EP 90 DI 10.1191/135245800678827617 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300MN UT WOS:000086256900006 PM 10773853 ER PT J AU Colman, MS Afshari, CA Barrett, JC AF Colman, MS Afshari, CA Barrett, JC TI Regulation of p53 stability and activity in response to genotoxic stress SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article DE adaptation; p53; MDM2; genotoxic stress; apoptosis ID DEPENDENT PROTEIN-KINASE; DNA-DAMAGE; MDM2 ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3'-KINASE; P53-DEPENDENT APOPTOSIS; DOWNSTREAM MEDIATORS; FEEDBACK LOOP; GENE-PRODUCT; PHOSPHORYLATION; ACTIVATION AB The p53 tumor suppressor is a universal sensor of genotoxic stress that regulates the transcription of genes required for cell-cycle arrest and apoptosis. In response to DN4 damage, the p53 protein is phosphorylated at its amino-terminus and becomes stabilized upon disruption of an interaction with its negative regulator, MDM2. Subsequent phosphorylation and acetylation of p53 promote different interactions with other proteins and with target gene regulatory elements to facilitate cell-cycle arrest, apoptosis, or adaptation in response to DNA damage. Downstream of p53, p21 is responsible for growth arrest in G1, but other p53 target genes are responsible for G2 cell-cycle arrest. In response to genotoxic insult, p53-induced apoptosis results from overlapping downstream pathways that both suppress mitogenic and survival signaling and promote pro-apoptotic signaling. Adaptation to DNA damage is manifested by p53-mediated expression of its negative regulator, MDM3. The frequency of observed mutations in p53 predicts that its inactivation is a requisite step in tumorigenesis, as p53 is mutated in approximately 50% of human tumors. Thus, it is likely that in the remaining tumors, genetic aberrations will occur in pathways that regulate p53 or in pathways directly downstream of p53. The advances in the understanding of p53 signaling over the Fast few years point to many potential overlapping signaling pathways, where mutations may occur as alternative modes to p53 mutation. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIEHS, Canc & Aging Grp, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Canc & Aging Grp, Mol Carcinogenesis Lab, NIH, POB 12233,MD C2-15, Res Triangle Pk, NC 27709 USA. NR 79 TC 127 Z9 136 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD APR PY 2000 VL 462 IS 2-3 BP 179 EP 188 DI 10.1016/S1383-5742(00)00035-1 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 306EW UT WOS:000086585200015 PM 10767629 ER PT J AU Fronza, G Inga, A Monti, P Scott, G Campomenosi, P Menichini, P Ottaggio, L Viaggi, S Burns, PA Gold, B Abbondandolo, A AF Fronza, G Inga, A Monti, P Scott, G Campomenosi, P Menichini, P Ottaggio, L Viaggi, S Burns, PA Gold, B Abbondandolo, A TI The yeast p53 functional assay: a new tool for molecular epidemiology. Hopes and facts SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article DE p53; mutation spectra; yeast functional assay ID CANCER-RELATED GENES; UV-INDUCED MUTATIONS; SKIN-CANCER; PYRIMIDINE DIMERS; ULTRAVIOLET-LIGHT; MAMMALIAN-CELLS; MODEL SYSTEMS; NITRIC-OXIDE; DNA; SPECIFICITY AB The assumption of molecular epidemiology that carcinogens leave fingerprints has suggested that analysis of the frequency, type, and site of mutations in genes frequently altered in carcinogenesis may provide clues to the identification of the factors contributing to carcinogenesis. In this mini-review, we revise the development, and validation of the yeast-based p53 functional assay as a new tool for molecular epidemiology. We show that this assay has some very interesting virtues but also has some drawbacks. The yeast functional assay can be used to determine highly specific mutation fingerprints in the human p53 cDNA sequence. Discrimination is possible when comparing mutation spectra induced by sufficiently different mutagens, However, we also reported that the same carcinogen may induce distinguishable mutation spectra due to known influencing factors. (C) 2000 Elsevier Science B.V. All rights reserved. C1 IST, Natl Canc Inst, Mutagenesis Lab, I-16132 Genoa, Italy. Univ Leeds, Sch Med, Leeds LS2 9JT, W Yorkshire, England. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 69198 USA. Univ Nebraska, Med Ctr, Dept Pharmaceut Sci, Omaha, NE 69198 USA. RP Fronza, G (reprint author), IST, Natl Canc Inst, Mutagenesis Lab, Largo Rossana Benzi 10, I-16132 Genoa, Italy. RI Campomenosi, Paola/C-9729-2011; OI Campomenosi, Paola/0000-0002-8853-1134 NR 41 TC 23 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD APR PY 2000 VL 462 IS 2-3 BP 293 EP 301 DI 10.1016/S1383-5742(00)00011-9 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 306EW UT WOS:000086585200025 PM 10767639 ER PT J AU Hussain, SP Harris, CC AF Hussain, SP Harris, CC TI Molecular epidemiology and carcinogenesis: endogenous and exogenous carcinogens SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE p53; nitric oxide; aflatoxin B(1); inducible nitric oxide synthase ID HEPATITIS-B-VIRUS; NITRIC-OXIDE SYNTHASE; P53 TUMOR-SUPPRESSOR; WILD-TYPE P53; ENDOTHELIAL GROWTH-FACTOR; TATA-BINDING PROTEIN; HUMAN HEPATOCELLULAR-CARCINOMA; LIVER-CANCER RISK; X-PROTEIN; TRANSCRIPTIONAL ACTIVATION AB Mutations of the C53 tumor suppressor gene are found in about 50% of all human cancers. The p53 mutation spectra in these cancers are providing clues to the etiology and molecular pathogenesis of cancer. Recent studies indicate that the p53 protein is involved in several vital cellular functions, such as gene transcription, DNA synthesis and repair, cell cycle arrest, senescence and programmed cell death. Mutations in the p53 gene can abrogate these functions and may contribute to genomic instability and progression to cancer. Characteristic p53 mutation spectra have been associated with dietary aflatoxin B(1) (AFB(1)) exposure and hepatocellular carcinoma (HCC); sunlight exposure and skin cancer; and cigarette smoking and lung cancer. The mutation spectrum also reveals those p53 mutants that provide cells with a selective clonal expansion advantage during the multistep process of carcinogenesis. Although a number of different exogenous carcinogens have been shown to selectively target p53, pieces of evidence supporting the endogenous insult of p53 are accumulating. Furthermore, analysis of a characteristic p53 mutation load in nontumorous human tissue can indicate previous carcinogen exposure and may identify individuals at an increased cancer risk. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov NR 148 TC 87 Z9 88 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD APR PY 2000 VL 462 IS 2-3 BP 311 EP 322 DI 10.1016/S1383-5742(00)00015-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 306EW UT WOS:000086585200027 PM 10767641 ER PT J AU Wolffe, AP Lebanc, BP AF Wolffe, AP Lebanc, BP TI Creating molecular clues to uncover gene function SO NATURE BIOTECHNOLOGY LA English DT News Item ID DNA C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2000 VL 18 IS 4 BP 379 EP 380 DI 10.1038/74426 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 303UY UT WOS:000086444300015 PM 10748513 ER PT J AU Wang, E Miller, LD Ohnmacht, GA Liu, ET Marincola, FM AF Wang, E Miller, LD Ohnmacht, GA Liu, ET Marincola, FM TI High-fidelity mRNA amplification for gene profiling SO NATURE BIOTECHNOLOGY LA English DT Article ID EXPRESSION PATTERNS; CDNA MICROARRAY; ARRAYS C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NCI, Med Branch, Div Clin Sci, NIH, Gaithersburg, MD USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008; Miller, Lance/A-5633-2009 NR 20 TC 529 Z9 552 U1 1 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2000 VL 18 IS 4 BP 457 EP 459 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 303UY UT WOS:000086444300034 PM 10748532 ER PT J AU Zamir, E Katz, M Posen, Y Erez, N Yamada, KM Katz, BZ Lin, S Lin, DC Bershadsky, A Kam, Z Geiger, B AF Zamir, E Katz, M Posen, Y Erez, N Yamada, KM Katz, BZ Lin, S Lin, DC Bershadsky, A Kam, Z Geiger, B TI Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts SO NATURE CELL BIOLOGY LA English DT Article ID TO-SUBSTRATE CONTACTS; KINASE RHO-KINASE; SIGNAL-TRANSDUCTION; MOLECULAR-INTERACTIONS; FOCAL ADHESIONS; STRESS FIBERS; INTEGRINS; FIBRONECTIN; ACTIN; COMPLEXES AB Here we use time-lapse microscopy to analyse cell-matrix adhesions in cells expressing one of two different cytoskeletal proteins, paxillin or tensin, tagged with green fluorescent protein (GFP), Use of GFP-paxillin to analyse focal contacts and GFP-tensin to study fibrillar adhesions reveals that both types of major adhesion are highly dynamic, Small focal contacts often translocate, by extending centripetally and contracting peripherally, at a mean rate of 19 micrometres per hour. Fibrillar adhesions arise from the medial ends of stationary focal contacts, contain alpha(5)beta(1) integrin and tensin but not other focal-contact components, and associate with fibronectin fibrils, Fibrillar adhesions translocate centripetally at a mean rate of 18 micrometres per hour in an actomyosin-dependent manner. We propose a dynamic model for the regulation of cell-matrix adhesions and for transitions between focal contacts and fibrillar adhesions, with the ability of the matrix to deform functioning as a mechanical switch. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Tel Aviv Med Ctr, Inst Hematol, IL-64239 Tel Aviv, Israel. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. RP Geiger, B (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. OI Yamada, Kenneth/0000-0003-1512-6805 NR 36 TC 355 Z9 363 U1 2 U2 38 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2000 VL 2 IS 4 BP 191 EP 196 PG 6 WC Cell Biology SC Cell Biology GA 302ZU UT WOS:000086397000011 PM 10783236 ER PT J AU Stewart, CL AF Stewart, CL TI Oct-4, scene 1: the drama of mouse development SO NATURE GENETICS LA English DT Editorial Material ID LEUKEMIA INHIBITORY FACTOR; TRANSCRIPTION FACTOR; STEM-CELLS; DEPENDS; IMPLANTATION; BLASTOCYST; EMBRYO AB A study by Niwa et al. shows that changes in the levels of the transcription factor Oct-4 regulate the differentiation of embryonic stem cells along three different pathways. These observations suggest a possible mechanism by which Oct-4 determines the formation of the mouse pre-implantation embryo. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Canc & Dev Biol, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Canc & Dev Biol, Frederick, MD 21702 USA. NR 10 TC 12 Z9 13 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2000 VL 24 IS 4 BP 328 EP 330 DI 10.1038/74129 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 299HK UT WOS:000086192800003 PM 10742086 ER PT J AU Kirsch, IR Green, ED Yonescu, R Strausberg, R Carter, N Bentley, D Leversha, MA Dunham, I Braden, VV Hilgenfeld, E Schuler, G Lash, AE Shen, GL Martelli, M Kuehl, WM Klausner, RD Ried, T AF Kirsch, IR Green, ED Yonescu, R Strausberg, R Carter, N Bentley, D Leversha, MA Dunham, I Braden, VV Hilgenfeld, E Schuler, G Lash, AE Shen, GL Martelli, M Kuehl, WM Klausner, RD Ried, T TI A systematic, high-resolution linkage of the cytogenetic and physical maps of the human genome SO NATURE GENETICS LA English DT Letter ID YAC CONTIG MAP C1 NCI, Med Branch, Dept Genet, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. NCI, Off Director, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NCI, NIH, Canc genet Branch, Bethesda, MD 20892 USA. Sander Ctr, Cambridge, England. RP Kirsch, IR (reprint author), NCI, Med Branch, Dept Genet, Bethesda, MD 20892 USA. NR 8 TC 34 Z9 35 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 APR PY 2000 VL 24 IS 4 BP 339 EP 340 DI 10.1038/74149 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 299HK UT WOS:000086192800007 PM 10742091 ER PT J AU Feldman, DE AF Feldman, DE TI Inhibition and plasticity SO NATURE NEUROSCIENCE LA English DT News Item ID EXPERIENCE-DEPENDENT PLASTICITY; LONG-TERM POTENTIATION; VISUAL-CORTEX; THALAMOCORTICAL SYNAPSES; SYNAPTIC PLASTICITY; CRITICAL PERIOD; MOUSE C1 NINDS, Neural Dev Sect, NIH, Bethesda, MD 20892 USA. RP Feldman, DE (reprint author), NINDS, Neural Dev Sect, NIH, Bldg 36 Rm 2CO2,MSC 4066,36 Convent Dr, Bethesda, MD 20892 USA. NR 15 TC 39 Z9 39 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2000 VL 3 IS 4 BP 303 EP 304 DI 10.1038/73849 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 330CN UT WOS:000087945400003 PM 10725911 ER PT J AU Shetty, HU Siarey, RJ Galdzicki, Z Stoll, J Rapoport, SI AF Shetty, HU Siarey, RJ Galdzicki, Z Stoll, J Rapoport, SI TI Ts65Dn mouse, a Down syndrome model, exhibits elevated myo-inositol in selected brain regions and peripheral tissues SO NEUROCHEMICAL RESEARCH LA English DT Article DE myo-inositol; Ts65Dn mouse; Down syndrome; brain; skeletal muscle; liver ID CULTURED HIPPOCAMPAL-NEURONS; DOWN-SYNDROME; MYOINOSITOL UPTAKE; OSMOREGULATORY CHANGES; CEREBROSPINAL-FLUID; CALCIUM CHANNELS; SKELETAL-MUSCLE; NERVOUS-SYSTEM; RAT-BRAIN; COTRANSPORTER AB myo-Inositol is elevated in the Down syndrome (DS; trisomy 21) brain and may play a role in mental retardation. In the present study, we examined brain regions and peripheral tissues of Ts65Dn mouse, a recently characterized genetic model of DS, for abnormal myo-inositol accumulation. A GC/MS technique was used to quantitate myo-inositol and other polyol species (ribitol, arabitol, xylitol, and 1,5-anhydrosorbitol) in tissues from the Ts65Dn mice and control diploid mice. myo-Inositol was found to be elevated in frontal cortex, hippocampus, and brain stem but not in cerebellum of the Ts65Dn mouse. Among peripheral organs examined, liver and skeletal muscle were found to excessively accumulate myo-inositol. In all tissues, concentrations of polyol internal controls were normal. The Ts65Dn mouse is useful to study the possible effect of elevated myo-inositol on cellular processes. C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. Texas Tech Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. RP Shetty, HU (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Room 6C 103,10 Ctr Dr,MSC 1582, Bethesda, MD 20892 USA. NR 30 TC 11 Z9 11 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 2000 VL 25 IS 4 BP 431 EP 435 DI 10.1023/A:1007592006005 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 313GG UT WOS:000086991500001 PM 10823574 ER PT J AU Bullmore, ET Horwitz, B Honey, G Brammer, M Williams, S Sharma, T AF Bullmore, ET Horwitz, B Honey, G Brammer, M Williams, S Sharma, T TI How good is good enough in path analysis of fMRI data? SO NEUROIMAGE LA English DT Article ID WORKING-MEMORY; VISUAL PATHWAYS; IMAGE-ANALYSIS; PET; CONNECTIVITY; REHEARSAL; ATTENTION; DYSLEXIA; STORAGE; NETWORK AB This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data. (C) 2000 Academic Press. C1 Kings Coll London, Inst Psychiat, London, England. NIDCD, NIH, Bethesda, MD USA. Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. RP Bullmore, ET (reprint author), Kings Coll London, Inst Psychiat, London, England. EM etb23@cam.ac.uk RI Williams, Steve/D-6979-2011; Brammer, Michael/B-7128-2012; Bullmore, Edward/C-1706-2012 OI Williams, Steve/0000-0003-4299-1941; Brammer, Michael/0000-0001-9800-2052; Bullmore, Edward/0000-0002-8955-8283 NR 46 TC 172 Z9 173 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD APR PY 2000 VL 11 IS 4 BP 289 EP 301 DI 10.1006/nimg.2000.0544 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 300KP UT WOS:000086252400003 PM 10725185 ER PT J AU Messer, CJ Eisch, AJ Carlezon, WA Whisler, K Shen, L Wolf, DH Westphal, H Collins, F Russell, DS Nestler, EJ AF Messer, CJ Eisch, AJ Carlezon, WA Whisler, K Shen, L Wolf, DH Westphal, H Collins, F Russell, DS Nestler, EJ TI Role for GDNF in biochemical and behavioral adaptations to drugs of abuse SO NEURON LA English DT Article ID MESOLIMBIC DOPAMINE SYSTEM; VENTRAL TEGMENTAL AREA; MICE LACKING GDNF; CHOLERA-TOXIN INFUSION; MESSENGER-RNA LEVELS; C-RET PROTOONCOGENE; NERVE GROWTH-FACTOR; CYCLIC-AMP SYSTEM; NEUROTROPHIC FACTOR; NUCLEUS-ACCUMBENS AB The present study examined a role for GDNF in adaptations to drugs of abuse. Infusion of GDNF into the ventral tegmental area (VTA), a dopaminergic brain region important for addiction, blocks certain biochemical adaptations to chronic cocaine or morphine as well as the rewarding effects of cocaine. Conversely, responses to cocaine are enhanced in rats by intra-VTA infusion of an anti-GDNF antibody and in mice heterozygous for a null mutation in the GDNF gene. Chronic morphine or cocaine exposure decreases levels of phosphoRet, the protein kinase that mediates GDNF signaling, in the VTA. Together, these results suggest a feedback loop, whereby drugs of abuse decrease signaling through endogenous GDNF pathways in the VTA, which then increases the behavioral sensitivity to subsequent drug exposure. C1 Yale Univ, Sch Med, Lab Mol Psychiat, New Haven, CT 06508 USA. Yale Univ, Sch Med, Yale Ctr Genes & Behav, New Haven, CT 06508 USA. Connecticut Mental Hlth Ctr, New Haven, CT 06508 USA. NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Nestler, EJ (reprint author), Yale Univ, Sch Med, Lab Mol Psychiat, New Haven, CT 06508 USA. RI Wolf, Daniel/H-2581-2013 FU NIDA NIH HHS [K08 DA000302-05] NR 64 TC 114 Z9 128 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 2000 VL 26 IS 1 BP 247 EP 257 DI 10.1016/S0896-6273(00)81154-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 309MA UT WOS:000086770500024 PM 10798408 ER PT J AU Marquez, C Treston, A Moody, E Jakowlew, S Moody, TW AF Marquez, C Treston, A Moody, E Jakowlew, S Moody, TW TI The metabolism of BW2258U89, a GRP receptor antagonist SO NEUROPEPTIDES LA English DT Article ID CELL LUNG-CANCER; GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; HUMAN ORPHAN RECEPTOR; SWISS 3T3 CELLS; NEUROMEDIN-B; CARCINOMA; GROWTH; CLONING; ANALOGS AB BW2258U89 is a gastrin releasing peptide (GRP) receptor antagonist which inhibits the proliferation of the neuroendocrine tumor small cell lung cancer (SCLC). Here the biological activity of BW2258U89 and its metabolite were investigated. Using mass spectroscopy (LC-ESI/MS) techniques, three major peaks for BW2258U89 were observed with mass/charge (m/z) ratios of 1081.6, 541.4 and 361.4. After metabolism by mouse plasma enzymes, the major product had a m/z ratio of 1082.5, 541.9 and 361.8 suggesting that BW2258U89 was deamidated. Deamidated (Da) BW2258U89 was synthesized and it inhibited (I-125-Tyr(4)) BB binding to NCI-H345 SCLC cells with an IC,, value of 450 nM; BW2258U89 had an IC50 value of 17 nM. BW2258U89 (1 mu M) antagonized the ability of 50 nM BE to elevate cytosolic Ca2+ in NCI-H345 cells, whereas 1 mu M (Da) BW2258U89 did not. One micromolar BVV2258U89 antagonized the increase in NCI-H345 c-fos mRNA caused by 10 nM BE, whereas 1 mu M (Da) BW2258U89 had little effect. One CIM BW2258U89 inhibited NCI-H345 clonal growth significantly whereas 1 mu M (Da) BW2258U89 did not. These data suggest that an amidated C-terminal is important for antagonism of SOLO GRP receptors by BW2258U89. (C) 2000 Harcourt Publishers Ltd. C1 NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20876 USA. RP Moody, TW (reprint author), NCI, Cell & Canc Biol Dept, Med Branch, Bldg KWC,Room 300,9610 Med Ctr Dr, Rockville, MD 20876 USA. NR 33 TC 8 Z9 8 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2000 VL 34 IS 2 BP 108 EP 115 DI 10.1054/npep.2000.0798 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 338NW UT WOS:000088427000005 PM 10985927 ER PT J AU Little, JT Kimbrell, TA Wassermann, EM Grafman, J Figueras, S Dunn, RT Danielson, A Repella, J Huggins, T George, MS Post, RM AF Little, JT Kimbrell, TA Wassermann, EM Grafman, J Figueras, S Dunn, RT Danielson, A Repella, J Huggins, T George, MS Post, RM TI Cognitive effects of 1-and 20-Hertz repetitive transcranial magnetic stimulation in depression: Preliminary report SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; SIMPLE REACTION-TIME; ELECTROCONVULSIVE-THERAPY; NORMAL VOLUNTEERS; INDUCTION; MEMORY; ANTIDEPRESSANT; SCOPOLAMINE; METAMEMORY; DISORDER AB Objective: To determine the cognitive effects of daily repetitive transcranial magnetic stimulation (rTMS) administered under the conditions of a treatment trial for major depression, Background: Although daily left dorsal prefrontal rTMS has improved mood in some patients with treatment-refractory depression, potential cognitive side effects of extended daily treatment have not been systematically studied. Method: In a randomized double-blind treatment study, 10 subjects (mean age, 42 +/- 15 years) with an episode of major depression received either 2 weeks of low-frequency (1 Hz) or high-frequency (20 Hz) rTMS (800 pulses, 20 trains over 20 minutes, 80% of motor threshold, 5 days per week) to the left dorsolateral prefrontal cortex and then were crossed over to the other treatment condition. Patients received cognitive testing at baseline and after the first and second weeks of low- or high-frequency rTMS, which was examined by repeated-measures ANOVA. Results: Of 16 cognitive measures tested after 1 or 2 weeks of rTMS compared with baseline status, none showed deterioration, and the only significant main treatment effect indicated improvement on a list-recall test from pre- to post-rTMS after 1 week (p <0.05). Conclusions: These preliminary data suggest no gross deleterious cognitive effects of 2 weeks of 1- or 20-Hz rTMS at 80% of motor threshold over the left prefrontal cortex. Further cognitive studies of the effects of rTMS at other parameters used in clinical trials for mood disorders remain to be undertaken. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Arkansas, Sch Med, Dept Psychiat, Little Rock, AR 72204 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, 10 Ctr Dr MSC-1272, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 42 TC 71 Z9 72 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD APR PY 2000 VL 13 IS 2 BP 119 EP 124 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 408AL UT WOS:000167304300006 PM 10780630 ER PT J AU Levy, JA Parasuraman, R Greenwood, PM Dukoff, R Sunderland, T AF Levy, JA Parasuraman, R Greenwood, PM Dukoff, R Sunderland, T TI Acetylcholine affects the spatial scale of attention: Evidence from Alzheimer's disease SO NEUROPSYCHOLOGY LA English DT Article ID INFORMATION-PROCESSING PERFORMANCE; VISUAL VIGILANCE TASK; VISUOSPATIAL ATTENTION; CHOLINERGIC SYSTEM; SENILE DEMENTIA; STIMULUS SENSITIVITY; SELECTIVE ATTENTION; FEATURE-INTEGRATION; DIVIDED ATTENTION; BASAL FOREBRAIN AB Location precues were used to manipulate the spatial scale of attention in visual search for a target in an array of letters in patients with dementia of the Alzheimer type (DAT) and in age-matched older controls. Cue size varied in the amount of spatial precision conferred. Scopolamine, a muscarinic antagonist, decreased overall arousal and broadened spatial attention after a precise precue (small and valid) to target location for DAT patients but not for controls, suggesting a selective effect for attentional impairment induced by cholinergic blockade. In contrast, physostigmine, a cholinesterase inhibitor, did not alter the distribution of spatial attention relative to no-drug baseline testing for patients. Results support a differential role for cholinergic mechanisms in the modulation of the spatial scale of visual attention. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. RP Inst Rehabil, Dept Rehabil Psychol & Neuropsychol, 261 Mack Ave,Suite 555, Detroit, MI 48201 USA. EM jlevy2@dmc.org FU NIA NIH HHS [AG12387, AG07569] NR 85 TC 20 Z9 20 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD APR PY 2000 VL 14 IS 2 BP 288 EP 298 DI 10.1037//0894-4105.14.2.288 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 321XM UT WOS:000087480700012 PM 10791868 ER PT J AU Roffman, JL Lipska, BK Bertolino, A Van Gelderen, P Olson, AW Khaing, ZZ Weinberger, DR AF Roffman, JL Lipska, BK Bertolino, A Van Gelderen, P Olson, AW Khaing, ZZ Weinberger, DR TI Local and downstream effects of excitotoxic lesions in the rat medial prefrontal cortex on in vivo H-1-MRS signals SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE N-acetylaspartate; ibotenic acid; prefrontal cortex; striatum; locomotor activity; glutamic acid decarboxylase-67 ID MAGNETIC-RESONANCE SPECTROSCOPY; VENTRAL TEGMENTAL AREA; DOPAMINE NEURONS; SCHIZOPHRENIC BRAINS; EFFERENT PROJECTIONS; CORTICAL REGULATION; NUCLEUS-ACCUMBENS; WORKING-MEMORY; IN-VIVO; STRIATUM AB The rat medial prefrontal cortex (mPFC) regulates subcortical dopamine transmission via projections to the striatum and ventral tegmental area. We used in vivo proton magnetic resonance spectroscopy (H-1-MRS) at 4.7 T to determine whether excitotoxic lesions of the mPFC result in alterations of N-acetylaspartate (NAA), a marker of neuronal integrity, both locally and downstream in the striatum. Lesioned rats exhibited persistent reductions of NAA and other metabolites within the prefrontal cortex, selective reductions of NAA were seen in the striatum, but not in the parietal cortex. Consistent with earlier reports, lesioned rats exhibited a transient enhancement in amphetamine-induced hyperlocomotion. Prefrontal NAA losses correlated with lesion extent. In the striatum, while there was no change in tissue volume, expression of striatal glutamic acid decarboxylase-67 mRNA was significantly reduced. In vivo NAA levels thus appear sensitive to both local and downstream alterations in neuronal integrity, and may signal meaningful effects at cellular and behavioral levels. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIH, HHMI, Res Scholars Program, Bethesda, MD 20892 USA. NIH, NCRR, NMR Res Ctr, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Intramural Res Program, Clin Brain Disorders Branch, NIH, Rm 4S-235 MSC 1379,10 Ctr Dr, Bethesda, MD 20892 USA. RI Bertolino, Alessandro/O-6352-2016; Lipska, Barbara/E-4569-2017 OI Bertolino, Alessandro/0000-0002-1251-1380; NR 43 TC 13 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2000 VL 22 IS 4 BP 430 EP 439 DI 10.1016/S0893-133X(99)00143-8 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 297XR UT WOS:000086108500010 PM 10700662 ER PT J AU Heath, EI Limburg, PJ Hawk, ET Forastiere, AA AF Heath, EI Limburg, PJ Hawk, ET Forastiere, AA TI Adenocarcinoma of the esophagus: Risk factors and prevention SO ONCOLOGY-NEW YORK LA English DT Article ID HIGH-GRADE DYSPLASIA; GASTROESOPHAGEAL REFLUX DISEASE; HELICOBACTER-PYLORI INFECTION; CALCIUM-CHANNEL BLOCKERS; SQUAMOUS-CELL CARCINOMA; NUTRITION INTERVENTION TRIALS; COLUMNAR-LINED ESOPHAGUS; BARRETTS-ESOPHAGUS; GASTRIC CARDIA; CANCER INCIDENCE AB Esophageal cancer, with an estimated number of 12,300 new cases in the year 2000, is relatively uncommon in the United States but produces a high number of annual deaths, estimated at 12,100, Moreover, the incidence of the adenocarcinoma histologic type of esophageal cancer has been rising over the past two decades. Identification of risk factors could lead to primary prevention, as well as earlier diagnosis, treatment, and increased survival. Multiple risk factors are associated with the development of esophageal adenocarcinoma, These include Barrett's esophagus, acid peptic disorders, motor disorders of the esophagus, other malignancies, medications, environmental exposures, diet, and nutrition. However, no one particular risk factor is responsible for the rising incidence of esophageal cancer. Several preventive strategies are under investigation using such agents as nonsteroidal anti-inflammatory drugs (NSAIDs) selenium, alpha-difluoro-methylornithine (DFMO), and retinoids, As we gain more insight into the biology of this disease, other risk factors will hopefully be identified that will enable us to develop effective prevention strategies and, thus, reverse the current rising incidence of esophageal carcinoma. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. NCI, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA. RP Johns Hopkins Oncol Ctr, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 91 TC 16 Z9 16 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2000 VL 14 IS 4 BP 507 EP 514 PG 8 WC Oncology SC Oncology GA 368QL UT WOS:000090129000013 PM 10826312 ER PT J AU Conley, BA Gore-Langton, RE Cheson, BD AF Conley, BA Gore-Langton, RE Cheson, BD TI Clinical trials - Referral resource SO ONCOLOGY-NEW YORK LA English DT Article ID NECK-CANCER; HEAD C1 NCI, Bethesda, MD 20892 USA. RP Conley, BA (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2000 VL 14 IS 4 BP 553 EP + PG 3 WC Oncology SC Oncology GA 368QL UT WOS:000090129000018 PM 10826315 ER PT J AU Iwata, F Reed, GF Caruso, RC Kuehl, EM Gahl, WA Kaiser-Kupfer, MI AF Iwata, F Reed, GF Caruso, RC Kuehl, EM Gahl, WA Kaiser-Kupfer, MI TI Correlation of visual acuity and ocular pigmentation with the 16-bp duplication in the HPS-1 gene of Hermansky-Pudlak syndrome, a form of albinism SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID LOCUS HETEROGENEITY AB Objective: Patients with the Hermansky-Pudlak syndrome (HPS), a form of albinism, were studied. The first purpose of this investigation was to determine if visual acuity was related to the presence or absence of the 16-bp duplication in the HPS-1 gene. The second was to study the correlation between the degree of ocular pigmentation and visual acuity within the two genetic groups described above. Design: Cross-sectional study of a series of consecutive patients. Participants: Forty-nine patients with HPS with or without the 16-bp duplication in HPS-1. Methods: Best corrected visual acuity (VA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, photographic gradings of iris transillumination and of visibility of choroidal Vessels in the macula (macular transparency). Main Outcome Measures: Association between VA and the presence or absence of the 16-bp duplication in HPS-1 and correlation between VA and the degree of iris transillumination (iris score) and macular transparency (fundus score), as determined by masked reading of photographs, with respect to the presence or absence of the 16-bp duplication in HPS-1 were the main outcome measures. Results: The VA of the better eye did not differ between the two genetic groups (P = 0.322, two-sided t test), Spearman's rank correlation between VA and iris scores in 39 eyes of 20 patients with the duplication was not statistically significant (P = 0.698) but was statistically significant in 36 eyes of 19 patients without the duplication (P < 0.001). Among all patients, the correlation was statistically significant (r = -0.36 in RE and r = -0.51 in LE). Spearman's rank correlation between VA and fundus scores in 36 eyes of 19 patients with and 34 eyes in 18 patients with and without the duplication was statistically significant (P = 0.035 and P = 0.008, respectively). Among all patients, it was also statistically significant (r = -0.39 in RE and r = -0.45 in LE). Conclusions: The mean VA of the better eye did not differ in patients with the 16-bp duplication compared with those without the duplication. There were statistically significant associations between VA and the iris score and the fundus score except for the VA and iris scores in patients with the 16-bp duplication. However, because of the variability of VA, these associations were not large enough for useful prediction of VA based on the degree of ocular pigmentation. (C) 2000 by the American Academy of Ophthalmology. C1 NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NEI, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Kaiser-Kupfer, MI (reprint author), NEI, Ophthalm Genet & Clin Serv Branch, NIH, 10 Ctr Dr,MSC 1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. NR 23 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 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2000 VL 107 IS 4 BP 783 EP 789 DI 10.1016/S0161-6420(99)00150-5 PG 7 WC Ophthalmology SC Ophthalmology GA 300LV UT WOS:000086255200038 PM 10768343 ER PT J AU Liu, DG Yao, ZJ Gao, Y Burke, TR AF Liu, DG Yao, ZJ Gao, Y Burke, TR TI Large scale preparation of cell permeable, non-phosphate-containing GRB2 SH2 domain inhibitors SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL LA English DT Article ID LIGANDS C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, NIH, Bldg 37, Rm 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 7 TC 5 Z9 5 U1 0 U2 0 PU ORGANIC PREP PROCEDURES INC PI NEWTON HIGHLANDS PA PO BOX 9, NEWTON HIGHLANDS, MA 02161 USA SN 0030-4948 J9 ORG PREP PROCED INT JI Org. Prep. Proced. Int. PD APR PY 2000 VL 32 IS 2 BP 197 EP 201 PG 5 WC Chemistry, Organic SC Chemistry GA 309WW UT WOS:000086793100010 ER PT J AU Sina, B AF Sina, B TI The Multilateral Initiative on Malaria: An action plan SO PARASITOLOGY TODAY LA English DT News Item C1 NIH, Fogarty Int Ctr, Washington, DC USA. RP Sina, B (reprint author), NIH, Fogarty Int Ctr, Washington, DC USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD APR PY 2000 VL 16 IS 4 BP 139 EP 140 DI 10.1016/S0169-4758(00)01639-2 PG 2 WC Parasitology SC Parasitology GA 299EA UT WOS:000086181700004 PM 10725897 ER PT J AU Appella, E Anderson, CW AF Appella, E Anderson, CW TI Signaling to p53: breaking the posttranslational modification code SO PATHOLOGIE BIOLOGIE LA English DT Article DE acetylation; cell-cycle chekpoint; phosphorylation; protein kinase; transcription factor ID DNA-BINDING FUNCTION; TUMOR-SUPPRESSOR P53; DEPENDENT PROTEIN-KINASE; DAMAGE-INDUCED PHOSPHORYLATION; NIJMEGEN BREAKAGE SYNDROME; C-TERMINAL DOMAIN; CELL-CYCLE; IN-VITRO; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION AB In unstressed cells, the tumor suppressor protein p53, a tetrameric transcription factor, is present in a latent state and is maintained at low levels through targeted degradation. A variety of cellular stresses including DNA damage, hypoxia, nucleotide depletion, viral infection, and cytokine-activated signaling pathways that transiently stabilize the p53 protein, cause it to accumulate in the nucleus, and activate it as a transcription factor. Activation leads either to growth arrest at the G(1)/S or G(2)/M transitions of the cell cycle or to apoptosis. The molecular mechanisms by which stabilization and activation occur are incompletely understood, but accumulating evidence points to roles for multiple posttranslational modifications in mediating these events through several potentially interacting but distinct pathways. Both the similar to 100 amino acid N-terminal and similar to 90 amino acid C-terminal domains are highly modified by phosphorylation and acetylation, whereas modifications to the central sequence-specific DNA binding domain have not been reported. Seven serines and one threonine in the first 46 residues of the transactivation domain and four to five serines in the carboxyl-terminal domain are now known to be phosphorylated, and Lys320 and Lys382 in the carboxyl-terminal domain (human p53) can be acetylated. Antibodies that recognize p53 only when it has been modified at specific sites have been developed by several laboratories, and studies with these have shown that most of the known posttranslational modifications are induced when cells are exposed to DNA-damaging agents. Exceptions are Ser378, which is reported to be constitutively phosphorylated, and Ser376, which is dephosphorylated in response to DNA damage. These recent results, coupled with biochemical and genetic studies, suggest that several amino-terminal phosphorylations can be important in stabilizing p53 in response to DNA damage and in directing acetylation at C-terminal sites. DNA damage-induced modifications to the C-terminus inhibit the ability of this domain to negatively regulate sequence-specific DNA binding either by inducing a conformational change in the protein or by inhibiting non-sequence-specific DNA binding by the C-terminus. C-terminal modifications also modulate the oligomerization state of p53, and may modulate nuclear import/export. Modifications in response to DNA damage to other components that interact with p53 may also be important. In most cases, clear roles for specific modifications, interactions among individual modifications, and the enzymes responsible for each modification remain to be defined. Nevertheless, the field appears poised for major advances in the understanding of the molecular mechanisms that regulate p53 function. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Anderson, CW (reprint author), Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. FU NIGMS NIH HHS [GM52825] NR 98 TC 134 Z9 135 U1 1 U2 4 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD APR PY 2000 VL 48 IS 3 BP 227 EP 245 PG 19 WC Pathology SC Pathology GA 336PJ UT WOS:000088311600007 PM 10858956 ER PT J AU Zapka, JG Oakes, JM Simons-Morton, DG Mann, NC Goldberg, R Sellers, DE Estabrook, B Gilliland, J Linares, AC Benjamin-Garner, R McGovern, P AF Zapka, JG Oakes, JM Simons-Morton, DG Mann, NC Goldberg, R Sellers, DE Estabrook, B Gilliland, J Linares, AC Benjamin-Garner, R McGovern, P TI Missed opportunities to impact fast response to AMI symptoms SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE coronary heart disease; patient-physician communication; care-seeking ID ACUTE MYOCARDIAL-INFARCTION; RAPID-EARLY-ACTION; THROMBOLYTIC THERAPY; PREHOSPITAL DELAY; CHEST PAIN; CORONARY-TREATMENT; PLANNED BEHAVIOR; CONTROLLED TRIAL; SEEKING; DISEASE AB The potential for reducing cardiovascular disease mortality rates lies both in prevention and treatment. The earlier treatment is administered, the greater the benefit. Thus, duration of time from onset of symptoms of acute myocardial infarction to administration of treatment is important. One major factor contributing to failure to receive efficacious therapy is the delay time from acute myocardial infarction (AMI) symptom onset to hospital arrival. This paper examines the relationship of several factors with regard to intentions to seek care promptly for symptoms of AMI. A random-digit dialed telephone survey (n = 1294) was conducted in 20 communities located in 10 states. People who said they would wait until they were very sure that symptoms were a heart attack were older, reported their insurance did not pay for ambulance services, and reported less confidence in knowing signs and symptoms in themselves. When acknowledging symptoms of a heart attack, African-Americans and people with more than a high school education reported intention to act quickly. No measures of personal health history, nor interaction with primary care physicians or cardiologists were significantly related to intention to act fast. The study confirms the importance of attribution and perceived self-confidence in symptom recognition in care seeking. The lack of significant role of health history (i.e. those with chronic conditions or risk factors) and clinician contact highlights missed opportunities for health care providers to educate and encourage patients about their risk and appropriate action. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. New England Res Inst, Watertown, MA 02172 USA. NHLBI, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Educ Dev Ctr, Newton, MA USA. Univ Alabama, Birmingham, AL USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Zapka, JG (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. FU NHLBI NIH HHS [HL53135, HL53142, HL54517, HL53149, HL53211, HL53141] NR 54 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD APR PY 2000 VL 40 IS 1 BP 67 EP 82 DI 10.1016/S0738-3991(99)00065-8 PG 16 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 309AV UT WOS:000086745800009 PM 10705066 ER PT J AU Cheng, TL Fields, C Brenner, R Wright, JL Schwarz, D Rhee, P Scheidt, PC AF Cheng, TL Fields, C Brenner, R Wright, JL Schwarz, D Rhee, P Scheidt, PC TI Assault-injured adolescents presenting to the emergency department: Causes and circumstances of injury SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. MedSTAR, Trauma, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 14 BP 3A EP 3A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300015 ER PT J AU Cheng, TL Schwarz, D Fields, C Wright, JL Brenner, R O'Donnell, R Rhee, P Scheidt, PC AF Cheng, TL Schwarz, D Fields, C Wright, JL Brenner, R O'Donnell, R Rhee, P Scheidt, PC TI Risk and protective factors for adolescent assault injury: A case control study SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NICHHD, Bethesda, MD 20892 USA. MedSTAR, Trauma, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 15 BP 3A EP 3A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300016 ER PT J AU Joffe, A Gaydos, C Waterfield, G Hauptman, P Quinn, T AF Joffe, A Gaydos, C Waterfield, G Hauptman, P Quinn, T TI Screening asymptomatic males for Chlamydia trachomatis in school based health centers SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Baltimore City Hlth Dept, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RI Gaydos, Charlotte/E-9937-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 34 BP 6A EP 6A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300035 ER PT J AU Brigandi, RA Klein, JD Moore, LS Holland, SM McKenzie, SE AF Brigandi, RA Klein, JD Moore, LS Holland, SM McKenzie, SE TI Persistent invasive multifocal salmonella infection in a child despite the presence of interferon gamma receptor (IFN gamma R) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 DuPont Hosp Children, Dept Pediat, Div Infect Dis, Wilmington, DE USA. DuPont Hosp Children, Dept Pediat, Div Hematol Oncol Res, Wilmington, DE USA. Christiana Care Hlth Syst, Infect Dis Lab, Wilmington, DE USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 85 BP 15A EP 15A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300086 ER PT J AU McCune, SK Rivera, O Abebe, DT Hill, JM Brenneman, DE Phillips, TM AF McCune, SK Rivera, O Abebe, DT Hill, JM Brenneman, DE Phillips, TM TI Chronic in utero hypoxia causes fetal growth retardation and profound alterations in CNS cytokine and growth factor expression SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 CNMC, Washington, DC USA. NICHD, Dev Neurobiol, NIH, Bethesda, MD USA. GWU, Immunol, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 435 BP 74A EP 74A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300436 ER PT J AU Ades, AM McCune, SK Cmic, LS Ring, M Brenneman, DE Hill, JM AF Ades, AM McCune, SK Cmic, LS Ring, M Brenneman, DE Hill, JM TI Vasoactive intestinal peptide dysfunction associated with a segmental trisomy model of Down syndrome SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 CNMC, Neonatol, Washington, DC USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. NICHD, Sect Devel & Molec Pharmacol, LDN, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 472 BP 80A EP 80A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300473 ER PT J AU Gafni, RI Weise, M Robrecht, DT De-Levi, S Baron, J AF Gafni, RI Weise, M Robrecht, DT De-Levi, S Baron, J TI Catch-up growth after glucocorticoid excess is associated with delayed senescence of the growth plate SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, DEB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 756 BP 128A EP 128A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300757 ER PT J AU Kasik, JW Stephan, DA Sperling, MA Menon, RK AF Kasik, JW Stephan, DA Sperling, MA Menon, RK TI Identification of a new member of the insulin/IGF/relaxin family SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 781 BP 133A EP 133A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300782 ER PT J AU Leschek, EW Troendle, JF Yanovski, JA Rose, SR Bernstein, DB Cutler, GB Baron, J AF Leschek, EW Troendle, JF Yanovski, JA Rose, SR Bernstein, DB Cutler, GB Baron, J TI Effect of growth hormone on testicular function and puberty in boys with non-growth hormone-deficient short stature: A double-blind, placebo-controlled study SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, Dev Endocrinol Branch, Bethesda, MD USA. NICHD, BMSB, NIH, Bethesda, MD USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 788 BP 134A EP 134A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300789 ER PT J AU Merke, DP Chrousos, GP Eisenhofer, G Keil, MF Rogol, AD Van Wyk, JJ Bornstein, SR AF Merke, DP Chrousos, GP Eisenhofer, G Keil, MF Rogol, AD Van Wyk, JJ Bornstein, SR TI Structure and function of the adrenal medulla are severely impaired in patients with classic 21-hydroxylase deficiency: Potential implication for cardiovascular fragility SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. Univ Virginia Hlth Sci, Dept Pediat, Charlottesville, VA USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 795 BP 135A EP 135A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300796 ER PT J AU Nguyen, TT Russell, DL Sovik, KN Nicholson, JC Keil, MF Pathomvanich, A Reynolds, J McDuffie, JR Yanovski, JA AF Nguyen, TT Russell, DL Sovik, KN Nicholson, JC Keil, MF Pathomvanich, A Reynolds, J McDuffie, JR Yanovski, JA TI Differences in the insulin secretion and sensitivity of overweight African American and Caucasian prepubertal children SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, Unit Growth & Obes, DEB, Bethesda, MD USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 799 BP 136A EP 136A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300800 ER PT J AU Russell, DL Nicholson, JC Pathoinvanich, A Nguyen, TT Sovik, KN McDuffe, JR Hill, SC Yanovski, JA AF Russell, DL Nicholson, JC Pathoinvanich, A Nguyen, TT Sovik, KN McDuffe, JR Hill, SC Yanovski, JA TI Differences in skeletal maturation and body mass index of African American and Caucasian children SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, DEB, Unit Growth & Obes, Bethesda, MD USA. NIH, CC, Dept Radiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 818 BP 139A EP 139A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300819 ER PT J AU Weise, M De-Levi, S Robrecht, DT Barnes, KM Gafni, RI Baron, J AF Weise, M De-Levi, S Robrecht, DT Barnes, KM Gafni, RI Baron, J TI Estrogen and epiphyseal fusion SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 833 BP 141A EP 141A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300834 ER PT J AU Brenner, RA Zhang, J Klebanoff, MA AF Brenner, RA Zhang, J Klebanoff, MA TI Differences in birthweight and blood pressure at age 7 years among twins SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, DESPR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 842 BP 143A EP 143A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300843 ER PT J AU Crain, EF Stout, JW AF Crain, EF Stout, JW TI Does the quality of asthma care for inner-city Hispanic children vary by the caretaker's primary spoken language? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIAID, NIEHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 852 BP 145A EP 145A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300853 ER PT J AU Dimaunahan, C Alper, R Adubato, S Damokosh, A Rogan, W AF Dimaunahan, C Alper, R Adubato, S Damokosh, A Rogan, W TI Correlations in developmental test scores over 3 years of follow-up in toddlers tested in English or Spanish SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Houston, TX USA. UMDNJ, Newark, NJ USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 861 BP 146A EP 146A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300862 ER PT J AU Hunt, CE Lesko, SM Yezina, RM McCoy, R Corwin, MJ Mitchell, AA Hoffman, HJ Willinger, M AF Hunt, CE Lesko, SM Yezina, RM McCoy, R Corwin, MJ Mitchell, AA Hoffman, HJ Willinger, M TI Usual sleep position, infant care practices, and health outcomes: A prospective longitudinal assessment SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Med Coll Ohio, Toledo, OH 43699 USA. Boston Univ, Sch Med, Sch Publ Hlth, Slone Epidemiol Unit, Brookline, MA 02146 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Unit, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Med, Boston, MA USA. NICHD, Epidemiol Stat & Data Syst Branch, NIH, Bethesda, MD USA. NICHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 876 BP 149A EP 149A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300877 ER PT J AU McCoy, RC Hunt, CE Lesko, SM Vezina, RM Corwin, MJ Mitchell, AA Hoffman, HJ Willinger, M AF McCoy, RC Hunt, CE Lesko, SM Vezina, RM Corwin, MJ Mitchell, AA Hoffman, HJ Willinger, M TI Population-based study of bed sharing and breastfeeding SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Med Coll Ohio, Toledo, OH 43699 USA. Boston Univ, Slone Epidemiol Unit, Sch Publ Hlth, Brookline, MA 02146 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. Natl Inst Deafness & Other Commun Disorders, Epidemiol Stat & Data Syst Branch, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 905 BP 154A EP 154A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300906 ER PT J AU Stout, JW Lozano, P Ludman, EJ Graham, EA Grothaus, L Curry, SJ AF Stout, JW Lozano, P Ludman, EJ Graham, EA Grothaus, L Curry, SJ TI Characteristics and racial comparisons of low income mothers who smoke SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NHLBI, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 937 BP 159A EP 159A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300938 ER PT J AU Mohan, P Post, J Glymph, C Fernandez-Larsson, B Alter, HJ Luban, NLC AF Mohan, P Post, J Glymph, C Fernandez-Larsson, B Alter, HJ Luban, NLC TI Clinical spectrum and natural history of hepatitis C (HCV) infection in children: A single institution experience SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 980 BP 167A EP 167A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300981 ER PT J AU Ward, LP McCune, SK AF Ward, LP McCune, SK TI Ontogenic gene expression of the alpha-2A adrenergic receptor in the intestines of cocaine-exposed rat embryos SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 994 BP 169A EP 169A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300995 ER PT J AU Brenner, R Simons-Morton, B Bhaskar, B Das, A Clemens, J AF Brenner, R Simons-Morton, B Bhaskar, B Das, A Clemens, J CA NIH-DC Initiat Immunizat Working Grp TI Predictors of immunization status in an urban setting SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, Bethesda, MD USA. RTI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1044 BP 178A EP 178A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301045 ER PT J AU Hunt, CE Durham, JK Guess, SJ Kapunini, L Golub, H Baird, TM AF Hunt, CE Durham, JK Guess, SJ Kapunini, L Golub, H Baird, TM CA CHIME Study Grp TI Telephone subsidy enhances participation of socio-economically disadvantaged families without telephones in collaborative home infant monitoring evaluation* (CHIME) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Med Coll Ohio, Toledo, OH 43699 USA. Univ Hawaii, Honolulu, HI 96822 USA. Boston Univ, Boston, MA 02215 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NICHD, Pregnancy & Perinatol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1162 BP 197A EP 197A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301162 ER PT J AU Scheidt, P Brenner, R Rossi, M Collins, M Mickalide, A Overpeck, M Reed, Y Boyle, K AF Scheidt, P Brenner, R Rossi, M Collins, M Mickalide, A Overpeck, M Reed, Y Boyle, K TI From surveillance to intervention: Identification of prevention strategies from an analysis of injury events SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. NICHD, NIH, Bethesda, MD USA. DC Gen Hosp, Dept Pediat, Washington, DC USA. Natl Safe Kids Campaign, Washington, DC USA. RTI, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1319 BP 224A EP 224A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301319 ER PT J AU Forlino, A Dawson, PA Lisi, V Marini, JC AF Forlino, A Dawson, PA Lisi, V Marini, JC TI Development of a mutation suppression approach to the gene therapy of osteogenesis imperfecta SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, HDB, NIH, Bethesda, MD USA. RI Dawson, Paul/B-1268-2012; Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1415 BP 240A EP 240A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301414 ER PT J AU Levy, HL Guldberg, P Guttler, F Hanley, WB Matalon, R Rouse, BM Trefz, F Azen, C de la Cruz, F Koch, R AF Levy, HL Guldberg, P Guttler, F Hanley, WB Matalon, R Rouse, BM Trefz, F Azen, C de la Cruz, F Koch, R TI Congenital heart disease in maternal phenylketonuria: Report from the maternal PKU collaborative study SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. John F Kennedy Inst, DK-2600 Glostrup, Denmark. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Texas, Med Branch, Galveston, TX 77550 USA. Childrens Hosp, Reutlingen, Germany. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1422 BP 241A EP 241A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301421 ER PT J AU McAndrew, PE Kaler, SG AF McAndrew, PE Kaler, SG TI Rapid mutational screening of the Menkes/occipital horn syndrome locus SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Ctr Genet Med, Childrens Res Inst, Washington, DC 20010 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1423 BP 241A EP 241A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301422 ER PT J AU Milunsky, JM Gropman, AL AF Milunsky, JM Gropman, AL TI Bilateral perisylvian abnormalities in two boys with 47,XYY SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1427 BP 242A EP 242A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301426 ER PT J AU Orvisky, E Park, J Stone, DL Tayebi, N Sidransky, E AF Orvisky, E Park, J Stone, DL Tayebi, N Sidransky, E TI Elevated levels of glucosylsphingosine in patients with Gaucher disease: Correlation with phenotype and genotype SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1432 BP 243A EP 243A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301431 ER PT J AU Porter, FD Krakowiak, PA Battaile, KP Steiner, RD Kratz, LE Kelley, RI Nwokoro, NA Wassif, CA AF Porter, FD Krakowiak, PA Battaile, KP Steiner, RD Kratz, LE Kelley, RI Nwokoro, NA Wassif, CA TI Smith-Lemli-Opitz syndrome: Human and mouse mutations SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 OHSU, Portland, OR USA. NICHD, HDB, NIH, Bethesda, MD USA. JHU, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1437 BP 244A EP 244A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301436 ER PT J AU Wong, EY Sabatino, DE Boulanger, L Garbarz, M Forget, BG Bodine, DM Gallagher, PG AF Wong, EY Sabatino, DE Boulanger, L Garbarz, M Forget, BG Bodine, DM Gallagher, PG TI Promoter and enhancer elements are required for expression of the human erythrocyte alpha-spectrin gene in vivo SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. Xavier Bichat, INSERM U409, Paris, France. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1501 BP 254A EP 254A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301499 ER PT J AU Bonville, CA Domachowske, JB Dyer, KD Easton, AJ Rosenberg, HF AF Bonville, CA Domachowske, JB Dyer, KD Easton, AJ Rosenberg, HF TI The role of MIP-1-alpha in the inflammatory response to paramyxoviruses in vivo SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Upstate Med Ctr, Syracuse, NY USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Warwick, Coventry CV4 7AL, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1515 BP 257A EP 257A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301513 ER PT J AU Conway, DH Schumann, KE Boyer, JD Manson, K Miller, N Foster, J Weiner, DB Bagarazzi, ML AF Conway, DH Schumann, KE Boyer, JD Manson, K Miller, N Foster, J Weiner, DB Bagarazzi, ML TI DNA vaccination with SIV accessory genes preserves CD4 cells and reduces viral loads after challenge of macaques SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 St Christophers Hosp Children, MCP Hahnemann Sch Med, Philadelphia, PA 19133 USA. Univ Penn, Philadelphia, PA 19104 USA. Primedica, Worcester, MA USA. NIAID, Bethesda, MD 20892 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1528 BP 259A EP 259A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301526 ER PT J AU Conway, DH Schumann, KE Boyer, JD Manson, K Miller, N Foster, J Weiner, DB Bagarazzi, ML AF Conway, DH Schumann, KE Boyer, JD Manson, K Miller, N Foster, J Weiner, DB Bagarazzi, ML TI CD4 cells preserved and viral loads reduced in rhesus macaques vaccinated with combination DNA vaccines SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. St Christophers Hosp Children, MCP Hahnemann Sch Med, Philadelphia, PA 19133 USA. NIAID, Bethesda, MD 20892 USA. Primedica, Worcester, MA USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1527 BP 259A EP 259A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301525 ER PT J AU Lipschultz, SE Easley, KA Orav, J Kaplan, S Starc, TJ Bricker, T Lai, WW Moodie, DS Sopko, G McIntosh, K Colan, SD AF Lipschultz, SE Easley, KA Orav, J Kaplan, S Starc, TJ Bricker, T Lai, WW Moodie, DS Sopko, G McIntosh, K Colan, SD TI Is antiretroviral therapy with zidovudine cardiotoxic to infants? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NHLBI, Pediat Pulm & Cardiac Complicat Vertically Transm, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1582 BP 268A EP 268A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301580 ER PT J AU Pikis, A Rodriguez, WJ Campos, JM Keith, JM AF Pikis, A Rodriguez, WJ Campos, JM Keith, JM TI Optochin-resistant Streptococcus pneumoniae (ORSP): Incidence and genesis SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NIDCR, Vaccine & Therapeut Dev Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1613 BP 273A EP 273A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301611 ER PT J AU Catalan, J Moriguchi, T Slotnick, B Salem, N AF Catalan, J Moriguchi, T Slotnick, B Salem, N TI Cognitive deficits in rats with low brain docosahexaenoic acid (DHA) assessed using olfaction SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 USUHS, Bethesda, MD USA. NIAAA, LMBB, Rockville, MD USA. American Univ, Washington, DC 20016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1679 BP 285A EP 285A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301677 ER PT J AU Uauy, R Rojas, CV Fuenzalida, L Murthy, M Greiner, R Salem, N AF Uauy, R Rojas, CV Fuenzalida, L Murthy, M Greiner, R Salem, N TI Effect of n-3 fatty acid deficiency on peroxisomal proliferator activated receptor PPAR alpha and beta gene expression in rat liver brain and retina SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Chile, INTA, Santiago 11, Chile. NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1760 BP 298A EP 298A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301758 ER PT J AU El-Mohandes, AAE El-Khorazary, MN Katta, P Herman, A Young, M AF El-Mohandes, AAE El-Khorazary, MN Katta, P Herman, A Young, M TI Prenatal care reduces the risk associations between illicit drug use (IDU) and permaturity, low birth weight (LBW) and small for gestational age (SGA) status SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 George Washington Univ, Washington, DC USA. Res Triangle Inst, Rockville, MD USA. NIH, Bethesda, MD 20892 USA. Dist Columbia Gen Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1815 BP 308A EP 308A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301813 ER PT J AU Walker, V Wade, N Meng, O Olivero, O Poirier, M O'Neill, JP Bighee, W Ness, R AF Walker, V Wade, N Meng, O Olivero, O Poirier, M O'Neill, JP Bighee, W Ness, R TI Biomarker of exposure and effect as indicators of genotoxicity arising from antiretroviral chemophophylaxis in children of HIV-infected women SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Wadsworth Ctr, Albany, NY USA. Albany Med Ctr, Albany, NY USA. Wadsworth Ctr, Albany, NY USA. NCI, Bethesda, MD 20892 USA. Univ Vermont, Burlington, VT 05405 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1935 BP 328A EP 328A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301933 ER PT J AU Capparelli, E Mirochnick, M Dankner, W Blanchard, S Mofenson, L Smith, E Cuipak, G AF Capparelli, E Mirochnick, M Dankner, W Blanchard, S Mofenson, L Smith, E Cuipak, G TI Population pharmacokinetics (PPK) of zidovudine (ZDV) in premature HIV exposed neonates SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UC San Diego, San Diego, CA USA. Boston Univ, Boston, MA 02215 USA. Harvard, SDAC, Cambridge, MA USA. NICHD, Bethesda, MD USA. Frontier Sci, Amherst, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2001 BP 339A EP 339A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302000 ER PT J AU Cotton, RB Hazinski, TA Morrow, JD Mellen, BG Zeldin, DC Lindstrom, D Lappaleinen, U Law, AB Steele, S AF Cotton, RB Hazinski, TA Morrow, JD Mellen, BG Zeldin, DC Lindstrom, D Lappaleinen, U Law, AB Steele, S TI Randomized trial of cimetidine to prevent lung injury in newborn premature infants SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Vanderbilt Univ, Dept Prevent Med, Nashville, TN USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2092 BP 354A EP 354A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302091 ER PT J AU Rigatto, H Wilson, CG Koshiya, N House, S Smith, JC AF Rigatto, H Wilson, CG Koshiya, N House, S Smith, JC TI Stationary organotypic culture of the pre-Botzinger complex from the newborn rat SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NINDS, Neural Control Lab, Bethesda, MD 20892 USA. NIH, Neurochem Lab, Bethesda, MD 20892 USA. Univ Manitoba, Winnipeg, MB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2209 BP 374A EP 374A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302208 ER PT J AU Seidner, SR Jobe, AH Ikegami, M AF Seidner, SR Jobe, AH Ikegami, M TI Surfactant metabolism following late surfactant treatment doses during BPD development in preterm baboons SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NHLBI, BPD Resource, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2220 BP 376A EP 376A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302219 ER PT J AU Schmidt, B Davis, P Moddemann, D Ohlsson, A Roberts, R Saigal, S Solimano, A Vincer, M Wright, L AF Schmidt, B Davis, P Moddemann, D Ohlsson, A Roberts, R Saigal, S Solimano, A Vincer, M Wright, L CA TIPP Investigators TI International randomized placebo-controlled trial of indomethacin prophylaxis in preterm infants (TIPP) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 McMaster Univ, Hamilton, ON L8S 4L8, Canada. Royal Hosp Women, Melbourne, Vic, Australia. Childrens Hosp, Winnipeg, MB R3A 1S1, Canada. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. IWK Grace Hlth Ctr, Halifax, NS, Canada. NICHD, Neonatal Res Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2547 BP 431A EP 431A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302546 ER PT J AU Stark, AR Carlo, W Bauer, C Donovan, E Oh, W Papile, LA Shankaran, S Tyson, JE Wright, LL Saha, S Poole, K AF Stark, AR Carlo, W Bauer, C Donovan, E Oh, W Papile, LA Shankaran, S Tyson, JE Wright, LL Saha, S Poole, K TI Serious complications in a randomized trial of early stress dose dexamethasone (DEX) in extremely low birth weight (ELBW) infants SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHD, Neonatal Res Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2565 BP 434A EP 434A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302564 ER PT J AU Leeder, JS Adcock, K Gaedigk, A Gotschall, R Wilson, JT Kearns, GL AF Leeder, JS Adcock, K Gaedigk, A Gotschall, R Wilson, JT Kearns, GL TI Delayed maturation of cytochrome P450 3A (CYP3A) activity in vivo in the first year of life SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Mercy Hosp, NICHD, PPRU, Kansas City, MO 64108 USA. Louisiana State Univ, Med Ctr, NICHD, PPRU, Shreveport, LA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2788 BP 472A EP 472A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302787 ER PT J AU Schnermann, J AF Schnermann, J TI NaCl transport deficiencies - hemodynamics to the rescue SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE aquaporin 1; Bartter's syndrome; glomerular filtration rate; knockout mice; Na channel; Na/H exchanger; Na,K,2Cl-cotransporter pseudohypoaldosteronism ID EPITHELIAL SODIUM-CHANNEL; DISTAL CONVOLUTED TUBULE; LUNG LIQUID CLEARANCE; THICK ASCENDING LIMB; BARTTERS-SYNDROME; WATER CHANNELS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; PSEUDOHYPOALDOSTERONISM TYPE-1; GENETIC-HETEROGENEITY; HYPOKALEMIC ALKALOSIS AB Hereditary defects in the renal handling of filtered NaCl and water have important implications for understanding the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Null mutations in the water channel aquaporin 1 (AQP1) or the Na/H exchanger NHE3, two major fluid transporters in the proximal tubule, are stares in which a reduction in proximal fluid absorption is accompanied by proportionate decrements in glomerular filtration rate. Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either AQP1 or NHE3 deficiency. On the other hand, severe syndromes of salt wasting are caused by transport deficiencies in the thick ascending limb or the collecting duct, indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. Loss of function of the Na,K,2Cl-cotransporter (NKCC2) or of the epithelial Na channel (ENaC) reduces Na absorption in thick ascending limbs or collecting ducts. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load, intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is remarkably insufficient, particularly in the immature kidney of the newborn. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Room 4 D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. NR 61 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD APR PY 2000 VL 439 IS 6 BP 682 EP 690 DI 10.1007/s004240000258 PG 9 WC Physiology SC Physiology GA 304AM UT WOS:000086460400002 PM 10784341 ER PT J AU Bustamante, JO Michelette, ERF Geibel, JP Hanover, JA McDonnell, TJ Dean, DA AF Bustamante, JO Michelette, ERF Geibel, JP Hanover, JA McDonnell, TJ Dean, DA TI Dendrimer-assisted patch-clamp sizing of nuclear pores SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE cardiac myocytes; cell nucleus; dendrimers; EGFP; gene activity; gene expression; ion channels; nuclear ion channels; nuclear pores; nucleocytoplasmic transport; patch-clamp; pEGFP; pore diameter ID CARDIAC MYOCYTES; ION-CHANNEL; MEMBRANE; ENVELOPE; CALCIUM; COMPLEX; TRANSLOCATION; MOLECULES; DEPLETION; STORE AB Macromolecular translocation (MMT) across the nuclear envelope (NE) occurs exclusively through the nuclear pore complex (NPC), Therefore, the diameter of the NPC aqueous/electrolytic channel (NPCC) is important for cellular structure and function. The NPCC diameter was previously determined to be congruent to 10 nm with electron microscopy (EM) using the translocation of colloidal gold particles. Here we present patch-clamp and fluorescence microscopy data from adult cardiomyocyte nuclei that demonstrate the use of patch-clamp for assessing NPCC diameter. Fluorescence microscopy with B-phycoerythrin (BPE, 240 kDa) conjugated to a nuclear localization signal (NLS) demonstrated that these nuclei were competent for NPC-mediated MMT (NPC-MMT). Furthermore, when exposed to an appropriate cell lysate, the nuclei expressed enhanced green fluorescence pro-rein (EGFP) after 5-10 h of incubation with the plasmid for this protein (pEGFP, 3.1 MDa). Nucleus-attached patch-clamp showed that colloidal gold particles were not useful probes; they modified NPCC gating. As a re suit of this finding, we searched for an inert class of par tides that could be used without irreversibly affecting NPCC gating and found that fluorescently labeled Starburst dendrimers, a distinct class of polymers, were useful. Our patch-clamp and fluorescence microscopy data with calibrated dendrimers indicate that the cardiomyocyte NPCC diameter varies between 8 and 9 nm. These studies open a new direction in the investigation of live, continuous NPC dynamics under physiological conditions. C1 Univ Tiradentes, Nucl Physiol Lab, BR-49030270 Aracaju, Sergipe, Brazil. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. NIDDK, Cell Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. Univ S Alabama, Coll Med, Dept Microbiol & Immunol, Mobile, AL 36688 USA. RP Bustamante, JO (reprint author), Univ Tiradentes, Nucl Physiol Lab, Rua B-508, BR-49030270 Aracaju, Sergipe, Brazil. FU NHLBI NIH HHS [R01 HL059956] NR 31 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD APR PY 2000 VL 439 IS 6 BP 829 EP 837 DI 10.1007/s004240051011 PG 9 WC Physiology SC Physiology GA 304AM UT WOS:000086460400020 PM 10784359 ER PT J AU Miners, JO Coulter, S Birkett, DJ Goldstein, JA AF Miners, JO Coulter, S Birkett, DJ Goldstein, JA TI Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes SO PHARMACOGENETICS LA English DT Article DE torsemide; cytochrome P450; CYP2C9; sulphaphenazole inhibition; polymorphism ID CYTOCHROME-P450 CYP2C9; GENETIC-ANALYSIS; ALLELIC VARIANT; POLYMORPHISM; CYP2C9-ASTERISK-3; PHARMACOKINETICS; (S)-WARFARIN; ASSOCIATION; PHENYTOIN; WARFARIN C1 Flinders Med Ctr, Dept Clin Pharmacol, Bedford Pk, SA 5042, Australia. Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Miners, JO (reprint author), Flinders Med Ctr, Dept Clin Pharmacol, Bedford Pk, SA 5042, Australia. NR 19 TC 38 Z9 41 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD APR PY 2000 VL 10 IS 3 BP 267 EP 270 DI 10.1097/00008571-200004000-00008 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 309BW UT WOS:000086748500008 PM 10803683 ER PT J AU Abo-Zena, RA Bobek, MB Dweik, RA AF Abo-Zena, RA Bobek, MB Dweik, RA TI Hypertensive urgency induced by an interaction of mirtazapine and clonidine SO PHARMACOTHERAPY LA English DT Article AB Mirtazapine is a new antidepressant with a tetracyclic chemical structure that is not related to selective serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors. The antidepressant effect results from stimulation of the noradrenergic system through antagonism at central alpha(2)-inhibitory receptors. Clonidine exerts its antihypertensive effect by stimulating these receptors to cause a reduction in endogenous release of norepinephrine. Therefore, the two agents have mechanisms of action that potentially oppose one another. We report: a case of hypertensive urgency that ensued after a patient stabilized on clonidine began taking mirtazapine. C1 Cleveland Clin Fdn, Dept Pharm Practice, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Crit Care Med, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pulm & Crit Care Med, Cleveland, OH 44195 USA. RP Abo-Zena, RA (reprint author), NIH, Dept Pharm, 10 Ctr Dr,Bldg 10,Room 1N-257, Bethesda, MD 20892 USA. NR 7 TC 16 Z9 16 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD APR PY 2000 VL 20 IS 4 BP 476 EP 478 DI 10.1592/phco.20.5.476.35061 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 300XE UT WOS:000086278400014 PM 10772378 ER PT J AU Prutkin, J Duffy, VB Etter, L Fast, K Gardner, E Lucchina, LA Snyder, DJ Tie, K Weiffenbach, J Bartoshuk, LM AF Prutkin, J Duffy, VB Etter, L Fast, K Gardner, E Lucchina, LA Snyder, DJ Tie, K Weiffenbach, J Bartoshuk, LM TI Genetic variation and inferences about perceived taste intensity in mice and men SO PHYSIOLOGY & BEHAVIOR LA English DT Review DE taste; supertasters; psychophysics; genetics; PROP; intensity coding ID BITTER-TASTE; 6-N-PROPYLTHIOURACIL PROP; HEDONIC RESPONSE; SENSITIVITY; PERCEPTION; MAGNITUDE; PSYCHOPHYSICS; PAPILLAE; SWEET; NERVE AB The study of genetic variation in taste produces parallels between mice and men. In mice, genetic variation across strains has been documented with psychophysical and anatomical measures as well as with recordings from whole nerves. In humans, the variation has been documented with psychophysical and anatomical measures. Whole-nerve recordings from animals and psychophysical ratings of perceived intensities from human subjects have a similar logical limitation: absolute comparisons across individuals require a standard stimulus that can be assumed equally intense to all. Comparisons across whole-nerve recordings are aided by single-fiber recordings. Comparisons across psychophysical ratings of perceived intensity have been aided by recent advances in methodology; these advances now reveal that the magnitude of genetic variation in human subjects is larger than previously suspected. In females, hormones further contribute to variation in taste. There is evidence that the ability to taste (particularly bitter) cycles with hormones in women of child-bearing age, rises to a maximum early in pregnancy and declines after menopause. Taste affects food preferences, which in turn affect dietary behavior and thus disease risks. Valid assessment of taste variation now permits measurement of the impact of taste variation on health. Advances in psychophysical methodology were essential to understanding genetic variation in taste. In turn, the association of perceived taste intensities with tongue anatomy now provides a new tool for psychophysics. The ability of a psychophysical scale to provide across-subject comparisons can be assessed through its ability to show the fungiform papillae density-taste association. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Connecticut, Sch Allied Hlth, Storrs, CT 06269 USA. Fairfield Univ, Dept Psychol, Fairfield, CT 06430 USA. Unilever Res US, Edgewater, NJ 07020 USA. Florida State Univ, Dept Psychol, Tallahassee, FL 32312 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Bartoshuk, LM (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. FU NIDCD NIH HHS [DC00283] NR 118 TC 100 Z9 100 U1 3 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR 1 PY 2000 VL 69 IS 1-2 BP 161 EP 173 DI 10.1016/S0031-9384(00)00199-2 PG 13 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 323UG UT WOS:000087582900016 PM 10854927 ER PT J AU Lindberg, DAB AF Lindberg, DAB TI Bio-medical electronics - Update SO PROCEEDINGS OF THE IEEE LA English DT Article C1 Univ Maryland, Natl Lib Med, Bethesda, MD 20894 USA. RP Lindberg, DAB (reprint author), Univ Maryland, Natl Lib Med, Bethesda, MD 20894 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9219 J9 P IEEE JI Proc. IEEE PD APR PY 2000 VL 88 IS 4 BP 590 EP 592 DI 10.1109/5.843004 PG 3 WC Engineering, Electrical & Electronic SC Engineering GA 318GT UT WOS:000087276100010 ER PT J AU Liu, JL Yakar, S LeRoith, D AF Liu, JL Yakar, S LeRoith, D TI Conditional knockout of mouse insulin-like growth factor-1 gene using the Cre/loxP system SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID SITE-SPECIFIC RECOMBINATION; FACTOR-I GENE; TRANSGENIC MICE; MESSENGER-RNA; IGF-I; POSTNATAL-GROWTH; SKELETAL-MUSCLE; CRE RECOMBINASE; ADIPOSE-TISSUE; FETAL GROWTH AB Insulin-like growth factor-1 (IGF-1) is an essential growth factor for normal intrauterine development and postnatal growth. Mice with a complete deficiency of IGF-1 (IGF-1-null mice), created by homologous recombination, were found to exhibit postnatal lethality, growth retardation, infertility, and profound defects in the development of major organ systems. Furthermore, IGF-1-null mice were resistant to growth hormone (GH) treatment in peri-pubertal somatic growth. Using the Cre/loxP-induced conditional knockout, system, we generated a mouse that lacks IGF-1 specifically in the liver, the primary site, of IGF-1 production. Interestingly, although circulating and serum levels of IGF-1 were decreased by approximate to 75% in these mice, they exhibited no defect in growth or development. When administered exogenously, GH stimulated IGF-1 production in several extra-hepatic tissues as well as body growth. The "Somatomedin hypothesis" originally proposed that circulating IGF-1 acting in various tissues mediate the effects of GH. These striking in viva results, obtained using homologous recombination technology, call for a major modification of the Somatomedin hypothesis. These gene targeting studies confirm that IGF-1 Is essential for GH-stimulated postnatal body growth. However, liver-derived (endocrine) IGF-1 is not essential for normal postnatal growth; though it does exert a negative feedback on GH secretion. Instead, local production of IGF-1, acting in a paracrine/autocrine fashion, appears to mediate GH-induced somatic growth. This review will discuss the effects of tissue-specific IGF-1 gene deficiency created by the Cre/loxP system Versus the conventional IGF-1 knockout. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12,10 Ctr Dr, Bethesda, MD 20892 USA. NR 61 TC 80 Z9 84 U1 5 U2 23 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD APR PY 2000 VL 223 IS 4 BP 344 EP + DI 10.1046/j.1525-1373.2000.22349.x PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 300HN UT WOS:000086247400004 PM 10721003 ER PT J AU Alexi, T Borlongan, CV Faull, RLM Williams, CE Clark, RG Gluckman, PD Hughes, PE AF Alexi, T Borlongan, CV Faull, RLM Williams, CE Clark, RG Gluckman, PD Hughes, PE TI Neuroprotective strategies for basal ganglia degeneration: Parkinson's and Huntington's diseases SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE neurotrophic factors; excitotoxicity; metabolic compromise; oxidative stress; energy supplements; antioxidants; cell transplantation; immunosuppressants; immunophilins; apoptosis; striatum; substantia nigra; caudate-putamen ID FIBROBLAST GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; MIDBRAIN DOPAMINERGIC-NEURONS; NITRIC-OXIDE SYNTHASE; METHYL-D-ASPARTATE; MEDIAL FOREBRAIN-BUNDLE; RAT SUBSTANTIA-NIGRA; NEUROTROPHIC FACTOR PREVENTS; CALCIUM-BINDING PROTEIN; QUINOLINIC ACID LESIONS AB There are three main mechanisms of neuronal cell death which may act separately or cooperatively to cause neurodegeneration. This lethal triplet of metabolic compromise, excitotoxicity, and oxidative stress causes neuronal cell death that is both necrotic and apoptotic in nature. Aspects of each of these three mechanisms are believed to play a role in the neurodegeneration that occurs in both Parkinsons and Huntington's diseases. Strategies to rescue or protect injured neurons usually involve promoting neuronal growth and function or interfering with neurotoxic processes. Considerable research has been done on testing a large array of neuroprotective agents using animal models which mimic these disorders. Some of these approaches have progressed to the clinical arena. Here, we review neuroprotective strategies which have been found to successfully ameliorate the neurodegeneration associated with Parkinson's and Huntington's diseases. First, we will give an overview of the mechanisms of cell death and the background of Parkinson's and Huntington's diseases. Then we will elaborate on a range of neuroprotective strategies, including neurotrophic factors, anti-excitotoxins, antioxidants, bioenergetic supplements, anti-apoptotics, immunosuppressants, and cell transplantation techniques. Most of these approaches hold promise as potential therapies in the treatment of these disorders. (C) 2000 Elsevier Science Ltd. All lights reserved. C1 Univ Auckland, Sch Med, Res Ctr Dev Med & Biol, Auckland, New Zealand. Univ Auckland, Sch Med, Dept Anat & Radiol, Auckland, New Zealand. Univ Auckland, Sch Med, Dept Pharmacol & Clin Pharmacol, Auckland, New Zealand. NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RP Univ Auckland, Sch Med, Res Ctr Dev Med & Biol, Auckland, New Zealand. EM t.alexi@auckland.ac.nz OI Borlongan, Cesar/0000-0002-2966-9782 NR 724 TC 200 Z9 216 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD APR PY 2000 VL 60 IS 5 BP 409 EP 470 DI 10.1016/S0301-0082(99)00032-5 PG 62 WC Neurosciences SC Neurosciences & Neurology GA 281FC UT WOS:000085146400001 PM 10697073 ER PT J AU Oriji, GK AF Oriji, GK TI Angiotensin II stimulates hypertrophic growth of cultured neonatal rat ventricular myocytes: roles of PKC and PGF2alpha SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PIGLET PARIETAL CORTEX; MYOCARDIAL-CELLS; GENE-EXPRESSION; PHORBOL; PROSTANOIDS; INCREASES; MUSCLE; ESTERS AB Angiotensin II (Ang II) has been shown to regulate growth in smooth muscle cells. Protein kinase C (PKC), which mediates Ang II action, has been implicated in myocardial cell hypertrophy. Acute pressure overload in the left ventricles has been demonstrated to produce prostaglandin F2 alpha (PGF2alpha) release. Therefore, we used cultured neonatal rat ventricular myocytes to study Ang II, PKC and PGF2alpha and their relationship to hypertrophy. The amount of PGF2alpha produced was determined by radioimmunoassay, Ang It-induced hypertrophy and PGF2alpha release. Pretreatment with 10-6M of PKC inhibitor, 1-(5-isoquinolinesulfonyl-methyl) piperazine (H7), blocked Ang II-induced hypertrophy and PGF2alpha release. In neonatal rat ventricular myocytes that were treated with either Ang II or PKC activator (Phorbol 12, 13, dibutyrate; PDBu), PKC enzyme assay showed PKC was translocated from the cytosol to the membrane which indicates activation. This suggests that PKC mediates, in part, Ang II-induced PGF2alpha release and hypertrophy. In summary, Ang II activates PKC, which causes PGF2alpha release and hypertrophy, and this PGF2alpha release and hypertrophy can be overcome by pretreatment with PKC inhibitor (C) 2000 Harcourt Publishers Ltd. C1 William Paterson Univ, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NHLBI, Endocrine Branch, Nihon Univ, Bethesda, MD 20892 USA. RP Oriji, GK (reprint author), William Paterson Univ, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NR 23 TC 6 Z9 8 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 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD APR PY 2000 VL 62 IS 4 BP 233 EP 237 DI 10.1054/plef.2000.0148 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 326WK UT WOS:000087760000004 PM 10882187 ER PT J AU Hoover, DM Shaw, J Gryczynski, Z Proudfoot, AEI Wells, T Lubkowski, J AF Hoover, DM Shaw, J Gryczynski, Z Proudfoot, AEI Wells, T Lubkowski, J TI The crystal structure of Met-RANTES: Comparison with native RANTES and AOP-RANTES SO PROTEIN AND PEPTIDE LETTERS LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; GLYCOSAMINOGLYCAN-BINDING; CHEMOKINE RECEPTORS; CC-CHEMOKINE; PLATELET FACTOR-4; HEPARAN-SULFATE; IDENTIFICATION; ACTIVATION; DOMAIN; ANTAGONIST AB Met-RANTES is a modified version of the chemokine RANTES, which has an additional amino acid at the amino terminus. To compare Met-RANTES with the native protein as well as with another antagonist, AOP-RANTES, we have solved the structure of Met-RANTES at 1.6 Angstrom by X-ray crystallography and investigated the dimerization of all three proteins by fluorescence anisotropy. The dimerization of AOP-RANTES shows an altered aggregation profile. The delineation of slight differences in binding sulfate anions by Met- and AOP-RANTES might be linked to specific yet different interactions between these proteins and glycosaminoglycans. C1 NCI, Program Struct Biol, Macromol Crystallog Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Ctr Fluorescence Spect, Baltimore, MD 21201 USA. NR 50 TC 11 Z9 12 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD APR PY 2000 VL 7 IS 2 BP 73 EP 82 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 310AF UT WOS:000086802600001 ER PT J AU Park, S Leppla, SH AF Park, S Leppla, SH TI Optimized production and purification of Bacillus anthracis lethal factor SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID PROTECTIVE ANTIGEN GENE; DEPENDENT ADENYLATE-CYCLASE; EDEMA FACTOR; NUCLEOTIDE-SEQUENCE; SIGNAL PEPTIDASES; MOLECULAR-CLONING; TOXIN; EXPRESSION; CELLS; TRANSFORMATION AB Bacillus anthracis lethal factor (LF) is a 90-kDa zinc metalloprotease that plays an important role in the virulence of the organism. LF has previously been purified from Escherichia coli and Bacillus anthracis, The yields and purities of these preparations were inadequate for crystal structure determination. In this study, the genes encoding wild-type LF and a mutated, inactive LF (LF-E687C) were placed in an E. coli-Bacillus shuttle vector so that LF was produced with the protective antigen (PA) signal peptide at its N-terminus. The resulting vectors, pSJ115 and pSJ121, express wild-type and mutated LF fusion proteins, respectively. Expression of the LF genes is under the control of the PA promoter and, during secretion, the PA signal peptide is cleaved to release the 90-kDa LF proteins. The wild-type and mutated LF proteins were purified from the culture medium using three chromatographic steps (Phenyl-Sepharose, Q-Sepharose, and hydroxyapatite). The purified proteins were greater than 95% pure and yields (20-30 mg/L) were higher than those obtained in other expression systems (1-5 mg/L). These proteins have been crystallized and are being used to solve the crystal structure of LF. Their potential use in anthrax vaccines is also discussed. (C) 2000 Academic Press. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM Leppla@nih.gov NR 36 TC 108 Z9 109 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 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2000 VL 18 IS 3 BP 293 EP 302 DI 10.1080/02726350008906840 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 302NA UT WOS:000086370400007 PM 10733882 ER PT J AU Bruno, S Bettati, S Manfredini, M Mozzarelli, A Bolognesi, M Deriu, D Rosano, C Tsuneshige, A Yonetani, T Henry, ER AF Bruno, S Bettati, S Manfredini, M Mozzarelli, A Bolognesi, M Deriu, D Rosano, C Tsuneshige, A Yonetani, T Henry, ER TI Oxygen binding by alpha(Fe2+)(2)beta(Ni2+)(2) hemoglobin crystals SO PROTEIN SCIENCE LA English DT Article DE allosteric models; hemoglobin crystals; microspectrophotometry; oxygen binding; X-ray crystallography ID T-STATE HEMOGLOBIN; VALENCY HYBRID HEMOGLOBIN; HUMAN ADULT HEMOGLOBIN; X-RAY-DIFFRACTION; DIMERIC HEMOGLOBIN; SINGLE-CRYSTALS; MOLECULAR CODE; AFFINITY; COOPERATIVITY; ALPHA AB Oxygen binding by hemoglobin fixed in the T state either by crystallization or by encapsulation in silica gels is apparently noncooperative. However, cooperativity might be masked by different oxygen affinities of alpha and beta subunits. Metal hybrid hemoglobins, where the noniron metal does not bind oxygen, provide the opportunity to determine the oxygen affinities of alpha and beta hemes separately. Previous studies have characterized the oxygen binding by alpha(Ni2+)(2)beta(Fe2+)(2) crystals. Here, we have determined the three-dimensional (3D) structure and oxygen binding of alpha(Fe2+)(2)beta(Ni2+)(2) crystals grown from polyethylene glycol solutions. Polarized absorption spectra were recorded at different oxygen pressures with light polarized parallel either to the b or c crystal axis by single crystal microspectrophotometry. The oxygen pressures at 50% saturation (p50s) are 95 +/- 3 and 87 +/- 4 Torr along the b and c crystal axes, respectively, and the corresponding Hill coefficients are 0.96 +/- 0.06 and 0.90 +/- 0.03. Analysis of the binding curves, taking into account the different projections of the a hemes along the optical directions, indicates that the oxygen affinity of alpha(1) hemes is 1.3-fold lower than alpha(2) hemes. Inspection of the 3D structure suggests that this inequivalence may arise from packing interactions of the Hb tetramer within the monoclinic crystal lattice. A similar inequivalence was found for the beta subunits of alpha(Ni2+)(2)beta(Fe2+)(2) crystals. The average oxygen affinity of the alpha subunits (p50 = 91 Torr) is about 1.2-fold higher than the beta subunits (p50 = 110 Torr). In the absence of cooperativity, this heterogeneity yields an oxygen binding curve of Hb A with a Hill coefficient of 0.999. Since the binding curves of Hb A crystals exhibit a Hill coefficient very close to unity, these findings indicate that oxygen binding by T-state hemoglobin is noncooperative, in keeping with the Monod, Wyman, and Changeux model. C1 Univ Parma, Inst Biochem Sci, I-43100 Parma, Italy. Univ Parma, Natl Inst Phys Matter, I-43100 Parma, Italy. Univ Genoa, IST, Ctr Adv Biotechnol, I-16132 Genoa, Italy. Univ Genoa, Dept Phys, Natl Inst Phys Matter, I-16132 Genoa, Italy. Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Mozzarelli, A (reprint author), Univ Parma, Inst Biochem Sci, I-43100 Parma, Italy. RI Rosano, Camillo/D-5386-2011; Henry, Eric/J-3414-2013; Mozzarelli, Andrea/C-3615-2014; Bruno, Stefano/A-4582-2011; Bolognesi, Martino/B-7924-2017; OI Rosano, Camillo/0000-0003-2949-9215; Henry, Eric/0000-0002-5648-8696; Mozzarelli, Andrea/0000-0003-3762-0062; Bolognesi, Martino/0000-0002-9253-5170; Bruno, Stefano/0000-0002-7890-2472 FU NHLBI NIH HHS [HL14508] NR 49 TC 11 Z9 11 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD APR PY 2000 VL 9 IS 4 BP 683 EP 692 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304VQ UT WOS:000086505200006 PM 10794410 ER PT J AU Likavec, AM Dickerman, RD Heiss, JD Liow, K AF Likavec, AM Dickerman, RD Heiss, JD Liow, K TI Retrospective analysis of surgical treatment outcomes for gelastic seizures: a review of the literature SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Review DE surgery; radiosurgery; hypothalamic hamartomas; gelastic seizures ID HYPOTHALAMIC HAMARTOMA; PRECOCIOUS PUBERTY; EPILEPSY; RESECTION; LAUGHTER; FITS; EEG AB Gelastic seizures are known to be refractory to medical treatment and to date surgical therapy has yet to pinpoint the best treatment for these refractory seizures. There has been a multitude of case reports published on gelastic seizures and different surgical treatments, thus we performed a review of the Literature on gelastic seizures and surgical treatments to elucidate the best surgical approaches for medically refractory gelastic seizures. (C) 2000 BEA Trading Ltd. C1 NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Likavec, AM (reprint author), Case Western Reserve Univ, Sch Med, 10900 Euclid Ave, Cleveland, OH 44106 USA. NR 33 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD APR PY 2000 VL 9 IS 3 BP 204 EP 207 DI 10.1053/seiz.1999.0352 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 316LN UT WOS:000087168700007 PM 10775517 ER PT J AU Long, EO Rajagopalan, S AF Long, EO Rajagopalan, S TI HLA class I recognition by killer cell Ig-like receptors SO SEMINARS IN IMMUNOLOGY LA English DT Review DE HLA class I; HLA-G; inhibitory receptor; major histocompatibility complex; natural killer ID HUMAN NATURAL-KILLER; MHC CLASS-I; INHIBITORY RECEPTOR; DIRECT BINDING; NK CLONES; AMINO-ACID; ANTIGEN RECOGNITION; FUNCTIONAL TRANSFER; PERIPHERAL-BLOOD; MEDIATED LYSIS AB Natural killer (NK) cell activation is regulated by a combination of positive and negative signals coming from repertoires of activating and inhibitory receptors expressed on the surface of each NK cell. Receptors specific for major histocompatibility complex (MHC) class I molecules on ta-get cells inhibit NK effector functions such as cytotoxicity and cytokine production. As reviewed here, the killer cell Ig-like receptor (KIR) family on, human NK cells includes receptors with activating as well as inhibitory potential, receptors that have no known ligand, and inhibitory receptors with well-defined specificities Sor MHC class I such as HLA-B and HLA-C. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 70 TC 75 Z9 76 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD APR PY 2000 VL 12 IS 2 BP 101 EP 108 DI 10.1006/smim.2000.0212 PG 8 WC Immunology SC Immunology GA 304UP UT WOS:000086502800002 PM 10764618 ER PT J AU DeBaun, MR King, AA White, N AF DeBaun, MR King, AA White, N TI Hypoglycemia in Beckwith-Wiedemann syndrome SO SEMINARS IN PERINATOLOGY LA English DT Review ID PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA; INFANCY; CHILDREN; CANCER; MOUSE C1 NCI, Div Canc Etiol, Genet Epidemiol Branc, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Div Hematol Oncol, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Endocrinol & Metab, Dept Pediat, St Louis, MO 63110 USA. RP DeBaun, MR (reprint author), NCI, Div Canc Etiol, Genet Epidemiol Branc, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 32 Z9 36 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 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD APR PY 2000 VL 24 IS 2 BP 164 EP 171 DI 10.1053/sp.2000.6366 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 306JU UT WOS:000086594200008 PM 10805171 ER PT J AU Milenic, DE AF Milenic, DE TI Radioimmunotherapy: Designer molecules to potentiate effective therapy SO SEMINARS IN RADIATION ONCOLOGY LA English DT Review ID SINGLE-CHAIN-FV; COMPLEMENTARITY-DETERMINING-REGION; MURINE MONOCLONAL-ANTIBODY; DISULFIDE-STABILIZED FV; INITIAL CLINICAL-EVALUATION; METASTATIC COLON-CARCINOMA; ANTIGEN-BINDING PROTEIN; ADVANCED BREAST-CANCER; ESCHERICHIA-COLI; PHASE-I C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Milenic, DE (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 8B12,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 118 TC 16 Z9 16 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 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 2000 VL 10 IS 2 BP 139 EP 155 DI 10.1016/S1053-4296(00)80051-X PG 17 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 303YM UT WOS:000086455600008 PM 10727603 ER PT J AU Narrow, WE Regier, DA Norquist, G Rae, DS Kennedy, C Arons, B AF Narrow, WE Regier, DA Norquist, G Rae, DS Kennedy, C Arons, B TI Mental health service use by Americans with severe mental illnesses SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article ID CATCHMENT-AREA-PROGRAM; ADDICTIVE-DISORDERS; UNITED-STATES; PREVALENCE; VALIDITY; CARE AB Background: The aim of this study was to determine the patterns and determinants of service use in severely mentally ill persons drawn from the National Institute of Mental Health Epidemiological Catchment Area (ECA) program, a community-based epidemiologic survey. This information provides a baseline against which to track ongoing changes in the US mental health service system. Methods: Severe mental illness (SMI) was defined according to US Senate Appropriations Committee guidelines. Comparisons were made with persons who had a mental disorder that did not meet these criteria (non-SMI). Sociodemographic factors, and 1-year volume and intensity of mental or addictive services use were determined. Differences between those who used services and those who did not were examined using logistic regression. Results: Persons with SMI differed from persons with non-SMI in most sociodemographic characteristics. A higher proportion of persons with SMI used ambulatory services, but the mean number of visits per person did not differ from the non-SMI population. Persons with SMI comprised the bulk of hospital inpatients admitted during a 1-year period. Several significant sociodemographic determinants of service use were found, with different patterns for general medical and specialty service use, pointing out potential barriers to care. Conclusions: As health care reform measures continue to be debated, attention to the service needs of the severely mentally ill is of crucial importance. Pre-managed care (pre-1993) baseline service use benchmarks will be essential to assess the impact of managed care on access to care, particularly for the severely mentally ill. Periodic collection of epidemiologic data on prevalence and service use would thus greatly facilitate service planning and addressing barriers to receiving mental health services in this population. C1 NIMH, NIH, Bethesda, MD 20892 USA. Amer Psychiat Inst Res & Educ, Washington, DC USA. NIMH, Div Serv & Intervent Res, Rockville, MD 20857 USA. Ctr Mental Hlth Serv, Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. RP Narrow, WE (reprint author), Rm 403,1400 K St NW, Washington, DC 20005 USA. FU NIMH NIH HHS [UO1 MH33870, UO1 MH33883, UO1 MH34224] NR 35 TC 71 Z9 72 U1 1 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD APR PY 2000 VL 35 IS 4 BP 147 EP 155 DI 10.1007/s001270050197 PG 9 WC Psychiatry SC Psychiatry GA 320MR UT WOS:000087405400001 PM 10868079 ER PT J AU Sher, L AF Sher, L TI Social events and scientific innovations may affect the content of delusions SO SOUTHERN MEDICAL JOURNAL LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Bldg 10,Room 3S-231,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 3 U1 0 U2 1 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD APR PY 2000 VL 93 IS 4 BP 440 EP 441 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 307PW UT WOS:000086662700022 PM 10798521 ER PT J AU Harukuni, I Bhardwaj, A Shaivitz, AB DeVries, AC London, ED Hurn, PD Traystman, RJ Kirsch, JR AF Harukuni, I Bhardwaj, A Shaivitz, AB DeVries, AC London, ED Hurn, PD Traystman, RJ Kirsch, JR TI sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion SO STROKE LA English DT Article DE cerebral infarction; cerebral ischemia, focal; excitotoxicity; ligands; rats ID MIDDLE CEREBRAL-ARTERY; DECREASES BRAIN INJURY; SIGMA-RECEPTOR LIGAND; INFARCT VOLUME; IN-VIVO; RATS; OCCLUSION; PIPERIDINE; GLUTAMATE; MODEL AB Background and Purpose-We previously showed that the intravenous administration of the potent sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine (PPBP) provides neuroprotection against transient focal cerebral ischemia and that the protection depends on treatment duration. We tested the hypothesis that PPBP would provide neuroprotection in a model of transient focal ischemia and 7 days of reperfusion in the rat as assessed with neurobehavioral outcome and infarction volume. Methods-Under the controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) with the intraluminal suture occlusion technique. We used laser Doppler flowmetry to assess MCAO, At 60 minutes after the onset of ischemia, rats were randomly assigned to 1 of 4 treatment groups in a blinded fashion and received a continuous intravenous infusion of control saline or 0.1, 1, or 10 mu mol . kg(-1) . h(-1) PPBP for 24 hours. Neurobehavioral evaluation was performed at baseline (3 to 4 days before MCAO) and at 3 and 7 days of reperfusion. Infarction volume was assessed with triphenyltetrazolium chloride staining on day 7 of reperfusion in all rats. Results-Triphenyltetrazolium chloride-determined infarction volume of ipsilateral cortex was smaller in rats treated with 10 mu mol . kg(-1) . h(-1) PPBP (n=15, 68+/-12 mm(3), 18+/-3% of contralateral structure, P<0.05) (mean+/-SEM) compared with corresponding rats treated with saline (n=15, 114+/-11 mm(3), 31+/-3% of contralateral structure). PPBP did not provide significant neuroprotection in the caudoputamen complex. Although MCAO was associated with several alterations in behavior, the treatment with PPBP had no effect on behavioral outcomes. Conclusions-The data demonstrate that the potent sigma(1)-receptor ligand PPBP decreases cortical infarction volume without altering neurobehavior after transient focal ischemia and prolonged reperfusion in the rat. C1 Johns Hopkins Univ, Sch Med, Dept Anesthesiol Crit Care Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. NIDA, Baltimore, MD 21224 USA. RP Kirsch, JR (reprint author), Johns Hopkins Hosp, Blalock 1412,600 N Wolfe St, Baltimore, MD 21287 USA. FU NINDS NIH HHS [NS20020] NR 37 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2000 VL 31 IS 4 BP 976 EP 981 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 300WR UT WOS:000086277200034 PM 10754008 ER PT J AU Simon, R AF Simon, R TI Reading and assessing reports of treatment studies in oncology SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID RANDOMIZED CLINICAL-TRIALS AB The year 1998 marked the 50th anniversary of the introduction of the modem clinical trial to medicine. This event transformed medicine into an experimental science; nevertheless, surgeons and oncologists still are confronted by a literature that contains conflicting and erroneous claims. This article reviews the principles of the modem clinical trial to provide guidance for reading the medical literature and assessing claims of therapeutic effectiveness. C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, NIH, 9000 Rockville Pike,Bldg EPN,Room 739, Bethesda, MD 20892 USA. NR 12 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD APR PY 2000 VL 80 IS 2 BP 487 EP + DI 10.1016/S0039-6109(05)70197-3 PG 9 WC Surgery SC Surgery GA 306RC UT WOS:000086609000005 PM 10836003 ER PT J AU Luzzio, FA Mayorov, AV Figg, WD AF Luzzio, FA Mayorov, AV Figg, WD TI Thalidomide metabolites. Part 1: Derivatives of (+)-2-(N-phthalimido)-gamma-hydroxyglutamic acid SO TETRAHEDRON LETTERS LA English DT Article DE amino acids and derivatives; cleavage reactions; imides; osmylation; oxidation ID ANGIOGENESIS AB A mild version of the Lemieux-Johnson olefin cleavage followed by a peroxide-mediated dialdehyde oxidation and esterification effected the conversion of 1-acyloxy-4-N-phthalimido-2-cyclopentenyl esters to gamma-oxygenated-N-phthalimidoglutamic ester derivatives. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Luzzio, FA (reprint author), Univ Louisville, Dept Chem, Louisville, KY 40292 USA. RI Mayorov, Alexander/G-5204-2014; Figg Sr, William/M-2411-2016 OI Mayorov, Alexander/0000-0002-0899-7138; NR 18 TC 13 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD APR 1 PY 2000 VL 41 IS 14 BP 2275 EP 2278 DI 10.1016/S0040-4039(00)00160-X PG 4 WC Chemistry, Organic SC Chemistry GA 307YE UT WOS:000086681100002 ER PT J AU Medina, DL Suzuki, K Pietrarelli, M Okajima, F Kohn, LD Santisteban, P AF Medina, DL Suzuki, K Pietrarelli, M Okajima, F Kohn, LD Santisteban, P TI Role of insulin and serum on thyrotropin regulation of thyroid transcription factor-1 and Pax-8 genes expression in FRTL-5 thyroid cells SO THYROID LA English DT Article ID GROWTH-FACTOR-I; RECEPTOR GENE; DOWN-REGULATION; CYCLIC-AMP; THYROGLOBULIN PROMOTER; HORMONAL-REGULATION; RESPONSIVE ELEMENT; RAT THYROGLOBULIN; BINDING-PROTEINS; NUCLEAR-PROTEIN AB Thyrotropin (TSH), via its cyclic adenosine monophosphate (cAMP) signal, decreases thyrotropin receptor (TSHR) gene expression in FRTL-5 thyroid cells, whereas it increases expression of the thyroglobulin (Tg) gene. Despite the opposite effects of TSH on TSHR and Tg expression, both genes are positively controlled by thyroid transcription factor-1 (TTF-1) and evidence has accumulated that TSH can decrease TTF-1 mRNA levels. Zn this report, we further characterize the action of TSH on TTF-1 in order to understand its different activities on the TSHR and Tg genes better. The effect of TSH on the TSHR requires the presence of insulin and serum and we show here that also both factors are necessary for the TSH effect to decrease TTF-1 mRNA levels. The decrease is paralleled by a downregulation of TTF-1 protein levels as well as by a decrease in TTF-1/DNA complex when the TTF-1 site of the TSHR promoter was used as probe. Again, the decrease requires insulin and serum. The TSH downregulation of TTF-1 mRNA levels is due to a decrease in its transcription rate. Using a luciferase-linked chimera construct spanning 5.18 kb of the TTF-1 5'-flanking region, we show that TSH decreases TTF-1 promoter activity and that this effect depends on insulin and serum. These data contrast with the action of TSH on Tg and Pax-8 gene expression. TSH increases Pax-8 mRNA levels and the increase is evident whether insulin and serum are present or not. Moreover, this increase is paralleled by an increase in Pax-8 protein binding to an oligonucleotide derived from the C site of the Tg promoter, which can bind both TTF-1 and Pax-8. The present data thus show that TTF-1 gene expression is interdependently regulated by TSH and serum growth factors including insulin. They also show this interdependent-regulation is not duplicated in the case of Pax-8. We suggest that these differences may contribute to the distinct ability of TSH to regulate TSHR versus Tg gene expression in FRLT-5 thyroid cells. C1 CSIC, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain. Univ Autonoma Madrid, Madrid, Spain. NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. RP Santisteban, P (reprint author), CSIC, Inst Invest Biomed Alberto Sols, Arturo Duperier 4, Madrid 28029, Spain. RI Santisteban, Pilar/E-7829-2016; OI Santisteban, Pilar/0000-0002-2758-796X; Medina, Diego L./0000-0002-7347-2645 NR 46 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2000 VL 10 IS 4 BP 295 EP 303 DI 10.1089/thy.2000.10.295 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310FZ UT WOS:000086817000003 PM 10807057 ER PT J AU Meng, QX Su, T Olivero, OA Poirier, MC Shi, XC Ding, XX Walker, VE AF Meng, QX Su, T Olivero, OA Poirier, MC Shi, XC Ding, XX Walker, VE TI Relationships between DNA incorporation, mutant frequency, and loss of heterozygosity at the TK locus in human lymphoblastoid cells exposed to 3 '-azido-3 '-deoxythymidine SO TOXICOLOGICAL SCIENCES LA English DT Article DE 3 '-azido-3 ' deoxythymidine; human lymphoblastoid cells; DNA incorporation; thymidine kinase; mutant frequency; loss of heterozygosity ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; BONE-MARROW-CELLS; AZIDOTHYMIDINE AZT; AUTOSOMAL LOCUS; DOUBLE-BLIND; ZIDOVUDINE; INDUCTION; MUTATIONS; MICE AB 3'-Azido-3'-deoxythymidine (AZT), a thymidine analogue widely used in the treatment of AIDS patients and for prevention of the onset of AIDS in HIV-seropositive individuals, causes tumors in mice ex-posed as adults or in utero. The purpose of this study was to investigate the potential mechanisms of AZT mutagenicity and carcinogenicity by quantifying the incorporation of AZT into cellular DNA, measuring AZT-induced thymidine kinase (TK) mutant frequencies (Mfs), and determining the percentage of loss of heterozygosity (LOH) in spontaneous or AZT-induced TK mutants in the human lymphoblastoid cell line, TK6. Cells were exposed to 300 mu M AZT for 0, 1, 3, or 6 days, or to 0, 33, 100, 300, or 900 mu M AZT for 3 days (n = 5 flasks/group). The effects of exposure concentration on incorporation of AZT into cellular DNA were evaluated by an AZT radioimmunoassay, and the effects of duration and concentration of AZT exposure on the TK MfS were assessed by a cell-cloning assay. AZT was incorporated into DNA in a dose-related manner at concentrations up to 300 mu M, above which no further increase was observed. TK Mf increased with the extended duration and with incremental concentrations of AZT exposure. There was a positive correlation (P = 0.036, coefficient = 0.903) between AZT-DNA incorporation and AZT-induced TK Mfs, suggesting that AZT incorporation into cellular DNA has a direct role in the genotoxicity of AZT. Southern blot analyses indicated that 84% (6.2 x 10(-6)/7.4 x 10(-6)) of AZT-induced mutants were attributable to LOH, consistent with the known mechanism of AZT as a DNA chain terminator. Considering the importance of LOH in human carcinogenesis, AZT-induced LOH warrants further study. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12203 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Walker, VE (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. FU NICHD NIH HHS [HD33648]; NIEHS NIH HHS [ES07462] NR 30 TC 39 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2000 VL 54 IS 2 BP 322 EP 329 DI 10.1093/toxsci/54.2.322 PG 8 WC Toxicology SC Toxicology GA 299XT UT WOS:000086224300007 PM 10774814 ER PT J AU Walker, NJ Tritscher, AM Sills, RC Lucier, GW Portier, CJ AF Walker, NJ Tritscher, AM Sills, RC Lucier, GW Portier, CJ TI Hepatocarcinogenesis in female Sprague-Dawley rats following discontinuous treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 17th Symposium on Chlorinated Dioxins and Related Compounds (Dioxin 97) CY AUG 25-29, 1997 CL INDIANAPOLIS, INDIANA DE TCDD; dioxin; carcinogenesis; altered hepatocellular foci; liver tumors; placental glutathione S-transferase; half-life ID ENZYME-ALTERED FOCI; CELL-PROLIFERATION; HEPATIC FOCI; PROMOTION; LIVER; TCDD; DIETHYLNITROSAMINE; MODEL; EXPOSURE; LESIONS AB In this study, rye investigated the time course of promotion of tumors and putatively preneoplastic altered hepatic foci in the livers of diethylnitrosamine (DEN)-initiated female Sprague-Dawley rats. These rats had been treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) under different dosing regimens, but we used the same administered biweekly dose of 1.75 mu g/kg of body weight. Animals were treated continuously for up to 60 weeks, or continuously for 30 weeks, followed by cessation of treatment for up to 30 weeks. In addition, TCDD treatment in these groups was begun either 2 or 18 weeks after initiation with DEN. Liver tumors were only observed in animals after 60 weeks on the study and were increased by continuous TCDD treatment, relative to controls. The incidence of hepatocellular adenoma and carcinoma combined, in animals treated with TCDD for 30 weeks followed by no TCDD treatment for 30 weeks (17%), was lower than in animals receiving either TCDD (79%) or vehicle control (corn oil) alone (55%) for 60 weeks. The lower liver-tumor incidence after cessation of TCDD treatment paralleled time-dependent decreases in the volume fraction occupied by placental glutathione S-transferase-positive altered hepatic foci and the number of foci per unit volume, but not the mean focus volume that exhibited a time-dependent increase after cessation of TCDD treatment. Cessation of TCDD treatment led to reductions in liver TCDD levels, and these changes were reflected in a cessation of reduced body weight because of TCDD treatment. These data indicate that liver-tumor promotion by TCDD in female rats is dependent upon continuous exposure to TCDD, and that alterations in patterns of TCDD exposure can have significant effects on tumor incidence not reflected by standard measures of dioxin exposure. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Walker, NJ (reprint author), NIEHS, Environm Toxicol Program, Bldg 101,Room D452,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010; Walker, Nigel/D-6583-2012 OI Portier, Christopher/0000-0002-0954-0279; Walker, Nigel/0000-0002-9111-6855 NR 21 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2000 VL 54 IS 2 BP 330 EP 337 DI 10.1093/toxsci/54.2.330 PG 8 WC Toxicology SC Toxicology GA 299XT UT WOS:000086224300008 PM 10774815 ER PT J AU Wyde, ME Seely, J Lucier, GW Walker, NJ AF Wyde, ME Seely, J Lucier, GW Walker, NJ TI Toxicity of chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in diethylnitrosamine-initiated ovariectomized rats implanted with subcutaneous 17 beta-estradiol pellets SO TOXICOLOGICAL SCIENCES LA English DT Article DE 2,3,7,8-tetrachlorodibenzo-p-dioxin; 17 beta-estradiol; hepatocarcinogenesis; clinical chemistry; subcutaneous pellets ID AH-RECEPTOR; CD1 MICE; TCDD; HEPATOCARCINOGENESIS; LIVER; MICROSOMES; METABOLISM; INCREASES; TAMOXIFEN; PROMOTION AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in female but not in male rats. Several lines of evidence suggest a key role of ovarian hormones, presumably estrogen, in the mechanism of TCDD-induced hepatocarcinogenesis. The aim of this current study was to determine the toxicity of co-treatment with TCDD and 17 beta-estradiol and assess the efficacy of 90-day subcutaneous constant release 17 beta-estradiol pellets. Ovariectomized (OVX) female Sprague-Dawley rats were initiated with diethylnitrosamine (DEN) and treated with TCDD for 20 or 30 weeks in the presence and absence of 17 beta-estradiol, TCDD concentrations were equivalent in livers of TCDD-treated sham operated and OVX rats following 20 weeks of treatment. Following 30 weeks of TCDD treatment, liver TCDD concentrations were higher in OVX rats than in intact rats. TCDD concentrations in livers of TCDD-treated OVX rats receiving supplemental 17 beta-estradiol were similar to intact rats following either 20 or 30 weeks of treatment. Mean hepatic background TCDD concentrations in untreated rats were 2-fold higher in intact rats compared to OVX rats, regardless of 17 beta-estradiol exposure following 20, but not 30 weeks of treatment. Serum indicators of hepatocellular and hepatobiliary toxicity indicated transient hepatotoxicity in TCDD-treated OVX rats receiving 17 beta-estradiol. Histopathological alterations indicated hepatotoxicity induced by exposure to TCDD following either 20 or 30 weeks of exposure. No excess hepatotoxicity was associated with 17 beta-estradiol-supplementation in TCDD-exposed OVX female Sprague-Dawley rats. Serum 17 beta-estradiol concentrations were not constant and resulted in supra-physiological levels that decreased over time, resulting in target physiological serum 17 beta-estradiol concentrations following several weeks of release. Treatment with 17 beta-estradiol resulted in uterine weights and total body weights comparable to sham-operated female rats. These data confirm the efficacy of supplemental subcutaneous 17 beta-estradiol pellets on the induction of estrogenic responses in TCDD-treated rats and indicate no increased hepatotoxicity associated with 17 beta-estradiol exposure in TCDD-treated rats. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. Pathco Inc, Res Triangle Pk, NC USA. RP Walker, NJ (reprint author), NIEHS, Lab Computat Biol & Risk Anal, MD D4-01,POB 12233, Res Triangle Pk, NC 27709 USA. RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 35 TC 6 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2000 VL 54 IS 2 BP 493 EP 499 DI 10.1093/toxsci/54.2.493 PG 7 WC Toxicology SC Toxicology GA 299XT UT WOS:000086224300025 PM 10774832 ER PT J AU Romach, EH Zhao, CQ Del Razo, LM Cebrian, ME Waalkes, MP AF Romach, EH Zhao, CQ Del Razo, LM Cebrian, ME Waalkes, MP TI Studies on the mechanisms of arsenic-induced self tolerance developed in liver epithelial cells through continuous low-level arsenite exposure SO TOXICOLOGICAL SCIENCES LA English DT Article DE arsenic; zinc; tolerance; metallothionein; cytotoxicity ID HAMSTER OVARY CELLS; HEPATIC METALLOTHIONEIN; DIMETHYLARSINIC ACID; REDUCED GLUTATHIONE; OXIDATIVE DAMAGE; ESCHERICHIA-COLI; RESISTANCE; TISSUES; MICE; EXPRESSION AB Arsenic (As) is a human carcinogen. Our prior work showed that chronic (>18 weeks) tow level (500 nM) arsenite (As3+) exposure induced malignant transformation in a rat liver epithelial cell line (TRL 1215). In these cells, metallothionein (MT) is hyper-expressible, a trait often linked to metal tolerance. Thus, this study examined whether the adverse effects of arsenicals and other metals were altered in these chronic arsenite-exposed (CAsE) cells. CAsE cells, which had been continuously exposed to 500 nM arsenite for 18 to 20 weeks, and control cells, were exposed to As3+, arsenate (As5+), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), antimony (Sb3+), cadmium (Cd2+), cisplatin (cis-Pt), and nickel (Ni2+) for 24 h and cell viability was determined by metabolic integrity. The lethal concentration for 50% of exposed cells (LC50) for As3+ nas 140 mu M in CAsE cells as compared to 26 mu M in control cells, a 5.4-fold increase in tolerance. CAsE cells were also very tolerant to the acute toxic effects of As5+ (LC50 4000 mu M) compared to control (LC50 180 mu M. The LC50 for DMA was 4.4-fold higher in CAsE cells than in control cells, but the LC50 for MMA was unchanged. There was a modest cross-tolerance to Sb3+, Cd2+, and cis-Pt in CAsE cells (LC50 1.5-3.0-fold higher) as compared to control. CASE cells were very tolerant to Ni2+ (LC50 > 8-fold higher). Culturing CAsE cells in As3+-free medium for 5 weeks did not alter As3+ tolerance, implicating an irreversible phenotypic change. Cellular accumulation of As was 87% less in CAsE cells than control and the accumulated As was mo, readily eliminated. Although accumulating much less As, a greater portion was converted to DMA in CAsE cells. Altered glutathione (GSH) Levels were not Linked with As tolerance. A maximal induction of MT by Zn produced only a 2.5-fold increase in tolerance to As3+ in control cells. Cell lines derived from MT normal mice (MT+/+) were only slightly more resistant (1.6-fold) to As3+ than cells from MT null mice (MT-/-). These results show that CAsE cells acquire tolerance to As3+, As5+, and DMA. It appears that this self-tolerance is based primarily on reduced cellular disposition of the metalloid and is not accounted for by changes in GSH or MT. C1 NIEHS, Inorgan Carcinogensis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. IPN, CINVESTAV, Mexico City 07738, DF, Mexico. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogensis Sect, Comparat Carcinogenesis Lab, NCI, Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 45 TC 72 Z9 79 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2000 VL 54 IS 2 BP 500 EP 508 DI 10.1093/toxsci/54.2.500 PG 9 WC Toxicology SC Toxicology GA 299XT UT WOS:000086224300026 PM 10774833 ER PT J AU Zimmerberg, J AF Zimmerberg, J TI Are the curves in all the right places? SO TRAFFIC LA English DT Article ID LYSOPHOSPHATIDIC ACID; FUSION; TRANSITION; MEMBRANES C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 12 TC 24 Z9 24 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD APR PY 2000 VL 1 IS 4 BP 366 EP 368 DI 10.1034/j.1600-0854.2000.010409.x PG 3 WC Cell Biology SC Cell Biology GA 325ZG UT WOS:000087706700009 PM 11208121 ER PT J AU Koch, CA Doppman, JL Patronas, NJ Nieman, LK Chrousos, GP AF Koch, CA Doppman, JL Patronas, NJ Nieman, LK Chrousos, GP TI Do glucocorticoids cause spinal epidural lipomatosis? When endocrinology and spinal surgery meet SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CUSHINGS-SYNDROME; RENAL-TRANSPLANTATION; CORTISOL SECRETION; RECEPTOR; HYPOTHYROIDISM; COMPLICATION; SECONDARY; PATIENT; STRESS AB Here, we report pathogenetic aspects of spinal epidural lipomatosis (SEL) based on a literature review. SEL is a rare entity but can cause significant morbidity. Its symptoms can be identical to those of more common disorders such as vertebral and disc disease, and cord lesions (for example, transverse myelitis, multiple sclerosis and syringomytelia). Therefore, it often goes undiagnosed. In addition, SEL occurs in patients on glucocorticoid therapy, which can lend to myopathy, thereby mimicking the motor symptoms of SEL. Glucocorticoids seem to play a major role in the development of SEL, although idiopathic SEL has also been reported. The latter occurs almost exclusively in obese individuals who may have concurrent hypercortisolism. Once clinically suspected SEL is best diagnosed by magnetic resonance imaging (MRI). Treatment of SEL is directed at reducing body weight in patients with idiopathic SEL, and at decreasing glucocorticoid excess ii patients with endogenous or exogenous hypercortisolism. In severe cases, decompressive laminectomy might become necessary to alleviate the neurological symptoms caused by spinal cord compression. C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHHD, Dev Endocrinol Branch, Bldg 10, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 45 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 2000 VL 11 IS 3 BP 86 EP 90 DI 10.1016/S1043-2760(00)00236-8 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 297MC UT WOS:000086085800002 PM 10707048 ER PT J AU Bolognesi, C Morasso, G AF Bolognesi, C Morasso, G TI Genotoxicity of pesticides: potential risk for consumers SO TRENDS IN FOOD SCIENCE & TECHNOLOGY LA English DT Article ID SISTER-CHROMATID EXCHANGES; CHROMOSOMAL-ABERRATIONS; OCCUPATIONAL EXPOSURE; IN-VIVO; ORGANOPHOSPHATE INSECTICIDE; PERIPHERAL LYMPHOCYTES; AGRICULTURAL-WORKERS; MICRONUCLEUS ASSAY; TEST SYSTEM; MUTAGENICITY C1 Natl Canc Inst, Toxicol Evaluat Unit, I-16132 Genoa, Italy. Natl Canc Inst, Dept Psychol, I-16132 Genoa, Italy. RP Bolognesi, C (reprint author), Natl Canc Inst, Toxicol Evaluat Unit, Largo R Benzi 10, I-16132 Genoa, Italy. NR 66 TC 53 Z9 56 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0924-2244 J9 TRENDS FOOD SCI TECH JI Trends Food Sci. Technol. PD APR-MAY PY 2000 VL 11 IS 4-5 SI SI BP 182 EP 187 DI 10.1016/S0924-2244(00)00060-1 PG 6 WC Food Science & Technology SC Food Science & Technology GA 392CD UT WOS:000166392300007 ER PT J AU Zeldin, DC Liao, JK AF Zeldin, DC Liao, JK TI Reply: cytochrome P450-derived eicosanoids and the vascular wall SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID EXPRESSION; HEART C1 NIEHS, Clin Studies Sect, NIH, Res Triangle Pk, NC 27709 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Zeldin, DC (reprint author), NIEHS, Clin Studies Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 8 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 2000 VL 21 IS 4 BP 127 EP 128 DI 10.1016/S0165-6147(00)01454-1 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QE UT WOS:000086663500004 ER PT J AU Usdin, TB AF Usdin, TB TI The PTH2 receptor and TIP39: a new peptide-receptor system SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID HORMONE-RELATED PROTEIN; PARATHYROID-HORMONE; PHYSIOLOGY C1 NIMH, Cell Biol Unit, Genet Lab, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Cell Biol Unit, Genet Lab, Bldg 36,Room 3D06,36 Convent Dr, Bethesda, MD 20892 USA. NR 20 TC 39 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 2000 VL 21 IS 4 BP 128 EP 130 DI 10.1016/S0165-6147(00)01455-3 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QE UT WOS:000086663500005 PM 10740285 ER PT J AU Wen, H AF Wen, H TI Feasibility of biomedical applications of Hall effect imaging SO ULTRASONIC IMAGING LA English DT Article DE bioimpedance; conductivity; dielectric; Hall; imaging; photoacoustic; tissue; tomography; ultrasound ID ULTRASOUND; TOMOGRAPHY; SYSTEM AB Hall effect imaging is a new technique for mapping the electrical properties of a sample. Its principle has been demonstrated in two- and three-dimensional phantom images. Based on the experimental data and theoretical understanding of this technique developed over the past few years, this paper addresses the most relevant question for biomedical applications: whether Hall effect imaging is ultimately applicable to complex biological systems such as the human body. The arguments are given at the basic physics level, so that the conclusion is independent of current technology status. These arguments are corroborated with imaging data of an aorta sample. The conclusion is that Hall effect imaging is not suited for quantifying the electrical constants in complex biological samples. This technique is able to produce high-resolution volume images of samples in vitro that reflect their electrical heterogeneity. However, quantitative measurements of electrical constants are not practical for complex samples. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1d-161, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 18 TC 18 Z9 18 U1 0 U2 9 PU DYNAMEDIA INC PI SILVER SPRING PA 2 FULHAM COURT, SILVER SPRING, MD 20902 USA SN 0161-7346 J9 ULTRASONIC IMAGING JI Ultrason. Imaging PD APR PY 2000 VL 22 IS 2 BP 123 EP 136 PG 14 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 368FW UT WOS:000090107900004 PM 11061463 ER PT J AU Bailly, JE McAuliffe, JM Skiadopoulos, MH Collins, PL Murphy, BR AF Bailly, JE McAuliffe, JM Skiadopoulos, MH Collins, PL Murphy, BR TI Sequence determination and molecular analysis of two strains of bovine parainfluenza virus type 3 that are attenuated for primates SO VIRUS GENES LA English DT Article DE bovine parainfluenza viruses; human parainfluenza viruses; attenuation determinants; host range; vaccine virus; nucleotide and amino acid sequence alignments ID RESPIRATORY SYNCYTIAL VIRUS; PARA-INFLUENZA VIRUS-3; AMINO-ACID-SEQUENCE; P-PROTEIN; NUCLEOCAPSID PROTEIN; NUCLEOTIDE-SEQUENCE; ADULT VOLUNTEERS; TERMINAL DOMAIN; MESSENGER-RNAS; NP-PROTEIN AB The Kansas/15626/84 (Ka) and Shipping Fever (SF) strains of bovine parainfluenza virus type 3 (BPIV3) replicate less efficiently than human PIV3 (HPIV3) in the upper and lower respiratory tract of rhesus monkeys, and BPIV3 Ka is also highly attenuated in humans and is in clinical trials as a candidate vaccine against HPIV3. To initiate an investigation of the genetic basis of the observed attenuation phenotype of BPIV3 in primates, the complete genomic sequences of Ka and SF genomes were determined and compared to those of BPIV3 strain 910N and two HPIV3 strains, JS and Wash/47885/57. There is a high degree of identity between the five PIV3 viruses in their 55 nucleotide (nt) leader (83.6%) and 44 nt trailer (93.2%) sequences. The five viruses display amino acid sequence identity ranging from 58.6% for the phosphoprotein to 89.7% for the matrix protein. Interestingly, the majority of amino acid residues found to be variable at a given position in a five-way protein alignment are nonetheless identical within the viruses of either host species (BPIV3 or HPIV3). These host-specific residues might be products of distinct selective pressures on BPIV3 and HPIV3 during evolution in their respective hosts. These host-specific sequences likely include ones which are responsible for the host range differences, such as the efficient growth of BPIV3 in bovines compared to its restricted growth in primates. It should now be possible using the techniques of reverse genetics to import sequences from BPIV3 into HPIV3 and identify those nt or protein sequences which attenuate HPIV3 for primates. This information should be useful in understanding virus-host interactions and in the development of vaccines to protect against HPIV3-induced disease. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Murphy, BR (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 54 TC 27 Z9 29 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD APR PY 2000 VL 20 IS 2 BP 173 EP 182 DI 10.1023/A:1008130917204 PG 10 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 303KY UT WOS:000086422100011 PM 10872880 ER PT J AU Yang, YH Jiang, L Yang, SL Zhu, LQ Wu, YJ Li, ZJ AF Yang, YH Jiang, L Yang, SL Zhu, LQ Wu, YJ Li, ZJ TI A mutant subtilisin E with enhanced thermostability SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE subtilisin E; site-directed mutagenesis; thermostability ID SITE-DIRECTED MUTAGENESIS; STABILITY; ALKALINE; PROTEASE; BPN' AB A mutant subtilisin E with remarkably thermostability is reported. It is more active against the typical substrate s-AAPF-pna than the wild-type subtilisin E. The time required for getting 50% residual activity of Ser236Cys subtilisin E at 60 degrees C in aqueous solution was approximately 80 min which is 4 times longer than that of wild-type subtilisin E. Similar to the wild-type subtilisin E, the amidase activity of Ser236Cys subtilisin E is dramatically reduced in the presence of dimethylformamide (DMF). C1 Acad Sinica, Shanghai Res Ctr Biotechnol, Shanghai 200233, Peoples R China. Acad Sinica, Inst Biophys, Beijing 100101, Peoples R China. RP Yang, YH (reprint author), NIEHS, LPC, NH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 12 TC 8 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD APR PY 2000 VL 16 IS 3 BP 249 EP 251 DI 10.1023/A:1008959825832 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 327TN UT WOS:000087809400007 ER PT J AU Charles, LG Xie, YC Restifo, NP Roessler, B Sanda, MG AF Charles, LG Xie, YC Restifo, NP Roessler, B Sanda, MG TI Antitumor efficacy of tumor-antigen-encoding recombinant poxvirus immunization in Dunning rat prostate cancer: implications for clinical genetic vaccine development SO WORLD JOURNAL OF UROLOGY LA English DT Article ID MEMBRANE ANTIGEN; CELLS; EXPRESSION; VIRUS; IMMUNOTHERAPY; MODEL; THERAPY; GENERATION; INJECTION; PSA AB One potential use for prostate-cancer-associated genes discovered through ongoing genetics studies entails the construction of virus- or plasmid-based recombinant vector vaccines encoding these new tumor-associated antigens (TAA) to induce TAA-specific immune responses for the prevention or therapy of prostate cancer. Clinical trials evaluating prototypes of such recombinant vaccines are under way. TAA-encoding recombinant vector vaccines, however, have not previously been evaluated in a prostate-cancer animal model. For assessment of the potential susceptibility of prostate cancer to genetic immunization strategies using TAA-encoding recombinant vectors. the antitumor efficacy of a model recombinant viral vector encoding a TAA was evaluated in rat Dunning prostate cancer. Recombinant vaccinia was chosen as a prototype virus vector encoding a TAA for these studies, and B-galactosidase was chosen as a model target TAA. C1 Univ Michigan, Sch Med, Dept Urol Surg, Taubman Ctr 2916, Ann Arbor, MI 48109 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Med Rheumatol, Ann Arbor, MI USA. Ann Arbor Vet Adm Med Ctr, Ann Arbor, MI USA. RP Sanda, MG (reprint author), Univ Michigan, Sch Med, Dept Urol Surg, Taubman Ctr 2916, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Restifo, Nicholas/A-5713-2008; Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [R29 CA71532-01] NR 32 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD APR PY 2000 VL 18 IS 2 BP 136 EP 142 DI 10.1007/s003450050186 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 314LH UT WOS:000087056900008 PM 10854149 ER PT J AU Sai, Y Dai, R Yang, TJ Krausz, KW Gonzalez, FJ Gelboin, HV Shou, M AF Sai, Y Dai, R Yang, TJ Krausz, KW Gonzalez, FJ Gelboin, HV Shou, M TI Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450 SO XENOBIOTICA LA English DT Article ID HUMAN-LIVER-MICROSOMES; IN-VITRO METABOLISM; MONOCLONAL-ANTIBODIES; SELECTIVE INHIBITORS; ENZYMES; OXIDATION; ACTIVATION; 2A6; IDENTIFICATION; DRUGS AB 1. The selectivity of eight chemical inhibitors has been extensively evaluated with 10 cDNA-expressed human cytochrome P450 isoforms (CYP). The results indicate that sulphaphenazole, quinidine and alpha-naphthoflavone are selective inhibitors of CYP2C9 (IC50 = 0.5-0.7 mu M), CYP2D6 (0.3-0.4 mu M) and CYP1A (0.05-5 mu M) respectively on the basis of the IC50, which are much lower than those of other P450 isoforms (> 10-fold). 2. Ketoconazole exhibited potent inhibition of both CYP3A4-catalysed metabolism of phenanthrene, testosterone, diazepam (IC50 = 0.03-0.5 mu M) and CYP1A1-calalysed deethylation of 7-ethoxycoumarin (0.33 mu M). The selectivity of ketoconazole for other P450s was highly related to the concentration used. 3. Diethyldithiocarbamate, orphenadrine and furafylline were shown separately to be less selective inhibitors of CYP2E1, CYP2B6 and CYP1A isoforms by a broad range of IC50 that overlap those observed with other P450 isoforms. 4. Furafylline, quinidine and alpha-naphthoflavone activated CYP3A4-catalysed phenanthrene metabolism by 1.7-, 2- and 15-fold respectively. 5. The selectivity of orphenadrine and ketoconazole was further examined by using inhibitory monoclonal antibodies (MAb). Inhibitory MAb specific for the individual P-450 isoforms may be of greater value than chemical inhibitors. C1 Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Shou, M (reprint author), Merck Res Labs, Dept Drug Metab, WP75A-203, W Point, PA 19486 USA. NR 42 TC 118 Z9 119 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD APR PY 2000 VL 30 IS 4 BP 327 EP 343 PG 17 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 310TG UT WOS:000086843000001 PM 10821163 ER PT J AU Clark, JA Mezey, E Lam, AS Bonner, TI AF Clark, JA Mezey, E Lam, AS Bonner, TI TI Distribution of the GABA(B) receptor subunit gb2 in rat CNS SO BRAIN RESEARCH LA English DT Article DE GABA(B) receptor; heteromeric; G protein-coupled receptor; metabotropic receptor; baclofen; GABA ID CENTRAL-NERVOUS-SYSTEM; METABOTROPIC GLUTAMATE RECEPTORS; MESSENGER-RNAS; EXPRESSION; PROTEIN; SITES AB We have identified and isolated human and rat cDNAs for a novel receptor, gb2, with 38% homology to the GABA(B) receptors gb1a and gb1b. These receptors comprise a new subfamily of seven transmembrane G protein-coupled receptors (GPCRs) that share structure and sequence similarities with the metabotropic glutamate receptors. In situ hybridization histochemistry using an antisense probe to this novel receptor mRNA shows a distribution in rat CNS nearly identical to that for the gb1 receptor, although some regions showed significant differences. Specifically, message levels for gb2 were virtually absent in the caudate/putamen, and significantly lower in the medial basal hypothalamus, septum and brainstem as compared with gb1 message levels. In contrast to gb1, gb2 mRNA was never detected in white matter suggesting that gb2 message is found exclusively in neurons. Finally, in rat brain regions showing significant overlap of message for gb1 and gb2, the transcripts are often found in the same cells. Data from our previous work showing that coexpression of gb2 with gb1 is necessary for expression of a functional receptor together with the detailed anatomical data presented here indicate that native GABA(B) receptors function as heteromeric proteins, the most abundant form being the gb1/gb2 receptor. However, the more limited distribution of gb2 receptor mRNA suggests that there are brain regions where GABA(B) receptors are composed of gb1 and as yet unidentified family members. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Basic Neurosci Program, Bethesda, MD 20892 USA. RP Clark, JA (reprint author), NIMH, Genet Lab, 36 Convent Dr,MSC 4094, Bethesda, MD 20892 USA. NR 29 TC 69 Z9 77 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 31 PY 2000 VL 860 IS 1-2 BP 41 EP 52 DI 10.1016/S0006-8993(00)01958-2 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 297KD UT WOS:000086081000005 PM 10727622 ER PT J AU Wei, HF Leeds, PR Qian, YN Wei, WL Chen, RW Chuang, DM AF Wei, HF Leeds, PR Qian, YN Wei, WL Chen, RW Chuang, DM TI beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE lithium chloride; beta-amyloid; Bcl-2; Alzheimer's disease ID ALZHEIMERS-DISEASE; PROTEIN; PHOSPHORYLATION; APOPTOSIS; BCL-2 AB Treatment of rat pheochromocytoma cells (PC 12) cells with beta-amyloid peptide-(1-42) for 24 h induced a concentration-dependent decrease in cellular redox activity in the dose range of 1 to 20 mu M. These effects were markedly attenuated by pretreatment with 2 mM LiCl for 7 days, whereas 1-day pretreatment was ineffective. Measurements of live and dead cells by double-staining with fluorescein diacetate and propidium iodide, respectively revealed that protracted lithium pretreatment attenuated PC 12 cell death induced by beta-amyloid-(1-42) and cerebellar granule cell death induced by beta-amyloid-(25-35). Preceding PC 12 cell death, beta-amyloid peptide elicited a slight decrease in protein levels of Bcl-2. Conversely, 7-day pretreatment with lithium resulted in an approximate doubling of Bcl-2 protein levels in cells treated with or without beta-amyloid peptide-(1-42). Lithium-induced Bcl-2 upregulation was temporally associated with the cytoprotective effects of this drug. Thus, lithium protection against beta-amyloid peptide neurotoxicity might involve Bcl-2 overexpression, and Lithium treatment for Alzheimer's disease should bit reexamined. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 NIMH, Biol Psychiat Branch, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Biol Psychiat Branch, Mol Neurobiol Sect, NIH, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 26 TC 89 Z9 92 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 31 PY 2000 VL 392 IS 3 BP 117 EP 123 DI 10.1016/S0014-2999(00)00127-8 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 302EJ UT WOS:000086352400001 PM 10762662 ER PT J AU Minton, AP AF Minton, AP TI Quantitative characterization of reversible macromolecular associations via sedimentation equilibrium: an introduction SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Review DE sedimentation equilibrium ID SMALL CENTRIFUGE TUBES; ANALYTICAL ULTRACENTRIFUGATION AB The measurement and analysis of sedimentation equilibrium provides one of the most powerful and widely applicable methods for the characterization of reversible associations of macromolecules in solution. Recent developments in instrumentation, experimental design, and data analysis have substantially broadened the range of systems to which this technique may be applied, simplified its application, and reduced the cost of acquiring analytical capability. C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 18 TC 11 Z9 12 U1 1 U2 4 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD MAR 31 PY 2000 VL 32 IS 1 BP 1 EP 5 PG 5 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 300BT UT WOS:000086233500001 PM 10762054 ER PT J AU Wolff, EC Wolff, J Park, MH AF Wolff, EC Wolff, J Park, MH TI Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; ENZYME-SUBSTRATE INTERMEDIATE; EUKARYOTIC CELL-PROLIFERATION; LIVER ALCOHOL-DEHYDROGENASE; HYPUSINE DEPLETION; SPERMIDINE; FLUORESCENCE; INHIBITION; POLYAMINES; FEATURES AB Deoxyhypusine is a modified lysine residue. It is formed posttranslationally in the precursor of eukaryotic initiation factor 5A (eIF5A) by deoxyhypusine synthase, employing spermidine as a butylamine donor. In the initial step of this reaction, deoxyhypusine synthase catalyzes the production of NADH through dehydrogenation of spermidine. Fluorescence measurements of this reaction revealed a -22-nm blue shift in the emission peak of NADH and a similar to 15-fold increase in peak intensity, characteristics of tightly bound NADH that were not seen by simply mixing NADH and enzyme. The fluorescent properties of the bound NADH can be ascribed to a hydrophobic environment and a rigidly held, open conformation of NADH, features in accord with the known crystal structure of the enzyme. Considerable fluorescence resonance energy transfer from tryptophan 327 in the active site to the dihydronicotinamide ring of NADH was seen. Upon addition of the eIF5A precursor, utilization of the enzyme-bound NADH for reduction of the eIF5A-imine intermediate to deoxyhypusine was reflected by a rapid decrease in the NADH fluorescence, indicating a transient hydride transfer mechanism as an integral part of the reaction. The number of NADH molecules bound approached four/enzyme tetramer; not all of the bound NADH was available for reduction of the eIF5A-imine intermediate. C1 NIDCR, NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP Wolff, EC (reprint author), NIDCR, NIH, Oral & Pharyngeal Canc Branch, Bldg 30,Rm 211, Bethesda, MD 20892 USA. NR 38 TC 17 Z9 17 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 MAR 31 PY 2000 VL 275 IS 13 BP 9170 EP 9177 DI 10.1074/jbc.275.13.9170 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500016 PM 10734052 ER PT J AU Sakaguchi, K Saito, S Higashimoto, Y Roy, S Anderson, CW Appella, E AF Sakaguchi, K Saito, S Higashimoto, Y Roy, S Anderson, CW Appella, E TI Damage-mediated phosphorylation of human p53 threonine 18 through a cascade mediated by a casein 1-like kinase - Effect on Mdm2 binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE; TRANSACTIVATION DOMAIN; CELL-GROWTH; PROTEIN-DNA; I ISOFORM; SIGNALS; ACID; SITE AB The p53 tumor suppressor protein is stabilized in response to ionizing radiation and accumulates in the nucleus. Stabilization is thought to involve disruption of the interaction between the p53 protein and Mdm2, which targets p53 for degradation. Here we show that the direct association between a p53 N-terminal peptide and Mdm2 is disrupted by phosphorylation of the peptide on Thr's but not by phosphorylation at other N-terminal sites, including Ser(15) and Ser(37). Thr(18) was phosphorylated in vitro by casein kinase (CK1); this process required the prior phosphorylation of Ser's Thr's was phosphorylated in vivo in response to DNA damage, and such phosphorylation required Ser's. Our results suggest that stabilization of p53 after ionizing radiation may result, in part, from an inhibition of Mdm(2) binding through a phosphorylation-phosphorylation cascade involving DNA damage-activated phosphorylation of p53 Ser(15) followed by phosphorylation of Thr(18). C1 NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Bose Inst, Dept Biophys, Calcutta 700054, W Bengal, India. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Appella, E (reprint author), NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bldg 37,Rm 1B03,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM52825] NR 43 TC 196 Z9 196 U1 0 U2 8 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 MAR 31 PY 2000 VL 275 IS 13 BP 9278 EP 9283 DI 10.1074/jbc.275.13.9278 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500031 PM 10734067 ER PT J AU Rogakou, EP Nieves-Neira, W Boon, C Pommier, Y Bonner, WM AF Rogakou, EP Nieves-Neira, W Boon, C Pommier, Y Bonner, WM TI Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CASPASE-ACTIVATED DNASE; INTERLEUKIN-1-BETA-CONVERTING ENZYME; CHROMATIN CONDENSATION; MORPHOLOGICAL-CHANGES; HL-60 CELLS; PROTEIN; CLEAVAGE; FAMILY; FAS; ENDONUCLEASE AB Histone H2AX is a ubiquitous member of the H2A histone family that differs from the other H2A histones by the presence of an evolutionarily conserved C-terminal motif, -KKATQASQEY. The serine residue in this motif becomes rapidly phosphorylated in cells and animals when DNA double-stranded breaks are introduced into their chromatin by various physical and chemical means. In the present communication we show that this phosphorylated form of H2AX, referred to as gamma-H2AX, appears during apoptosis concurrently with the initial appearance of high molecular weight DNA fragments. gamma-H2AX forms before the appearance of internucleosomal DNA fragments and the externalization of phosphatidylserine to the outer membrane leaflet. gamma-H2AX formation is inhibited by N-benzyloxycarbonyl-Val-AlaAsp-fluoromethyl ketone and the inhibitor of caspase-activated DNase, and it is induced when DNase I and restriction enzymes are introduced into cells, suggesting that any apoptotic endonuclease is sufficient to induce gamma-H2AX formation. These results indicate that gamma-H2AX formation is an early chromatin modification following initiation of DNA fragmentation during apoptosis. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Rogakou, EP (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Rm 5D21, Bethesda, MD 20892 USA. NR 62 TC 415 Z9 425 U1 1 U2 13 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 MAR 31 PY 2000 VL 275 IS 13 BP 9390 EP 9395 DI 10.1074/jbc.275.13.9390 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500047 PM 10734083 ER PT J AU Fei, YJ Romero, MF Krause, M Liu, JC Huang, W Ganapathy, V Leibach, FH AF Fei, YJ Romero, MF Krause, M Liu, JC Huang, W Ganapathy, V Leibach, FH TI A novel H+-coupled oligopeptide transporter (OPT3) from Caenorhabditis elegans with a predominant function as a H+ channel and an exclusive expression in neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-GLUCOSE COTRANSPORTER; BETA-LACTAM ANTIBIOTICS; PEPTIDE TRANSPORTER; CLONING; INTESTINE; CULTURES; KIDNEY AB We have cloned and functionally characterized a novel, neuron-specific, H+-coupled oligopeptide transporter (OPT3) from Caenorhabditis elegans that functions predominantly as a H+ channel. The opt3 gene is similar to 4.4 kilobases long and consists of 13 exons. The cDNA codes for a protein of 701 amino acids with 11 putative transmembrane domains. When expressed in mammalian cells and in Xenopus laevis oocytes, OPT3 cDNA induces H+-coupled transport of the dipeptide glycylsarcosine, Electrophysiological studies of the transport function of OPT3 in Xenopus oocytes show that this transporter, although capable of mediating H+-coupled peptide transport, functions predominantly as a H+ channel. The H+ channel activity of OPT3 is similar to 3-4-fold greater than the H+/peptide cotransport activity as determined by measurements of H+ gradient-induced inward currents in the absence and presence of the dipeptide using the two-microelectrode voltage clamp technique, A downhill influx of H+ was accompanied by a large intracellular acidification as evidenced from the changes in intracellular pH using an ion-selective microelectrode. The H+ channel activity exhibits a K-0.5(H) of 1.0 mu M at a membrane potential of -50 mV. At the level of primary structure, OPT3 has moderate homology with OPT1 and OPT2, two other Hf-coupled oligopeptide transporters previously cloned from C. elegans, Expression studies using the opt3::gfp fusion constructs in transgenic C. elegans demonstrate that opt3 gene is exclusively expressed in neurons. OPT3 may play an important physiological role as a pH balancer in the maintenance of H+ homeostasis in C. elegans. C1 Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. Case Western Reserve Univ, Dept Physiol & Biophys, Sch Med, Cleveland, OH 44106 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fei, YJ (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, 1120 15th St,CB2507, Augusta, GA 30912 USA. OI Krause, Michael/0000-0001-6127-3940 FU NIDDK NIH HHS [DK 28389] NR 37 TC 22 Z9 27 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 31 PY 2000 VL 275 IS 13 BP 9563 EP 9571 DI 10.1074/jbc.275.13.9563 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500070 PM 10734106 ER PT J AU Kam, JL Miura, K Jackson, TR Gruschus, J Roller, P Stauffer, S Clark, J Aneja, R Randazzo, PA AF Kam, JL Miura, K Jackson, TR Gruschus, J Roller, P Stauffer, S Clark, J Aneja, R Randazzo, PA TI Phosphoinositide-dependent activation of the ADP-ribosylation factor GTPase-activating protein ASAP1 - Evidence for the pleckstrin homology domain functioning as an allosteric site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; BRUTONS TYROSINE KINASE; PHOSPHOLIPASE-D; PH DOMAIN; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE; CHOLERA-TOXIN; FACTOR ARNO; ARF; BINDING AB The ADP-ribosylation factor (Arf) family of GTP-binding proteins are regulators of membrane traffic and the actin cytoskeleton. Both negative and positive regulators of Arf, the centaurin beta family of Arf GTPase-activating proteins (GAPs) and Arf guanine nucleotide exchange factors, contain pleckstrin homology (PH) domains and are activated by phosphoinositides, To understand how the activities are coordinated, we have examined the role of phosphoinositide binding for Arf GAP function using ASAP1/centaurin beta 4 as a model, In contrast to Arf exchange factors, phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P(2)) specifically activated Arf GAP, D3 phosphorylated phosphoinositides were less effective. Activation involved PtdIns-4,5-P(2) binding to the PH domain; however, in contrast to the Arf exchange factors and contrary to predictions based on the current paradigm for PH domains as independently functioning recruitment signals, we found the following: (i) the PH domain was dispensable for targeting to PDGF-induced ruffles; (ii) activation and recruitment could be uncoupled; (iii) the PH domain was necessary for activity even in the absence of phospholipids; and (iv) the Arf GAP domain influenced localization and lipid binding of the PH domain. Furthermore, PtdIns-4,5-P(2) binding to the PH domain caused a conformational change in the Arf GAP domain detected by limited proteolysis. Thus, these data demonstrate that PH domains can function as allosteric sites. In addition, differences from the published properties of the Arf exchange factors suggest a model in which feedforward and feedback loops involving lipid metabolites coordinate GTP binding and hydrolysis by Arf. C1 NCI, Div Basic Sci, Cellular Oncol Lab, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. UCL Royal Free & Univ Coll Med Sch, London NW3 2PF, England. Nutrimed Biotech, Langmuir Lab, Ithaca, NY 14850 USA. RP Randazzo, PA (reprint author), NCI, Div Basic Sci, Cellular Oncol Lab, 37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov FU NIGMS NIH HHS [GM 49594, GM 51138] NR 49 TC 88 Z9 91 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 31 PY 2000 VL 275 IS 13 BP 9653 EP 9663 DI 10.1074/jbc.275.13.9653 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500081 PM 10734117 ER PT J AU Frank, EG Cheng, NQ Do, CC Cerritelli, ME Bruck, I Goodman, MF Egelman, EH Woodgate, R Steven, AC AF Frank, EG Cheng, NQ Do, CC Cerritelli, ME Bruck, I Goodman, MF Egelman, EH Woodgate, R Steven, AC TI Visualization of two binding sites for the Escherichia coli UmuD ' C-2 complex (DNA pol V) on RecA-ssDNA filaments SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA repair; electron microscopy; homologous recombination; SOS mutagenesis ID SINGLE-STRANDED-DNA; SOS MUTAGENESIS; HOMOLOGOUS RECOMBINATION; LEXA REPRESSOR; ELECTRON-MICROGRAPHS; BIOCHEMICAL BASIS; PROTEIN COMPLEX; CLEAVAGE; PURIFICATION; INHIBITION AB The heterotrimeric UmuD'C-2 complex of Escherichia coli has recently been shown to possess intrinsic DNA polymerase activity (DNA pol V) that facilitates error-prone translesion DNA synthesis (SOS mutagenesis). When overexpressed in vivo, UmuD'C-2 also inhibits homologous recombination. In both activities, UmuD'C-2 interacts with RecA nucleoprotein filaments. To examine the biochemical and structural basis of these reactions, we have analyzed the ability of the UmuD'C-2 complex to bind to RecA-ssDNA filaments in vitro. As estimated by a gel retardation assay, binding saturates at a stoichiometry of approximately one complex per two RecA monomers. Visualized by cryo-electron microscopy under these conditions, UmuD'C-2 is seen to bind uniformly along the filaments, such that the complexes are completely submerged in the deep helical groove. This mode of binding would impede access to DNA in a RecA filament, thus explaining the ability of UmuD'C-2 to inhibit homologous recombination. At sub-saturating binding, the distribution of UmuD'C-2 complexes along RecA-ssDNA filaments was characterized by immunogold labelling with anti-UmuC antibodies. These data revealed preferential binding at filament ends (most likely, at one end). End-specific binding is consistent with genetic models whereby such binding positions the UmuD'C-2 complex (pol V) appropriately for its role in SOS mutagenesis. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Univ So Calif, Hedco Mol Biol Labs, Dept Biol Sci, Los Angeles, CA 90089 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. RI Egelman, Edward/A-2488-2009 FU NIGMS NIH HHS [GM35269] NR 62 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 31 PY 2000 VL 297 IS 3 BP 585 EP 597 DI 10.1006/jmbi.2000.3591 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325XM UT WOS:000087702200005 PM 10731413 ER PT J AU Turunen, M Peters, JM Gonzalez, FJ Schedin, S Dallner, G AF Turunen, M Peters, JM Gonzalez, FJ Schedin, S Dallner, G TI Influence of peroxisome proliferator-activated receptor alpha on ubiquinone biosynthesis SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ubiquinone; mevalonate pathway; PPAR alpha; peroxisomal proliferators; aminotriazole ID RAT-LIVER MICROSOMES; PPAR-ALPHA; TISSUE DISTRIBUTION; DOLICHYL-PHOSPHATE; SYNTHASE GENE; MOUSE; MECHANISM; PRENYLTRANSFERASE; METHYLTRANSFERASE; EXPRESSION AB The control of ubiquinone biosynthesis by peroxisome proliferators was investigated using peroxisome proliferator activated receptor alpha (PPAR alpha)-null mice. Administration of 2-(diethylhexyl)phthalate to control mice resulted in elevated ubiquinone levels in the liver, while dolichol, dolichyl-P and cholesterol concentrations remained unchanged. In PPAR alpha-null mice, the level of these Lipids were similar to control levels and administration of the peroxisome proliferator did not increase the levels of ubiquinone. The increase in ubiquinone levels was the result of increased synthesis. Induction was most pronounced in Liver, kidney and heart, which have relatively high, levels of PPAR alpha. When the tissue concentration of hydrogen peroxide was elevated by inhibition of catalase activity with aminotriazole, the amount of ubiquinone was not increased, suggesting that the induction of ubiquinone synthesis occured through a direct mechanism. The activities of branch-point enzymes FPP-synthase, squalene synthase, cis-prenyltransferase, trans-prenyltransferase and NPHB-transferase were substantially increased in control but not in PPAR alpha-null mice after treatment with peroxisome proliferators. These data suggest that the induction of ubiquinone biosynthesis after administration of peroxisome proliferators is dependent on the PPAR alpha through regulation of some of the mevalonate pathway enzymes. (C) 2000 Academic Press. C1 Stockholm Univ, Dept Biochem, S-10691 Stockholm, Sweden. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Turunen, M (reprint author), Stockholm Univ, Dept Biochem, S-10691 Stockholm, Sweden. RI Peters, Jeffrey/D-8847-2011 NR 41 TC 29 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 31 PY 2000 VL 297 IS 3 BP 607 EP 614 DI 10.1006/jmbi.2000.3596 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325XM UT WOS:000087702200007 PM 10731415 ER PT J AU Takahashi, H Kim, JI Min, HJ Sato, K Swartz, KJ Shimada, I AF Takahashi, H Kim, JI Min, HJ Sato, K Swartz, KJ Shimada, I TI Solution structure of hanatoxin1, a gating modifier of voltage-dependent K+ channels: Common surface features of gating modifier toxins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE cystine knot motif; gating modifier; hanatoxin; nuclear magnetic resonance; potassium channel ID NUCLEAR MAGNETIC-RESONANCE; OMEGA-GRAMMOTOXIN-SIA; KAPPA-CONOTOXIN PVIIA; FUNNEL-WEB SPIDER; POTASSIUM CHANNEL; 3-DIMENSIONAL STRUCTURE; SODIUM-CHANNEL; SEA-ANEMONE; PROTEIN STRUCTURES; DISTANCE GEOMETRY AB The three-dimensional structure of hanatoxin1 (HaTx1) was determined by using NMR spectroscopy. HaTx1 is a 35 amino acid residue peptide toxin that inhibits the drk1 voltage-gated K+ channel not by blocking the pore, but by altering the energetics of gating. both the amino acid sequence of HaTx1 and its unique mechanism of action distinguish this toxin from the previously described K+ channel inhibitors. Unlike most other K+ channel-blocking toxins, HaTx1 adopts an "inhibitor cystine knot" motif and is composed of two beta-strands, strand I for residues 19-21 and strand II for residues 28-30, connected by four chain reversals. A comparison of the surface features of HaTx1 with those of other gating modifier toxins of voltage-gated Ca2+ and Na+ channels suggests that the combination of a hydrophobic patch and surrounding charged residues is principally responsible for the binding of gating modifier toxins to voltage-gated ion channels. (C) 2000 Academic Press. C1 Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 506712, South Korea. Mitsubishi Kasei Inst Life Sci, Machida, Tokyo 1940031, Japan. NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. RP Shimada, I (reprint author), Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. FU Intramural NIH HHS [ZIA NS002945-13] NR 52 TC 104 Z9 109 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 31 PY 2000 VL 297 IS 3 BP 771 EP 780 DI 10.1006/jmbi.2000.3609 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325XM UT WOS:000087702200019 PM 10731427 ER PT J AU Hagen, SJ Eaton, WA AF Hagen, SJ Eaton, WA TI Two-state expansion and collapse of a polypeptide SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE cytochrome c; molten globule; collapse; temperature-jump; denatured states ID PROTEIN-FOLDING KINETICS; UNFOLDED CYTOCHROME-C; MOLTEN GLOBULE; FLEXIBLE COIL; HOMOPOLYMER; DIFFUSION; TRANSITION; DYNAMICS; THERMODYNAMICS; APOMYOGLOBIN AB The initial phase of folding for many proteins is presumed to be the collapse of the polypeptide chain from expanded to compact, but still denatured, conformations. Theory and simulations suggest that this collapse may be a two-state transition, characterized by barrier-crossing kinetics, while the collapse of homopolymers and random heteropolymers is continuous and multi-phasic. A new rapid-mixing flow technique has been used to resolve the late stages of polypeptide collapse,at time scales greater than or equal to 45 mu s. We have used a laser temperature-jump with fluorescence spectroscopy to resolve the complete time-course of the collapse of denatured cytochrome c with nanosecond time resolution. We find the process to be exponential in time and thermally activated, with an apparent activation energy similar to 9 k(B)T (after correction for solvent viscosity). These results indicate that polypeptide collapse is kinetically a two-state transition. Because of the observed free energy barrier, the time scale of polypeptide collapse is dramatically slower than is predicted by Langevin models for homopolymer collapse. (C) 2000 Academic Press. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. NR 43 TC 46 Z9 48 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 31 PY 2000 VL 297 IS 3 BP 781 EP 789 DI 10.1006/jmbi.2000.3508 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 325XM UT WOS:000087702200020 PM 10731428 ER PT J AU Marshall, E Pennisi, E Roberts, L Collins, F AF Marshall, E Pennisi, E Roberts, L Collins, F TI In the crossfire: Collins on genomes, patents, and 'rivalry' SO SCIENCE LA English DT News Item C1 Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 31 PY 2000 VL 287 IS 5462 BP 2396 EP 2398 DI 10.1126/science.287.5462.2396 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299MK UT WOS:000086202200013 PM 10766612 ER PT J AU Yasutomo, K Doyle, C Miele, L Germain, RN AF Yasutomo, K Doyle, C Miele, L Germain, RN TI The duration of antigen receptor signalling determines CD4(+) versus CD8(+) T-cell lineage fate SO NATURE LA English DT Article ID CLASS-II INTERACTION; TRANSGENIC MICE; TYROSINE KINASE; THYMOCYTES; COMMITMENT; DIFFERENTIATION; SPECIFICITY; EXPRESSION; ACTIVATION; MECHANISM AB Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4(+) (helper) or CD8(+) (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins'. These precursors have unique, clonally distributed T-cell receptors with unpredictable specificity for the self-MHC molecules involved in this differentiation process', However, the mature T cells that emerge express only the CD4 (MHC class II-binding) or CD8 (MHC class I-binding) co-receptor that complements the MHC class-specificity of the T-cell receptor. How this matching of co-receptor-defined lineage and T-cell-receptor specificity is achieved remains unknown(1,3,4), as does whether signalling by the T-cell receptors, co-receptors and/ or general cell-fate regulators such as Notch-1 (refs 5, 6) contributes to initial lineage choice, to subsequent differentiation processes or to both. Here we show that the CD4 versus CD8 lineage fate of immature thymocytes is controlled by the co-receptor-influenced duration of initial T-cell receptor-dependent signalling. Notch-1 does not appear to be essential for this fate determination, but it is selectively required for CD8(+) T-cell maturation after commitment directed by T-cell receptors, This indicates that the signals constraining CD4 versus CD8 lineage decisions are distinct from those that support subsequent differentiation events such as silencing of co-receptor loci. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Canc Immunol Program, Maywood, IL 60153 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 30 TC 187 Z9 195 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 30 PY 2000 VL 404 IS 6777 BP 506 EP 510 DI 10.1038/35006664 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 300MX UT WOS:000086257700051 PM 10761920 ER PT J AU Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, EE Ried, T Nussenzweig, A AF Difilippantonio, MJ Zhu, J Chen, HT Meffre, E Nussenzweig, MC Max, EE Ried, T Nussenzweig, A TI DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation SO NATURE LA English DT Article ID V(D)J RECOMBINATION; MICE; P53; TRANSPOSITION; GROWTH; RAG1; GENE AB Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers(1). Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80(-/-) mice have only a slightly earlier onset of cancer(2,3). Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80(-/-) p53(-/-) mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Genet, NIH, Bethesda, MD 20892 USA. Rockefeller Inst, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Inst, Howard Hughes Med Inst, New York, NY 10021 USA. US FDA, Lab Cell Regulat, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 30 TC 383 Z9 391 U1 2 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 30 PY 2000 VL 404 IS 6777 BP 510 EP 514 DI 10.1038/35006670 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 300MX UT WOS:000086257700052 PM 10761921 ER PT J AU Quinn, TC Wawer, MJ Sewankambo, N Serwadda, D Li, CJ Wabwire-Mangen, F Meehan, MO Lutalo, T Gray, RH AF Quinn, TC Wawer, MJ Sewankambo, N Serwadda, D Li, CJ Wabwire-Mangen, F Meehan, MO Lutalo, T Gray, RH CA Rakai Project Study Grp TI Viral load and heterosexual transmission of human immunodeficiency virus type 1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 RNA LEVELS; TRANSFUSION RECIPIENTS; SEXUAL TRANSMISSION; SEMEN; MEN; REDUCTION; BLOOD; RISK AB Background and Methods: We examined the influence of viral load in relation to other risk factors for the heterosexual transmission of human immunodeficiency virus type 1 (HIV-1). In a community-based study of 15,127 persons in a rural district of Uganda, we identified 415 couples in which one partner was HIV-1-positive and one was initially HIV-1-negative and followed them prospectively for up to 30 months. The incidence of HIV-1 infection per 100 person-years among the initially seronegative partners was examined in relation to behavioral and biologic variables. Results: The male partner was HIV-1-positive in 228 couples, and the female partner was HIV-1-positive in 187 couples. Ninety of the 415 initially HIV-1-negative partners seroconverted (incidence, 11.8 per 100 person-years). The rate of male-to-female transmission was not significantly different from the rate of female-to-male transmission (12.0 per 100 person-years vs. 11.6 per 100 person-years). The incidence of seroconversion was highest among the partners who were 15 to 19 years of age (15.3 per 100 person-years). The incidence was 16.7 per 100 person-years among 137 uncircumcised male partners, whereas there were no seroconversions among the 50 circumcised male partners (P<0.001). The mean serum HIV-1 RNA level was significantly higher among HIV-1-positive subjects whose partners seroconverted than among those whose partners did not seroconvert (90,254 copies per milliliter vs. 38,029 copies per milliliter, P=0.01). There were no instances of transmission among the 51 subjects with serum HIV-1 RNA levels of less than 1500 copies per milliliter; there was a significant dose-response relation of increased transmission with increasing viral load. In multivariate analyses of log-transformed HIV-1 RNA levels, each log increment in the viral load was associated with a rate ratio of 2.45 for seroconversion (95 percent confidence interval, 1.85 to 3.26). Conclusions: The viral load is the chief predictor of the risk of heterosexual transmission of HIV-1, and transmission is rare among persons with levels of less than 1500 copies of HIV-1 RNA per milliliter. (N Engl J Med 2000;342:921-9.) (C) 2000, Massachusetts Medical Society. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Makerere Univ, Fac Med, Kampala, Uganda. RP Quinn, TC (reprint author), Johns Hopkins Univ, Div Infect Dis, 720 Rutland Ave,Ross 1159, Baltimore, MD 21205 USA. RI Quinn, Thomas/A-2494-2010; OI Sewankambo, Nelson/0000-0001-9362-053X FU NIAID NIH HHS [R01 AI34826S, R01 AI34826B]; NICHD NIH HHS [5P30HD06826] NR 50 TC 1819 Z9 1847 U1 10 U2 68 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 30 PY 2000 VL 342 IS 13 BP 921 EP 929 DI 10.1056/NEJM200003303421303 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 299DC UT WOS:000086179700003 PM 10738050 ER PT J AU Shennan, MG Badin, AC Walsh, S Summers, A From, L McKenzie, M Goldstein, AM Tucker, MA Hogg, D Lassam, N AF Shennan, MG Badin, AC Walsh, S Summers, A From, L McKenzie, M Goldstein, AM Tucker, MA Hogg, D Lassam, N TI Lack of germline CDK6 mutations in familial melanoma SO ONCOGENE LA English DT Article DE familial melanoma; CDK6 ID DEPENDENT KINASE CDK6; TUMOR-SUPPRESSOR; CYCLIN-D; P16; RETINOBLASTOMA; BINDING; P16(INK4A); PREVALENCE; INHIBITION; PROTEIN AB Germline mutations in genes encoding several components of the retinoblastoma pathway have been linked with inherited predisposition to melanoma, Most commonly, such mutations involve CDKN2A, a cyclin-dependant kinase inhibitor of two kinases, CDK4 and CDK6, which phosphorylate the retinoblastoma protein (pRB) and thereby promote passage through the G(1)/S cell-cycle restriction point. Less frequently, germline mutations in the CDK4 gene have also been linked with an increased risk of melanoma, Despite the sequence and functional homology between CDK4 and CDK6, the role of germline mutations in CDK6 in melanoma predisposition is unknown. We detected no CDK6 mutations within the p16 (CDKN2A) binding domain in index cases from 60 melanoma-prone kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK4 coding region. We conclude that germline mutations in CDK6 do not make a significant contribution to melanoma predisposition. C1 Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada. New York Gen Hosp, New York, NY USA. Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Dermatol, Toronto, ON, Canada. Toronto Sunnybrook Reg Canc Ctr, Div Med Oncol, Toronto, ON, Canada. NCI, Bethesda, MD 20892 USA. RP Lassam, N (reprint author), Univ Toronto, Dept Med, Room 7360,Med Sci Bldg, Toronto, ON M5S 1A8, Canada. RI Tucker, Margaret/B-4297-2015 NR 24 TC 16 Z9 17 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 30 PY 2000 VL 19 IS 14 BP 1849 EP 1852 DI 10.1038/sj.onc.1203507 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 301DG UT WOS:000086292500013 PM 10777219 ER PT J AU Green, SW Malkovska, I O'Suilivan, MG Brown, KE AF Green, SW Malkovska, I O'Suilivan, MG Brown, KE TI Rhesus and pig-tailed macaque parvoviruses: Identification of two new members of the erythrovirus genus in monkeys SO VIROLOGY LA English DT Article ID SIMIAN PARVOVIRUS; CYNOMOLGUS MONKEYS; SEVERE ANEMIA; BONE-MARROW; B19; INFECTION; CLONING; GENOME AB We have previously reported the identification of a novel simian parvovirus in cynomolgus monkeys, which causes severe anemia in immunosuppressed cynomolgus monkeys and is currently being studied as an animal model for human B19 infection. We now report two similar outbreaks of anemia in rhesus and pig-tailed macaques associated with two distinct but similar simian parvoviruses (pig-tailed macaque and rhesus parvovirus). Both viruses have been cloned and over 5000 nucleotides sequenced from each virus. The viruses show marked similarities to other members of the Erythrovirus genus in the Parvoviridae family. (C) 2000 Academic Press. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA. RP Brown, KE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2000 VL 269 IS 1 BP 105 EP 112 DI 10.1006/viro.2000.0215 PG 8 WC Virology SC Virology GA 299XK UT WOS:000086223600012 PM 10725203 ER PT J AU Qiu, JM Handa, A Kirby, M Brown, KE AF Qiu, JM Handa, A Kirby, M Brown, KE TI The interaction of heparin sulfate and adeno-associated virus 2 SO VIROLOGY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; HERPES-SIMPLEX VIRUS; CELL-SURFACE; FACTOR RECEPTOR; PROTEOGLYCAN BIOSYNTHESIS; TRANSGENE EXPRESSION; POLIOVIRUS RECEPTOR; INITIAL INTERACTION; TYROSINE KINASE; HIV-1 INFECTION AB Recently heparan sulfate was proposed as the host cell receptor for the dependovirus, adeno-associated virus type 2 (AAV2). We show that although heparan sulfate on the cell surface may contribute to the binding of AAV2 to permissive cells, the amount of heparan sulfate on the cell surface as determined by flow cytometry using tour different monoclonal antibodies does not correlate with AAV2 binding to cells or recombinant AAV2 transduction efficiency. Experiments with either mutant CHO cells or cells treated with chlorate to remove sulfate groups showed that sulfation was not absolutely required for infection or binding: in the absence of cell surface sulfation, recombinant AAV2 was still able to be transduced in previously permissive cells. Heparin is commonly used as a substitute in studies of the interaction between heparan sulfate and ligand, and we demonstrate that the binding affinity of AAV2/heparin is low, with a K-d value of similar to 2.0 nM. A study of the direct interaction between AAV2 and artificial glycosaminoglycans showed that a high degree of sulfation on heparin was critical for the ability to bind AAV2 and compete rAAV2 transduction and that both O- and N-sulfate groups are required. Overall, our data suggest that, as has been shown for other viruses, the presence of a high-affinity AAV2 receptor mediates AAV2 infection in addition to the low-affinity heparan sulfate binding. (C) 2000 Academic Press. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Qiu, JM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 59 TC 59 Z9 59 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2000 VL 269 IS 1 BP 137 EP 147 DI 10.1006/viro.2000.0205 PG 11 WC Virology SC Virology GA 299XK UT WOS:000086223600015 PM 10725206 ER PT J AU Campbell, MS Pletnev, AG AF Campbell, MS Pletnev, AG TI Infectious cDNA clones of Langat tick-borne flavivirus that differ from their parent in peripheral neurovirulence SO VIROLOGY LA English DT Article ID DENGUE TYPE-4 VIRUSES; ENCEPHALITIS-VIRUS; SEQUENCE-ANALYSIS; VIRULENCE; PROTEINS; GENES; CONSTRUCTION; ATTENUATION; MUTANTS; GENOME AB Tick-borne flavivirus strain Langat TP21 (LGT TP21) recovered from ticks, is naturally attenuated for humans but retains demonstrable neurovirulence and peripheral virulence ("neuroinvasiveness'') for mice. Previously a mutant, strain E5, less virulent for mice was derived from LGT TP21. Multiple attempts ta prepare a full-length infectious TP21 cDNA from cDNA fragments cloned in E. coli were uniformly unsuccessful. A more informative sequence than that obtained from these cloned cDNA fragments and similar E5 cDNA fragments was derived from RT-PCR fragments that had not been cloned in E. coli. Comparison of the RT-PCR consensus sequence of TP21 and E5 identified only seven amino acid differences that might be responsible for the observed difference in virulence of these strains for mice. Eleven independent infectious cDNA clones of TP21 were recovered using two overlapping long RT-PCR fragments, importantly low-titered virus used to prepare cDNA as template for PCR was harvested early in the growth cycle to minimize the frequency of deletion mutants that accumulated late in infection. The four analyzed rescued clones exhibited clone-specific minimal divergence from the consensus sequence but this limited variation was associated with diminished peripheral virulence for immunocompetent mice. Manipulation of these clones should facilitate elucidation of LGT virulence. (C) 2000 Academic Press. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0740,Bldg 7,Room 236, Bethesda, MD 20892 USA. NR 27 TC 48 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2000 VL 269 IS 1 BP 225 EP 237 DI 10.1006/viro.2000.0220 PG 13 WC Virology SC Virology GA 299XK UT WOS:000086223600023 PM 10725214 ER PT J AU Barchi, JJ Huang, XL Appella, DH Christianson, LA Durell, SR Gellman, SH AF Barchi, JJ Huang, XL Appella, DH Christianson, LA Durell, SR Gellman, SH TI Solution conformations of helix-forming beta-amino acid homooligomers SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SECONDARY STRUCTURE; PEPTIDE FOLDAMERS; GAMMA-HEXAPEPTIDE; NUCLEIC-ACIDS; SIDE-CHAINS; FORCE-FIELD; OLIGOMERS; PROTEINS; NMR; SIMULATION AB The conformational properties of beta-peptides comprised of enantiomerically pure trans-2-aminocyclohexanecarboxylic acid (ACHC) or trans-2-aminocyclopentanecarboxylic acid (ACPC) units were studied by NMR spectroscopy in organic solvents. In pyridine-d(5) solution, ACPC hexamer 1 and ACPC octamer 2 displayed well-defined helical structures characterized by a series of 12-membered hydrogen-bonded rings ("12-helix"). The solution structures calculated from the NMR-derived constraints were very similar to the conformations found previously for 1 and 2 in the solid state. ACHC tetramer 3 displayed a different sort of helical conformation, characterized by a series of 14-membered hydrogen-bonded rings ("14-helix"), in methanol-d(3) solution. This solution conformation is similar to that previously found in the crystal structure of 3. C1 NCI, Div Basic Sci, Med Chem Lab, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. RP Barchi, JJ (reprint author), NCI, Div Basic Sci, Med Chem Lab, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 58 TC 102 Z9 102 U1 0 U2 24 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 MAR 29 PY 2000 VL 122 IS 12 BP 2711 EP 2718 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 299NL UT WOS:000086204700004 ER PT J AU Veeranna, GJ Shetty, KT Takahashi, M Grant, P Pant, HC AF Veeranna, GJ Shetty, KT Takahashi, M Grant, P Pant, HC TI Cdk5 and MAPK are associated with complexes of cytoskeletal proteins in rat brain SO MOLECULAR BRAIN RESEARCH LA English DT Article DE cytoskeletal protein; phosphorylation; proline-directed kinase; multimeric complex ID CYCLIN-DEPENDENT KINASE-5; CDC2-LIKE KINASE; TAU-PROTEIN; NEUROFILAMENT PROTEINS; SQUID AXOPLASM; SPINAL-CORD; TAIL DOMAIN; PHOSPHORYLATION; SUBUNIT; MICROTUBULE AB Neurofilament proteins, the major cytoskeletal components of large myelinated axons, are highly phosphorylated by second messenger-dependent and -independent kinases. These kinases, together with tubulins and other cytoskeletal proteins, have been shown to bind to neurofilament preparations. Cdk5 and Erk2, proline-directed kinases in neuronal tissues, phosphorylate the Lys-Ser-Pro (KSP) repeats in tail domains of NF-H, NF-M, and other axonal proteins such as tau and synapsin. In neurofilament and microtubule preparations from rat brain, we demonstrated by Western blot analysis that cdk5, a neuronal cyclin dependent kinase and Erk1/2 were associated with complexes of NF proteins, tubulins and tau. Using P13(suc1) affinity chromatography, a procedure known to bind cdc2-like kinases in proliferating cells with high affinity, we obtained a P13 complex from a rat brain extract exhibiting the same profiles of cdk5 and Erk2 bound to cytoskeletal proteins. The phosphorylation activities of these preparations and the effect of the cdk5 inhibitor, butyrolactone, were consistent with the presence of active kinases. Finally, during a column fractionation and purification of Erk kinases from rat brain extracts, fractions enriched in Erk kinase activity also exhibited co-elution of phosphorylated NF-H, tubulin, tau and cdk5. We suggest that in mammalian brain, different kinases, their regulators and phosphatases form multimeric complexes with cytoskeletal proteins and regulate multisite phosphorylation from synthesis in the cell body to transport and assembly in the axon. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NIMHANS, Bangalore, Karnataka, India. Yokohama Univ, Sch Med, Dept Psychiat, Yokohama, Kanagawa, Japan. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D20, Bethesda, MD 20892 USA. NR 43 TC 21 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAR 29 PY 2000 VL 76 IS 2 BP 229 EP 236 DI 10.1016/S0169-328X(00)00003-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 306ET UT WOS:000086584900005 ER PT J AU Wodarz, D Page, KM Arnaout, RA Thomsen, AR Lifson, JD Nowak, MA AF Wodarz, D Page, KM Arnaout, RA Thomsen, AR Lifson, JD Nowak, MA TI A new theory of cytotoxic T-lymphocyte memory: implications for HIV treatment SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Synposium on Immunological Memory CY MAR 10-11, 1999 CL LONDON, ENGLAND SP Royal Soc London DE cytotoxic T-lymphocyte memory; HIV; primary infection; secondary infection; therapy; mathematical modelling ID CELL-MEDIATED-IMMUNITY; II-DEFICIENT MICE; MHC CLASS-I; CHORIOMENINGITIS VIRUS; CD40 LIGAND; CTL MEMORY; B-CELLS; INFECTION; ANTIGEN; RESPONSES AB We use simple mathematical models to examine the dynamics of primary and secondary cytotoxic T-lymphocyte (CTL) responses to viral infections. In particular, we are interested in conditions required to resolve the infection and to protect the host upon secondary challenge. While protection against reinfection is only effective in a restricted set of circumstances, we find that resolution of the primary infection requires persistence of CTL precursors (CTLp), as well as a fast rate of activation of the CTLp. Since these are commonly the defining characteristics of CTL memory, we propose that CTL memory may have evolved in order to clear the virus during primary challenge. We show experimental data from lymphocytic choriomeningitis virus infection in mice, supporting our theory on CTL memory. We adapt our models to HIV and find that immune impairment during the primary phase of the infection may result in the failure to establish CTL memory which in turn leads to viral persistence. Based on our models we suggest conceptual treatment regimes which ensure establishment of CTL memory. This would allow the immune response to control HIV in the long term in the absence of continued therapy. C1 Inst Adv Study, Princeton, NJ 08540 USA. Univ Oxford, Inst Math, Ctr Math Biol, Oxford OX1 3LB, England. Univ Oxford, Dept Zool, Wellcome Trust Ctr Epidemiol Infect Dis, Oxford OX1 3PS, England. Univ Copenhagen, Panum Inst, Inst Med Microbiol & Immunol, DK-2200 Copenhagen N, Denmark. NCI, Lab Retroviral Pathogenesis, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Wodarz, D (reprint author), Inst Adv Study, Olden Lane, Princeton, NJ 08540 USA. RI Nowak, Martin/A-6977-2008; OI Thomsen, Allan Randrup/0000-0002-2392-9803 NR 67 TC 60 Z9 61 U1 0 U2 1 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD MAR 29 PY 2000 VL 355 IS 1395 BP 329 EP 343 PG 15 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 303FB UT WOS:000086410400004 PM 10794051 ER PT J AU Gonzalez, I Ohsawa, N Singer, RH Devillers, M Ashizawa, T Balasubramanyam, A Cooper, TA Khajavi, M Lia-Baldini, AS Miller, G Philips, AV Timchenko, LT Waring, J Yamagata, H Barbet, JP Klesert, TR Tapscott, SJ Roses, AD Wagner, M Baiget, M Martorell, L Browne, GB Eymard, B Gourdon, G Junien, C Seznec, H Carey, N Gosling, M Maire, P Gennarelli, M Sato, S Ansved, T Kvist, U Eriksson, M Furling, D Chen, EJ Housman, DE Luciano, B Siciliano, M Spring, N Shimizu, M Eddy, E Morris, GE Krahe, R Furuya, H Adelman, J Pribnow, D Furutama, D Mathieu, J Hilton-Jones, D Kinoshita, M Abbruzzese, C Sinden, RR Wells, RD Pearson, CE Kobayashi, T Johansson, A Salvatori, S Perryman, B Swanson, MS Gould, FK Harris, SE Johnson, K Mitchell, AM Monckton, DG Winchester, CL Antonini, G Day, JW Liquori, C Ranum, LPW Westerlaken, J Wieringa, B Griffith, JD Michalowski, S Moore, H Hamshere, M Korade, Z Thornton, CA Jaeger, H Lehmann, F Moorman, JR Mounsey, JP Mahadevan, MS AF Gonzalez, I Ohsawa, N Singer, RH Devillers, M Ashizawa, T Balasubramanyam, A Cooper, TA Khajavi, M Lia-Baldini, AS Miller, G Philips, AV Timchenko, LT Waring, J Yamagata, H Barbet, JP Klesert, TR Tapscott, SJ Roses, AD Wagner, M Baiget, M Martorell, L Browne, GB Eymard, B Gourdon, G Junien, C Seznec, H Carey, N Gosling, M Maire, P Gennarelli, M Sato, S Ansved, T Kvist, U Eriksson, M Furling, D Chen, EJ Housman, DE Luciano, B Siciliano, M Spring, N Shimizu, M Eddy, E Morris, GE Krahe, R Furuya, H Adelman, J Pribnow, D Furutama, D Mathieu, J Hilton-Jones, D Kinoshita, M Abbruzzese, C Sinden, RR Wells, RD Pearson, CE Kobayashi, T Johansson, A Salvatori, S Perryman, B Swanson, MS Gould, FK Harris, SE Johnson, K Mitchell, AM Monckton, DG Winchester, CL Antonini, G Day, JW Liquori, C Ranum, LPW Westerlaken, J Wieringa, B Griffith, JD Michalowski, S Moore, H Hamshere, M Korade, Z Thornton, CA Jaeger, H Lehmann, F Moorman, JR Mounsey, JP Mahadevan, MS CA IDMC TI New nomenclature and DNA testing guidelines for myotonic dystrophy type 1(DM1) SO NEUROLOGY LA English DT Article ID UNSTABLE CTG REPEAT; MUSCULAR-DYSTROPHY; EXPANSION; FAMILY; PHENOTYPE; MYOPATHY; GENE; SIZE C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Alfred I Dupont Inst, Wilmington, DE 19899 USA. Aino Inst Aging Res, Osaka, Japan. Albert Einstein Coll Med, Bronx, NY 10467 USA. Assoc Francais Myopathies, Paris, France. Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. Ehime Univ, Matsuyama, Ehime 790, Japan. Fac Med Cochin Port Royal, Paris, France. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Hosp Santa Creu & St Pau, Barcelona, Spain. Hop La Pitie Salpetriere, Paris, France. Hop Necker Enfants Malad, Paris, France. Univ London Imperial Coll Sci Technol & Med, Sch Med, London, England. INSERM, U129, Paris, France. IRCCS Fatebenefratelli, Brescia, Italy. Jichi Med Sch, Minami Kawachi, Tochigi, Japan. Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Laval, Med Ctr, Quebec City, PQ, Canada. MIT, Cambridge, MA 02139 USA. MD Anderson Hosp & Tumor Inst, Houston, TX USA. Natl Inst Basic Biol, Okazaki, Aichi 444, Japan. NIH, Res Triangle Pk, NC USA. NE Wales Inst, Wrexham, Wales. Ohio State Univ, Columbus, OH 43210 USA. Omuta Rosai Hosp, Omuta, Japan. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Osaka Med Coll, Osaka, Japan. Univ Quebec, Chicoutimi, PQ, Canada. Radcliffe Infirm, Oxford OX2 6HE, England. Saitama Med Sch, Moroyama, Saitama, Japan. San Camillo Hosp, Rome, Italy. Texas A&M Univ, Houston, TX USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Tokyo Med & Dent Univ, Tokyo, Japan. Univ Umea Hosp, S-90185 Umea, Sweden. Univ Padua, Padua, Italy. Univ Colorado, Denver, CO 80202 USA. Univ Florida, Coll Med, Gainesville, FL USA. Univ Glasgow, Glasgow, Lanark, Scotland. Univ La Sapienza, Rome, Italy. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Nijmegen, Nijmegen, Netherlands. Univ N Carolina, Chapel Hill, NC USA. Univ Nottingham, Nottingham NG7 2RD, England. Univ Pittsburgh, Pittsburgh, PA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Ulm, Ulm, Germany. Univ Virginia, Charlottesville, VA USA. Univ Wisconsin, Madison, WI USA. RP Ashizawa, T (reprint author), Baylor Coll Med, Dept Neurol, 1 Baylor Plaza,SM1801, Houston, TX 77030 USA. RI Gennarelli, Massimo/B-1377-2010; Gourdon, Genevieve/F-2996-2013; Wieringa, Berend/A-5346-2011 OI Wieringa, Berend/0000-0001-9192-8020 NR 19 TC 120 Z9 122 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 28 PY 2000 VL 54 IS 6 BP 1218 EP 1221 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 297XY UT WOS:000086109300004 ER PT J AU Masaki, KH Losonczy, KG Izmirlian, G Foley, DJ Ross, GW Petrovitch, H Havlik, R White, LR AF Masaki, KH Losonczy, KG Izmirlian, G Foley, DJ Ross, GW Petrovitch, H Havlik, R White, LR TI Association of vitamin E and C supplement use with cognitive function and dementia in elderly men SO NEUROLOGY LA English DT Article DE dementia; vitamin E; vitamin C; aged (more than 60 years of age); Japanese-Americans; men ID RANDOMIZED CONTROLLED TRIAL; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; ALPHA-TOCOPHEROL; PLASMA-CONCENTRATIONS; OLDER PERSONS; PREVALENCE; HYPERTENSION; ANTIOXIDANT; POPULATION AB Objective: To determine whether use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning. Methods: The Honolulu-Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study were obtained from a subsample of the cohort interviewed in 1982, and from the entire cohort from a mailed questionnaire in 1988 and the dementia prevalence survey in 1991 to 1993. The subjects included 3,385 men, age 71 to 93 years, whose use of vitamin E and C supplements had been ascertained previously. Cognitive performance was assessed with the Cognitive Abilities Screening Instrument, and subjects were stratified into four groups: low, low normal, mid normal, and high normal. For the dementia analyses, subjects were divided into five mutually exclusive groups: AD (n = 47), vascular dementia (n = 35), mixed/other types of dementia (n = 50), low cognitive test scorers without diagnosed dementia (n = 254), and cognitively intact (n = 2,999; reference). Results: In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements in 1988 (odds ratio [OR], 0.12; 95% CI, 0.02 to 0.88). They were also protected against mixed/other dementia (OR, 0.31; 95% CI, 0.11 to 0.89). No protective effect was found for Alzheimer's dementia (OR, 1.81; 95% CI, 0.91 to 3.62). Among those without dementia, use of either vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination (OR, 1.25; 95% CI, 1.04 to 1.50), and use of both vitamin E and C together had borderline significance (OR, 1.18; 95% CI, 0.995 to 1.39). Conclusions: These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life. C1 Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Div Geriatr Med, Honolulu, HI 96822 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, Honolulu, HI USA. RP Masaki, KH (reprint author), Honolulu Heart Program, 347 N Kuakini St,HPM 9, Honolulu, HI 96817 USA. FU NCI NIH HHS [R01-CA-33644]; NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 46 TC 217 Z9 231 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 28 PY 2000 VL 54 IS 6 BP 1265 EP 1272 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 297XY UT WOS:000086109300013 PM 10746596 ER PT J AU Boyer, PL Sarafianos, SG Arnold, E Hughes, SH AF Boyer, PL Sarafianos, SG Arnold, E Hughes, SH TI Analysis of mutations at positions 115 and 116 in the dNTP binding site of HIV-1 reverse transcriptase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; TEMPLATE-PRIMER; PALM SUBDOMAINS; TYPE-1; RESISTANCE; FIDELITY; FINGERS; SENSITIVITY; REPLICATION AB We have examined amino acid substitutions at residues 115 and 116 in the reverse transcriptase (RT) of HIV-1, A number of properties were examined, including polymerization and processivity on both DNA and RNA templates, strand displacement, ribonucleotide misincorporation, and resistance to nucleoside analogs. The RT variants Tyr-215-Phe and Phe-116-Tyr are similar to wild-type HIV-1 RT in most but not all, respects. In contrast, the RT variant Tyr-115-Val is significantly impaired in polymerase activity compared with wild-type RT; however, Tyr-115-Val is able to incorporate ribonucleotides as well as deoxyribonucleotides during polymerization and is resistant to a variety of nucleoside analogs. C1 NCI, HIV Drug Resistance Program, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, POB B,Bldg 539,Room 130A, Ft Detrick, MD 21702 USA. OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [R37 AI027690, AI 09578, AI 27690, F32 AI009578]; NIGMS NIH HHS [GM 56609] NR 34 TC 45 Z9 45 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3056 EP 3061 DI 10.1073/pnas.97.7.3056 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200020 PM 10737786 ER PT J AU Marmorstein, AD Csaky, KG Baffi, J Lam, L Rahaal, F Rodriguez-Boulan, E AF Marmorstein, AD Csaky, KG Baffi, J Lam, L Rahaal, F Rodriguez-Boulan, E TI Saturation of, and competition for entry into, the apical secretory pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; RETINAL-PIGMENT EPITHELIUM; SITE-DIRECTED MUTAGENESIS; MDCK CELLS; GENE-THERAPY; INFLUENZA HEMAGGLUTININ; CYSTEINE RESIDUES; QUALITY-CONTROL; PROTEIN; GLYCOSYLATION AB To investigate mechanisms of apical sorting in the secretory pathway of epithelial cells, we expressed varying amounts of the 165 amino acid isoform of vascular endothelial growth factor (VEGF(165)) and transforming growth factor beta 1 (TGF-beta 1) via replication defective adenoviruses, Apical sorting of both proteins was efficient at low expression levels but saturated or was reversed at high expression levers. High expression levels of TGF-beta 1 were effective at competing VEGF(165) out of the apical pathway; however. VEGF(165) did not compete out TGF-beta 1. Tunicamycin inhibition experiments showed that the apical polarity of VEGF(165) was independent of N-glycosylation. We conclude that the apical sorting of these two molecules is a saturable, signal-mediated process, involving competition for apical sorting receptors. The sorting of the two proteins does not appear to involve N-glycans as sorting signals, or lectin sorters. The observations are particularly relevant to gene therapy because they demonstrate that overexpression of a transgene can result in undesirable missorting of the encoded protein. C1 Cornell Univ Med Coll, Margaret M Dyson Vis Res Inst, Dept Ophthalmol, New York, NY 10021 USA. Cornell Univ Med Coll, Dept Cell Biol, New York, NY 10021 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Rodriguez-Boulan, E (reprint author), Cornell Univ Med Coll, Margaret M Dyson Vis Res Inst, Dept Ophthalmol, 1300 York Ave, New York, NY 10021 USA. FU NEI NIH HHS [R01 EY08538, F32 EY06669, F32 EY006669, R01 EY008538] NR 39 TC 45 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3248 EP 3253 DI 10.1073/pnas.070049497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200053 PM 10725401 ER PT J AU Brown, P Rau, EH Johnson, BK Bacote, AE Gibbs, CJ Gajdusek, DC AF Brown, P Rau, EH Johnson, BK Bacote, AE Gibbs, CJ Gajdusek, DC TI New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600 degrees C suggests an inorganic template of replication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transmissible spongiform encephalopathy; scrapie; prion; medical waste; incineration ID PURE-SILICA ZEOLITES; STRUCTURE DIRECTION; PROTEINS; LIFE AB One-gram samples from a pool of crude brain tissue from hamsters infected with the 263K strain of hamster-adapted scrapie agent were placed in covered quartz-glass crucibles and exposed for either 5 or 15 min to dry heat at temperatures ranging from 150 degrees C to 1,000 degrees C Residual infectivity in the treated samples was assayed by the intracerebral inoculation of dilution series into healthy weanling hamsters, which were observed for 10 months; disease transmissions were verified by Western blot testing for proteinase-resistant protein in brains from clinically positive hamsters. Unheated control tissue contained 9.9 log(10)LD(50)/g tissue; after exposure to 150 degrees C, titers equaled or exceeded 6 log(10)LD(50)/g and after exposure to 300 degrees C, titers equated or exceeded 4 log(10)LD(50)/g. Exposure to 600 degrees C completely ashed the brain samples, which, when reconstituted with saline to their original weights, transmitted disease to 5 of 35 inoculated hamsters, No transmissions occurred after exposure to 1,000 degrees C. These results suggest that an inorganic molecular template with a decomposition paint near 600 degrees C is capable of nucleating the biological replication of the scrapie agent. C1 NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NIH, Environm Protect Branch, Div Safety, Off Res Serv, Bethesda, MD 20892 USA. CNRS, Inst Alfred Fessard, F-91198 Gif Sur Yvette, France. RP Brown, P (reprint author), NINDS, Cent Nervous Syst Studies Lab, NIH, Bldg 36,Room 4A-05,36 Convent Dr,MSC 4122, Bethesda, MD 20892 USA. RI Ducey, Thomas/A-6493-2011 NR 31 TC 70 Z9 71 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3418 EP 3421 DI 10.1073/pnas.050566797 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200083 PM 10716712 ER PT J AU Davidson, BL Stein, CS Heth, JA Martins, I Kotin, RM Derksen, TA Zabner, J Ghodsi, A Chiorini, JA AF Davidson, BL Stein, CS Heth, JA Martins, I Kotin, RM Derksen, TA Zabner, J Ghodsi, A Chiorini, JA TI Recombinant adeno-associated virus type 2, 4, and 5 vectors: Transduction of variant cell types and regions in the mammalian central nervous system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEDIATED GENE-TRANSFER; HEPARAN-SULFATE PROTEOGLYCAN; IN-VIVO EXPRESSION; ADENOASSOCIATED VIRUS; TYROSINE-HYDROXYLASE; AAV VECTORS; FACTOR-IX; BRAIN; PERSISTENT; EFFICIENT AB Recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in the central nervous system (CNS), but it is not known how other rAAV serotypes perform as CNS gene transfer vectors. Serotypes 4 and 5 are distinct from rAAV2 and from each other in their capsid regions, suggesting that they may direct binding and entry into different cell types. In this study, we examined the tropisms and transduction efficiencies of P-galactosidase-encoding vectors made from rAAV4 and rAAV5 compared with similarly designed rAAV2-based vectors. Injection of rAAV5 beta-galactosidase (beta gal) or rAAV4 beta gal into the lateral ventricle resulted in stable transduction of ependymal cells, with approximately 10-fold more positive cells than in mice injected with rAAV2 beta gal. Major differences between the three vectors were revealed upon striatal injections. Intrastriatal injection of rAAV4 beta gal resulted again in striking ependyma-specific expression of transgene, with a notable absence of transduced cells in the parenchyma. rAAV2 beta gal and rAAV5 beta gal intrastriatal injections led to beta-gal-positive parenchymal cells, but unlike rAAV2 beta gal, rAAV5 beta gal transduced both neurons and astrocytes. The number of transgene-positive cells in rAAV5 beta gal-injected brains was 130 and 5,000 times higher than in rAAV2 beta gal-injected brains at 3 and 15 wk, respectively. Moreover, transgene-positive cells were widely dispersed throughout the injected hemisphere in rAAV5 beta gal-transduced animals. Together, our data provide in vivo support for earlier in vitro work, suggesting that rAAV4 and rAAV5 gain cell entry by means of receptors distinct from rAAV2. These differences could be exploited to improve gene therapy for CNS disorders. C1 Univ Iowa, Coll Med, Dept Internal Med, Program Gene Therapy, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Neurosurg, Iowa City, IA 52242 USA. NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Davidson, BL (reprint author), Univ Iowa, Coll Med, Dept Internal Med, Program Gene Therapy, Iowa City, IA 52242 USA. RI kotin, robert/B-8954-2008 FU NICHD NIH HHS [HD 33531, R01 HD033531] NR 36 TC 433 Z9 449 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3428 EP 3432 DI 10.1073/pnas.050581197 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200085 PM 10688913 ER PT J AU Halberg, RB Katzung, DS Hoff, PD Moser, AR Cole, CE Lubet, RA Donehower, LA Jacoby, RF Dove, WF AF Halberg, RB Katzung, DS Hoff, PD Moser, AR Cole, CE Lubet, RA Donehower, LA Jacoby, RF Dove, WF TI Tumorigenesis in the multiple intestinal neoplasia mouse: Redundancy of negative regulators and specificity of modifiers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYPOSIS-COLI; P53; MICE; APOPTOSIS; GENE; PREDISPOSES; EXPRESSION; MUTATIONS; DEFICIENT; RADIATION AB The interaction between mutations in the tumor-suppressor genes Ape and p53 was studied in congenic mouse strains to minimize the influence of polymorphic modifiers. The multiplicity and invasiveness of intestinal adenomas of Apc(Min/+) (Min) mice was enhanced by deficiency for p53, In addition, the occurrence of desmoid fibromas was strongly enhanced by p53 deficiency. The genetic modifier Mom1 and the pharmacological agents piroxicam and difluoromethylornithine each reduced intestinal adenoma multiplicity in the absence of p53 function. Mom1 showed no influence on the development of desmoid fibromas, whereas the combination of piroxicam and difluoromethylornithine exerted a moderate effect, The ensemble of tumor suppressors and modifiers of a neoplastic process can be usefully analyzed in respect to tissue specificity and synergy. C1 Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. Univ Wisconsin, Dept Biostat, Madison, WI 53706 USA. Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53792 USA. NCI, Chemoprevent Branch, Div Canc Prevent, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Dove, WF (reprint author), Univ Wisconsin, McArdle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA. RI Hoff, Peter/H-4040-2011 FU NCI NIH HHS [N01 CN 65122, CA 07175, CA 50585, F32 CA077946, R01 CA063677, R37 CA063677, T32 CA009565]; NEI NIH HHS [T32 EY007119] NR 39 TC 87 Z9 88 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 MAR 28 PY 2000 VL 97 IS 7 BP 3461 EP 3466 DI 10.1073/pnas.050585597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200091 PM 10716720 ER PT J AU Wang, JJ Jani-Sait, SN Escalon, EA Carroll, AJ de Long, PJ Kirsch, IR Aplan, PD AF Wang, JJ Jani-Sait, SN Escalon, EA Carroll, AJ de Long, PJ Kirsch, IR Aplan, PD TI The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the BHLHB1 gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOOP-HELIX PROTEIN; DNA-BINDING MOTIF; REGION; RECEPTOR; ENCODES; LOCUS; DIFFERENTIATION; ONCOPROTEIN; INHIBITION; TRANSLIN AB We have cloned the genomic breakpoints for a balanced t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic: leukemia, Sequence analysis of the genomic breakpoints indicated that the translocation had been mediated by an illegitimate V(D)J recombination event that disrupted the T-cell receptor (TCR) alpha locus and placed the TCR alpha locus enhancer on the derivative 21 chromosome. We identified a previously unreported transcript, designated BHLHB1 (for basic domain, helix-loop-helix protein, class B, 1) that had been activated by the translocation, BHLHB1 mapped to the region of chromosome 21 that has been proposed to be responsible, at least in part, for the learning deficits seen in children with Down's syndrome, Although BHLHB1 expression normally is restricted to neural tissues, T-cell lymphoblasts with the t(14;21)(q11,2;q22) also expressed high levels of BHLHB1 mRNA. Expression of BHLHB1 dramatically inhibited E2A-mediated transcription activation in NIH 3T3 fibroblasts and Jurkat T cells. This observation suggests that BHLHB1, similar to SCL/TAL1, may exert a leukemogenic effect through a functional inactivation of E2A or related proteins. C1 Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Biochem, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Clin Cytogenet, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA. Miami Childrens Hosp, Div Hematol Oncol, Miami, FL 33155 USA. Univ Alabama, Dept Human Genet, Birmingham, AL 35294 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Aplan, PD (reprint author), NCI, Div Clin Sci, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [CA16056, P30 CA016056] NR 36 TC 53 Z9 54 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3497 EP 3502 DI 10.1073/pnas.97.7.3497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200097 PM 10737801 ER PT J AU Garcia, RAG Vasudevan, K Buonanno, A AF Garcia, RAG Vasudevan, K Buonanno, A TI The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID D-ASPARTATE RECEPTOR; NICOTINIC ACETYLCHOLINE-RECEPTOR; EPSILON-SUBUNIT GENE; NMDA-RECEPTOR; NEUROMUSCULAR-JUNCTION; TYROSINE KINASES; POSTSYNAPTIC DENSITY; TRANSCRIPTION FACTOR; SYNAPTIC EXPRESSION; HIPPOCAMPAL-NEURONS AB Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1-4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain, Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90. PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with beta(2)-syntrophin, which has a single PDZ domain, As with N-methyl-D-aspartate (NMDA) receptors, ErbB-4 interacts with the first two PDZ domains of PSD-95, Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals, The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. C1 NIH, Mol Neurobiol Unit, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NIH, Mol Neurobiol Unit, Bethesda, MD 20892 USA. NR 70 TC 206 Z9 219 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3596 EP 3601 DI 10.1073/pnas.070042497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200114 PM 10725395 ER PT J AU Mezey, E Toth, ZE Cortright, DN Arzubi, MK Krause, JE Elde, R Guo, A Blumberg, PM Szallasi, A AF Mezey, E Toth, ZE Cortright, DN Arzubi, MK Krause, JE Elde, R Guo, A Blumberg, PM Szallasi, A TI Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PRIMARY SENSORY NEURONS; NEONATAL CAPSAICIN TREATMENT; SUBSTANCE-P; PARAVENTRICULAR NUCLEUS; LOCUS-CERULEUS; PREOPTIC AREA; SPINAL-CORD; 5-HYDROXYTRYPTAMINE; HYPOTHALAMUS; BRAIN AB The cloned vanilloid receptor VR1 has attracted recent attention as a molecular integrator of painful stimuli on primary sensory neurons. The existence of vanilloid-sensitive neurons in the brain is, however, controversial. In this study, we have used an antibody and a complementary RNA probe to explore the distribution of neurons that express VR1 in rat and in certain areas of human brain. In the rat, we observed VR1-expressing neurons throughout the whole neuroaxis, including all cortical areas (in layers 3 and 5), several members of the limbic system (e.g., hippocampus, central amygdala, and both medial and lateral habenula), striatum, hypothalamus, centromedian and paraventricular thalamic nuclei, substantia nigra, reticular formation, locus coeruleus, cerebellum, and inferior olive. VR1-immunopositive cells also were found in the third and fifth layers of human parietal cortex. Reverse transcription-PCR performed with rat VR1-specific primers verified the expression of VR1 mRNA in cortex, hippocampus, and hypothalamus. In the central nervous system, neonatal capsaicin treatment depleted VR1 mRNA from the spinal nucleus of the trigeminal nerve, but not from other areas such as the inferior olive. The finding that VR1 is expressed not only in primary sensory neurons but also in several brain nuclei is of great importance in that it places VRs in a much broader perspective than pain perception. VRs in the brain (and putative endogenous vanilloids) may be involved in the control of emotions, learning, and satiety, just to name a few exciting possibilities. C1 NINDS, NIH, Basic Neurosci Program, Bethesda, MD 20892 USA. NIMH, Bethesda, MD 20892 USA. Neurogen Corp, Branford, CT 06405 USA. Univ Minnesota, Dept Cell Biol & Anat, Minneapolis, MN 55455 USA. NCI, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, NIH, Basic Neurosci Program, Bldg 36,3D-06, Bethesda, MD 20892 USA. NR 50 TC 523 Z9 540 U1 3 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3655 EP 3660 DI 10.1073/pnas.060496197 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200124 PM 10725386 ER PT J AU Butefisch, CM Davis, BC Wise, SP Sawaki, L Kopylev, L Classen, J Cohen, LG AF Butefisch, CM Davis, BC Wise, SP Sawaki, L Kopylev, L Classen, J Cohen, LG TI Mechanisms of use-dependent plasticity in the human motor cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; METHYL-D-ASPARTATE; HORIZONTAL CONNECTIONS; MAGNETIC STIMULATION; LAMOTRIGINE; DEXTROMETHORPHAN; EXCITABILITY; BRAIN; PHARMACOKINETICS; ANTICONVULSANT AB Practicing movements results in improvement in performance and in plasticity of the motor cortex. To identify the underlying mechanisms, we studied use-dependent plasticity in human subjects premedicated with drugs that influence synaptic plasticity. Use-dependent plasticity was reduced substantially by dextromethorphan (an N-methyl-D-aspartate receptor blocker) and by lorazepam [a gamma-aminobutyric acid (GABA) type A receptor-positive allosteric modulator]. These results identify N-methyl-D-aspartate receptor activation and GABAergic inhibition as mechanisms operating in use-dependent plasticity in intact human motor cortex and point to similarities in the mechanisms underlying this form of plasticity and long-term potentiation. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, NIH, Bethesda, MD 20892 USA. Univ Rostock, Neurol Klin, D-18055 Rostock, Germany. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N234, Bethesda, MD 20892 USA. NR 31 TC 338 Z9 341 U1 3 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3661 EP 3665 DI 10.1073/pnas.050350297 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200125 PM 10716702 ER PT J AU Schiltz, RL Nakatani, Y AF Schiltz, RL Nakatani, Y TI The PCAF acetylase complex as a potential tumor suppressor SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE E1A; GCN5; P300; CBP; HAT ID HISTONE ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTIONAL COACTIVATORS P300; NUCLEAR RECEPTOR COACTIVATOR; YEAST PUTATIVE ADAPTERS; HUMAN ADENOVIRUS TYPE-5; TATA-BINDING PROTEIN; CELL-CYCLE ARREST; SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE; IN-VIVO C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Schiltz, RL (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, 9000 Rockville Pike,Bldg 6,Room 416, Bethesda, MD 20892 USA. NR 107 TC 54 Z9 58 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAR 27 PY 2000 VL 1470 IS 2 BP M37 EP M53 DI 10.1016/S0304-419X(99)00037-2 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 299NT UT WOS:000086205300001 PM 10722926 ER PT J AU Ames, B AF Ames, B TI Causes and prevention of cancer: The synthetic chemical distraction. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Calif Berkeley, NIEHS, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 53-AGRO BP U70 EP U70 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100255 ER PT J AU Anfinrud, PA AF Anfinrud, PA TI Ultrafast time-resolved studies of ligand dynamics ln Myoglobin: Watching proteins as they function. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 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 AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 1009-CHED BP U440 EP U440 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102399 ER PT J AU Bax, A AF Bax, A TI Solution NMR of isotopically enriched proteins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Chem Phys Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 143-PHYS BP U289 EP U289 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246201602 ER PT J AU Bax, A Delaglio, F Cornilescu, G Ramirez, BE Koenig, B Chou, JJ AF Bax, A Delaglio, F Cornilescu, G Ramirez, BE Koenig, B Chou, JJ TI NMR of weakly aligned macromolecules. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Phys Chem Lab, Bethesda, MD 20892 USA. RI Chou, James/N-9840-2013; Cornilescu, Gabriel/H-3113-2011 OI Cornilescu, Gabriel/0000-0002-1204-8904 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 484-PHYS BP U349 EP U349 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246201941 ER PT J AU Boyd, MR AF Boyd, MR TI Some perspectives on anticancer drug discovery and development: Where are we now and where are we going?. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 241-ORGN BP U131 EP U131 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200724 ER PT J AU Brenneman, DE Spong, CY Hauser, J Gozes, I AF Brenneman, DE Spong, CY Hauser, J Gozes, I TI Neuroprotective peptides prevent neuronal and embryonic death. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 315-MEDI BP U58 EP U58 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200313 ER PT J AU Burke, TG Bom, D Kruszewski, S Zimmer, SG Yang, D Bingcang, AL Pommier, Y Kohlhagen, G Perez-Soler, R Strode, JT Du, W Gabarda, A Chavan, AJ Latus, LJ Curran, DP AF Burke, TG Bom, D Kruszewski, S Zimmer, SG Yang, D Bingcang, AL Pommier, Y Kohlhagen, G Perez-Soler, R Strode, JT Du, W Gabarda, A Chavan, AJ Latus, LJ Curran, DP TI Novel drug design and formulation strategies for optimal topoisomerase I inhibition by camptothecin anticancer agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Kentucky, Coll Pharm, Lexington, KY 40506 USA. Univ Kentucky, Tigen Pharmaceut Inc, Lexington, KY 40506 USA. Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. Univ Kentucky, Sch Med, Lexington, KY 40506 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Med Oncol, New York, NY 10016 USA. Tigen Pharmaceut, Lexington, KY 40508 USA. RI Kruszewski, Stefan/H-3265-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 348-BIOT BP U225 EP U225 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101072 ER PT J AU Burke, TR Gao, Y Yao, ZJ Wu, L Voigt, JH Zhang, ZY AF Burke, TR Gao, Y Yao, ZJ Wu, L Voigt, JH Zhang, ZY TI Phosphotyrosyl-based motifs in the structure-based design of protein-tyrosine phosphatase inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RI Yao, Zhu-Jun/E-7635-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 27-MEDI BP U7 EP U7 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200027 ER PT J AU Cannizzaro, CM Marison, IW von Stockar, U AF Cannizzaro, CM Marison, IW von Stockar, U TI Astaxanthin production by Phaffia rhodozyma. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NCI, DCTD, DTP, Biol Resources Branch, Bethesda, MD 20892 USA. NCI, DCTD, DTP, Nat Prod Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 331-BIOT BP U222 EP U222 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101055 ER PT J AU Chiang, VL Li, LG Tsai, CJ Harding, SA Hu, WJ Osakabe, K Tsao, CC Lung, J Wu, LG Joshi, C Umezawa, T Popko, JL AF Chiang, VL Li, LG Tsai, CJ Harding, SA Hu, WJ Osakabe, K Tsao, CC Lung, J Wu, LG Joshi, C Umezawa, T Popko, JL TI Lignin, hydroxycinnamate esters, and cellulose biosynthesis in angiosperm trees: A new view of a coordinated network for plant cell-wall integrity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Michigan Technol Univ, Sch Forestry, Plant Biotechnol Res Ctr, Houghton, MI 49931 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Natl Inst Agrobiol Resources, Dept Biotechnol, Tsukuba, Ibaraki 3058602, Japan. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RI Tsai, CJ/C-2450-2009 OI Tsai, CJ/0000-0002-9282-7704 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 84-CELL BP U270 EP U270 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101298 ER PT J AU Clore, GM AF Clore, GM TI Structures of proteins and protein complexes beyond 40 kDa. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 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 AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 12-PHYS BP U270 EP U270 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246201471 ER PT J AU Colliver, JD AF Colliver, JD TI Patterns and extent of abuse of smokable substances. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDR, Epidemiol Res Branch, DESPR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 1-TOXI BP U473 EP U473 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102553 ER PT J AU Du, X AF Du, X TI Purification and characterization of the ADP-D-glycero-D-mannoheptose synthetase from Helicobactor pylori. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Diagnon Corp, Dept Res & Dev, Rockville, MD USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 168-BIOL BP U153 EP U153 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100722 ER PT J AU Eaton, WA Munoz, V Hagen, SJ Jas, GS Lapidus, LJ Henry, ER Hofrichter, A AF Eaton, WA Munoz, V Hagen, SJ Jas, GS Lapidus, LJ Henry, ER Hofrichter, A TI Mechanisms in protein folding. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Phys Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 65-PHYS BP U277 EP U277 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246201524 ER PT J AU Empedocles, S Wong, E Adams, E Bruchez, M Phillips, V Trent, J Bittner, M AF Empedocles, S Wong, E Adams, E Bruchez, M Phillips, V Trent, J Bittner, M TI Nanocrystals: A new material for high-sensitivity, multicolor bioassays. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Quantum Dot Corp, Syst Div, Palo Alto, CA 94303 USA. NIH, Canc Genet Lab, NHGRI, Bethesda, MD 20892 USA. RI Bruchez, Marcel/C-2271-2009 OI Bruchez, Marcel/0000-0002-7370-4848 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 212-IEC BP U755 EP U755 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246104057 ER PT J AU Everall, NJ Chalmers, JM Kidder, LH Lewis, EN Schaeberle, M Levin, I AF Everall, NJ Chalmers, JM Kidder, LH Lewis, EN Schaeberle, M Levin, I TI Mapping and imaging orientation, crystallinity, and chemical composition in polymer articles using IR and Raman microscopies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ICI, Wilton Res Ctr, Cleveland TS90 8JE, England. Spectral Dimens Inc, Olney, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 249-PMSE BP U502 EP U502 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246202828 ER PT J AU Gabrielsen, B Stackhouse, T Muszynski, K Keefer, L Kwak, L Rybak, S Cragg, G Drake, J Carroll, K Marquis, S Sybert, K AF Gabrielsen, B Stackhouse, T Muszynski, K Keefer, L Kwak, L Rybak, S Cragg, G Drake, J Carroll, K Marquis, S Sybert, K TI National Cancer Institute (NCI): Partnerships for the development of therapeutic technologies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Fairview Ctr, Frederick, MD 21702 USA. NCI, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 31-MEDI BP U8 EP U8 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200031 ER PT J AU Gussio, R Zaharevitz, DW McGrath, CF Pattabiraman, N Newhouse, JS Sausville, EA AF Gussio, R Zaharevitz, DW McGrath, CF Pattabiraman, N Newhouse, JS Sausville, EA TI Effects of the CDK1 receptor environment on the molecular properties of paullones: A quantum mechanical characterization. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Dev Therapeut Program, Frederick, MD 21702 USA. NCI, Adv Biomed Comp Ctr, Bethesda, MD 20892 USA. Maui High Performance Comp Ctr, Maui, HI 96753 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 36-MEDI BP U9 EP U9 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200036 ER PT J AU Horkay, F Hecht, AM Geissler, E AF Horkay, F Hecht, AM Geissler, E TI Neutron-scattering investigations on filled polymer gels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 158-POLY BP U379 EP U379 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246202109 ER PT J AU Horkay, F Tasaki, I Basser, PJ AF Horkay, F Tasaki, I Basser, PJ TI Thermodynamic properties of polyacrylate networks swollen in physiological salt solutions. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 355-BIOT BP U226 EP U226 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101079 ER PT J AU Hsin, LW Dersch, CM Horel, R Rothman, RB Rice, KC AF Hsin, LW Dersch, CM Horel, R Rothman, RB Rice, KC TI Synthesis and dopamine transporter activity of phenylsubstituted 1-{2-[bis(4-fluorophenyl)methoxy]-ethyl}-4-(2-hydroxypropyl)piperazines as potential cocaine treatment medications. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD, Med Chem Lab, Bethesda, MD 20892 USA. NIDA, Clin Psychopharmacol Sect, IRP, NIH, Lexington, KY 40583 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 103-MEDI BP U21 EP U21 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200103 ER PT J AU Huang, WR Zhang, PL Song, YH Wong, P Tran, K Sinha, U Scarborough, RM Zhu, BY AF Huang, WR Zhang, PL Song, YH Wong, P Tran, K Sinha, U Scarborough, RM Zhu, BY TI Design, synthesis, and structure-activity relationships of substituted aniline-based factor Xa inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Lab Drug Discovery Res & Dev, FCRDC, S San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 240-ORGN BP U131 EP U131 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200723 ER PT J AU Jacobson, KA Moro, S West, PL Ji, XD AF Jacobson, KA Moro, S West, PL Ji, XD TI Interactions of flavones and other phytochemicals with adenosine receptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 197-AGFD BP U56 EP U56 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100196 ER PT J AU Jas, GS AF Jas, GS TI Effect of viscosity on the kinetics of alpha-helix and beta-hairpin formation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 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 AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 1005-CHED BP U439 EP U440 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102395 ER PT J AU Jerina, DM AF Jerina, DM TI Diol epoxides and DNA. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 35-TOXI BP U478 EP U478 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102579 ER PT J AU Keefer, LK AF Keefer, LK TI Tony Dipple's contributions to the nitric oxide field. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 40-TOXI BP U479 EP U479 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102584 ER PT J AU Kim, YC Brown, SG Harden, TK Boyer, JL Dubyak, G King, BF Burnstock, G Jacobson, KA AF Kim, YC Brown, SG Harden, TK Boyer, JL Dubyak, G King, BF Burnstock, G Jacobson, KA TI Structure-activity relationships of pyridoxal phosphate derivatives as potent and selective antagonists of P2X receptors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Royal Free Sch Med, London, England. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Case Western Reserve Univ, Dept Physiol Biophys, Cleveland, OH USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 102-MEDI BP U21 EP U21 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200102 ER PT J AU Kirk, KL AF Kirk, KL TI Fluorinated pharmaceuticals. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 16-FLUO BP U662 EP U662 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246103595 ER PT J AU Lee, RE Protopopova, MN Crooks, ET Voskull, M Wilson, M Schoolnik, GK Barry, CE AF Lee, RE Protopopova, MN Crooks, ET Voskull, M Wilson, M Schoolnik, GK Barry, CE TI Combining genomics and combinatorial chemistry to explore the antitubercular action of ethambutol diamine libraries. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Rockville, MD 20852 USA. Sequella Inc, Drug Discovery, Rockville, MD 20849 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 151-MEDI BP U30 EP U30 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200151 ER PT J AU Liao, W Tang, M Li, JJ Lee, LM Cao, Y AF Liao, W Tang, M Li, JJ Lee, LM Cao, Y TI EBV encoded latent membrane protein 1 increase expression of immunoglobulin kappa light chain through NF kappa B in nasopharyngeal carcinoma SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Hunan Med Univ, Inst Canc Res, Changsha 410078, Hunan, Peoples R China. Natl Canc Inst, Gene Regulat Sect, Frederick, MD 21702 USA. Frederick Canc Res & Dev Ctr, SAIC Frederick, Recombinant DNA Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 45-BIOT BP U166 EP U166 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100776 ER PT J AU Long, YQ Lung, FDT Voigt, JH Roller, PP AF Long, YQ Lung, FDT Voigt, JH Roller, PP TI Conformational requirements for high affinity binding of a novel nonphosphorylated cyclic peptide ligand to the Grb2-SH2 domain. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 62-MEDI BP U13 EP U13 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200062 ER PT J AU Luzzio, FA Mayorov, AV Figg, WD AF Luzzio, FA Mayorov, AV Figg, WD TI Thalidomide metabolites: Preparation of (+)-2-(N-phthalimido)-4-hydroxyglutamic acid derivatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Louisville, Louisville, KY 40292 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 780-ORGN BP U227 EP U227 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246201259 ER PT J AU Moro, S Hoffmann, C Jacobson, KA AF Moro, S Hoffmann, C Jacobson, KA TI Role of the extracellular loops of G protein-coupled receptors in ligand recognition: A molecular modeling study of the human P2Y1 receptor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Padua, Dept Pharmaceut Sci, I-35131 Padua, Italy. NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 226-MEDI BP U42 EP U42 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200225 ER PT J AU Moschel, RC AF Moschel, RC TI Twenty-four years of carcinogenesis research with Tony Dipple. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 34-TOXI BP U478 EP U478 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102578 ER PT J AU Mu, L Nicklaus, M Sarafianos, S Ford, H Mitsuya, H Marquez, V AF Mu, L Nicklaus, M Sarafianos, S Ford, H Mitsuya, H Marquez, V TI Dynamic conformation changes of furanose ring: A major influence of nucleoside structure on enzyme catalytic activity and inhibition. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Med Chem Lab, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. NIH, Expt Retrovirol Sect, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 93-COMP BP U602 EP U602 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246103259 ER PT J AU Ponten, I AF Ponten, I TI Effects of sequence context and adduct structure on mutations induced by site-specific PAH diol epoxide-DNA adducts. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 36-TOXI BP U478 EP U478 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102580 ER PT J AU Ramos, LA Kroth, H Sayer, JM Jerina, DM Dipple, A AF Ramos, LA Kroth, H Sayer, JM Jerina, DM Dipple, A TI Effect of cytosine methylation in a CpG sequence on the mutagenicity of specifically located trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-deoxyguanosine adducts in E-coli. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 72-TOXI BP U484 EP U484 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102615 ER PT J AU Rick, SW AF Rick, SW TI Studies of water, aqueous solutions, and proteins using polarizable potential models. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 307-PHYS BP U324 EP U324 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246201766 ER PT J AU Rogers, HG Rogers, RD Brechbiel, MW AF Rogers, HG Rogers, RD Brechbiel, MW TI Synthesis of difunctionalized macrocyclic chelates based on cyclam and cyclen. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Natl Canc Ctr, Chem Sect, Bethesda, MD 20892 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 175-INOR BP U797 EP U797 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246104311 ER PT J AU Saavedra, JE Bonifant, CL Fitzhugh, AL Keefer, LK Citro, ML AF Saavedra, JE Bonifant, CL Fitzhugh, AL Keefer, LK Citro, ML TI Synthesis of labile diazeniumdiolate prodrugs for controlled delivery of nitric oxide. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 113-TOXI BP U492 EP U492 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102655 ER PT J AU Sampson, AE Lee, RE Barry, CE AF Sampson, AE Lee, RE Barry, CE TI Antimycobacterial drug activation: The major whole cell metabolite of both ethionamide and isoniazid is a 4-pyridylmethanol. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIAID, Host Def Lab, TB Res Sect 3, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 148-MEDI BP U29 EP U30 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200148 ER PT J AU Seidman, MM Majumdar, A Puri, N Khorlin, A Dyatkina, N AF Seidman, MM Majumdar, A Puri, N Khorlin, A Dyatkina, N TI Targeted gene knockout mediated by triple helix-forming oligonucleotides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. Genelab Technol Inc, Redwood City, CA 94065 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 41-TOXI BP U479 EP U479 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102585 ER PT J AU Srinivasan, A Saavedra, JE Ji, XH Flippen-Anderson, J Pal, A Hu, X Singh, SV Keefer, LK AF Srinivasan, A Saavedra, JE Ji, XH Flippen-Anderson, J Pal, A Hu, X Singh, SV Keefer, LK TI Glutathione S-transferase-catalyzed nitric-oxide generation from an O-2-aryl diazeniumdiolate. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, IRSP, SAIC, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Frederick, MD 21702 USA. USN, Res Lab, Washington, DC 20375 USA. Mercy Hosp, Canc Res Lab, Pittsburgh, PA 15219 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 87-TOXI BP U487 EP U487 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102630 ER PT J AU Stadtman, T AF Stadtman, T TI Selenoenzymes: Chemical forms of selenium and roles in catalysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 168-IEC BP U748 EP U748 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246104014 ER PT J AU Szczepanik, MB Pande, P Laux, WG Debrabant, A Dwyer, D Johnson, RA AF Szczepanik, MB Pande, P Laux, WG Debrabant, A Dwyer, D Johnson, RA TI Inhibition of Leishmania donovani 3 '-nucleotidase by 9-substituted adenine derivatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SUNY Stony Brook, Hlth Sci Ctr, Stony Brook, NY 11794 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 36-BIOL BP U130 EP U130 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100592 ER PT J AU Szeliga, J Dipple, A Amin, S AF Szeliga, J Dipple, A Amin, S TI Comparison of 5,6-and 5,9-dimethylchrysene dihydrodiol epoxide in the reaction with DNA. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. Amer Hlth Fdn, Naylor Dana Inst Dis Prevent, Valhalla, NY 10595 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 70-TOXI BP U484 EP U484 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102613 ER PT J AU Tamamura, H Bienfait, B Nacro, K Lewin, NE Blumberg, PM Marquez, VE AF Tamamura, H Bienfait, B Nacro, K Lewin, NE Blumberg, PM Marquez, VE TI Conformationally constrained analogs of diacylglycerol (DAG): The contrast between sn-1 and sn-2 DAG lactones in binding to protein kinase C (PK-C). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Div Basic Sci, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 41-MEDI BP U10 EP U10 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200041 ER PT J AU Trudell, ML Lomenzo, SA Izenwasser, S Gerdes, RM Katz, JL Kopajtic, T AF Trudell, ML Lomenzo, SA Izenwasser, S Gerdes, RM Katz, JL Kopajtic, T TI Synthesis, dopamine transporter affinity and dopamine uptake inhibition of meperidine analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDA, Div Intramural Res, Baltimore, MD 21224 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 324-MEDI BP U60 EP U60 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200322 ER PT J AU Tycko, R Antzutkin, ON Balbach, JJ Reed, J AF Tycko, R Antzutkin, ON Balbach, JJ Reed, J TI Structure of beta-amyloid peptide fibrils by multiple-quantum NMR. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Phys Chem Lab, Bethesda, MD 20892 USA. Lulea Univ Technol, Div Inorgan CHem, S-95187 Lulea, Sweden. Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 28-PMSE BP U469 EP U469 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246202608 ER PT J AU Tziatzios, C Durchschlag, H Gonzalez, JJ Albertini, E Prados, P de Mendoza, J Eschbaumer, C Schubert, US Schuck, P Schubert, D AF Tziatzios, C Durchschlag, H Gonzalez, JJ Albertini, E Prados, P de Mendoza, J Eschbaumer, C Schubert, US Schuck, P Schubert, D TI Characterization of supramolecular assemblies by analytical ultracentrifugation: Potential, problems, and application to Co coordination arrays and calixarenes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Frankfurt, Inst Biophys, D-60590 Frankfurt, Germany. Univ Regensburg, Inst Biophys & Phys Biochem, D-93040 Regensburg, Germany. Univ Autonoma Madrid Contoblanco, Dept Quim Organ, E-28049 Madrid, Spain. Tech Univ Munich, D-85747 Garching, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 606-POLY BP U456 EP U457 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246202554 ER PT J AU Wang, PY Brank, A Christman, JK MacKerell, AD Banavali, NK Marquez, VE AF Wang, PY Brank, A Christman, JK MacKerell, AD Banavali, NK Marquez, VE TI Synthesis of conformationally locked carbocyclic DNA abasic sites. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, DBS, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 50-MEDI BP U11 EP U11 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200050 ER PT J AU Webb, TR Jacobson, KA Melman, N Lvovskiy, D Ji, XD AF Webb, TR Jacobson, KA Melman, N Lvovskiy, D Ji, XD TI Utilization of a unified pharmacophore query in the discovery of new antagonists of the adenosine receptor family. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ChemBridge Corp, San Diego, CA 92127 USA. NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 310-MEDI BP U57 EP U57 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200308 ER PT J AU Zhu, JW Graf, SJ Burnette, AF Reeb, S Testerman, R Wang, SD McCloud, TG Collins, R Creekmore, SP Newman, D AF Zhu, JW Graf, SJ Burnette, AF Reeb, S Testerman, R Wang, SD McCloud, TG Collins, R Creekmore, SP Newman, D TI Wortmannin fermentation process development and optimization. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NCI, DCTD, DTP, Biol Resources Branch, Bethesda, MD 20892 USA. NCI, DCTD, DTP, Nat Prod Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 332-BIOT BP U222 EP U223 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101056 ER PT J AU Zhu, JW Roach, J Liu, CL Reeb, S Testerman, R Tucker, J Poole, K Giardina, S Wang, SD Creekmore, SP AF Zhu, JW Roach, J Liu, CL Reeb, S Testerman, R Tucker, J Poole, K Giardina, S Wang, SD Creekmore, SP TI Fed-batch fermentation with optimum filtration recovery process for the GMP production of soluble recombinant staphylococcus enterotoxin B vaccine in E-coli. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Biopharmaceut Dev Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, DCTD, Biol Resources Branch, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 241-BIOT BP U208 EP U208 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100968 ER PT J AU Ziffer, H Ma, JY Mekonnena, B Weiss, E Katz, E Kyle, DF AF Ziffer, H Ma, JY Mekonnena, B Weiss, E Katz, E Kyle, DF TI Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Colgate Univ, Hamilton, NY 13346 USA. Walter Reed Army Med Ctr, Dept Parasitol, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 143-MEDI BP U29 EP U29 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200143 ER PT J AU Nakai, M Qin, ZH Wang, YM Chase, TN AF Nakai, M Qin, ZH Wang, YM Chase, TN TI NMDA and non-NMDA receptor-stimulated I kappa B-alpha degradation: differential effects of the caspase-3 inhibitor DEVD center dot CHO, ethanol and free radical scavenger OPC-14117 SO BRAIN RESEARCH LA English DT Article DE apoptosis; caspase-3; ethanol; neurodegeneration; striatum; glutamate receptor agonist ID D-ASPARTATE RECEPTORS; TRANSCRIPTION FACTOR; HIPPOCAMPAL-NEURONS; PROTEASOME INHIBITOR; SYNAPTIC ACTIVATION; KAINATE RECEPTORS; GENE-EXPRESSION; RAT STRIATUM; BRAIN; GLUTAMATE AB The excitotoxic response of striatal neurons to NMDA and non-NMDA receptor agonists involves the nuclear translocation of transcription factor nuclear factor-kappa B (NF-kappa B) due to I kappa B-alpha degradation. Resultant augmentation in c-Myc, p53 and cyclin D1 expression presages the apoptotic-like destruction of these cells in vivo. To differentiate molecular events triggered by intrastriatally injected quinolinic acid (QA, 60 nmol) and kainic acid (KA, 2.5 nmol), we compared the effects of a caspase-3 inhibitor (DEVD . CHO, 8 mu g intrastriatally), a free radical scavenger (OPC-14117; 600 mg/kg, orally) and ethanol (2.14-8.6 mu mol, intrastriatally or 25-100 mmol/kg, orally) on changes induced by these glutamatergic agonists on NF-kappa B cascade components and the apoptotic death of rat striatal neurons in vivo. The results indicated that the QA induced degradation of I kappa B-alpha is almost totally mediated by a caspase-3-dependent mechanism, while KA-induced I kappa B-alpha degradation is only partially dependent on caspase-3. OPC-14117 attenuated the effects of QA but not KA on I kappa B-alpha degradation, suggesting that oxidative stress contributes to the QA- but not the KA-induced degradation of I kappa B-alpha. In contrast, ethanol inhibited the KA- but not the QA-induced degradation of I kappa B-alpha and the ensuing DNA fragmentation and loss of striatal GABAergic neurons. It would now appear that NF-kappa B activation in striatal neurons induced by NMDA or KA receptor stimulation involves different biochemical mechanisms. Since excitotoxicity associated with NF-kappa B activation may contribute to neuronal degenerative disorders such as Huntington's disease, a more detailed understanding of biochemical events underlying ionotrophic glutamate receptor-stimulated cell death may assist in the discovery of alternative approaches to interdicting the deleterious consequences of excitotoxic insult. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Rm 5C103,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 59 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 24 PY 2000 VL 859 IS 2 BP 207 EP 216 DI 10.1016/S0006-8993(00)01959-4 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 297JZ UT WOS:000086080600004 PM 10719066 ER PT J AU Arteca, GA Cachau, RE Valuri, K AF Arteca, GA Cachau, RE Valuri, K TI Structural complexity of hydrogen-bonded networks SO CHEMICAL PHYSICS LETTERS LA English DT Article ID LIQUID WATER; PROTEIN BACKBONES; MOLECULAR SHAPE; HYDRATION; BEHAVIOR; DYNAMICS; PATTERNS; KNOTS AB The molecular shape of a network can be characterized in detail by using information on its geometry and topology. In the case of permanent networks (e.g., those formed by a polymer melt), the structural complexity is usually measured in terms of entanglements within a chain and between chains. In this work, we show that this viewpoint can also be extended to the structural analysis of transient networks (e.g., those found in liquids with hydrogen bonding). For the hydrogen-bonded networks within clusters of simulated liquid water, we show the existence of power-law scaling in the averaged entanglement complexity as a function of cluster size. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Laurentian Univ, Dept Chim & Biochim, Sudbury, ON P3E 2C6, Canada. NCI, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. RP Laurentian Univ, Dept Chim & Biochim, Ramsey Lake Rd, Sudbury, ON P3E 2C6, Canada. EM gustavo@nickel.laurentian.ca NR 30 TC 5 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 EI 1873-4448 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD MAR 24 PY 2000 VL 319 IS 5-6 BP 719 EP 724 DI 10.1016/S0009-2614(00)00174-3 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 298CL UT WOS:000086121700045 ER PT J AU Jiang, RF Gao, BC Prasad, K Greene, LE Eisenberg, E AF Jiang, RF Gao, BC Prasad, K Greene, LE Eisenberg, E TI Hsc70 chaperones clathrin and primes it to interact with vesicle membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COATED VESICLES; UNCOATING ATPASE; ASSEMBLY PROTEIN; MEDIATED ENDOCYTOSIS; MOLECULAR CHAPERONE; NERVE-TERMINALS; RECEPTOR; ADAPTERS; AUXILIN; BASKETS AB When Hsc70 uncoats clathrin-coated vesicles in an auxilin- and ATP dependent reaction, a single round of rapid uncoating occurs followed by very slow steady-state uncoating. We now show that this biphasic time course occurs because Hsc70 sequentially forms two types of complex with the dissociated clathrin triskelions. The first round of clathrin uncoating is driven by formation of a pre steady-state assembly protein (AP)-clathrin-Hsc70-ADP complex. Then, following exchange of ADP with ATP, a steady-state AP-clathrin-Hsc70-ATP complex forms that ties up Hsc70, preventing further uncoating, This steady-state complex forms only during uncoating in the presence of APs; in the absence of APs, Hsc70 rapidly dissociates from the uncoated clathrin and continues to carry out uncoating, Whether it is complexed with ATP or ADP, the steady-state complex has very different properties from the pre-steady-state complex in that it cannot be immunoprecipitated by anti-clathrin antibodies and is readily dissociated by fast protein liquid chromatography. Remarkably, when the steady-state complex is incubated with uncoated vesicle membranes in ATP, the pre steady state complex reforms, suggesting that the clathrin triskelions in the steady-state complex rebind to the membranes and are again uncoated by Hsc70. We propose that Hsc70 not only uncoats clathrin but also chaperones it to prevent it from inappropriately polymerizing in the cell cytosol and primes it to reform clathrin coated pits. C1 NHLBI, Cell Biol Lab, Sect Cell Physiol, NIH, Bethesda, MD 20892 USA. RP Eisenberg, E (reprint author), NHLBI, Cell Biol Lab, Sect Cell Physiol, NIH, Bldg 10,Rm B1-22, Bethesda, MD 20892 USA. NR 44 TC 59 Z9 59 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 MAR 24 PY 2000 VL 275 IS 12 BP 8439 EP 8447 DI 10.1074/jbc.275.12.8439 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700028 PM 10722678 ER PT J AU Kim, JK Gavrilova, O Chen, Y Reitmann, ML Shulman, GI AF Kim, JK Gavrilova, O Chen, Y Reitmann, ML Shulman, GI TI Mechanism of insulin resistance in A-ZIP/F-1 fatless mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FREE FATTY-ACID; SKELETAL-MUSCLE; GLYCOGEN-SYNTHESIS; DIABETES-MELLITUS; GLUCOSE-UPTAKE; NIDDM; RATS; PATHOGENESIS; TRIGLYCERIDE; GLYCOLYSIS AB Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may be related to alterations in fat metabolism, Fatless mice have been created using dominant-negative protein (A-ZIP/F-1) targeted gene expression in the adipocyte and shown to develop diabetes. To understand the mechanism responsible for the insulin resistance in these mice, we conducted hyperinsulinemic-euglycemic clamps in awake fatless and wild type littermates before the development of diabetes and examined insulin action and signaling in muscle and liver, We found the fatless mice to be severely insulin-resistant, which could be attributed to defects in insulin action in muscle and liver. Both of these abnormalities were associated with defects in insulin activation of insulin receptor substrate-1 and -2-associated phosphatidylinositol S-kinase activity and a 2-fold increase in muscle and liver triglyceride content. We also show that upon transplantation of fat tissue into these mice, triglyceride content in muscle and liver returned to normal as does insulin signaling and action, In conclusion, these results suggest that the development of insulin resistance in type 2 diabetes may be due to alterations in the partitioning of fat between the adipocyte and muscle/liver leading to accumulation of triglyceride in the latter tissues with subsequent impairment of insulin signaling and action. C1 Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, New Haven, CT 06536 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06536 USA. NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. RP Shulman, GI (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, 295 Congress Ave,Box 9812,BCMM 254C, New Haven, CT 06536 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU NIDDK NIH HHS [R01 DK-40936, P30 DK-45735, R01 DK040936] NR 32 TC 264 Z9 272 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 24 PY 2000 VL 275 IS 12 BP 8456 EP 8460 DI 10.1074/jbc.275.12.8456 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700030 PM 10722680 ER PT J AU Choi, YC Park, GT Kim, TS Sunwoo, IN Steinert, PM Kim, SY AF Choi, YC Park, GT Kim, TS Sunwoo, IN Steinert, PM Kim, SY TI Sporadic inclusion body myositis correlates with increased expression and cross-linking by transglutaminases 1 and 2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-AMYLOID PROTEIN; HUMAN NEUROMUSCULAR-JUNCTIONS; HUMAN EPIDERMAL-KERATINOCYTES; CORNIFIED CELL-ENVELOPE; TISSUE TRANSGLUTAMINASE; ALZHEIMERS-DISEASE; PEPTIDE; MUSCLE; ENZYME; IDENTIFICATION AB Sporadic inclusion body myositis (SIBM) is characterized by vacuolar degeneration of muscle fibers and intrafiber clusters of paired helical filaments with abnormal amyloid deposition. Because of their potential involvement in other degenerative disorders, we have examined the expression of transglutaminases (TGases) in normal and SIBM tissues. We report that at least two different enzymes, the ubiquitous TGase 2 as well as the TGase 1 enzyme, are present in muscle tissues. However, in comparison with normal tissue, the expression of TGases 1 and 2 was increased 2.5- and 4-fold in SIBM, accompanied by about a 20-fold higher total TGase activity. By immunohistochemical staining, in normal muscle, TGase 2 expression was restricted to some endomysial connective tissue elements, whereas TGase 1 and beta-amyloid proteins were not detectable. In SIBM muscle, both TGases 1 and 2 as well as amyloid proteins were brightly expressed and co-localized in the vacuolated muscle fibers, but none of these proteins colocalized with inflammatory cell markers. Next, we isolated high molecular weight insoluble proteins from SIBM muscle tissue and showed that they were cross-linked by about 6 residues/1000 residues of the isopeptide bond. Furthermore, by amino acid sequencing of solubilized tryptic peptides, they contain amyloid and skeletal muscle proteins, Together, these findings suggest that elevated expression of TGases 1 and 2 participate in the formation of insoluble amyloid deposits in SIBM tissue and in this way may contribute to progressive and debilitating muscle disease. C1 Yonsei Univ, Coll Med, Dept Pathol, Seoul 135270, South Korea. NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Neurol, Seoul 135270, South Korea. RP Choi, YC (reprint author), Yonsei Univ, Yongdong Severance Hosp, Coll Med, Dept Neurol, Seoul 135270, South Korea. NR 58 TC 46 Z9 46 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 MAR 24 PY 2000 VL 275 IS 12 BP 8703 EP 8710 DI 10.1074/jbc.275.12.8703 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700062 PM 10722712 ER PT J AU Topol, LZ Bardot, B Zhang, QY Resau, J Huillard, E Marx, M Calothy, G Blair, DG AF Topol, LZ Bardot, B Zhang, QY Resau, J Huillard, E Marx, M Calothy, G Blair, DG TI Biosynthesis, post-translation modification, and functional characterization of Drm/Gremlin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE MORPHOGENETIC PROTEINS; GROWTH-FACTOR; SPEMANN ORGANIZER; IDENTIFICATION; FIBROBLASTS; EXPRESSION; RECEPTORS; CERBERUS; CLEAVAGE; CLONING AB Down-regulated by mos (Drm)/Gremlin is a highly conserved protein whose properties and expression pattern suggest a role in early development, tissue-specific differentiation, and cell transformation. We have investigated the biosynthesis and processing of Drm expressed endogenously in rat fibroblasts or overexpressed following transient or stable transfection. Analysis of metabolically labeled cells revealed that Drm exists in secreted and cell-associated forms that exhibit similar mobilities in SDS-polyacrylamide gel electrophoresis. Protein analysis indicated that Drm is present in two major species: a slow migrating glycosylated form and a nonglycosylated form. Both forms of Drm are able to undergo phosphorylation. Drm is released into the media within 30 min of synthesis and is detectable for up to 4-5 h, whereas the cell-associated form has a half-life of about 1 h, Confocal immunofluorescent microscopy indicates that Drm is present both on the external surface of expressing cells, as well as within the endoplasmic reticulum and the Golgi. Both glycosylated and nonglycosylated forms of Drm exhibit identical distributions and are able to antagonize bone morphogenetic protein signaling. Like the soluble form, the cell-associated forms are capable of binding I-125-bone morphogenetic protein-4. These properties are consistent with a role for Drm in interfering with signaling and indicate that Drm may act at the cell surface during tissue development and transformation. C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA. Ctr Univ Orsay, Inst Curie, CNRS, UMR 146, F-91405 Orsay, France. NCI, Frederick Canc Res & Dev Ctr, Adv BioSci Labs Inc, Basic Res Program, Frederick, MD 21702 USA. RP Blair, DG (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 36 TC 88 Z9 91 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 MAR 24 PY 2000 VL 275 IS 12 BP 8785 EP 8793 DI 10.1074/jbc.275.12.8785 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700073 PM 10722723 ER PT J AU Yahata, T de Caestecker, MP Lechleider, RJ Andriole, S Roberts, AB Isselbacher, KJ Shioda, T AF Yahata, T de Caestecker, MP Lechleider, RJ Andriole, S Roberts, AB Isselbacher, KJ Shioda, T TI The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MELANOCYTE-SPECIFIC GENE; B-CELL COACTIVATOR; MOLECULAR-CLONING; TUMOR-SUPPRESSOR; NUCLEAR-PROTEIN; ACTIVATION; PROMOTER; DOMAIN; SMAD4/DPC4; EXPRESSION AB The MSG1 nuclear protein has a strong transcriptional activating activity but does not bind directly to DNA, When cotransfected, MSG1 enhances transcription mediated by the Smad transcription factors in mammalian cells in a manner dependent on ligand-induced Smad hetero-oligomerization. However, the mechanism of this MSG1 effect has been unknown. We now show that MSG1 directly binds to the p300/cAMP-response element-binding protein-binding protein (CBP) transcriptional coactivators, which in turn bind to the Smads, and enhances Smad-mediated transcription in a manner dependent on p300/CBP, The C-terminal transactivating domain of MSG1 is required for binding to p300/CBP and enhancement of Smad-mediated transcription; the viral VP16 transactivating domain could not substitute for it. In the N-terminal region of MSG1, we identified a domain that is necessary and sufficient to direct the specific interaction of MSG1 with Smads, We also found that the Hsc70 heat-shock cognate protein also forms complex with MSG1 in vivo suppressing both binding of MSG1 to p300/CBP and enhancement of Smad-mediated transcription by MSG1, These results indicate that MSG1 interacts with both the DNA-binding Smad proteins and the p300/CBP coactivators through its N- and C-terminal regions, respectively, and enhances the functional link between Smads and p300/CBP. C1 Massachusetts Gen Hosp E, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Shioda, T (reprint author), Ctr Canc, Lab Tumor Biol, Bldg 149,7th Floor,13th St, Charlestown, MA 02129 USA. EM shioda@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA82230] NR 50 TC 85 Z9 97 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 MAR 24 PY 2000 VL 275 IS 12 BP 8825 EP 8834 DI 10.1074/jbc.275.12.8825 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700078 PM 10722728 ER PT J AU Fang, SY Jensen, JP Ludwig, RL Vousden, KH Weissman, AM AF Fang, SY Jensen, JP Ludwig, RL Vousden, KH Weissman, AM TI Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR P53; DNA-DAMAGE; IN-VITRO; DOMAIN; DEGRADATION; BINDING; PATHWAY; PHOSPHORYLATION; IDENTIFICATION; PROTEASOME AB Mdm2 has been shown to regulate p53 stability by targeting the p53 protein for proteasomal degradation. We now report that Mdm2 is a ubiquitin protein ligase (E3) for p53 and that its activity is dependent on its RING finger. Furthermore, we show that Mdma mediates its own ubiquitination in a RING finger-dependent manner, which requires no eukaryotic proteins other than ubiquitin-activating enzyme (El) and an ubiquitin-conjugating enzyme (E2). It is apparent, therefore, that Mdma manifests an intrinsic capacity to mediate ubiquitination, Mutation of putative zinc coordination residues abrogated this activity, as did chelation of divalent cations. After cation chelation, the full activity could be restored by addition of zinc. We further demonstrate that the degradation of p53 and Mdma in cells requires additional potential zinc coordinating residues beyond those required for the intrinsic activity of Mdm2 in vitro. Replacement of the Mdm2 RING with that of another protein (Praja1) reconstituted ubiquitination and proteasomal degradation of Mdma. However, this RING was ineffective in ubiquitination and proteasomal targeting of p53, suggesting that there may be specificity at the level of the RING in the recognition of heterologous substrates. C1 NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Weissman, AM (reprint author), NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bldg 10,Rm 1B34,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Fang, Shengyun/H-3802-2011 NR 74 TC 691 Z9 710 U1 8 U2 41 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 MAR 24 PY 2000 VL 275 IS 12 BP 8945 EP 8951 DI 10.1074/jbc.275.12.8945 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700092 PM 10722742 ER PT J AU Adams, MD Celniker, SE Holt, RA Evans, CA Gocayne, JD Amanatides, PG Scherer, SE Li, PW Hoskins, RA Galle, RF George, RA Lewis, SE Richards, S Ashburner, M Henderson, SN Sutton, GG Wortman, JR Yandell, MD Zhang, Q Chen, LX Brandon, RC Rogers, YHC Blazej, RG Champe, M Pfeiffer, BD Wan, KH Doyle, C Baxter, EG Helt, G Nelson, CR Miklos, GLG Abril, JF Agbayani, A An, HJ Andrews-Pfannkoch, C Baldwin, D Ballew, RM Basu, A Baxendale, J Bayraktaroglu, L Beasley, EM Beeson, KY Benos, PV Berman, BP Bhandari, D Bolshakov, S Borkova, D Botchan, MR Bouck, J Brokstein, P Brottier, P Burtis, KC Busam, DA Butler, H Cadieu, E Center, A Chandra, I Cherry, JM Cawley, S Dahlke, C Davenport, LB Davies, A de Pablos, B Delcher, A Deng, ZM Mays, AD Dew, I Dietz, SM Dodson, K Doup, LE Downes, M Dugan-Rocha, S Dunkov, BC Dunn, P Durbin, KJ Evangelista, CC Ferraz, C Ferriera, S Fleischmann, W Fosler, C Gabrielian, AE Garg, NS Gelbart, WM Glasser, K Glodek, A Gong, FC Gorrell, JH Gu, ZP Guan, P Harris, M Harris, NL Harvey, D Heiman, TJ Hernandez, JR Houck, J Hostin, D Houston, DA Howland, TJ Wei, MH Ibegwam, C Jalali, M Kalush, F Karpen, GH Ke, ZX Kennison, JA Ketchum, KA Kimmel, BE Kodira, CD Kraft, C Kravitz, S Kulp, D Lai, ZW Lasko, P Lei, YD Levitsky, AA Li, JY Li, ZY Liang, Y Lin, XY Liu, XJ Mattei, B McIntosh, TC McLeod, MP McPherson, D Merkulov, G Milshina, NV Mobarry, C Morris, J Moshrefi, A Mount, SM Moy, M Murphy, B Murphy, L Muzny, DM Nelson, DL Nelson, DR Nelson, KA Nixon, K Nusskern, DR Pacleb, JM Palazzolo, M Pittman, GS Pan, S Pollard, J Puri, V Reese, MG Reinert, K Remington, K Saunders, RDC Scheeler, F Shen, H Shue, BC Siden-Kiamos, I Simpson, M Skupski, MP Smith, T Spier, E Spradling, AC Stapleton, M Strong, R Sun, E Svirskas, R Tector, C Turner, R Venter, E Wang, AHH Wang, X Wang, ZY Wassarman, DA Weinstock, GM Weissenbach, J Williams, SM Woodage, T Worley, KC Wu, D Yang, S Yao, QA Ye, J Yeh, RF Zaveri, JS Zhan, M Zhang, GG Zhao, Q Zheng, LS Zheng, XQH Zhong, FN Zhong, WY Zhou, XJ Zhu, SP Zhu, XH Smith, HO Gibbs, RA Myers, EW Rubin, GM Venter, JC AF Adams, MD Celniker, SE Holt, RA Evans, CA Gocayne, JD Amanatides, PG Scherer, SE Li, PW Hoskins, RA Galle, RF George, RA Lewis, SE Richards, S Ashburner, M Henderson, SN Sutton, GG Wortman, JR Yandell, MD Zhang, Q Chen, LX Brandon, RC Rogers, YHC Blazej, RG Champe, M Pfeiffer, BD Wan, KH Doyle, C Baxter, EG Helt, G Nelson, CR Miklos, GLG Abril, JF Agbayani, A An, HJ Andrews-Pfannkoch, C Baldwin, D Ballew, RM Basu, A Baxendale, J Bayraktaroglu, L Beasley, EM Beeson, KY Benos, PV Berman, BP Bhandari, D Bolshakov, S Borkova, D Botchan, MR Bouck, J Brokstein, P Brottier, P Burtis, KC Busam, DA Butler, H Cadieu, E Center, A Chandra, I Cherry, JM Cawley, S Dahlke, C Davenport, LB Davies, A de Pablos, B Delcher, A Deng, ZM Mays, AD Dew, I Dietz, SM Dodson, K Doup, LE Downes, M Dugan-Rocha, S Dunkov, BC Dunn, P Durbin, KJ Evangelista, CC Ferraz, C Ferriera, S Fleischmann, W Fosler, C Gabrielian, AE Garg, NS Gelbart, WM Glasser, K Glodek, A Gong, FC Gorrell, JH Gu, ZP Guan, P Harris, M Harris, NL Harvey, D Heiman, TJ Hernandez, JR Houck, J Hostin, D Houston, DA Howland, TJ Wei, MH Ibegwam, C Jalali, M Kalush, F Karpen, GH Ke, ZX Kennison, JA Ketchum, KA Kimmel, BE Kodira, CD Kraft, C Kravitz, S Kulp, D Lai, ZW Lasko, P Lei, YD Levitsky, AA Li, JY Li, ZY Liang, Y Lin, XY Liu, XJ Mattei, B McIntosh, TC McLeod, MP McPherson, D Merkulov, G Milshina, NV Mobarry, C Morris, J Moshrefi, A Mount, SM Moy, M Murphy, B Murphy, L Muzny, DM Nelson, DL Nelson, DR Nelson, KA Nixon, K Nusskern, DR Pacleb, JM Palazzolo, M Pittman, GS Pan, S Pollard, J Puri, V Reese, MG Reinert, K Remington, K Saunders, RDC Scheeler, F Shen, H Shue, BC Siden-Kiamos, I Simpson, M Skupski, MP Smith, T Spier, E Spradling, AC Stapleton, M Strong, R Sun, E Svirskas, R Tector, C Turner, R Venter, E Wang, AHH Wang, X Wang, ZY Wassarman, DA Weinstock, GM Weissenbach, J Williams, SM Woodage, T Worley, KC Wu, D Yang, S Yao, QA Ye, J Yeh, RF Zaveri, JS Zhan, M Zhang, GG Zhao, Q Zheng, LS Zheng, XQH Zhong, FN Zhong, WY Zhou, XJ Zhu, SP Zhu, XH Smith, HO Gibbs, RA Myers, EW Rubin, GM Venter, JC TI The genome sequence of Drosophila melanogaster SO SCIENCE LA English DT Review ID DNA-REPLICATION; CHROMOSOME DYNAMICS; GENE-EXPRESSION; HETEROCHROMATIN; PROTEINS; FAMILY; PREDICTION; CHROMATIN AB The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the similar to 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and Contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes similar to 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity. C1 Celera Genom, Rockville, MD 20850 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, BDGP, Berkeley, CA 94720 USA. Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA. Univ Calif Berkeley, Dept Cell & Mol Biol, BDGP, Berkeley, CA 94720 USA. European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England. Neomorph Inc, Berkeley, CA 94710 USA. Genetixxpress Pty Ltd, Sydney, NSW 2108, Australia. IMIM UPF, Dept Med Informat, Barcelona 08003, Spain. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. FORTH, Inst Mol Biol & Biotechnol, Iraklion, Greece. EMBL, EDGP, Heidelberg, Germany. Univ Calif Berkeley, Dept Cell & Mol Biol, Berkeley, CA 94710 USA. Genoscope, F-91000 Evry, France. Univ Calif Davis, Sect Mol & Cellular Biol, Davis, CA 95618 USA. Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. Univ Rennes 2, Fac Med, Sch Med, EDGP,CNRS,UPR 41, F-35043 Rennes, France. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, EDGP, E-28049 Madrid, Spain. Salk Inst Biol Studies, Mol Biol & Virol Lab, La Jolla, CA 92037 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85721 USA. Univ Arizona, Ctr Insect Sci, Tucson, AZ 85721 USA. Univ Montpellier, Sch Med, EDGP, Inst Genet Humaine,CNRS,CRBM, F-34396 Montpellier 5, France. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. Inst Genom Res, Rockville, MD 20850 USA. Sanger Ctr, EDGP, Cambridge CB10 1SA, England. Univ Tennessee, Dept Biochem, Memphis, TN 38163 USA. Univ Dundee, Dept Anat & Physiol, EDGP, Dundee DD1 4HN, Scotland. Open Univ, Dept Biol Sci, Milton Keynes MK7 6AA, Bucks, England. Carnegie Inst Sci, HHM Embryol, Baltimore, MD 21210 USA. Motorola Biochip Syst, Tempe, AZ 85284 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Howard Hughes Med Inst, BDGP, Berkeley, CA 94720 USA. RP Celera Genom, 45 W Gude Dr, Rockville, MD 20850 USA. RI Holt, Robert/C-3303-2009; Abril Ferrando, Josep/B-3877-2014; Lasko, Paul/C-6761-2014; Berman, Benjamin/D-5942-2014; Marion-Poll, Frederic/D-8882-2011; OI Abril Ferrando, Josep/0000-0001-7793-589X; Lasko, Paul/0000-0002-4037-3501; Marion-Poll, Frederic/0000-0001-6824-0180; Deslattes Mays, Anne/0000-0001-7951-3439; Burtis, Kenneth/0000-0002-9644-3265; Lewis, Suzanna/0000-0002-8343-612X; Rubin, Gerald/0000-0001-8762-8703 FU Howard Hughes Medical Institute; NHGRI NIH HHS [P50-HG00750, U54 HG003273] NR 82 TC 3777 Z9 7203 U1 58 U2 547 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 24 PY 2000 VL 287 IS 5461 BP 2185 EP 2195 DI 10.1126/science.287.5461.2185 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296WE UT WOS:000086049100033 PM 10731132 ER PT J AU Rubin, GM Yandell, MD Wortman, JR Miklos, GLG Nelson, CR Hariharan, IK Fortini, ME Li, PW Apweiler, R Fleischmann, W Cherry, JM Henikoff, S Skupski, MP Misra, S Ashburner, M Birney, E Boguski, MS Brody, T Brokstein, P Celniker, SE Chervitz, SA Coates, D Cravchik, A Gabrielian, A Galle, RF Gelbart, WM George, RA Goldstein, LSB Gong, FC Guan, P Harris, NL Hay, BA Hoskins, RA Li, JY Li, ZY Hynes, RO Jones, SJM Kuehl, PM Lemaitre, B Littleton, JT Morrison, DK Mungall, C O'Farrell, PH Pickeral, OK Shue, C Vosshall, LB Zhang, J Zhao, Q Zheng, XQH Zhong, F Zhong, WY Gibbs, R Venter, JC Adams, MD Lewis, S AF Rubin, GM Yandell, MD Wortman, JR Miklos, GLG Nelson, CR Hariharan, IK Fortini, ME Li, PW Apweiler, R Fleischmann, W Cherry, JM Henikoff, S Skupski, MP Misra, S Ashburner, M Birney, E Boguski, MS Brody, T Brokstein, P Celniker, SE Chervitz, SA Coates, D Cravchik, A Gabrielian, A Galle, RF Gelbart, WM George, RA Goldstein, LSB Gong, FC Guan, P Harris, NL Hay, BA Hoskins, RA Li, JY Li, ZY Hynes, RO Jones, SJM Kuehl, PM Lemaitre, B Littleton, JT Morrison, DK Mungall, C O'Farrell, PH Pickeral, OK Shue, C Vosshall, LB Zhang, J Zhao, Q Zheng, XQH Zhong, F Zhong, WY Gibbs, R Venter, JC Adams, MD Lewis, S TI Comparative genomics of the eukaryotes SO SCIENCE LA English DT Review ID DROSOPHILA-MELANOGASTER; INNATE IMMUNITY; CAENORHABDITIS-ELEGANS; MOLECULAR-CLONING; RECEPTOR FAMILY; CYTOCHROME-C; PROTEIN; GENE; BINDING; GASTRULATION AB A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease. C1 Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley Drosophila Genome Project, Berkeley, CA 94720 USA. Celera Genom, Rockville, MD 20850 USA. Genetixxpress, Sydney, NSW 2108, Australia. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. EMBL, EBI, Cambridge CB10 1SD, England. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98109 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NINDS, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley Drosophila Genome Project, Berkeley, CA 94720 USA. Neomorphic, Berkeley, CA 94710 USA. Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Pharmacol, La Jolla, CA 92093 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. BC Canc Res Ctr, Genome Sequence Ctr, Vancouver, BC V52 4E6, Canada. Univ Maryland, Cell & Mol Biol Program, Baltimore, MD 21201 USA. CNRS, Ctr Genet Mol, F-91198 Gif Sur Yvette, France. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. NCI, Regulat Cell Growth Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Ft Detrick, MD 21702 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Rubin, GM (reprint author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. RI Jones, Steven/C-3621-2009; OI Lewis, Suzanna/0000-0002-8343-612X; O'Farrell, Patrick/0000-0003-0011-2734; Rubin, Gerald/0000-0001-8762-8703 FU NHGRI NIH HHS [P4IHG00739, P50HG00750]; NIGMS NIH HHS [R01 GM037193, R01 GM037193-14, R01 GM037193-15, R01 GM060988, R01 GM060988-01]; NINDS NIH HHS [R01 NS040296, R01 NS040296-01] NR 84 TC 1120 Z9 1153 U1 9 U2 106 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 24 PY 2000 VL 287 IS 5461 BP 2204 EP 2215 DI 10.1126/science.287.5461.2204 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296WE UT WOS:000086049100035 PM 10731134 ER PT J AU Stevens, B Fields, RD AF Stevens, B Fields, RD TI Response of Schwann cells to action potentials in development SO SCIENCE LA English DT Article ID INCREASES INTRACELLULAR CALCIUM; PERIPHERAL NERVOUS-SYSTEM; DIFFERENTIAL REGULATION; NEUROMUSCULAR-JUNCTION; DEPENDENT REGULATION; MYELINATION; PATTERNS; L1; MECHANISMS; ACTIVATION AB Sensory axons become functional late in development when Schwann cells (SC) stop proliferating and differentiate into distinct phenotypes, We report that impulse activity in premyelinated axons can inhibit proliferation and differentiation of SCs. This neuron-glial signaling is mediated by adenosine triphosphate acting through PZ receptors on SCs and intracellular signaling pathways involving Ca(2+), Ca(2+)/calmodulin kinase, mitogen-activated protein kinase, cyclic adenosine 3',5'-monophosphate response element binding protein, and expression of c-fos and Krox-24. Adenosine triphosphate arrests maturation of SCs in an immature morphological stage and prevents expression of O4, myelin basic protein, and the formation of myelin. Through;this mechanism, functional activity in the developing nervous system could delay terminal differentiation of SCs until exposure to appropriate axon-derived signals. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38,49 Convent Dr, Bethesda, MD 20892 USA. EM fields@helix.nih.gov NR 32 TC 170 Z9 172 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 24 PY 2000 VL 287 IS 5461 BP 2267 EP 2271 DI 10.1126/science.287.5461.2267 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296WE UT WOS:000086049100052 PM 10731149 ER PT J AU Faure, S Meyer, L Costagliola, D Vaneensberghe, C Genin, E Autran, B Delfraissy, JF McDermott, DH Murphy, PM Debre, P Theodorou, I Combadiere, C AF Faure, S Meyer, L Costagliola, D Vaneensberghe, C Genin, E Autran, B Delfraissy, JF McDermott, DH Murphy, PM Debre, P Theodorou, I Combadiere, C CA French ALT IMMUNOCO Study Grp SEROCO Study Grp TI Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX(3)CR1 SO SCIENCE LA English DT Article ID DISEASE PROGRESSION; GENETIC RESTRICTION; INFECTION; CCR5; FRACTALKINE; IDENTIFICATION; PATHOGENESIS; TRANSMISSION; RESISTANCE; MICROGLIA AB Human immunodeficiency virus (HIV) enters cells in vitro via CD4 and a coreceptor. Which of 15 known coreceptors are important in vivo is poorly defined but may be inferred from disease-modifying mutations, as for CCR5, Here two single nucleotide polymorphisms are described in Caucasians in CX(3)CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine. HIV-infected patients homozygous for CX(3)CR1-1249 M280, a variant haplotype affecting two amino acids (isoleucine-249 and methionine-280), progressed to AIDS more rapidly than those with other haplotypes. Functional CX(3)CR1 analysis showed that fractalkine binding is reduced among patients homozygous for this particular haplotype. Thus, CX(3)CR1-1249 M280 is a recessive genetic risk factor in HIV/AIDS. C1 Hop La Pitie Salpetriere, Lab Immunol Cellulaire & Tissulaire, CNRS, UMR 7627, Paris, France. Hop Bicetre, Fac Med, Dept Epidemiol, INSERM,U292, Le Kremlin Bicetre, France. Fac Med St Antoine, INSERM SC4, Paris, France. Hop Bicetre, INSERM, U155, Le Kremlin Bicetre, France. Hop Bicetre, Serv Med Interne, Le Kremlin Bicetre, France. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. CHU Bichat, INSERM, U479, Paris, France. RP Theodorou, I (reprint author), Hop La Pitie Salpetriere, Lab Immunol Cellulaire & Tissulaire, CNRS, UMR 7627, Paris, France. EM ioannis.theodorou@psl.ap-hop-paris.fr RI Genin, Emmanuelle/C-4974-2013; Combadiere, Christophe/I-5639-2013; Costagliola, Dominique/H-5849-2011; OI Genin, Emmanuelle/0000-0003-4117-2813; Combadiere, Christophe/0000-0002-1755-4531; Costagliola, Dominique/0000-0003-0765-0869; McDermott, David/0000-0001-6978-0867 NR 33 TC 226 Z9 236 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 24 PY 2000 VL 287 IS 5461 BP 2274 EP 2277 DI 10.1126/science.287.5461.2274 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296WE UT WOS:000086049100054 PM 10731151 ER PT J AU Delon, J AF Delon, J TI Quick guide - The immunological synapse SO CURRENT BIOLOGY LA English DT Editorial Material ID T-CELL ACTIVATION C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Delon, J (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 9 Z9 10 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 23 PY 2000 VL 10 IS 6 BP R214 EP R214 DI 10.1016/S0960-9822(00)00392-4 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348GV UT WOS:000088977900003 PM 10744986 ER PT J AU Singh, SB Malamas, MS Hohman, TC Nilakantan, R Carper, DA Kitchen, D AF Singh, SB Malamas, MS Hohman, TC Nilakantan, R Carper, DA Kitchen, D TI Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING SITE; SIMULATION AB Aldose reductase (AR) has been implicated in the etiology of the secondary complications of diabetes. This enzyme catalyzes the reduction of glucose to sorbitol using nicotinamide adenine dinucleotide phosphate as an essential cofactor. AR has been localized at the sites of tissue damage, and inhibitors of this enzyme prevent the development of neuropathy, nephropathy, retinopathy, and cataract formation in animal models of diabetes. The crystal structure of AR complexed with zopolrestat, a potent inhibitor of AR, has been described.(1) We have generated a model of the AR-inhibitor complex based on the reported C alpha coordinates of the protein and results of a structure-activity relationship study using four structurally distinct classes of inhibitors, recombinant human AR, and four single-site-directed mutants of this enzyme. The effects of the site-directed mutations on residues within the act ive site of the enzyme were evaluated by average interaction energy calculations and by calculations of carbon atom surface area changes. These values correlated well with the IC50 values for zopolrestat with the wildtype and mutant enzymes, validating the model. On the basis of the zopolrestat-binding model, we have proposed binding models for 10 other AR inhibitors. Our models have enabled us to gain a qualitative understanding of the binding domains of the enzyme and how different inhibitors impact the size and shape of the binding site. C1 Wyeth Ayerst Res, CN 8000, Princeton, NJ 08543 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Singh, SB (reprint author), Merck Res Labs, RY50SW100,POB 2000, Rahway, NJ 07065 USA. OI Kitchen, Douglas/0000-0001-8988-759X NR 14 TC 24 Z9 25 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 MAR 23 PY 2000 VL 43 IS 6 BP 1062 EP 1070 DI 10.1021/jm990168z PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 296ZD UT WOS:000086055900004 PM 10737739 ER PT J AU Robarge, MJ Agoston, GE Izenwasser, S Kopajtic, T George, C Katz, JL Newman, AH AF Robarge, MJ Agoston, GE Izenwasser, S Kopajtic, T George, C Katz, JL Newman, AH TI Highly selective chiral N-substituted 3 alpha-[bis(4 '-fluorophenyl)methoxy]tropane analogues for the dopamine transporter: Synthesis and comparative molecular field analysis SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID LIGAND-BINDING DOMAINS; ACID METHYL-ESTERS; MONOAMINE TRANSPORTERS; UPTAKE INHIBITORS; COCAINE BINDING; CLONING; POTENT; COMFA; EXPRESSION; QSAR AB In a continuing effort to further characterize the role of the dopamine transporter in the pharmacological effects of cocaine, a series of chiral and achiral N-substituted analogues of 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane (5) has been prepared as potential selective dopamine transporter ligands. These novel compounds displaced [H-3]WIN 35,428 binding from the dopamine transporter in rat caudate putamen with K-i values ranging from 13.9 to 477 nM. Previously, it was reported that 5 demonstrated a significantly higher affinity for the dopamine transporter than the parent drug, 3 alpha-(diphenylmethoxy)tropane (3; benztropine). However, 5 remained nonselective over muscarinic mi receptors (dopamine transporter, K-i = 11.8 nM; m(1), K-i = 11.6 nM) which could potentially confound the interpretation of behavioral data, for this compound and other members of this series. Thus, significant effort has been directed toward developing analogues that retain high affinity at the dopamine transporter but have decreased affinity at muscarinic sites. Recently, it was discovered that by replacing the N-methyl group of 5 with the phenyl-n-butyl substituent (6) retention of high binding affinity at the dopamine transporter (K-i = 8.51 nM) while decreasing affinity at muscarinic receptors (K-i = 576 nM) was achieved, resulting in 68-fold selectivity. In the present series, a further improvement in the selectivity for the dopamine transporter was accomplished, with the chiral analogue (S)N-(2-amino-3-methyl-n-butyl)-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane(10b) showing a 136-fold selectivity for the dopamine transporter versus muscarinic mi receptors (K-i = 29.5 nM versus K-i = 4020 nM, respectively). In addition, a comparative molecular field analysis (CoMFA) model was derived to correlate the binding affinities of all the N-substituted 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues that we have prepared with their 3D-structural features. The best model (q(2) = 0.746) was used to accurately predict binding affinities of compounds in the training set and in a test set. The CoMFA coefficient contour plot for this model, which provides a visual representation of the chemical environment of the binding domain of the dopamine transporter, can now be used to design and/or predict the binding affinities of novel drugs within this class of dopamine uptake inhibitors. C1 NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Izenwasser, Sari/G-9193-2012 FU NIDA NIH HHS [DA09045] NR 42 TC 38 Z9 38 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 MAR 23 PY 2000 VL 43 IS 6 BP 1085 EP 1093 DI 10.1021/jm990265s PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 296ZD UT WOS:000086055900006 PM 10737741 ER PT J AU Kim, YC Ji, XD Melman, N Linden, J Jacobson, KA AF Kim, YC Ji, XD Melman, N Linden, J Jacobson, KA TI Anilide derivatives of an 8-phenylxanthine carboxylic congener are highly potent and selective antagonists at human A(2B) adenosine receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RAT-BRAIN; FUNCTIONALIZED CONGENERS; A(3) RECEPTOR; HIGH-AFFINITY; THEOPHYLLINE; EFFICIENT; AGONISTS; CLONING; BINDING; ANALOGS AB No highly selective antagonists of the A(2B) adenosine receptor (AR) have been reported; however such antagonists have therapeutic potential as antiasthmatic agents. Here we report the synthesis of potent and selective A(2B) receptor antagonists. The structure-activity relationships (SAR) of 8-phenyl-1,3-di-(n-propyl)xanthine derivatives in binding to recombinant human A(2B) ARs in HEK-293 cells (HEK-A(2B)) and at other AR subtypes were explored. Various amide derivatives of 8-[4-[[carboxymethyl]oxy]phenyl]-1,3-di-(n-propyl)xanthine, 4a, were synthesized. A comparison of aryl, alkyl, and aralkyl amides demonstrated that simple anilides, particularly those substituted in the para-position with electron-withdrawing groups, such as nitro, cyano, and acetyl, bind selectively to human A(2B) receptors in the range of 1-3 nM. The unsubstituted anilide 12 had a K-i value at A(2B) receptors of 1.48 nM but was only moderately selective versus human A(1)/A(2A) receptors and nonselective versus rat A(1) receptors. Highly potent and selective A(2B) antagonists were a p-aminoacetophenone derivative 20 (K-i value 1.39 nM) and a p-cyanoanilide 27 (K-i value 1.97 nM). Compound 27 was 400-, 245-, and 123-fold selective for human A(2B) receptors versus human A(1)/A(2A)/A(3) receptors, respectively, and 8.5- and 310-fold selective versus rat A(1)/A(2A) receptors, respectively. Substitution of the 1,3-dipropyl groups with 1,3-diethyl offered no disadvantage for selectivity, and high affinities at A(2B) receptors were maintained. Substitution of the p-carboxymethyloxy group of 4a and its amides with acrylic acid decreased affinity at A(2B) receptors while increasing affinity at A(1) receptors. 1,3-Di(cyclohexylmethyl) groups greatly reduced affinity at ARs, although the p-carboxymethyloxy derivative 9 was moderately selective for A(2B) receptors. Several selective A(2B) antagonists inhibited NECA-stimulated calcium mobilization in HEK-A(2B) cells. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Internal Med & Mol Physiol & Biol Phys, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Jacobson, KA (reprint author), NIDDK, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NHLBI NIH HHS [HL37942, HL56111] NR 42 TC 148 Z9 152 U1 0 U2 2 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 MAR 23 PY 2000 VL 43 IS 6 BP 1165 EP 1172 DI 10.1021/jm990421v PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 296ZD UT WOS:000086055900014 PM 10737749 ER PT J AU El-Omar, EM Carrington, M Chow, WH McColl, KEL Bream, JH Young, HA Herrera, J Lissowska, J Yuan, CC Rothman, N Lanyon, G Martin, M Fraumeni, JF Rabkin, CS AF El-Omar, EM Carrington, M Chow, WH McColl, KEL Bream, JH Young, HA Herrera, J Lissowska, J Yuan, CC Rothman, N Lanyon, G Martin, M Fraumeni, JF Rabkin, CS TI Interleukin-1 polymorphisms associated with increased risk of gastric cancer SO NATURE LA English DT Article ID HELICOBACTER-PYLORI INFECTION; NECROSIS-FACTOR-ALPHA; DUODENAL-ULCER DISEASE; ACID-SECRETION; RECEPTOR; CELLS; PATHWAYS AB Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease(1). The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion(2), whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy(3), which are presumptive precursors of gastric cancer(4). Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are hi near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine(5) and a powerful inhibitor of gastric acid secretion(6,7). Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Aberdeen, Dept Med & Therapeut, Aberdeen, Scotland. NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. Univ Glasgow, Western Infirm, Dept Med & Therapeut, Glasgow G11 6NT, Lanark, Scotland. NCI, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. RP El-Omar, EM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. OI Lissowska, Jolanta/0000-0003-2695-5799 NR 30 TC 1489 Z9 1584 U1 7 U2 62 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 23 PY 2000 VL 404 IS 6776 BP 398 EP 402 DI 10.1038/35006081 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 298BG UT WOS:000086119000053 PM 10746728 ER PT J AU Sun, ZM Arendt, CW Ellmeier, W Schaeffer, EM Sunshine, MJ Gandhi, L Annes, J Petrzilka, D Kupfer, A Schwartzberg, PL Littman, DR AF Sun, ZM Arendt, CW Ellmeier, W Schaeffer, EM Sunshine, MJ Gandhi, L Annes, J Petrzilka, D Kupfer, A Schwartzberg, PL Littman, DR TI PKC-theta is required for TCR-induced NF-kappa B activation in mature but not immature T lymphocytes SO NATURE LA English DT Article ID PROTEIN-KINASE-C; CELL ACTIVATION; SIGNAL-TRANSDUCTION; TRANSGENIC MICE; IL-2 PROMOTER; RECEPTOR; INTERLEUKIN-2; VAV; THYMOCYTES; EPSILON AB Productive interaction of a T lymphocyte with an antigen-presenting cell results in the clustering of the T-cell antigen receptor (TCR) and the recruitment of a large signalling complex to the site of cell-cell contact(1,2). Subsequent signal transduction resulting in cytokine gene expression requires the activation of one or more of the multiple isoenzymes of serine/threonine-specific protein kinase C (PKC)(3). Among the several PKC isoenzymes expressed in T cells, PKC-theta is unique in being rapidly recruited to the site of TCR clustering(4). Here we show that PKC-theta is essential for TCR-mediated T-cell activation, but is dispensable during TCR-dependent thymocyte development. TCR-initiated NF-kappa B activation was absent from PKC-theta(-/-) mature T lymphocytes, but was intact in thymocytes. Activation of NF-kappa B by tumour-necrosis factor alpha and interleukin-1 was unaffected in the mutant mice. Although studies in T-cell lines had suggested that PKC-B regulates activation of the JNK signalling pathway(5,6), induction of JNK was normal in T cells from mutant mice. These results indicate that PKC-theta functions in a unique pathway that links the TCR signalling, complex to the activation of NF-kappa B in mature T lymphocytes. C1 NYU, Sch Med, Mol Pathogenesis Program, Sjirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, Denver, CO 80262 USA. RP Littman, DR (reprint author), NYU, Sch Med, Mol Pathogenesis Program, Sjirball Inst Biomol Med, New York, NY 10016 USA. NR 28 TC 690 Z9 716 U1 1 U2 17 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 23 PY 2000 VL 404 IS 6776 BP 402 EP 407 DI 10.1038/35006090 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 298BG UT WOS:000086119000054 PM 10746729 ER PT J AU Yanovski, JA Yanovski, SZ Sovik, KN Nguyen, TT O'Neil, PM Sebring, NG AF Yanovski, JA Yanovski, SZ Sovik, KN Nguyen, TT O'Neil, PM Sebring, NG TI A prospective study of holiday weight gain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BODY-MASS INDEX; SEASONAL AFFECTIVE-DISORDER; UNITED-STATES; SMOKING CESSATION; US ADULTS; WOMEN; OVERWEIGHT; PREVALENCE; AGE; OBESITY AB Background: It is commonly asserted that the average American gains 5 lb (2.3 kg) or more over the holiday period between Thanksgiving and New Year's Day, yet few data support this statement. Methods: To estimate actual holiday-related weight variation, we measured body weight in a convenience sample of 195 adults. The subjects were weighed four times at intervals of six to eight weeks, so that weight change was determined for three periods: preholiday (from late September or early October to mid-November), holiday (from mid-November to early or mid-January), and postholiday (from early or mid-January to late February or early March). A final measurement of body weight was obtained in 165 subjects the following September or October. Data on other vital signs and self-reported health measures were obtained from the patients in order to mask the main outcome of interest. Results: The mean (+/-SD) weight increased significantly during the holiday period (gain, 0.37+/-1.52 kg; P<0.001), but not during the preholiday period (gain, 0.18+/-1.49 kg; P=0.09) or the postholiday period (loss, 0.07+/-1.14 kg; P=0.36). As compared with their weight in late September or early October, the study subjects had an average net weight gain of 0.48+/-2.22 kg in late February or March (P=0.003). Between February or March and the next September or early October, there was no significant additional change in weight (gain, 0.21 kg+/-2.3 kg; P=0.13) for the 165 participants who returned for follow-up. Conclusions: The average holiday weight gain is less than commonly asserted. Since this gain is not reversed during the spring or summer months, the net 0.48-kg weight gain in the fall and winter probably contributes to the increase in body weight that frequently occurs during adulthood. (N Engl J Med 2000;342:861-7.) (C)2000, Massachusetts Medical Society. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Nutr Res Coordinat, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Nutr, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [ZIA HD000641-14]; NICHD NIH HHS [Z01 HD-00641, Z01 HD000641] NR 45 TC 139 Z9 141 U1 0 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 23 PY 2000 VL 342 IS 12 BP 861 EP 867 DI 10.1056/NEJM200003233421206 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 296FU UT WOS:000086014100006 PM 10727591 ER PT J AU Cannon, RO Balaban, RS AF Cannon, RO Balaban, RS TI Chest pain in women with normal coronary angiograms SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ARTERY DISEASE; SYNDROME-X; HEART; MANAGEMENT; INVIVO; STRESS C1 NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 25 Z9 25 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 23 PY 2000 VL 342 IS 12 BP 885 EP 887 DI 10.1056/NEJM200003233421209 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 296FU UT WOS:000086014100009 PM 10727594 ER PT J AU Mangan, D Selwitz, RH Genco, R AF Mangan, D Selwitz, RH Genco, R TI Infections associated with diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Buffalo, NY 14214 USA. RP Mangan, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 5 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 23 PY 2000 VL 342 IS 12 BP 896 EP 896 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 296FU UT WOS:000086014100024 PM 10733379 ER PT J AU Tremain, R Marko, M Kinnimulki, V Ueno, H Bottinger, E Glick, A AF Tremain, R Marko, M Kinnimulki, V Ueno, H Bottinger, E Glick, A TI Defects in TGF beta signaling overcome senescence of mouse keratinocytes expressing v-ras(Ha) SO ONCOGENE LA English DT Article DE TGF beta 1; keratinocytes; replicative senescence; ras oncogene ID GROWTH-FACTOR-BETA; CELL-CYCLE ARREST; TUMOR-SUPPRESSOR GENE; SQUAMOUS CARCINOMA-CELLS; HARVEY-RAS ONCOGENE; HUMAN BREAST-CANCER; BENIGN SKIN TUMORS; II RECEPTOR; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSGENIC MICE AB Previous studies have shown that TGF beta 1 expression is upregulated in mouse keratinocytes infected with a v-ras(Ha) retrovirus, although the functional significance of this has not been clear. Here we show that v-ras(Ha) retrovirus transduced primary mouse keratinocytes undergo hyperproliferation followed by a TGF beta 1 dependent G1 growth arrest and senescence. The growth arrest is accompanied by a 15-fold increase in total TGF beta 1 secreted and a fourfold increase in secreted active TGF beta 1. When cultured in the presence of a neutralizing antibody to TGF beta 1, the senescence response is suppressed. Levels of the TGF beta 1 target p15(ink4b) increase during senescence as does association of this kinase inhibitor with cyclinD/cdk4 complexes. However, p16(ink4a), p53 and p19(ARF) expression also increase during senescence. Genetic analysis shows that TGF beta 1 null and dominant negative T beta RII expressing v-ras(Ha) keratinocytes resist the G1 growth arrest and do not senescence. This resistance is associated with low expression of p15(ink4b) and p16(ink4a), constitutive Rb phosphorylation and high levels of cdk4 and cdk2 kinase activity. In contrast, inactivation of TGF beta 1 secretion or response does not block the induction of p53 and p19(ARF), but the level of p21(waf1), a p53 target gene, is reduced in cyclin D/cdk4 and cyclin E/cdk2 complexes. Thus, although multiple senescence pathways are activated in response to a ras oncogene, inactivation of TGF beta 1 secretion or response is sufficient to block the senescence program. Since v-ras(Ha) transduced TGF beta 1-/- keratinocytes form squamous cell carcinomas following skin grafting, these results suggest that in mouse keratinocytes, defects in TGF beta 1 signaling accelerate malignant progression by overcoming oncogene induced replicative senescence. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Kyushu Univ, Sch Med, Dept Cardiol, Fukuoka 812, Japan. