FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ruffini, PA Biragyn, A Kwak, LW AF Ruffini, PA Biragyn, A Kwak, LW TI Recent advances in multiple myeloma immunotherapy SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE idiotype; multiple myeloma; tumor-specific immunotherapy ID CYTOTOXIC T-LYMPHOCYTES; STEM-CELL TRANSPLANTATION; DENDRITIC CELLS; IDIOTYPE VACCINATION; ANTITUMOR IMMUNITY; TUMOR; DONOR; MALIGNANCIES; GENERATION; ANTIGENS AB Multiple myeloma (MM) responds to, but is not cured by, chemotherapy and may therefore be amenable to tumor-specific immunization in the setting of minimal residual disease. The diotype of the monoclonal immunoglobulin expressed by the tumor provides a clear tumor-specific antigen. Patients with follicular lymphoma have unequivocally established that idiotypic vaccination, administered when patients have minimal residual disease, has an antitumor effect and potential to improve the clinical outcome. This result and preclinical studies demonstrating that MM cells display idiotypic peptides on their surface in a form suitable for recognition and killing by host T cells, foster the application of idiotypic vaccination in MM. The current vaccine production involves idiotype protein purification for each patient followed by conjugation to exogenous, immunogenic carriers in order to break immunological tolerance. Furthermore, recent advances in molecular cloning and development of novel antigen delivery systems are making it possible to streamline the production of equally or more effective idiotypic vaccines. Particularly, DNA vaccines utilising genetic carriers to target idiotype on dendritic cells in vivo have proven successful in preclinical models. Additional candidate T cell antigens, such as MUC1, the cancer-testis antigens, and telomerase have been identified as potential targets for immunization, The possibility of using whole myeloma cells as a source of tumor antigens for immunotherapy is also being actively explored. Finally, clinical studies have begun in which dendritic cells are generated ex vivo, loaded with tumor antigen(s), and reinfused to immunize patients. (C) 2002 Editions scientifiques et medicales Elsevier SAS. C1 NCI, Canc Res Ctr, Expt Transplantat & Immunol Branch, Ft Detrick, MD 21702 USA. RP Ruffini, PA (reprint author), NCI, Canc Res Ctr, Expt Transplantat & Immunol Branch, POB B,Bldg 567,Rm 207, Ft Detrick, MD 21702 USA. NR 26 TC 8 Z9 8 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAY PY 2002 VL 56 IS 3 BP 129 EP 132 AR UNSP S0753332202001695/FLA DI 10.1016/S0753-3322(02)00169-5 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 552VK UT WOS:000175640600002 PM 12046683 ER PT J AU Song, YS Goel, A Basrur, V Roberts, PEA Mikovits, JA Inman, JK Turpin, JA Rice, WG Appella, E AF Song, YS Goel, A Basrur, V Roberts, PEA Mikovits, JA Inman, JK Turpin, JA Rice, WG Appella, E TI Synthesis and biological properties of amino acid amide ligand-based pyridinioalkanoyl thioesters as anti-HIV agents SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOCAPSID PROTEIN P7; ZINC FINGERS; ANTIRETROVIRAL THERAPY; NONINFECTIOUS VIRUS; INHIBITORS; TYPE-1; PEPTIDE; 2,2'-DITHIOBISBENZAMIDES; BENZISOTHIAZOLONES AB Hyper-mutable retroviruses such as HIV can become rapidly resistant to drugs used to treat infection, Strategies for coping with drug-resistant strains of virus include combination therapies. using viral protease and reverse transcriptase inhibitors. Another approach is the development of antiviral agents that attack mutationally nonpermissive targets that have functions essential for viral replication. Thus, the highly conserved nucleocapsid protein. NCp7, was chosen as a prime target in our search for novel anti-HIV agents that can overcome the problem of viral drug resistance. Recently, we reported (J. Med. Chem. 1999 42, 67) a novel chemotype, the pyridinioalkanoyl thioesters (PATEs), based on 2-mercaptobenzamides as the thiol component and having its amide nitrogen substituted with various phenylsulfonyl moieties. These compounds were identified as relatively nontoxic anti-HIV agents in the XTT cytoprotection assay. In this study. we wish to report a separate genre of active PATEs wherein the thiol component consists of an N-2-mercaptobenzoyl-amino acid derivative. Active derivatives (EC50 < 10 muM) reported herein were confined to amino acid primary amides or methyl amides having side chains no larger than isobutyl. Amino acids terminating in free carboxyl or carboxylic acid ester groups were mostly inactive. Selected compounds were shown to be active on chronically infected CEM/SK-1, TNFalpha-induced U1. ACH-2 cells and virucidal on cell-free virus, latently infected U I cells and acutely infected primary peripheral blood mononuclear cells (PBMCs). (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Achill Pharmaceut Inc, New Haven, CT 06511 USA. SAIC Frederick, Lab Antiviral Drug Mechanisms, Ft Detrick, MD 21702 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. So Res Inst, Infect Dis Res Dept, Frederick, MD 21702 USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 37 TC 20 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAY PY 2002 VL 10 IS 5 BP 1263 EP 1273 AR PII S0968-0896(01)00392-3 DI 10.1016/S0968-0896(01)00392-3 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 539HX UT WOS:000174865400006 PM 11886789 ER PT J AU Dolan, EA Venable, RM Pastor, RW Brooks, BR AF Dolan, EA Venable, RM Pastor, RW Brooks, BR TI Simulations of membranes and other interfacial systems using P2(1) and pc periodic boundary conditions SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; LIPID BILAYERS; PHOSPHOLIPID-BILAYER; COMPUTER-SIMULATION; SURFACE-TENSION; LIQUID/LIQUID INTERFACES; MELITTIN; PEPTIDES; ENERGY; AREA AB We demonstrate the ease and utility of simulating heterogeneous interfacial systems with P2(1) and Pc periodic boundary conditions which allow, for example, lipids in a membrane to switch leaflets. In preliminary tests, P2(1) was shown to yield equivalent results to P1 in simulations of bulk water, a water/vacuum interface, and pure DPPC bilayers with an equal number of lipids per leaflet; equivalence of Pc and P1 was also demonstrated for the former two systems. P2(1) was further tested in simulations involving the spreading of an octane film on water, and equilibration of a DPPC bilayer from an initial condition containing different numbers of lipids in the two leaflets. Lastly, a simulation in P2(1) of a DOPC/melittin membrane showed significant passage of lipids to the melittin-containing leaflet from the initial distribution, and lends insight into the condensation of lipids by melittin. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20854 USA. RP Brooks, BR (reprint author), Bldg 50,Rm 3406,50 South Dr,MSC 8014, Bethesda, MD 20892 USA. NR 33 TC 35 Z9 36 U1 2 U2 12 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2002 VL 82 IS 5 BP 2317 EP 2325 PG 9 WC Biophysics SC Biophysics GA 546EQ UT WOS:000175259600004 PM 11964222 ER PT J AU Dimitriadis, EK Horkay, F Maresca, J Kachar, B Chadwick, RS AF Dimitriadis, EK Horkay, F Maresca, J Kachar, B Chadwick, RS TI Determination of elastic moduli of thin layers of soft material using the atomic force microscope SO BIOPHYSICAL JOURNAL LA English DT Article ID MECHANICAL-PROPERTIES; CELLS; INDENTATION; SAMPLES; FILMS; TESTS; AFM AB We address three problems that limit the use of the atomic force microscope when measuring elastic moduli of soft materials at microscopic scales. The first concerns the use of sharp cantilever tips, which typically induce local strains that far exceed the linear material regime. We show that this problem can be alleviated by using microspheres as probes, and we establish the criteria for their use. The second relates to the common use of the Hertz contact mechanics model, which leads to significant errors when applied to thin samples. We develop novel, simple to use corrections to apply for such cases. Samples that are either bonded or not bonded to a rigid substrate are considered. The third problem concerns the difficulty in establishing when contact occurs on a soft material. We obtain error estimates for the elastic modulus resulting from such uncertainty and discuss the sensitivity of the estimation methods to error in contact point. The theoretical and experimental results are compared to macroscopic measurements on poly(vinyl-alcohol) gels. C1 NICHHD, Div Bioengn & Phys Sci, Off Res Serv, Off Director,NIH, Bethesda, MD 20892 USA. NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Dimitriadis, EK (reprint author), NICHHD, Div Bioengn & Phys Sci, Off Res Serv, Off Director,NIH, 13 South Dr,MSC 5766,Bldg 13-3N17, Bethesda, MD 20892 USA. NR 41 TC 517 Z9 534 U1 13 U2 191 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2002 VL 82 IS 5 BP 2798 EP 2810 PG 13 WC Biophysics SC Biophysics GA 546EQ UT WOS:000175259600047 PM 11964265 ER PT J AU Kalache, KD Chaoui, R Marks, B Wauer, R Bollmann, R AF Kalache, KD Chaoui, R Marks, B Wauer, R Bollmann, R TI Does fetal tracheal fluid flow during fetal breathing movements change before the onset of labour? SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID LUNG LIQUID; UNCOMPLICATED PREGNANCIES; RESPIRATORY-DISTRESS; DOPPLER ASSESSMENT; ELECTIVE DELIVERY; VAGINAL DELIVERY; CESAREAN-SECTION; PATTERNS; BIRTH; TERM AB Objective To examine changes in intra-tracheal fluid flow parameters during fetal breathing movements throughout the second half of pregnancy in the normally developing human fetus. Design Prospective cross-sectional study. Setting Fetal medicine unit at the Charite University Hospital in Berlin. Methods Assessment of tracheal fluid flow was attempted in 340 healthy fetuses (GA 20-40 weeks) in which fetal breathing movements were seen by B-mode scan. Colour Doppler was applied to visualise the tracheal fluid flow, followed by spectral Doppler to record the velocity waveforms. The records of 53 fetuses divided into five gestational age groups (20-23, 24-27, 28-31, 32-35 and 36-40 weeks of gestation) containing 40 or more continuous breathing cycles (inspiration and expiration) were considered for analysis. Only regular breathing phases were examined and the volume obtained by integration of the tracheal fluid flow displaced during fetal breathing movements was calculated. Results The intra-tracheal flow volume moved during inspiration (Vi) and expiration (Ve) increased until 36 weeks of gestation after which there was a flattening until term. This suggests either a reduction of lung liquid production or a diminished lung liquid volume. The median difference between Vi and Ve was positive in the first four age groups and negative in the last one suggesting that, in mature fetuses, the effect of fetal breathing movements no longer results in an influx. Conclusions Our data demonstrate a modification in fetal behaviour that manifests itself during the last four weeks before birth and has the potential to reduce lung liquid volume. C1 Humboldt Univ Hosp, Fac Med, Dept Obstet & Gynaecol, Fetal Med Unit, Berlin, Germany. Humboldt Univ Hosp, Fac Med, Clin Neonatol, Berlin, Germany. RP Kalache, KD (reprint author), Wayne State Univ, Hutzel Hosp, NICHD, NIH,Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD MAY PY 2002 VL 109 IS 5 BP 514 EP 519 AR PII S1470-0328(02)01265-X DI 10.1111/j.1471-0528.2002.01265.x PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 582AW UT WOS:000177328400008 PM 12066940 ER PT J AU Maciejewski, JP Risitano, A Sloand, EM Nunez, O Young, NS AF Maciejewski, JP Risitano, A Sloand, EM Nunez, O Young, NS TI Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia SO BLOOD LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING-FACTOR; MYELODYSPLASTIC SYNDROMES; IMMUNOSUPPRESSIVE THERAPY; ANTITHYMOCYTE GLOBULIN; EVOLUTION; LEUKEMIA; CYCLOSPORINE; MORPHOLOGY AB A serious complication of aplastic anemia (AA) is its evolution to clonal hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually associated with the appearance of a cytogenetic abnormality in bone marrow cells. We present here an analysis of a cohort of 30 patients with otherwise typical AA in whom clonal karyotypic evolution was observed during frequent periodic marrow examinations. The actuarial risk for this complication has been estimated in other studies at around 15% at 5 years. Conversion from normal to abnormal karyotype occurred at a constant rate after initial diagnosis, with about 50% of cases developing within the first 30 months. Transient chromosomal abnormalities were infrequent. Clinically, AA patients with clonal cytogenetic patterns were heterogenous; a variety of karyotypic defects with numerical and structural abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy 8, structural and numerical abnormalities of chromosome 13, deletion of Y chromosome, and complex cytogenetic abnormalities. Unlike in primary MDS, aberrancies of chromosome 5 and 20 were infrequent. The clinical course depended on the specific abnormal cytogenetic pattern. Most deaths related to leukemic transformation occurred in patients with abnormalities of chromosome 7 or complex cytogenetic alterations or both. Evolution of chromosome 7 abnormalities was seen most often in refractory patients who had failed to respond to therapy. In contrast, trisomy 8 developed in patients with good hematologic responses who often required chronic immunosuppression with cyclosporine A (CsA), and survival was excellent. Although AA patients with monosomy 7 showed a similar prognosis to those with primary MDS, trisomy 8 in AA appears to have a more favorable prognosis than in MDS. (C) 2002 by The American Society of Hematology. C1 NIH, Hematol Branch, Natl Heart Lung & Blood Inst, Bethesda, MD USA. RP Maciejewski, JP (reprint author), Cleveland Clin Taussig Canc Ctr, Hematopoiesis & Expt Hematol Sect, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 40 TC 108 Z9 120 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2002 VL 99 IS 9 BP 3129 EP 3135 DI 10.1182/blood.V99.9.3129 PG 7 WC Hematology SC Hematology GA 545EU UT WOS:000175204300008 PM 11964274 ER PT J AU Cong, PJ Raffeld, M Teruya-Feldstein, J Sorbara, L Pittaluga, S Jaffe, ES AF Cong, PJ Raffeld, M Teruya-Feldstein, J Sorbara, L Pittaluga, S Jaffe, ES TI In situ localization of follicular lymphoma: description and analysis by laser capture microdissection SO BLOOD LA English DT Article ID T(14-18) CHROMOSOMAL TRANSLOCATION; NON-HODGKINS-LYMPHOMAS; BREAKPOINT-CLUSTER REGION; POLYMERASE CHAIN-REACTION; MOLECULAR ANALYSIS; BCL-2 GENE; 14-18 TRANSLOCATION; STRUCTURAL-ANALYSIS; EXPRESSION; PROTEIN AB From 1992 to 2000, we identified 23 lymph node biopsies with focal germinal centers (GCs) containing centrocytes staining strongly for bcl-2 protein, whereas most of the remaining lymph node showed bcl-2-negative follicular hyperplasia. We propose the designation In situ localization of follicular lymphoma (FL) for this phenomenon. In 2 additional cases, l follicles with features of In situ FL were identified In association with other low-grade B-cell lymphomas. To Investigate the clonality of the bcl-2(+) follicles, we performed laser capture microdissection of bcl-2(+) and bcl-2 follicles from the same lymph node In 5 cases, and analyzed them In parallel by polymerase chain reaction (PCR) amplification of Immunoglobulin heavy chain (IgH) genes. In 4 of 5 cases the bcl-2(+) follicles contained monoclonal IgH gene rearrangements, whereas the bcl-2(-) GCs exhibited a polyclonal ladder. A BCL2/JH gene rearrangement was detected in 6 of 14 (43%) evaluable cases. There were 5 patients with synchronous evidence of FL at another site. There were 13 patients who, without a prior diagnosis of FL, had clinical follow-up; one developed FL In an adjacent lymph node within one year, and 2 manifested FL at 13 and 72 months, respectively. There are 10 patients who have not yet shown other evidence of FL. These results suggest that at least close to half of these cases (8/18; 44%) represent homing to and early colonization of reactive GCs by FL. Other cases might represent FL at the earliest stage of development, or a preneoplastic event, requiring a second hit for neoplastic transformation. These findings provide Insight Into the pathophysiology of early FL, and Illustrate the utility of immunohistochemistry for early diagnosis. (C) 2002 by The American Society of Hematology. C1 NCI, Ctr Canc Res, Hematopathol Sect, Pathol Lab, Bethesda, MD USA. RP Jaffe, ES (reprint author), Bldg 10,Rm 2N202,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 39 TC 113 Z9 120 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2002 VL 99 IS 9 BP 3376 EP 3382 DI 10.1182/blood.V99.9.3376 PG 7 WC Hematology SC Hematology GA 545EU UT WOS:000175204300040 PM 11964306 ER PT J AU Bodine, DM AF Bodine, DM TI Suppression of position effects and variegated expression with insulator elements. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 7 BP 326 EP 326 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000011 ER PT J CA NHGRI TI Gene therapy approaches for the Wiskott-Aldrich syndrome. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 9 BP 326 EP 327 PG 2 WC Hematology SC Hematology GA 584TC UT WOS:000177484000013 ER PT J AU Dunbar, CE AF Dunbar, CE TI Insights into hematopoiesis from primate gene-marking trials. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 12 BP 327 EP 328 PG 2 WC Hematology SC Hematology GA 584TC UT WOS:000177484000016 ER PT J AU Hickstein, DD AF Hickstein, DD TI Canine leukocyte adhesion deficiency - An animal model for hematopoietic stem cell therapy. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NR 0 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 23 BP 331 EP 331 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000027 ER PT J AU Kohn, DB Candotti, F Podsakoff, G Engel, B Carbonaro, D Choi, C Cho, G Smogorsweska, M Church, J Shuman, S Muul, L AF Kohn, DB Candotti, F Podsakoff, G Engel, B Carbonaro, D Choi, C Cho, G Smogorsweska, M Church, J Shuman, S Muul, L TI Clinical trials of retroviral-mediated gene transfer to hematopoietic stem cells for ADA-deficient SCID and pediatric HIV-1 infection. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. USC, Keck Sch Med, Los Angeles, CA USA. Childrens Hosp, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 29 BP 333 EP 334 PG 2 WC Hematology SC Hematology GA 584TC UT WOS:000177484000033 ER PT J AU Lucas, ML Pilon, AM Seidel, NE Anderson, SM Orlic, D Bodine, DM AF Lucas, ML Pilon, AM Seidel, NE Anderson, SM Orlic, D Bodine, DM TI Comparison of retrovirus receptor mRNA levels and pseudotyped retrovirus transduction of mouse and human hematopoietic stem cells. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, Flow Cytometry Core Facil, Hematopoiesis Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 34 BP 335 EP 335 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000038 ER PT J AU Malech, HL Brenner, S Choi, U Roesler, J AF Malech, HL Brenner, S Choi, U Roesler, J TI Novel approaches to achieve high levels of genetic correction of chronic granulomatous disease as assessed in vivo in the NOD/SCID mouse-human chimeric marrow model. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 37 BP 336 EP 337 PG 2 WC Hematology SC Hematology GA 584TC UT WOS:000177484000041 ER PT J AU Moayeri, M Ramezani, A Morgan, RA Hawley, TS Hawley, RG AF Moayeri, M Ramezani, A Morgan, RA Hawley, TS Hawley, RG TI Toward hematopoietic stem cell gene therapy for hemophilia A: Recombinant factor VIII production from advanced expression systems. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 40 BP 338 EP 338 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000044 ER PT J AU Nemeth, MJ Cline, AP Garrett, LJ Curtis, DJ Anderson, SM Bodine, DM AF Nemeth, MJ Cline, AP Garrett, LJ Curtis, DJ Anderson, SM Bodine, DM TI Identification and characterization of HMG-4, a nuclear protein expressed in Hematopoietic Stem Cells and erythroid cells. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, Transgen Mouse Core Facil, Flow Cytometry Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 43 BP 339 EP 340 PG 2 WC Hematology SC Hematology GA 584TC UT WOS:000177484000047 ER PT J AU Noguchi, CT Yu, XB Rogers, H Beleslin-Cokic, B Epstein, R AF Noguchi, CT Yu, XB Rogers, H Beleslin-Cokic, B Epstein, R TI Erythropoietin stimulation of differentiating progenitor cells - Not for red cells only. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 45 BP 340 EP 340 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000049 ER PT J AU Orlic, D Cline, A Clevenger, R Chimenti, S Hoyt, R Anversa, P Bodine, DN AF Orlic, D Cline, A Clevenger, R Chimenti, S Hoyt, R Anversa, P Bodine, DN TI Hematopoietic stem cells regenerate myocardium in ischemia-induced heart disease: An experimental model. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 New York Med Coll, Valhalla, NY 10595 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 48 BP 341 EP 341 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000052 ER PT J AU Puck, JM Tsail, EJ Levin, T Kirby, MR Hsu, AP Seidel, NE Porada, C Zanjani, E Bodine, DM Malech, HL AF Puck, JM Tsail, EJ Levin, T Kirby, MR Hsu, AP Seidel, NE Porada, C Zanjani, E Bodine, DM Malech, HL TI Development of XSCID gene therapy for posttransplant patients with persistent immune defects. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Univ Nevada, Reno, NV 89557 USA. NIH, HHMI, Res Scholars Program, Bethesda, MD USA. NIH, Genet & Mol Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 55 BP 343 EP 343 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000059 ER PT J AU Puck, JM Hay, BN Hsu, AP Fischer, R Tsai, E Uzel, G Buckley, RH Malech, HL AF Puck, JM Hay, BN Hsu, AP Fischer, R Tsai, E Uzel, G Buckley, RH Malech, HL TI Patients with atypical X-linked severe combined immunodeficiency (XSCID) may benefit from hematopoietic stem cell gene therapy. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Durham, NC USA. NIH, HHMI, Res Scholar Program, Bethesda, MD USA. NIH, Genet & Mol Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 54 BP 343 EP 343 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000058 ER PT J AU Schmidt, M Muessig, A Horn, P Glimm, H Wissler, M Olsson, K Woods, NB de Sio, FS Sellers, S Tisdale, JF Dunbar, CE Karlsson, S Naldini, L Kiem, HP von Kalle, C AF Schmidt, M Muessig, A Horn, P Glimm, H Wissler, M Olsson, K Woods, NB de Sio, FS Sellers, S Tisdale, JF Dunbar, CE Karlsson, S Naldini, L Kiem, HP von Kalle, C TI Evidence for retroviral and lentiviral vector integration into repopulating hematopoietic stem cells of large animals and humans. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Univ Freiburg, Inst Mol Med & Cell Res, D-79106 Freiburg, Germany. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Turin, Sch Med, Inst Canc Res & Treatment, IRCCS,Lab Gene Transfer & Therapy, I-10060 Candiolo, Italy. Lund Univ, Dept Mol Med & Gene Therapy, S-22184 Lund, Sweden. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Freiburg, Dept Internal Med 1, D-79106 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 66 BP 346 EP 346 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000070 ER PT J AU Weisbein, JL Frazar, TF Garrett, LJ Cline, AP Seidel, NF Gallagher, PG Bodine, DM AF Weisbein, JL Frazar, TF Garrett, LJ Cline, AP Seidel, NF Gallagher, PG Bodine, DM TI Analysis of globin gene expression directed by red cell membrane promoters in transgenic mice and mouse erythroid cells transduced with retrovirus vectors. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. NHGRI, Hematopoiesis Sect, Transgen Mouse Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 67 BP 346 EP 347 PG 2 WC Hematology SC Hematology GA 584TC UT WOS:000177484000071 ER PT J AU Hillis, AE Wityk, RJ Barker, PB Beauchamp, NJ Gailloud, P Murphy, K Cooper, O Metter, EJ AF Hillis, AE Wityk, RJ Barker, PB Beauchamp, NJ Gailloud, P Murphy, K Cooper, O Metter, EJ TI Subcortical aphasia and neglect in acute stroke: the role of cortical hypoperfusion SO BRAIN LA English DT Article DE cerebrovascular disease; stroke; aphasia; hemispatial neglect ID POSITRON EMISSION TOMOGRAPHY; PERFUSION-WEIGHTED MRI; COMPUTED-TOMOGRAPHY; CEREBRAL PERFUSION; VISUAL NEGLECT; BLOOD-PRESSURE; WERNICKES AREA; METABOLISM; LESIONS; THALAMOTOMY AB We have hypothesized that most cases of aphasia or hemispatial neglect due to acute, subcortical infarct can be accounted for by concurrent cortical hypoperfusion. To test this hypothesis, we demonstrate: (i) that pure subcortical infarctions are associated with cortical hypoperfusion in subjects with aphasia/neglect; (ii) that reversal of cortical hypoperfusion is associated with resolution of the aphasia; and (iii) that aphasia/neglect strongly predicts cortical ischaemia and/or hypoperfusion. We prospectively evaluated a consecutive series of 115 patients who presented within 24 h of onset or progression of stroke symptoms, with MRI sequences including diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI), and detailed testing for aphasia or hemispatial neglect. The association between aphasia or neglect and cortical infarct (or dense ischaemia) on DWI and cortical hypoperfusion indicated by PWI, was evaluated with chi-squared analyses. Fisher exact tests were used for analyses with small samples. Cases of DWI lesion restricted to subcortical white matter and/or grey matter structures (n = 44) were examined for the presence of aphasia or neglect, and for the presence of cortical hypoperfusion. In addition, subjects who received intervention to restore perfusion were evaluated with DWI, PWI, and cognitive tests before and after intervention. Finally, the positive predictive value of the cognitive deficits for identifying cortical abnormalities on DWI and PWI were calculated from all patients. Of the subjects with only subcortical lesions on DWI in this study (n = 44), all those who had aphasia or neglect showed concurrent cortical hypoperfusion. Among the patients who received intervention that successfully restored cortical perfusion, 100% (six out of six) showed immediate resolution of aphasia. In the 115 patients, aphasia and neglect were much more strongly associated with cortical hypoperfusion (chi(2) = 57.3 for aphasia; chi(2) = 28.7 for neglect; d.f. = 1; P < 0.000001 for each), than with cortical infarct/ischaemia on DWI (χ(2) = 8.5 for aphasia; χ(2) = 9.7 for neglect; d.f. = 1; P < 0.005 for each). Aphasia showed a much higher positive predictive value for cortical abnormality on PWI (95%) than on DWI (62%), as did neglect (100% positive predictive value for PWI versus 74% for DWI). From these data we conclude that aphasia and neglect due to acute subcortical stroke can be largely explained by cortical hypoperfusion. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Cognit Sci, Baltimore, MD 21287 USA. NIA, Baltimore, MD 21287 USA. RP Hillis, AE (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, Meyer 5-185,600 N Wolfe St, Baltimore, MD 21287 USA. FU NIDCD NIH HHS [K23 DC000174, K23 DC00174-01] NR 50 TC 157 Z9 164 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2002 VL 125 BP 1094 EP 1104 DI 10.1093/brain/awf113 PN 5 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 552NR UT WOS:000175626900016 PM 11960898 ER PT J AU Milner, JA AF Milner, JA TI Strategies for cancer prevention: the role of diet SO BRITISH JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Conference on Recent Scientific Research on Inlin and Oligofructose CY FEB, 2001 CL LONDON, ENGLAND SP ORAFTL DE diet; cancer; polymorphism; genes; phytochemicals ID ABERRANT CRYPT FOCI; RAT MAMMARY-GLAND; METHYLENETETRAHYDROFOLATE REDUCTASE; COLORECTAL-CANCER; DNA METHYLATION; BREAST-CANCER; IN-VITRO; MTHFR POLYMORPHISM; CELL-PROLIFERATION; TUMOR ANGIOGENESIS AB Linkages between diet habits and cancer risk have surfaced from a multitude of epidemiological and preclinical studies. Collectively these studies provide rather compelling evidence that dietary components modify the incidence and biological behavior of tumors. While the risk of breast, prostate, colon, lung and liver cancers are frequently associated with dietary patterns, inconsistencies are not uncommon. These inconsistencies likely reflect the multi-factorial and complex nature of cancer and the specificity that individual dietary constituents have in modifying cancer related genetic pathways. The complexity of defining the role of diet is underscored by the numerous and diverse essential and non-essential components that may alter one or more phases of the cancer process. The explosive increase in the recognition of genes and pathways for regulating cell growth and development, and evaluating the response to hormones and other chemicals synthesized by the body, offers exciting opportunities for unraveling the molecular targets by which dietary components influence cancer prevention. It is recognized that all cells have unique 'signatures' that are characterized by active and inactive genes and cellular products. It is certainly plausible that bridging knowledge about these unique cellular characteristics with the molecular targets for nutrients can be used to assist in optimizing nutrition and minimizing cancer risk. C1 Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NCI, Nutr Sci Res Grp, Div Canc Prevent, Rockville, MD 20892 USA. RP Milner, JA (reprint author), Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NR 78 TC 14 Z9 16 U1 1 U2 4 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD MAY PY 2002 VL 87 SU 2 BP S265 EP S272 DI 10.1079/BJN/2002547 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 567DG UT WOS:000176469700019 PM 12088528 ER PT J AU Nirmalan, PK Thulasiraj, RD Maneksha, V Rahmathullah, R Ramakrishnan, R Padmavathi, A Munoz, SR Ellwein, LB AF Nirmalan, PK Thulasiraj, RD Maneksha, V Rahmathullah, R Ramakrishnan, R Padmavathi, A Munoz, SR Ellwein, LB TI A population based eye survey of older adults in Tirunelveli district of south India: blindness, cataract surgery, and visual outcomes SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; MADURAI INTRAOCULAR-LENS; RURAL DISTRICT; SHUNYI COUNTY; CHINA; PREVALENCE; ACUITY; NEPAL AB Aims: To assess the prevalence of vision impairment, blindness, and cataract surgery and to evaluate S visual acuity outcomes after cataract surgery in a south Indian population. Methods: Cluster sampling was used to randomly select a cross sectional sample of people greater than or equal to50 years of age living in the Tirunelveli district of south India. Eligible subjects in 28 clusters were enumerated through a door to door household survey. Visual acuity measurements and ocular examinations were performed at a selected site within each of the clusters in early 2000, The principal cause of visual impairment was identified for eyes with presenting visual acuity <6/18. Independent replicate testing for quality assurance monitoring was performed in subjects with reduced vision and in a sample of those with normal vision for six of the study clusters, Results: A total of 5795 people in 3986 households were enumerated and 5411 (93.37%) were examined. The prevalence of presenting and best corrected visual acuity greater than or equal to6/18 in both eyes was 59.4% and 75.7%, respectively, Presenting vision <6/60 in both eyes (the definition of blindness in India) was found in 11.0%, and in 4.6% with best correction. Presenting blindness was associated with older age, female sex, and illiteracy. Cataract was the principal cause of blindness in at least one eye in 70.6% of blind people. The prevalence of cataract surgery was 11.8%-with an estimated 56.5% of the cataract blind already operated on. Surgical coverage was inversely associated with illiteracy and with Female sex in rural areas. Within the cataract operated sample, 31.7% had presenting visual acuity greater than or equal to6/1 8 in both eyes and 11.8% were <6/60; 40% were bilaterally operated on, with 63% pseudophakic. Presenting vision was <6/60 in 40.7% of aphakic eyes and in 5.1% of pseudophakic eyes; with best correction the percentages were 17.6% and 3.7%, respectively. Refractive error, including uncorrected aphakia, was the main cause of visual impairment in cataract operated eyes. Vision <6/18 was associated with cataract surgery in government, as opposed to that in non-governmental/private facilities. Age, sex, literacy, and area of residence were not predictors of visual outcomes. Conclusion: Treatable blindness, particularly that associated with cataract and refractive error,, remains a significant problem among older adults in south Indian populations, especially in females, the illiterate, and those living in rural areas. Further study is needed to better understand why a significant proportion of the cataract blind are not taking advantage of free of charge eye care services offered by the Aravind Eye Hospital and others in the district. While continuing to increase cataract surgical volume to reduce blindness, emphasis must also be placed on improving postoperative visual. acuity outcomes. C1 NEI, NIH, Bethesda, MD 20892 USA. Aravind Eye Hosp, Madurai, Tamil Nadu, India. Aravind Eye Hosp, Tirunelveli, India. Univ La Frontera, Unidad Epidemiol Clin, Temuco, Chile. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr,Room 6A-51, Bethesda, MD 20892 USA. EM ellwein@nel.nih.gov NR 27 TC 97 Z9 100 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 2002 VL 86 IS 5 BP 505 EP 512 DI 10.1136/bjo.86.5.505 PG 8 WC Ophthalmology SC Ophthalmology GA 547BU UT WOS:000175313400006 PM 11973242 ER PT J AU Shah, PJ Glabus, MF Goodwin, GM Ebmeier, KP AF Shah, PJ Glabus, MF Goodwin, GM Ebmeier, KP TI Chronic, treatment-resistant depression and right fronto-striatal atrophy SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; MOOD DISORDERS; SCHIZOPHRENIA; ABNORMALITIES; DOPAMINE; ANATOMY; MATTER AB Background Treatment-resistant depression (TRID) is relatively common but its neurobiological basis is poorly understood. Fronto-striatal structural brain changes have been reported in patients with depression but their association with treatment resistance and chronicity has not been established. Method Magnetic resonance images of 20 patients with TRD were compared with images of 20 recovered patients and 20 healthy controls. Images were compared using a voxel-based analysis (VBA) method; the results were validated by conventional volumetric analysis. The clinical associations of magnetic resonance imaging (MRI) changes with illness duration and severity were examined by VBA. Results Only the TRD group exhibited right fronto-striatal atrophy, and subtle MRI changes in the left hippocampus on VBA. Atrophy was confirmed on volumetric analysis, the degree correlating with the cumulative number of electroconvulsive therapy (ECT) treatments received, suggesting an acquired deficit. Conclusions This is the first study to demonstrate fronto-striatal atrophy in patients with depression with poor outcome: the atrophy is more marked in those with more severe illness. Declaration of interest Support from the Royal College of Physicians (Edinburgh) and the Medical Research Council Brain Metabolism Unit. C1 NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX1 2JD, England. Univ Edinburgh, Dept Psychiat, Edinburgh EH8 9YL, Midlothian, Scotland. RP Ebmeier, KP (reprint author), Univ Edinburgh, Royal Edinburgh Hosp, Dept Psychiat, Morningside Pk, Edinburgh EH10 5HF, Midlothian, Scotland. OI Ebmeier, Klaus/0000-0002-5190-7038 NR 27 TC 71 Z9 75 U1 0 U2 7 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 2002 VL 180 BP 434 EP 440 DI 10.1192/bjp.180.5.434 PG 7 WC Psychiatry SC Psychiatry GA 547ZM UT WOS:000175363200011 PM 11983641 ER PT J AU Abraham, J Bakke, S Rutt, A Meadows, B Merino, M Alexander, R Schrump, D Bartlett, D Choyke, P Robey, R Hung, E Steinberg, SM Bates, S Fojo, T AF Abraham, J Bakke, S Rutt, A Meadows, B Merino, M Alexander, R Schrump, D Bartlett, D Choyke, P Robey, R Hung, E Steinberg, SM Bates, S Fojo, T TI A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma - Continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a p-glycoprotein antagonist SO CANCER LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-18, 1999 CL ATLANTA, GEORGIA SP Amer Soc Clin Oncol DE combination chemotherapy; drug resistance reversal; adrenocortical carcinoma (ACC); P-glycoprotein (Pgp); mitotane; doxorubicin; etoposide; vincristine ID ADRENAL-CORTICAL CARCINOMA; SOUTHWEST-ONCOLOGY-GROUP; MULTIDRUG-RESISTANCE; CISPLATIN; DISEASE; CANCER AB BACKGROUND. Adrenocortical carcinoma (ACC) is rare, nearly always fatal, and to the authors' knowledge has few nonsurgical treatment options, Based on in vitro studies demonstrating the efficacy of mitotane as a P-glycoprotein (Pgp) antagonist, and expression of high levels of Pgp in ACC, the authors conducted a study of infusional doxorubicin, vincristine, and etoposide with oral mitotane +/- surgical resection in patients with metastatic ACC. METHODS. Thirty-six patients with metastatic ACC received daily oral mitotane (mean, 4.6 g/day) and 96-hour infusional doxorubicin (10 mg/m(2)/day), etoposide (75 mg/m(2)/day), and vincristine (0.4 mg/m(2)/day). Four responding patients (11%) underwent surgery. RESULTS. Thirty-five patients were evaluable; all had metastatic disease. Eleven patients had not undergone resection of the primary tumor. Approximately 53% of patients had functional tumors. A total of 190 cycles were administered to 36 patients. Responses were observed in 8 patients (22%): 1 complete, 4 partial, and 3 minor responses. The mean duration of response was 12.4 months. Using a landmark method, the median survival of patients who did not respond to chemotherapy was 11.6 months from a point 4 months after the initiation of therapy, whereas that of 8 patients who demonstrated a response to chemotherapy was 34.3 months from that same landmark. High levels of Pgp expression were documented in nine of nine tumors. Mitotane levels > 10 mug/mL, previously shown to antagonize Pgp in vitro, were achieved in 25 of 36 patients (69%). However, rhodamine efflux from CD56-positive cells was not impaired, suggesting poor in vivo Pgp inhibition. The predominant Grade 3/4 toxicity (according to the Common Toxicity Criteria of the National Cancer Institute) was neutropenia. in 66% of cycles; however, fever occurred in only 3% of cycles. Daily mitotane was associated with Grade 1/2 nausea, diarrhea, fatigue, and neuropsychiatric changes in 31 of 36 patients (86%). CONCLUSIONS. Using a combination regimen of daily mitotane with infusional doxorubicin, vincristine, and etoposide in patients with metastatic ACC, responses were observed in 22% of patients. The superiority of this combination over single-agent mitotane is uncertain. The side effects of mitotane made treatment difficult. More effective Pgp antagonists are needed. (C) 2002 American Cancer Society. C1 NCI, Med Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Surg Pathol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 78 Z9 81 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2002 VL 94 IS 9 BP 2333 EP 2343 DI 10.1002/cncr.10487 PG 11 WC Oncology SC Oncology GA 547AQ UT WOS:000175310200003 PM 12015757 ER PT J AU Negri, E Ron, E Franceschi, S La Vecchia, C Preston-Martin, S Kolonel, L Kleinerman, RA Mabuchi, K Jin, F Wingren, G Hallquist, A Levi, F Linos, A Fraumeni, JF AF Negri, E Ron, E Franceschi, S La Vecchia, C Preston-Martin, S Kolonel, L Kleinerman, RA Mabuchi, K Jin, F Wingren, G Hallquist, A Levi, F Linos, A Fraumeni, JF TI Risk factors for medullary thyroid carcinoma: a pooled analysis SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; epidemiology; medullary thyroid carcinoma; risk ID RET PROTOONCOGENE MUTATIONS; ENDOCRINE NEOPLASIA TYPE-2; CIGARETTE-SMOKING; CANCER; 2A; DISEASE; WOMEN; 2B AB Objective: To investigate risk factors for medullary thyroid cancer (MTC). Methods: We conducted a pooled analysis of 14 case-control studies from Europe, North America, and Asia, including 67 medullary cancers (43 women and 24 men) diagnosed in ten studies. Of the original 4776, we selected five controls per case matched on study, gender, and age. The pooled odds ratios (OR) were estimated using conditional logistic regression. Results: Education, weight, and body mass were not associated with MTC, but a significant positive relationship was seen with height (OR = 2.6 for highest vs lowest tertile). Significant excess risks were associated with a history of thyroid nodules (OR = 12), hypertension (OR = 2.3), gallbladder disease (OR = 4.3), and allergies (OR = 2.2). Among current smokers, a decreased risk of MTC was observed with increasing number of cigarettes. The risk was significantly elevated among women having a first birth after age 25 years, but no clear pattern emerged for other reproductive factors. Conclusions: Although the number of MTC was small, we detected several significant associations, including prior thyroid and other diseases. C1 Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy. NCI, Bethesda, MD 20892 USA. Int Agcy Res Canc, Field & Intervent Studies Unit, F-69372 Lyon, France. Univ Milan, Ist Stat Med & Biometria, I-20122 Milan, Italy. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. Radiat Effects Res Fdn, Hiroshima 732, Japan. Shanghai Canc Inst, Shanghai, Peoples R China. Linkoping Univ, Dept Hlth & Environm, Div Environm & Occupat Med, Linkoping, Sweden. Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. CHU Vaudois, Inst Univ Med Sociale & Prevent, Registre Vaudois Tumeurs, CH-1011 Lausanne, Switzerland. Athens Med Sch, Dept Epidemiol, Athens, Greece. RP Negri, E (reprint author), Mario Negri Inst Pharmacol Res, Via Eritrea 62, I-20157 Milan, Italy. RI Negri, Eva/B-7244-2013; OI Negri, Eva/0000-0001-9712-8526; Kleinerman, Ruth/0000-0001-7415-2478; La Vecchia, Carlo/0000-0003-1441-897X NR 29 TC 27 Z9 27 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 2002 VL 13 IS 4 BP 365 EP 372 DI 10.1023/A:1015263718760 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 546LR UT WOS:000175276000009 PM 12074506 ER PT J AU Buetow, KH Klausner, RD Fine, H Kaplan, R Singer, DS Strausberg, RL AF Buetow, KH Klausner, RD Fine, H Kaplan, R Singer, DS Strausberg, RL TI Cancer Molecular Analysis Project: Weaving a rich cancer research tapestry SO CANCER CELL LA English DT Review AB The Cancer Molecular Analysis Project (CMAP) of the NCl is integrating diverse cancer research data to elucidate fundamental etiologic processes, enable development of novel therapeutic approaches, and facilitate the bridging of basic and clinical science. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Buetow, KH (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 3 TC 13 Z9 13 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2002 VL 1 IS 4 BP 315 EP 318 DI 10.1016/S1535-6108(02)00065-X PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TW UT WOS:000178352100005 PM 12086845 ER PT J AU Wang, H Oliver, P Nan, L Wang, SY Wang, Z Rhie, JK Zhang, RW Hill, DL AF Wang, H Oliver, P Nan, L Wang, SY Wang, Z Rhie, JK Zhang, RW Hill, DL TI Radiolabeled 2 '-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2 '-fluoro-5-methyldeoxyuracil-beta-D-arabinofuranoside (FMAU) as tumor-imaging agents in mice SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the American-Association-for-Cancer-Research CY MAR 24-28, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res DE FAU; FMAU; positron emission tomography; functional imaging agent; human tumor xenograft ID POSITRON-EMISSION-TOMOGRAPHY; THYMIDYLATE SYNTHASE EXPRESSION; IN-VIVO; F-18 FLUORODEOXYGLUCOSE; DNA INCORPORATION; CANCER; PET; CELLS; PHARMACOKINETICS; PROLIFERATION AB Purpose: The purpose of the present study was to evaluate, in conjunction with the National Cancer Institute, the feasibility of using two thymidine analogs, 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU, NSC-678515) and 2'-fluoro-5-methyldeoxyuracil-beta-D-arabinofuranoside (FMAU, NSC-678516), as 18-fluorine-labeled positron emission tomography (PET) imaging agents. Methods: The in vivo distribution and DNA incorporation of [2-C-14]FAU, [2-C-14]FMAU, and [2(-14)C] thymidine (as a control) were studied in SCID mice bearing human xenografts of T-cell leukemia CCRF-CEM. Levels of drug-associated radioactivity in blood, tumor and normal tissues including liver, kidneys, heart, lungs, spleen, brain, and skeletal muscle were determined. Results: At 1 h after dosing, radioactivity from all three compounds was distributed in a generally nonspecific manner, except that spleen and tumor tissue had relatively high concentrations of radioactivity from [C-14] thymidine. At 4 h after dosing, the concentrations of radioactivity from [C-14]thymidine and [C-14]FMAU were relatively high in spleen and tumor tissue, and that from [C-14]FAU was highest in tumor tissue. The tumor/skeletal muscle concentration ratios were 2.25 +/- 0.69 and 3.07 +/- 0.42 for [C-14]FAU and [C-14]FMAU, respectively. At 24 h after dosing, only spleen and tumor tissues contained appreciable amounts of radioactivity from either compound. In tumor tissue, the levels of radioactivity from [C-14]FMAU were two- to threefold greater than those from [C-14] thymidine or [C-14]FAU. Examination of purified genomic DNA from tumor, liver, kidneys, brain, and skeletal muscle showed that, at 24 h after dosing, only DNA from tumor tissue contained appreciable concentrations of radioactivity. Radioactivity from [14C]FMAU in tumor DNA was 45% greater than that from [C-14] thymidine and about threefold greater than that from [C-14]FAU. Conclusions: The extent of accumulation of [C-14]FMAU in tumor tissue and incorporation into tumor DNA indicate that[F-18]FMAU could be useful as a functional PET tumor imaging agent. C1 Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. NCI, Rockville, MD 20852 USA. RP Hill, DL (reprint author), Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. FU NCI NIH HHS [N01-CM-07111] NR 30 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 2002 VL 49 IS 5 BP 419 EP 424 DI 10.1007/s00280-002-0433-7 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 561AL UT WOS:000176113700010 PM 11976837 ER PT J AU Wu, K Kim, HT Rodriguez, JL Hilsenbeck, SG Mohsin, SK Xu, XC Lamph, WW Kuhn, JG Green, JE Brown, PH AF Wu, K Kim, HT Rodriguez, JL Hilsenbeck, SG Mohsin, SK Xu, XC Lamph, WW Kuhn, JG Green, JE Brown, PH TI Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INITIAL CLINICAL-TRIAL; BREAST-CANCER CELLS; 9-CIS-RETINOIC ACID; POSTMENOPAUSAL WOMEN; TAMOXIFEN; CHEMOPREVENTION; PREVENTION; RALOXIFENE; CARCINOMA; LIGAND AB Retinoids have been used in the clinic for the prevention and treatment of human cancers. They regulate several cellular processes including growth, differentiation, and apoptosis. Previously, we demonstrated that a pan-agonist retinoid 9-cis retinoic acid was able to suppress mammary tumorigenesis in the C3(1)-SV40 T-antigen (Tag) transgenic mouse model. However, significant toxicity was seen with this naturally occurring retinoid. We hypothesized that the cancer preventive effects of retinoids could be dissected from the toxic effects by using receptor-selective retinoids. In this study, we used TTNPB, an retinoic acid receptor-selective retinoid, and LGD1069, an retinoid X receptor-selective retinoid, to preferentially activate retinoic acid receptors and retinoid X receptors. In vitro, both compounds were able to inhibit the growth of T47D breast cancer cells. We then determined whether these retinoids prevented mammary tumorigenesis. C3(1)-SV40 Tag mice were treated daily by gastric gavage with vehicle, two different doses of TTNPB (0.3 or 3.0 mug/kg), or two different doses of LGD1069 (10 or 100 mg/kg). Mice were treated from approximately 6-8 weeks to 7-8 months of age. Tumor size and number were measured twice each week, and toxicities were recorded daily. Our data show that LGD1069 suppresses mammary tumorigenesis in C3(1)-SV40 Tag transgenic mice with no observable toxicity, whereas TTNPB had a modest chemopreventive effect, yet was very toxic. Median time to tumor development was 129 days in vehicle-treated mice versus 156 days in mice treated with 100 mg/kg LGD1069 (P = 0.05). In addition, tumor multiplicity was reduced by similar to50% in mice treated with LGD1069 (2.9 for vehicle, 2.4 for 10 mg/kg LGD1069, and 1.4 for 100 mg/kg, P less than or equal to 0.03). TTNPB-treated mice showed a delayed median time to tumor development (131 days for vehicle versus 154 days for 3.0 mug/kg TTNPB; P less than or equal to 0.05), but no changes were seen in tumor multiplicity. However, toxicity (skin erythema, hair loss) was seen in all of the mice treated with TTNPB. These data demonstrate that receptor-selective retinoids suppress mammary tumorigenesis in transgenic mice and that preventive effects of retinoids can be separated from their toxicity, demonstrating that receptor-selective retinoids are promising agents for the prevention of breast cancer. C1 Baylor Coll Med, Breast Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Breast Ctr, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Ligand Pharmaceut Inc, Dept Retinoid Res, San Diego, CA 92121 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Brown, PH (reprint author), Baylor Coll Med, Breast Ctr, Dept Med, 1 Baylor Plaza,MS-600, Houston, TX 77030 USA. FU NCI NIH HHS [CA54174, CA78480, P30CA54174] NR 32 TC 110 Z9 112 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2002 VL 11 IS 5 BP 467 EP 474 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 552AV UT WOS:000175596900006 PM 12010861 ER PT J AU Engel, LS Rothman, N Knott, C Lynch, CF Logsden-Sackett, N Tarone, RE Alavanja, MC AF Engel, LS Rothman, N Knott, C Lynch, CF Logsden-Sackett, N Tarone, RE Alavanja, MC TI Factors associated with refusal to provide a buccal cell sample in the agricultural health study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ATTITUDES; RELATIVES AB Epidemiological studies are increasingly collecting buccal cells and other sources of DNA for genetic analysis. However, high refusal rates raise concerns about possible selection bias. This study examines the subject characteristics associated with refusal or failure to provide a buccal cell sample. Subjects were male farmers in the Agricultural Health Study, which is being conducted in Iowa and North Carolina. As part of a 5-year follow-up, cohort members were contacted by telephone and asked to participate in a telephone interview and to consent to providing a buccal cell sample using a kit that was mailed to them. Demographic, lifestyle, disease, and occupational characteristics were compared between consenters who returned a sample ("compliers"), nonconsenters ("refusers"), and consenters who failed to return a sample ("noncompliers"). Compliers (n = 8794), refusers (n = 3178), and noncompliers (n = 3008) were quite similar, although compliers tended to be slightly older. Although some significant differences between these groups were observed, the magnitude of these differences was generally small, usually no more than a few percentage points. In conclusion, this study found little difference between male farmers who agreed to provide buccal cell samples versus those who either refused to provide a sample or who agreed but failed to return the sample. Observed differences were typically small and would be unlikely to compromise etiologic associations identified in such a prospective study. In short, there appears to be little selection bias in the Agricultural Health Study buccal cell collection process, further supporting the use of such mailed collection kits in epidemiological research. C1 NCI, Occupational Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Battelles Ctr Publ Hlth Res & Evaluat, Durham, NC USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. RP Engel, LS (reprint author), NCI, Occupational Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 8113, Bethesda, MD 20892 USA. NR 10 TC 13 Z9 13 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2002 VL 11 IS 5 BP 493 EP 496 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 552AV UT WOS:000175596900010 PM 12010865 ER PT J AU Alexander, HR AF Alexander, HR TI Surgical approaches to liver metastases SO CANCER JOURNAL LA English DT Article; Proceedings Paper CT 3rd National Oncology Forum CY OCT 13-14, 2001 CL WASHINGTON, D.C. DE hepatic neoplasms; liver metastases; surgery; chemotherapy; regional therapy ID TUMOR-NECROSIS-FACTOR; ISOLATED HEPATIC PERFUSION; COLORECTAL-CANCER METASTASES; WHOLE-BODY HYPERTHERMIA; ISOLATED LIMB PERFUSION; DISEASE-FREE SURVIVAL; PHASE HELICAL CT; FACTOR-ALPHA; PROGNOSTIC FACTORS; OCULAR MELANOMA AB Metastases confined to the liver from tumors arising in the gastrointestinal tract or other sites represent a significant clinical problem. Although the majority of patients present with disease that is not amenable to resection based on the size, number, or anatomic distribution of tumors, for selected patients with limited extent of disease surgical resection can result in long-term survival. In patients with colorectal cancer, a number of adverse prognostic factors have been identified that are associated with shortened survival following hepatic resection. The role of adjuvant hepatic artery infusion and systemic chemotherapy following resection in this patient population has been the topic of several prospective random assignment trials. For patients with unresectable metastases confined to liver, a number of regional therapies are in clinical development and share the advantages of intensifying therapy at the site of tumor while minimizing or eliminating unnecessary systemic exposure and toxicity. One such approach is vascular isolation and perfusion, also known as isolated hepatic perfusion or IHP, in which the liver is treated with high dose chemotherapy and/or biological agents under hyperthermic conditions. Although only a limited number of centers have reported substantial experience with this procedure, it appears to have significant efficacy even in patients with advanced tumor burden or those with tumors refractory to other types of therapy. The status of IHP is presented. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2B07, Bethesda, MD 20892 USA. NR 84 TC 2 Z9 2 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2002 VL 8 SU 1 BP S68 EP S81 PG 14 WC Oncology SC Oncology GA 564JR UT WOS:000176311700009 PM 12075704 ER PT J AU Iwanaga, Y Jeang, KT AF Iwanaga, Y Jeang, KT TI Expression of mitotic spindle checkpoint protein hsMAD1 correlates with cellular proliferation and is activated by a gain-of-function p53 mutant SO CANCER RESEARCH LA English DT Article ID KINETOCHORE LOCALIZATION; DNA-DAMAGE; MAD2; INSTABILITY; KINASE; ARREST; CANCER; IDENTIFICATION; APOPTOSIS; MITOSIS AB Human mitotic arrest deficiency protein 1, hsMAD1, is a component the mitotic spindle assembly checkpoint (MSC) that monitors fidelity chromosomal segregation and guards against emergence of cellular an uploidy. Because aneuploidy is a pervasive characteristic of human cancers, understanding how MSC genes are regulated is important. Here, v have analyzed human genomic sequences upstream of the 5' most h MAD1 coding exon and have identified a 1.5-kb fragment with promoter activity. The hsMad1 promoter, consistent with characteristics of house-keeping genes, is highly GC rich and is devoid of a TATA-box. Mutation analyses revealed a core region spanning -73 to -31 as being essential for hsMad1 transcription. Surprisingly, although MSC function, prototypically induced by microtubule inhibitors, is active selectively during mitosis, we found the hsMad1 promoter to be expressed predominantly in and to respond not to microtubule inhibitor but to mitogenic stimulus. 1 primary, as well as transformed cells, intracellular levels of hsMAD1 correlated with the proliferative status of cells. The hsMad1 promoter was also activated preferentially by a gain-of-function p53 mutant. Take together, our results suggest that hsMAD1 might link p53 function to the generation of cellular aneuuploidy and that heightened activation of h Mad1 by gain-of-function p53 mutants could contribute to the worse prognosis of certain cancers. C1 NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 41 TC 36 Z9 38 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 MAY 1 PY 2002 VL 62 IS 9 BP 2618 EP 2624 PG 7 WC Oncology SC Oncology GA 546GG UT WOS:000175265000028 PM 11980658 ER PT J AU Varis, A Wolf, M Monni, O Vakkari, ML Kokkola, A Moskaluk, C Frierson, H Powell, SM Knuutila, S Kallioniemi, A El-Rifai, W AF Varis, A Wolf, M Monni, O Vakkari, ML Kokkola, A Moskaluk, C Frierson, H Powell, SM Knuutila, S Kallioniemi, A El-Rifai, W TI Targets of gene amplification and overexpression at 17q in gastric cancer SO CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-II-ALPHA; HUMAN BREAST-CANCER; CDNA MICROARRAYS; COPY-NUMBER; CELL-LINES; EXPRESSION; ERBB2; PROLIFERATION; C-ERBB-2; ONCOGENE AB DNA copy number gains and amplifications at 17q are frequent in gastric cancer, yet systematic analyses of the 17q amplicon have not been performed. In this study, we carried out a comprehensive analysis of copy number and expression levels of 636 chromosome 17-specific genes in gastric cancer by using a custom-made chromosome 17-specific cDNA microarray. Analysis of DNA copy number changes by comparative genomic hybridization on cDNA microarray revealed increased copy numbers of 11 known genes (ERBB2, TOP2A, GRB7, ACLY PIP5K2B, MPRL45, MKP-L, LHX1, MLN51, MLN64, and RPL27) and seven expressed sequence tags (ESTs) that mapped to 17q12-q21 region. To investigate the genes transcribed at the 17q, we performed gene expression analyses on an identical cDNA microarray. Our expression analysis showed overexpression of 8 genes (ERBB2, TOP2A, GRB2, AOC3, AP2B1, KRT14, JUP, and ITGA3) and two ESTs. Of the commonly amplified transcripts, an uncharacterized EST AA552509 and the TOP2A gene were most frequently overexpressed in 82% of the samples. Additional studies will be initiated to understand the possible biological and clinical significance of these genes in gastric cancer development and progression. C1 Univ Virginia Hlth Syst, Digest Hlth Ctr Excellence, Charlottesville, VA 22908 USA. Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA 22908 USA. Univ Helsinki, Dept Med Genet, Helsinki 00290, Finland. Univ Helsinki, Cent Hosp, Dept Med Genet, Helsinki 00290, Finland. Univ Helsinki, Biomedicum Biochip Ctr, Helsinki 00290, Finland. Univ Helsinki, Cent Hosp, Biomedicum Biochip Ctr, Helsinki 00290, Finland. Univ Helsinki, Dept Surg, Helsinki 00290, Finland. Univ Helsinki, Cent Hosp, Dept Surg, Helsinki 00290, Finland. NIH, Canc Genet Branch, NHGRI, Bethesda, MD 20892 USA. Univ Tampere, Canc Genet Lab, Tampere 33014, Finland. RP El-Rifai, W (reprint author), Univ Virginia Hlth Syst, Digest Hlth Ctr Excellence, POB 800708, Charlottesville, VA 22908 USA. OI Kallioniemi, Anne/0000-0003-3552-8158 NR 28 TC 115 Z9 129 U1 0 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 MAY 1 PY 2002 VL 62 IS 9 BP 2625 EP 2629 PG 5 WC Oncology SC Oncology GA 546GG UT WOS:000175265000029 PM 11980659 ER PT J AU Gelmann, EP Steadman, DJ Ma, J Ahronovitz, N Voeller, HJ Swope, S Abbaszadegan, M Brown, KM Strand, K Hayes, RB Stampfer, MJ AF Gelmann, EP Steadman, DJ Ma, J Ahronovitz, N Voeller, HJ Swope, S Abbaszadegan, M Brown, KM Strand, K Hayes, RB Stampfer, MJ TI Occurrence of NKX3.1 C154T polymorphism in men with and without prostate cancer and studies of its effect on protein function SO CANCER RESEARCH LA English DT Article ID SERUM RESPONSE FACTOR; VITAMIN-D-RECEPTOR; TRANSCRIPTION FACTOR-I; ANDROGEN RECEPTOR; HOMEOBOX GENE; DNA-BINDING; PHOSPHORYLATION SITES; SUSCEPTIBILITY LOCUS; SURVEILLANCE SERIES; INTERPRETING TRENDS AB NKX3.1, a member of the NK class of homeodomain proteins, is expressed primarily in the adult prostate and has growth suppression and differentiating effects in prostate epithelial cells. A C-T polymorphism at nucleotide 154 (NKX3.1 C154T) is present in similar to11% of healthy men with equal distribution among whites and blacks. In a cohort of 1253 prostate cancer patients and age-matched controls, the presence of the polymorphism was associated with a 1.8-fold risk of having stage C or D prostate cancer or Gleason score greater than or equal to7 (confidence interval. 1.01-3.22). The NKX3.1 C154T polymorphism codes for a variant protein that contains an arginine-to-cysteine substitution at amino acid 52 (R52C) adjacent to a protein kinase C phosphorylation site at serine 48. Substitution of cysteine for arginine 52 or of alanine for serine 48 (S48A) reduced phosphorylation at serine 48 in vitro and in vivo. Phosphorylation of wild-type NKX3.1, but not of NKX3.1 R52C or NKX3.1 S48A, diminished binding in vitro to a high-affinity DNA binding sequence. NKX3.1 also serves as a transcriptional coactivator of serum response factor. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate to phosphorylate NKX3.1 had no effect on NKX3.1 coactivation of serum response factor. Neither the R52C nor the S48A substitution affected serum response factor coactivation by NKX3.1 We conclude that the polymorphic NKX3.1 allele codes for a variant protein with altered DNA binding activity that may affect prostate cancer risk. C1 Georgetown Univ, Sch Med, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Neurosci, Washington, DC 20007 USA. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. George Washington Univ Genet, Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. RP Gelmann, EP (reprint author), Georgetown Univ, Sch Med, Lombardi Canc Ctr, Dept Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [CA42182, CA78327, CA58684]; NIEHS NIH HHS [ES09888] NR 50 TC 25 Z9 26 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 MAY 1 PY 2002 VL 62 IS 9 BP 2654 EP 2659 PG 6 WC Oncology SC Oncology GA 546GG UT WOS:000175265000034 PM 11980664 ER PT J AU Ji, L Nishizaki, M Gao, BN Burbee, D Kondo, M Kamibayashi, C Xu, K Yen, N Atkinson, EN Fang, BL Lerman, MI Roth, JA Minna, JD AF Ji, L Nishizaki, M Gao, BN Burbee, D Kondo, M Kamibayashi, C Xu, K Yen, N Atkinson, EN Fang, BL Lerman, MI Roth, JA Minna, JD TI Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; BRONCHIAL EPITHELIUM; EPIGENETIC INACTIVATION; ALLELE LOSS; P53; INDUCTION; GROWTH; IDENTIFICATION; OVEREXPRESSION; ABNORMALITIES AB A group of candidate tumor suppressor genes (designated CACNA2D2, PL6, 101F6, NPRL2, BLU, RASSF1, FUS1, HYAL2, and HYAL1) has been identified in a 120-kb critical tumor homozygous deletion region (found in lung and breast cancers) of human chromosome 3p21.3. We studied the effects of six of these 3p21.3 genes (101F6, NPRL2, BLU, FUS1, HYAL2, and HYAL1) on tumor cell proliferation and apoptosis in human lung cancer cells by recombinant adenovirus-mediated gene transfer in vitro and in vivo. We found that forced expression of wild-type FUS1, 101F6, and NPRL2 genes significantly inhibited tumor cell growth by induction of apoptosis and alteration of cell cycle processes in 3p21.3 120-kb region-deficient (homozygous) H1299 and A549 cells but not in the 3p21.3 120-kb region-heterozygous H358 and the normal human bronchial epithelial cells. Intratumoral injection of Ad-101F6, Ad-FUS1, Ad-NPRL2, and Ad-HYAL2 vectors or systemic administration of protamine-complexed vectors significantly suppressed growth of H1299 and A549 tumor xenografts and inhibited A549 experimental lung metastases in nu/nu mice. Together, our results, coupled with other studies demonstrating a tumor suppressor role for the RASSSF1A isoform, suggest that multiple contiguous genes in the 3p21.3 120-kb chromosomal region may exhibit tumor suppressor activity in vitro and in vivo. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Pharmacol Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. RP Ji, L (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, Box 445,1515 Holcombe Blvd, Houston, TX 77030 USA. RI KONDO, Masashi/I-7378-2014 FU NCI NIH HHS [2P50-CA70970-04, CA 16672, CA71618, P01 CA070970, P01 CA078778, P01 CA78778-01A1, P30 CA016672, P50 CA070907, R01 CA071618] NR 27 TC 130 Z9 153 U1 1 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 MAY 1 PY 2002 VL 62 IS 9 BP 2715 EP 2720 PG 6 WC Oncology SC Oncology GA 546GG UT WOS:000175265000043 PM 11980673 ER PT J AU Okoji, RS Yu, RC Maronpot, RR Froines, JR AF Okoji, RS Yu, RC Maronpot, RR Froines, JR TI Sodium arsenite administration via drinking water increases genome-wide and Ha-ras DNA hypomethylation in methyl-deficient C57BL/6J mice SO CARCINOGENESIS LA English DT Article ID MOUSE-LIVER TUMORS; DISEASE ENDEMIC AREA; INDUCED MALIGNANT TRANSFORMATION; CHOLINE-DEVOID DIET; GENE-EXPRESSION; METHYLTRANSFERASE ACTIVITY; 5-METHYLCYTOSINE CONTENT; ENZYMATIC METHYLATION; CHROMATIN STRUCTURE; BREAST-CANCER AB Arsenic is an established human carcinogen. Deficiencies in available animal models have inhibited a detailed analysis of the mechanism of arsenic induced cancer. This study sought to determine the role of a methyl-deficient diet in combination with sodium arsenite on the genomic methylation status and Ha-ras methylation status of C57BL/ 6J male mice hepatic DNA. Mice were administered arsenic as sodium arsenite via drinking water at 0, 2.6, 4.3, 9.5 or 14.6 mg sodium arsenite/kg/day. Administration occurred 7 days a week for 130 days. Dose-related effects on the liver were evident in mice administered arsenic and methyl-deficient diets. Most prominent were observations of steatosis and microgranulomas. Sodium arsenite increased genomic hypomethylation in a dose dependent manner and methyl-deficiency and sodium arsenite reduced the frequency of methylation at several cytosine sites within the promoter region of the oncogenic gene, Ha-ras. Methylation changes were prominent in a 500 by non-CpG island-like region of the Ha-ras promoter and less prominent in a 525 by CpG island-like region. DNA methylation plays an important role in the physiological expression of many genes including Ha-ras. Significantly reduced methylation at a key regulatory region of Ha-ras in the mouse liver may have relevance to understanding arsenic-induced perturbations in the methylation patterns of cellular growth genes involved in the formation of tumors. These findings highlight the effect of sodium arsenite on inherent methylation processes within the hepatic cell. C1 Univ Calif Los Angeles, Sch Publ Hlth, Ctr Environm & Occupat Hlth, Los Angeles, CA 90095 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Froines, JR (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Ctr Environm & Occupat Hlth, 650 Charles E Young Dr S, Los Angeles, CA 90095 USA. FU NIEHS NIH HHS [5P30ES07048-06] NR 66 TC 68 Z9 76 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2002 VL 23 IS 5 BP 777 EP 785 DI 10.1093/carcin/23.5.777 PG 9 WC Oncology SC Oncology GA 556ZB UT WOS:000175879000013 PM 12016150 ER PT J AU Berrigan, D Perkins, SN Haines, DC Hursting, SD AF Berrigan, D Perkins, SN Haines, DC Hursting, SD TI Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice SO CARCINOGENESIS LA English DT Article ID BODY-WEIGHT; LIFE-SPAN; DIETARY RESTRICTION; CANCER PREVENTION; SHORT-TERM; AGE; GROWTH; RATS; GENOTYPE; LIVER AB Heterozygous p53-deficient (p53(+/-)) mice, a potential model for human Li-Fraumeni Syndrome, have one functional allele of the p53 tumor suppressor gene. These mice are prone to spontaneous neoplasms, most commonly sarcoma and lymphoma; the median time to death of p53+/- mice is 18 months. We have shown previously that juvenile-onset calorie restriction (CR) to 60% of ad libitum (AL) intake delays tumor development in young p53-null (-/-) mice by a p53-independent and insulin-like growth factor 1 (IGF-1)-related mechanism. To determine whether CR is effective when started in adult p53-deficient mice, and to compare chronic CR with an intermittent fasting regimen, male p53+/- mice (7-10 months old, 31-32 mice/group) were randomly assigned to the following regimens: (i) AL (AIN-76A diet), (ii) CR to 60% of AL intake or (iii) 1 day/week fast. Food availability on non-fasting days was controlled to prevent compensatory over feeding. Relative to the AL group, CR significantly delayed (P = 0.001) the onset of tumors in adult mice, whereas the 1 day/week fast caused a moderate delay (P = 0.039). Substantial variation in longevity and maximum body weight within treatments was not correlated with variation in growth characteristics of individual mice. In a separate group of p53 +/- mice treated for 4 weeks (n = five mice per treatment), plasma IGF-1 levels in CR versus AL mice were reduced by 20% (P < 0.01) and leptin levels were reduced by 71% (P < 0.01); fasted mice had intermediate levels of leptin and IGF-1. Our findings that CR or a 1 day/week fast suppressed carcinogenesis-even when started late in life in mice predestined to develop tumors due to decreased p53 gene dosage support efforts to identify suitable interventions influencing energy balance in humans as a tool for cancer prevention. C1 NCI, Div Canc Prevent, Off Prevent Oncol, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, SAIC, Frederick, MD 21702 USA. RP Hursting, SD (reprint author), NCI, Div Canc Prevent, Off Prevent Oncol, 6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 33 TC 111 Z9 112 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2002 VL 23 IS 5 BP 817 EP 822 DI 10.1093/carcin/23.5.817 PG 6 WC Oncology SC Oncology GA 556ZB UT WOS:000175879000018 PM 12016155 ER PT J AU Stillwell, WG Sinha, R Tannenbaum, SR AF Stillwell, WG Sinha, R Tannenbaum, SR TI Excretion of the N-2-glucuronide conjugate of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine and its relationship to CYP1A2 and NAT2 activity levels in humans SO CARCINOGENESIS LA English DT Article ID BORNE CARCINOGEN 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE; HETEROCYCLIC AROMATIC-AMINES; LOS-ANGELES-COUNTY; CYTOCHROME P4501A2; METABOLIC-ACTIVATION; DNA-ADDUCTS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; IDENTIFICATION; EXPOSURE; MEIQX AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic aromatic amine formed in meat products during cooking. The genotoxity of PhIP requires an initial cytochrome P450-mediated N-oxidation followed by N-O-esterification catalyzed generally by N-acetyltransferases and sulfotransferases. This study examined the urinary excretion of N-2-(beta-1-glucosiduronyl)-2-hydroxyamino-1-methyl-6-phenylimidazo[4,5- b]pyridine-the major human urinary N-oxidation metabolite of PhIP-and determined its relationship to individual activity levels of cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2). The subjects (33 males and 33 females) in the dietary study were phenotyped for their CYP1A2 and NAT2 activity prior to consumption of meat-based diet, and urine collections were obtained 0-12 and 12-24 h after ingestion of the meal. Acidic hydrolysis of N-2-(beta-1-glucosiduronyl)-2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine and its d(3)-analog to form their respective deaminated products 2-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (2-OH-PhIP) was used in the assay. The products after derivatization were analyzed by capillary gas chromatography-negative ion chemical ionization mass spectrometry with selective ion monitoring. The amount of N-2-(beta-1-glucosiduronyl)-2-hydroxyamino-lmethyl-6-phenylimidazo[4,5-b]pyridine measured as the acid hydrolysis product 2-OH-PhIP in the 0-12 h urine was 20.2 +/- 8.0% (mean +/- SD) of the ingested dose; the median was 18.8% and the range varied from 5.4 to 39.6% within the group. In a subset (n = 18) of samples from individual urine collected from the 12-24 h period, an average value of 4.4 +/- 2.5% (+/- SD) of the dose was recovered. The excretion of N-2-(beta-1-glucosiduronyl)-2-hydroxyamino-lmethyl-6-phenylimidazo[4,5-b]pyridine in the 0-12 h urine was significantly related to the quantity of PhIP ingested for all subjects (r = 0.52, P <0.0001). Linear regression analysis of the relationship between the excretion level of N-2-(β-1-glucosiduronyl)-2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine, adjusted for meat intake and CYP1A2 activity in the combined group of males and females showed a low association (r = 0.25, P = 0.05). There was no association between the amount of N-2-(β-1-glucosiduronyl)-2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine and NAT2 activity levels of the subjects nor with the age of the subjects. N-2-(β-1-glucosiduronyl)-2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine comprised a significant proportion of the ingested dose in some individuals; however, considerable variation was found within the group. The results indicate that inter-individual differences in the rates of N-oxidation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, as well as phase II glucuronidation reactions regulate the formation of this metabolite in humans. C1 MIT, Div Biol Engn, Cambridge, MA 02139 USA. NCI, Nutr Epidemiol Branch, NIH, Rockville, MD 20892 USA. RP Tannenbaum, SR (reprint author), MIT, Div Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NIEHS NIH HHS [ES05622] NR 40 TC 29 Z9 29 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2002 VL 23 IS 5 BP 831 EP 838 DI 10.1093/carcin/23.5.831 PG 8 WC Oncology SC Oncology GA 556ZB UT WOS:000175879000020 PM 12016157 ER PT J AU Yu, MS Jones, ML Gong, M Sinha, R Schut, HAJ Snyderwine, EG AF Yu, MS Jones, ML Gong, M Sinha, R Schut, HAJ Snyderwine, EG TI Mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the mammary gland of Big Blue rats on high- and low-fat diets SO CARCINOGENESIS LA English DT Article ID SPRAGUE-DAWLEY RATS; DNA ADDUCT FORMATION; IN-VIVO; HETEROCYCLIC AMINES; BREAST-CANCER; CARCINOGENESIS; MUTATIONS; COLON; RISK; FOOD AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a food-borne mutagen and mammary gland carcinogen in female rats. A high-fat diet has been shown to increase the incidence of PhIP-induced mammary gland tumors. The current study used Big Blue rats harboring the lambda lacI mutational reporter transgene, to address whether the promotional effect of a high-fat diet is mediated via modulation in mammary gland mutagenesis. Big Blue rats were given 10 doses of PhIP (75 mg/kg, p.o.) and placed on defined low-fat (5% corn oil) or high-fat (23.5% corn oil) diet for 6 weeks prior to collecting mammary glands. The lacI mutant frequency (mean standard error, n = 3 rats) was 231 +/- 15 ( x 10(-6)) and 193 +/- 12 ( x 10(-6)) in the low- and high-fat group, respectively. Values were increased 12-fold over control but were not significantly different between the two diets. In a parallel study, diet did not alter the mutant frequency induced by 7,12-dimethylbenz[a]anthracene (DMBA) (125 mg/kg, p.o.) in the mammary gland. The findings suggest that the promotion by the high-fat diet is not mediated via an increase in mutations. Consistent with the high potency of DMBA as a mammary carcinogen, the mutant frequency was 20-30% higher with DMBA than with PhIP. Sixty-nine and 56 PhIP-induced lacI mutants were sequenced from the low- and high-fat diet groups, respectively. While the percentage of various types of mutations was identical between the diet groups, some difference in the distribution of mutations along the lacI gene was observed. The mutation spectrum in the mammary gland from rats on both diets was consistent with the formation of PhIP-guanine adducts which were detected by a P-32-post-labeling assay. Guanine base substitutions accounted for similar to85% of all mutations irrespective of diet. Single base pair deletions at guanine occurred in 11-17% of mutants. G:C to T:A transversions were the predominant base substitution mutation accounting for 35-43% of all mutations. The majority of all guanine mutations (74%) occurred at guanine bases adjacent to another G: C pair. Five out of 125 (4%) mutations involved a guanine deletion in the 5'-GGGA-3' sequence, a PhIP signature mutation reported previously. Twelve out of 125 (10%) mutations involved the guanine base in the sequence 5'-CAG(Purine)-3' (Pu). The findings from these studies suggest that 5'-CAG(Pu)-3' is an additional characteristic target site for PhIP-guanine adduct-induced mutations in vivo in the mammary gland. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Ctr Canc Res, Bldg 37,Room 3C28,37 Convent Dr,MSC-425, Bethesda, MD 20892 USA. NR 44 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2002 VL 23 IS 5 BP 877 EP 884 DI 10.1093/carcin/23.5.877 PG 8 WC Oncology SC Oncology GA 556ZB UT WOS:000175879000026 PM 12016163 ER PT J AU Grieshaber, S Swanson, JA Hackstadt, T AF Grieshaber, S Swanson, JA Hackstadt, T TI Determination of the physical environment within the Chlamydia trachomatis inclusion using ion-selective ratiometric probes SO CELLULAR MICROBIOLOGY LA English DT Article ID PHAGOSOME-LYSOSOME FUSION; COXIELLA-BURNETII; INTRACELLULAR PH; HELA-CELLS; MEMBRANE; INFECTION; CALCIUM; NUCLEOTIDES; INDICATORS; METABOLISM AB Chlamydia trachomatis is an obligate intracellular bacterium with a biphasic life cycle that takes place entirely within a membrane-bound vacuole termed an inclusion. The chlamydial inclusion is non-fusogenic with endosomal or lysosomal compartments but intersects a pathway involved in transport of sphingomyelin from the Golgi apparatus to the plasma membrane. The physical conditions within the mature chlamydial inclusion are unknown. We used ratiometric imaging with membrane-permeant, ion-selective fluorescent dyes for microanalyis of the physical environment within the inclusion. Determination of H+, Na+, K+ and Ca2+ concentrations using CFDA (carboxy fluorescein diacetate) or BCECF-AM (2' ,7' -bis (2-carboxyethyl)-5,6-carboxyfluorescein acetoxymethyl ester, SBFI-AM, PBFI-AM and fura-PE3-acetomethoxyester (Fura-PE3-AM), respectively, indicated that all ions assayed within the lumenal space of the inclusion approximated the concentrations within the cytoplasm. Stimulation of purinergic receptors by addition of extracellular ATP triggered a dynamic Ca2+ response that occurred simultaneously within the cytoplasm and interior of the inclusion. The chlamydial inclusion thus appears to be freely permeable to cytoplasmic ions. These results have implications for nutrient acquisition by chlamydiae and may contribute to the non-fusogenicity of the inclusion with endocytic compartments. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov RI Swanson, Joel/P-4362-2014 OI Swanson, Joel/0000-0003-0900-8212 FU NIAID NIH HHS [R01 AI035950, R01 AI035950-09, AI 35950] NR 33 TC 36 Z9 37 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD MAY PY 2002 VL 4 IS 5 BP 273 EP 283 DI 10.1046/j.1462-5822.2002.00191.x PG 11 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 553KR UT WOS:000175674800002 PM 12027956 ER PT J AU Chao, LL Weisberg, J Martin, A AF Chao, LL Weisberg, J Martin, A TI Experience-dependent modulation of category-related cortical activity SO CEREBRAL CORTEX LA English DT Article ID INFERIOR PREFRONTAL CORTEX; HUMAN VISUAL-CORTEX; POSITRON EMISSION TOMOGRAPHY; EVENT-RELATED FMRI; TEMPORAL CORTEX; FUNCTIONAL MRI; BIOLOGICAL MOTION; OBJECTS; RETRIEVAL; MEMORY AB Naming pictures of objects from different categories (e.g. animals or tools) evokes maximal responses in different brain regions. However, these 'category-specific' regions typically respond to other object categories as well. Here we used stimulus familiarity to further investigate category representation. Naming pictures of animals and tools elicited category-related activity in a number of previously identified regions. This activity was reduced for familiar relative to novel stimuli. Reduced activation occurred in all object-responsive areas in the ventral occipito-temporal cortex, regardless of which category initially produced the maximal response. This suggests that object representations in the ventral occipito-temporal cortex are not limited to a discrete area, but rather are widespread and overlapping. In other regions (e.g. the lateral temporal and left premotor cortices), experience-dependent reductions were category specific. Together, these findings suggest that category-related activations reflect the retrieval of information about category-specific features and attributes. C1 Vet Adm Med Ctr, San Francisco, CA 94121 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Chao, LL (reprint author), Vet Adm Med Ctr, 4150 Clement St,114Q, San Francisco, CA 94121 USA. RI martin, alex/B-6176-2009 NR 61 TC 143 Z9 144 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2002 VL 12 IS 5 BP 545 EP 551 DI 10.1093/cercor/12.5.545 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 544LR UT WOS:000175159800010 PM 11950772 ER PT J AU Sakurai, T Qu, W Sakurai, MH Waalkes, MP AF Sakurai, T Qu, W Sakurai, MH Waalkes, MP TI A major human arsenic metabolite, dimethylarsinic acid, requires reduced glutathione to induce apoptosis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID GENE-EXPRESSION; IN-VITRO; MALIGNANT NEOPLASMS; CELLS; INHIBITION; MECHANISM; TOXICITY; LIVER; MODULATION; TRIOXIDE AB Inorganic arsenicals are important environmental toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenicals often undergo methylation, forming compounds such as dimethyarsinic acid (DMA). Recent evidence indicates DMA is a complete carcinogen in rodents while evidence for inorganic arsenicals as carcinogens in rodents remains equivocal. Thus, we studied the molecular mechanisms of in vitro cytolethality of DMA compared to that of the trivalent inorganic arsenical, sodium arsenite, using a rat liver epithelial cell line (TRL 1215). Arsenite was very cytotoxic in these cells (LC50 = 35 muM after 48 h of exposure). With arsenite exposure, most dead cells showed histological and biochemical evidence of necrosis. Arsenite cytotoxicity increased markedly when cellular GSH was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO). In contrast, DMA was nearly 3 orders of magnitude less cytotoxic (LC50 = 1.5 mM) although evidence showed the predominating form of death was apoptosis. Surprisingly, GSH depletion actually decreased DMA-induced apoptosis. A glutathione scavenger, diethyl maleate (DEM), and a glutathione reductase inhibitor, carmustine, also prevented DMA-induced apoptosis. These data indicate that DMA requires intracellular GSH to induce apoptosis. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyzes GSH-substrate conjugation, acivicin, an inhibitor of gamma-glutamyltranspeptidase (GGT) which catalyzes the initial breakdown of GSH-substrate conjugates, and aminooxyacetic acid (AOAA), an inhibitor of beta-lyase which catalyzes the final breakdown of GSH-substrate conjugates, all were effective in suppressing DMA-induced apoptosis. These findings indicate that DMA likely is conjugated in some form with GSH, and that it is this conjugate that induces apoptosis during subsequent metabolic reactions. C1 NIEHS, Inorgan Carcinogenesis Section, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Section, Comparat Carcinogenesis Lab, NCI,NIH, Res Triangle Pk, NC 27709 USA. FU PHS HHS [G-5-0111] NR 60 TC 47 Z9 48 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 2002 VL 15 IS 5 BP 629 EP 637 DI 10.1021/tx0101604 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 554KW UT WOS:000175735400004 PM 12018983 ER PT J AU Goldstein, S Samuni, A Aronovitch, Y Godinger, D Russo, A Mitchell, JB AF Goldstein, S Samuni, A Aronovitch, Y Godinger, D Russo, A Mitchell, JB TI Kinetics of paraquat and copper reactions with nitroxides: The effects of nitroxides on the aerobic and anoxic toxicity of paraquat SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ESCHERICHIA-COLI; OXIDATIVE DAMAGE; SUPEROXIDE; CELLS; RADICALS; MECHANISMS; MIMICS; IRON; DNA AB The toxicity of paraquat (PQ(2+)) is attributed to intracellularly formed PQ(.+), O-2(.-), H2O2, and secondary (OH)-O-. radicals generated through Fenton-like reactions. Yet, no antidote for PQ(2+) toxicity in human has been found also due to poor cell permeability of many common antioxidants that remove toxic species predominantly extracellularly. Cell-permeable nitroxides, which scavenge xenobitic-derived deleterious radicals and detoxify redox-active metal ions, would be expected to ameliorate PQ(2+) toxicity. We have studied using pulse radiolysis the kinetics of the reactions of 2,2,6,6-tetramethyl-piperidinoxyl (TPO) and 4-OH-TPO with PQ(.+) and (CuL2)-L-II (L = 1,10-phenanthroline, 2,2'-bipyridyl) in the absence and presence of DNA. We found that the rate constant for the reaction of PQ(.+) with the nitroxides is about 4 orders of magnitude lower than that with O-2. In addition, the rate of the reaction of the nitroxides with (CuL2)-L-I decreases as [DNA] increases, which suggests that nitroxides react significantly slower with bound metal ions. These results explain the failure of 4-OH-TPO to protect bacterial and mammalian cells from PQ(2+) toxicity under air. In contrast, the rate of the reaction of PQ(.+) with (CuL2)-L-II was unaffected by DNA. Furthermore, copper toxicity has been attributed mainly to Cu-I and was observed predominantly for cells subjected to anoxic conditions. It implied that nitroxides would be effective protectants if PQ(2+) induces toxicity also under anoxia. Surprisingly, we found that pQ(2+) toxicity under anoxia was even greater than that under air, and under these conditions 4-OH-TPO protected the cells from PQ. These results indicate that the mechanism underlying the anoxic toxicity of pQ(2+) differs from that operating in the presence of oxygen, and that reduced transition metal ions are most probably the species responsible for PQ(2+) anoxic toxicity. C1 Hebrew Univ Jerusalem, Sch Med, Dept Physical Chem & Mol Biol, IL-91940 Jerusalem, Israel. NCI, Radiat Biol Branch, Clin Oncol Program, Div Canc Treatment,NIH, Bethesda, MD 20892 USA. RP Samuni, A (reprint author), Hebrew Univ Jerusalem, Sch Med, Dept Physical Chem & Mol Biol, IL-91940 Jerusalem, Israel. NR 24 TC 8 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 2002 VL 15 IS 5 BP 686 EP 691 DI 10.1021/tx0155956 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 554KW UT WOS:000175735400011 PM 12018990 ER PT J AU Sneller, MC AF Sneller, MC TI Granuloma formation, implications for the pathogenesis of vasculitis SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 10th International Vasculitis and ANCA Workshop CY APR 25-28, 2002 CL CLEVELAND, OHIO ID INTERFERON-GAMMA-RECEPTOR; BACILLE CALMETTE-GUERIN; MYCOBACTERIUM-TUBERCULOSIS INFECTION; GIANT-CELL ARTERITIS; WEGENERS-GRANULOMATOSIS; CYTOKINE PROFILES; T-CELLS; MICE; DEFICIENCY; RESPONSES C1 NIAID, Immunol Dis Sect, LIR, NIH, Bethesda, MD 20892 USA. RP Sneller, MC (reprint author), NIAID, Immunol Dis Sect, LIR, NIH, Bldg 10,Room 11B13,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 31 Z9 34 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD MAY PY 2002 VL 69 IS 5 SU 2 BP 40 EP 43 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 592TD UT WOS:000177952200009 ER PT J AU Barron, KS AF Barron, KS TI Kawasaki disease: Etiology, pathogenesis, and treatment SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 10th International Vasculitis and ANCA Workshop CY APR 25-28, 2002 CL CLEVELAND, OH ID TUMOR-NECROSIS-FACTOR; INTRAVENOUS GAMMA-GLOBULIN; CORONARY-ARTERY ANEURYSMS; EPSTEIN-BARR-VIRUS; BETA FAMILY REPERTOIRE; FACTOR-ALPHA; ACUTE-PHASE; CHLAMYDIA-PNEUMONIAE; ENDOTHELIAL-CELLS; T-CELLS C1 NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Barron, KS (reprint author), NIAID, Div Intramural Res, NIH, Bldg 10,Room 4A30,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kbarron@niaid.nih.gov NR 111 TC 13 Z9 15 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD MAY PY 2002 VL 69 IS 5 SU 2 BP 69 EP 78 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 592TD UT WOS:000177952200015 ER PT J AU Nagineni, CN Detrick, B Hooks, JJ AF Nagineni, CN Detrick, B Hooks, JJ TI Transforming growth factor-beta expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE immunopathogenesis; retinochoroiditis; TGF-beta; Toxoplasma gondii ID INTERCELLULAR-ADHESION MOLECULE-1; OCULAR TOXOPLASMOSIS; TGF-BETA; GENE-EXPRESSION; PROTECTIVE ROLE; MESSENGER-RNA; SECRETION; IMMUNOREGULATION; INTERLEUKIN-6; INFLAMMATION AB Retinochoroiditis caused by Toxoplasma gondii infection results in inflammation and necrosis of the retina. We have used human retinal pigment epithelial cultures (HRPE) as an in vitro model to investigate the role of TGF-beta in T. gondii-induced retinochoroiditis. RT-PCR analyses showed enhanced steady state levels of TGF-beta1 and TGF-beta2 mRNA in T. gondii-infected HRPE. Uninfected HRPE secrete TGF-beta1 in a latent form while 10-30% of the secreted TGF-beta2 was in the active form. T. gondii infection induced a significant increase (P < 0.01) in total TGF-β1 and TGF-β2 secretion by HRPE. In addition, soluble extracts of T gondii (ST) stimulated secretion of both TGF-β1 and TGF-β2 significantly (P < 0.01). Interestingly, T. gondii infection as well as ST of the parasites completely inhibited secretion of the active form of TGF-beta2. Studies evaluating the effect of TGF-beta on T. gondii replication in HRPE revealed that TGF-beta enhanced parasite replication. The interactions between host retinal cells and T. gondii may play an active role in the pathogenesis of retinochoroiditis. C1 NEI, Immunol & Virol Sect, Immunobiol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunobiol Lab, NIH, Bldg 10,Room 6 N 228, Bethesda, MD 20892 USA. NR 32 TC 29 Z9 29 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 2002 VL 128 IS 2 BP 372 EP 378 DI 10.1046/j.1365-2249.2002.01815.x PG 7 WC Immunology SC Immunology GA 577UB UT WOS:000177079400025 PM 11985530 ER PT J AU Neckers, L AF Neckers, L TI Heat shock protein 90 inhibition by 17-allylamino-17-demethoxygeldanamycin: A novel therapeutic approach for treating hormone-refractory prostate cancer - Commentary SO CLINICAL CANCER RESEARCH LA English DT Article ID ANDROGEN RECEPTOR GENE; IMPORTANT BIOLOGIC ACTIVITIES; IN-VIVO; GELDANAMYCIN; HSP90; DESTABILIZATION; AMPLIFICATION; HER-2/NEU; BINDS; HETEROCOMPLEX C1 NCI, Cell & Canc Biol Branch, Rockville, MD 20850 USA. RP Neckers, L (reprint author), NCI, Cell & Canc Biol Branch, 9610 Rockville, Rockville, MD 20850 USA. NR 37 TC 57 Z9 58 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 962 EP 966 PG 5 WC Oncology SC Oncology GA 551EY UT WOS:000175547700004 PM 12006507 ER PT J AU Leonard, DGB Travis, LB Addya, K Dores, GM Holowaty, EJ Bergfeldt, K Malkin, D Kohler, BA Lynch, CF Wiklund, T Stovall, M Hall, P Pukkala, E Slater, DJ Felix, CA AF Leonard, DGB Travis, LB Addya, K Dores, GM Holowaty, EJ Bergfeldt, K Malkin, D Kohler, BA Lynch, CF Wiklund, T Stovall, M Hall, P Pukkala, E Slater, DJ Felix, CA TI p53 mutations in leukemia and myelodysplastic syndrome after ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; ACUTE LYMPHOBLASTIC-LEUKEMIA; THERAPY-RELATED LEUKEMIA; MYELOID-LEUKEMIA; SECONDARY LEUKEMIAS; MLL GENE; GEL-ELECTROPHORESIS; ALKYLATING-AGENTS; CISPLATIN; POLYMORPHISM AB Purpose: Although p53 mutations occur in alkylating agent-related leukemias, their frequency and spectrum in leukemias after ovarian cancer have not been addressed. The purpose of this study was to examine p53 mutations in leukemias after ovarian cancer, for which treatment with platinum analogues was widely used. Experimental Design: Adequate leukemic or dysplastic cells were available in 17 of 82 cases of leukemia or myelodysplastic syndrome that occurred in a multicenter, population-based cohort of 23,170 women with ovarian cancer. Eleven of the 17 received platinum compounds and other alkylating agents with or without DNA topoisomerase II inhibitors and/or radiation. Six received other alkylating agents, in one case, with radiation. Genomic DNA was extracted and p53 exons 5, 6, 7, and 8 were amplified by PCR. Mutations and loss of heterozygosity were analyzed on the WAVE instrument (Transgenomic) followed by selected analysis by sequencing. Results: Eleven p53 mutations involving all four exons studied and one polymorphism were identified. Genomic DNA analyses were consistent with loss of heterozygosity for four of the mutations. The 11 mutations occurred in 9 cases, such that 6 of 11 leukemias after platinum-based regimens (55%) and 3 of 6 leukemias after other treatments (50%) contained p53 mutations. Two leukemias that occurred after treatment with platinum analogues contained two mutations. Among eight mutations in leukemias after treatment with platinum analogues, there were four G-to-A transitions and one G-to-C transversion. Conclusions: p53 mutations are common in leukemia and myelodysplastic syndrome after multiagent therapy for ovarian cancer. The propensity for G-to-A transitions may reflect specific DNA damage in leukemias after treatment with platinum analogues. C1 Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Karolinska Inst, Karolinska Univ Hosp, SE-17777 Stockholm, Sweden. Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON MG5 1X8, Canada. New Jersey Dept Hlth & Senior Serv, Trenton, NJ 08625 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. Univ Helsinki, Cent Hosp, FIN-00290 Helsinki, Finland. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland. Canc Care Ontario, Toronto, ON M5G 2L7, Canada. RP Felix, CA (reprint author), Childrens Hosp Philadelphia, Div Oncol, Leonard & Madlyn Abramson Pediat Res Bldg,Room 90, Philadelphia, PA 19104 USA. RI Bergfeldt, Kjell/C-3581-2012 FU NCI NIH HHS [CA85469, N01-CP-50134, CA77683, CA80175] NR 69 TC 20 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 973 EP 985 PG 13 WC Oncology SC Oncology GA 551EY UT WOS:000175547700006 PM 12006509 ER PT J AU Frankel, AE Powell, BL Hall, PD Case, LD Kreitman, RJ AF Frankel, AE Powell, BL Hall, PD Case, LD Kreitman, RJ TI Phase I trial of a novel diphtheria toxin/granulocyte macrophage colony-stimulating factor fusion protein (DT(388)GMCSF) for refractory or relapsed acute myeloid leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; RECOMBINANT IMMUNOTOXIN; TOXIN; INTERLEUKIN-18; CANCER; CELLS; EXPRESSION; SURVIVAL; RECEPTOR; DTGM AB Purpose: Patients with relapsed or refractory acute myeloid leukemia have a poor prognosis. We tested the safety and efficacy of a diphtheria fusion protein [diphtheria toxin (DT)(388) granulocyte-macrophage colony-stimulating factor (GMCSF)] directed against the GMCSF receptor that is strongly expressed by leukemic blasts. Experimental Design: DT(388)GMCSF fusion protein containing the catalytic and translocation domains of DT388 fused to human GMCSF was administered in an interpatient dose escalation trial by 15 min i.v. infusion daily for up to 5 days. Results: The maximal tolerated dose was 4 mug/kg/day. The dose-limiting toxicity was liver injury and occurred at the 4.5-5-mug/kg/day dose level. Among nine treated patients at these doses, one patient developed liver failure, and one patient had transient hepatic encephalopathy. There was a positive correlation between peak serum DT(388)GMCSF levels and serum aspartate aminotransferase (P = 0.0002). DT(388)GMCSF did not damage hepatic cell lines in vitro; however, DT(388)GMCSF binds macrophages and induces cytokine release in vitro. Among the treated patients, we observed an early elevation in serum levels of interleukin (IL)-18 and a later rise in IL-8 but no significant changes in IL-1beta, IL-6, IFNgamma, macrophage inflammatory protein-1alpha, tumor necrosis factor a or IL-12. The IL-18 elevations occurred before elevations of liver enzymes and correlated with peak aspartate aminotransferase levels (P = 0.005). Of the 31 patients who were resistant to chemotherapy, I had a complete remission and 2 had partial remissions; all 3 of these patients were treated at or above the maximal tolerated dose, all 3 responding patients had baseline marrow blast percentage of <30%, whereas only 6 of the non-responding 28 patients had less than 30% marrow blasts. Five of these six patients were treated with subtherapeutic doses. Eight (42%) of 19 patient courses at <4 mug/kg/day and 8 (40%) of 20 patient courses at 4-5 mug/kg/day showed marrow blast reductions at day 12. Patients with higher pretreatment anti-DT(388)GMCSF levels had significantly lower peak DT(388)GMCSF levels (P = 0.0001). Conclusions: DT(388)GMCSF can produce complete and partial remissions in patients with chemotherapy-resistant acute myeloid leukemia, but methods to prevent liver injury are needed before more widespread application of this novel agent. C1 Wake Forest Univ, Bowman Gray Sch Med, Baptist Med Ctr, Winston Salem, NC 27157 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Frankel, AE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Baptist Med Ctr, Hanes 4046,Med Ctr Dr, Winston Salem, NC 27157 USA. FU NCI NIH HHS [1R01CA76178, 1R21CA90550]; NCRR NIH HHS [M01RR07122] NR 29 TC 98 Z9 113 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 1004 EP 1013 PG 10 WC Oncology SC Oncology GA 551EY UT WOS:000175547700009 PM 12006512 ER PT J AU Keith, B Guo, XD Zentko, S Harold, N Schuler, B Quinn, M Shapiro, J Grem, JL AF Keith, B Guo, XD Zentko, S Harold, N Schuler, B Quinn, M Shapiro, J Grem, JL TI Impact of two weekly schedules of oral eniluracil given with fluorouracil and leucovorin on the duration of dihydropyrimidine dehydrogenase inhibition SO CLINICAL CANCER RESEARCH LA English DT Article ID BLOOD MONONUCLEAR-CELLS; PHASE-I; 5-ETHYNYLURACIL 776C85; SOLID TUMORS; 5-FLUOROURACIL; INACTIVATOR; CANCER; PHARMACOKINETICS; SORIVUDINE; VIVO AB Purpose: This study determined the effect of different weekly dosing schedules of 5-fluorouracil (5-FU)/leucovorin (LV)/eniluracil on dihydropyrimidine dehydrogenase (DPD) activity and plasma uracil levels. Methods: Plasma and mononuclear cells were isolated from peripheral blood samples obtained before, during, and at various times after 5-FU/LV/eniluracil therapy. Two schedules were studied: 20 mg of eniluracil p.o. plus 30 mg of LV p.o. on days 1-3 with a single dose of 5-FU given day 2, or 30 mg of LV p.o. on days 1-2 with a single dose of eniluracil and 5-FU on day 2. DPD activity was determined with a radioisotopic enzyme assay; the reaction products were separated by high-performance liquid chromatography. Plasma uracil levels were determined by gas chromatography-mass spectroscopy. Results: During oral therapy, DPD activity was profoundly depressed, and uracil levels were strikingly elevated with both schedules. With the daily-for-3-days schedule, DPD activity was similar to baseline values by 3 weeks after the earlier eniluracil dose, whereas it appeared to recover earlier in patients receiving the single-dose schedule, reaching baseline values by 2 weeks. Although baseline uracil values did not predict DPD activity accurately, plasma uracil levels >0.95 muM were associated with significantly lower DPD activity (median, 18.4 versus 287.6 pmol/min/mg). Conclusions: When eniluracil is given with 5-FU/LV, DPD inhibition appears to be influenced by schedule, and the time to recovery is much longer than has been observed with eniluracil given alone. C1 NCI, Navy Med Oncol, Natl Naval Med Ctr, Canc Therapeut Branch,Ctr Canc Res, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), NCI, Navy Med Oncol, Natl Naval Med Ctr, Canc Therapeut Branch,Ctr Canc Res, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 32 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 1045 EP 1050 PG 6 WC Oncology SC Oncology GA 551EY UT WOS:000175547700014 PM 12006517 ER PT J AU Chan, DC Gera, L Stewart, JM Helfrich, B Zhao, TLM Feng, WY Chan, KK Covey, JM Bunn, PA AF Chan, DC Gera, L Stewart, JM Helfrich, B Zhao, TLM Feng, WY Chan, KK Covey, JM Bunn, PA TI Bradykinin antagonist dimer, CU201, inhibits the growth of human lung cancer cell lines in vitro and in vivo and produces synergistic growth inhibition in combination with other antitumor agents SO CLINICAL CANCER RESEARCH LA English DT Article ID GASTRIN-RELEASING PEPTIDE; IN-VIVO; NEUROPEPTIDE; EXPRESSION; RECEPTORS; PHENOTYPE; THERAPY AB Small cell lung cancers (SCLCs), many non-SCLCs, and other cancers have neuroendocrine features, including paracrine and autocrine growth stimulation by various neuropeptides. Interference with this pathway is an attractive target for novel therapies. We developed a novel bradykinin antagonist dimer, CU201 (B9870), that acts as a "biased agonist" for neuropeptides by blocking G(alphaq) signaling and activating G(alpha12,13) signaling. CU201 induced apoptosis and complete growth inhibition in various lung cancer and other cancer cell lines. CU201 was 10-fold more potent than substance P derivatives and was stable in serum for >7 days. In this study, we evaluated the ability of CU201 to produce additive or synergistic growth inhibition in combination with various antitumor agents used in lung cancer therapy. We found that CU201 produced additive or synergistic growth inhibition when combined with doxorubicin, etoposide, cisplatin, vinorelbine, and paclitaxel for SCLC lines and with paclitaxel and ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, for non-SCLC cell lines. Pharmacokinetic parameters associated with the i.v. administration of CU201 were evaluated in normal mice, and the effects of CU201 on the growth of human lung cancer xenografts were evaluated in athymic nude mice. In CD2F1 mice given an i.v. bolus infusion of 5 mg/kg, the c(max) was 5773 ng/ml (5 muM), and the decay was biexponential. When fitted to a two-compartment model, the t(1/2alpha) was 14.4 min, and the t(1/2beta) was 44.3 h, indicating a long terminal half-life consistent with the prolonged in vitro effects. CU201 inhibited the growth of human lung cancers in athymic nude mice by the intratumoral, s.c., and i.p. routes at a dose of 5 mg/kg/day. This dose is >10-fold less than the dose of substance P derivatives used to inhibit SCLC xenografts in nude mice. We conclude that CU201 should undergo further preclinical toxicology studies in its development as a novel targeted therapy for the treatment of lung cancers with neuroendocrine features. These studies are in progress through the NCI RAID mechanism. C1 Univ Colorado, Ctr Canc, Lung Canc Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80262 USA. Ohio State Univ, Coll Pharm, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. Carcinex Inc, Boulder, CO 80301 USA. RP Chan, DC (reprint author), Univ Colorado, Ctr Canc, Lung Canc Program, Box B171,4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [1R43CA86581-01, N01-CM07019, CA 