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Glick, A (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bld 37 3B-19, Bethesda, MD 20892 USA. NR 82 TC 77 Z9 78 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 23 PY 2000 VL 19 IS 13 BP 1698 EP 1709 DI 10.1038/sj.onc.1203471 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 297LG UT WOS:000086083800010 PM 10763827 ER PT J AU Zenklusen, JC Hodges, LC LaCava, M Green, ED Conti, CJ AF Zenklusen, JC Hodges, LC LaCava, M Green, ED Conti, CJ TI Definitive functional evidence for a tumor suppressor gene on human chromosome 7q31.1 neighboring the Fra7G site SO ONCOGENE LA English DT Article DE human chromosome 7; prostate carcinoma; tumor suppressor gene; microcell fusion; tumorigenesis ID COMMONLY DELETED REGION; PRIMARY BREAST-CANCER; LONG ARM; SQUAMOUS-CELL; FREQUENT LOSS; HETEROZYGOSITY; HUMAN-CHROMOSOME-7; CARCINOMAS; ADENOCARCINOMA; TUMORIGENICITY AB We have previously shown that loss of heterozygosity (LOH) on human chromosome (hchr) 7 at q31.1 is common in a variety of tumors of epithelial origin. Frequent LOH of a specific chromosomal marker is indicative of a closely linked tumor suppressor gene (TSG). However, recent reports have also indicated that such a high frequency of LOH could be due to the presence in this region of the second most common aphidicolin-inducible fragile site in the human genome (Fra7G), To address this controversy, we introduced single copies of hchr7 or hchr12 into a highly aggressive human prostate carcinoma cell line (PC3) by microcell-mediated transfer. The tumorigenicity of six clones of PC3/hchr7 hybrids and three clones of PCRhchr12 hybrids, obtained in four separate fusion experiments, were studied in BALB/c nude mice. All but one of the PC3/hchr7 hybrids increased tumor latency by at least twofold, whereas none of the PC3/hchr12 hybrids delayed tumor onset. No differences in the in vitro growth rate Here observed among any of the cell lines assayed (parental and hybrids) suggesting that the observed tumor suppression was due to factors other than cell cycle regulation. Deletion mapping of the PC3/hchr7 tumors obtained after reversion to the malignant phenotype revealed a common region of loss centred around 7q31.1, supporting the TSG hypothesis. The smallest commonly deleted region was similar to 1.5 Mb in size and flanked by the markers D7S486 and D7S655. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20982 USA. Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA. RP Zenklusen, JC (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, 49 Convent Dr,Room 2C28, Bethesda, MD 20982 USA. NR 29 TC 34 Z9 38 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 23 PY 2000 VL 19 IS 13 BP 1729 EP 1733 DI 10.1038/sj.onc.1203488 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 297LG UT WOS:000086083800014 PM 10763831 ER PT J AU Jones, JM Huang, JD Mermall, V Hamilton, BA Mooseker, MS Escayg, A Copeland, NG Jenkins, NA Meisler, MH AF Jones, JM Huang, JD Mermall, V Hamilton, BA Mooseker, MS Escayg, A Copeland, NG Jenkins, NA Meisler, MH TI The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a SO HUMAN MOLECULAR GENETICS LA English DT Article ID BRAIN MYOSIN-V; G-PROTEIN; UNCONVENTIONAL MYOSIN; PURKINJE-CELLS; DILUTE LOCUS; MUTATIONS; AMPLIFICATION AB Exon shuffling is thought to be an important mechanism for evolution of new genes. Here we show that the mouse neurological mutation flailer (flr) expresses a novel gene that combines the promoter and first two exons of guanine nucleotide binding protein beta 5 (Gnb5) with the C-terminal exons of the closely linked Myosin 5A (MyoVA) gene (Myo5a), The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport. Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells. The flailer protein thus has a dominant-negative mechanism of action with a recessive mode of inheritance due to the dependence of competitive binding on the ratio between mutant and wild-type proteins. The chromosomal arrangement of Myo5a upstream of Gnb5 is consistent with non-homologous recombination as the mutational mechanism. To our knowledge, flailer is the first example of a mammalian mutation caused by germ line exon shuffling between unrelated genes. C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Meisler, MH (reprint author), Univ Michigan, Dept Human Genet, 4708 Med Sci 2, Ann Arbor, MI 48109 USA. FU NIDDK NIH HHS [TDK 25387]; NIGMS NIH HHS [GM 24872]; NIMH NIH HHS [R01 MH059207] NR 31 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 22 PY 2000 VL 9 IS 5 BP 821 EP 828 DI 10.1093/hmg/9.5.821 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 299CC UT WOS:000086177400018 PM 10749990 ER PT J AU Mills, JL Levine, RJ Morrow, JD AF Mills, JL Levine, RJ Morrow, JD TI Prostacyclin and thromboxane and the development of preeclampsia - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN USA. RP Mills, JL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 22 PY 2000 VL 283 IS 12 BP 1568 EP 1569 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 293MV UT WOS:000085857300031 ER PT J AU Emanuel, EJ Fairclough, DL Slutsman, J Emanuel, LL AF Emanuel, EJ Fairclough, DL Slutsman, J Emanuel, LL TI Understanding economic and other burdens of terminal illness: The experience of patients and their caregivers SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE terminally ill; terminal care; cost of illness; caregivers; physician role ID PHYSICIAN-ASSISTED SUICIDE; MENTAL-HEALTH; UNITED-STATES; CARE; EUTHANASIA; CANCER; ATTITUDES; FAMILIES; ADULTS; NEEDS AB Background: Terminal illness imposes substantial burdens-economic and otherwise-on patients and caregivers. The cause of these burdens is not understood. Objective: To determine the mechanism for economic and noneconomic burdens of terminal illness and to identify potential ameliorating interventions. Design: In-person interviews of terminally ill patients and their caregivers. Setting: Six randomly selected U.S. sites: Worcester, Massachusetts; St. Louis, Missouri; Tucson, Arizona; Birmingham, Alabama; Brooklyn, New York; and Mesa County, Colorado. Participants: 988 terminally ill patients and 893 caregivers. Measurements: Needs for transportation, nursing care, homemaking, and personal care; subjective perception of economic burden; expenditure of more than 10% of household income on health care costs; caregiver depression and sense of interference with his or her life; and patient consideration of euthanasia or physician-assisted suicide. Results: Of all patients, 34.7% had substantial care needs. Patients who had substantial care needs were more likely to report that they had a subjective sense of economic burden (44.9% compared with 35.3%; difference, 9.6 percentage points [95% CI, 3.1 to 16.1]; P = 0.005); that 10% of their household income was spent on health care (28.0% compared with 17.0%; difference, 11.0 percentage points [CI, 4.8 to 17.1]; P less than or equal to 0.001); and that they or their families had to take out a loan or mortgage, spend their savings, or obtain an additional job (16.3% compared with 10.2%; difference, 6.1 percentage points [CI, 1.4 to 10.6]; P = 0.004). Patients with substantial care needs were more likely to consider euthanasia or physician-assisted suicide (P = 0.001). Caregivers of these patients were more likely to have depressive symptoms (31.4% compared with 24.8%; difference, 6.6 percentage points [CI, 0.4 to 12.8]; P = 0.01) and to report that caring for the patients interfered with their lives (35.6% compared with 24.3%; difference, 11.3 percentage points [CI, 5.0 to 17.7]; P = 0.001). Caregivers of patients whose physicians listened to patients' and caregivers' needs had fewer burdens. Conclusions: Substantial care needs are an important cause of the economic and other burdens imposed by terminal illness. Through empathy, physicians may be able to ameliorate some of these burdens. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. AMC Canc Res Ctr, Denver, CO USA. Johns Hopkins Univ, Baltimore, MD USA. Amer Med Assoc, Inst Eth, Chicago, IL 60610 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 30 TC 233 Z9 236 U1 4 U2 28 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 21 PY 2000 VL 132 IS 6 BP 451 EP + PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 293CV UT WOS:000085834700004 PM 10733444 ER PT J AU Sondej, M Seok, YJ Badawi, P Koo, BM Nam, TW Peterkofsky, A AF Sondej, M Seok, YJ Badawi, P Koo, BM Nam, TW Peterkofsky, A TI Topography of the surface of the Escherichia coli phosphotransferase system protein enzyme IIA(glc) that interacts with lactose permease SO BIOCHEMISTRY LA English DT Article ID SALMONELLA-TYPHIMURIUM; ADENYLATE-CYCLASE; ALLOSTERIC REGULATION; SUGAR-TRANSPORT; PHOSPHOENOLPYRUVATE; GLUCOSE; EXPRESSION; DOMAIN; IIIGLC; PURIFICATION AB The unphosphorylated form of enzyme IIA(glc) of the Escherichia coli phosphoenolpyruvate: sugar phosphotransferase system inhibits transport catalyzed by lactose permease. We (Seok et al. (1997) Proc. Natl. Acad. Sci, U.S.A. 94, 13515-13519) previously characterized the area on the cytoplasmic face of lactose permease that interacts with enzyme IIA(glc), using radioactive enzyme IIA(glc). Subsequent studies (Sondej et al. (1999) Proc. Natl. Acad. Sci, U.S.A. 96, 3525-3530) suggested consensus binding sequences on proteins that interact with enzyme IIA(glc). The present study characterizes a region on the surface of enzyme IIA(glc) that interfaces with lactose permease. Acetylation of lysine residues by sulfosuccinimidyl acetate treatment of enzyme IIA(glc), but not lactose permease, reduced the degree of interaction between the two proteins. To localize the lysine residue(s) on enzyme IIA(glc) that is(are) involved in the regulatory interaction, selected lysine residues were mutagenized. Conversion of nine separate lysines to glutamic acid resulted in proteins that were still capable of phosphoryl acceptance from HPr. Except for Lys69, all the modified proteins were as effective as the wild-type enzyme IIA(glc) in a test for binding to lactose permease, The Lys69 mutant was also defective in phosphoryl transfer to glucose permease. To derive further information concerning the contact surface, additional selected residues in the vicinity of Lys69 were mutagenized and tested for binding to lactose permease. On the basis of these studies, a model for the region of the surface of enzyme IIAp(glc) that interacts with lactose permease is proposed. C1 NHLBI, Biochim Genet Lab, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Seoul 151742, South Korea. RP Peterkofsky, A (reprint author), NHLBI, Biochim Genet Lab, NIH, Bldg 36,Room 4C-11, Bethesda, MD 20892 USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 21 PY 2000 VL 39 IS 11 BP 2931 EP 2939 DI 10.1021/bi9919596 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 296KL UT WOS:000086023500013 PM 10715113 ER PT J AU Hsich, E Segal, BH Pagano, PJ Rey, FE Paigen, B Deleonardis, J Hoyt, RF Holland, SM Finkel, T AF Hsich, E Segal, BH Pagano, PJ Rey, FE Paigen, B Deleonardis, J Hoyt, RF Holland, SM Finkel, T TI Vascular effects following homozygous disruption of p47(phox) - An essential component of NADPH oxidase SO CIRCULATION LA English DT Article DE apolipoproteins; atherosclerosis; blood pressure ID MESSENGER-RNA EXPRESSION; SMOOTH-MUSCLE CELLS; ANGIOTENSIN-II; NADH/NADPH OXIDASE; SUPEROXIDE PRODUCTION; FIBROBLASTS; GENERATION; SYSTEM; MICE AB Background-Evidence suggests that the vessel wall contains an oxidase similar, if not identical, to phagocytic NADPH oxidase, We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure. Methods and Results-An examination of aortic rings from wild-type mice and mice with homozygous targeted disruptions in p47(phox) revealed that p47(phox) knockout mice had a reduction in vascular superoxide production. However, analyses of apoE -/- p47(phox) +/+ and apoE -/- p47p(hox) -/- strains of mice demonstrated no significant differences in atherosclerotic lesion sizes. Similarly, analyses of wild-type and p47(phox) knockout mice revealed no differences in either basal blood pressure or the rise in blood pressure seen after the pharmacological inhibition of nitric oxide synthase, Conclusions-NADPH oxidase contributes to basal vascular superoxide production. However, the absence of a functional oxidase does not significantly affect the progression of atherosclerosis in the standard mouse apoE -/- model, nor does it significantly influence basal blood pressure. C1 NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA. RP Finkel, T (reprint author), NHLBI, Mol Biol Lab, NIH, Bldg 10-6N-240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 23 TC 121 Z9 124 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 21 PY 2000 VL 101 IS 11 BP 1234 EP 1236 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 295HR UT WOS:000085961100006 PM 10725280 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 Temporal repolarization lability in hypertrophic cardiomyopathy caused by beta-myosin heavy-chain gene mutations SO CIRCULATION LA English DT Article DE cardiomyopathy, hypertrophic; genetics; electrocardiography ID SUDDEN CARDIAC DEATH; QT-INTERVAL; PROGNOSTIC IMPLICATIONS; DILATED CARDIOMYOPATHY; ALPHA-TROPOMYOSIN; TROPONIN-T; HIGH-RISK; HEART; VARIABILITY; DISTINCT AB Background-Certain genetic mutations associated with hypertrophic cardiomyopathy (HCM) carry an increased risk of sudden death. QT variability identifies patients at a high risk for sudden death from ventricular arrhythmias. We tested whether patients with HCM caused by beta-myosin heavy-chain (beta-MHC) gene mutations exhibit labile ventricular repolarization using beat-to-beat QT variability analysis. Methods and Results-We measured the QT variability index and heart rate-QT interval coherence from Holter monitor recordings in 36 patients with HCM caused by known beta-MHC gene mutations and in 26 age- and sex-matched controls. There were 7 distinct beta-MHC gene mutations in these 36 patients; 9 patients had HCM caused by the malignant Arg(403)Gln mutation and 8 patients had HCM caused by the more benign Leu(908)Val mutation. The QT variability index was higher in HCM patients than in controls (-1.24+/-0.17 versus -1.58+/-0.38, P<0.01), and the greatest abnormality was detected in patients with the Arg(403)Gln mutation (-0.99+/-0.49 versus -1.46+/-0.43 in controls, P<0.05). In keeping with this finding, coherence was lower for the entire HCM group than for controls (P<0.001). Coherence was also significantly lower in patients with the Arg(403)Gln mutation compared with controls (P<0.05). Conclusions-These findings suggest that (1) patients with HCM caused by beta-MHC gene mutations exhibit labile repolarization quantified by QT variability analysis and, hence, may be more at risk for sudden death from ventricular arrhythmias, and (2) indices of QT variability may be particularly abnormal in patients with beta-MHC gene mutations that are associated with a poor prognosis. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. RP Berger, RD (reprint author), Johns Hopkins Hosp, Carnegie 592,600 N Wolfe St, Baltimore, MD 21287 USA. FU NHLBI NIH HHS [P50HL52307, R29HL54584] NR 35 TC 79 Z9 80 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 21 PY 2000 VL 101 IS 11 BP 1237 EP 1242 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 295HR UT WOS:000085961100007 PM 10725281 ER PT J AU Tajima, K Koshinuma, M Nakamura, A Gershfeld, NL AF Tajima, K Koshinuma, M Nakamura, A Gershfeld, NL TI Sponge-vesicle transformation in binary mixtures of ionized phospholipid bilayers SO LANGMUIR LA English DT Article ID TEMPERATURE; STATE; DISPERSIONS; MEMBRANES AB The ionized phospholipids NaDLPG and NaDMPG each undergo a transformation from a sponge phase to unilamellar vesicles at a critical temperature T* (Koshinuma; et al. Langmuir 1999, 15, 3430). The present study examines the dependence of TY On composition in aqueous bilayer dispersions of binary mixtures of these Lipids. The surface pressure of the saturated solutions show a maximum at T* that is a monotonic function of the lipid composition in the bilayer. The lipid composition in the equilibrium aqueous solution was also measured. At T*, and only at this temperature, the lipid composition of the bilayer and equilibrium solution become identical. These properties are shown to be a natural consequence of the surface pressure maximum at T*, and are indicative of the physical uniqueness of the critical bilayer state. In general, when aqueous dispersions of bilayer-forming multicomponent mixtures of phospholipids exhibit a surface pressure maximum at a critical temperature T*, the lipid composition of the solution and bilayer phases become identical. This property is a characteristic of the general class of indifferent states. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Gershfeld, NL (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM ngo@cu.nih.gov NR 19 TC 3 Z9 3 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 21 PY 2000 VL 16 IS 6 BP 2576 EP 2580 DI 10.1021/la9911640 PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 295TT UT WOS:000085984500025 ER PT J AU Lipman, EA Hale, DDS Monnier, JD Tuthill, PG Danchi, WC Townes, CH AF Lipman, EA Hale, DDS Monnier, JD Tuthill, PG Danchi, WC Townes, CH TI Interferometric observations of IRC+10011 and IRC+10420 in the mid-infrared SO ASTROPHYSICAL JOURNAL LA English DT Article DE circumstellar matter; infrared : stars; stars : AGB and post-AGB; stars : individual (IRC+10011, IRC+10420); techniques : interferometric ID LATE-TYPE STARS; CIRCUMSTELLAR DUST SHELLS; OXYGEN-RICH STARS; MASS-LOSS RATES; SPECKLE INTERFEROMETRY; VLA OBSERVATIONS; COOL HYPERGIANT; EVOLVED STARS; OH/IR STARS; IRC +10420 AB The 11 mu m fringe visibilities of IRC + 10011 (= CIT3) and IRC + 10420 have been measured at baselines ranging from 2 to 14 m with a two-telescope interferometer. The visibility data provide one-dimensional profiles of these two stars and their immediate surroundings with higher resolution in this spectral range than is presently possible with a single-aperture telescope. Spherically symmetric radiative transfer models suggest that IRC + 10011 is surrounded by a dust shell with an inner radius subtending 0 ".033, which falls off in density as r(-1.5), slightly slower than the r(-2) expected for constant dust outflow. IRC + 10420 appears to have a dust shell of inner radius 0 ".12, the density of which drops very slowly compared with that in a constant outflow. This implies decreasing outflow or a significant emission in the past. C1 Univ Calif Berkeley, Space Sci Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. RP Lipman, EA (reprint author), NIH, Bldg 5,Room 114, Bethesda, MD 20892 USA. RI Lipman, Everett/D-1696-2009 NR 43 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0004-637X J9 ASTROPHYS J JI Astrophys. J. PD MAR 20 PY 2000 VL 532 IS 1 BP 467 EP 473 DI 10.1086/308569 PN 1 PG 7 WC Astronomy & Astrophysics SC Astronomy & Astrophysics GA 301VF UT WOS:000086330400042 ER PT J AU Kunick, C Schultz, C Lemcke, T Zaharevitz, DW Gussio, R Jalluri, RK Sausville, EA Leost, M Meijer, L AF Kunick, C Schultz, C Lemcke, T Zaharevitz, DW Gussio, R Jalluri, RK Sausville, EA Leost, M Meijer, L TI 2-substituted paullones: CDK1/cyclin B-inhibiting property and in vitro antiproliferative activity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID CANCER; SCREEN AB 9-Trifluoromethyl-paullones with a carbon chain in the 2-position were synthesized by palladium-catalyzed coupling reactions of a 2-iodoprecursor with terminal alkenes or alkynes, respectively. The introduction of a 2-cyanoethyl substituent led to a significant enhancement of CDK1/cyclin B inhibiting property and in vitro antiproliferative activity. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Hamburg, Inst Pharm, Abt Pharmazeut Chem, D-20146 Hamburg, Germany. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. CNRS, Biol Stn, F-29682 Roscoff, France. RP Kunick, C (reprint author), Univ Hamburg, Inst Pharm, Abt Pharmazeut Chem, Bundesstr 45, D-20146 Hamburg, Germany. NR 15 TC 58 Z9 60 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAR 20 PY 2000 VL 10 IS 6 BP 567 EP 569 DI 10.1016/S0960-894X(00)00048-2 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 294NG UT WOS:000085916900011 PM 10741555 ER PT J AU Inaba, K Turley, S Iyoda, T Yamaide, F Shimoyama, S Sousa, CRE Germain, RN Mellman, I Steinman, RM AF Inaba, K Turley, S Iyoda, T Yamaide, F Shimoyama, S Sousa, CRE Germain, RN Mellman, I Steinman, RM TI The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE dendritic cell; maturation; MHC class II-peptide complex; lysosome; inflammation ID MHC CLASS-II; EPIDERMAL LANGERHANS CELLS; CD8(+) T-CELLS; INVARIANT CHAIN; DOWN-REGULATION; IN-VITRO; DEVELOPMENTAL REGULATION; ENDOCYTIC COMPARTMENT; CHEMOKINE RECEPTOR; EXOGENOUS PROTEIN AB During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma membrane. Using cells arrested in the immature state, we now find that DCs also regulate the initial intracellular formation of immunogenic MHC class II-peptide complexes. Immature DCs internalize the protein antigen, hen egg lysozyme (HEL), into late endosomes and lysosomes rich in MHC class II molecules. There, despite extensive colocalization of HEL protein and MHC class II products, MHC class II-peptide complexes do not form unless the DCs are exposed to inflammatory mediators such as tumor necrosis factor alpha, CD40 ligand, or lipoplolysaccharide. The control of T cell receptor (TCR) ligand formation was observed using the C4H3 monoclonal antibody to detect MHC class II-MEL peptide complexes by now cytometry and confocal microscopy, and with HEL specific 3A9 transgenic T cells to detect downregulation of the TCR upon MHC-peptide encounter. Even the binding of preprocessed HEL peptide to MHC class II is blocked in immature DCs, including the formation of C4H3 epitope in MHC class II compartments, suggesting an arrest to antigen presentation at the peptide-loading step, rather than an enhanced degradation of MHC class II-peptide complexes at the cell surface, as described in previous work. Therefore, the capacity of late endosomes and lysosomes to produce MHC class II-peptide complexes can be strictly controlled during DC differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of TCR ligands. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributes to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice. C1 Rockefeller Univ, Lab Cell Physiol & Immunol, New York, NY 10021 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. Kyoto Univ, Grad Sch Biostudies, Immunobiol Lab, Kyoto 6068502, Japan. RP Steinman, RM (reprint author), Rockefeller Univ, Lab Cell Physiol & Immunol, 405 Bronk Bldg,1230 York Ave, New York, NY 10021 USA. RI Steinman, Ralph/F-7729-2012 FU NIAID NIH HHS [R37 AI034098, AI-13013, AI-34098, AI-39672, R01 AI013013] NR 61 TC 286 Z9 292 U1 3 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 20 PY 2000 VL 191 IS 6 BP 927 EP 936 DI 10.1084/jem.191.6.927 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 296YY UT WOS:000086055400003 PM 10727455 ER PT J AU Schlissel, MS Durum, SD Muegge, K AF Schlissel, MS Durum, SD Muegge, K TI The interleukin 7 receptor is required for T cell receptor gamma locus accessibility to the V(D)J recombinase SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE recombination; T lymphocytes; interleukins; chromatin; immunology ID SEVERE COMBINED IMMUNODEFICIENCY; GENE REARRANGEMENT; DEFICIENT MICE; VDJ RECOMBINATION; IL-7 RECEPTOR; ENHANCER; BCL-2; IDENTIFICATION; LYMPHOPOIESIS; EXPRESSION AB Defects in the interleukin (IL)-7 signal transduction pathway lead to severe immunodeficiency in humans and in mice. In IL-7 receptor-deficient (IL-7R(-/-)) mice, lymphoid precursors show a reduced survival rate and variable/diversity/joining region V(D)J recombination is variously affected in different loci, being arrested in the T cell receptor (TCR)-gamma locus, aberrant in the immunoglobulin heavy chain (IgH) locus, and delayed in the TCR)-gamma locus. Here, we analyze the recombination defect of the TCR-gamma locus. Using ligation-mediated polymerase chain reaction, we sought intermediates of the recombination process. In the absence of the IL-7 signal, no initiation of recombination of the TCR-gamma locus was observed, whereas recombination intermediates at the TCR-beta locus could be detected. Thus, the failure to rearrange the TCR-gamma locus is due to a failure to initiate cleavage rather than a failure to religate broken DNA ends. V(D)J recombination was previously thought to begin at the pro-T2 stage of T cell, development after the arrest of IL-7R(-/-) thymocytes at the pro-T1 stage. However, here we show that both TCR-gamma and -beta recombination intermediates are readily detectable in normal T1 cells, but only TCR-beta intermediates were detected in IL-7R(-/-) T1 cells, supporting a mechanistic role for IL-7 in TCR-gamma locus rearrangement. Since reduced recombination activating gene (rag) expression has been reported in the absence of the IL-7 signal, we directly tested whether the TCR-gamma locus is accessible to cleavage by recombinant Rag proteins in vitro. We found a reduction in chromatin accessibility for Rag-mediated cleavage in IL-7R(-/-) thymocytes compared with wild-type. Thus, IL-7 controls recombination at the TCR-gamma locus by regulating locus accessibility. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp, SAIC Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NCI, Mol Immunoregulat Lab, Sci Applicat Int Corp, SAIC Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Muegge, K (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp, SAIC Frederick Canc Res & Dev Ctr, Bldg 560,Rm 31-45, Frederick, MD 21702 USA. FU NIAID NIH HHS [R37 AI040227, AI40227, R01 AI040227]; PHS HHS [N01-C0-56000] NR 32 TC 73 Z9 74 U1 2 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 20 PY 2000 VL 191 IS 6 BP 1045 EP 1050 DI 10.1084/jem.191.6.1045 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 296YY UT WOS:000086055400013 PM 10727465 ER PT J AU Pichierri, P Franchitto, A Mosesso, P de Santis, LP Balajee, AS Palitti, F AF Pichierri, P Franchitto, A Mosesso, P de Santis, LP Balajee, AS Palitti, F TI Werner's syndrome lymphoblastoid cells are hypersensitive to topoisomerase II inhibitors in the G2 phase of the cell cycle SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE Werner's syndrome; topoisomerase II inhibitors; recombination and DNA repair; chromosomal aberrations ID ESCHERICHIA-COLI RECQ; DNA HELICASE; CHROMOSOMAL-ABERRATIONS; SYNDROME GENES; SGS1; HOMOLOG; DRUGS; LINES; YEAST; INSTABILITY AB Werner's syndrome (WS) is a rare autosomal recessive human disorder and the patients exhibit many symptoms of accelerated ageing in their early adulthood. The gene (WRN) responsible for WS has been biochemically characterised as a 3'-5' helicase and is homologous to a number of RecQ superfamily of helicases. The yeast SGS1 helicase is considered as a human WRN homologue and SGS1 physically interacts with topoisomerases II and III. In view of this, it has been hypothesised that the WRN gene may also interact with topoisomerases II and III. The purpose of this study is to determine whether the loss of function of WRN protein alters the sensitivity of WS cells to agents that block the action of topoisomerase II. This study deals with the comparison of the chromosomal damage induced by the two anti-topoisomerase II drugs, VP-16 and amsacrine, in both G1 and G2 phases of the cell cycle, in lymphoblastoid cells from WS patients and from a healthy donor. Our results show that the WS cell lines are hypersensitive to chromosome damage induced by VP-16 and amsacrine only in the G2 phase of the cell cycle, No difference either in the yield of the induced aberrations or SCEs was found after treatment of cells at G1 stage. These data might suggest that in WS cells, because of the mutation of the WRN protein, the inhibition of topoisomerase II activity results in a higher rate of misrepair, probably due to some compromised G2 phase processes involving the WRN protein. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Tuscia, Dipartimento Agrobiol & Agrochim, I-01100 Viterbo, Italy. NIA, NIH, Mol Genet Lab, Baltimore, MD USA. RP Palitti, F (reprint author), Univ Tuscia, Dipartimento Agrobiol & Agrochim, Via S Camillo Lellis SNC, I-01100 Viterbo, Italy. RI Franchitto, Annapaola/K-7564-2016 OI Mosesso, Pasquale/0000-0001-5648-1366; Franchitto, Annapaola/0000-0003-4232-4727 NR 31 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD MAR 20 PY 2000 VL 459 IS 2 BP 123 EP 133 DI 10.1016/S0921-8777(99)00065-8 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 297MP UT WOS:000086086900005 PM 10725663 ER PT J AU Pazman, C Castelli, JC Wen, XL Somogyi, R AF Pazman, C Castelli, JC Wen, XL Somogyi, R TI Large-scale identification of differentially expressed genes during neurogenesis SO NEUROREPORT LA English DT Article DE differential display; NGF; PC12; spinal cord ID EUKARYOTIC MESSENGER-RNA; DISPLAY; PCR; CLONING; PRIMERS AB We report here a modified mRNA differential display method and its application for the analysis of differential gene expression in NGF-treated PC12 cells and in embryonic rat spinal cord. The optimized protocol is based on low fidelity priming of multiple cDNAs followed by high fidelity amplification. In PC12 cells induction by nerve growth factor (NGF) altered the expression of 4% of the 466 transcripts evaluated. During neurogenesis of the spinal cord we found that 30% of the 288 examined products changed. The differential expression of the characterized genes was confirmed by independent quantitative PCR. We conclude this method is suitable for the identification of increases and decreases of mRNA levels and allows the discovery of differentially expressed unknown transcripts. NeuroReport 11:719-724 (C) 2000 Lippincott Williams & Wilkins. C1 NINDS, Neurophysiol Lab, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Pazman, C (reprint author), Uniformed Serv Univ Hlth Sci, Dept Biochem, Bethesda, MD 20814 USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 20 PY 2000 VL 11 IS 4 BP 719 EP 724 DI 10.1097/00001756-200003200-00013 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 297KZ UT WOS:000086083200018 PM 10757507 ER PT J AU Ogawa, O Umegaki, H Ishiwata, K Asai, Y Ikari, H Oda, K Toyama, H Ingram, DK Roth, GS Iguchi, A Senda, M AF Ogawa, O Umegaki, H Ishiwata, K Asai, Y Ikari, H Oda, K Toyama, H Ingram, DK Roth, GS Iguchi, A Senda, M TI In vivo imaging of adenovirus-mediated over-expression of dopamine D-2 receptors in rat striatum by positron emission tomography SO NEUROREPORT LA English DT Article DE adenoviral vector; dopamine D-2 receptor; gene transfer; positron emission tomography; striatum ID C-11 RACLOPRIDE; GENE-EXPRESSION; NEURONS; DISEASE; AGE; PET; D1 AB PET was used to provide in vivo imaging of the over-expression of dopamine D-2 receptor (D2R) induced by adenovirus vector-mediated gene transfer in rat striatum. The uptake of three kinds of D2R-specific ligands, [C-11]raclopride, [C-11]nemonapride and [C-11]N-methylspiperone, measured by PET was higher in the striatum injected with the vectors for D2R than the contralateral striatum injected with a control vector 2-3 days after injection. However, the uptake of [C-11]SCH 23390, a dopamine D-1 receptor specific ligand, or [C-11]beta-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata. Co-injection of excess unlabeled raclopride inhibited the uptake of [C-11]raclopride. At day 16 the increased uptake of [C-11]raclopride declined to basal level, consistent with past in vitro assessment of this vector. In vivo imaging of D2R will permit longitudinal assessment of the efficiency of this and similar vectors in rat brain that can be related to functional changes being observed. NeuroReport 11:743-748 (C) 2000 Lippincott Williams & Wilkins. C1 Nagoya Univ, Grad Sch Med, Dept Geriatr, Showa Ku, Aichi 4668550, Japan. Tokyo Metropolitan Inst Gerontol, Positron Med Ctr, Itabashi Ku, Tokyo 1730022, Japan. NIA, Gerontol Res Ctr, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Umegaki, H (reprint author), Nagoya Univ, Grad Sch Med, Dept Geriatr, Showa Ku, 65 Tsuruma Cho, Aichi 4668550, Japan. NR 24 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 20 PY 2000 VL 11 IS 4 BP 743 EP 748 DI 10.1097/00001756-200003200-00018 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 297KZ UT WOS:000086083200023 PM 10757512 ER PT J AU Gail, MH Greene, MH AF Gail, MH Greene, MH TI Gail model and breast cancer SO LANCET LA English DT Letter C1 NCI, Div Canc Genet & Epidemiol, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Div Canc Genet & Epidemiol, Bethesda, MD 20892 USA. NR 4 TC 17 Z9 17 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 18 PY 2000 VL 355 IS 9208 BP 1017 EP 1017 DI 10.1016/S0140-6736(05)74761-9 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 296YH UT WOS:000086054000055 PM 10768462 ER PT J AU Sellers, JR AF Sellers, JR TI Myosins: a diverse superfamily SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE myosin II; myosin IV; myosin VI-VIII; myosin X-XV ID HEAVY-CHAIN GENE; VERTEBRATE NONMUSCLE MYOSIN; SMOOTH-MUSCLE MYOSIN; REGULATORY LIGHT-CHAIN; RABBIT SKELETAL-MUSCLE; KINASE RHO-KINASE; UNCONVENTIONAL MYOSIN; MOTOR DOMAIN; DICTYOSTELIUM-DISCOIDEUM; SCHIZOSACCHAROMYCES-POMBE AB Myosins constitute a large superfamily of actin-dependent molecular motors. Phylogenetic analysis currently places myosins into 15 classes. The conventional myosins which form filaments in muscle and non-muscle cells form class II. There has been extensive characterization of these myosins and much is known about their function. With the exception of class I and class V myosins, little is known about the structure, enzymatic properties, intracellular localization and physiology of most unconventional myosin classes. This review will focus on myosins from class IV, VI, VII, VIII, X, XI, XII, XIII, XIV and XV. In addition, the function of myosin II in non-muscle cells will also be discussed. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sellers, JR (reprint author), NHLBI, NIH, Bldg 10,Room 8N202, Bethesda, MD 20892 USA. NR 165 TC 451 Z9 471 U1 8 U2 81 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAR 17 PY 2000 VL 1496 IS 1 BP 3 EP 22 DI 10.1016/S0167-4889(00)00005-7 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299NK UT WOS:000086204600002 PM 10722873 ER PT J AU Adler, E Hoon, MA Mueller, KL Chandrashekar, J Ryba, NJP Zuker, CS AF Adler, E Hoon, MA Mueller, KL Chandrashekar, J Ryba, NJP Zuker, CS TI A novel family of mammalian taste receptors SO CELL LA English DT Article ID ALPHA-GUSTDUCIN; CHORDA TYMPANI; G-PROTEIN; RAT; TRANSDUCTION; CELLS; AMILORIDE; GENES; NERVE; MICE AB In mammals, taste perception is a major mode of sensory input. We have identified a novel family of 40-80 human and rodent G protein-coupled receptors expressed in subsets of taste receptor cells of the tongue and palate epithelia. These candidate taste receptors (T2Rs) are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. Notably, a single taste receptor cell expresses a large repertoire of T2Rs, suggesting that each cell may be capable of recognizing multiple tastants. T2Rs are exclusively expressed in taste receptor cells that contain the G protein alpha subunit gustducin, implying that they function as gustducin-linked receptors. In the accompanying paper, we demonstrate that T2Rs couple to gustducin in vitro, and respond to bitter tastants in a functional expression assay. C1 NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Biol, Dept Neurosci, La Jolla, CA 92093 USA. RP Ryba, NJP (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Bldg 10, Bethesda, MD 20892 USA. NR 40 TC 730 Z9 779 U1 17 U2 92 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 17 PY 2000 VL 100 IS 6 BP 693 EP 702 DI 10.1016/S0092-8674(00)80705-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 295TK UT WOS:000085983800011 PM 10761934 ER PT J AU Chandrashekar, J Mueller, KL Hoon, MA Adler, E Feng, LX Guo, W Zuker, CS Ryba, NJP AF Chandrashekar, J Mueller, KL Hoon, MA Adler, E Feng, LX Guo, W Zuker, CS Ryba, NJP TI T2Rs function as bitter taste receptors SO CELL LA English DT Article ID G-PROTEIN; SUCROSE OCTAACETATE; EXPRESSION; GUSTDUCIN; NERVE; MICE; RAT; TRANSDUCTION; COUPLE; SWEET AB Bitter taste perception provides animals with critical protection against ingestion of poisonous compounds. In the accompanying paper, we report the characterization of a large family of putative mammalian taste receptors (T2Rs). Here we use a heterologous expression system to show that specific T2Rs function as bitter taste receptors. A mouse T2R (mT2R-5) responds to the bitter tastant cycloheximide, and a human and a mouse receptor (hT2R-4 and mT2R-8) responded to denatonium and 6-n-propyl-2-thiouracil. Mice strains deficient in their ability to detect cycloheximide have amino acid substitutions in the mT2R-5 gene; these changes render the receptor significantly less responsive to cycloheximide. We also expressed mT2R-5 in insect cells and demonstrate specific tastant-dependent activation of gustducin, a G protein implicated in bitter signaling. Since a single taste receptor cell expresses a large repertoire of T2Rs, these findings provide a plausible explanation for the uniform bitter taste that is evoked by many structurally unrelated toxic compounds. C1 NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Biol, Dept Neurosci, La Jolla, CA 92093 USA. Aurora Biosci, San Diego, CA 92121 USA. RP Zuker, CS (reprint author), NIH, Natl Inst Dent & Craniofacial Res, Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 745 Z9 781 U1 33 U2 122 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 17 PY 2000 VL 100 IS 6 BP 703 EP 711 DI 10.1016/S0092-8674(00)80706-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 295TK UT WOS:000085983800012 PM 10761935 ER PT J AU Xu, D Neville, R Finkel, T AF Xu, D Neville, R Finkel, T TI Homocysteine accelerates endothelial cell senescence SO FEBS LETTERS LA English DT Article DE atherosclerosis; intracellular adhesion molecule-1; redox; telomere; aging ID WERNER-SYNDROME; PROTEIN; CERULOPLASMIN; APOPTOSIS; COPPER; MODEL; P53 AB In this study we demonstrate that exposure of cultured endothelial cells to homocysteine significantly accelerates the rate of endothelial senescence. Examination of telomere length demonstrates that homocysteine increases the amount of telomere length lost per population doubling. The effects of homocysteine on both senescence and telomere length are inhibited by treatment with the peroxide scavenger catalase, Chronic exposure of endothelial cells to homocysteine also increases the expression of two surface molecules linked to vascular disease, intracellular adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-I), Interestingly, the level of expression of both ICAM-1 and PAI-1 correlates with the degree of endothelial senescence, Taken together, these results suggest that homocysteine accelerates the rate of cellular senescence through a redox-dependent pathway. In addition, it suggests that chronic oxidative stress in the vessel wall may hasten the rate of senescence and that the senescent endothelial cell may in turn be pro-atherogenic, (C) 2000 Federation of European Biochemical Societies. C1 NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Sch Med, Dept Surg, Washington, DC USA. RP Finkel, T (reprint author), NHLBI, Mol Biol Lab, NIH, Bldg 10-7B-15,10 Ctr Dr, Bethesda, MD 20892 USA. NR 19 TC 134 Z9 147 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 17 PY 2000 VL 470 IS 1 BP 20 EP 24 DI 10.1016/S0014-5793(00)01278-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 296AX UT WOS:000086001800005 PM 10722838 ER PT J AU Rajagopal, V Kreitman, RJ AF Rajagopal, V Kreitman, RJ TI Recombinant toxins that bind to the urokinase receptor are cytotoxic without requiring binding to the alpha(2)-macroglobulin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMINOGEN-ACTIVATOR RECEPTOR; PSEUDOMONAS EXOTOXIN-A; CIRCULARLY PERMUTED INTERLEUKIN-4; SINGLE-CHAIN IMMUNOTOXIN; CANCER CELL-LINES; DIPHTHERIA-TOXIN; KDEL RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; MALIGNANT ASTROCYTOMA; TRANSFERRIN RECEPTOR AB The alpha(2-)macroglobulin receptor (alpha(2)MR) has been reported to mediate the internalization of the urokinase plasminogen activator receptor (uPAR) via ligand binding to both receptors. To target malignant uPAR-expressing cells and to determine whether uPAR can internalize without ligand binding to alpha(2)MR, we engineered two recombinant toxins, ATF-PE38 and ATF-PE38KDEL. Each consists of the amino-terminal fragment (ATF) of human urokinase and a truncated form of Pseudomonas exotoxin (PE) devoid of domain Ia, which binds alpha(2)MR. ATF-PE38 and ATF-PE38KDEL were cytotoxic: toward malignant uPAR-bearing cells, with IC50 values as low as 0.02 ng/ml (0.3 pw). Cytotoxicity could be blocked using either recombinant urokinase or free ATF, indicating that the cytotoxicity of the recombinant toxins was specific. Radiolabeled ATF-PE38 had high affinity for uPAR (K-d = 0.4-8 nM) on a variety of different malignant cell types and internalized at a rate similar to that of ATF. The cytotoxicity was not diminished by receptor-associated protein, which binds and shields the alpha(2)MR from other proteins, or by incubation with phorbol myristate acetate, which is known to decrease the number of alpha(2)MRs in U937 cells or by antibodies to ar,MR. Therefore, these recombinant toxins appear to internalize via uPAR without association with the alpha(2)MR. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, 37-4B27,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 74 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 17 PY 2000 VL 275 IS 11 BP 7566 EP 7573 DI 10.1074/jbc.275.11.7566 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294LT UT WOS:000085913300023 PM 10713063 ER PT J AU Fujii, T Garcia-Bermejo, ML Bernabo, JL Caamano, J Ohba, M Kuroki, T Li, LW Yuspa, SH Kazanietz, MG AF Fujii, T Garcia-Bermejo, ML Bernabo, JL Caamano, J Ohba, M Kuroki, T Li, LW Yuspa, SH Kazanietz, MG TI Involvement of protein kinase C delta (PKC delta) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells - Lack of proteolytic cleavage of PKC delta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ICE-LIKE PROTEASE; TYROSINE PHOSPHORYLATION; 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED APOPTOSIS; HUMAN KERATINOCYTES; TUMOR PROMOTERS; ACTIVATION; EXPRESSION; INDUCTION; OVEREXPRESSION; GROWTH AB Phorbol esters, the activators of protein kinase C (PKC), induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. The role of individual PKC isozymes as mediators of this effect has not been thoroughly examined to date. To study the involvement of the novel isozyme PRC delta we used a replication-deficient. adenovirus (PKC delta AdV), which allowed for a tightly controlled expression of PKC delta in LNCaP cells. A significant reduction in cell number was observed after infection of LNCaP cells with PKC delta AdV. Overexpression of PKC delta markedly enhanced the apoptotic effect of phorbol 12-myristate 13-acetate in LNCaP cells. PKC delta-mediated apoptosis was substantially reduced by the pan-caspase inhibitor z-VAD and by Bcl-2 overexpression. Importantly, and contrary to other cell types, PKC delta-mediated apoptosis does not involve its proteolytic cleavage by caspase-3, suggesting that allosteric activation of PHC delta is sufficient to trigger apoptosis in LNCaP cells. In addition, phorbol ester-induced apoptosis was blocked by a kinase-deficient mutant of PHC delta, supporting the concept that PKC delta plays an important role in the regulation of apoptotic cell death in LNCaP prostate cancer cells. C1 Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. Showa Univ, Sch Pharmaceut Sci, Dept Microbiol, Shinagawa Ku, Tokyo 1428555, Japan. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Kazanietz, MG (reprint author), Univ Penn, Sch Med, Ctr Expt Therapeut, 816 Biomed Res Bldg 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Kuroki, Toshio/A-9500-2011; Garcia-Bermejo, Maria Laura/E-1542-2015; Caamano, Jorge/I-6778-2012 OI Kuroki, Toshio/0000-0001-6369-4351; Caamano, Jorge/0000-0003-3530-7056 NR 55 TC 174 Z9 178 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 17 PY 2000 VL 275 IS 11 BP 7574 EP 7582 DI 10.1074/jbc.275.11.7574 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294LT UT WOS:000085913300024 PM 10713064 ER PT J AU Tian, L Nelson, DL Stewart, DM AF Tian, L Nelson, DL Stewart, DM TI Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOSKELETAL-ASSOCIATED PROTEIN; ACTIN-DEPOLYMERIZING PROTEIN; SRC HOMOLOGY-3 DOMAINS; N-WASP; SIGNALING PATHWAYS; TYROSINE KINASES; LIVING CELLS; T-CELLS; IDENTIFICATION; CDC42 AB The Wiskott-Aldrich syndrome is an inherited X-linked immunodeficiency characterized by thrombocytopenia, eczema, and a tendency toward lymphoid malignancy. Lymphocytes from affected individuals have cytoskeletal abnormalities, and monocytes show impaired motility. The Wiskott-Aldrich syndrome protein (WASP) is a multi-domain protein involved in cytoskeletal organization. In a two-hybrid screen, we identified the protein Cdc42-interacting protein 4 (CIP4) as a WASP interactor. CIP4, like WASP, is a Cdc42 effector protein involved in cytoskeletal organization. We found that the WASP-CIP4 interaction is mediated by the binding of the Src homology 3 domain of CIP4 to the proline-rich segment of WASP. Cdc42 was not required for this interaction. Go-expression of CIP4 and green fluorescent protein-WASP in COS-7 cells led to the association of WASP with microtubules. In vitro experiments showed that CIP4 binds to microtubules via its NH2 terminus. The region of CIP4 responsible for binding to active Cdc42 was localizes to amino acids 383-417, and the mutation I398S abrogated binding. Deletion of the Cdc42-binding domain of CIP4 did not affect the colocalization of WASP with microtubules in vivo. We conclude that CIP4 can mediate the association of WASP with microtubules. This may facilitate transport of WASP to sites of substrate adhesion in hematopoietic cells. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Stewart, DM (reprint author), NCI, Metab Branch, NIH, Rm 4N-115,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 57 TC 128 Z9 135 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 17 PY 2000 VL 275 IS 11 BP 7854 EP 7861 DI 10.1074/jbc.275.11.7854 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294LT UT WOS:000085913300060 PM 10713100 ER PT J AU Fedele, M Benvenuto, G Pero, R Majello, B Battista, S Lembo, F Vollono, E Day, PM Santoro, M Lania, L Bruni, CB Fusco, A Chiariotti, L AF Fedele, M Benvenuto, G Pero, R Majello, B Battista, S Lembo, F Vollono, E Day, PM Santoro, M Lania, L Bruni, CB Fusco, A Chiariotti, L TI A novel member of the BTB/POZ family, PATZ, associates with the RNF4 RING finger protein and acts as a transcriptional repressor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; DNA-BINDING; POZ-DOMAIN; HMGI-C; REGULATED EXPRESSION; HISTONE DEACETYLASE; INTERACTION MOTIF; GENE; RECEPTOR; ALPHA AB We have identified a novel human gene encoding a 59-kDa POZ-AT hook-zinc finger protein (PATZ) that interacts with RNF4, a mediator of androgen receptor activity, and acts as a transcriptional repressor. PATZ cDNA was isolated through a two-hybrid interaction screening using the RING finger protein RNF4 as a bait. In vitro and in vivo interaction between RNF4 and PATZ was demonstrated by protein-protein affinity chromatography and coimmunoprecipitation experiments. Such interaction occurred through a small region of PATZ containing an AT-hook DNA binding domain. Immunofluorescence staining and confocal microscopy showed that PATZ localizes in distinct punctate nuclear regions and colocalizes with RNF4. Functional analysis was pe;formed by cotransfection assays: PATZ acted as a transcriptional repressor, whereas its partner RNF4 behaved as a transcriptional activator. When both proteins were overexpressed a strong repression of the basal transcription was observed, indicating that the association of PATZ with RNF4 switches activation to repression, In addition, RNF4 was also found to associate with HMGI(Y), a chromatin-modeling factor containing AT-hook domains. C1 Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol L Calif, CNR, Ctr Endocrinol & Oncol Sperimentale, I-80131 Naples, Italy. Univ Naples Federico II, Dipartimento Genet Biol Mol & Gen, I-80134 Naples, Italy. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Univ Catanzaro Magna Graecia, Dipartimento Med Sperimentale & Clin G Salvatore, I-88100 Catanzaro, Italy. RP Chiariotti, L (reprint author), Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol L Calif, CNR, Ctr Endocrinol & Oncol Sperimentale, Via S Pansini 5, I-80131 Naples, Italy. RI Fedele, Monica/C-1417-2015; Pero, Raffaela/L-1461-2015; OI Pero, Raffaela/0000-0003-2182-5530; Fusco, Alfredo/0000-0003-3332-5197; CHIARIOTTI, Lorenzo/0000-0001-6097-4171 NR 46 TC 56 Z9 62 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 17 PY 2000 VL 275 IS 11 BP 7894 EP 7901 DI 10.1074/jbc.275.11.7894 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294LT UT WOS:000085913300065 PM 10713105 ER PT J AU Hofmann, A Proust, J Dorowski, A Schantz, R Huber, R AF Hofmann, A Proust, J Dorowski, A Schantz, R Huber, R TI Annexin 24 from Capsicum annuum - X-ray structure and biochemical characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR REPLACEMENT; PHOSPHOLIPID-BINDING; PROTEIN; IDENTIFICATION; EXPRESSION; PROGRAM; GENE; P35 AB This work provides the first three-dimensional structure of a member of the plant annexin family and correlates these findings with biochemical properties of this protein. Annexin 24(Ca32) from Capsicum annuum was purified as a native protein fr om bell pepper and was also prepared by recombinant techniques. To overcome the problem of precipitation of the recombinant wildtype protein in crystallization trials, two mutants were designed. Whereas an N-terminal truncation mutant turned out to be an unstable protein, the N-terminal His-tagged annexin 24(Ca32) was crystallized, and the three-dimensional structure was determined by x-ray diffraction at 2.8 Angstrom resolution, The structure refined to an R-factor of 0.216 adopts the typical annexin fold; the detailed structure, however, is different from non-plant annexins, especially in domains I and III and in the membrane binding loops on the convex side. Within the unit cell there are two molecules per asymmetric unit, which differ in conformation of the LQB-loop. Both conformers show Trp-35 on the surface. The loop-out conformation is stabilized by tight interactions of this tryptophan with residue side chains of a symmetry-related molecule and enforced by a bound sulfate. Characterization of this plant annexin using biophysical methods revealed calcium-dependent binding to phospholipid vesicles with preference for phosphatidylcholine over phosphatidylserine and magnesium-dependent phosphodiesterase activity in vitro as shown with adenosine triphosphate as the substrate. A comparative unfolding study of recombinant annexin 24(Ca32) wild type and of the His-tag fusion protein indicates higher stability of the latter. The effect of this N-terminal modification is also visible from CD spectra. Both proteins were subjected to a FURA-2-based calcium influx assay, which gave high influx rates for the wild-type but greatly reduced influx rates for the fusion protein. We therefore conclude that the N-terminal domain is indeed a major regulatory element modulating different annexin properties by allosteric mechanisms. C1 Max Planck Inst Biochem, Abt Strukturforsch, D-82152 Martinsried, Germany. CNRS, Inst Biol Mol Plantes, F-67084 Strasbourg, France. RP Hofmann, A (reprint author), NCI, Macromol Crystallog Lab, Program Struct Biol, FCRDC, Frederick, MD 21702 USA. RI Hofmann, Andreas/B-9515-2008 OI Hofmann, Andreas/0000-0003-4408-5467 NR 41 TC 62 Z9 74 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 17 PY 2000 VL 275 IS 11 BP 8072 EP 8082 DI 10.1074/jbc.275.11.8072 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294LT UT WOS:000085913300088 PM 10713128 ER PT J AU Corton, JC Lapinskas, PJ Gonzalez, FJ AF Corton, JC Lapinskas, PJ Gonzalez, FJ TI Central role of PPAR alpha in the mechanism of action of hepatocarcinogenic peroxisome proliferators SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE peroxisome proliferators; receptor-mediated carcinogenesis; peroxisome proliferator-activated receptor; transcriptional activation; hepatocarcinogenesis ID ACTIVATED RECEPTOR-ALPHA; GLUTAMYL-TRANSFERASE TRANSPEPTIDASE; RATS FOLLOWING EXPOSURE; ENOYL-COA HYDRATASE; DNA-SYNTHESIS; LIVER-TUMORS; FATTY-ACIDS; GENE-EXPRESSION; CLOFIBRIC ACID; ELEVATED 8-HYDROXYDEOXYGUANOSINE AB Peroxisome proliferators (PP) are a large class of structurally dissimilar chemicals. These chemicals have diverse effects in rodents and humans, including regulation of lipid metabolism, growth promotion, and induction of hepatocarcinogenesis. Most, if not all, effects of PP are mediated by three members of the nuclear receptor superfamily called PP-activated receptors (PPAR). In this review, we discuss the evidence that PPAR alpha, the predominant PPAR in the, liver is involved in the growth promoting and hepatocarcinogenic effects of PP. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. DuPont Life Sci Enterprise, Haskell Labs, Stine Haskell Res Ctr, Newark, DE 19714 USA. NIH, Lab Metab, Bethesda, MD 20892 USA. RP Corton, JC (reprint author), Chem Ind Inst Toxicol, POB 12137,6 Davis Dr, Res Triangle Pk, NC 27709 USA. EM corton@ciit.org NR 90 TC 80 Z9 84 U1 0 U2 4 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 MAR 17 PY 2000 VL 448 IS 2 BP 139 EP 151 DI 10.1016/S0027-5107(99)00232-8 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 297AE UT WOS:000086058300003 PM 10725468 ER PT J AU Hasmall, SC James, NH Macdonald, N Gonzalez, FJ Peters, JM Roberts, RA AF Hasmall, SC James, NH Macdonald, N Gonzalez, FJ Peters, JM Roberts, RA TI Suppression of mouse hepatocyte apoptosis by peroxisome proliferators: role of PPAR alpha and TNF alpha SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE nafenopin; apoptosis; PPAR alpha null mice; transforming growth factor beta (Tgf-beta); tumour necrosis factor alpha (TNF alpha); peroxisome proliferator activated receptor alpha; (PPAR alpha); phenobarbitone; DNA synthesis ID TUMOR-NECROSIS-FACTOR; DNA-SYNTHESIS; RAT-LIVER; SPECIES-DIFFERENCES; CELL REPLICATION; IN-VITRO; RECEPTOR; NAFENOPIN; WY-14,643; ACID AB Peroxisome proliferators (PPs) are a diverse group of nongenotoxic chemicals that in rodents cause hepatic peroxisome proliferation, liver enlargement, increased replicative DNA synthesis and suppression of apoptosis. The effects of PPs in vivo can be reproduced in vitro where PPs can induce mouse hepatocyte DNA synthesis and suppress both spontaneous apoptosis and that induced by transforming growth factor beta (TGF beta). In vitro, high concentrations (> 500 U/ml) of exogenous tumour necrosis factor alpha (TNF alpha) [M. Rolfe, N.H. James, R.A. Roberts, TNF alpha suppresses apoptosis and induces S-phase in rodent hepatocytes: a mediator of the hepatocarcinogenicity of peroxisome proliferators?, Carcinogenesis 18 (1997) 2277-2280] are also able to stimulate hepatocyte DNA synthesis and suppress apoptosis, implicating TNF alpha in mediating or permitting the liver growth response to PPs. Here, using cultured mouse hepatocytes isolated from PPAR alpha null mice, we have examined the role of the peroxisome proliferator activated receptor cw (PPAR alpha) in mediating the suppression of apoptosis caused by PPs. In addition we have investigated further the role of TNF alpha in mediating the rodent response to PPs. The PP nafenopin (50 mu M) was unable to stimulate DNA synthesis measured by bromodeoxyuridine incorporation in these PPAR alpha null mouse hepatocytes (96% of control), unlike epidermal growth factor, a growth factor used as a positive control. In assays of apoptosis using H33258 staining of chromatin condensation, nafenopin was unable to suppress either spontaneous or TGF beta 1-induced apoptosis. In contrast, high concentrations of TNF alpha (> 500 U/ml) were able to both stimulate DNA synthesis (204% of control) and suppress apoptosis in PPAR alpha null hepatocytes (40% and 38% of control for spontaneous and TGF beta 1-induced apoptosis respectively). However, TNF alpha could not stimulate beta-oxidation of palmitoyl CoA in either PPAR alpha null mouse or B6C3F1 (PPAR alpha wild type) mouse hepatocytes. These data confirm the dependence of the response to PPs on PPAR alpha by demonstrating that PPAR alpha mediates the suppression of hepatocyte apoptosis in response to PPs. In addition, the data provide evidence that high concentrations of TNF alpha can modulate DNA synthesis and apoptosis in the absence of PPs and PPAR alpha. Thus, in vivo, physiological levels of TNF alpha may be permissive for a PPAR alpha-dependent growth response to PPs. (C) 2000 Elsevier Science B.V. All rights reserved. C1 AstraZeneca Cent Toxicol Lab, Alderley Pk SK10 4TJ, Cheshire, England. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Hasmall, SC (reprint author), AstraZeneca Cent Toxicol Lab, Alderley Pk SK10 4TJ, Cheshire, England. RI Peters, Jeffrey/D-8847-2011 NR 38 TC 39 Z9 40 U1 1 U2 1 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 MAR 17 PY 2000 VL 448 IS 2 BP 193 EP 200 DI 10.1016/S0027-5107(99)00236-5 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 297AE UT WOS:000086058300007 PM 10725472 ER PT J AU Dori, A Maric, D Maric, I Masalha, R Barker, JL Silverman, WF AF Dori, A Maric, D Maric, I Masalha, R Barker, JL Silverman, WF TI Striatal matrix neurons of the rat differentiate in culture from dissociated fetal progenitor cells isolated by buoyant density centrifugation SO NEUROSCIENCE LETTERS LA English DT Article DE development; basal ganglia; pattern formation; neural differentiation; neural progenitor ID SYSTEMS; NEUROGENESIS; DARPP-32; INPUT AB The adult striatum is composed of interlacing compartments known as patches (striosomes) and matrix, which differ with respect to a host of architectonic, biochemical and developmental parameters. We have exploited the 2-phase development of the striatum, employing buoyant-density fractionation to separate proliferating/undifferentiated neu rat precursors from the differentiated neurons of the E19 striatum. Primary cell cultures were established for the collected fractions, and immunohistochemistry for maturational and compartment-specific markers performed. The results indicate that the least buoyant, striatal precursors concentrate principally in the low buoyancy fraction of the gradient, and in culture express known matrix phenotype markers in an appropriate time frame. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, Dept Morphol, IL-84105 Beer Sheva, Israel. Soroka Med Ctr, Dept Neurol, IL-84105 Beer Sheva, Israel. NINCDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Silverman, WF (reprint author), Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, Dept Morphol, IL-84105 Beer Sheva, Israel. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 17 PY 2000 VL 282 IS 1-2 BP 77 EP 80 DI 10.1016/S0304-3940(00)00888-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 301DB UT WOS:000086292000020 PM 10713400 ER PT J AU May, A Bohr, VA AF May, A Bohr, VA TI Gene-specific repair of gamma-ray-induced DNA strand breaks in colon cancer cells: No coupling to transcription and no removal from the mitochondrial genome SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HAMSTER OVARY CELLS; OXIDATIVE DAMAGE; COCKAYNE-SYNDROME; RINR-38 CELLS; NUCLEAR-DNA; SITES; REGIONS; INVITRO AB We have measured gene-specific DNA damage and repair of alkaline-sensitive sites and DNA strand breaks after gamma-irradiation. Although fairly high doses are used in order to introduce sufficient DNA damage, Foe find that there is efficient and almost complete repair within 2 h. Human colon cancer cells were exposed to gamma-irradiation, and the repair was measured in various nuclear regions and in the mitochondrial genome. In the essential housekeeping gene, dihydrofolate reductase (DHFR), there was about 80% repair of the strand breaks after 2 h. There was no difference in the repair activities between the two individual DNA strands of the DHFR gene, and thus no evidence of strand bias, or transcription coupling of the repair process. There was no preferential repair of the DHFR gene compared to repair in an inactive, X-linked, noncoding gene. We can thus not detect any nuclear heterogeneity of the formation and repair of these lesions. In contrast, the formation and processing of gamma-irradiation introduced lesions differ in the mitochondrial DNA. Here, we detect about twofold more alkaline-sensitive sites and strand breaks after gamma-irradiation than observed in the DHFR gene. The repair of these lesions is deficient in the mitochondria, where only about 25% are removed within 2 h. (C) 2000 Academic Press. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP May, A (reprint author), NIA, Genet Mol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 28 Z9 40 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 16 PY 2000 VL 269 IS 2 BP 433 EP 437 DI 10.1006/bbrc.2000.2264 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 296KM UT WOS:000086023600026 PM 10708571 ER PT J AU Coppock, D Kopman, C Gudas, J Cina-Poppe, DA AF Coppock, D Kopman, C Gudas, J Cina-Poppe, DA TI Regulation of the quiescence-induced genes: Quiescin Q6, decorin, and ribosomal protein S29 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE quiescence; senescence; quiescin Q6; decorin; S29; trypsinization; cell cycle; sulfhydryl oxidase ID GROWTH-FACTOR-BETA; CYCLIN-DEPENDENT KINASES; CONTACT INHIBITION; HUMAN FIBROBLASTS; EXPRESSION; CELLS; ARREST; PROTEOGLYCANS; INDUCTION; SUPPRESSION AB The transition from growth to quiescence is deeply deranged in cancer cells. Expression of the quiescence-induced genes, quiescin Q6, decorin, and S29, was examined in important physiological states and in several cell types. Senescent fibroblasts expressed neither Q6 nor decorin mRNAs. The quiescins were induced in serum-deprived cultures. Trypsinized cells, which rapidly reattached to the culture dish, expressed Q6, S29, and decorin mRNAs at reduced levels, compared to those that remained in suspension. Expression of Q6 and S29 mRNAs in endothelial cells was low in growth phase and high in quiescent cells. Q6 and S29 mRNAs were found in a large variety of human tissues. The quiescin Q6 protein was detected in WI38 cell extracts and in conditioned medium from quiescent cells. A complex regulation of the quiescins by growth and attachment status in specific cell types may he of importance in pathological growth regulation and the development of cancer, (C) 2000 Academic Press. C1 Winthrop Univ Hosp, Oncol Res Lab, Mineola, NY 11501 USA. SUNY Stony Brook, Dept Med, Moscow 117901, Russia. NCI, NIH, Bethesda, MD 20892 USA. RP Coppock, D (reprint author), Winthrop Univ Hosp, Oncol Res Lab, 222 Stn Plaza N,300, Mineola, NY 11501 USA. NR 42 TC 59 Z9 61 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 16 PY 2000 VL 269 IS 2 BP 604 EP 610 DI 10.1006/bbrc.2000.2324 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 296KM UT WOS:000086023600056 PM 10708601 ER PT J AU Zahuczky, G Boross, P Bagossi, P Emri, G Copeland, TD Oroszlan, S Louis, JM Tozser, J AF Zahuczky, G Boross, P Bagossi, P Emri, G Copeland, TD Oroszlan, S Louis, JM Tozser, J TI Cloning of the bovine leukemia virus proteinase in Escherichia coli and comparison of its specificity to that of human T-cell leukemia virus proteinase SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE BLV proteinase; HTLV-1 proteinase; oligopeptide substrate; substrate specificity; inhibitor binding ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-PROTEASE INHIBITORS; BACTERIAL EXPRESSION; GAG; POLYPROTEINS; PRECURSOR; CLEAVAGE; KINETICS; BINDING; ANALOG AB The protinase of bovine leukemia virus (BLV) was cloned into pMal-c2 vector with N-terminal or with N- as well as C-terminal flanking sequences, and expressed in fusion with maltose binding protein. The proteinase self-processed itself from the fusion protein during expression and formed inclusion bodies. The enzyme was purified from inclusion bodies by cation-exchange chromatography followed by gel filtration. Specificity of the enzyme was compared to that of human T-cell leukemia proteinase type I. Although the two viruses belong to the same subfamily of retroviruses, the differences in their proteinase specificity, based on kinetics with oligopeptide substrates representing naturally occurring cleavage sites as well as on inhibition pattern, appear to be pronounced. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Debrecen, Sch Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Special Program Prot Chem, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Virol & Carcinogenesis Lab, Frederick, MD 21702 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tozser, J (reprint author), Univ Debrecen, Sch Med, Dept Biochem & Mol Biol, POB 6, H-4012 Debrecen, Hungary. EM tozser@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 37 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD MAR 16 PY 2000 VL 1478 IS 1 BP 1 EP 8 DI 10.1016/S0167-4838(99)00240-X PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 297NJ UT WOS:000086088700001 PM 10719169 ER PT J AU Stevens, DA Schwartz, HJ Lee, JY Moskovitz, BL Jerome, DC Catanzaro, A Bamberger, DM Weinmann, AJ Tuazon, CU Judson, MA Platts-Mills, TAE DeGraff, AC Grossman, J Slavin, RG Reuman, P AF Stevens, DA Schwartz, HJ Lee, JY Moskovitz, BL Jerome, DC Catanzaro, A Bamberger, DM Weinmann, AJ Tuazon, CU Judson, MA Platts-Mills, TAE DeGraff, AC Grossman, J Slavin, RG Reuman, P TI A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY FEB 26-MAR 03, 1999 CL ORLANDO, FLORIDA SP Amer Acad Allergy Asthma & Immunol ID INVASIVE ASPERGILLOSIS; THERAPY; CRITERIA; KETOCONAZOLE; FLUCONAZOLE; INVITRO AB Background: Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. The main treatment is systemic corticosteroids, but data from uncontrolled studies suggest that itraconazole, an orally administered antifungal agent, may be an effective adjunctive therapy. Methods: We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met immunologic and pulmonary-function criteria for corticosteroid-dependent allergic bronchopulmonary aspergillosis. A response was defined as a reduction of at least 50 percent in the corticosteroid dose, a decrease of at least 25 percent in the serum IgE concentration, and one of the following: an improvement of at least 25 percent in exercise tolerance or pulmonary-function tests or resolution or absence of pulmonary infiltrates. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks. Results: There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). The rate of adverse events was similar in the two groups. In the subsequent open-label phase, 12 of the 33 patients who had not had a response during the double-blind phase (36 percent) had responses, and none of the patients who had a response in the double-blind phase of the trial had a relapse. Conclusions: For patients with corticosteroid-dependent allergic bronchopulmonary aspergillosis, the addition of itraconazole can lead to improvement in the condition without added toxicity. (N Engl J Med 2000;342:756-62.) (C)2000, Massachusetts Medical Society. C1 Santa Clara Valley Med Ctr, Dept Med, San Jose, CA 95128 USA. Stanford Univ, Sch Med, Dept Med, Div Infect Dis & Geog Med, Stanford, CA USA. NIAID, Mycoses Study Grp, NIH, Bethesda, MD USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Alabama, Birmingham, AL USA. Janssen Pharmaceut, Titusville, NJ USA. Vet Affairs Med Ctr, Long Beach, CA USA. Univ Missouri, Sch Med, Dept Med, Kansas City, MO 64108 USA. Wayne State Univ, Div Infect Dis, Detroit, MI USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Med Univ S Carolina, Div Pulm & Crit Care, Charleston, SC USA. Univ Virginia, Dept Med, Charlottesville, VA USA. Univ Connecticut, Dept Med, Hartford, CT 06112 USA. Vivra Res, Tucson, AZ USA. St Louis Univ, Sch Med, St Louis, MO USA. NIAID, Mycoses Study Grp, NIH, Bethesda, MD USA. RP Stevens, DA (reprint author), Santa Clara Valley Med Ctr, Dept Med, 751 S Bascom Ave, San Jose, CA 95128 USA. OI Judson, Marc/0000-0002-4663-7985 FU NIAID NIH HHS [N0-AI-15082, N0-AI-65296, R01-AI-30840] NR 45 TC 242 Z9 258 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 16 PY 2000 VL 342 IS 11 BP 756 EP 762 DI 10.1056/NEJM200003163421102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 293HW UT WOS:000085846900002 PM 10717010 ER PT J AU Dalakas, MC Park, KY Semino-Mora, C Lee, HS Sivakumar, K Goldfarb, LG AF Dalakas, MC Park, KY Semino-Mora, C Lee, HS Sivakumar, K Goldfarb, LG TI Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MICE LACKING DESMIN; ALPHA-B-CRYSTALLIN; MYOFIBRILLAR MYOPATHY; INTERMEDIATE FILAMENTS; NULL MUTATION; MUSCLE; POSITIVITY; EXPRESSION; PROTEINS; VACUOLES AB Background: Myofibrillar myopathies are a heterogeneous group of inherited or sporadic skeletal myopathies associated with cardiomyopathy. Among the myofibrillar proteins that accumulate within the muscle fibers of affected patients, the one found most consistently is desmin, an intermediate-filament protein responsible for the structural integrity of the myofibrils. Skeletal and cardiac myopathy develops in mice that lack desmin, suggesting that mutations in the desmin gene may be pathogenic. Methods: We examined 22 patients from 8 families with dominantly inherited myofibrillar or desmin-related myopathy and 2 patients with sporadic disease and analyzed the desmin gene for mutations, using complementary DNA (cDNA) amplified from muscle-biopsy specimens and genomic DNA extracted from blood lymphocytes. Restriction-enzyme analysis was used to confirm the mutations. Expression vectors containing normal or mutant desmin cDNA were introduced into cultured cells to determine whether the mutant desmin formed intermediate filaments. Results: Six missense mutations in the coding region of the desmin gene that cause the substitution of an amino acid were identified in 11 patients (10 members of 4 families and 1 patient with sporadic disease); a splicing defect that resulted in the deletion of exon 3 was identified in the other patient with sporadic disease. Mutations were clustered in the carboxy-terminal part of the rod domain, which is critical for filament assembly. In transfected cells, the mutant desmin was unable to form a filamentous network. Seven of the 12 patients with mutations in the desmin gene had cardiomyopathy. Conclusions: Mutations in the desmin gene affecting intermediate filaments cause a distinct myopathy that is often associated with cardiomyopathy and is termed "desmin myopathy.'' The mutant desmin interferes with the normal assembly of intermediate filaments, resulting in fragility of the myofibrils and severe dysfunction of skeletal and cardiac muscles. (N Engl J Med 2000;342:770-80.) (C)2000, Massachusetts Medical Society. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Rm 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. NR 31 TC 257 Z9 271 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 16 PY 2000 VL 342 IS 11 BP 770 EP 780 DI 10.1056/NEJM200003163421104 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 293HW UT WOS:000085846900004 PM 10717012 ER PT J AU Lubin, JH Pottern, LM Stone, BJ Fraumeni, JF AF Lubin, JH Pottern, LM Stone, BJ Fraumeni, JF TI Respiratory cancer in a cohort of copper smelter workers: Results from more than 50 years of follow-up SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arsenic; dose-response relationship; immunologic; lung neoplasms; occupational diseases ID ARSENIC EXPOSURE; DRINKING-WATER; LUNG-CANCER; DOSE-RESPONSE; MORTALITY EXPERIENCE; BLADDER-CANCER; TIN MINERS; OCCUPATIONAL EXPOSURE; DIABETES-MELLITUS; URANIUM MINERS AB Several studies have linked inhalation of airborne arsenic with increased risk of respiratory cancer, but few have analyzed the shape of the exposure-response curve. In addition, since inhaled airborne arsenic affects systemic levels of inhaled arsenic, there is concern that inhaled arsenic may be associated with cancers of the skin, bladder, kidney, and liver, which have been linked to ingested arsenic. The authors followed 8,014 white male workers who were employed for 12 months or more prior to 1957 at a Montana copper smelter from January 1, 1938 through December 31, 1989. A total of 4,930 (62%) were deceased, including 446 from respiratory cancer. Significantly increased standardized mortality ratios (SMRs) were found for all causes (SMR = 1.14), all cancers (SMR = 1.13), respiratory cancer (SMR = 1.55), diseases of the nervous system and sense organs (SMR = 1.31), nonmalignant respiratory diseases (SMR = 1.56), emphysema (SMR = 1.73), ill-defined conditions (SMR = 2.26), and external causes (SMR = 1.35). Internal analyses revealed a significant, linear increase in the excess relative risk of respiratory cancer with increasing exposure to inhaled airborne arsenic. The estimate of the excess relative risk per mg/m(3)-year was 0.21/(mg/m(3)-year) (95% confidence interval: 0.10, 0.46). No other cause of death was related to inhaled arsenic exposure. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 66 TC 54 Z9 54 U1 0 U2 4 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2000 VL 151 IS 6 BP 554 EP 565 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 295NU UT WOS:000085975400003 PM 10733037 ER PT J AU Cooper, GS Baird, DD Weinberg, CR Ephross, SA Sandler, DP AF Cooper, GS Baird, DD Weinberg, CR Ephross, SA Sandler, DP TI Age at menopause and childbearing patterns in relation to mortality SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE menopause; mortality; parity ID NATURAL MENOPAUSE; HEALTH AB Several studies have reported increased mortality risk with early natural menopause. More recently, mortality risk was reported to be reduced among women who gave birth at age greater than or equal to 40 years. The association between reproductive history and mortality was explored among 826 women in a prospective study involving 18,959 person-years of follow-up (from age 50 to 1990-1991) and 108 deaths, After adjustment for age and other covariates, the risk ratio among parous women was 1.53 (95% confidence interval: 0.58, 4.07) for natural menopause at age less than or equal to 45 years compared with greater than or equal to 51 years. In contrast to a previous report, however, the highest estimated mortality risk was seen among women who gave birth in their forties (adjusted risk ratio = 2.14, 95% confidence interval: 1.05, 4.38) compared with having a last birth at ages 30-34 years. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. GlaxoWellcome, Worldwide Epidemiol Dept, Res Triangle Pk, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018 FU NCRR NIH HHS [M01-RR00064] NR 9 TC 40 Z9 40 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2000 VL 151 IS 6 BP 620 EP 623 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 295NU UT WOS:000085975400010 PM 10733044 ER PT J AU Borchers, C Peter, JF Hall, MC Kunkel, TA Tomer, KB AF Borchers, C Peter, JF Hall, MC Kunkel, TA Tomer, KB TI Identification of in-gel digested proteins by complementary peptide mass fingerprinting and tandem mass spectrometry data obtained on an electrospray ionization quadrupole time-of-flight mass spectrometer SO ANALYTICAL CHEMISTRY LA English DT Article ID SEQUENCE DATABASES; RAPID IDENTIFICATION; TAGS AB The present study reports a procedure developed for the identification of SDS-polyacrylamide gel electrophoretically separated proteins using an electrospray ionization quadrupole time-of-flight mass spectrometer (Q-TOF MS) equipped with pressurized sample introduction. It is based on in-gel digestion of the proteins without previous reduction/alkylation and on the capability of the Q-TOF MS to provide data suitable for peptide mass fingerprinting database searches and for tandem mass spectrometry (MS/MS) database searches (sequence tags), Omitting the reduction/alkylation step reduces sample contamination and sample loss, resulting in increased sensitivity. Omitting this step can leave disulfide-connected peptides in the analyte that can lead to misleading or ambiguous results from the peptide mass fingerprinting database search. This uncertainty, however, is overcome by MS/MS analysis of the peptides, Furthermore, the two complementary MS approaches increase the accuracy of the assignment of the unknown protein. This procedure is thus, highly sensitive, accurate, and rapid. In combination with pressurized nanospray sample introduction, it is suitable for automated sample handling. Here, we apply this approach to identify protein contaminants observed during the purification of the yeast DNA mismatch repair protein M1h1. C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 23 TC 64 Z9 65 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 15 PY 2000 VL 72 IS 6 BP 1163 EP 1168 DI 10.1021/ac990937m PG 6 WC Chemistry, Analytical SC Chemistry GA 295NR UT WOS:000085975200009 PM 10740854 ER PT J AU Olsen, V Loh, YP AF Olsen, V Loh, YP TI In vivo processing of nonanchored yapsin 1 (Yap3p) SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE proprotein; aspartic protease ID OPIOMELANOCORTIN-CONVERTING ENZYME; YEAST ASPARTIC PROTEASE-3; ALPHA-FACTOR; GENE-PRODUCT; PROTEINASE-A; CATHEPSIN-D; MF-ALPHA; ACTIVATION; IDENTIFICATION; PURIFICATION AB A C-terminally truncated form of yapsin 1 (yeast aspartic protease 3) was overexpressed in yeast and its processing through the secretory pathway was followed by pulse-labeling and immunoprecipitation studies. In the soluble cell extract, three forms of yapsin 1-87, 74, and 18 kDa-were found. Identification of these forms of yapsin 1 using different antisera suggests that the 87-kDa form is pro-yapsin 1, which is processed into two subunits, alpha (18 kDa) and beta (74 kDa), by cleavage at a loop region not found in traditional aspartic proteases. By use of a temperature-sensitive mutant strain, sec18, the generation of the two subunits was found to occur in the endoplasmic reticulum. An active site-mutated yapsin 1 was not processed into the two subunits, suggesting that this process occurs in an autocatalytic manner. (C) 2000 Academic Press. C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 34 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 15 PY 2000 VL 375 IS 2 BP 315 EP 321 DI 10.1006/abbi.1999.1665 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 296HL UT WOS:000086018900011 PM 10700387 ER PT J AU Wagner, PD Vu, ND AF Wagner, PD Vu, ND TI Histidine to aspartate phosphotransferase activity of nm23 proteins: phosphorylation of aldolase C on Asp-319 SO BIOCHEMICAL JOURNAL LA English DT Article DE cell motility; metastasis; nucleoside diphosphate kinases ID NUCLEOSIDE-DIPHOSPHATE KINASE; ATP-CITRATE-LYASE; MESSENGER-RNA; TUMOR-METASTASIS; ESCHERICHIA-COLI; BACTERIAL CHEMOTAXIS; GENE; EXPRESSION; SEQUENCE; SITE AB nm23 genes have been implicated in the suppression of tumour metastasis and cell motility; however, the biochemical mechanisms for these suppressions are not known. We have previously described the transfer of phosphate from the catalytic histidine residues of nm23 proteins to an aspartic or a glutamic residue on one or more 43 kDa proteins in detergent extracts of bovine brain membranes. To gain a better understanding of this transferase activity, we partly purified this 43 kDa protein and identified aldolases A and C as the major 43 kDa proteins present in the preparation. Aldolase was purified from brain cytosol; its phosphorylation by rat liver nm23 proteins and by recombinant human nm23-H1 was examined. The site of phosphorylation was identified as Asp-319 on aldolase C. The equivalent residue on aldolase A, a glutamic residue, was not phosphorylated. Aldolase C was rapidly phosphorylated by wild-type nm23-H1 but was not phosphorylated, or was phosphorylated very slowly, by either nm23-H1(P968) Or nm23-H1(S120G), mutants of nm23-H1 that do not suppress cell motility. This is the first identification of a protein that is phosphorylated on an aspartic residue by nm23 proteins. The sequence around Asp-319 of aldolase C has some similarities to those around the histidine residues on ATP-citrate lyase and succinic thiokinase that are phosphorylated by nm23 proteins. C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Wagner, PD (reprint author), NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 44 TC 46 Z9 48 U1 0 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 2000 VL 346 BP 623 EP 630 DI 10.1042/0264-6021:3460623 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 300KX UT WOS:000086253100009 PM 10698688 ER PT J AU Carballo, E Lai, WS Blackshear, PJ AF Carballo, E Lai, WS Blackshear, PJ TI Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; FINGER TRANSCRIPTION FACTOR; HEMATOPOIETIC STEM-CELLS; AU-RICH ELEMENTS; BONE-MARROW; FACTOR-ALPHA; GM-CSF; FACTOR EXPRESSION; STROMAL CELLS; RESPONSE-GENE AB Deficiency of tristetraprolin (TTP), the prototype of the CCCH zinc finger proteins, results in a complex inflammatory syndrome in mice. Most aspects of the syndrome are secondary to excess circulating tumor necrosis factor (TNF)-alpha, a consequence of increased stability of TNF-alpha messenger RNA (mRNA) in TTP-deficient macrophages. TTP can bind directly to the AU-rich element in TNF-alpha mRNA, increasing its lability, Here we show that TTP deficiency also results in increased cellular production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased stability of its mRNA, apparently secondary to decreased deadenylation. Similar findings were observed in mice also lacking both types of TNF-alpha receptors, excluding excess TNF-alpha production as a cause of the increased GM-CSF mRNA levels and stability. TTP appears to be a physiological regulator of GM-CSF mRNA deadenylation and stability. (C) 2000 by The American Society of Hematology. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, MD A2-05,POB 12233, Res Triangle Pk, NC 27709 USA. NR 51 TC 315 Z9 319 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2000 VL 95 IS 6 BP 1891 EP 1899 PG 9 WC Hematology SC Hematology GA 293DW UT WOS:000085837100002 PM 10706852 ER PT J AU Roesler, J Curnutte, JT Rae, J Barrett, D Patino, P Chanock, SJ Goerlach, A AF Roesler, J Curnutte, JT Rae, J Barrett, D Patino, P Chanock, SJ Goerlach, A TI Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease SO BLOOD LA English DT Article ID RESPIRATORY BURST OXIDASE; PHAGOCYTE NADPH OXIDASE; CONVERSION; MUTATIONS; COMPONENTS; ACTIVATION; MECHANISMS; SEQUENCES; P40(PHOX); BINDING AB Chronic granulomatous disease (CGD) is an inherited disease caused by defects in the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase of phagocytes, Genetic lesions in any of 4 components of this antimicrobial enzyme have been detected. Family-specific mutations are found in 3 of 4 forms of CGD due to deficiencies of the gp91-phox, p22-phox, and p67-phox genes. In p47-phox-deficient CGD (autosomal recessive form A47 degrees) patients, a GT deletion (Delta GT) at the beginning of exon 2 of the p47-phox gene has been reported in 19 of 20 alleles. This GT deletion is also characteristic for the recently identified p47-phox pseudogenes, To explore a possible link between these findings, a sequence analysis of 28 unrelated, racially diverse A47 degrees CGD patients and 37 healthy individuals was performed. The GT deletion in exon 2 was present on all alleles in 25 patients. Only 3 patients but all healthy individuals contained the GTGT and Delta GT sequences. A total of 22 patients carried additional pseudogene-specific intronic sequences on all alleles, either only in intron 1 or in Intron 1 and Intron 2, which lead to different types of chimeric DNA strands. It Is concluded that recombination events between the p47-phox gene and its highly homologous pseudogenes result in the incorporation of Delta GT into the p47-phox gene, thereby leading to the high frequency of GT deletion in A47 degrees CGD patients. (C) 2000 by The American Society of Hematology. C1 Genentech Inc, Dept Immunol, S San Francisco, CA 94080 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Antioquia, Sch Med, Medellin, Colombia. RP Curnutte, JT (reprint author), Genentech Inc, Dept Immunol, 1 DNA Way,Bldg 12,Mailstop 34, S San Francisco, CA 94080 USA. RI Gorlach, Agnes/B-3494-2013 NR 34 TC 62 Z9 67 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2000 VL 95 IS 6 BP 2150 EP 2156 PG 7 WC Hematology SC Hematology GA 293DW UT WOS:000085837100038 PM 10706888 ER PT J AU Ramsey, SD Andersen, MR Etzioni, R Moinpour, C Peacock, S Potosky, A Urban, N AF Ramsey, SD Andersen, MR Etzioni, R Moinpour, C Peacock, S Potosky, A Urban, N TI Quality of life in survivors of colorectal carcinoma SO CANCER LA English DT Article; Proceedings Paper CT Conference on Research Issues in Cancer Survivorship CY MAR 09-10, 1998 CL BETHESDA, MARYLAND SP NCI DE health-related quality of life; colorectal carcinoma; Health Utilities Index; Functional Assessment of Cancer Therapy ID OF-LIFE; PROSTATE-CANCER; BREAST-CANCER; HEALTH; COSTS; STAGE; COLON; LUNG AB BACKGROUND. Colon carcinoma is a common malignancy that accounts for a substantial share of all cancer-related morbidity and mortality. However, little is known with regard to general and disease specific quality of life in survivors of colorectal carcinoma, particularly from community-based samples of cases across stage and survival times from diagnosis. METHODS, Subjects with colorectal carcinoma were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registry. Subjects completed two self-administered surveys: the Functional Assessment of Cancer Therapy Scales for Colorectal Cancer (FACT-C) and the Wealth Utilities Index (HUI) Mark III. RESULTS. One hundred seventy-three respondents (average age: 70.4 years, 71.4% female) completed the survey. In the first 3 years after diagnosis, quality of life was lower and varied substantially among respondents. After 3 years, respondents in all TNM stages of disease except Stage IV reported a relatively uniform and high quality of life. Pain, functional well-being, and social well-being were affected most substantially across all stages and times from diagnosis. Low income status was associated with worse outcomes for pain, ambulation, and social and emotional well-being. Only emotional well-being scores improved significantly over time in both surveys. CONCLUSIONS. Those individuals who achieve a long term remission from colorectal carcinoma may experience a relatively high quality of life, although deficits remain for several areas, particularly in those of low socioeconomic status. Sampling design may have excluded the most severely ill patients. Cancer 2000;88: 1294-1303. (C) 2000 American Cancer Society. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. SW Oncol Grp, Seattle, WA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mailstop MP 804,1100 Fairview Ave N,Box 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [N01-CN-65034-2, N01-CN-05320] NR 23 TC 220 Z9 225 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2000 VL 88 IS 6 BP 1294 EP 1303 DI 10.1002/(SICI)1097-0142(20000315)88:6<1294::AID-CNCR4>3.0.CO;2-M PG 10 WC Oncology SC Oncology GA 294QG UT WOS:000085921400004 PM 10717609 ER PT J AU Frisch, M Goodman, MT AF Frisch, M Goodman, MT TI Human papillomavirus-associated carcinomas in Hawaii and the mainland US SO CANCER LA English DT Article DE human papillomaviruses; cervical neoplasms; vulvar/vaginal neoplasms; anal neoplasms; penile neoplasms; tonsillar neoplasms; Hawaii; US ID ANAL CANCER; INFECTION; RISK AB BACKGROUND. To the authors' knowledge, human papillomavirus (HPV)-associated carcinomas in Hawaii have not been studied in detail. METHODS. Surveillance, Epidemiology, and End Results data (from 1973-1996) were used to study rare of incidence patterns of squamous cell carcinomas (SCCs) of the uterine cervix, vulva/vagina, anus, penis, and palatine tonsils among Asian/Pacific Islanders and whites in Hawaii and among whites in the U.S. in general. RESULTS. With the exception of invasive cervical SCC, male and female Asian/ Pacific Islanders in Hawaii had considerably lower incidence rates of HPV-associated SCCs than Hawaii whites and U.S. whites. Among women, Hawaii whites and U.S. whites had rather similar rates of invasive anogenital and tonsillar SCCs, but in situ SCC of the cervix or vulva/vagina was diagnosed less often among Asian/Pacific Islanders and whites in Hawaii than among whites in the general U.S. Among men, Hawaii whites had higher rates than U.S. whites of both anal and tonsillar, but not penile, SCCs. Among Hawaiian men with anal carcinoma, 43% (15 of 35) had remained unmarried versus 3% (2 of 65) of Hawaiian women with anal carcinoma. CONCLUSIONS. Asian/Pacific Islanders in Hawaii generally have lower incidence rates of HPV-associated SCCs than whites. However, low ratios of in situ to invasive cervical SCCs suggest that many Hawaii women, notably Asian/Pacific Islanders, are not diagnosed and treated for cervical neoplasias at a preinvasive stage. The high rate of incidence of anal SCC in male Hawaiian whites and the high proportions of unmarried men among patients with this disease suggest the transmission of HPV through homosexual contact. These men may be targeted in future screening programs for anal carcinoma. Cancer 2000;88:1464-9, (C) 2000 American Cancer Society. C1 Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Bethesda, MD USA. Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. RP Frisch, M (reprint author), Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, 5 Artillerivej, DK-2300 Copenhagen, Denmark. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 FU NCI NIH HHS [N01-PC-67001] NR 23 TC 32 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2000 VL 88 IS 6 BP 1464 EP 1469 DI 10.1002/(SICI)1097-0142(20000315)88:6<1464::AID-CNCR26>3.0.CO;2-O PG 6 WC Oncology SC Oncology GA 294QG UT WOS:000085921400026 PM 10717631 ER PT J AU Smith, MA Freidlin, B Ries, LAG Simon, R AF Smith, MA Freidlin, B Ries, LAG Simon, R TI Increased incidence rates but no space-time clustering of childhood astrocytoma in Sweden, 1973-1992 - A population-based study of pediatric brain tumors SO CANCER LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), NCI, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2000 VL 88 IS 6 BP 1492 EP 1493 DI 10.1002/(SICI)1097-0142(20000315)88:6<1492::AID-CNCR30>3.0.CO;2-7 PG 2 WC Oncology SC Oncology GA 294QG UT WOS:000085921400030 PM 10717635 ER PT J AU Feldman, AL Restifo, NP Alexander, HR Bartlett, DL Hwu, P Seth, P Libutti, SK AF Feldman, AL Restifo, NP Alexander, HR Bartlett, DL Hwu, P Seth, P Libutti, SK TI Antiangiogenic gene therapy of cancer utilizing a recombinant adenovirus to elevate systemic endostatin levels in mice SO CANCER RESEARCH LA English DT Article ID ANGIOGENESIS; GROWTH AB Gene therapy represents a possible alternative to the chronic delivery of recombinant antiangiogenic proteins to cancer patients. Inducing normal host tissues to produce high circulating levels of these proteins may be more effective than targeting antiangiogenic genes to tumor tissue specifically. Previously reported gene therapy approaches in mice have achieved peak circulating endostatin levels of 8-33 ng/ml. Here we report plasma endostatin levels of 1770 ng/ml after administration of a recombinant adenovirus. Growth of MC38 adenocarcinoma, which is relatively resistant to adenoviral infection, was inhibited by 40%. These findings encourage gene delivery approaches that use the host as a "factory" to produce high circulating levels of antiangiogenic agents. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Human Gene Therapy Res Inst, Des Moines, IA 50309 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Feldman, Andrew/D-5028-2012; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 17 TC 117 Z9 138 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2000 VL 60 IS 6 BP 1503 EP 1506 PG 4 WC Oncology SC Oncology GA 297UR UT WOS:000086101500007 PM 10749112 ER PT J AU Englert, CR Baibakov, GV Emmert-Buck, MR AF Englert, CR Baibakov, GV Emmert-Buck, MR TI Layered expression scanning: Rapid molecular profiling of tumor samples SO CANCER RESEARCH LA English DT Article ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION; SEQUENCE TAGS; HUMAN-GENOME; CANCER; TISSUE; MICROARRAY; PATTERNS; DNA AB Layered expression scanning is a new approach to comprehensive molecular analysis of tumor samples that uses a layered array of capture membranes coupled to antibodies or DNA sequences to perform multiplex protein or mRNA analysis. Cell or tissue samples are transferred through a series of individual capture layers, each linked to a separate antibody or DNA sequence. As the biomolecules traverse the membrane set, each targeted protein or mRNA is specifically captured by the layer containing its antibody or cDNA sequence. The two-dimensional relationship of the cell populations is maintained during the transfer process, thereby producing a molecular profile of each cell type present, Reduction-to-practice of the technique is demonstrated by analysis of prostate-specific antigen (PSA) protein, gelatinase A protein, and POV1 (PB39) cDNA. As layered expression scanning technology progresses, we envision a laboratory method that will have multiple applications for high-throughput molecular profiling of normal and tumor samples. C1 NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 45 Z9 47 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2000 VL 60 IS 6 BP 1526 EP 1530 PG 5 WC Oncology SC Oncology GA 297UR UT WOS:000086101500012 PM 10749117 ER PT J AU Im, YH Kim, HT Lee, C Poulin, D Welford, S Sorensen, PHB Denny, CT Kim, SJ AF Im, YH Kim, HT Lee, C Poulin, D Welford, S Sorensen, PHB Denny, CT Kim, SJ TI EWS-FLI1, EWS-ERG, and EWS-ETV1 oncoproteins of Ewing tumor family all suppress transcription of transforming growth factor beta type II receptor gene SO CANCER RESEARCH LA English DT Article ID GASTRIC-CANCER CELLS; ETS-FAMILY; SARCOMA TRANSLOCATION; TGF-BETA; EXPRESSION; MEMBER; FUSES AB Ewing sarcoma-specific chromosomal translocations fuse the EWS gene to a subset of ets transcription factor family members, most commonly the FLII gene and Less frequently ERG, ETV1, E1A-F, or FEV, These fusion proteins art thought to act as aberrant transcription factors that bind DNA through their Ets DNA binding domain. Recently, we have shown (K-B. Hahm et al., Nat. Genet., 23: 222-227, 1999) that the transforming growth factor beta (TGB-beta) type II receptor (TGF-beta RII), a putative tumor suppressor gene, is a target of the EWS-FLI1 fusion protein. Here, me also examined effects of EWS-ETV1 and EWS-ERG on expression of the TGF-beta RII gene. We show that relative to the control, NIH-3T3 cell lines stably transfected with the EWS-FLI1, EWS-ERG, or EWS-ETV1 gene fusion ex-press reduced levels of TGF-beta RII. mRNA and protein, and that these cell lines have reduced TGF-beta sensitivity, Cotransfection of these fusion genes and the TGF-beta RII promoter suppresses TGF-beta RII promoter activity and also FLI1-, ERG-, or ETV1-induced promoter activity. These results indicate that transcriptional repression of TGF-beta RII is an important target of the EWS-FLI1, EWS-ERG, or EWS-ETV1 oncogene, and that EWS-ets fusion proteins may function as dominant negative forms of ets transcription factors. C1 NCI, Lab Cell Regulat & Carcinogenesis, DBS, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Johnson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Pediat, Gwyne Hazen Cherry Mem Labs, Div Hematol Oncol, Los Angeles, CA 90024 USA. Womens & Childrens Hosp, Dept Pathol, Vancouver, BC V6H 3V4, Canada. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, DBS, Bldg 41,Room B1106, Bethesda, MD 20892 USA. NR 32 TC 71 Z9 75 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2000 VL 60 IS 6 BP 1536 EP 1540 PG 5 WC Oncology SC Oncology GA 297UR UT WOS:000086101500014 PM 10749119 ER PT J AU Domachowske, JB Bonville, CA Dyer, KD Easton, AJ Rosenberg, HF AF Domachowske, JB Bonville, CA Dyer, KD Easton, AJ Rosenberg, HF TI Pulmonary eosinophilia and production of MIP-1 alpha are prominent responses to infection with pneumonia virus of mice SO CELLULAR IMMUNOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMATE RIBONUCLEASE GENES; AIRWAY EPITHELIAL-CELLS; IL-5 TRANSGENIC MICE; MOLECULAR-CLONING; CATIONIC PROTEIN; CC-CHEMOKINE; SCHISTOSOMA-MANSONI; ANTIVIRAL ACTIVITY AB Human eosinophils secrete two distinct ribonucleases that have antiviral activity against pathogens of the family Paramyxoviridae. To examine the role of eosinophils and their ribonucleases in host defense against paramyxovirus pathogens in vivo we have developed a mouse model involving a viral pathogen that naturally targets a rodent host. In this work we describe infection of Balb/c mice with pneumonia virus of mice (PVM, strain J3666), a paramyxovirus pathogen found frequently among rodent populations. We show here that pulmonary eosinophilia is an immediate response to infection with PVM, with bronchoalveolar lavage fluid containing 12-14% eosinophils obtained as early as day 3 postinoculation, Infection is accompanied by the production of macrophage inflammatory protein-1-alpha (MIP-1 alpha), a chemokine that has been associated with the pulmonary eosinophilia observed in response to respiratory syncytial virus infection in humans and with enhanced clear ance of influenza virus in mice. Interestingly, we observed no changes in expression of the chemoattractants eotaxin and RANTES in response to PVM infection, and interleukin-5 remained undetectable throughout. These responses-clinical pathology, viral recovery, pulmonary eosinophilia, and production of MIP-1 alpha-will provide a means for exploring the role of eosinophils, eosinophil secretory ribonucleases, and eosinophil chemoattractants in host defense against PVM and related paramyxovirus pathogens in vivo. (C) 2000 Academic Press. C1 NIAID, LHD, NIH, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Pediat, Syracuse, NY 13210 USA. Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. RP Domachowske, JB (reprint author), NIAID, LHD, NIH, 9000 Rockville Pike,Bldg 10,Room 11N104, Bethesda, MD 20892 USA. NR 64 TC 50 Z9 50 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR 15 PY 2000 VL 200 IS 2 BP 98 EP 104 DI 10.1006/cimm.2000.1620 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 307KK UT WOS:000086652300005 PM 10753501 ER PT J AU Arndt, SO Vogt, AB Markovic-Plese, S Martin, R Moldenhauer, G Wolpl, A Sun, YS Schadendorf, D Hammerling, GJ Kropshofer, H AF Arndt, SO Vogt, AB Markovic-Plese, S Martin, R Moldenhauer, G Wolpl, A Sun, YS Schadendorf, D Hammerling, GJ Kropshofer, H TI Functional HLA-DM on the surface of B cells and immature dendritic cells SO EMBO JOURNAL LA English DT Article DE antigen presentation; autoimmunity; MHC class II; multiple sclerosis; peptide editing ID MHC CLASS-II; MYELIN BASIC-PROTEIN; INVARIANT CHAIN COMPLEXES; DR MOLECULES; ANTIGEN PRESENTATION; INTRACELLULAR-TRANSPORT; PEPTIDE BINDING; RESTRICTED PRESENTATION; ENDOSOMAL COMPARTMENT; LYSOSOMAL MEMBRANE AB HLA-DM (DM) plays a critical role in antigen presentation through major histocompatibility complex (MHC) class II molecules. DM functions as a molecular chaperone by keeping class II molecules competent for antigenic peptide loading and serves as an editor by favoring presentation of high-stability peptides. Until now, DM has been thought to exert these activities only in late endosomal/lysosomal compartments of antigen-presenting cells. Here we show that a subset of DM resides at the cell surface of B cells and immature dendritic cells. Surface DM engages in complexes with putatively empty class II molecules and controls presentation of those antigens that rely on loading on the cell surface or in early endosomal recycling compartments. For example, epitopes derived from myelin basic protein that are implicated in the autoimmune disease multiple sclerosis are down-modulated by DM, but are presented in the absence of DM. Thus, this novel concept of functional DM on the surface may be relevant to both protective immune responses and autoimmunity. C1 German Canc Res Ctr, Dept Mol Immunol, D-69120 Heidelberg, Germany. DRK Blutspendezentrale Ulm, D-89081 Ulm, Germany. Klinikum Mannheim, Clin Cooperat Unit Dermatooncol, D-68135 Mannheim, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Kropshofer, H (reprint author), Basel Inst Immunol, CH-4005 Basel, Switzerland. NR 81 TC 60 Z9 63 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 15 PY 2000 VL 19 IS 6 BP 1241 EP 1251 DI 10.1093/emboj/19.6.1241 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 296NU UT WOS:000086031100009 PM 10716924 ER PT J AU Baldwin, WS Barrett, JC Petranka, J Murphy, E AF Baldwin, WS Barrett, JC Petranka, J Murphy, E TI Attenuation of receptor-mediated growth in estrogen-dependent cells by melatonin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Anderson Coll, Anderson, SC USA. Clemson Univ, CIET, Clemson, SC USA. Natl Inst Environm Sci, RTP, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A269 EP A269 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101557 ER PT J AU Bearer, EL Breakefield, XO Schuback, D Reese, TS LaVail, JH AF Bearer, EL Breakefield, XO Schuback, D Reese, TS LaVail, JH TI Retrograde transport of human Herpes simplex virus: Live imaging allows a biochemical dissection of the reguisite viral proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brown Univ, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NINDS, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A712 EP A712 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104124 ER PT J AU Breen, CM Sykes, DS Toomey, B Miller, DS AF Breen, CM Sykes, DS Toomey, B Miller, DS TI Strychnine stimulates Na-glutarate cotransport in membrane vesicles from rat renal cortex SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 MAR 15 PY 2000 VL 14 IS 4 BP A353 EP A353 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102041 ER PT J AU Breslow, RA Graubard, BI Sinha, R Subar, AF AF Breslow, RA Graubard, BI Sinha, R Subar, AF TI Diet and lung cancer in a National Health Interview Survey cohort. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CDC, Atlanta, GA 30341 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A37 EP A37 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100215 ER PT J AU Brooks, HL Terris, J Schultheis, PJ Lorenz, JN Shull, GE Knepper, MA AF Brooks, HL Terris, J Schultheis, PJ Lorenz, JN Shull, GE Knepper, MA TI Profiling renal tubular Na transporter abundance in NHE3 null mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Cincinnati, Cincinnati, OH USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A355 EP A355 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102055 ER PT J AU Chen, H Tucker, KL Heineman, EF Graubard, BI Markin, R Weisenburger, DD Potischman, NA Ward, MH AF Chen, H Tucker, KL Heineman, EF Graubard, BI Markin, R Weisenburger, DD Potischman, NA Ward, MH TI Relationship between nutrient intakes and esophageal adenocarcinoma SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Tufts Univ, Boston, MA 02111 USA. Univ Nebraska, Med Ctr, Omaha, NE 68198 USA. Univ Massachusetts, Amherst, MA 01003 USA. RI Tucker, Katherine/A-4545-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A257 EP A257 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101488 ER PT J AU Chou, CL Kador, K Wade, J Knepper, MA AF Chou, CL Kador, K Wade, J Knepper, MA TI Colocalization of type 1 ryanodine receptor with aquaporin 2 in rat inner medullary collecting duct (IMCD) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A345 EP A345 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101994 ER PT J AU Combs, CA Stary, CM Balaban, RS Hogan, MC AF Combs, CA Stary, CM Balaban, RS Hogan, MC TI NADH fluorescence of isolated skeletal muscle fibers with work: Comparison of muscle types and the effects of oxygen supply. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, LCE, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A51 EP A51 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100295 ER PT J AU Combs, CA Balaban, RS AF Combs, CA Balaban, RS TI Enzyme dependant fluorescence recovery after photobleaching (ED-FRAP): Application to imaging dehydrogenase activity in living single cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, LCE, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A50 EP A50 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100288 ER PT J AU da Cunha, V Milstein, S Katusic, ZS Rubanyi, GM Dole, WP Kauser, K AF da Cunha, V Milstein, S Katusic, ZS Rubanyi, GM Dole, WP Kauser, K TI Effect of vascular tetrahydrobiopterin content on nitric oxide-mediated relaxation in mouse aorta. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Berlex Biosci, Cardiovasc Res, Richmond, CA 94804 USA. Mayo Clin, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A401 EP A401 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102319 ER PT J AU de la Pena, M Wrathall, LS Sobel, ME AF de la Pena, M Wrathall, LS Sobel, ME TI Identification of an ortholog of human E2 small nucleolar RNA in Drosophila melanogaster. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Pathol Lab, Mol Pathol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A724 EP A724 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104190 ER PT J AU Diamond, AM Hu, YJ Mehta, R Das Gupta, TK Rotimi, C Prewitt, TE Cooper, RS Hatfield, DL Dolan, ME Galdyshev, VN AF Diamond, AM Hu, YJ Mehta, R Das Gupta, TK Rotimi, C Prewitt, TE Cooper, RS Hatfield, DL Dolan, ME Galdyshev, VN TI Genetic variation and functional consequences of a polymorphism in the 3 '-untranslated region of the 15 kDa selenoprotein SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL 60612 USA. Howard Univ, Washington, DC 20059 USA. Loyola Univ, Maywood, IL 60153 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Nebraska, Lincoln, NE 68588 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A296 EP A296 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101712 ER PT J AU Dixon, LB Radimer, K Winkleby, M AF Dixon, LB Radimer, K Winkleby, M TI Differences in foods, dietary nutrients, and serum nutrients between food insufficient and food sufficient low income adults, NHANES III, 1988-1994. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A730 EP A730 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104225 ER PT J AU Dobbins, DE Joe, B Remmers, EF Wilder, RL AF Dobbins, DE Joe, B Remmers, EF Wilder, RL TI A radiation hybrid map of a severity QTL for collagen-induced arthritis located on rat chromosome 10. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A190 EP A190 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101097 ER PT J AU Earthman, CP Reid, PM Harper, IT Ravussin, E Howell, WH AF Earthman, CP Reid, PM Harper, IT Ravussin, E Howell, WH TI Nesting energy expenditure (REE) to body cell mass (BCM) ratio to assess metabolic status in HIV infection SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arizona, Tucson, AZ USA. Virginia Tech, Blacksburg, VA 24061 USA. NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A791 EP A791 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104573 ER PT J AU Earthman, CP Reid, PM Harper, IT Ravussin, E Howell, WH AF Earthman, CP Reid, PM Harper, IT Ravussin, E Howell, WH TI Validation of bioimpedance spectroscopy to measure body composition change in HIV infection SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arizona, Tucson, AZ USA. Virginia Tech, Blacksburg, VA USA. NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A497 EP A497 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102879 ER PT J AU Ecelbarger, CA Kim, GH Knepper, MA Welling, P Wade, JB AF Ecelbarger, CA Kim, GH Knepper, MA Welling, P Wade, JB TI Regulation of abundance of the renal outer medullary potassium channel (ROMK) in rat SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A373 EP A373 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102157 ER PT J AU Grande, J Warner, G Gray, K Walker, H Nath, K Kopp, J AF Grande, J Warner, G Gray, K Walker, H Nath, K Kopp, J TI Role of transforming growth factor beta 1 as a signaling intermediate in reactive oxygen species mediated collagen IV production. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A555 EP A555 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103213 ER PT J AU Habib, KE Rice, KC Chrousos, GP Gold, PW AF Habib, KE Rice, KC Chrousos, GP Gold, PW TI CRH-1 receptor antagonism exerts antidepressant- and anxiolytic-like effects in attenuating stress ulcerogenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A388 EP A388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102244 ER PT J AU Hartman, T Woodson, K Stolzenberg-Solomon, R Virtamo, J Selhub, J Albanes, D AF Hartman, T Woodson, K Stolzenberg-Solomon, R Virtamo, J Selhub, J Albanes, D TI A prospective study of the B-vitamins pyridoxal 5 ' phosphate (B6), B12, and folate on lung cancer risk in older men. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Penn State Univ, University Pk, PA 16802 USA. NCI, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. Tufts Univ, Boston, MA 02111 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A37 EP A37 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100212 ER PT J AU Hatfield, DL Moustafa, ME Gladyshev, VN Carlson, BA Feigenbaum, L Lee, BJ Diamond, AM AF Hatfield, DL Moustafa, ME Gladyshev, VN Carlson, BA Feigenbaum, L Lee, BJ Diamond, AM TI Overexpression of selenocysteine tRNA(Sec) in transgenic mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Nebraska, Lincoln, NE 68588 USA. NCI, BRL, NIH, Bethesda, MD 20892 USA. SAIC, FCRDC, Frederick, MD 21702 USA. Seoul Natl Univ, IMBG, LMG, Seoul 151742, South Korea. Univ Illinois, Chicago, IL USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A296 EP A296 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101711 ER PT J AU Huang, X Herreman, K Blackman, M Rubinstein, S Pabst, K Harman, SM Gabellero, B AF Huang, X Herreman, K Blackman, M Rubinstein, S Pabst, K Harman, SM Gabellero, B TI Effect of growth hormone on protein turnover in the elderly SO FASEB JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Ctr Human Nutr, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A766 EP A766 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104427 ER PT J AU Johnson, SM DelNegro, C Koshiya, N Smith, JC AF Johnson, SM DelNegro, C Koshiya, N Smith, JC TI Characterization and modulation of the spontaneous respiratory rhythm generated in a novel in vitro preparation: The pre-Btzinger Complex "island". SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A642 EP A642 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103714 ER PT J AU Kant, AK Schatzkin, A Graubard, BI Schairer, C AF Kant, AK Schatzkin, A Graubard, BI Schairer, C TI A prospective study of diet quality and mortality in women. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CUNY, Flushing, NY 11367 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A257 EP A257 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101491 ER PT J AU Klett, CPR Bonner, TI AF Klett, CPR Bonner, TI TI The M1 muscarinic receptor mRNA is alternatively spliced in the rat SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Mississippi, Med Ctr, Dept Physiol, Jackson, MS 39047 USA. NIMH, Genet Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A649 EP A649 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103753 ER PT J AU Koshiya, N Smith, JC AF Koshiya, N Smith, JC TI Subthreshold voltage-activated persistent sodium conductance (g(N alpha P)) in inspiratory pacemaker neurons of pre-Botzinger complex SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A642 EP A642 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103711 ER PT J AU Laurent, P Walsh, P Wood, CM Gilmour, K Perry, SF Wang, Y Part, P Chevalier, C AF Laurent, P Walsh, P Wood, CM Gilmour, K Perry, SF Wang, Y Part, P Chevalier, C TI Vesicles traffic in gill pavement cells of urea secreting fish SO FASEB JOURNAL LA English DT Meeting Abstract C1 CNRS, F-67087 Strasbourg, France. Univ Miami, NIEHS, Miami, FL 33149 USA. McMaster Univ, Hamilton, ON L8S 4K1, Canada. Carleton Univ, Ottawa, ON K1S 5B6, Canada. Univ Ottawa, Ottawa, ON K1N 6N5, Canada. SECJRC, I-21020 Ispra, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A599 EP A599 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103467 ER PT J AU Li, C Wang, W Sardeli, C Kwon, TH Knepper, MA Nielsen, S Frokiaer, J AF Li, C Wang, W Sardeli, C Kwon, TH Knepper, MA Nielsen, S Frokiaer, J TI Downregulation of AQP1, AQP2, and AQP3 in rats with bilateral ureteral obstruction (BUO). SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Aarhus, Aarhus, Denmark. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A345 EP A345 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101993 ER PT J AU Liang, W Hoang, Q Benovic, JL Fishman, PH AF Liang, W Hoang, Q Benovic, JL Fishman, PH TI Overexpression of beta-arrestin and GRK2 equalizes differences in agonist-mediated internalization of human beta(1)- and beta(2)-adrenergic Receptors. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, LMCN, Membrane Biochem Sect, NIH, Bethesda, MD USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A785 EP A785 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104537 ER PT J AU Marks, WB Burke, RE AF Marks, WB Burke, RE TI The form of motoneurons maximizes the volume of tissue invaded, weighted by connectivity to soma. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A543 EP A543 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103143 ER PT J AU Martin, KR Kari, FW Barrett, JC French, JE AF Martin, KR Kari, FW Barrett, JC French, JE TI The antioxidant N-acetyl-L-cysteine (NAC) increases mitogenesis but decreases apoptosis in mitogen-stimulated splenocytes from a cancer-prone transgenic mouse. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A493 EP A493 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102852 ER PT J AU Masilamani, S Turner, PL Reyes, I DiBona, G Knepper, MA AF Masilamani, S Turner, PL Reyes, I DiBona, G Knepper, MA TI Dysregulation of NA transporters in a rat model of congestive heart failure SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA 52242 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A372 EP A372 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102153 ER PT J AU Masilamani, S Kim, GH Wang, X Wade, JB Knepper, MA AF Masilamani, S Kim, GH Wang, X Wade, JB Knepper, MA TI Time-course regulation of the epithelial sodium channel (ENAC) and the thiazide-sensitive cotransporter (TSC) in response to dietary salt restriction. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A340 EP A340 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101963 ER PT J AU Matheny, SL Buck, TB Yoshiji, H Bunce, OR Thorgeirsson, UP AF Matheny, SL Buck, TB Yoshiji, H Bunce, OR Thorgeirsson, UP TI A transgenic model to study the multifunctional aspect of tissue inhibitor of metalloproteinases-1(TIMP-1) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Georgia, Athens, GA 30602 USA. Nara Med Univ, Nara, Japan. NCI, LCCTP, TBCS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A279 EP A279 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101613 ER PT J AU Miller, DS Masereeuw, R Russel, F Terlouw, S AF Miller, DS Masereeuw, R Russel, F Terlouw, S TI Nephrotoxin signalling through endothelin (ET) and protein kinase C (PKC) in teleost renal proximal tubules SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Nijmegen, Dept Pharmacol, Nijmegen, Netherlands. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 MAR 15 PY 2000 VL 14 IS 4 BP A409 EP A409 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102366 ER PT J AU Miller, DS Masereeuw, R Russel, F Terlouw, S AF Miller, DS Masereeuw, R Russel, F Terlouw, S TI Ca- and nephrotoxin-induced endothelin (ET) release in teleost renal proximal tubules SO FASEB JOURNAL LA English DT Meeting Abstract C1 Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. Univ Nijmegen, Dept Pharmacol, Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 MAR 15 PY 2000 VL 14 IS 4 BP A409 EP A409 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102363 ER PT J AU Nagineni, CN Detrick, B Hooks, JJ AF Nagineni, CN Detrick, B Hooks, JJ TI Inflammatory mediators and Toxoplasma gondii infection induce transforming growth factor-beta secretion by human retinal pigment epithelial cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A178 EP A178 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101028 ER PT J AU Park, JB Levine, M AF Park, JB Levine, M TI Intracellular accumulation of ascorbic acid is inhibited by flavonoids via blocking both dehydroascorbic acid and ascorbic acid uptakes in the transformed cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 ARS, PL, BHNRC, USDA, Beltsville, MD USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A491 EP A491 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102843 ER PT J AU Patterson, BH Wastney, ME Levander, QA Boston, RC AF Patterson, BH Wastney, ME Levander, QA Boston, RC TI Estimating population parameters from crossover tracer studies using selenium as an example. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20007 USA. Univ Penn, Kennett Square, PA 19348 USA. USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A512 EP A512 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102964 ER PT J AU Pawlosky, R Novotny, JA Hibbeln, J Wegher, B Salem, N AF Pawlosky, R Novotny, JA Hibbeln, J Wegher, B Salem, N TI A compartmental model for the metabolism of essential fatty acids in humans. SO FASEB JOURNAL LA English DT Meeting Abstract C1 ARS, Beltsville Human Nutr Ctr, USDA, Beltsville, MD 20705 USA. NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A251 EP A251 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101452 ER PT J AU Picciano, MF Raiten, DJ AF Picciano, MF Raiten, DJ TI Bioavailability of nutrients and other bioactive components of dietary supplements: Into the next millenium. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, ODS, Bethesda, MD USA. NICHD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A297 EP A297 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101714 ER PT J AU Pinilla, C Houghten, RA Wilson, D Gran, B Martin, R AF Pinilla, C Houghten, RA Wilson, D Gran, B Martin, R TI Identification and optimization of antigens for T cells clones of clinical relevance SO FASEB JOURNAL LA English DT Meeting Abstract C1 Torrey Pines Inst Mol Studies, San Diego, CA USA. Mixture Sci Inc, San Diego, CA USA. NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A84 EP A84 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100483 ER PT J AU Radimer, KL Brown, C Thompson, FE Subar, A Schatzkin, A AF Radimer, KL Brown, C Thompson, FE Subar, A Schatzkin, A TI Disparities in low-fat food reporting between food frequency questionnaires (FFQs) and 24-hour dietary recalls. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 MAR 15 PY 2000 VL 14 IS 4 BP A759 EP A759 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104392 ER PT J AU Radimer, KL Subar, A Thompson, FE Brown, C Schatzkin, A AF Radimer, KL Subar, A Thompson, FE Brown, C Schatzkin, A TI Food reporting discrepancies between food frequency questionnaires (FFQs) and 24-hour dietary recalls SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 MAR 15 PY 2000 VL 14 IS 4 BP A759 EP A759 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104390 ER PT J AU Sardeli, C Li, CL Kwon, TH Knepper, MA Nielsen, S Frokiaer, J AF Sardeli, C Li, CL Kwon, TH Knepper, MA Nielsen, S Frokiaer, J TI Aquaporin-2 (AQP2) expression is increased in rat kidneys after ovariectomy (OVX) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Aarhus, Aarhus, Denmark. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A345 EP A345 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101995 ER PT J AU Song, XY Zeng, L Jin, WW Pilo, CM Frank, ME Wahl, SM AF Song, XY Zeng, L Jin, WW Pilo, CM Frank, ME Wahl, SM TI Therapeutic effects of human chorionic gonadotropin on streptococcal cell wall-induced arthritis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A190 EP A190 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101100 ER PT J AU Sorensen, AM Terris, J Masilamani, S Sawin, L DiBona, G Knepper, MA AF Sorensen, AM Terris, J Masilamani, S Sawin, L DiBona, G Knepper, MA TI Sodium transporter abundance profiling along the nephron: Effects of renal denervation in rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Iowa, Med Ctr, Iowa City, IA 52242 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A374 EP A374 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102166 ER PT J AU Subar, AF Midthune, D Kulldorff, M Brown, CC Thompson, FE Kipnis, V Schatzkin, A AF Subar, AF Midthune, D Kulldorff, M Brown, CC Thompson, FE Kipnis, V Schatzkin, A TI An evaluation of alternative approaches to constructing a nutrient database for a food frequency questionnaire SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Kulldorff, Martin/H-4282-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAR 15 PY 2000 VL 14 IS 4 BP A559 EP A559 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918103233 ER PT J AU Sweet, DH Miller, DS Pritchard, JB AF Sweet, DH Miller, DS Pritchard, JB TI Subcellular localization of an organic cation transporter (rOCT2)/green fluorescent protein fusion construct. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A353 EP A353 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102044 ER PT J AU Tonellato, PJ Lu, J Chen, D Wang, Z Twigger, S Black, A Eppig, J Schuler, G Jacob, HJ AF Tonellato, PJ Lu, J Chen, D Wang, Z Twigger, S Black, A Eppig, J Schuler, G Jacob, HJ TI Rat genome database SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Coll Wisconsin, Informat Res Ctr, Milwaukee, WI 53233 USA. Med Coll Wisconsin, Lab Genet Res, Milwaukee, WI 53233 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A330 EP A330 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101908 ER PT J AU Torti, SV Abeysinghe, RD Greene, B Willingham, MC Sausville, EA Narayanan, V Planalp, RP Brechbiel, MW Torti, FM AF Torti, SV Abeysinghe, RD Greene, B Willingham, MC Sausville, EA Narayanan, V Planalp, RP Brechbiel, MW Torti, FM TI Pathways of iron chelator action SO FASEB JOURNAL LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NCI, Bethesda, MD 20892 USA. Univ New Hampshire, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A752 EP A752 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918104351 ER PT J AU Turner, PL Masilamani, S Reyes, I Knepper, MA AF Turner, PL Masilamani, S Reyes, I Knepper, MA TI Inhibition of nitric oxide (NO) synthesis is associated with a selective increase in the renal abundance of the thiazide-sensitive NaCl cotransporter (TSC). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A372 EP A372 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102156 ER PT J AU Vallon, V Verkman, AS Schnermann, J AF Vallon, V Verkman, AS Schnermann, J TI Luminal hypotonicity in proximal tubule and flow dependence of loop of Henle fluid absorption in aquaporin-1 knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A345 EP A345 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101992 ER PT J AU Vallon, V Chen, M Schnermann, J Briggs, J AF Vallon, V Chen, M Schnermann, J Briggs, J TI Cloning and expression of an angiotensinogen-life gene in Zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A140 EP A140 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100807 ER PT J AU Vallon, V Schnermann, J AF Vallon, V Schnermann, J TI Macular densa-mediated reduction of nephron filtration rate in bNOS knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 15 PY 2000 VL 14 IS 4 BP A133 EP A133 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100769 ER PT J AU Wang, W Kwon, TH Li, C Flyvbjerg, A Knepper, MA Frokiaer, J Nielsen, S AF Wang, W Kwon, TH Li, C Flyvbjerg, A Knepper, MA Frokiaer, J Nielsen, S TI Altered expression of renal aquaporins and Na-transporters in rats treated with the calcium blocker nifedipine SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Aarhus, Aarhus, Denmark. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A344 EP A344 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101990 ER PT J AU Wang, W Kwon, TH Li, C Knepper, MA Frokiaer, J Nielsen, S AF Wang, W Kwon, TH Li, C Knepper, MA Frokiaer, J Nielsen, S TI Decreased expression or renal aquaporins and sodium transporters in polyuric hypercalcemic rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Aarhus, Aarhus, Denmark. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A344 EP A344 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101987 ER PT J AU Wang, X Masilamani, S Knepper, MA AF Wang, X Masilamani, S Knepper, MA TI Na transport proteins mediating increased renal Na excretion in aldosterone escape. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A340 EP A340 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101966 ER PT J AU Weinstein, SJ McGlynn, KA Ziegler, RG AF Weinstein, SJ McGlynn, KA Ziegler, RG TI Risk of invasive cervical cancer is decreased with a common (C677T) methylenetetrahydrofolate reductase (MTHFR) polymorphism SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A36 EP A36 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918100211 ER PT J AU Yang, T Huang, Y Arend, L Park, J Briggs, J Schnermann, J AF Yang, T Huang, Y Arend, L Park, J Briggs, J Schnermann, J TI Low chloride transport stimulates expression of COX-2 in macula densa (MD) cells through MAP kinases SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A407 EP A407 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918102356 ER PT J AU Zhong, Z Wheeler, MD Connor, HD Yin, M Mason, RP Thurman, RG AF Zhong, Z Wheeler, MD Connor, HD Yin, M Mason, RP Thurman, RG TI Viral gene delivery of superoxide dismutase prevents Cylosporin A (CsA)-induced hydroxyl radical production in the rat kidney. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 2000 VL 14 IS 4 BP A200 EP A200 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 294NV UT WOS:000085918101156 ER PT J AU Kadiiska, MB Gladen, BC Baird, DD Dikalova, AE Sohal, RS Hatch, GE Jones, DP Mason, RP Barrett, JC AF Kadiiska, MB Gladen, BC Baird, DD Dikalova, AE Sohal, RS Hatch, GE Jones, DP Mason, RP Barrett, JC TI Biomarkers of oxidative stress study: Are plasma antioxidants markers of CC1(4) poisoning? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE CCl4; rat; plasma; alpha-tocopherol; coenzyme Q; ascorbic acid; glutathione; uric acid; total antioxidant capacity; free radicals ID CARBON-TETRACHLORIDE HEPATOTOXICITY; ALPHA-TOCOPHEROL; ASCORBIC-ACID; VITAMIN-C; PULSE-RADIOLYSIS; FREE-RADICALS; LIVER; METABOLISM; INVIVO; RATS AB Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl4 poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl4 on plasma levels of alpha-tocopherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric acid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl4 would result in losses of antioxidants from plasma. Concentrations of alpha-tocapherol and CoQ were decreased in CCl4-treated rats. Because of concomitant decreases in cholesterol and triglycerides, it was impossible to dissociate oxidation of alpha-tocopherol and the loss of CoQ from generalized lipid changes, due to liver damage. Ascorbic acid levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma changes caused by liver malfunction and rupture of liver cells together with a decrease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant status of the plasma. (C) 2000 Elsevier Science Inc. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. So Methodist Univ, Dallas, TX 75275 USA. US EPA, Natl Hlth & Environm Effects Res Lab, NIH, Res Triangle Pk, NC 27711 USA. Emory Univ, Atlanta, GA 30322 USA. RP Kadiiska, MB (reprint author), NIEHS, NIH, POB 12233,MD F0-02, Res Triangle Pk, NC 27709 USA. NR 46 TC 100 Z9 104 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2000 VL 28 IS 6 BP 838 EP 845 DI 10.1016/S0891-5849(00)00198-2 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 311PN UT WOS:000086893200002 PM 10802213 ER PT J AU Hahn, SM Krishna, MC DeLuca, AM Coffin, D Mitchell, JB AF Hahn, SM Krishna, MC DeLuca, AM Coffin, D Mitchell, JB TI Evaluation of the hydroxylamine Tempol-H as an in vivo radioprotector SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radical; nitroxide; radiation protector; electron paramagnetic resonance; Tempol ID SUPEROXIDE-DISMUTASE MIMICS; NITROXIDES; INHIBITION; MODEL AB Nitroxides are stable free radical compounds that protect against the toxicity of reactive oxygen species in vitro and in vivo. Tempol (Aldrich, Milwaukee, WI, USA) is a cell-permeable hydrophilic nitroxide and has been shown to be an in vitro and in vivo radioprotector. The limitations of Tempol as a systemic radioprotector are that it causes substantial reductions in arterial blood pressure when administered intravenously and is associated with seizure activity. Furthermore, Tempol is rapidly reduced to its hydroxylamine form, Tempol-H, which limits the period of time the active form of the nitroxide is available for radioprotection. Based on initial pharmacological and blood pressure experiments performed in mice, we hypothesized that the systemic administration of Tempol-H in vivo would lead to an equilibration between Tempol and Tempol-H that would limit the toxicity of the nitroxide and provide in vivo radioprotection. Tempol-H was administered in increasing doses via an intraperitoneal route to C3H mice. The maximally tolerated dose was found to be 325 mg/kg. The whole-blood pharmacology of Tempol-H was investigated with electron paramagnetic resonance spectroscopy. These studies demonstrated the appearance of Tempol in whole blood immediately after intraperitoneal injection, suggesting that rapid oxidation of Tempol-H to Tempol takes place in vivo. Although the peak concentration of Tempol in whole blood after administration of Tempol-H did not reach the same levels as those observed when Tempol is administered, the whole-blood levels of Tempol were similar by 10 min after injection. Tempol-H provided protection against the lethality of whole-body radiation in C3H mice at 30 d with a dose modification factor of 1.3, which is similar to the results obtained with Tempol. Hemodynamic measurements in C3H mice after intravenous injection showed that Tempol-H produced little effect on blood pressure or pulse compared with Tempol. Tempol-H is a systemic in vivo radioprotector of C3H mice and is associated with less hemodynamic toxicity than Tempol. (C) 2000 Elsevier Science Inc. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69,Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 62 Z9 66 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2000 VL 28 IS 6 BP 953 EP 958 DI 10.1016/S0891-5849(00)00176-3 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 311PN UT WOS:000086893200016 PM 10802227 ER PT J AU Choi, J Appella, E Donehower, LA AF Choi, J Appella, E Donehower, LA TI The structure and expression of the murine wildtype p53-induced phosphatase 1 (Wip1) gene SO GENOMICS LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; PROTEIN PHOSPHATASE; FISSION YEAST; TRANSCRIPTION FACTOR; KINASE; STRESS; GROWTH; P53; PP2C AB The human wildtype p53-induced phosphatase I (Wip1; GenBank symbol Ppm1d) gene encodes a type 2C protein phosphatase (PP2C) that is induced by ionizing radiation in a p53-dependent manner. We have cloned and sequenced the mouse Wip1 gene and its encoded mRNA, The mouse Wip1 gene is composed of six exons and spans over 36 kb of DNA, The mouse cDNA sequence predicts a 598-amino-acid protein with a molecular mass of roughly 66 kDa. comparison of human and mouse Wip1 sequences revealed 83% overall identity at the amino acid level, The 5'-flanking region of exon 1 had promoter elements characteristic of a housekeeping gene. The Wip1 coding sequences share conserved functional regions with other PP2Cs from a diverse array of species. Expression of Wip1 mRNA was detected ubiquitously in adult and embryonic tissues, though expression in the testis was much higher than in other tissues. Wip1 has been mapped near the p53 gene on mouse chromosome 11. (C) 2000 Academic Press. C1 Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NCI, Div Basic Sci, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Donehower, LA (reprint author), Baylor Coll Med, Div Mol Virol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NCI NIH HHS [CA54897] NR 26 TC 39 Z9 41 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 2000 VL 64 IS 3 BP 298 EP 306 DI 10.1006/geno.2000.6134 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 303DX UT WOS:000086406500008 PM 10756097 ER PT J AU Salazar, E Zaremba, S Arlen, PM Tsang, KY Schlom, J AF Salazar, E Zaremba, S Arlen, PM Tsang, KY Schlom, J TI Agonist peptide from a cytotoxic T-lymphocyte epitope of human carcinoembryonic antigen stimulates production of TC1-type cytokines and increases tyrosine phosphorylation more efficiently than cognate peptide SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; CELL-RECEPTOR LIGAND; AUTOIMMUNE ENCEPHALOMYELITIS; DIFFERENTIAL ACTIVATION; TCR; CLONES; ANTAGONISTS; VACCINE; IDENTIFICATION AB The identification of an agonist peptide (YLSGADLNL, designated CAP1-6D) to an immunodominant cytotoxic T-lymphocyte (CTL) epitope (designated CAP1) of human carcinoembryonic antigen (CEA) has previously been reported. The agonist peptide harbors a single amino acid substitution at a non-MHC anchor residue and is proposed to exert its effects at the level of the T-cell receptor (TCR). The type and magnitude of cytokines produced by CAP1-reactive CTL upon stimulation with the agonist peptide, CAP1-6D, were compared to those obtained upon stimulation with the cognate CAP1 peptide. In addition, early events in the TCR signaling pathway were examined for differences in tyrosine phosphorylation. Upon stimulation with the agonist peptide CAP 1-6D, several different CPA-specific CTL lines exhibited a marked shift in the peptide dose response, which resulted in as much as a 1,000-fold increase in the levels of GM-CSF and gamma-IFN produced as compared with the use of the CAP1 peptide. However, levels of IL-4 and IL-10, which are associ- ated with anti-inflammatory effects, were very low or nonexistent. The cytokine profile of CAP1- and CAP1-6D-specific CTL is consistent with a Tcl-type CTL. Consistent with these findings, CPA-specific CTL showed increased tyrosine phosphorylation of TCR signaling proteins ZAP-70 and TCR zeta chains in response to both peptides. However, when CAP1-6D was compared with the wild-type peptide, the increase in ZAP-70 phosphorylation was greater than the increase in 5 phosphorylation. CTL generated with the CAP 1-6D agonist were shown capable of lysis of human carcinoma cells expressing native CEA. The ability to upregulate the production of GM-CSF, gamma-IFN, TNF alpha and IL-2 with the agonist peptide, as compared with CAP1, may help in initiating or sustaining anti-tumor immune responses and thus potentially prove to be useful in the treatment of CEA-positive tumors. Published 2000 Wiley-Liss, Inc.(dagger). C1 NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, NIH, 10 Ctr Dr,Room 8B07, Bethesda, MD 20892 USA. NR 43 TC 58 Z9 60 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 2000 VL 85 IS 6 BP 829 EP 838 DI 10.1002/(SICI)1097-0215(20000315)85:6<829::AID-IJC16>3.0.CO;2-K PG 10 WC Oncology SC Oncology GA 290DM UT WOS:000085661000016 PM 10709104 ER PT J AU Trent, J AF Trent, J TI The application of microarray analysis to the discovery of cancer causing genes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S BP I4 EP I4 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702795 ER PT J AU Agarwal, RK Sun, SH Chan, CC Caspi, RR AF Agarwal, RK Sun, SH Chan, CC Caspi, RR TI Enhancement of experimental autoimmune uveitis (EAU) by pertussis toxin (PTX) in a genetically resistant rat strain: Innate and adaptive responses at optimal and supraoptimal doses of PTX. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1986B232 BP S377 EP S377 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701985 ER PT J AU Ahmed, F Tomarev, SI AF Ahmed, F Tomarev, SI TI Characterization of the rat MYOC/TIGR gene and its promoter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LMDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4360B307 BP S821 EP S821 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704429 ER PT J AU Alexander, C Bernstein, SL Auburger, G AF Alexander, C Bernstein, SL Auburger, G TI Fine-mapping of 31 ESTs at the OPA1 locus on chromosome 3q28-q29 and expression analysis of 5 candidate ESTs. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Dept Ophthalmol, Lab Mol Res, Baltimore, MD USA. Inst Ophthalmol, Dept Ophthalmol, London, England. NHGRI, NIH, Bethesda, MD USA. Dept Ophthalmol, Lab Mol Res, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 166B166 BP S32 EP S32 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700166 ER PT J AU Alexandridou, A Sall, J Hernandez, E Csaky, KG Cousins, SW AF Alexandridou, A Sall, J Hernandez, E Csaky, KG Cousins, SW TI Susceptibility of mice to basal laminar deposit (BLD) formation: Role of aging and blue light exposure SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 827B202 BP S160 EP S160 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700826 ER PT J AU Andley, UP Song, Z Wawrousek, EF Bassnett, S Fleming, TP AF Andley, UP Song, Z Wawrousek, EF Bassnett, S Fleming, TP TI Lens epithelial cells derived from alpha B-crystallin knockout mice demonstrate hyperproliferation and genomic instability SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Washington Univ, Sch Med, St Louis, MO USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3103B201 BP S584 EP S584 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703173 ER PT J AU Ansari, RR Datiles, MB AF Ansari, RR Datiles, MB TI Clinical tests of a new instrument for the early detection of cataracts: Preliminary results. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NASA, Glenn Res Ctr, NCMR, FC, Cleveland, OH 44135 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 11B11 BP S3 EP S3 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700012 ER PT J AU Avichezer, D Silver, PB Chan, CC Caspi, RR AF Avichezer, D Silver, PB Chan, CC Caspi, RR TI Putative MHC/TCR contact residues of peptide 1-20 of IRBP defined by immunological recognition of alanine-substituted analogs. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1977B223 BP S375 EP S375 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701976 ER PT J AU Aymerich, MS Alberdi, E Martinez, A Becerra, SP AF Aymerich, MS Alberdi, E Martinez, A Becerra, SP TI Characterization localization of pigment epithelium-derived factor (PEDF) receptors in bovine retina. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. Univ Basque Country, Leioa, Spain. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4620B567 BP S869 EP S869 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704689 ER PT J AU Ayres, LM Caruso, RC Byrnes, GA Mazur, DO Blice, JP AF Ayres, LM Caruso, RC Byrnes, GA Mazur, DO Blice, JP TI Visual function after epiretinal membrane surgery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Dept Ophthalmol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1771B17 BP S338 EP S338 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701770 ER PT J AU Ayyagari, R Kakuk, LE Lagali, P Griesinger, IB Baig, M MacDonald, IM Maumenee, IH Chandrasekharappa, SC Guru, SC Sieving, PA Wong, P AF Ayyagari, R Kakuk, LE Lagali, P Griesinger, IB Baig, M MacDonald, IM Maumenee, IH Chandrasekharappa, SC Guru, SC Sieving, PA Wong, P TI Physical and transport map of autosomal dominant macular degeneration (adMD) interval on chromosome 6q and characterization of candidate genes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1024B399 BP S196 EP S196 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701023 ER PT J AU Baffi, JS Byrnes, G Chan, CC Csaky, KG AF Baffi, JS Byrnes, G Chan, CC Csaky, KG TI Effects of vascular endothelial growth factor (VEGF) overexpression in-vivo in rat via adenovirus gene transfer SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Ocular Gene Therapy Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Natl Naval Hosp, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4432B379 BP S834 EP S834 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704501 ER PT J AU Becker, MD Crespo, S Planck, SR Naramura, M Rosenbaum, JT AF Becker, MD Crespo, S Planck, SR Naramura, M Rosenbaum, JT TI Intraocular in vivo imaging of activated T-lymphocytes expressing green-fluorescent protein (GFP). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. NIH, Bethesda, MD 20892 USA. RI Becker, Matthias/A-8733-2014 OI Becker, Matthias/0000-0003-4933-7010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 551 BP S106 EP S106 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700550 ER PT J AU Berger, RB Shen, DF Buggage, RR Tuaillon, N Lu, B Gerard, C Chan, CC AF Berger, RB Shen, DF Buggage, RR Tuaillon, N Lu, B Gerard, C Chan, CC TI Lack of ocular inflammation in MCP-1 deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1998B244 BP S379 EP S379 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701997 ER PT J AU Buggage, RR Matteson, DM Shen, D Sun, B Chan, CC AF Buggage, RR Matteson, DM Shen, D Sun, B Chan, CC TI Effect of progesterone on experimental autoimmune uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1993B239 BP S378 EP S378 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701992 ER PT J AU Carosa, E Kozmik, Z Horwitz, J Robison, G Piatigorsky, J AF Carosa, E Kozmik, Z Horwitz, J Robison, G Piatigorsky, J TI Aldehyde dehydrogenase/Omega-crystallin of the scallop lens. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3110B208 BP S585 EP S585 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703180 ER PT J AU Carper, DA John, M Chen, Z Wang, RR Ma, W Spector, A AF Carper, DA John, M Chen, Z Wang, RR Ma, W Spector, A TI Differential display analysis of hydrogen peroxide resistant alpha TN4 mouse lens epithelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1733 BP S329 EP S329 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701732 ER PT J AU Caruso, RC Fitzgibbon, EJ Kaiser-Kupfer, MI AF Caruso, RC Fitzgibbon, EJ Kaiser-Kupfer, MI TI Fixation in patients with juvenile macular dystrophy: Scanning laser ophthalmoscope and scleral search coil measurements SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4700B647 BP S884 EP S884 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704769 ER PT J AU Chan, CC Shen, DF Buggage, RR Robinson, M Smith, JA AF Chan, CC Shen, DF Buggage, RR Robinson, M Smith, JA TI Molecular pathology of conjuctival B and T cell lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 5060 BP S952 EP S952 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246705127 ER PT J AU Chen, W Piatigorsky, J Duncan, MK AF Chen, W Piatigorsky, J Duncan, MK TI Mechanism of mouse beta B1-crystallin gene expression in lens fiber cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Delaware, Dept Biol Sci, Newark, DE USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3325B423 BP S627 EP S627 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703395 ER PT J AU Cheng, QF Rao, PV Zigler, JS AF Cheng, QF Rao, PV Zigler, JS TI Cataractogenic effect of the isoprenylation inhibitor perillic acid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Lab Mech Ocular Dis, Bethesda, MD 20892 USA. Duke Univ, Dept Ophthalmol, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1109B484 BP S211 EP S211 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701108 ER PT J AU Chew, EY Ferris, FL Csaky, KG Murphy, RP Schachat, A Bigio, M Thompson, D AF Chew, EY Ferris, FL Csaky, KG Murphy, RP Schachat, A Bigio, M Thompson, D TI Results of the early treatment diabetic retinopathy study (ETDRS) follow-up study. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Glaser Murphy Treatment Ctr, Towson, MD USA. Johns Hopkins Univ, Baltimore, MD USA. EMMES Corp, Potomac, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 5056 BP S951 EP S951 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246705123 ER PT J AU Chin, M Nagineni, CN Chesky, L Detrick, B Hooks, JJ AF Chin, M Nagineni, CN Chesky, L Detrick, B Hooks, JJ TI Cytokine induction of cyclooxygenase gene expression in human retinal pigment epithelial (RPE) cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4124B71 BP S777 EP S777 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704193 ER PT J AU Christiansen, SP Peterson, DC Prill, R Youle, RL McLoon, LK AF Christiansen, SP Peterson, DC Prill, R Youle, RL McLoon, LK TI Acute and chronic effects of the immunotoxin ricin-Mab 35, in extraocular muscle. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2213B459 BP S419 EP S419 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702211 ER PT J AU Clarke, GA Robinson, MR Reed, GF Magone, MT Whitcup, SM AF Clarke, GA Robinson, MR Reed, GF Magone, MT Whitcup, SM TI The effect of cytomegalovirus retinitis on the blood-ocular barriers in patients receiving highly active antiretroviral therapy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 505 BP S96 EP S96 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700504 ER PT J AU Connaughton, VP Bender, AM Nelson, R AF Connaughton, VP Bender, AM Nelson, R TI GABA-evoked responses in zebrafish retinal bipolar cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. American Univ, Washington, DC 20016 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3295B393 BP S621 EP S621 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703365 ER PT J AU Cornwall, MC Poitry, S Tsacopoulos, M Wiggert, B Crouch, RK AF Cornwall, MC Poitry, S Tsacopoulos, M Wiggert, B Crouch, RK TI Spatial and temporal resolution of retinol fluorescence in salamander rods and cones. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Dept Physiol, Boston, MA 02118 USA. Univ Geneva, Dept Physol, Geneva, Switzerland. NEI, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3174B272 BP S598 EP S598 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703244 ER PT J AU Cousins, SW Norat, EV Csaky, KG AF Cousins, SW Norat, EV Csaky, KG TI Monocytes from patients with age-related macular degeneration (AMD) exhibit wide variation in TNF-alpha mRNA content. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4444B391 BP S836 EP S836 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704513 ER PT J AU Coyle, BM Papagiotas, SS Libby, D Piatigorsky, J West-Mays, JA AF Coyle, BM Papagiotas, SS Libby, D Piatigorsky, J West-Mays, JA TI Misexpression of AP-2 alpha transcription factor in transgenic mice causes ectopic proliferation in the developing lens. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Tufts Univ, New England Med Ctr, Vis Res Labs, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. NEI, LMDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1731 BP S329 EP S329 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701730 ER PT J AU Crawford, MA Smith, JA Buggage, RR Chan, CC AF Crawford, MA Smith, JA Buggage, RR Chan, CC TI Detection of Fabry's disease using conjunctival swab SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2428B674 BP S458 EP S458 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702426 ER PT J AU Creaven, T Davis, J Kim, A Piatigorsky, J AF Creaven, T Davis, J Kim, A Piatigorsky, J TI Conditionality immortalized corneal cell lines that undergo differentiative changes in culture. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1369B744 BP S261 EP S261 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701368 ER PT J AU Csaky, KG Gonzalez, AA Zhang, C Willermain, F Cousins, SW AF Csaky, KG Gonzalez, AA Zhang, C Willermain, F Cousins, SW TI Myeloperoxidase-catalyzed oxidative injury to retinal pigment epithelium (RPE) can cause cell membrane blebbing without cell death SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Free Univ Brussels, Hosp St Pierre, Dept Ophthalmol, Brussels, Belgium. Bascom Palmer Eye Inst, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2177B423 BP S412 EP S412 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702175 ER PT J AU Cui, W Tomarev, SI Duncan, MK AF Cui, W Tomarev, SI Duncan, MK TI MAFB and Prox1 function synergistically to regulate chicken beta B1-crystallin gene expression. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Delaware, Dept Biol Sci, Newark, DE USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1729 BP S329 EP S329 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701728 ER PT J AU Curcio, CA Millican, CL Kruth, HS AF Curcio, CA Millican, CL Kruth, HS TI Cholesterol accumulates with age in human Bruch's membrane SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Alabama, Dept Ophthalmol, Birmingham, AL 35294 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 591 BP S115 EP S115 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700590 ER PT J AU Davis, J Kays, WT Duncan, M Piatigorsky, J AF Davis, J Kays, WT Duncan, M Piatigorsky, J TI Altered ALDH3 and TKT expression and stratification defects in the corneas of Pax6 mutant mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Delaware, Newark, DE 19716 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1370B745 BP S261 EP S261 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701369 ER PT J AU de Iongh, RU Deng, C McAvoy, JW AF de Iongh, RU Deng, C McAvoy, JW TI Effect of null mutation of the fgfr3 gene on lens differentiation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Sydney, Inst Biomed Res, Sydney, NSW 2006, Australia. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4603B550 BP S866 EP S866 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704672 ER PT J AU Fan, J Hollowell, GP Chepelinsky, AB AF Fan, J Hollowell, GP Chepelinsky, AB TI Identification of peptide sequences interacting with the transcription factor AP2 alpha variants using phage display libraries. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3329B427 BP S627 EP S627 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703399 ER PT J AU Fine, HF Whitcup, SM Nussenblatt, RB Caruso, RC AF Fine, HF Whitcup, SM Nussenblatt, RB Caruso, RC TI Hypotony and cyclodialysis cleft in uveitis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1945B191 BP S370 EP S370 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701944 ER PT J AU Frederikse, P Rodrigues, S Carper, D Chen, Z AF Frederikse, P Rodrigues, S Carper, D Chen, Z TI Alternatively spliced Alzheimer precursor protein mRNAs and proteins in lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pharmacol & Physiol, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Ophthalmol, Newark, NJ 07103 USA. NEI, LMOD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3330B428 BP S627 EP S627 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703400 ER PT J AU Gao, CY Ledee, DR Zelenka, PS AF Gao, CY Ledee, DR Zelenka, PS TI CDK5 and its activator p35 are expressed in the corneal epithelium. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1376B751 BP S262 EP S262 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701375 ER PT J AU Garland, DL Colvis, CM Duglas-Taylor, Y Werth, K Kowalak, JA Janjani, A AF Garland, DL Colvis, CM Duglas-Taylor, Y Werth, K Kowalak, JA Janjani, A TI Identification of in vivo degradation products of alpha B- and alpha A-crystallin in Soemmerring's rings. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 512 BP S98 EP S98 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700511 ER PT J AU Gerber, S Chandrasekharappa, S Sumegi, J Ellegde, S Bonneau, D Rozet, JM Perrault, I Ducroq, D Munnich, A Kaplan, J AF Gerber, S Chandrasekharappa, S Sumegi, J Ellegde, S Bonneau, D Rozet, JM Perrault, I Ducroq, D Munnich, A Kaplan, J TI Mutation screening of five candidate genes in 10 families affected with Usher syndrome type 1A. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Hop Necker Enfants Malad, INSERM U393, Paris, France. NIDDK, Metab Dis Branch, Bethesda, MD USA. Univ Nebraska, Dept Pathol & Microbiol, Omaha, NE 68182 USA. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. RI Rozet, Jean-Michel/E-5737-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1017B392 BP S195 EP S195 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701016 ER PT J AU Gouras, P Kong, J Kjeldbye, H Salchow, D Tsang, SH Redmond, TM AF Gouras, P Kong, J Kjeldbye, H Salchow, D Tsang, SH Redmond, TM TI RPE transplantation slows loss of retinal function in an animal model of leber congenital amaurosis (LCA) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Columbia Univ, New York, NY 10027 USA. Med Univ Lubeck, Lubeck, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 529 BP S101 EP S101 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700528 ER PT J AU Grimm, C Wenzel, A Hafezi, F Williams, TP Yu, S Redmond, TM Reme, CE AF Grimm, C Wenzel, A Hafezi, F Williams, TP Yu, S Redmond, TM Reme, CE TI Rhodopsin regeneration kinetics determine light damage susceptibility of photoreceptors. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Florida State Univ, Tallahassee, FL 32306 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 100B100 BP S20 EP S20 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700101 ER PT J AU Hermandez, E Alexandridou, A Sall, J Csaky, KG Cousins, SW AF Hermandez, E Alexandridou, A Sall, J Csaky, KG Cousins, SW TI Relationship between plasma lipidemia and basal laminar deposit (BLD) formation in the mouse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 826B201 BP S160 EP S160 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700825 ER PT J AU Hertle, RW FitzGibbon, EJ Caruso, RC Dell'Osso, LF AF Hertle, RW FitzGibbon, EJ Caruso, RC Dell'Osso, LF TI Clinical radiographic and electrophysiologic findings in patients with Achiasma. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. VA Med Ctr, Cleveland, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3737B835 BP S702 EP S702 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703806 ER PT J AU Hollowell, GP Fan, J Ohtaka-Maruyama, C Zelenka, PS Chepelinsky, AB AF Hollowell, GP Fan, J Ohtaka-Maruyama, C Zelenka, PS Chepelinsky, AB TI Transcription factor AP2 alpha gene expression in the lens. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3328B426 BP S627 EP S627 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703398 ER PT J AU Hollyfield, JG Foletta, VC Acharya, S Rayborn, ME Lee, JW Rodriguez, IR Young, WS AF Hollyfield, JG Foletta, VC Acharya, S Rayborn, ME Lee, JW Rodriguez, IR Young, WS TI SPACRCAN: A novel hyaluronan binding proteoglycan present in the IPM and pineal gland SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NIMH, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4662B609 BP S877 EP S877 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704731 ER PT J AU Holmes, JM Birch, EE Repka, MX Saunders, RA Hertle, RW Leske, DA Kip, KE Beck, RW AF Holmes, JM Birch, EE Repka, MX Saunders, RA Hertle, RW Leske, DA Kip, KE Beck, RW TI The amblyopia treatment study visual acuity protocol. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Mayo Clin & Mayo Fdn, Pediat Eye Dis Investigator Grp, Rochester, MN 55905 USA. Retina Fdn SW, Dallas, TX USA. Johns Hopkins Univ, Baltimore, MD USA. Med Univ S Carolina, Charleston, SC 29425 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3752B850 BP S705 EP S705 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703821 ER PT J AU Hough, RB Piatigorsky, J AF Hough, RB Piatigorsky, J TI The isolation and initial characterization of two putative corneal enzyme-crystallins in the rabbit: ALDH1 and TKT SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1372B747 BP S261 EP S261 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701371 ER PT J AU Hwang, BJ Abramson, MA Feldman, DE Beaudet, AL Feller, MB AF Hwang, BJ Abramson, MA Feldman, DE Beaudet, AL Feller, MB TI Absence of eye-specific layers in the dLGN of a transgenic mouse lacking retinal waves. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH, HHMI, Res Scholars Program, Bethesda, MD 20814 USA. NINDS, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4975B922 BP S935 EP S935 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246705043 ER PT J AU Jaworski, CJ Moreira, EF Rodriguez, IR AF Jaworski, CJ Moreira, EF Rodriguez, IR TI Bioinformatics and data mining reveal a multi-gene family of oxysterol binding proteins: cDNA sequence and characterization of 2 novel members, OSBP-5 and OSBP-8. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4681B628 BP S880 EP S880 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704750 ER PT J AU Jernigan, HM Blum, PS Pabst, DM Zigler, JS AF Jernigan, HM Blum, PS Pabst, DM Zigler, JS TI Increased phospholipid synthesis in the cataractous lenses of strain 13/N guinea-pigs. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Tennessee, Ctr Hlth Sci, Dept Biochem, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Ophthalmol, Memphis, TN 38163 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1116B491 BP S213 EP S213 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701115 ER PT J AU Jones, LS King, BA Yuan, P Robinson, MR O'Donnell, WR Whitcup, SM Rubin, BI AF Jones, LS King, BA Yuan, P Robinson, MR O'Donnell, WR Whitcup, SM Rubin, BI TI Acetazolamide release rates from intraocular lenses. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Howard Univ Hosp, Washington, DC USA. NIH, OD, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4058B5 BP S766 EP S766 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704127 ER PT J AU Kador, PF Takahashi, Y Akagi, Y Blessing, K Koelsch, E Wyman, M AF Kador, PF Takahashi, Y Akagi, Y Blessing, K Koelsch, E Wyman, M TI Age-dependent retinal capillary pericyte degeneration in galactose ? fed dogs. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. Fukui Univ, Dept Ophthalmol, Fukui 910, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2139B385 BP S405 EP S405 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702137 ER PT J AU Keane-Myers, AM Miyazaki, D Liu, G Benichou, G Ono, SJ AF Keane-Myers, AM Miyazaki, D Liu, G Benichou, G Ono, SJ TI Induction of allergic conjunctivitis with a single 14 aa peptide from the major cat allergen, Feld1. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1915B161 BP S365 EP S365 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701914 ER PT J AU Kennedy, MC Gery, I AF Kennedy, MC Gery, I TI Induction of experimental autoimmune uveoretinitis (EAU) in DA rats with Incomplete Freund's Adjuvant (IFA). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1990B236 BP S377 EP S377 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701989 ER PT J AU Kim, SJ Vistica, BP Wawrousek, E Agarwal, RK Gery, I AF Kim, SJ Vistica, BP Wawrousek, E Agarwal, RK Gery, I TI Th1 and Th2 cells in experimental ocular inflammation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. NIH, HHMI, Res Scholars Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 553 BP S106 EP S106 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700552 ER PT J AU King, BA Ross, ML Byrnes, G Csaky, KG Baffi, J Silk, W Robinson, MR AF King, BA Ross, ML Byrnes, G Csaky, KG Baffi, J Silk, W Robinson, MR TI Intraocular micro-implants releasing triamcinolone acetonide for use in rat models SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH, Bioengn & Phys Sci Program, OD, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4087B34 BP S770 EP S770 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704156 ER PT J AU Kinyoun, JL Kalina, RE Chew, EY Chan, CC AF Kinyoun, JL Kalina, RE Chew, EY Chan, CC TI Neovascularization in von Hippel-Lindau disease: Absence of vascular endothelial growth factor in vitreous specimens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1881B127 BP S358 EP S358 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701880 ER PT J AU Kunert, KS Tisdale, AS Danjo, Y Keane-Myers, AM Gipson, IK AF Kunert, KS Tisdale, AS Danjo, Y Keane-Myers, AM Gipson, IK TI Acute and chronic stimulation of goblet cell mucin content in mouse conjunctiva SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3996 BP S752 EP S752 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704065 ER PT J AU Kuszak, JR Al-Ghoul, KJ Novak, LA Garland, D AF Kuszak, JR Al-Ghoul, KJ Novak, LA Garland, D TI Correlative structural and functional changes in lenses from rats with experimentally induced diabetes. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Rush Presbyterian St Lukes Med Ctr, Dept Pathol, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Dept Ophthalmol, Chicago, IL 60612 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1117B492 BP S213 EP S213 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701116 ER PT J AU Lee, JW Chen, Q Rayborn, ME Crabb, JW Hollyfield, JG Rodriguez, LR AF Lee, JW Chen, Q Rayborn, ME Crabb, JW Hollyfield, JG Rodriguez, LR TI SPACR in the IPM: Lambda glycoprotein in human and a proteoglycan in the mouse. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4661B608 BP S877 EP S877 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704730 ER PT J AU Lizak, MJ Kador, PF AF Lizak, MJ Kador, PF TI Observation of aldose reductase activity in rabbit lenses in vivo, by localized magnetic resonance spectroscopy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1125B500 BP S215 EP S215 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701124 ER PT J AU Lopez, P Caruso, RC Kaiser-Kupfer, MI AF Lopez, P Caruso, RC Kaiser-Kupfer, MI TI A comparison of Lanthony's desaturated 15 hue test with the Farnsworth-Munsell 100 hue test for the quantification of color vision deficiencies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1871B117 BP S356 EP S356 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701870 ER PT J AU Lytton, SD Silver, PB Lindbland, M Holmgren, J Wiggert, B Chan, CC Caspi, RR AF Lytton, SD Silver, PB Lindbland, M Holmgren, J Wiggert, B Chan, CC Caspi, RR TI Cholera toxin B subunit-retinal protein conjugates as oral vaccine against experimental autoimmune uveitis (EAU). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1984B230 BP S376 EP S376 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701983 ER PT J AU Ma, W Reszka, KJ Zhou, W Chignell, CF Spector, A AF Ma, W Reszka, KJ Zhou, W Chignell, CF Spector, A TI Investigation of the mechanism of action of microperoxidase-11, a potential anti-cataract agent SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. VA Med Ctr, Iowa City, IA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1099B474 BP S209 EP S209 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701098 ER PT J AU Magone, MT Raz, E Whitcup, SM Chan, CC AF Magone, MT Raz, E Whitcup, SM Chan, CC TI Systemic or topical administration of immunostimulatory DNA inhibits early and late phases of murine allergic conjunctivitis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 549 BP S106 EP S106 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700548 ER PT J AU Mahdi, RM Li, W Chepelinsky, AB Egwuagu, CE AF Mahdi, RM Li, W Chepelinsky, AB Egwuagu, CE TI SOCS (suppressors of cytokine signaling) genes are constitutively and differentially expressed in rodent lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3340B438 BP S630 EP S630 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703410 ER PT J AU Manitto, MP Martina, E Brancato, R Dean, M Allikmets, R Fumagalli, A Soriani, N Ferrari, M Cremonesi, L AF Manitto, MP Martina, E Brancato, R Dean, M Allikmets, R Fumagalli, A Soriani, N Ferrari, M Cremonesi, L TI Mutation analysis of the ABCR gene in Italian patients with Stargardt disease. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Hosp San Raffaele, Dept Ophthalmol, Milan, Italy. Univ Hosp San Raffaele, Dept Visual Sci, Milan, Italy. NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Univ Hosp San Raffaele, Unit Genet & Mol Diagnost, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 736B111 BP S143 EP S143 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700735 ER PT J AU Miller, AD Robinson, GS Smith, LEL Becerra, SP AF Miller, AD Robinson, GS Smith, LEL Becerra, SP TI Regulation of pigment epithelium-derived factor (PEDF) production by oxygen. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4619B566 BP S869 EP S869 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704688 ER PT J AU Moiseyev, GP Zhang, J Ablonczy, Z Chen, Y Yu, S Redmond, TM Crouch, RK Ma, JX AF Moiseyev, GP Zhang, J Ablonczy, Z Chen, Y Yu, S Redmond, TM Crouch, RK Ma, JX TI Purification and characterization of two forms of bovine RPE65. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4487B434 BP S844 EP S844 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704556 ER PT J AU Moreira, EF Jaworski, C Lee, JW Rodriguez, IR AF Moreira, EF Jaworski, C Lee, JW Rodriguez, IR TI Cloning of a novel retina specific oxysterol binding protein (OSBP2) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4680B627 BP S880 EP S880 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704749 ER PT J AU Murata, M Sato, S AF Murata, M Sato, S TI Vascular endothelial growth factor (VEGF) enhances the expression of receptors and activates mitogen-activated protein (MAP) kinase of dog retinal capillary endothelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Ideta Eye Hosp, Kumamoto, Japan. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3381B479 BP S637 EP S637 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703450 ER PT J AU Nagineni, CN Pardhasaradhi, K Detrick, D Hook, JJ AF Nagineni, CN Pardhasaradhi, K Detrick, D Hook, JJ TI Expression of angiogenic regulators, angiogenin, VEGF and PEDF by human retinal pigment epithelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4454B401 BP S838 EP S838 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704523 ER PT J AU Nees, D Wawrousek, EF Piatigorsky, J AF Nees, D Wawrousek, EF Piatigorsky, J TI A homozygous knockout of aldehyde dehydrogenase 3 in mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3995 BP S752 EP S752 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704064 ER PT J AU Nemesure, B He, Q Hejtmancik, F Hennis, A Leske, MC AF Nemesure, B He, Q Hejtmancik, F Hennis, A Leske, MC CA Barbados Family Study Grp TI Open-angle glaucoma in black families: The Barbados Family Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 SUNY Stony Brook, Dept Prevent Med, Med Ctr, Stony Brook, NY 11794 USA. NEI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2810 BP S527 EP S527 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702881 ER PT J AU Padgaonkar, VA Carper, DA Leverenz, VR Chen, SC Dang, L Unakar, NJ Reddy, VN Giblin, FJ AF Padgaonkar, VA Carper, DA Leverenz, VR Chen, SC Dang, L Unakar, NJ Reddy, VN Giblin, FJ TI Effect of hyperbaric oxygen on antioxidant enzyme mRNA levels in cultured human lens epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Oakland Univ, Eye Res Inst, Rochester, MI 48063 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1087B462 BP S207 EP S207 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701086 ER PT J AU Pennesi, G Sun, SH David, CS Hargrave, PA McDowell, JH Wiggert, B Chan, CC Caspi, RR AF Pennesi, G Sun, SH David, CS Hargrave, PA McDowell, JH Wiggert, B Chan, CC Caspi, RR TI A humanized model of experimental autoimmune uveitis in HLA transgenic mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 554 BP S107 EP S107 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700553 ER PT J AU Posey-Marcos, EL Rodriguez, IR AF Posey-Marcos, EL Rodriguez, IR TI The cytotoxic effects of oxysterols on retinal pigmented epithelial cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 592 BP S115 EP S115 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700591 ER PT J AU Qtaishat, NM Redmond, TM Pepperberg, DR AF Qtaishat, NM Redmond, TM Pepperberg, DR TI Acute radiolabelling of retinoids in eye tissues of normal and RPE65 knockout mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1046B421 BP S200 EP S200 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701045 ER PT J AU Redmond, TM Soto-Prior, A Gentleman, S AF Redmond, TM Soto-Prior, A Gentleman, S TI Features of the RPE65-related protein family: Insights into structure and function SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3263B361 BP S615 EP S615 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703333 ER PT J AU Remington, JL Gao, CY Cai, H Zelenka, PS David, LL Duncan, MK AF Remington, JL Gao, CY Cai, H Zelenka, PS David, LL Duncan, MK TI General utility of the beta B1 crystallin promoter to drive protein expression in lens fiber cells of transgenic mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Delaware, Newark, DE USA. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3326B424 BP S627 EP S627 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703396 ER PT J AU Ren, ZX Li, A Shastry, BS Padma, T Ayyagari, R Scott, MH Parks, MM Kaiser-Kupfer, MI Hejtmancik, JF AF Ren, ZX Li, A Shastry, BS Padma, T Ayyagari, R Scott, MH Parks, MM Kaiser-Kupfer, MI Hejtmancik, JF TI Mutation of gamma crastallin gene on chromosome 2q33-q35 and the autosomal dominant zonular pulverulent cataract. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, OGCSB, NIH, Bethesda, MD 20892 USA. Oakland Univ, Eye Res Inst, Rochester, MI USA. Osmania Univ, Dept Genet, Hyderabad 500007, Andhra Pradesh, India. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 508 BP S97 EP S97 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700507 ER PT J AU Robinson, MR Ross, ML Lutz, RJ King, BA Yuan, P Gogolak, L Whitcup, SM AF Robinson, MR Ross, ML Lutz, RJ King, BA Yuan, P Gogolak, L Whitcup, SM TI Sustained-release intraocular device for carboxyamide-amino-imidizole: A novel angiostatic agent SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, OD, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4085B32 BP S770 EP S770 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704154 ER PT J AU Robinson, WG Cook-Ashby, JC Soto, I Kelley, MA Glover, JP Jacot, JL AF Robinson, WG Cook-Ashby, JC Soto, I Kelley, MA Glover, JP Jacot, JL TI Identification of vasculogenic-like precursor cells in the galactose-fed rat model of diabetic retinal microangiopathies. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2140B386 BP S405 EP S405 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702138 ER PT J AU Rodriguez, IR Moreira, EF Sage, EH Kantorow, M AF Rodriguez, IR Moreira, EF Sage, EH Kantorow, M TI Localization of SPARC to the outer plexiform layer of the monkey retina and secretion by the macular RPE. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, Bethesda, MD 20892 USA. Hope Heart Inst, Seattle, WA USA. W Virginia Univ, Dept Biol, Morgantown, WV 26506 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3258B356 BP S613 EP S613 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703328 ER PT J AU Ross, ML Lutz, RJ Yuan, P King, BA Whitcup, SM Robinson, MR AF Ross, ML Lutz, RJ Yuan, P King, BA Whitcup, SM Robinson, MR TI Sustained-release intraocular implant for 2-methoxyestradiol: An angiostatic agent for the treatment of choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NIH, OD, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4084B31 BP S770 EP S770 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704153 ER PT J AU Russell, P Johnson, M AF Russell, P Johnson, M TI Myocilin/TIGR and the obstruction of pores in PVPF filters SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. Northwestern Univ, Evanston, IL USA. RI Johnson, Mark/B-6921-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4046 BP S763 EP S763 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704115 ER PT J AU Samuel, W Kutty, RK Kutty, G Duncan, T Wiggert, B AF Samuel, W Kutty, RK Kutty, G Duncan, T Wiggert, B TI Stearoyl-CoA desaturase is expressed in human retinal pigment epithelial cells and is regulated by retinoic acid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4469B416 BP S841 EP S841 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704538 ER PT J AU Seigel, GM Bernard, D Greene, N Nussbaum, R Wagner, J Pearce, DA Mitchison, H AF Seigel, GM Bernard, D Greene, N Nussbaum, R Wagner, J Pearce, DA Mitchison, H TI Retinal apoptosis and lipofuscin accumulation in a CLN3 knock-out mouse model of Batten Disease. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. UCL Royal Free & Univ Coll, Sch Med, London, England. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2124B370 BP S402 EP S402 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702122 ER PT J AU Sergeev, YV Rostapshova, OV Hejtmancik, JF AF Sergeev, YV Rostapshova, OV Hejtmancik, JF TI Conformational stability of mutant beta A3-crystallin containing the modified connection peptide. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3112B210 BP S586 EP S586 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703182 ER PT J AU Shadrach, KG Rayborn, ME Acharya, S Rodriguez, IR Hollyfield, JG AF Shadrach, KG Rayborn, ME Acharya, S Rodriguez, IR Hollyfield, JG TI SPACR and SPACRCAN in the IPM of the primate, Macaca mulatta SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4663B610 BP S877 EP S877 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704732 ER PT J AU Sheliga, BM Brown, VJ Miles, FA Bethesda, NEI AF Sheliga, BM Brown, VJ Miles, FA Bethesda, NEI TI Analysis of voluntary saccadic eye movements in a double-step task. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LSR, Bethesda, MD 20892 USA. Univ St Andrews, St Andrews KY16 9AJ, Fife, Scotland. RI Brown, Verity/A-5235-2011 OI Brown, Verity/0000-0001-5762-1797 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1628B1003 BP S308 EP S308 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701627 ER PT J AU Shen, DF Buggage, RR Eng, HC Chang, MA Chan, CC AF Shen, DF Buggage, RR Eng, HC Chang, MA Chan, CC TI Cytokine gene expression in different strains of mice with endotoxin-induced uveitis (EIU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Durham, NC USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1999B245 BP S379 EP S379 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701998 ER PT J AU Singer, JH Feller, MB AF Singer, JH Feller, MB TI Modulation of L-type calcium channels alters the propagation of correlated activity in the developing mouse retina. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NINDS, Synapse Format & Funct Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4974B921 BP S935 EP S935 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246705042 ER PT J AU Skiba, NP Hopp, JA Makino, ER Bohm, A Simonds, WF Arshavsky, VY AF Skiba, NP Hopp, JA Makino, ER Bohm, A Simonds, WF Arshavsky, VY TI The role of G protein beta 5 subunit in regulating transducin GTPase. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Biomed Res Inst, Boston, MA 02114 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1697 BP S322 EP S322 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701696 ER PT J AU Skolik, SA AF Skolik, SA TI An anti-angiogenesis "Protective Factor" may exist in some patients with co-existing IDDM and severe arthritis which is associated with long term protection from development of diabetic retinopathy (DR) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Marshall Univ, Sch Med, Univ Retina Associates, Huntington, WV USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2162B408 BP S409 EP S409 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702160 ER PT J AU Smith, JA Stern, ME Gao, J Schwalb, TK Rupp, DC Whitcup, SM AF Smith, JA Stern, ME Gao, J Schwalb, TK Rupp, DC Whitcup, SM TI Conjunctival inflammation in non-Sjogren's syndrome and Sjogren's syndrome keratoconjunctivitis sicca. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. Allergan Inc, Biol Sci, Irvine, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1450B825 BP S276 EP S276 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701449 ER PT J AU Sosne, G Chan, CC Thai, K Kennedy, M Kleinman, HK AF Sosne, G Chan, CC Thai, K Kennedy, M Kleinman, HK TI Thymosin beta 4 promotes corneal epithelial cell migration in vitro and accelerates wound healing in vivo. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Henry Ford Hosp, Eye Care Serv, Detroit, MI 48202 USA. NEI, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Sch Med, Bethesda, MD 20814 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4830B777 BP S908 EP S908 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704898 ER PT J AU Soto-Prior, A Liu, S Henningsgaard, AA Yu, S Redmond, TM AF Soto-Prior, A Liu, S Henningsgaard, AA Yu, S Redmond, TM TI The upstream region of the RPE65 gene confers RPE-specific activity both in vivo and in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2060B306 BP S390 EP S390 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702059 ER PT J AU Stone, LS Krauzlis, RJ AF Stone, LS Krauzlis, RJ TI Precision of the motion direction signals underlying pursuit eye-movements and perception in humans. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NASA, Ames Res Ctr, Moffett Field, CA 94035 USA. Salk Inst, La Jolla, CA USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1669 BP S316 EP S316 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701668 ER PT J AU Strunnikova, N Silk, W Baffi, J Csaky, K AF Strunnikova, N Silk, W Baffi, J Csaky, K TI Detection of high level of HSP27 heat shock protein in retinal pigment epithelium (ARPE-19) and in photoreceptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 968B343 BP S186 EP S186 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700967 ER PT J AU Su, SB Silver, PB Zhang, MF Chan, CC Caspi, RR AF Su, SB Silver, PB Zhang, MF Chan, CC Caspi, RR TI Pertussis toxin prevents experimental autoimmune uveitis induced by adoptive transfer of uveitogenic T cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1987B233 BP S377 EP S377 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701986 ER PT J AU Tanemoto, K Tomarev, SI AF Tanemoto, K Tomarev, SI TI Transcriptional regulation of the human MYOC/TIGR promoter in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LMDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4359B306 BP S821 EP S821 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704428 ER PT J AU Tomarev, SI Tanemoto, K Ahmed, F Zinovieva, R Duncan, MK Semina, E AF Tomarev, SI Tanemoto, K Ahmed, F Zinovieva, R Duncan, MK Semina, E TI Analysis of MYOC/TIGR promoter activity in vitro and in transgenic mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, LMDB, Bethesda, MD 20892 USA. Univ Delaware, Newark, DE USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4361B308 BP S822 EP S822 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704430 ER PT J AU Tsilou, E Rubin, BI Caruso, RC Reed, G Hejtmancik, JF Iwata, F Redman, J Kaiser-Kupfer, MI AF Tsilou, E Rubin, BI Caruso, RC Reed, G Hejtmancik, JF Iwata, F Redman, J Kaiser-Kupfer, MI TI Natural history of Usher syndrome and comparison of severity of Usher type I and II. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4685B632 BP S881 EP S881 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704754 ER PT J AU Velez, G King, BA Yuan, P Whitcup, SM Robison, MR AF Velez, G King, BA Yuan, P Whitcup, SM Robison, MR TI Thalidomide analogue (EM-138) sustained release implants to treat choroidal neovascularization associated with macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, OD, Bethesda, MD 20892 USA. NIH, Dept Pharmaceut, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 941B316 BP S180 EP S180 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246700940 ER PT J AU Vistica, BP Zhang, M Janardhan, S Wawrousek, EF Lee, RS Gery, I AF Vistica, BP Zhang, M Janardhan, S Wawrousek, EF Lee, RS Gery, I TI T cell-induced ocular inflammation in double transgenic mice is accompanied by bias toward TH2 cytokine production. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1992B238 BP S378 EP S378 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701991 ER PT J AU Wang, P Sun, SH Silver, PB Chen, CC Wiggert, B Agarwal, RK Caspi, RR AF Wang, P Sun, SH Silver, PB Chen, CC Wiggert, B Agarwal, RK Caspi, RR TI Downregulation of experimental autoimmune uveoretinitis (EAU) by Methimazole. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1985B231 BP S377 EP S377 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701984 ER PT J AU Wang-Su, ST David, LL Lampi, KJ Yang, S Calvin, HI Garland, D Andley, UP Wagner, BJ AF Wang-Su, ST David, LL Lampi, KJ Yang, S Calvin, HI Garland, D Andley, UP Wagner, BJ TI Proteome comparison of human lens epithelial cells with cultured HLE B-3 cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, Sch Med, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Oregon Hlth Sci Univ, Dept Oral Mol Biol, Portland, OR 97201 USA. Univ Med & Dent New Jersey, Sch Med, Dept Ophthalmol, Newark, NJ 07103 USA. NEI, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 3108B206 BP S585 EP S585 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246703178 ER PT J AU Wheelock, RH Russell, P AF Wheelock, RH Russell, P TI Myocilin interacts with alpha B-crystallin in human U373MG cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4045 BP S762 EP S762 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704114 ER PT J AU Whitcup, SM Gogolak, L Ross, ML Lutz, RJ Yuan, P King, BA Robinson, MR AF Whitcup, SM Gogolak, L Ross, ML Lutz, RJ Yuan, P King, BA Robinson, MR TI Sustained-release methotrexate implants for the treatment of intraocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, OD, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4086B33 BP S770 EP S770 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704155 ER PT J AU Willennain, F Skolik, SA Baffi, JS Velu, T Caspers-Velu, L Csaky, KG AF Willennain, F Skolik, SA Baffi, JS Velu, T Caspers-Velu, L Csaky, KG TI Vascular endothelial growth factor (VEGF(165)) overexpression in subretinal pigment epithelium transplantation in the rat: Possible alteration of immune privilege SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Ocular Gene Therapy Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Free Univ Brussels, Hop St Pierre, Dept Ophthalmol, B-1050 Brussels, Belgium. Free Univ Brussels, Hop St Pierre, Dept Oncol, B-1050 Brussels, Belgium. Marshall Univ, Huntington, WV USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4547B494 BP S856 EP S856 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704616 ER PT J AU Wistow, GJ Bernstein, S Behal, A Smith, D AF Wistow, GJ Bernstein, S Behal, A Smith, D TI NEIBANK: EST analysis and bioinformatics for ocular genomics. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4631B578 BP S871 EP S871 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704700 ER PT J AU Xu, ZP Wawrousek, EF Sax, CM Piatigorsky, J AF Xu, ZP Wawrousek, EF Sax, CM Piatigorsky, J TI Transketolase in the cornea: Species-specificity, production in darkness and creation of hemizygous mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1371B746 BP S261 EP S261 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701370 ER PT J AU Ye, HQ Chan, CC Whitcup, SM Smith, JA AF Ye, HQ Chan, CC Whitcup, SM Smith, JA TI Conjunctival epithelial keratin expression in ocular surface disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2422B668 BP S457 EP S457 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702420 ER PT J AU Zelenka, PS Negash, S Wang, HS Guo, HT Haque, MR Gao, CY AF Zelenka, PS Negash, S Wang, HS Guo, HT Haque, MR Gao, CY TI A role for CDK5 in epithelial cell adhesion and migration. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Taipei 112, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 4799B746 BP S903 EP S903 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246704867 ER PT J AU Zhang, C Csaky, KG AF Zhang, C Csaky, KG TI Human RPE demonstrates cell death and blebbing without caspase activation or nuclear fragmentation in response to apoptotic stimuli SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 2178B424 BP S412 EP S412 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246702176 ER PT J AU Zhang, MF Chan, CC Vistica, BP Sim, SJ Hung, V Wiggert, B Gery, I AF Zhang, MF Chan, CC Vistica, BP Sim, SJ Hung, V Wiggert, B Gery, I TI Copolymer 1 inhibits experimental autoimmune uveoretinitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2000 VL 41 IS 4 SU S MA 1991B237 BP S378 EP S378 PG 1 WC Ophthalmology SC Ophthalmology GA 300HF UT WOS:000086246701990 ER PT J AU Gordin, F Chaisson, RE Matts, JP Miller, C Garcia, MD Hafner, R Valdespino, JL Coberly, J Schechter, M Klukowicz, AJ Barry, MA O'Brien, RJ AF Gordin, F Chaisson, RE Matts, JP Miller, C Garcia, MD Hafner, R Valdespino, JL Coberly, J Schechter, M Klukowicz, AJ Barry, MA O'Brien, RJ CA Terry Beirn Community Programs Cli Adult AIDS Clinical Trials Grp Pan Amer Hlth Org Ctr Dis Control Prevention Study G TI Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons - An international randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESISTANT TUBERCULOSIS; ACTIVE TUBERCULOSIS; UNITED-STATES; DRUG-USERS; THERAPY; RISK; PROGRESSION; PROPHYLAXIS; OUTBREAK AB Context Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. Objective To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection. Design Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997. Setting Outpatient clinics in the United States, Mexico, Haiti, and Brazil. Participants A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result. Interventions Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791). Main Outcome Measures The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group. Results Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P =.28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P =.83), HIV progression and/or death (P =.09), or overall adverse events (P =.27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P =.01). Neither regimen appeared to, lead to the development of drug-resistant tuberculosis. Conclusions Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs. C1 Vet Affairs Med Ctr, Washington, DC 20422 USA. Georgetown Univ, Washington, DC USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Univ Minnesota, Sch Publ Hlth, Community Programs Clin Res AIDS, Ctr Stat, Minneapolis, MN USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. NIAID, Div AIDS, Bethesda, MD 20892 USA. Univ Fed Rio de Janeiro, Dept Prevent Med, Hosp Univ Clementino Fraga Filho, Infect Dis Serv, BR-21941 Rio De Janeiro, Brazil. St Michaels Med Ctr, Div Pulm, Newark, NJ USA. Boston Publ Hlth Commiss, Boston, MA USA. Ctr Dis Control & Prevent, Div TB Eliminat, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. RP Gordin, F (reprint author), Vet Affairs Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. NR 34 TC 186 Z9 190 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 15 PY 2000 VL 283 IS 11 BP 1445 EP 1450 DI 10.1001/jama.283.11.1445 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 290UR UT WOS:000085696700029 PM 10732934 ER PT J AU Rick, SW Cachau, RE AF Rick, SW Cachau, RE TI The nonplanarity of the peptide group: Molecular dynamics simulations with a polarizable two-state model for the peptide bond SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID HELIX-COIL TRANSITIONS; MECHANICS FORCE-FIELDS; WATER MODEL; GAS-PHASE; MACROMOLECULAR STRUCTURES; ATOM POLARIZABILITIES; EFFECTIVE POTENTIALS; QUANTUM DYNAMICS; EXCESS PROTON; LIQUID WATER AB The general properties of the peptide bond can be described from a linear combination of two states: a single bond neutral form and a double bond zwitterionic form. However, environmental effects can shift the balance of the linear combination. This would cause the rigidity of torsional rotations of the peptide bond to be environmentally dependent and, in fact, an analysis of protein structures in the protein data bank reveals a different degree of nonplanarity for different secondary structure elements. A potential is presented in which the peptide bond is treated as a linear combination of two states; the coefficients of the two states are updated as the simulation progresses using an extended Lagrangian formalism. The model is applied to the helix/coil transition of polyalanine. Fluctuations in the planarity of the peptide dihedral angle are found to increase the rate constant for the coil to helix transition by a factor of two. (C) 2000 American Institute of Physics. [S0021-9606(00)50411-5]. C1 NCI, Frederick Canc Res & Dev Ctr, Adv Biomed Comp Ctr, SAIC Frederick, Winston Salem, NC 27102 USA. RP Rick, SW (reprint author), NCI, Frederick Canc Res & Dev Ctr, Adv Biomed Comp Ctr, SAIC Frederick, Winston Salem, NC 27102 USA. NR 83 TC 32 Z9 34 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 15 PY 2000 VL 112 IS 11 BP 5230 EP 5241 DI 10.1063/1.481078 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 290QT UT WOS:000085687900038 ER PT J AU Braun, MC Lahey, E Kelsall, BL AF Braun, MC Lahey, E Kelsall, BL TI Selective suppression of IL-12 production by chemoattractants SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA-PRODUCTION; BLOOD MONONUCLEAR-CELLS; COLON EPITHELIAL-CELLS; HUMAN DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; CD4(+) T-CELLS; INTERLEUKIN-12 PRODUCTION; HUMAN MONOCYTES; RECEPTOR EXPRESSION; DOWN-REGULATION AB We investigated the ability of chemoattractants to affect IL-12 production by human monocytes and dendritic cells. We found that pretreatment of monocytes with macrophage chemoattractant proteins (MCP-1 to -4), or C5a, but not stromal-derived factor-1, macrophage inflammatory protein-1 alpha, RANTES, or eotaxin, inhibited IL-12 p70 production in response to stimulation with Staphylococcus aureus, Cowan strain 1 (SAC), and IFN-gamma, The production of TNF-alpha and IL-10, however, was minimally affected by any of the chemoattractants. The degree of inhibition of IL-12 p70 production by MCP-1 to -4 was donor dependent and was affected by the autocrine inhibitory effects of IL-10, In contrast, C5a profoundly suppressed IL-12 production in an n-10-independent fashion. Neither TGF-beta 1 nor PGE(2) was important for the suppression of IL-12 by any of the chemoattractants tested. The accumulation of mRNA for both IL-12 p35 and p40 genes was inhibited by chemokine pretreatment. Interestingly, MCP-1 to -4 and C5a did not suppress IL-12 production by monocyte-derived dendritic cells (DC) stimulated with CD40 ligand and IFN-gamma or by SAC and IFN-gamma, suggesting that these factors may act at the site of inflammation to suppress IL-12 and IFN-gamma production rather than in the lymph node to affect T cell priming. Despite the inability of C5a to inhibit IL-PZ production by DCs, the receptor for C5a (CD88) was expressed by these cells, and recombinant C5a induced a Ca2+ flux. Taken together, these results define a range of chemoattractant molecules with the ability to suppress IL-12 production by human monocytes and have broad implications for the regulation of immune responses in vivo. C1 NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Clin Invest Lab,NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), NIAID, Immune Cell Interact Unit, Mucosal Immun Sect, Clin Invest Lab,NIH, Bldg 10-11N238,10 Ctr Dr, Bethesda, MD 20892 USA. NR 61 TC 123 Z9 123 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3009 EP 3017 PG 9 WC Immunology SC Immunology GA 291YF UT WOS:000085766800022 PM 10706689 ER PT J AU Jankovic, D Kullberg, MC Noben-Trauth, N Caspar, P Paul, WE Sher, A AF Jankovic, D Kullberg, MC Noben-Trauth, N Caspar, P Paul, WE Sher, A TI Single cell analysis reveals that IL-4 receptor/Stat6 signaling is not required for the in vivo or in vitro development of CD4(+) lymphocytes with a Th2 cytokine profile SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; T-HELPER CELL; FC-EPSILON-RI; SCHISTOSOMA-MANSONI; IFN-GAMMA; CUTANEOUS LEISHMANIASIS; DEFICIENT MICE; IN-VIVO; INTERLEUKIN-4-DEFICIENT MICE; MONOCLONAL-ANTIBODIES AB The concept that IL-4 is the primary signal for Th2 lymphocyte differentiation has recently been put in doubt by studies in which the production of Th2-associated cytokines was detected in mice deficient in IL-4 synthesis or IL-4R triggering. In this study, we formally demonstrate by single cell analysis that CD4(+) lymphocytes with a classical Th2 phenotype (IL-4(+),IL-5(+), IFN-gamma(-), IL-2(-)) develop in significant numbers in helminth-infected mice deficient in either IL-4R alpha-chain or Stat6, While an expanded population of Th1 (IL-4(-), IL-5(-), IFN-gamma(+), IL-2(+)) lymphocytes was observed in the same animals, surprisingly, cells with a mixed Th0 cytokine pattern were rare. The cytokine production phenotypes of the Th1 and Th2 subpopulations generated in infected Stat6-deficient mice were unaffected by in vitro neutralization of endogenous IL-4 or IFN-gamma, Nevertheless, while addition of exogenous rIL-12 resulted in transitory IFN-gamma production by Th2 lymphocytes from both wild-type and Stat6-deficient mice, IL-4 synthesis was preserved in the former, but temporarily ablated in the latter cells. Importantly, IL-4(+) IFN-gamma(-) and IL-4(-) IFN-gamma(+) populations similar to those arising in helminth-infected Stat6;deficient mice could also be generated in vitro by repetitive polyclonal stimulation of CD4(+)CD62L(high) lymphocytes from uninfected mice of the same strain. Together, the results of these single cell analysis experiments demonstrate that n-4R/Stat6 signaling, while influencing the final frequency of Th2 lymphocytes, is not essential for Th2 cell development, and suggest that this pathway has a previously unrecognized function in stabilizing Th2 populations once they have emerged. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 68 TC 182 Z9 189 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3047 EP 3055 PG 9 WC Immunology SC Immunology GA 291YF UT WOS:000085766800026 PM 10706693 ER PT J AU Kim, MG Flomerfelt, FA Lee, KN Chen, C Schwartz, RH AF Kim, MG Flomerfelt, FA Lee, KN Chen, C Schwartz, RH TI A putative 12 transmembrane domain cotransporter expressed in thymic cortical epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID THYMOCYTE DEVELOPMENT; MICE; GENE; DIFFERENTIATION; SEQUENCE; MOUSE; PROTEIN; MICROENVIRONMENT; MATURATION; TRANSPORT AB We have isolated a full-length cDNA clone (thymic stromal origin (TSO)-1C12) from a SCID thymus library using a probe from a PCR-based subtractive library enriched for sequences from fetal thymic stromal cells. TSO-1C12 mRNA is expressed mainly in the thymic cortex and is highly enriched in SCID thymus. Expression per cell is highest during fetal thymus development and decreases after day 16. Antipeptide Abs immunoprecipitated a hydrophobic, plasma membrane glycoprotein (thymic stromal cotransporter, TSCOT) whose translated sequence has weak homology to bacterial antiporters and mammalian cation cotransporters with 12 transmembrane domains. TSCOT represents a new member of this superfamily that is highly expressed in thymic cortical epithelial cells. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room 111, Bethesda, MD 20892 USA. NR 32 TC 18 Z9 19 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3185 EP 3192 PG 8 WC Immunology SC Immunology GA 291YF UT WOS:000085766800042 PM 10706709 ER PT J AU Bosco, MC Rapisarda, A Massazza, S Melillo, G Young, H Varesio, L AF Bosco, MC Rapisarda, A Massazza, S Melillo, G Young, H Varesio, L TI The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1 alpha and-1 beta in macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MESSENGER-RNA EXPRESSION; INTERFERON-GAMMA; NITRIC-OXIDE; INDOLEAMINE 2,3-DIOXYGENASE; IFN-GAMMA; GENE-EXPRESSION; DIFFERENTIAL REGULATION; ANTIMICROBIAL ACTIVITY; MURINE MACROPHAGES AB We previously found that the tryptophan catabolite picolinic acid (PA) is a costimulus for the activation of macrophage effector functions. In this study, we have investigated the ability of PA to modulate the expression of chemokines in macrophages. We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1 alpha and MIP-1 beta (MIPs) mRNA expression in mouse macrophages in a dose- and time-dependent fashion and through a de novo protein synthesis-dependent process. The induction by PA occurred within 3 h of treatment and reached a peak in 12 h, The stimulatory effects of PA were selective for MIPs because other chemokines, including monocyte chemoattractant protein-1, RANTES, IFN-gamma-inducible protein-10, MIP-2, and macrophage-derived chemokine, were not induced under the same experimental conditions and were not an epiphenomenon of macrophage activation because IFN-gamma did not affect MIPs expression. Induction of both MIP-1 alpha and MIP-1 beta by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control. Iron chelation could be involved in MIPs induction by PA because iron sulfate inhibited the process and the iron;chelating agent, desferrioxamine, induced MIPs expression, We propose the existence of a new pathway leading to inflammation initiated by tryptophan catabolism that can communicate with the immune system through the production of PA, followed by secretion of chemokines by macrophages, These results establish the importance of PA as an activator of macrophage proinflammatory functions, providing the first evidence that this molecule can be biologically active without the need for a costimulatory agent. C1 Ist Giannina Gaslini, Mol Biol Lab, I-16147 Genova Quarto, Italy. NCI, Frederick Canc Res & Dev Ctr, DTP Tumnor Hypoxia Program, Ft Detrick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Bosco, MC (reprint author), Ist Giannina Gaslini, Mol Biol Lab, Lgo Gerolamo Gaslini 5, I-16147 Genova Quarto, Italy. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 FU Telethon [A.075] NR 65 TC 65 Z9 66 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3283 EP 3291 PG 9 WC Immunology SC Immunology GA 291YF UT WOS:000085766800054 PM 10706721 ER PT J AU Kuroiwa, T Schlimgen, R Illei, GG McInnes, IB Boumpas, DT AF Kuroiwa, T Schlimgen, R Illei, GG McInnes, IB Boumpas, DT TI Distinct T cell/renal tubular epithelial cell interactions define differential chemokine production: Implications for tubulointerstitial injury in chronic glomerulonephritides SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; ADHESION MOLECULE-1; IN-VITRO; CHEMOTACTIC CYTOKINES; RHEUMATOID-ARTHRITIS; RANTES PRODUCTION; BETA-CHEMOKINES; DIRECT-CONTACT; TNF-ALPHA; ACTIVATION AB Chemokines can promote interstitial fibrosis that is, in turn, a strong predictor of renal failure in chronic glomerulonephritides (GN), Resident renal cells, including renal tubular epithelial cells (RTEC), represent a prominent source of chemokine expression. Evaluating those factors responsible for sustained chemokine production by RTEC during GN is therefore crucial. The contribution of interstitial T cells to such expression, and in particular the precise mature of their interactions with RTEC, are poorly understood. Activated T cell/RTEC coculture induced production of high levels of monocyte chemoattractant protein-1 (MCP-1), RANTES, and IFN-inducible protein-ill from RTEC. Using double-chamber cultures and activated T cell plasma membrane preparations we demonstrated that both cell contact and soluble factors contributed to RTEC chemokine production, Importantly, different chemokines exhibited distinct activation requirements, Thus; for RANTES cell contact was essential, but not sufficient. In contrast, either soluble factors or cell contact induced MCP-1 and IFN-inducible protein-10 production, although both pathways were required for a maximal response. Neutralization experiments identified critical roles in this process for proinflammatory cytokines such as TNF-alpha, IL-1 beta, and IFN-gamma as well as membrane molecules such as LFA-1, Cn40 ligand, and membrane bound TNF-alpha. Finally, chemotactic bioassays of T cell/RTEC coculture supernatants demonstrated 80% reduction of monocyte migration following MCP-1 neutralization, indicating a dominant role for this chemokine. In summary, activation of renal tubular cells by infiltrating T cells can amplify and perpetuate local inflammatory responses through chemokine production differentially mediated by soluble and cell contact-dependent factors. Recognition of this regulatory diversity has important implications in the choice of potential therapeutic targets in GN. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Kuroiwa, T (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N218M10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. NR 49 TC 66 Z9 71 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2000 VL 164 IS 6 BP 3323 EP 3329 PG 7 WC Immunology SC Immunology GA 291YF UT WOS:000085766800059 PM 10706726 ER PT J AU Wilk, A Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Grajkowski, A Phillips, LR Beaucage, SL TI Deoxyribonucleoside cyclic N-acylphosphoramidites as a new class of monomers for the stereocontrolled synthesis of oligothymidylyl- and oligodeoxycytidylyl- phosphorothioates SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEOSIDE BICYCLIC OXAZAPHOSPHOLIDINES; PHASE STEREOSELECTIVE SYNTHESIS; SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S; DINUCLEOTIDE PHOSPHOROTHIOATES; NONBONDED INTERACTIONS; OLIGODEOXYRIBONUCLEOTIDES; OLIGONUCLEOTIDES; CLEAVAGE AB A simple and straightforward synthesis of the pyrimidine 2'-deoxyribonucleoside cyclic N-acylphosphoramidites R-P-1 and S-P-1 is described. Specifically, (+/-)-2-amino-1-phenylethanol 2 was chemoselectively N-acylated to 4 by treatment with ethyl fluoroacetate 3 followed by reaction with hexaethylphosphorus triamide to afford the cyclic N-acylphosphoramidite 5 as a mixture of diastereomeric rotamers (5a and 5b). Condensation of N-4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2-deoxycytidine 8 with 5 in the presence of 1H-tetrazole gave, after silica gel chromatography, pure R-P-1 and S-P-1. P-31 NMR studies indicated that when Rp-l or Sp-l is reacted with 3'-O-acetylthymidine and N,N,N',N'-tetramethylguanidine in CD3CN, the dinucleoside phosphotriester S-P-9 or R-P-9 is formed in near quantitative yield with total P-stereospecificity (delta(P) 144.2 or 143.9 ppm, respectively). Sulfurization of Sp-9 or R-P-9 generated the P-stereodefined dinucleoside phosphorothioate R-P-11 or S-P-11 (delta(P) 71.0 or 71.2 ppm, respectively). The 2'-deoxycytidine cyclic N-acylphosphoramidite derivatives R-P-1 and S-P-1 were subsequently applied to the solid-phase synthesis of [R-P,R-P]- and [S-P,S-P] -trideoxycytidilyl diphosphorothioate d(CPSCPSC), and [R-P,S-P,R-P]-tetradeoxycytidilyl triphosphorothioate d(CPSCPSCPSC) Following deprotection, reversed-phase (RP) HPLC analysis of these oligonucleotide analogues showed a single peak for each oligomer. By comparison, RP-HPLC analysis of purified P-diastereomeric d(CPSCPSC) and d(CPSCPSCPSC) prepared from standard 2-cyanoethyl deoxyribonucleoside phosphoramidites exhibited 4 and 8 peaks, respectively, each peak corresponding to a specific P-diastereomer (see Figure 3A). The thymidine cyclic N-acylphosphoramidite derivatives R-P-14 and S-P-14 were also prepared, purified, and used successfully in the solid-phase synthesis of [R-P](11)-d[(T-PS)(11)T]. Thus, the application of deoxyribonucleoside cyclic N-acyl phosphoramidites to P-stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates may offer a compelling alternative to the methods currently used for such syntheses. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 60 Z9 60 U1 0 U2 9 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 MAR 15 PY 2000 VL 122 IS 10 BP 2149 EP 2156 DI 10.1021/ja991773u PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 296WZ UT WOS:000086050900002 ER PT J AU Cornilescu, G Bax, A Case, DA AF Cornilescu, G Bax, A Case, DA TI Large variations in one-bond (C alpha-13C beta)-C-13 J couplings in polypeptides correlate with backbone conformation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; DENSITY-FUNCTIONAL THEORY; SPIN-SPIN COUPLINGS; CHEMICAL-SHIFTS; HUMAN UBIQUITIN; PROTEIN COMPLEXES; NMR-SPECTROSCOPY; AMINO-ACIDS; CONSTANTS; C-13 AB One-bond (1)J(C alpha C beta) scalar couplings, measured in the protein ubiquitin, exhibit a strong dependence on the local backbone conformation. Empirically, the deviation from the (1)J(C alpha C beta) value measured in the corresponding free amino acid, can be expressed as Delta(1)J(C alpha C beta) = 1.3 + 0.6 cos(psi - 61 degrees) + 2.2 cos[2(psi - 61 degrees)] - 0.9 cos[2(phi + 20 degrees)] +/- 0.5 Hz, where phi and psi are the intraresidue polypeptide backbone torsion angles obtained from ubiquitin's X-ray structure. The relation between (1)J(C alpha C beta) and backbone torsion angles is confirmed by density functional theory (DFT) calculations on the peptide analogue Ace-Ala-NMe. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Cornilescu, Gabriel/H-3113-2011 OI Cornilescu, Gabriel/0000-0002-1204-8904 NR 43 TC 23 Z9 23 U1 0 U2 3 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 MAR 15 PY 2000 VL 122 IS 10 BP 2168 EP 2171 DI 10.1021/ja993609c PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 296WZ UT WOS:000086050900004 ER PT J AU Daly, MB Offit, K Li, F Glendon, G Yaker, A West, D Koenig, B McCredie, M Venne, V Nayfield, S Seminara, D AF Daly, MB Offit, K Li, F Glendon, G Yaker, A West, D Koenig, B McCredie, M Venne, V Nayfield, S Seminara, D TI Participation in the cooperative family registry for breast cancer studies: Issues of informed consent SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENETIC RESEARCH; ETHICAL ISSUES C1 Fox Chase Canc Ctr, Cheltenham, PA 19012 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. No Calif Canc Ctr, Union City, CA USA. Stanford Univ, Sch Med, Ctr Biomed Eth, Stanford, CA 94305 USA. New S Wales Canc Council, Kings Cross, NSW, Australia. Huntsman Canc Res Ctr, Salt Lake City, UT USA. NCI, Bethesda, MD 20892 USA. RP Daly, MB (reprint author), Fox Chase Canc Ctr, 510 Township Line Rd, Cheltenham, PA 19012 USA. FU NCI NIH HHS [CA95003] NR 12 TC 7 Z9 7 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 MAR 15 PY 2000 VL 92 IS 6 BP 452 EP 456 DI 10.1093/jnci/92.6.452 PG 5 WC Oncology SC Oncology GA 292KX UT WOS:000085794200009 PM 10716962 ER PT J AU Herrero, R Hildesheim, A Bratti, C Sherman, ME Hutchinson, M Morales, J Balmaceda, I Greenberg, MD Alfaro, M Burk, RD Wacholder, S Plummer, M Schiffman, M AF Herrero, R Hildesheim, A Bratti, C Sherman, ME Hutchinson, M Morales, J Balmaceda, I Greenberg, MD Alfaro, M Burk, RD Wacholder, S Plummer, M Schiffman, M TI Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RISK-FACTORS; INTRAEPITHELIAL NEOPLASIA; HPV DNA; CANCER; WOMEN; PREVALENCE; ASSOCIATION; COLOMBIA; TYPE-52; LESIONS AB Background: Human papillomavirus (HPV) is the main cause of cervical neoplasia, Because few population-based studies have investigated the prevalence of type-specific infection in relation to cervical disease, we studied a high-risk population, estimating the prevalence of HPV infection and the risk associated with various HPV types. Methods: We screened 9175 women in Guanacaste, Costa Rica, to obtain a referent standard final diagnosis, and tested 3024 women for more than 40 types of HPV with a polymerase chain reaction-based system. Results: Among women with normal cytology, HPV infections peaked first in women younger than 25 gears, and they peaked again at age 55 years or older with predominantly non-cancer-associated types of HPV and uncharacterized HPV types. Low-grade squamous intraepithelial lesions (LSILs) (n = 189) decreased consistently with age. The prevalence of high-grade squamous intraepithelial lesions (HSILs) (n = 128) peaked first around age 30 years and again at age 65 years or older. Seventy-three percent of LSILs were HPV positive, with HPV16 being the predominant type (16% of positive subjects). HPV was found in 89% of HSILs and 88% of cancers, with HPV16 being strongly predominant (51% and 53% of positive subjects). Virtually all HSILs and cancers had cancer-associated HPV types, with high odds ratios (ORs) and attributable fractions around 80%, Risk for HPV16 was particularly high (OR for HSILs = 320, 95% confidence interval [CI] = 97-1000; OR for cancer = 710, 95% CI = 110-4500), Conclusions: We confirm the early decline of HPV infection with age but note increased prevalence after menopause, which could be related to a second peak of HSILs, an observation that warrants further investigation, At least 80% of HPVs involved in cervical carcinogenesis in this population have been characterized. Polyvalent vaccines including the main cancer-associated HPV types may be able to prevent most cases of cervical disease in this region. C1 Minist Hlth, San Jose, Costa Rica. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Caja Costarricense Seguro Social, San Jose, Costa Rica. Johns Hopkins Med Inst, Dept Pathol & Gynecol & Obstet, Baltimore, MD 21205 USA. Brown Univ, Women & Infants Hosp, Providence, RI 02912 USA. Omnia Corp, Philadelphia, PA USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. RP Herrero, R (reprint author), Proyecto Epidemiol Guanacaste, POB 301-6151, San Jose, Costa Rica. FU NCI NIH HHS [CA54273] NR 46 TC 395 Z9 418 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 MAR 15 PY 2000 VL 92 IS 6 BP 464 EP 474 DI 10.1093/jnci/92.6.464 PG 11 WC Oncology SC Oncology GA 292KX UT WOS:000085794200011 PM 10716964 ER PT J AU Guidi, AJ Berry, DA Broadwater, G Perloff, M Norton, L Barcos, MP Hayes, DF AF Guidi, AJ Berry, DA Broadwater, G Perloff, M Norton, L Barcos, MP Hayes, DF TI Association of angiogenesis in lymph node metastases with outcome of breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CARCINOMA IN-SITU; TUMOR ANGIOGENESIS; MICROVESSEL DENSITY; PROGNOSTIC-SIGNIFICANCE; FACTOR EXPRESSION; INDICATOR; MARKERS AB Background: Microvessel density (MVD) is a measure of the extent of new blood vessel growth or angiogenesis, which is required for tumor progression. Increased MVD in primary breast cancers appears to adversely affect disease-free survival and overall survival in patients with breast cancer. However, the clinical implications of angiogenesis in breast cancer metastases have not been well studied. The purpose of this study was to compare intratumoral MVD in primary breast cancer tissues with MVD in axillary lymph node metastases and to evaluate the relationships among primary- and metastatic-tumor MVD, disease-free survival, and overall survival in patients with lymph node-positive, stage II breast cancer who were treated with adjuvant chemotherapy in Cancer and Leukemia Group B Protocol 8082, Methods: Immunostaining for factor VIII-related antigen was performed on tissue sections from 47 primary tumors and 91 axillary lymph nodes containing metastases from 110 patients with lymph node-positive breast cancer. Sections were examined for the presence or absence of focal areas of relatively intense neovascularization (vascular hot spots), and a quantitative assessment of intratumoral MVD was performed. Results: The presence of vascular hot spots in axillary lymph node metastases, but not primary breast cancers, was associated with statistically significantly decreased disease-free survival (P = .006) and overall survival (P = .004) by univariate analysis. Similarly, increased MVD in metastases, but not in primary tumors, was statistically significantly associated with diminished overall survival in these patients (P = .02), In multivariate analysis, the number of positive axillary lymph nodes and the presence of vascular hot spots in axillary lymph node metastases predicted decreased disease-free survival (P = .0001 and .02, respectively) and overall survival (P = .0001 and .007, respectively). All P values were two-sided. Conclusion: This pilot study suggests that assessing neovascularization in axillary lymph node metastases may provide clinically useful information regarding survival in patients with primary breast cancer. C1 N Shore Med Ctr, Salem, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Georgetown Univ, Lombardi Canc Ctr, Breast Canc Program, Washington, DC 20007 USA. RP Hayes, DF (reprint author), Georgetown Univ, Lombardi Canc Ctr, Breast Canc Program, 3970 Reservoir Rd NW,RB504E, Washington, DC 20007 USA. FU NCI NIH HHS [CA31946, CA64507, CA77651] NR 30 TC 51 Z9 55 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 MAR 15 PY 2000 VL 92 IS 6 BP 486 EP 492 DI 10.1093/jnci/92.6.486 PG 7 WC Oncology SC Oncology GA 292KX UT WOS:000085794200014 PM 10716967 ER PT J AU Nelson, NJ AF Nelson, NJ TI Scientific interest in Newcastle disease virus is reviving - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Off Canc Commun, Off Director, Bethesda, MD 20892 USA. RP Nelson, NJ (reprint author), NIH, Bldg 31,Rm 10A-19, Bethesda, MD 20892 USA. NR 6 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 MAR 15 PY 2000 VL 92 IS 6 BP 493 EP 494 PG 2 WC Oncology SC Oncology GA 292KX UT WOS:000085794200016 ER PT J AU Lin, XK Parsels, LA Voeller, DM Allegra, CJ Maley, GF Maley, F Chu, E AF Lin, XK Parsels, LA Voeller, DM Allegra, CJ Maley, GF Maley, F Chu, E TI Characterization of a cis-acting regulatory element in the protein coding region of thymidylate synthase mRNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COLON-CANCER-CELLS; MESSENGER-RNA TRANSLATION; 3' UNTRANSLATED REGION; ESCHERICHIA-COLI; 5-FLUOROURACIL; BINDING; IDENTIFICATION; INTERFERON; SYNTHETASE; EXPRESSION AB Thymidylate synthase CTS) functions as an RNA-binding protein by interacting with two different sequences on its own mRNA, One site is located in the 5'-upstream region of human TS mRNA while the second site is located within the protein coding region corresponding to nt 434-634, In this paper, a 70 nt RNA sequence, corresponding to nt 480-550, was identified that binds TS protein with an affinity similar to that of full-length TS mRNA and TS434-634 RNA, In vitro translation studies confirmed that this sequence is critical for the translational autoregulatory effects of TS, To document in vivo biological significance, TS sequences contained within this region were cloned onto the 5'-end of a luciferase reporter plasmid and transient transfection experiments were performed using H630 human colon cancer cells, In cells transfected with p644/TS434-634 or p644/TS480-550, luciferase activity was decreased 2.5-fold when compared to cells transfected with p644 plasmid alone, Luciferase mRNA levels were identical for each of these conditions as determined by RNase protection and RT-PCR analysis. Immunoprecipitation of TS ribonucleoprotein complexes revealed a direct interaction between TS protein and TS480-550 RNA in transfected H630 cells. Treatment with 5-fluorouridine resulted in a nearly 2-fold increase in luciferase activity only in cells transfected with p644/TS434-634 and p644/TS480-550. This study identifies a 70 nt TS response element in the protein coding region of TS mRNA with in vitro and in vivo translational regulatory activity. C1 VA Connecticut Healthcare Canc Ctr, W Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Med & Pharmacol, Yale Canc Ctr, New Haven, CT 06520 USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. NCI, Med Branch, Bethesda, MD 20814 USA. RP Chu, E (reprint author), VA Connecticut Healthcare Canc Ctr, 111-D,950 Campbell Ave, W Haven, CT 06516 USA. FU NCI NIH HHS [CA 44355, CA75712, R01 CA075712, P30 CA016359, CA16359] NR 32 TC 55 Z9 60 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 2000 VL 28 IS 6 BP 1381 EP 1389 DI 10.1093/nar/28.6.1381 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294DX UT WOS:000085897000012 PM 10684933 ER PT J AU Dunson, DB Weinberg, CR AF Dunson, DB Weinberg, CR TI Accounting for unreported and missing intercourse in human fertility studies SO STATISTICS IN MEDICINE LA English DT Article ID POSTERIOR DISTRIBUTIONS; MARKOV-CHAINS; MONTE-CARLO; PROBABILITY; CONCEPTION; OVULATION; PREGNANCY; SURVIVAL; MODELS; CYCLE AB In prospective studies of human fertility that attempt to identify days of ovulation, couples record each day whether they had intercourse. Depending on the design of the study, couples either (I) mark the dates of intercourse on a chart or (II) mark 'yes' or 'no' for each day of the menstrual cycle. If protocol I is used, intercourse dates that couples fail to record are indistinguishable from dates of no intercourse. Consequently, estimates of day-specific fecundability are biased upwards. If protocol II is used, data from menstrual cycles with missing intercourse information must be discarded in order to fit current fertility models. We propose methods to account for unreported and missing intercourse under the assumption that the missingness mechanism is independent of time conditional on the unobservable true intercourse status. We use probit mixture models to allow for heterogeneity among couples, both in fecundability and in the missingness and non-reporting mechanisms. Markov chain Monte Carlo (MCMC) techniques are used for Bayesian estimation. The methods are generally applicable to the analysis of aggregated Bernoulli outcomes when there is uncertainty in whether a given trial, out of a series of trials, was completed. We illustrate the methods by application to two prospective fertility studies. Published in 2000 by John Wiley & Sons, Ltd. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 29 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2000 VL 19 IS 5 BP 665 EP 679 DI 10.1002/(SICI)1097-0258(20000315)19:5<665::AID-SIM391>3.0.CO;2-P PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 293RK UT WOS:000085866700003 PM 10700738 ER PT J AU Davies, DR AF Davies, DR TI Paul Sigler - Obituary SO STRUCTURE WITH FOLDING & DESIGN LA English DT Biographical-Item C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Davies, DR (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0969-2126 J9 STRUCT FOLD DES JI Struct. Fold. Des. PD MAR 15 PY 2000 VL 8 IS 3 BP R67 EP R68 DI 10.1016/S0969-2126(00)00113-1 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 295AP UT WOS:000085943900004 ER PT J AU Krizek, DR Rick, ME AF Krizek, DR Rick, ME TI A rapid method to visualize von Willebrand Factor multimers by using agarose gel electrophoresis, immunolocalization and luminographic detection SO THROMBOSIS RESEARCH LA English DT Article DE von Willebrand Factor; multimers; method; von Willebrand disease classification ID VONWILLEBRAND-FACTOR MULTIMERS; SENSITIVE VISUALIZATION; PROTEIN; DISEASE; PLASMA; VIII; COMPLEX AB A highly sensitive and rapid clinical method for the visualization of the multimeric structure of von Willebrand Factor in plasma and platelets is described. The method utilizes submerged horizontal agarose gel electrophoresis, followed by transfer of the von Willebrand Factor onto a polyvinylidine fluoride membrane, and immunolocalization and luminographic visualization of the von Willebrand Factor multimeric pattern. This method distinguishes type 1 from types 2A and 2B von Willebrand disease, allowing timely evaluation and classification of von Willebrand Factor in patient plasma. It also allows visualization of the unusually high molecular weight multimers present in platelets. There are several major advantages to this method including rapid processing, simplicity of gel preparation, high sensitivity to low concentrations of von Willebrand Factor, and elimination of radioactivity. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIH, Hematol Serv, CC, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Rick, ME (reprint author), NIH, Hematol Serv, CC, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 2C 390,10 Ctr Dr, Bethesda, MD 20892 USA. NR 20 TC 33 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD MAR 15 PY 2000 VL 97 IS 6 BP 457 EP 462 DI 10.1016/S0049-3848(99)00196-6 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 291BA UT WOS:000085711900010 PM 10704655 ER PT J AU Drotschmann, K Shcherbakova, PV Kunkel, TA AF Drotschmann, K Shcherbakova, PV Kunkel, TA TI Mutator phenotype due to loss of heterozygosity in diploid yeast strains with mutations in MSH2 and MLH1 SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT XXXVIIth European Congress of Toxicology CY JUN 27-30, 1999 CL OSLO, NORWAY SP Royal Norewgian Minist Hlth & Social Aff, Norsk Hydro, Nycomed Amersham & Statoil DE mismatch repair; MSH2; MLH1; colon cancer ID MISMATCH REPAIR PROTEINS; SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION; HETERODIMER; BINDING; CELLS; EXTRACTS; HMSH2; PCNA; GENE AB Mutations in mismatch repair (MMR) genes predispose humans to cancer. Particularly prevalent are frameshift and point mutations in MSH2 and MLH1, two genes whose products are required for the early steps in MMR. In normal tissues of persons predisposed to hereditary non-polyposis colon cancer (HNPCC), these mutations are usually present in only one allele. In tumor cells of these patients, the second, wild type allele is typically found to be deleted or inactivated by point mutation. This suggests that loss of heterozygosity (LOH) results in a strong mutator phenotype that could eventually lead to the onset of disease. Here we demonstrate that diploid yeast strains that are heterozygous for MSH2 and MLH1 alleles have an elevated mutation rate. We further show that this effect results not from saturation of the MMR capacity of all cells in the population, but rather from loss of the wild type allele in a subpopulation of heterozygous cells. These results have implications for understanding the mechanisms of carcinogenesis in humans. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 22 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 15 PY 2000 VL 112 BP 239 EP 244 DI 10.1016/S0378-4274(99)00276-3 PG 6 WC Toxicology SC Toxicology GA 300NZ UT WOS:000086260200033 PM 10720737 ER PT J AU Thorgeirsson, SS Factor, VM Snyderwine, EG AF Thorgeirsson, SS Factor, VM Snyderwine, EG TI Transgenic mouse models in carcinogenesis research and testing SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT XXXVIIth European Congress of Toxicology CY JUN 27-30, 1999 CL OSLO, NORWAY SP Royal Norewgian Minist Hlth & Social Aff, Norsk Hydro, Nycomed Amersham & Statoil DE transgenics; liver carcinogenesis; mice ID GROWTH-FACTOR-ALPHA; LIVER EPITHELIAL-CELLS; EXPRESSING C-MYC; MICE; OVEREXPRESSION; TUMORIGENESIS; DISRUPTION AB Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human TGF-alpha cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing both the interaction of nuclear oncogenes and growth factors in tumorigenesis. In addition, these mice provide an experimental model to test how environmental chemicals might interact with the c-myc and TGF-alpha transgenes during the neoplastic process. We show experimental evidence that co-expression of TGF-alpha and c-myc transgenes in mouse liver promotes overproduction of ROS and thus creates an oxidative stress environment. This phenomenon may account for the massive DNA damage and acceleration of hepatocarcinogenesis observed in the TGF-alpha/c-myc mouse model. Also, the role of mutagenesis in hepatocarcinogenesis induced by 2-amino-3,8-dimethylimidazo(4,5-f)-quinoxaline (MeIQx) was demonstrated in C57BL/lacZ (Muta(TM) Mice) and double transgenic c-myc/lacZ mice that carry the lacZ mutation reporter gene. The MeLQx hepatocarcinogenicity was associated with an increase in in vivo mutagenicity as scored by mutations in the lacZ reporter gene. These results suggest that transgenic mouse models may provide important tools for testing both the carcinogenic potential of environmental chemicals and the interaction/cooperation of these compounds with specific genes during the neoplastic process. Published by Elsevier Science Ireland Ltd. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Room 3C28,Bldg 37,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 12 TC 36 Z9 38 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 15 PY 2000 VL 112 BP 553 EP 555 DI 10.1016/S0378-4274(99)00224-6 PG 3 WC Toxicology SC Toxicology GA 300NZ UT WOS:000086260200075 PM 10720779 ER PT J AU Kondo, T Morita, K Watarai, Y Auerbach, MB Taub, DD Novick, AC Toma, H Fairchild, RL AF Kondo, T Morita, K Watarai, Y Auerbach, MB Taub, DD Novick, AC Toma, H Fairchild, RL TI Early increased chemokine expression and production in murine allogeneic skin grafts is mediated by natural killer cells SO TRANSPLANTATION LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MHC CLASS-I; ALLOGRAFT-REJECTION; TRANSPLANT REJECTION; LUNG INJURY; NK CELLS; T-CELLS; EPITHELIAL-CELLS; CC-CHEMOKINES; CYTOKINE AB Background Increased expression of chemokine mRNA is observed in allogeneic but not syngeneic skin grafts 3-4 days aft:er transplantation. The recipient cells mediating this early inflammatory response in allografts remain unidentified, Methods. Isogeneic and allogeneic skin grafts were transplanted to euthymic and athymic nude mice. mRNA expression and protein production of macrophage inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and the murine homolog of Gro alpha, i.e. KC, from graft homogenates retrieved 3-4 days posttransplantation was tested by Northern blot hybridization and ELISA. To deplete NK cells, recipients were treated with anti-asialo GM1 (ASGM1) antisera or with anti-NK1.1 mAb before transplantation. Results. Express:ion of KC, MIP-1 alpha, and MIP-1 beta mRNA was equivalent in C57BL/6 allogeneic skin grafts and BALB/c isografts at day 2 posttransplant. At day 3 posttransplant, chemokine mRNA levels decreased in isografts but were maintained at high levels in the allografts. Increased early chemokine mRNA was also observed in C57BL/6, but not BALB/c(++) grafts on BALB/c athymic(nu/nu) recipients. Treatment of allograft recipients with ASGM1 or with anti-NK1.1 antibody eliminated NM cells from the spleen and allograft infiltrating cell populations and decreased early chemokine mRNA levels in allografts 60-70%, Analyses of allograft homogenates indicated increased levels of KC, MIP-l alpha, and MIP-1 beta protein at day 4 posttransplant that were decreased in recipients depleted of NR cells, Early chemokine mRNA levels were equivalent in isogeneic and semiallogeneic Fl grafts. Conclusions, Early chemokine mRNA expression and protein production in allogeneic skin grafts is amplified by recipient natural killer (NM) cells. These results indicate a novel. function for infiltrating NK cells in mediating early increased intra-allograft chemokine production and inflammation during the initiation of acute rejection. C1 Cleveland Clin Fdn, Dept Urol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. Tokyo Womens Med Coll, Dept Urol, Tokyo, Japan. Hokkaido Univ, Dept Urol, Sapporo, Hokkaido 060, Japan. NIA, Baltimore, MD 21224 USA. RP Fairchild, RL (reprint author), Cleveland Clin Fdn, Dept Urol, NB3-79,9500 Euclid Ave, Cleveland, OH 44195 USA. FU NIAID NIH HHS [AI40459] NR 56 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2000 VL 69 IS 5 BP 969 EP 977 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 298NG UT WOS:000086145600050 PM 10755559 ER PT J AU Zhau, MS Kashanchi, F Jiang, H Ge, H Brady, JN AF Zhau, MS Kashanchi, F Jiang, H Ge, H Brady, JN TI Phosphorylation of the RAP74 subunit of TFIIF correlates with Tat-activated transcription of the HIV-1 long terminal repeat SO VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; HUMAN-IMMUNODEFICIENCY-VIRUS; INITIATION-FACTOR TFIIF; FACTOR P-TEFB; BASAL TRANSCRIPTION; TRANSACTIVATOR TAT; TAF(II)250-DEPENDENT TRANSCRIPTION; PROMOTER SELECTIVITY; KINASE DOMAIN; CYCLIN T1 AB Transcription from the HIV-1 long terminal repeat (LTR) is regulated by the viral transactivator Tat, which increases RNA polymerase II (RNAP II) processivity. Previous reports have demonstrated that phosphorylation of the RNAP II carboxy-terminal domain by TFIIH and P-TEFb is important for Tat transactivation. Our present results demonstrate that phosphorylation of the RAP74 subunit of TFIIF is also an important step in Tat transactivation. Interestingly, while the general transcription factor TFIIF is required for both basal and Tat-activated transcription, phosphorylation of the RAP74 subunit occurs in the presence of Tat end correlates with a high level of transcription activity. Using a biotinylated DNA template transcription assay, we provide evidence that RAP74 is phosphorylated by TAF(II)250 during Tat-activated transcription. Depletion of RAP74 from the HeLa nuclear extract inhibited HIV-1 LTR-driven basal transcription and Tat transactivation. The addition of TFIIF, reconstituted from recombinant RAP30 and RAP74, to the depleted HeLa nuclear extract resulted in restoration of Tat transactivation. Of importance,the exogenous RAP74 was rapidly phosphorylated in the presence of Tat. These results suggest that RAP74 phosphorylation is one important step, of several, in the Tat transactivation cascade. (C) 2000 Academic Press. C1 NCI, Virus Tumor Biol Sect, LRBGE, Div Basic Sci, Bethesda, MD 20892 USA. NICHHD, Mol Embryol Lab, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, LRBGE, Div Basic Sci, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov NR 62 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 15 PY 2000 VL 268 IS 2 BP 452 EP 460 PG 9 WC Virology SC Virology GA 296MW UT WOS:000086029000025 ER PT J AU Ford, H Dai, F Mu, L Siddiqui, MA Nicklaus, MC Anderson, L Marquez, VE Barchi, JJ AF Ford, H Dai, F Mu, L Siddiqui, MA Nicklaus, MC Anderson, L Marquez, VE Barchi, JJ TI Adenosine deaminase prefers a distinct sugar ring conformation for binding and catalysis: Kinetic and structural studies SO BIOCHEMISTRY LA English DT Article ID NMR COUPLING-CONSTANTS; PSEUDOROTATIONAL EQUILIBRIUM; PENTOFURANOSE MOIETY; H-1-NMR SPECTROSCOPY; NUCLEOSIDES; HIV; INHIBITORS; THERMODYNAMICS; CHEMOTHERAPY; QUANTITATION AB Several recent X-ray crystal structures of adenosine deaminase (ADA) in complex with various adenosine surrogates have illustrated the preferred mode of substrate binding for this enzyme. To define more specific structural details of substrate preferences for binding and catalysis, we have studied the ADA binding efficiencies and deamination kinetics of several synthetic adenosine analogues in which the furanosyl ring is biased toward a particular conformation. NMR solution studies and pseudorotational analyses were used to ascertain the preferred furanose ring puckers (P, nu(MAX)) and rotamer distributions (chi and gamma) of the nucleoside analogues. It was shown that derivatives which are biased toward a "Northern" (3'-endo, N) sugar ring pucker were deaminated up to 65-fold faster and bound more tightly to the enzyme than those that preferred a "Southern" (2'-endo, S) conformation. This behavior, however, could be modulated by other structural factors. Similarly, purine riboside inhibitors of ADA that prefer the N hemisphere were more potent inhibitors than S analogues. These binding propensities were corroborated by detailed molecular modeling studies. Docking of both N- and S-type analogues into the ADA crystal structure coordinates showed that N-type substrates formed a stable complex with ADA, whereas for S-type substrates, it was necessary for the sugar pucker to adjust to a 3'-endo (N-type) conformation to remain in the ADA substrate binding site. These data outline the intricate structural details for optimum binding in the catalytic cleft of ADA. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Barchi, JJ (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, 37 Convent Dr,MSC4255,Bldg 37,Rm 5C02, Bethesda, MD 20892 USA. RI Nicklaus, Marc/N-4183-2014; Barchi Jr., Joseph/N-3784-2014 NR 59 TC 57 Z9 58 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 14 PY 2000 VL 39 IS 10 BP 2581 EP 2592 DI 10.1021/bi992112c PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294HF UT WOS:000085905300016 PM 10704207 ER PT J AU Shane, BS Smith-Dunn, DL deBoer, JG Glickman, BW Cunningham, ML AF Shane, BS Smith-Dunn, DL deBoer, JG Glickman, BW Cunningham, ML TI Subchronic administration of phenobarbital alters the mutation spectrum of lacI in the livers of Big Blue (R) transgenic mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE phenobarbital; in vivo mutations; Big Blue (R) mice; oxazepam; mutation spectrum ID OXIDATIVE DNA-DAMAGE; MOUSE-LIVER; CELL-PROLIFERATION; LIPID-PEROXIDATION; HEPATOCARCINOGEN OXAZEPAM; CARCINOGENIC RISK; ENZYME-INDUCTION; IN-VIVO; ASSAY; 8-HYDROXY-2'-DEOXYGUANOSINE AB Phenobarbital (PHE) is a liver carcinogen in B6C3F1 mice and a weak mutagen that does not appear to form DNA adducts. To investigate PHE mutagenicity in vivo, B6C3F1 Big Blue(R) male transgenic mice harboring the lambda LIZ shuttle vector containing the lad target gene were fed PHE at 2500 ppm for 180 days. A modest increase in the mutant frequency (MF) from 5.02 +/- 2.4 x 10(-5) in the control group to 6.88 +/- 0.754 x 10(-5) in the PHE-treated group, which was marginally different (p < 0.05), was obtained. To better assess the relevance of this increase in MF, a random collection of mutants from each PHE-exposed mouse was sequenced. After correcting for clonal expansion, which is the most conservative approach, the MF in the PHE-treated mice decreased to 6.39 +/- 1.02 x 10(-5), an insignificant difference (p = 0.10) from that in control group. Despite this modest increase in MF, the mutation spectrum obtained from the PHE-exposed group was significantly different (p < 0.02) from the spontaneously derived spectrum in untreated mice. In the PHE-exposed mice, an increase in the mutation frequency of G:C > T:A and G:C > C:G transversions was recorded while the mutation frequency of G:C > A:T transitions remained the same in the two spectra, It is postulated that the increase in transversions at G:C base pairs found in the PHE-derived spectrum is likely due to oxidative damage as a result of induction of CYP2B isozymes by the chronic administration of PHE. Results from this study demonstrate that PHE alters the spectrum of mutations, rather than inducing a significant global increase in the MF. The PHE-derived spectrum of lacI mutants from the liver of Big Blue(R) B6C3F1 male mice was remarkably similar (p = 0.8) to that generated by oxazepam (OX), a compound which also induces CYP2B isozymes following chronic administration of the drug. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Louisiana State Univ, Inst Environm Studies, Baton Rouge, LA 70803 USA. Univ Victoria, Ctr Environm Hlth, Victoria, BC V8W 3N5, Canada. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Shane, BS (reprint author), Louisiana State Univ, Inst Environm Studies, 42 Atkinson Hall, Baton Rouge, LA 70803 USA. FU NCI NIH HHS [CA72534] NR 61 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 14 PY 2000 VL 448 IS 1 BP 69 EP 80 DI 10.1016/S0027-5107(00)00002-6 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 293LQ UT WOS:000085853600008 PM 10751624 ER PT J AU Rivaud-Pechoux, S Vidailhet, M Gallouedec, G Litvan, I Gaymard, B Pierrot-Deseilligny, C AF Rivaud-Pechoux, S Vidailhet, M Gallouedec, G Litvan, I Gaymard, B Pierrot-Deseilligny, C TI Longitudinal ocular motor study in corticobasal degeneration and progressive supranuclear palsy SO NEUROLOGY LA English DT Article DE eye movements; corticobasal degeneration; supranuclear palsy ID PARKINSONIAN SYNDROMES; EYE-MOVEMENTS; DIAGNOSIS; ACCURACY AB Objective: To evaluate the usefulness of ocular motor information in the early diagnosis of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Methods: Seven PSP patients, six CBD patients, and three atypical CBD patients were followed longitudinally with repeated electrooculographic (EOG) recordings, at 6-month intervals, to search for features that could confirm or modify the diagnosis. Visually guided saccades and antisaccades were studied. Data from clinical evaluations were independently collected. Results: PSP patients had decreased saccade velocity throughout the disease course. Patients with probable CBD showed preserved saccade velocity;but important increased saccade latency ipsilateral to the apraxia side. Similar to patients with PSP, those with atypical CBD features exhibited clinically evident abnormalities of vertical saccades and early slowing of horizontal saccade velocity, but no increase in saccade latency or early square-wave jerks. When clinical "telltale signs" appeared and the clinical diagnosis was reviewed independent of EOG recording, the three patients with atypical CBD features were diagnosed as having PSP although new or overlapping syndromes cannot be excluded. Conclusions: Consecutive EOG recordings help diagnose atypical CBD and PSP disorders earlier. C1 Hop La Pitie Salpetriere, INSERM, U289, F-75651 Paris 13, France. Hop La Pitie Salpetriere, Serv Neurol 1, F-75651 Paris, France. Hop St Antoine, Serv Neurol, F-75571 Paris, France. Henry M Jackson Fdn, Cognit Neuropharmacol Unit, Med Neurol Branch, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Rivaud-Pechoux, S (reprint author), Hop La Pitie Salpetriere, INSERM, U289, 47 Bd Hop, F-75651 Paris 13, France. OI Litvan, Irene/0000-0002-3485-3445 NR 8 TC 70 Z9 71 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2000 VL 54 IS 5 BP 1029 EP 1032 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 292GK UT WOS:000085785700006 PM 10720270 ER PT J AU McArthur, JC Yiannoutsos, C Simpson, DM Adornato, BT Singer, EJ Hollander, H Marra, C Rubin, M Cohen, BA Tucker, T Navia, BA Schifitto, G Katzenstein, D Rask, C Zaborski, L Smith, ME Shriver, S Millar, L Clifford, DB AF McArthur, JC Yiannoutsos, C Simpson, DM Adornato, BT Singer, EJ Hollander, H Marra, C Rubin, M Cohen, BA Tucker, T Navia, BA Schifitto, G Katzenstein, D Rask, C Zaborski, L Smith, ME Shriver, S Millar, L Clifford, DB CA AIDS Clinical Trials Grp Team 291 TI A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection SO NEUROLOGY LA English DT Article DE nerve growth factor; HIV-associated sensory neuropathy; pain; analgesic; dideoxynucleoside ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; CUTANEOUS C-FIBERS; PERIPHERAL NEUROPATHY; SKIN BIOPSY; PAIN; REINNERVATION; INNERVATION; THRESHOLDS; DENSITY AB Objective: To evaluate the safety and efficacy of recombinant human nerve growth factor (rhNGF) in HN-associated sensory neuropathy (SN) within a multicenter, placebo-controlled, randomized trial (ACTG 291.). Background: SN affects 30% of individuals with AIDS, is worsened by neurotoxic antiretrovirals, and its treatment is often ineffective. NGF is trophic for small sensory neurons and stimulates the regeneration of damaged nerve fibers. Methods: A total of 270 patients with HIV-associated SN were randomized to receive placebo, 0.1 mu g/kg rhNGF, or 0.3 mu g/kg rhNGF by double-blinded subcutaneous injection twice weekly for 18 weeks. The primary outcome was change in self-reported neuropathic pain intensity (Gracely Pain Scale). Secondary outcomes included an assessment of global improvement in neuropathy by patients and investigators, neurologic examination, use of prescription analgesics, and quantitative sensory testing. In a subset, epidermal nerve fiber densities were determined in punch skin biopsies. Results: Both doses of NGF produced significant improvements in average and maximum daily pain compared with placebo. Positive treatment effects were also observed for global pain assessments (p = 0.001) and for pin sensitivity (p = 0.019). No treatment differences were found with respect to mood, analgesic use, or epidermal nerve fiber densities. Injection site pain was the most frequent adverse event, and resulted in unblinding in 39% of subjects. Severe transient myalgic pain occurred in eight patients, usually from accidental overdosing. There were no changes in HN RNA levels or other laboratory indices. Conclusions: We found a positive effect of recombinant human nerve growth factor on neuropathic pain and pin sensitivity in HIV-associated sensory neuropathy. rhNGF was safe and well tolerated, but injection site pain was frequent. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Neurol, New York, NY USA. Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Cornell Univ, Dept Neurol, New York, NY USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. Genentech Inc, S San Francisco, CA 94080 USA. NIAID, Bethesda, MD 20892 USA. AIDS Clin Trials Grp Operat, Rockville, MD USA. Frontier Sci & Technol Res Fdn, Amherst, NY USA. Washington Univ, Dept Neurol, St Louis, MO USA. RP McArthur, JC (reprint author), 600 N Wolfe St, Baltimore, MD 21287 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCRR NIH HHS [RR00722]; NIAID NIH HHS [AI27668]; NINDS NIH HHS [NS32228] NR 41 TC 173 Z9 181 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2000 VL 54 IS 5 BP 1080 EP 1088 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 292GK UT WOS:000085785700014 PM 10720278 ER PT J AU Lee, JS Ngo, H Kim, D Chung, JH AF Lee, JS Ngo, H Kim, D Chung, JH TI Erythroid Kruppel-like factor is recruited to the CACCC box in the beta-globin promoter but not to the CACCC box in the gamma-globin promoter: The role of the neighboring promoter elements SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SICKLE-CELL ANEMIA; GENE-EXPRESSION; FACTOR EKLF; IN-VIVO; TRANSCRIPTION FACTOR; LOCUS; SP1; IDENTIFICATION; COMPETITION; THALASSEMIA AB The programmed expression of the five beta-like globin genes (epsilon, (A)gamma, (G)gamma, delta, and beta) is characterized by a series of switches that are developmentally regulated. The (A)gamma- and (G)gamma- (fetus) to beta-globin (adult) switch depends on transcription factor erythroid Kruppel-like factor (EKLF), which, like Sp1, binds to CACCC boxes. EKLF is essential for the expression of the beta-globin but not the gamma-globin gene. Because both gamma-globin and beta-globin promoters contain the CACCC box, and their promoter elements are similar, it is not known why the two promoters behave so differently. In this report, we searched for the functional differences between the two promoters by studying their ability to recruit EKLF, We used the in vivo PIN*POINT assay to show that EKLF is recruited to the beta-globin promoter but not to the gamma-globin promoter. We show that this selectivity is a result of differences in surrounding promoter elements and not CACCC box alone. One of the differences between the two promoters with a functional consequence is the CCTTG repeat that is present in the gamma-globin promoter but not in the beta-globin promoter. The repeat, when inserted in the beta-globin promoter, decreases EKLF recruitment to and activity of the beta-globin promoter, suggesting that the repeat functions as a suppressor element. The CCTTG repeat can also suppress the SV40 promoter in cis, and the suppressor factor binding to the repeat can be squelched with a plasmid containing a high copy number of the repeat. These findings may have implications in designing drug targets for treatment of beta-globin disorders. C1 NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. RP Chung, JH (reprint author), NHLBI, Lab Mol Hematol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 32 TC 22 Z9 23 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2468 EP 2473 DI 10.1073/pnas.040476297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400014 PM 10706605 ER PT J AU Sauna, ZE Ambudkar, SV AF Sauna, ZE Ambudkar, SV TI Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIDRUG-RESISTANCE; TRANSITION-STATE; BINDING-PROTEIN; LABELING SITES; NUCLEOTIDE; TRANSPORT; CELLS; RECONSTITUTION; STOICHIOMETRY; PURIFICATION AB P-glycoprotein (Pgp) is an ATP-dependent hydrophobic natural product anticancer drug efflux pump whose overexpression confers multidrug resistance to tumor cells. The work reported here deals with the elucidation of the energy requirement for substrate interaction with Pgp during the catalytic cycle. We show that the K-d (412 nM) of the substrate analogue [I-125]iodoarylazidoprazoin for Pgp is not altered by the presence of the nonhydrolyzable nucleotide 5'-adenylylimididiphosphate and vanadate (K-d = 403 nM), Though binding of nucleotide per se does not affect interactions with the substrate, ATP hydrolysis results in a dramatic conformational change where the affinity of [I-125]iodoarylazidoprazoin for Pgp trapped in transition-state conformation (Pgp . ADP . vanadate) is reduced >30-fold. To transform Pgp from this intermediate state of low affinity for substrate to the next catalytic cycle, i.e., a conformation that binds substrate with high affinity, requires conditions that permit ATP hydrolysis. Additionally, there is an inverse correlation (R-2 = 0.96) between 8AzidoADP (or ADP) release and the recovery of substrate binding. These results suggest that the release of nucleotide is necessary for reactivation but not sufficient. The hydrolysis of additional molecule(s) of ATP (or 8AzidoATP) is obligatory for the catalytic cycle to advance to completion. These data are consistent with the observed stoichiometry of two ATP molecules hydrolyzed for the transport of every substrate molecule. Our data demonstrate two distinct roles for ATP hydrolysis in a single turnover of the catalytic cycle of Pgp, one in the transport of substrate and the other in effecting conformational changes to reset the pump for the next catalytic cycle. C1 NCI, Cell Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 1B-22,37 Convent Dr, Bethesda, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 40 TC 175 Z9 176 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2515 EP 2520 DI 10.1073/pnas.97.6.2515 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400022 PM 10716986 ER PT J AU Lee, SR Bar-Noy, S Kwon, J Levine, RL Stadtman, TC Rhee, SG AF Lee, SR Bar-Noy, S Kwon, J Levine, RL Stadtman, TC Rhee, SG TI Mammalian thioredoxin reductase: Oxidation of the C-terminal cysteine/selenocysteine active site forms a thioselenide, and replacement of selenium with sulfur markedly reduces catalytic activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; PURIFICATION; MECHANISM; CELLS AB Mammalian cytosolic thioredoxin reductase (TrxR) has a redox center, consisting of Cys(59)/Cys(64) adjacent to the flavin ring of FAD and another center consisting of Cys(497)/selenocysteine (SeCys)(498) near the C terminus. We now show that the C-terminal Cys(497)-SH/SeCys(498)-. Se- of NADPH-reduced enzyme, after anaerobic dialysis, was converted to a thioselenide on incubation with excess oxidized Trx (TrxS(2)) or H2O2. The Cys(59)-SH/Cys(64)-SH pair also was oxidized to a disulfide. At lower concentrations of TrxS(2), the Cys(59)-SH/Cys(64)-SH center was still converted to a disulfide, presumably by reduction of the thioselenide to Cys(497)-SH/SeCys(498)-Se-. Specific alkylation of SeCys(498) completely blocked the TrxS(2)-induced oxidation of Cys(59)-SH/Cys(64)-SH, and the alkylated enzyme had negligible NADPH-disulfide oxidoreductase activity. The effect of replacing SeCys(498) with Cys was determined by using a mutant form of human placental TrxR1 expressed in Escherichia coli, The NADPH-disulfide oxidoreductase activity of the purified Cys(497)/Cys(498) mutant enzyme was 6% or 11% of that of wild-type rat liver TrxR1 with 5,5'-dithiobis(2-nitrobenzoic add) or TrxS(2) respectively, as substrate. Disulfide formation induced by excess TrxS(2) in the mutant form was 12% of that of the wild type. Thus, SeCys has a critical redox function during the catalytic cycle, which is performed poorly by Cys. C1 NHLBI, Labs Cell Signaling, NIH, Bethesda, MD 20892 USA. NHLBI, Labs Biochem, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Labs Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 20 TC 191 Z9 198 U1 1 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2521 EP 2526 DI 10.1073/pnas.050579797 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400023 PM 10688911 ER PT J AU Yamaji, R Adamik, R Takeda, K Togawa, A Pacheco-Rodriguez, G Ferrans, VJ Moss, J Vaughan, M AF Yamaji, R Adamik, R Takeda, K Togawa, A Pacheco-Rodriguez, G Ferrans, VJ Moss, J Vaughan, M TI Identification and localization of two brefeldin A-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors in a macromolecular complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GTP-BINDING PROTEIN; GOLGI MEMBRANES; HOMOLOGY DOMAINS; SEC7 DOMAIN; ARF; YEAST; PLECKSTRIN; EXPRESSION; CONTAINS; COATOMER AB Two brefeldin A (BFA)-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors, 200-kDa BIG1 and 190-kDa BIG2, were copurified from bovine brain cytosol associated with >670-kDa macromolecular complexes. When observed by immunofluorescence in Hela S3 and HepG2 cells, endogenous BIG1 and coexpressed BIG2 were distributed in a punctate pattern throughout the cytosol, and also concentrated in the perinuclear region, where endogenous BIG1 and BIG2 each partially colocalized with Golgi-specific 58K protein and gamma-adaptin. On Western blot analysis, both BIG1 and BIG2 were clearly more abundant in the cytosol than in the microsomal fractions. After density gradient centrifugation of a microsomal fraction, BIG1 and BIG2 were recovered in the same fraction as beta-CDP, a marker for Golgi membranes. When cytosol from HeLa S3 cells was subjected to gel filtration and fractions were analyzed by Western blotting, the largest percentages of both BIG1 and BIG2 were detected in fractions containing proteins with a molecular mass of >670 kDa, Western blotting using anti-peptide antibodies specific for BIG1 or BIG2 demonstrated that approximate to 70% of BIG2 was immunoprecipitated along with 100% of BIG1 by the anti-BIG1 IgG, and approximate to 75% of BIG1 was coprecipitated with 100% of BIG2 by the anti-BIG2 IgG, All observations were consistent with the conclusion that significant fractions of BIG1 and BIG2 exist as components of the same macromolecular complexes in bovine brain cytosol and are similarly localized in cultured cells. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Yamaji, R (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 5N-307,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. RI Yamaji, Ryoichi/E-5850-2011 NR 31 TC 84 Z9 89 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2567 EP 2572 DI 10.1073/pnas.97.6.2567 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400031 PM 10716990 ER PT J AU Oh, SP Seki, T Goss, KA Imamura, T Yi, Y Donahoe, PK Li, L Miyazono, K ten Dijke, P Kim, S Li, E AF Oh, SP Seki, T Goss, KA Imamura, T Yi, Y Donahoe, PK Li, L Miyazono, K ten Dijke, P Kim, S Li, E TI Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; TGF-BETA; ENDOTHELIAL-CELLS; I RECEPTOR; PLASMINOGEN-ACTIVATOR; EXPRESSION; UROKINASE; GENE; VASCULOGENESIS; COMPLEX AB The activin receptor-like kinase 1 (ALK1) is a type I receptor for transforming growth factor-beta (TGF-beta) family proteins. Expression of ALK1 in blood vessels and mutations of the ALK1 gene in human type II hereditary hemorrhagic telangiectasia patients suggest that ALK1 may have an important role during vascular development, To define the function of ALK1 during development, we inactivated the ALK1 gene in mice by gene targeting. The ALK1 homozygous embryos die at midgestation, exhibiting severe vascular abnormalities characterized by excessive fusion of capillary plexes into cavernous vessels and hyperdilation of large vessels. These vascular defects are associated with enhanced expression of angiogenic factors and proteases and are characterized by deficient differentiation and recruitment of vascular smooth muscle cells. The blood vessel defects in ALK1-deficient mice are reminiscent of mice lacking TGF-beta 1, TGF-beta type II receptor (T beta R-II), or endoglin, suggesting that ALK1 may mediate TGF-beta 1 signal in endothelial cells. Consistent with this hypothesis, we demonstrate that ALK1 in endothelial cells binds to TGF-beta 1 and T beta R-II. Furthermore, the ALK1 signaling pathway can inhibit TGF-beta 1-dependent transcriptional activation mediated by the known TGF-beta 1 type I receptor, ALK5. Taken together, our results suggest that the balance between the ALK1 and ALK5 signaling pathways in endothelial cells plays a crucial role in determining vascular endothelial properties during angiogenesis. C1 Univ Florida, Dept Physiol, Gainesville, FL 32610 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Wayne State Univ, Dept Internal Med, Detroit, MI 48202 USA. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 1708455, Japan. RP Oh, SP (reprint author), Univ Florida, Dept Physiol, POB 100274, Gainesville, FL 32610 USA. FU NICHD NIH HHS [HD32112, R01 HD032112] NR 39 TC 540 Z9 562 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2626 EP 2631 DI 10.1073/pnas.97.6.2626 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400041 PM 10716993 ER PT J AU Migueles, SA Sabbaghian, MS Shupert, WL Bettinotti, MP Marincola, FM Martino, L Hallahan, CW Selig, SM Schwartz, D Sullivan, J Connors, M AF Migueles, SA Sabbaghian, MS Shupert, WL Bettinotti, MP Marincola, FM Martino, L Hallahan, CW Selig, SM Schwartz, D Sullivan, J Connors, M TI HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEUTRALIZING ANTIBODY-RESPONSES; TYPE-1 INFECTION; ANKYLOSING-SPONDYLITIS; CLINICAL COURSE; NEF SEQUENCES; T-CELL; PROGRESSION; INDIVIDUALS; SURVIVORS; ABSENCE AB A unique cohort of HIV-1-infected long term non progressors (LTNP) with normal CD4(+) T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0.001], Antigen-specific CD8(+) T cells were enumerated by flow cytometric detection of intracellular IFN-gamma in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8+ T cell responses were observed between B*57(+) LTNP and five B*57(+) progressors (P = 0.4). Although similar frequencies of peptide specific CD8(+) T cells were also found, the gag-specific CD8(+) T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease, They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57(+) LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication. C1 NCI, Immunoregulat Lab, NIAID, NIH, Bethesda, MD 20892 USA. NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Australian Red Cross Blood Serv NSW, Sydney, NSW 2000, Australia. RP Connors, M (reprint author), NCI, Immunoregulat Lab, NIAID, NIH, Bldg 10,Room 11B-09,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA. NR 42 TC 640 Z9 654 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2709 EP 2714 DI 10.1073/pnas.050567397 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400056 PM 10694578 ER PT J AU Sen, M Lauterbach, K El-Gabalawy, H Firestein, GS Corr, M Carson, DA AF Sen, M Lauterbach, K El-Gabalawy, H Firestein, GS Corr, M Carson, DA TI Expression and function of wingless and frizzled homologs in rheumatoid arthritis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 1999 Meeting of the American-College-of-Rheumatology CY 1999 CL BOSTON, MASSACHUSETTS SP Amer Coll Rheumatol DE synovium; fibroblast; cytokine; wnt ID WNT GENE FAMILY; NF-KAPPA-B; SYNOVIAL-FLUID; GROWTH-FACTOR; CELLS; PROTEINS; TRANSFORMATION; HEMATOPOIESIS; INDUCTION; CATENIN AB Rheumatoid arthritis (RA) is accompanied by synovial inflammation, proliferation, and cartilage destruction. The reasons the activation of synovial fibroblasts often persists despite antiinflammatory therapy are not known. One possibility is that the synovial membrane becomes gradually repopulated with immature mesenchymal and bone marrow cells with altered properties. To explore this hypothesis, we have investigated the expression in RA synovial tissues of various embryonic growth factors from the wingless (wnt) and frizzled (fi) families, which have been implicated in cell-fate determination in both bone marrow progenitors and limb-bud mesenchyme, Reverse transcriptase-PCR analysis revealed expression of five wnt(wnt1, 5a, 10b, 11, and 13) and three fi (fz2, 5, and 7) isoforms in RA synovial tissues. Osteoarthritis synovial tissues expressed much less wnt5a and fz5, Northern blotting confirmed the overexpression of wnt5a and fz5 in RA synovial tissues, in comparison to a panel of normal adult tissues. Compared with normal synovial fibroblasts, cultured RA fibroblastlike synoviocytes expressed higher levels of IL-6, IL-8, and IL-15. Transfection of normal fibroblasts with a wnt5a expression vector reproduced this pattern of cytokine expression and stimulated IL-15 secretion. These results suggest that the unusual phenotypic properties of RA fibroblasts may be attributable partly to their replacement with primitive fibroblast-like synoviocytes with characteristics of immature bone marrow and mesenchymal cells. Clear delineation of the signaling pathway(s) initiated by the wnt5a/fz5 ligand-receptor pair in the RA synovium may yield new targets for therapeutic intervention. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, La Jolla, CA 92093 USA. NIAMSD, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. RP Sen, M (reprint author), Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. FU NIAMS NIH HHS [AR44850, T32 AR007567, AR07567, AR40770] NR 36 TC 189 Z9 203 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2791 EP 2796 DI 10.1073/pnas.050574297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400070 PM 10688908 ER PT J AU Tesauro, M Thompson, WC Rogliani, P Qi, L Chaudhary, PP Moss, J AF Tesauro, M Thompson, WC Rogliani, P Qi, L Chaudhary, PP Moss, J TI Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: Cleavage of proteins with aspartate vs. glutamate at position 298 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MISSENSE GLU298ASP VARIANT; MYOCARDIAL-INFARCTION; GENE; POLYMORPHISM AB An endothelial nitric oxide synthase (eNOS) polymorphism in exon 7 (894 G/T) resulting in glutamate or aspartate, respectively, at position 298 on the protein is correlated with severity of cardiopulmonary diseases. Because glutamate and aspartate are considered to be conservative replacements, the polymorphism was thought to be a marker for a functional locus elsewhere in the gene, We now show in transfected cells, primary human endothelial cells, and human hearts, that eNOS with aspartate, but not glutamate, at position 298 is cleaved, resulting in the generation of 100-kDa and 35-kDa products, Recombinant or native eNOS was examined by immunoblotting either in lysates (COS7) or after partial purification over 2',5'-ADP-Sepharose and calmodulin-Sepharose, Immunoblotting after SDS/PAGE with a carboxyl-terminal antibody showed a single major protein band in the predicted position for eNOS at 135 kDa. An additional band at approximately 100 kDa was present only in the recombinant 298Asp eNOS and in the eNOS synthesized by primary cells and heart tissue with a G/T genotype, Using an eNOS amino-terminal-specific antibody, an immunoreactive band at approximately 35 kDa, corresponding to the residual N-terminal cleavage fragment, was observed in those cells with a T genotype, Thus, eNOS with aspartate but not glutamate at position 298 is cleaved, resulting in the generation of N-terminal 35-kDa and C-terminal 100-kDa fragments. Thus, the eNOS gene with polymorphisms at nucleotide 894 generates protein products with differing susceptibility to cleavage, suggesting that, in contrast to prior predictions, this polymorphism has a functional effect on the eNOS protein. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Tesauro, M (reprint author), NIH, Room 6DDS,Bldg 10,10 Ctr Dr,MSC 1434, Bethesda, MD 20892 USA. OI Rogliani, Paola/0000-0001-7801-5040 NR 14 TC 381 Z9 402 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 MAR 14 PY 2000 VL 97 IS 6 BP 2832 EP 2835 DI 10.1073/pnas.97.6.2832 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400077 PM 10717002 ER PT J AU Wong, PC Waggoner, D Subramaniam, JR Tessarollo, L Bartnikas, TB Culotta, VC Price, DL Rothstein, J Gitlin, JD AF Wong, PC Waggoner, D Subramaniam, JR Tessarollo, L Bartnikas, TB Culotta, VC Price, DL Rothstein, J Gitlin, JD TI Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURONS; MICE; GENE; ALS; PROPERTY; MUTATION; DISEASE; SUPEROXIDE-DISMUTASE-1; DEGENERATION AB Recent studies in Saccharomyces cerevisiae suggest that the delivery of copper to Cu/Zn superoxide dismutase (SOD1) is mediated by a cytosolic protein termed the copper chaperone for superoxide dismutase (CCS). To determine the role of CCS in mammalian copper homeostasis, we generated mice with targeted disruption of CCS alleles (CCS-/- mice). Although CCS-/- mice are viable and possess normal levels of SOD1 protein, they reveal marked reductions in SOD1 activity when compared with control littermates, Metabolic labeling with (CU)-C-64 demonstrated that the reduction of SOD1 activity in CCS-/- mice is the direct result of impaired Cu incorporation into SOD1 and that this effect was specific because no abnormalities were observed in Cu uptake, distribution, or incorporation into other cuproenzymes. Consistent with this loss of SOD1 activity, CCS-/- mice showed increased sensitivity to paraquat and reduced female fertility, phenotypes that are characteristic of SOD1-deficient mice. These results demonstrate the essential role of any mammalian copper chaperone and have important implications for the development of novel therapeutic strategies in familial amyotrophic lateral sclerosis. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Wong, PC (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 558 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI rothstein, jeffrey/C-9470-2013 FU NIDDK NIH HHS [DK44464, R01 DK044464, R37 DK044464]; NIGMS NIH HHS [R01 GM050016, R37 GM050016]; NINDS NIH HHS [NS37145, NS37771] NR 31 TC 183 Z9 185 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2886 EP 2891 DI 10.1073/pnas.040461197 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400087 PM 10694572 ER PT J AU Giannakakou, P Gussio, R Nogales, E Downing, KH Zaharevitz, D Bollbuck, B Poy, G Sackett, D Nicolaou, KC Fojo, T AF Giannakakou, P Gussio, R Nogales, E Downing, KH Zaharevitz, D Bollbuck, B Poy, G Sackett, D Nicolaou, KC Fojo, T TI A common pharmacophore for epothilone and taxanes: Molecular basis for drug resistance conferred by tubulin mutations in human cancer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MICROTUBULE-STABILIZING AGENTS; BETA-TUBULIN; PACLITAXEL TAXOL(R); SOLUTION-PHASE; AMINO-ACIDS; DISCODERMOLIDE; PHOTOLABELS; CHEMISTRY; BINDING AB The epothilones are naturally occurring antimitotic drugs that share with the taxanes a similar mechanism of action without apparent structural similarity. Although photoaffinity labeling and electron crystallographic studies have identified the taxane-binding site on beta-tubulin, similar data are not available for epothilones. To identify tubulin residues important for epothilone binding, we have isolated two epothilone-resistant human ovarian carcinoma sublines derived in a single-step selection with epothilone A or B, These epothilone-resistant sublines exhibit impaired epothilone- and taxane-driven tubulin polymerization caused by acquired beta-tubulin mutations (beta 274(Thr-->lle) and beta 282(Arg-->Gln)) located in the atomic model of alpha beta-tubulin near the taxane-binding site. Using molecular modeling, we investigated the conformational behavior of epothilone, which led to the identification of a common pharmacophore shared by taxanes and epothilones. Although two binding modes for the epothilones were predicted, one mode was identified as the preferred epothilone conformation as indicated by the activity of a potent pyridine-epothilone analogue. In addition, the structure-activity relationships of multiple taxanes and epothilones in the tubulin mutant cells can be fully explained by the model presented here, verifying its predictive value. Finally, these pharmacophore and activity data from mutant cells were used to model the tubulin binding of sarcodictyins, a distinct class of microtubule stabilizers, which in contrast to taxanes and the epothilones interact preferentially with the mutant tubulins, The unification of taxane, epothilone, and sarcodictyin chemistries in a single pharmacophore provides a framework to study drug-tubulin interactions that should assist in the rational design of agents targeting tubulin. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NCI, Target Struct Based Drug Discovery, Informat Technol Branch, NIH, Frederick, MD 21702 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, NIH, Frederick, MD 21702 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RP Giannakakou, P (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 370 Z9 384 U1 0 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2000 VL 97 IS 6 BP 2904 EP 2909 DI 10.1073/pnas.040546297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 294ZR UT WOS:000085941400090 PM 10688884 ER PT J AU Kornyshev, AA Leikin, S AF Kornyshev, AA Leikin, S TI Twist in chiral interaction between biological helices SO PHYSICAL REVIEW LETTERS LA English DT Article ID LIQUID-CRYSTALLINE PHASES; X-RAY-DIFFRACTION; ELECTROSTATIC INTERACTION; DNA; INVITRO; INVIVO; PITCH AB Using an exact solution for the pair interaction potential, we show that long, rigid, chiral molecules with helical surface charge patterns have a preferential interaxial angle similar to root RH/L, where L is the length of the molecules, R is the closest distance between their axes, and H is the helical pitch. Estimates based on this formula suggest a solution for the puzzle of small interaxial angles in alpha-helix bundles and in cholesteric phases of DNA. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Res Ctr, D-52425 Julich, Germany. Univ Calif Santa Barbara, Inst Theoret Phys, Santa Barbara, CA 93106 USA. RP Leikin, S (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 12A,Rm 2041, Bethesda, MD 20892 USA. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 23 TC 34 Z9 35 U1 0 U2 2 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAR 13 PY 2000 VL 84 IS 11 BP 2537 EP 2540 DI 10.1103/PhysRevLett.84.2537 PG 4 WC Physics, Multidisciplinary SC Physics GA 292JZ UT WOS:000085791900064 PM 11018929 ER PT J AU Taha, TE Kumwenda, NI Hoover, DR Biggar, RJ Broadhead, RL Cassol, S van der Hoven, L Markakis, D Liomba, GN Chiphangwi, JD Miotti, PG AF Taha, TE Kumwenda, NI Hoover, DR Biggar, RJ Broadhead, RL Cassol, S van der Hoven, L Markakis, D Liomba, GN Chiphangwi, JD Miotti, PG TI Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age SO AIDS LA English DT Article DE CD4 lymphocyte; children; HIV; mortality; perinatal HIV infection; viral load ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISEASE PROGRESSION; INFECTED INFANTS; FILTER-PAPER; RNA; TRANSMISSION; BLOOD AB Objective: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. Design: A prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). Methods: Morbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan-Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. Results: Of 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log(10) viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log(10) increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (greater than or equal to 250 000 copies/ml median value) had the worst survival; children with high CD4 cell counts (greater than or equal to 15%) and low viral loads (< 250 000 copies/ml) had the best survival. Conclusion: As in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries. (C) 2000 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Program Infect Dis, Baltimore, MD 21205 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Malawi, Coll Med, Blantyre, Malawi. Ottawa Gen Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada. RP Taha, TE (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Program Infect Dis, Room E6011,615 N Wolfe St, Baltimore, MD 21205 USA. FU NIAID NIH HHS [N01-AI-35173-117] NR 19 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 10 PY 2000 VL 14 IS 4 BP 453 EP 459 DI 10.1097/00002030-200003100-00021 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 298TT UT WOS:000086155800021 PM 10770550 ER PT J AU Baumann, MH Elmer, GI Goldberg, SR Ambrosio, E AF Baumann, MH Elmer, GI Goldberg, SR Ambrosio, E TI Differential neuroendocrine responsiveness to morphine in Lewis, Fischer 344, and ACI inbred rats SO BRAIN RESEARCH LA English DT Article DE corticosterone; prolactin; morphine; Lewis; Fischer 344; stress ID CORTICOTROPIN-RELEASING HORMONE; MESOLIMBIC DOPAMINE SYSTEM; BRAIN REWARD REGIONS; INDIVIDUAL VULNERABILITY; LOCOMOTOR-ACTIVITY; STRESS INCREASES; OPIOID-PEPTIDES; STRAINS; COCAINE; CORTICOSTERONE AB Preclinical evidence suggests there is a link between the responsiveness to stress and the propensity to self-administer drugs of abuse. Our previous findings, for example, have shown a significant positive correlation between the locomotor response to novelty and the acquisition of morphine self-administration in Lewis (LEW), Fischer 344 (F344) and ACI inbred rat strains. As an extension of this work, we now report on the neuroendocrine responses (i.e., corticosterone and prolactin secretion) evoked by morphine administration in these same inbred strains. Male LEW, F344, and ACI rats were surgically prepared with indwelling jugular catheters 7 days prior to the study, Following a habituation period, rats were treated with i.p. saline or morphine (1, 5 or 10 mg/kg), Repeated blood samples were withdrawn via the catheters immediately before and at 20, 40, 60 and 120 min after injection. Plasma samples were assayed for hormone levels by radioimmunoassay. No differences in baseline corticosterone levels were found across strains. There was a significant effect of genotype on the corticosterone response to saline injection (i.e., mild stress), with F344 rats exhibiting sustained elevations in corticosterone compared to LEW and ACI rats; Morphine-induced stimulation of corticosterone release differed significantly across strains, and in this case LEW rats displayed a reduced sensitivity to morphine. Similar to the corticosterone results, LEW rats also had blunted prolactin responses to morphine when compared to F344 rats. Our data demonstrate that genotype is an important factor modulating the neuroendocrine sensitivity to morphine. It is noteworthy that LEW rats acquire self-administration more rapidly than F344 or ACI rats, yet LEW rats display reduced corticosterone responses to stress and morphine. Taking into account the particular conditions of this study (high i.p. doses used here vs. low i.v. doses in self-administration studies), our results do not suggest that corticosterone response to stress and morphine is related to vulnerability to intravenous opiate self-administration. The data, however, are consistent with the idea of that genetic factors might influence the sensitivity to the morphine-induced effects of glucocorticoids across these inbred strains. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Nacl Educ Distancia, Dept Psicobiol, Fac Psicol, E-28040 Madrid, Spain. NIDA, Clin Pharmacol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Preclin Pharmacol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Catonsville, MD 21228 USA. RP Ambrosio, E (reprint author), Univ Nacl Educ Distancia, Dept Psicobiol, Fac Psicol, Ciudad Univ, E-28040 Madrid, Spain. NR 46 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 10 PY 2000 VL 858 IS 2 BP 320 EP 326 DI 10.1016/S0006-8993(99)02479-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 292VB UT WOS:000085814800010 PM 10708683 ER PT J AU Lelievre, V Caigneaux, E Muller, JM Falcon, J AF Lelievre, V Caigneaux, E Muller, JM Falcon, J TI Extracellular adenosine deprivation induces epithelial differentiation of HT29 cells: evidence for a concomitant adenosine A(1)/A(2) receptor balance regulation SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE adenosine receptor; colon adenocarcinoma; HT29 cell; adenosine deaminase; epithelial differentiation ID HUMAN COLONIC ADENOCARCINOMA; SODIUM-BUTYRATE; CARCINOMA-CELLS; PROLIFERATION; CANCER; A(1); MODULATION; SUBTYPES; ANALOGS; GROWTH AB HT29 cells display an undifferentiated phenotype in culture. However. numerous treatments are able to induce both epithelial differentiation and cell growth inhibition. We have previously demonstrated that adenosine and its analogues act through specific adenosine receptors to modulate cell proliferation in HT29 and other human colon adenocarcinoma cell lines. Among the treatments tested, the most potent inhibition of HT29 cell growth was induced by deprivation of extracellular adenosine using adenosine deaminase. Here, we investigated the capacity of adenosine deaminase to initiate epithelial differentiation. After 1 month of daily addition of 10 U/ml adenosine deaminase to the culture medium, HT29 cells were cloned by limited dilution. Among the clones obtained, we focused our attention on clone 13. Microscopic visualization and proliferation studies indicated that cells from this clone grew very slowly and in a pseudo-monolayer, in marked contrast with the situation observed in the mother HT29 cell line. In addition, clone 13 cells displayed epithelial features that mimic the enterocytic differentiation of Caco-2 cells. These modifications were accompanied by dramatic changes in the activity of adenosine receptors, as demonstrated by pharmacological studies. In contrast to the original HT29 cells, clone 13 as well as Caco-2 cells displayed (i) a very low number of adenosine A, receptors, and (ii) increases in intracellular cAMP levels when challenged with adenosine analogues, it is hypothesized that a loss of adenosine A, receptors, with no change or a concomitant increase in adenosine A(2) receptors, results in the emergence of adenosine Az receptor-mediated differentiation and inhibition of proliferation, through a cAMP-dependent pathway. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Poitiers, Fac Sci, UMR 6558, Labs Biol Interact Cellulaires, F-86022 Poitiers, France. Univ Poitiers, Fac Sci, UMR 6558, Labs Neuroendocrinol Cellulaire, F-86022 Poitiers, France. RP Falcon, J (reprint author), NICHHD, Neuroendocrinol Sect, Dev Neurobiol Lab, NIH, 49-5A38,49 Convent Dr, Bethesda, MD 20892 USA. RI FALCON, Jack/I-5302-2013 OI FALCON, Jack/0000-0002-7572-6581 NR 27 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 10 PY 2000 VL 391 IS 1-2 BP 21 EP 29 DI 10.1016/S0014-2999(00)00048-0 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296DG UT WOS:000086007300003 PM 10720631 ER PT J AU DePetrillo, PB Bennett, AJ Speers, D Suomi, SJ Shoaf, SE Karimullah, K Higley, JD AF DePetrillo, PB Bennett, AJ Speers, D Suomi, SJ Shoaf, SE Karimullah, K Higley, JD TI Ondansetron modulates pharmacodynamic effects of ketamine on electrocardiographic signals in rhesus monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ketamine; ondansetron; 5-HT (5-hydroxytryptamine, serotonin); heart rate; electrocardiography; fractal ID BEZOLD-JARISCH REFLEX; HEART-RATE-VARIABILITY; CEREBROSPINAL-FLUID; 5-HT3 RECEPTOR; 5-HYDROXYINDOLEACETIC ACID; RATE DYNAMICS; NTS; AGE AB Electrocardiographic signal dynamics were examined in rhesus monkeys (Macaca mulatta) before and after treatment with ketamine and/or ondansetron. Ketamine exerts differential pharmacodynamic effects on behavior in animals stratified according to a measure of central serotonergic turnover. We hypothesized that measures of serotonergic turnover might explain some of the variance in the electrocardiographic (ECG) response to ketamine. Electrocardiographic recordings of animals were obtained at baseline, after administration of either saline or ondansetron (0.125 mg/kg), and after administration of ketamine (15 mg/kg). Electrocardiographic signal dynamics were measured using an algorithm that extracts the Hurst parameter(H) of the interbeat interval (IBI) time-series. H decreased after ketamine administration, (mean +/- S.E.M,), 0.33 +/- 0.03 vs. 0.12 +/- 0.02, P less than or equal to 0.001, n = 10. Cerebrospinal fluid 5-hydroxyindole-3-acetic acid (5-HIAA) concentrations, a measure of serotonergic turnover, predicted the monkeys' response to ketamine, H = 0.001 (5-HIAA, pmol/ml)-0.130, R = 0.66, P less than or equal to 0.003, n = 18. Ondansetron attenuated the response to ketamine, 0.14 +/- 0.02 vs. 0.08 +/- 0.02, P less than or equal to 0.05, n = 8, ondansetron vs, saline. These data provide evidence that naturally occurring differences in serotonin function alter the ECG response of the animals to ketamine and that activation of the serotonin type-3 receptor by ketamine is involved. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIAAA, Clin Studies Lab, Unit Clin & Biochem Pharmacol, Div Intramural Clin & Biochem Res,NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Primate Unit, Div Intramural Clin & Biochem Res,NIH, Poolesville, MD USA. Thomson Labs, Intelligent Syst, Rockville, MD 20850 USA. NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NIAAA, Clin Studies Lab, Unit Pharmacokinet Studies, Div Intramural Clin & Biochem Res,NIH, Bethesda, MD 20892 USA. RP DePetrillo, PB (reprint author), NIAAA, Clin Studies Lab, Unit Clin & Biochem Pharmacol, Div Intramural Clin & Biochem Res,NIH, 10-3C103,10 Ctr Dr,MSC 1256, Bethesda, MD 20892 USA. NR 31 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 10 PY 2000 VL 391 IS 1-2 BP 113 EP 119 DI 10.1016/S0014-2999(00)00056-X PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296DG UT WOS:000086007300014 PM 10720642 ER PT J AU Saiardi, A Caffrey, JJ Snyder, SH Shears, SB AF Saiardi, A Caffrey, JJ Snyder, SH Shears, SB TI Inositol polyphosphate multikinase (ArgRIII) determines nuclear mRNA export in Saccharomyces cerevisiae (vol 468, pg 28, 2000) SO FEBS LETTERS LA English DT Correction C1 NIEHS, Lab Signal Transduct, Inositide Signaling Sect, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Shears, SB (reprint author), NIEHS, Lab Signal Transduct, Inositide Signaling Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 10 PY 2000 VL 469 IS 2-3 BP 213 EP 213 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 294VA UT WOS:000085930000016 ER PT J AU Santala, A Saarinen, J Kovanen, P Kuusela, P AF Santala, A Saarinen, J Kovanen, P Kuusela, P TI Activation of interstitial collagenase, MMP-1, by Staphylococcus aureus cells having surface-bound plasmin: a novel role of plasminogen receptors of bacteria (vol 461, pg 153, 1999) SO FEBS LETTERS LA English DT Correction C1 NIEHS, Lab Signal Transduct, Inositide Signaling Sect, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Santala, A (reprint author), NIEHS, Lab Signal Transduct, Inositide Signaling Sect, POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 10 PY 2000 VL 469 IS 2-3 BP 213 EP 213 DI 10.1016/S0014-5793(00)01261-8 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 294VA UT WOS:000085930000017 ER PT J AU Du, Y Tsai, S Keller, JR Williams, SC AF Du, Y Tsai, S Keller, JR Williams, SC TI Identification of an interleukin-3-regulated aldoketo reductase gene in myeloid cells which may function in autocrine regulation of myelopoiesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTOR; COLONY-STIMULATING FACTOR; REPRESENTATIONAL DIFFERENCE ANALYSIS; MESSENGER-RNA EXPRESSION; TRANSCRIPTION FACTOR; RAT-LIVER; C/EBP-EPSILON; GRANULOCYTIC DIFFERENTIATION; NEUTROPHIL DIFFERENTIATION; ALDEHYDE REDUCTASE AB The EML hematopoietic progenitor cell line is a model system for studying molecular events regulating myeloid commitment and terminal differentiation. We used representational difference analysis to identify genes that are expressed differentially during myeloid differentiation of EML cells. One gene (named mAKRa) encoded a novel member of the aldoketo reductase (AKR) superfamily of cytosolic NAD(P)(H)-dependent oxidoreductases. mAKRa mRNA was detected in murine hematopoietic tissues including bone marrow, spleen, and thymus. In myeloid cell lines, mAKRa was expressed at highest levels in cells representative of promyelocytes. mAKRa mRNA levels increased rapidly in response to interleukin-3 over the first 24 h of EML cell differentiation when the cells undergo lineage commitment and extensive proliferation, mAKRa mRNA levels decreased later in the differentiation process particularly when the EML cells were cultured with granulocyte/macrophage colony-stimulating factor and retinoic acid to induce terminal granulocytic maturation. mAKRa mRNA levels decreased during retinoic acid-induced terminal granulocytic differentiation of the MPRO promyelocyte cell line. AKRs act as molecular switches by catalyzing the interconversion or inactivation of bioactive molecules including steroids and prostaglandins. We propose that mAKRa may catalyze the production or catabolism of autocrine factors that promote the proliferation and/or lineage commitment of early myeloid progenitors. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. Texas Tech Univ, Hlth Sci Ctr, Univ Med Ctr, SW Canc Ctr, Lubbock, TX 79430 USA. Mt Sinai Sch Med, New York, NY 10029 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Williams, SC (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, 3601 4th St, Lubbock, TX 79430 USA. NR 57 TC 13 Z9 13 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 MAR 10 PY 2000 VL 275 IS 10 BP 6724 EP 6732 DI 10.1074/jbc.275.10.6724 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600007 PM 10702227 ER EF