46934, CA58187] NR 33 TC 35 Z9 37 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 1280 EP 1287 PG 8 WC Oncology SC Oncology GA 551EY UT WOS:000175547700046 PM 12006549 ER PT J AU Arcos-Burgos, M Castellanos, FX Lopera, F Pineda, D Palacio, JD Garcia, M Henao, GC Palacio, LG Berg, K Bailey-Wilson, JE Muenke, M AF Arcos-Burgos, M Castellanos, FX Lopera, F Pineda, D Palacio, JD Garcia, M Henao, GC Palacio, LG Berg, K Bailey-Wilson, JE Muenke, M TI Attention-deficit/hyperactivity disorder (ADHD): feasibility of linkage analysis in a genetic isolate using extended and multigenerational pedigrees SO CLINICAL GENETICS LA English DT Article DE attention-deficit/hyperactivity disorder; ADHD; behavior; complex trait; genetic homogeneity; genetic isolate; genetic linkage analysis ID DEFICIT HYPERACTIVITY DISORDER; INTERNATIONAL DIAGNOSTIC INTERVIEW; UTAH RATING-SCALE; FAMILIAL ASSOCIATION; SEGREGATION ANALYSIS; COLOMBIA; POPULATION; COMMUNITY; SYMPTOMS; MUTATION AB Segregation analyses converge in explaining the predisposition to attention-deficit/hyperactivity disorder (ADHD) as the consequence of a major gene and exclude purely environmental or cultural transmission. As a result of the ADHD phenotype restrictions, collection of extended families or design of linkage studies using families has been extremely difficult and thus currently linkage studies have been performed using only concordant or discordant sib-pairs rather than large families. On the other hand, intergenerational studies are represented by the transmission disequilibrium test (TDT) using trios. We collected pedigree data on ADHD from the Paisa community from Antioquia, Colombia, a genetic isolate. The goal of this study was to genetically map a putative gene predisposing to ADHD in a set of 27 multigenerational Paisa families. Here we present the results of a power simulation using SIMLINK to detect linkage of ADHD. ADHD was assumed to be a dichotomous trait with incomplete penetrance and a phenocopy rate of 3% in males and 0.2% in females. We simulated cosegregation of the trait and a marker locus in our pedigrees. We assumed Hardy-Weinberg and linkage equilibrium, equally frequent marker alleles and evaluated power at several recombination fractions between the trait and marker loci. Also, the ADHD trait was assumed to be genetically heterogeneous and different functions of age-dependent penetrance were simulated. We found exceptionally good power to detect linkage (expected LOD > 14 if theta is 0.1 or less), and that the presence of heterogeneity up to 50% does not affect substantially the projected LOD scores even for a theta recombination value of 0.05 (eLOD > 5.87). Having now obtained blood samples and confirmatory interviews in five families (representing 20% of the projected number of families), we performed a new analysis. The expected mean LOD in these five families reached values close to 10 and remained invariant when heterogeneity and different penetrance models were considered. We discuss the relative benefits of using extended and multigenerational families for genetic mapping studies as opposed to using nuclear families, affected sib pairs or sporadic cases which require the collection of over 1000 analytical units to get the same power exhibited by the small number of pedigrees described here. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Natl Inst Mental Hlth, NIH, Bethesda, MD 20892 USA. Univ Antiquia, Neurosci Grp, Medellin, Colombia. Univ Antioquia, Populat Genet Mutacarcinogenesis & Genet Epidemio, Medellin, Colombia. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Rm 10C103, Bethesda, MD 20892 USA. RI Garcia-Barrera, Mauricio/H-3850-2016; OI Garcia-Barrera, Mauricio/0000-0002-4302-4964; Palacio, Juan David/0000-0002-1584-4391; Bailey-Wilson, Joan/0000-0002-9153-2920 NR 51 TC 24 Z9 24 U1 4 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2002 VL 61 IS 5 BP 335 EP 343 DI 10.1034/j.1399-0004.2002.610503.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 569CQ UT WOS:000176583100005 PM 12081716 ER PT J AU Rosenzweig, SD Holland, SM AF Rosenzweig, SD Holland, SM TI Untitled SO CLINICAL IMMUNOLOGY LA English DT Letter C1 NIAID, Host Def Lab, Clin Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. RP Rosenzweig, SD (reprint author), NIAID, Host Def Lab, Clin Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2002 VL 103 IS 2 BP 210 EP 210 DI 10.1006/clim.2002.5203 PG 1 WC Immunology SC Immunology GA 560KZ UT WOS:000176082400013 ER PT J AU Chirgwin, K Hafner, R Leport, C Remington, J Andersen, J Bosler, EM Roque, C Rajicic, N McAuliffe, V Morlat, P Jayaweera, DT Vilde, JL Luft, BJ AF Chirgwin, K Hafner, R Leport, C Remington, J Andersen, J Bosler, EM Roque, C Rajicic, N McAuliffe, V Morlat, P Jayaweera, DT Vilde, JL Luft, BJ CA AIDS Clinical Trials Grp 237 Agenc TI Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; AIDS; THERAPY; COMBINATION; PHARMACOKINETICS; TRIMETHOPRIM; CLINDAMYCIN; SUSPENSION; 566C80; VIRUS AB In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis. C1 SUNY, Dept Med, Brooklyn, NY USA. SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. NYU, New York, NY USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Palo Alto Med Fdn, Palo Alto, CA USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Miami, Coral Gables, FL 33124 USA. Hop Bichat Claude Bernard, Serv Malad Infect & Trop, F-75877 Paris 18, France. Hop St Andre, Serv Med Interne & Malad Infect, Bordeaux, France. RP Chirgwin, K (reprint author), Merck Res Labs, POB 4,UNB121, W Point, PA 19486 USA. OI Luft, Benjamin/0000-0001-9008-7004 NR 23 TC 47 Z9 54 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2002 VL 34 IS 9 BP 1243 EP 1250 DI 10.1086/339551 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539YR UT WOS:000174901600012 PM 11941551 ER PT J AU Samak, MJ Coronado, BE Greene, T Wang, SR Kusek, JW Beck, GJ Levey, AS AF Samak, MJ Coronado, BE Greene, T Wang, SR Kusek, JW Beck, GJ Levey, AS TI Cardiovascular disease risk factors in chronic renal insufficiency SO CLINICAL NEPHROLOGY LA English DT Article ID ISCHEMIC-HEART-DISEASE; BLOOD-PRESSURE; HYPERTENSION; FRAMINGHAM; FAILURE; COHORT; UREMIA AB Background: Coronary heart disease (CHD) is an important cause of morbidity and mortality in end-stage renal disease (ESRD). Prevention of CHD in ESRD requires identification and treatment of coronary risk factors in chronic renal insufficiency (CRI). Methods: We evaluated the prevalence of "traditional coronary risk factors" in CRI in 1,795 patients enrolled in the baseline period of Modification of Diet in Renal Disease (MDRD) Study. Using a cross-sectional design, we determined the relationship of these risk factors to the level of glomerular filtration rate (GFR) and proteinuria. We also predicted the CHD risk in the MDRD Study baseline cohort using the coronary point score. Results: 64.0% had blood pressure greater than or equal to 130/85 mmHg despite antihypertensive therapy. 64.2% had LDL cholesterol greater than or equal to 130 mg/dl, while 38.3% had HDL cholesterol < 35 mg/dl. After adjustment for age, gender and the presence of diabetes, GFR was inversely associated with systolic blood pressure and positively associated with HDL cholesterol, but not associated with total or LDL cholesterol. After adjustment for age, gender and the presence of diabetes, proteinuria was positively associated with systolic and diastolic blood pressure, total serum cholesterol and LDL cholesterol, and inversely associated with HDL cholesterol. Nonetheless, the predicted CHD risk, even at a very low GFR, was similar to the risk in the general population and lower than the observed rate of de novo CHD in incident dialysis patients. Conclusions: "Traditional coronary risk factors" are highly prevalent in CRI and vary with the level of renal function. However, the coronary point score does not appear to explain the extent of increased CHD risk in ESRD. Non-traditional risk factors may also contribute to CHD in ESRD. C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. RP Samak, MJ (reprint author), Tufts Univ New England Med Ctr, 750 Washington St, Boston, MA 02111 USA. FU NIDDK NIH HHS [K23 NIDDK 02904-01] NR 18 TC 34 Z9 46 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD MAY PY 2002 VL 57 IS 5 BP 327 EP 335 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 546HK UT WOS:000175268500001 PM 12036190 ER PT J AU Mayer-Proschel, M Liu, Y Xue, HP Wu, YY Carpenter, MK Rao, MS AF Mayer-Proschel, M Liu, Y Xue, HP Wu, YY Carpenter, MK Rao, MS TI Human neural precursor cells - an in vitro characterization SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the Association-for-Research-in-Nervous-and-Mental-Diseases CY NOV 30-DEC 01, 2001 CL NEW YORK, NEW YORK SP Charles A Dana Fdn, Abbott Labs, Aventis Pharmaceut, Bristol Myers Squibb Pharmaceut Res Inst, GlaxoSmithKline, Janssen Pharmaceutica, Merck Res Labs, Neuronyx, Organon Pharmaceut, Pfizer Pharmaceut Grp, Pharmacia, Sanofi Synthelabo Res DE neuroepithelial precursor cells; E-NCAM; self-renewal; neuroblast; A2B5; development; astrocyte; oligodendrocyte; neuron ID CENTRAL-NERVOUS-SYSTEM; EMBRYONIC STEM-CELLS; OLIGODENDROCYTE PROGENITOR CELLS; ADULT HUMAN BRAIN; HUMAN FETAL BRAIN; IN-VITRO; SPINAL-CORD; WHITE-MATTER; RESTRICTED PRECURSORS; NEURONAL PRECURSORS AB We have compared the properties of human neural precursors isolated from fetal tissue with progenitor and precursor cells identified from rodent fetal tissue and human excretory/secretory (ES) cells. We have identified multipotent human neuroepithelial precursor cells (hNEPs) that are fibroblast growth factor dependent, grow in adherent culture, and differentiate into neurons, astrocytes, and oligodendrocytes in mass and clonal cultures. A subset of these multipotent cells express an antigen recognized by the AC133/2 antibody. hNEPs appear similar to rodent-derived NEP cells, and unlike other human multipotent precursor cell populations, do not require Leukemia Inhibitory Factor (LIF) or Epithelial Growth Factor (EGF) for their survival. hNEPs constitute a small fraction of the cells present at any stage examined and three additional dividing populations can be identified based on expression of epitopes recognized by E-NCAM, A2B5 and CD44. E-NCAM + cells co-express neuronal markers and can differentiate into multiple classes of neurons. Two types of A2B5 + cells can be distinguished: a small neuronal population that co-expresses E-NCAM immunoreactivity and a larger glial population that is E-NCAM negative. CD44 + cells do not express neuronal markers or oligodendrocytic markers but co-express astrocytic markers and likely represent an astrocyte precursor cell. Dividing E-NCAM +, A2B5 + and CD44 + cells can be identified in differentiating human ES cell cultures and the properties of these cells appear similar to cells present in fetal tissue. Published by Elsevier Science B.V. C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Rochester, Dept Biomed Genet, Rochester, NY 14642 USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. Geron Corp, Menlo Pk, CA 94025 USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 74 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD MAY PY 2002 VL 2 IS 1-2 BP 58 EP 69 AR PII S1566-2772(02)00007-5 DI 10.1016/S1566-2772(02)00007-5 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 592NY UT WOS:000177944800007 ER PT J AU Abernethy, DR AF Abernethy, DR TI Loratadine/nefazodone interaction - Reply SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID K+ CHANNELS; TERFENADINE; LORATADINE C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Abernethy, DR (reprint author), NIA, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 2002 VL 71 IS 5 BP 403 EP 403 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 552ZL UT WOS:000175650300013 ER PT J AU Zarchin, N Meilin, S Rifkind, J Mayevsky, A AF Zarchin, N Meilin, S Rifkind, J Mayevsky, A TI Effect of aging on brain energy-metabolism SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the International-Society-of-Oxygen-Transport CY AUG 20-25, 2000 CL NIJMEGEN, NETHERLANDS SP Int Soc Oxygen Transport DE aging brain; anoxia; cerebral blood flow; metabolic oscillations; mitochondrial NADH; multiparameter monitoring AB The aging process involves morphological and functional changes in cerebral vasculature and deterioration of mitochondrial number and function. Furthermore, slow oscillations of cerebral blood flow and oxidative metabolism occur in animals under different pathological conditions such as ischemia. The aim of this study was to evaluate the effect of aging on energy-metabolism of the rat brain during anoxia and nom-loxia and to further investigate the occurrence of oscillations under normoxia in the aging brain. Simultaneous hemodynamical (CBF), biochemical (NADH/ NAD ratio) and electrical activity from the cerebral cortex were measured by means of a multiparametric assembly (MPA) system. Exposure of adult rats to anoxia (100% N-2) resulted in a 36 +/- 2%, elevation of NADH. Furthrmore, exposure of the aged group to anoxia caused NADH elevation as low as 9.6 +/- 4% (P < 0.05). The changes in the NADH levels were followed by an increase in CBE In addition, during the normoxic periods, hemodynamic oscillations were recorded in the old animals. This study suggests that the structural and functional changes that occur in vessels in the aging brain cause disability of cerebromicrovessels to optimally deliver nutrients and oxygen to the brain, affecting the mitochondrial ability to respond to anoxia. Furthermore, this study supports the approach that the hemodynamic oscillations are related to the development of a pathological state and are not a normal cerebral function. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIA, Gerontol Res Ctr, LCMB, NIH, Baltimore, MD 21224 USA. RP Mayevsky, A (reprint author), Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NR 11 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD MAY PY 2002 VL 132 IS 1 BP 117 EP 120 AR PII S1095-6433(01)00537-2 DI 10.1016/S1095-6433(01)00537-2 PG 4 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 559PD UT WOS:000176033800016 PM 12062199 ER PT J AU Wang, XS Chen, JX Carr, DB Bell, BS Pickle, LW AF Wang, XS Chen, JX Carr, DB Bell, BS Pickle, LW TI Geographic statistics visualization: Web-based linked micromap plots SO COMPUTING IN SCIENCE & ENGINEERING LA English DT Article C1 George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA. NCI, Bethesda, MD 20892 USA. RP Wang, XS (reprint author), George Mason Univ, Dept Comp Sci, Fairfax, VA 22030 USA. NR 4 TC 6 Z9 7 U1 0 U2 4 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1521-9615 J9 COMPUT SCI ENG JI Comput. Sci. Eng. PD MAY-JUN PY 2002 VL 4 IS 3 BP 90 EP 94 DI 10.1109/5992.998645 PG 5 WC Computer Science, Interdisciplinary Applications SC Computer Science GA 543YL UT WOS:000175131400013 ER PT J AU Boulanger, A Redmond, TM AF Boulanger, A Redmond, TM TI Expression and promoter activation of the Rpe65 gene in retinal pigment epithelium cell lines SO CURRENT EYE RESEARCH LA English DT Article DE RPE65; retinal pigment epithelium; cell lines; gene expression; gene promoter ID LEBER CONGENITAL AMAUROSIS; BETA-CAROTENE; MICROSOMAL PROTEIN; IN-VITRO; IDENTIFICATION; TRANSCRIPTION; MUTATIONS; RNA; REGION AB Purpose. To examine the expression and promoter activation of the retinal pigment epithelium (RPE)-preferentially expressed Rpe65 gene in the commonly available RPE cell lines. Methods. Reverse transcription coupled to polymerase chain reaction (RT-PCR) was performed after total RNA extraction from different RPE (ARPE-19, monkey, hTERT-RP1 and D407) and non-RPE (COS-7, HeLa, HepG2 and HS27) cell lines. Promoter activity was assayed by transient transfection of luciferase reporter constructs containing nested deletions of the 5' flanking region of the mouse Rpe65 gene. The involvement of a putative TATA box in the basal promoter expression was studied by site-directed mutagenesis in D407 cells and binding of TATA box-related transcription factors to that region was demonstrated by Electrophoretic Mobility Shift Assays (EMSA). Results. Expression of the human RPE65 cDNA was observed in all the RPE cell lines tested, and in COS-7 cells (monkey RPE65 cDNA). Transient transfections of the mouse Rpe65 promoter/luciferase transgene containing nested deletions of the Rpe65 5' flanking region showed that fragments containing bases -655 to +48 and -1240 to +48 generated specific promoter activity only in the D407 cell line. A promoter fragment from -49 to +48 directed basal promoter activity in all the cell lines tested. Part of this basal activity was due to a putative TATA box that specifically binds transcription factors contained in a D407 nuclear extract. Conclusion. Although transcription of the Rpe65 gene occurs in all the tested cell lines, we find that the D407 cell line is the only one capable of directing specific mouse Rpe65 promoter activity. This limits the study of the transcriptional regulation of the mouse Rpe65 gene in vitro to this particular cell line. C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. RP Redmond, TM (reprint author), NEI, LRCMB, NIH, Bldg 6,Rm 339,6 Ctr Dr Msc 2740, Bethesda, MD 20892 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 21 TC 9 Z9 11 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 2002 VL 24 IS 5 BP 368 EP 375 DI 10.1076/ceyr.24.5.368.8523 PG 8 WC Ophthalmology SC Ophthalmology GA 611UJ UT WOS:000179035900005 PM 12434305 ER PT J AU Itoh, M Kudoh, T Dedekian, M Kim, CH Chitnis, AB AF Itoh, M Kudoh, T Dedekian, M Kim, CH Chitnis, AB TI A role for iro1 and iro7 in the establishment of an anteroposterior compartment of the ectoderm adjacent to the midbrain-hindbrain boundary SO DEVELOPMENT LA English DT Article DE midbrain-hindbrain boundary; trigeminal ganglia; neural crest; patterning; compartment; morpholino; zebrafish ID IROQUOIS HOMEOBOX GENES; NEURAL PLATE; VERTEBRATE DEVELOPMENT; ORGANIZER FORMATION; ECTOPIC EXPRESSION; DEVELOPING HEART; XENOPUS HOMOLOG; NERVOUS-SYSTEM; ZEBRAFISH; DROSOPHILA AB We have identified a novel Iroquois (Iro) gene, iro7, in zebrafish. iro7 is expressed during gastrulation along with iro1 in a compartment of the dorsal ectoderm that includes the prospective midbrain-hindbrain domain, the adjacent neural crest and the trigeminal placodes in the epidermis. The iro1 and iro7 expression domain is expanded in headless and masterblind mutants, which are characterized by exaggerated Wnt signaling. Early expansion of iro1 and iro7 expression in these mutants correlates with expansion of the midbrain-hindbrain boundary (MHB) domain, the neural crest and trigeminal neurons, raising the possibility that iro1 and iro7 have a role in determination of these ectodermal derivatives. A knockdown of iro7 function revealed that iro7 is essential for the determination of neurons in the trigeminal placode. In addition, a knockdown of both iro1 and iro7 genes uncovered their essential roles in neural crest development and establishment of the isthmic organizer at the MHB. These results suggest a new role for Iro genes in establishment of an ectodermal compartment after Wnt signaling in vertebrate development. Furthermore, analysis of activator or repressor forms of iro7 suggests that iro1 and iro7 are likely to function as repressors in establishment of the isthmic organizer and neural crest, and Iro genes may have dual functions as repressors and activators in neurogenesis. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Chitnis, AB (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM chitnisa@mail.nih.gov NR 58 TC 78 Z9 78 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD MAY PY 2002 VL 129 IS 10 BP 2317 EP 2327 PG 11 WC Developmental Biology SC Developmental Biology GA 560CF UT WOS:000176063600001 PM 11973265 ER PT J AU Lespinet, O Nederbragt, AJ Cassan, M Dictus, WJAG van Loon, AE Adoutte, A AF Lespinet, O Nederbragt, AJ Cassan, M Dictus, WJAG van Loon, AE Adoutte, A TI Characterisation of two snail genes in the gastropod mollusc Patella vulgata. Implications for understanding the ancestral function of the snail-related genes in Bilateria SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE mesoderm formation; snail/slug and scratch gene family; mollusc; Patella vulgata; epithelial-mesenchymal transitions (EMT) ID ZINC-FINGER GENE; TRANSCRIPTION FACTOR SNAIL; PROSPECTIVE NEURAL CREST; DROSOPHILA-MELANOGASTER; PROTEIN SEQUENCES; ANIMAL PHYLOGENY; MUTANT EMBRYOS; WILD-TYPE; EXPRESSION; MESODERM AB Snail genes have been found to play a role in mesoderm formation in two of the three clades of bilaterians, deuterostomes (comprising the chordates) and ecdysozoans (comprising the arthropods). No clear data are available on the role these genes play in development of the mesoderm in the third clade, that of lophotrochozoans (comprising annelids and molluscs). We identified two new members of the snail gene family in the gastropod mollusc Patella vulgata. Phylogenetic analysis showed that the two genes clearly belong to the snail sub-family. Their expression patterns do not indicate a role during early mesoderm formation. In fact, contrary to expectations, the snail genes of Patella were mostly expressed in the ectoderm. In view of the location of their expression sites, we suggest that these genes could be involved in regulating epithelial-mesenchymal transitions (EMT) and cell motility, as has recently been demonstrated for snail genes in vertebrates. This may well correspond to the ancestral function of these genes. The results are discussed in the light of the evolutionary origin of the mesoderm. Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/10.1007/s00427-002-0228-1. C1 CNRS, Ctr Genet Mol, UPR 2167, F-91198 Gif Sur Yvette, France. Univ Utrecht, Dept Dev Biol, NL-3584 Utrecht, Netherlands. RP Lespinet, O (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Lespinet, Olivier/C-1235-2008; Nederbragt, Alexander/B-8013-2010 OI Lespinet, Olivier/0000-0002-4961-7461; Nederbragt, Alexander/0000-0001-5539-0999 NR 60 TC 22 Z9 22 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD MAY PY 2002 VL 212 IS 4 BP 186 EP 195 DI 10.1007/s00427-002-0228-1 PG 10 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 560DB UT WOS:000176065800003 PM 12012233 ER PT J AU West-Mays, JA Coyle, BM Piatigorsky, J Papagiotas, S Libby, D AF West-Mays, JA Coyle, BM Piatigorsky, J Papagiotas, S Libby, D TI Ectopic expression of AP-2 alpha transcription factor in the lens disrupts fiber cell differentiation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE differentiation; lens; AP-2 alpha transcription factor; cell adhesion ID MAJOR INTRINSIC PROTEIN; FACTOR AP-2; EPITHELIAL-CELLS; MOUSE LENS; E-CADHERIN; CRYSTALLIN GENE; TRANSGENIC MICE; MYC PROTEIN; N-CADHERIN; ADHESION AB AP-2alpha is a developmentally important transcription factor which has been implicated in the regulation of cell growth, programmed cell death, and differentiation. To investigate the specific function of AP-2alpha in differentiation of the lens, AP-2alpha was expressed in the differentiating lens fiber cells under control of the alphaA-crystallin promoter. Normally, AP-2alpha is selectively expressed in lens epithelial cells and expression terminates at the lens equator, where epithelial cells terminally differentiate into fiber cells. Ectopic expression of the AP-2alpha gene in the fiber cell compartment resulted in bilateral cataracts and microphthalmia in mice by 2 weeks of age. Histological evaluation of embryonic and adult transgenic lenses revealed a significant reduction in lens size and anterior shifting of the transitional zone. Two aspects of fiber cell differentiation were also blocked, including the migration of newly formed fiber cells and an inhibition in fiber cell denucleation. Correlated with these defects were expanded expression of E-cadherin in the lens transitional zone and reduced expression of the fiber cell-specific protein MIP (major intrinsic protein). Together, these data demonstrate that AP-2alpha acts as a negative regulator of terminal fiber cell differentiation through the regulation of genes involved in cell adhesion and migration. (C) 2002 Elsevier Science (USA). C1 Tufts Univ, New England Med Ctr, Dept Ophthalmol, Boston, MA 02111 USA. Tufts Univ, Ctr Vis Res, Boston, MA 02111 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP West-Mays, JA (reprint author), Tufts Univ, New England Med Ctr, Dept Ophthalmol, 750 Washington St, Boston, MA 02111 USA. FU NEI NIH HHS [R01 EY011910-04, R01 EY011910, EY 11910, R01 EY011910-03, R01 EY011910-05A1, EY12651, P30 EY13078, R01 EY011910-02] NR 50 TC 32 Z9 32 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 2002 VL 245 IS 1 BP 13 EP 27 DI 10.1006/dbio.2002.0624 PG 15 WC Developmental Biology SC Developmental Biology GA 548EV UT WOS:000175376400002 PM 11969252 ER PT J AU Luo, T Matsuo-Takasaki, M Thomas, ML Weeks, DL Sargent, TD AF Luo, T Matsuo-Takasaki, M Thomas, ML Weeks, DL Sargent, TD TI Transcription factor AP-2 is an essential and direct regulator of epidermal development in Xenopus SO DEVELOPMENTAL BIOLOGY LA English DT Article DE bone morphogenetic protein; gastrulation; antisense oligonucleotide; epidermis ID NEURAL INDUCTION; GENE-EXPRESSION; DNA-BINDING; LAEVIS EMBRYOGENESIS; MOUSE EMBRYOGENESIS; DROSOPHILA HOMOLOG; EMBRYOS; COMPETENCE; INHIBITION; CLONING AB Expression of the Xenopus homolog of the mammalian transcription factor AP-2alpha (XAP-2) is activated throughout the animal hemisphere shortly after the midblastula transition, and becomes restricted to prospective epidermis by the end of gastrulation, under the control of BMP signal modulation. Elevated expression in the future neural crest region begins at this time. Ectopic expression of XAP-2 can restore transcription of epidermal genes in neuralized ectoderm, both in ectodermal explants and in the intact embryo. Likewise, loss of XAP-2 function, accomplished by injection of antisense oligonucleotides or by overexpression of antimorphic XAP-2 derivatives, leads to loss of epidermal and gain of neural gene expression. These treatments also result in gastrulation failure. Thus, AP-2 is a critical regulator of ectodermal determination that is required for normal epidermal development and morphogenesis in the frog embryo. (C) 2002 Elsevier Science (USA). C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. RP Sargent, TD (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RI Weeks, Daniel/F-6216-2010 FU NHLBI NIH HHS [HL 42252] NR 48 TC 75 Z9 77 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 2002 VL 245 IS 1 BP 136 EP 144 DI 10.1006/dbio.2002.0621 PG 9 WC Developmental Biology SC Developmental Biology GA 548EV UT WOS:000175376400011 PM 11969261 ER PT J AU Sordella, R Classon, M Hu, KQ Matheson, SF Brouns, MR Fine, B Zhang, L Takami, H Yamada, Y Settleman, J AF Sordella, R Classon, M Hu, KQ Matheson, SF Brouns, MR Fine, B Zhang, L Takami, H Yamada, Y Settleman, J TI Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development SO DEVELOPMENTAL CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; CAMP RESPONSE ELEMENT; INSULIN-RECEPTOR; BINDING PROTEIN; P190 RHOGAP; ROK-ALPHA; I GENE; GROWTH; INDUCTION; FAMILY AB Rho GTPases regulate several aspects of tissue morphogenesis during animal development. We found that mice lacking the Rho-inhibitory protein, p190-B RhoGAP, are 30% reduced in size and exhibit developmental defects strikingly similar to those seen in mice lacking the CREB transcription factor. In p190-B RhoGAP-deficient mice, CREB phosphorylation is substantially reduced in embryonic tissues. Embryo-derived cells contain abnormally high levels of active Rho protein, are reduced in size, and exhibit defects in CREB activation upon exposure to insulin or IGF-1. The cell size defect is rescued by expression of constitutively activated CREB, and in wild-type cells, expression of activated Rho or dominant-negative CREB results in reduced cell size. Together, these results suggest that activity of the Rho GTPase modulates a signal from insulin/IGFs to CREB that determines cell size and animal size during embryogenesis. C1 MGH Canc Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Settleman, J (reprint author), MGH Canc Ctr, Charlestown, MA 02129 USA. OI Matheson, Stephen/0000-0003-0561-8152 NR 46 TC 92 Z9 93 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY PY 2002 VL 2 IS 5 BP 553 EP 565 DI 10.1016/S1534-5807(02)00162-4 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 552CW UT WOS:000175601600009 PM 12015964 ER PT J AU Ito, Y Bringas, P Mogharei, A Zhao, JS Deng, CX Chai, Y AF Ito, Y Bringas, P Mogharei, A Zhao, JS Deng, CX Chai, Y TI Receptor-regulated and inhibitory Smads are critical in regulating transforming growth factor beta-mediated Meckel's cartilage development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Meckel's cartilage; Smad2; Smad7; TGF-beta signaling ID MAD-RELATED PROTEIN; TOOTH DEVELOPMENT; NEURAL CREST; EXPRESSION; MICE; SKELETAL; LACKING; MORPHOGENESIS; ANTAGONIST; EFFECTORS AB The proper development of Meckel's cartilage is critical for craniofacial skeletogenesis, because it serves as the primordium for the formation of mandible, malleus, incus, and sphenomandibular ligament. Cranial neural crest (CNC) cells contribute significantly to the formation of Meckel's cartilage. Members of the transforming growth factor beta (TGF-beta) family control the proliferation and differentiation of CNC cells during craniofacial skeletogenesis. TGF-beta signaling is transduced from the cell membrane to the nucleus by means of specific type I and type II receptors and phosphorylated Smad proteins. Here we demonstrate that application of TGF-beta promotes chondrogenesis by specifically increasing proliferation of CNC-derived chondrocytes and production of extracellular matrix. To understand the molecular regulation of TGF-beta signaling, we have examined the biological function of both TGF-beta receptor-regulated and inhibitory Smads during Meckel's cartilage development. The expression patterns of Smad2, 3, and 7 are identical to the ones of endogenous TGF-beta and its cognate receptors during Meckel's cartilage development, establishing the potential that these intracellular signaling Smads may regulate TGF-beta-mediated chondrogenesis. Func tional haploinsufficiency of Smad2 delays TGF-beta-mediated Meckel's cartilage development. Overproduction of Smad7 severely inhibits Meckel's cartilage formation, indicating a negative feedback on TGF-beta signaling by inhibitory Smad is critical in orchestrating TGF-beta-mediated gene regulation during embryonic chondrogenesis. The effectiveness of TGF-beta signaling is highly sensitive to the level of Smad gene expression. (C) 2002 Wiley-Liss, Inc. C1 Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, Los Angeles, CA 90033 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. RP Chai, Y (reprint author), Univ So Calif, Ctr Craniofacial Mol Biol, Sch Dent, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA. RI deng, chuxia/N-6713-2016 FU NIDCR NIH HHS [DE 12711, DE 12941] NR 51 TC 46 Z9 52 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 2002 VL 224 IS 1 BP 69 EP 78 DI 10.1002/dvdy.10088 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 547BT UT WOS:000175313300007 PM 11984875 ER PT J AU DiPietro, JA Bornstein, MH Costigan, KA Pressman, EK Hahn, CS Painter, K Smith, BA Yi, LJ AF DiPietro, JA Bornstein, MH Costigan, KA Pressman, EK Hahn, CS Painter, K Smith, BA Yi, LJ TI What does fetal movement predict about behavior during the first two years of life.? SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE motor behavior; temperament; fetal movement ID MOTOR-ACTIVITY LEVEL; INDIVIDUAL-DIFFERENCES; SEX-DIFFERENCES; DOPPLER ACTOCARDIOGRAM; INFANT TEMPERAMENT; PRETERM INFANTS; STABILITY; ANTECEDENTS; CONTINUITY; PREGNANCY AB This study evaluated whether motor activity prior to birth is predictive of motor behavior and temperament in neonates, infants, and toddlers. Three measures of fetal motor activity (activity level, amplitude, and number of movements) were collected at 24, 30, and 36 it weeks of gestation in 52 healthy fetuses using Doppler-based actography. Postnatal data collection included a neurobehavioral assessment at 2-weeks postpartum (n = 41), and laboratory-based behavioral observations at 1 and 2 years of age (ns = 35). Individual stability in motor activity was present during gestation. Predictive relations between fetal movement and neonatal behavior were inconsistent: significant but small positive associations were detected between motor behavior at 36 weeks and neonatal irritability and motor development. Fetal activity level at 36 weeks was positively associated with observed 1-year activity level for boys (but inversely N- related for girls) and maternal report of activity level at 2 years. Fetal movement was consistently and negatively predictive of distress to limitations at 1 year and behavioral inhibition at 2 Years, accounting for 21 to 43% of the variance in these measures, Intrafetal variability in motor behavior make this a relatively unstable metric for prediction to neonatal maturational outcomes, which are relatively constrained, but fetal motor activin, appears to predict temperament attributes related to regulatory behaviors in early childhood. (C) 2002 Wiley Periodicals, Inc. C1 Johns Hopkins Univ, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. NICHHD, Bethesda, MD 20892 USA. Johns Hopkins Univ, Div Maternal Fetal Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Psychol, Baltimore, MD 21218 USA. RP DiPietro, JA (reprint author), Johns Hopkins Univ, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. OI Pressman, Eva/0000-0002-2556-9290 FU NICHD NIH HHS [R01 HD 27592, R01 HD027592] NR 56 TC 44 Z9 44 U1 6 U2 18 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD MAY PY 2002 VL 40 IS 4 BP 358 EP 371 DI 10.1002/dev.10025 PG 14 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 544RL UT WOS:000175174100002 PM 12115294 ER PT J AU Thierry, KL Spence, MJ AF Thierry, KL Spence, MJ TI Source-monitoring training facilitates preschoolers' eyewitness memory performance SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID CHILDRENS MEMORY; YOUNG-CHILDREN; DEVELOPMENTAL PATTERNS; FORENSIC INTERVIEWS; ANALOGICAL TRANSFER; FREE-RECALL; SUGGESTIBILITY; QUESTIONS; TESTIMONY; SUGGESTIONS AB Preschool children are more susceptible to misleading postevent information than are older children and adults. One reason for young children's suggestibility is their failure to monitor the source of their memories. as in, for example, discriminating whether an event was seen live versus on television, The authors investigated whether source - monitoring training would decrease preschoolers' suggestibility. Thirty-six 3-4-year-olds observed target five and video events and were then given source-monitoring or recognition (control) training on nontarget events. Following training, all children answered 24 misleading and nonmisleading target-event questions. Children given source-monitoring training were more accurate than control group children in response to misleading and nonmisleading yes-no questions and in response to nonmisleading, open-ended questions. Implications for strategy development, dual representation, and child witness interviewing are discussed. C1 Univ Texas, Sch Human Dev, Dallas, TX 75230 USA. RP Thierry, KL (reprint author), NICHHD, Sect Social & Emot Dev, Rockledge Ctr 1, 6705 Rockledge Dr,Suite 8048, Bethesda, MD 20892 USA. EM thierryk@mail.nih.gov NR 50 TC 26 Z9 28 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2002 VL 38 IS 3 BP 428 EP 437 DI 10.1037//0012-1649.38.3.428 PG 10 WC Psychology, Developmental SC Psychology GA 545LC UT WOS:000175217900008 PM 12005385 ER PT J AU Ilercil, A Devereux, RB Roman, MJ Paranicas, M O'Grady, MJ Lee, ET Welty, TK Fabsitz, RR Howard, BV AF Ilercil, A Devereux, RB Roman, MJ Paranicas, M O'Grady, MJ Lee, ET Welty, TK Fabsitz, RR Howard, BV TI Associations of insulin levels with left ventricular structure and function in American Indians - The Strong Heart Study SO DIABETES LA English DT Article ID BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ECHOCARDIOGRAPHIC ASSESSMENT; ESSENTIAL-HYPERTENSION; BODY-MASS; HYPERTROPHY; RESISTANCE; GEOMETRY; HYPERINSULINEMIA AB We evaluated the association of insulin and echocardiographic left ventricular (LV) measurements in 1,388 (45% men) nondiabetic American Indian participants in the Strong Heart Study (SHS). Significant (all P < 0.05) relations were found in men and women between log(10) fasting insulin and LV mass (r = 0.24 and 0.26), left atrial diameter (r = 0.25 and 0.28), posterior wall thickness (r = 0.20 and 0.26), septal thickness (r = 0.19 and 0.24), LV diameter (r = 0.17 and 0.16), and cardiac output (r = 0.20 and 0.24) and in women relative wall thickness (r = 0.11) and peripheral resistance (r = -0.17). In regression analyses, adjusting for BMI, age, height, and systolic pressure, fasting insulin was independently correlated with cardiac output in men and relative wall thickness and septal thickness in women (all P < 0.05). The 97th percentiles of fasting insulin (25 muU/ml for men, and 23 muU/ml for women) in 163 apparently normal (BMI < 26; blood pressure < 140/90; and absence of diabetes, valvular disease, LV wall motion abnormality, or antihypertensive treatment) SHS participants were used to separate normal from elevated fasting insulin levels. Adjusting for age, BMI, and height, men with elevated insulin levels had larger LV diameters (5.41 vs. 5.16 cm; P = 0.05), higher cardiac output (5.5 vs. 4.9 l/min; P < 0.001), and lower peripheral resistance (1,487 vs. 1,666; P = 0.01), paralleling results of regression analyses. Positive relations between insulin and heart size in nondiabetic adults are largely due to associations with body size; after adjustments for covariates, fasting insulin levels are related to greater LV size and cardiac output in men and more concentric LV geometry in women. C1 Albert Einstein Coll Med, Montefiore Med Ctr, Bronx, NY 10467 USA. Cornell Med Ctr, Dept Med, New York, NY USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. NHLBI, Bethesda, MD 20892 USA. MedStar Res Inst, Washington, DC USA. RP Devereux, RB (reprint author), New York Presbyterian Hosp, Weill Cornell Med Ctr, Div Cardiol, 525 E 68th St, New York, NY 10021 USA. NR 45 TC 48 Z9 50 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2002 VL 51 IS 5 BP 1543 EP 1547 DI 10.2337/diabetes.51.5.1543 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550FF UT WOS:000175492400030 PM 11978654 ER PT J AU Kovacs, P Yang, XL Permana, PA Bogardus, C Baier, LJ AF Kovacs, P Yang, XL Permana, PA Bogardus, C Baier, LJ TI Polymorphisms in the oxygen-regulated protein 150 gene (ORP150) are associated with insulin resistance in Pima Indians SO DIABETES LA English DT Article ID DIABETES-MELLITUS; EXPRESSION; SECRETION AB The ORP150 gene that encodes the human oxygen-regulated protein (150 kDa) maps to chromosome 11q23, a region previously reported to be linked to type 2 diabetes and obesity in Pima Indians. This gene was also found to be differentially expressed in global gene expression studies comparing muscle mRNA from insulin-resistant versus insulin-sensitive subjects. Therefore, ORP150 was analyzed as a candidate gene for susceptibility to diabetes. Twelve variants were identified, and three unique representative polymorphisms were genotyped in 1,338 Pima Indians. None of these polymorphisms were associated with diabetes, but two polymorphisms were significantly associated with measures insulin resistance. These data indicate that ORP150 has a role in insulin action but does not have a major role in determining susceptibility to type 2 diabetes in Pima Indians. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85016 USA. RP Baier, LJ (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix Epidemiol & Clin Res Branch, 4212 N 16th St, Phoenix, AZ 85016 USA. NR 15 TC 17 Z9 18 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2002 VL 51 IS 5 BP 1618 EP 1621 DI 10.2337/diabetes.51.5.1618 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550FF UT WOS:000175492400040 PM 11978664 ER PT J AU Fingerlin, TE Erdos, MR Watanabe, RM Wiles, KR Stringham, HM Mohlke, KL Silander, K Valle, TT Buchanan, TA Tuomilehto, J Bergman, RN Boehnke, M Collins, FS AF Fingerlin, TE Erdos, MR Watanabe, RM Wiles, KR Stringham, HM Mohlke, KL Silander, K Valle, TT Buchanan, TA Tuomilehto, J Bergman, RN Boehnke, M Collins, FS TI Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort SO DIABETES LA English DT Article ID SUSCEPTIBILITY LOCUS; INSULIN SENSITIVITY; MELLITUS; CHROMOSOME-2; POPULATION; REVEALS; FINLAND; SAMPLE AB Variations in the calpain-10 gene have recently been reported to be associated with type 2 diabetes in a Mexican-American population. We typed three single nucleotide polymorphisms (SNPs) in the calpain-10 gene (SNPs 43, 56, and 63) to test for association between variation at these loci and type 2 diabetes and diabetes-related traits in 1,603 Finnish subjects: two samples of 526 (Finland-U.S. Investigation of NIDDM Genetics [FUSION) 1) and 255 (FUSION 2) index case subjects with type 2 diabetes, 185 and 414 unaffected spouses and offspring of FUSION 1 index case subjects or their affected siblings, and 223 elderly normal glucose-tolerant control subjects. We found no significant differences in allele, genotype, haplotype, or haplogenotype frequencies between index case subjects with diabetes and the elderly and spouse control populations (all P > 0.087). Although variation in these three SNPs was associated with variation in some type 2 diabetes-related traits within each of the case and control groups, no consistent pattern of the implicated variant or combination of variants was discerned. We conclude that variation in these three SNPs in the calpain-10 gene is unlikely to confer susceptibility to type 2 diabetes in this Finnish cohort. C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Natl Inst Publ Hlth, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ So Calif, Dept Med, Keck Sch Med, Los Angeles, CA USA. Univ So Calif, Dept Physiol & Biophys, Keck Sch Med, Los Angeles, CA 90089 USA. RP Boehnke, M (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, 1420 Washington Heights, Ann Arbor, MI 48109 USA. FU NHGRI NIH HHS [HG00040]; NIDDK NIH HHS [DK09525, R01 DK029867, DK27619, DK29867] NR 12 TC 54 Z9 56 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2002 VL 51 IS 5 BP 1644 EP 1648 DI 10.2337/diabetes.51.5.1644 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550FF UT WOS:000175492400045 PM 11978669 ER PT J AU Ahvazi, B Kim, HC Kee, SH Nemes, Z Steinert, PM AF Ahvazi, B Kim, HC Kee, SH Nemes, Z Steinert, PM TI Three-dimensional structure of the human transglutaminase 3 enzyme: binding of calcium ions changes structure for activation SO EMBO JOURNAL LA English DT Article DE activation; calcium binding; transglutaminase; X-ray structure ID CORNIFIED CELL-ENVELOPE; COAGULATION FACTOR-XIII; CROSS-LINKING; EPIDERMAL-KERATINOCYTES; PROTRANSGLUTAMINASE-E; SUBSTRATE PROPERTIES; INCREASED EXPRESSION; PROTEIN; LORICRIN; TRICHOHYALIN AB Transglutaminase (TGase) enzymes catalyze the formation of covalent cross-links between protein-bound glutamines and lysines in a calcium-dependent manner, but the role of Ca2+ ions remains unclear. The TGase 3 isoform is widely expressed and is important for epithelial barrier formation. It is a zymogen, requiring proteolysis for activity. We have solved the three-dimensional structures of the zymogen and the activated forms at 2.2 and 2.1 Angstrom resolution, respectively, and examined the role of Ca2+ ions. The zymogen binds one ion tightly that cannot be exchanged. Upon proteolysis, the enzyme exothermally acquires two more Ca2+ ions that activate the enzyme, are exchangeable and are functionally replaceable by other lanthanide trivalent cations. Binding of a Ca2+ ion at one of these sites opens a channel which exposes the key Trp236 and Trp327 residues that control substrate access to the active site. Together, these biochemical and structural data reveal for the first time in a TGase enzyme that Ca2+ ions induce structural changes which at least in part dictate activity and, moreover, may confer substrate specificity. C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ahvazi, B (reprint author), NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 48 TC 67 Z9 68 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 2002 VL 21 IS 9 BP 2055 EP 2067 DI 10.1093/emboj/21.9.2055 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 548NG UT WOS:000175393700001 PM 11980702 ER PT J AU Abad, V Meyers, JL Weise, M Gafni, RI Barnes, KM Nilsson, O Bacher, JD Baron, J AF Abad, V Meyers, JL Weise, M Gafni, RI Barnes, KM Nilsson, O Bacher, JD Baron, J TI The role of the resting zone in growth plate chondrogenesis SO ENDOCRINOLOGY LA English DT Article ID LONGITUDINAL BONE-GROWTH; HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; INDIAN HEDGEHOG; CHONDROCYTE DIFFERENTIATION; HYPERTROPHIC CHONDROCYTES; POSTNATAL-GROWTH; RETINOIC ACID; PROLIFERATION; CARTILAGE AB In mammals, growth of long bones occurs at the growth plate, a catilage structure that contains three principal layers: the resting, proliferative, and hypertrophic zones. The function of the resting zone is not well understood. We removed the proliferative and hypertrophic zones from the rabbit distal ulnar growth plate in vivo, leaving only the resting zone. Within 1 wk, a complete proliferative and hypertrophic zone often regenerated. Next, we manipulated growth plates in vivo to place resting zone cartilage ectopically alongside the proliferative columns. Ectopic resting zone cartilage induced a 90-degree shift in the orientation of nearby proliferative zone chondrocytes and seemed to inhibit their hypertrophic differentiation. Our findings suggest that resting zone cartilage makes important contributions to endochondral bone formation at the growth plate: 1) it contains stem-like cells that give rise to clones of proliferative chondrocytes; 2) it produces a growth plate-orienting factor, a morphogen, that directs the alignment of the proliferative clones into columns parallel to the long axis of the bone; and 3) it may also produce a morphogen that inhibits terminal differentiation of nearby proliferative zone chondrocytes and thus may be partially responsible for the organization of the growth plate into distinct zones of proliferation and hypertrophy. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Karolinska Hosp & Inst, Astrid Lindgren Childrens Hosp, Dept Woman & Child Hlth, Pediat Endocrinol Unit Q2 08, SE-17176 Stockholm, Sweden. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 30 TC 119 Z9 128 U1 3 U2 10 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2002 VL 143 IS 5 BP 1851 EP 1857 DI 10.1210/en.143.5.1851 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544QB UT WOS:000175170500033 PM 11956168 ER PT J AU Hoppin, JA Brock, JW Davis, BJ Baird, DD AF Hoppin, JA Brock, JW Davis, BJ Baird, DD TI Reproducibility of urinary phthalate metabolites in first morning urine samples SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biologic markers; environmental exposure; phthalates; reliability; urine; women's health ID BUTYL BENZYL PHTHALATE; RATS; DI(2-ETHYLHEXYL)PHTHALATE; WOMEN AB Phthalates are ubiquitous in our modern environment because of their use in plastics and cosmetic products. Phthalate monoesters-primarily monoethylhexyl phthalate and monobutyl phthalateare reproductive and developmental toxicants in animals. Accurate measures of phthalate exposure a-re needed to assess their human health effects. Phthalate monoesters have a biologic half-life of approximately 12 hr, and little is known about the temporal variability and daily reproducibility of urinary measures in humans. To explore these aspects, we measured seven phthalate monoesters and creatinine concentration in two consecutive first-morning urine specimens from 46 African-American women, ages 35-49 years, residing in the Washington, DC, area in 1996-1997. We measured phthalate monoesters using high-pressure liquid chromatography followed by tandem mass spectrometry on a triple quadrupole instrument using atmospheric pressure chemical ionization. We detected four phthalate monoesters in all subjects, with median levels of 31 ng/mL for monobenzyl phthalate (mBzP), 53 ng/mL for monobutyl phthalate (mBP), 211 ng/mL for monoethyl phthalate (mEP), and 7.3 ng/mL for monoethylhexyl phthalate (mEHP). These were similar to concentrations reported for other populations using spot urine specimens. Phthalate levels did not differ between the two sampling days. The Pearson correlation coefficient between the concentrations on the 2 days was 0.8 for mBP, 0.7 for mEHP, 0.6 for mEP, and 0.5 for mBzP. These results suggest that even with the short half-lives of phthalates, women's patterns of exposure may be sufficiently stable to assign an exposure level based on a single first morning void urine measurement. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 27 TC 149 Z9 156 U1 5 U2 21 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2002 VL 110 IS 5 BP 515 EP 518 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 552NL UT WOS:000175626400027 PM 12003755 ER PT J AU Vojta, PJ Friedman, W Marker, DA Clickner, R Rogers, JW Viet, SM Muilenberg, ML Thorne, PS Arbes, SJ Zeldin, DC AF Vojta, PJ Friedman, W Marker, DA Clickner, R Rogers, JW Viet, SM Muilenberg, ML Thorne, PS Arbes, SJ Zeldin, DC TI First national survey of lead and allergens in housing: Survey design and methods for the allergen and endotoxin components SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE asthma; data collection; house dust mite; indoor allergens ID INNER-CITY CHILDREN; DER-P-I; FEL-D-I; INDOOR ALLERGENS; RISK-FACTORS; DUST MITE; F-I; COCKROACH ALLERGENS; LOS-ALAMOS; NEW-MEXICO AB From July 1998 to August 1999, the U.S. Department of Housing and Urban Development and the National Institute of Environmental Health Sciences conducted the first National Survey of Lead and Allergens in Housing. The purpose of the survey was to assess children's potential household exposure to lead, allergens, and bacterial endotoxins. We surveyed a sample of 831 homes, representing 96 million permanently occupied, noninstitutional housing units that permit resident children. We administered questionnaires to household members, made home observations, and took environmental samples. This article provides general background information on the survey, an overview of the survey design, and a description of the data collection and laboratory methods pertaining to the allergen and endotoxin components. We collected dust samples from a bed, the bedroom floor, a sofa or chair, the living room floor, the kitchen floor, and a basement floor and analyzed them for cockroach allergen Bla g 1, the dust mite allergens Der f 1 and Der p 1, the cat allergen Fel d 1, the dog allergen Can f 1, the rodent allergens Rat n 1 and mouse urinary protein, allergens of the fungus Alternaria alternata, and endotoxin. This article provides the essential context for subsequent reports that will describe the prevalence of allergens and endotoxin in U.S. households, their distribution by various housing characteristics, and their associations with allergic diseases such as asthma and rhinitis. C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. US Dept Housing & Urban Dev, Off Hlth Homes & Lead Hazard Control, Washington, DC USA. Westat Corp, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Iowa City, IA USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, 111 Alexander Dr,Mail Drop D2-02, Res Triangle Pk, NC 27709 USA. NR 32 TC 49 Z9 49 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2002 VL 110 IS 5 BP 527 EP 532 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 552NL UT WOS:000175626400030 PM 12003758 ER PT J AU Steinberg, K Beck, J Nickerson, D Garcia-Closas, M Gallagher, M Caggana, M Reid, Y Cosentino, M Ji, J Johnson, D Hayes, RB Earley, M Lorey, F Hannon, H Khoury, MJ Sampson, E AF Steinberg, K Beck, J Nickerson, D Garcia-Closas, M Gallagher, M Caggana, M Reid, Y Cosentino, M Ji, J Johnson, D Hayes, RB Earley, M Lorey, F Hannon, H Khoury, MJ Sampson, E TI DNA banking for epidemiologic studies: A review of current practices SO EPIDEMIOLOGY LA English DT Article DE biological specimen bank; cryopreservation; DNA; lymphocyte transformation; blood spots ID WHOLE GENOME AMPLIFICATION; SICKLE-CELL DISEASE; BASE-LINE CHARACTERISTICS; DRIED BLOOD SPECIMENS; FILTER-PAPER; GENETIC-ANALYSIS; NUCLEATED CELLS; CYSTIC-FIBROSIS; STORAGE; MOUTHWASH AB To study genetic risk factors for common diseases, researchers have begun collecting DNA specimens in large epidemiologic studies and surveys. However, little information is available to guide researchers in selecting the most appropriate specimens. In an effort to gather the best information for the selection of specimens for these studies, we convened a meeting of scientists engaged in DNA banking for large epidemiologic studies. In this discussion, we review the information presented at that meeting in the context of recent published information. Factors to be considered in choosing the appropriate specimens for epidemiologic studies include quality and quantity of DNA, convenience of collection and storage, cost, and ability to accommodate future needs for genotyping, We focus on four types of specimens that are stored in these banks: (1) whole blood preserved as dried blood spots; (2) whole blood from which genomic DNA is isolated, (3) immortalized lymphocytes from whole blood or separated lymphocytes, prepared immediately or subsequent to cryopreservation; and (4) buccal epithelial cells. Each of the specimens discussed is useful for epidemiologic studies according to specific needs, which we enumerate in our conclusions. C1 CDCP, Mol Biol Branch, Div Environm Hlth Lab Sci, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Univ Washington, Seattle, WA 98195 USA. Coriell Inst Med Res, Camden, NJ USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. New York State Dept Hlth, Wadsworth Ctr, Div Genet Disorders, Albany, NY USA. Amer Type Culture Collect, Manassas, VA USA. Boston Biomed Inc, Biotech Res Lab, Gaithersburg, MD USA. Pacific Res & Sci Serv, Ctr Blood, San Francisco, CA USA. Calif Dept Hlth, Genet Dis Branch, Berkeley, CA USA. Ctr Dis Control & Prevent, Off Genet & Dis Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Steinberg, K (reprint author), CDCP, Mol Biol Branch, Div Environm Hlth Lab Sci, Natl Ctr Environm Hlth, MS F-24,4770 Buford Highway NE, Atlanta, GA 30341 USA. RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 63 TC 74 Z9 75 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 BP 246 EP 254 DI 10.1097/00001648-200205000-00003 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 544QF UT WOS:000175170900002 PM 11964924 ER PT J AU Hartge, P Chatterjee, N Wacholder, S Brody, LC Tucker, MA Struewing, JP AF Hartge, P Chatterjee, N Wacholder, S Brody, LC Tucker, MA Struewing, JP TI Breast cancer risk in ashkenazi BRCA1/2 mutation carriers: Effects of reproductive history SO EPIDEMIOLOGY LA English DT Article DE breast cancer; BRCA1/2 mutation; reproduction; epidemiology ID ESTIMATING PENETRANCE; JEWISH INDIVIDUALS; FAMILY HISTORY; KIN-COHORT; PREGNANCY; AGE; VALIDATION; FREQUENCY; DESIGNS; MODELS AB Background. Younger age at first birth and greater parity generally reduce the risk of developing breast cancer, but whether this reduced risk holds in women with a mutation in the BRCA1 or BRCA2 gene is unknown. Methods. In a Washington DC community-based study conducted in 1996, we tested 5318 Ashkenazi Jews for three BRCA1/2 founder mutations and identified 120 mutation carriers. Applying an extension of the "kin-cohort" analysis, we compared the effects of reproduction on breast cancer risk in carriers and noncarriers. We also used a case-case analysis among 288 participants who had been diagnosed with breast cancer. Results. In noncarriers, the estimated relative risk (RR) of breast cancer rose 5% with each 5-year increment in age at first birth (RR = 1.05; 95% confidence interval [CI] = 0.97-1.15). By contrast, the estimated risk in mutation carriers fell with each 5-year increment in age (RR = 0.65; 95% Cl = 0,37-1.16). Among the 288 participants who were breast cancer survivors themselves, the comparison of carriers with noncarriers also showed no protection associated with early birth in the presence of a mutation in BRCA1 or BRCA2. Conclusions. It is not yet clear whether the recognized breast cancer risk factors operate in the same way in women who carry a mutation in the BRCA1 or BRCA2 genes. C1 NCI, Div Canc Epidemol & Genet, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemol & Genet, EPS 8090,6120 Execut Blvd, Bethesda, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 26 TC 29 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 BP 255 EP 261 DI 10.1097/00001648-200205000-00004 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 544QF UT WOS:000175170900003 PM 11964925 ER PT J AU McConnell, R Berhane, K Gilliland, F Islam, T Gauderman, WJ London, SJ Avol, E Rappaport, EB Margolis, HG Peters, JM AF McConnell, R Berhane, K Gilliland, F Islam, T Gauderman, WJ London, SJ Avol, E Rappaport, EB Margolis, HG Peters, JM TI Indoor risk factors for asthma in a prospective study of adolescents SO EPIDEMIOLOGY LA English DT Article DE asthma; etiology; indoor allergen; pets; dog; humidity ID HOUSE-DUST MITE; CHILDHOOD ASTHMA; NATURAL-HISTORY; RESPIRATORY HEALTH; EARLY EXPOSURE; CAT ALLERGEN; ADULT LIFE; CHILDREN; PREVALENCE; HOME AB Background. The risk of asthma associated with pets and other indoor exposures has been examined in both cross-sectional and prospective studies of younger children. However, there has been little investigation of the effect of the indoor environment on incident asthma in adolescents. Methods. Risk factors for the development of asthma were examined in a cohort of 3535 Southern California school children with no history of asthma at 1993 entry into the study, who were followed for up to 5 years. Newly diagnosed cases of asthma were identified by yearly interview report, A total of 265 children reported a new diagnosis of asthma during the follow-up period; 163 of these had reported no history of wheeze at baseline. The risk associated with indoor exposures assessed by questionnaire at entry into the study was examined using Cox proportional hazards models. Results. In children with no history of wheezing, an increased risk of developing asthma was associated with a humidifier (relative risk [RR] = 1.7; 95% confidence interval [CI] = 1.2-2.4), any pet (RR = 1.6; 95% Cl = 1.0-2.5), or specifically a dog (RR = 1.4; 95% Cl = 1.0-2.0) in the home. An estimated 32% of new asthma cases could be attributed to pets. Conclusions. We conclude that furry pets are a common and potentially remediable risk factor for new onset asthma in adolescents. Our results suggest that a humidifier in the home may contribute to the onset of asthma in this age group. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Calif Air Resources Board, Sacramento, CA USA. RP McConnell, R (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1540 Alcazar St,Suite 236, Los Angeles, CA 90089 USA. OI London, Stephanie/0000-0003-4911-5290 FU NHLBI NIH HHS [1R01HL61768]; NIEHS NIH HHS [1P01ESO939581-01, 5P30ES07048-05] NR 52 TC 39 Z9 39 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 BP 288 EP 295 DI 10.1097/00001648-200205000-00009 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 544QF UT WOS:000175170900008 PM 11964930 ER PT J AU Kamel, F Umbach, DM Munsat, TL Shefner, JM Hu, H Sandler, DP AF Kamel, F Umbach, DM Munsat, TL Shefner, JM Hu, H Sandler, DP TI Lead exposure and amyotrophic lateral sclerosis SO EPIDEMIOLOGY LA English DT Article DE amyotrophic lateral sclerosis; motor neuron disease; lead; occupational exposure; x-ray fluorescence; biomarker ID MOTOR-NEURON-DISEASE; X-RAY-FLUORESCENCE; BONE LEAD; BLOOD LEAD; CEREBROSPINAL-FLUID; OCCUPATIONAL EXPOSURES; ANTECEDENT EVENTS; CIGARETTE-SMOKING; RISK-FACTORS; POPULATION AB Background. Previous interview-based studies have suggested that exposure to neurotoxicants including metals might be related to ALS. Methods. We evaluated the relation of lead exposure to ALS, using both biological measures and interviews, in a case-control study conducted in New England from 1993 to 1996. Cases (N = 109) were recruited at two hospitals in Boston, MA. Population controls (N = 256) identified by random-digit dialing were frequency-matched to cases by age, sex, and region of residence within New England. Results. Risk of ALS was associated with self-reported occupational exposure to lead (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.1-3.3), with a dose response for lifetime days of lead exposure. Blood and bone lead levels were measured in most cases (N = 107) and in a subset of controls (N = 41). Risk of ALS was associated with elevations in both blood and bone lead levels. ORs were 1.9 (95% Cl = 1.4-2.6) for each mug/dl increase in blood lead, 3.6 (95% Cl = 0.6-20.6) for each unit increase in log-transformed patella lead, and 2.3 (95% CI 0.4-14.5) for each unit increase in log-transformed tibia lead. Conclusions. These results are consistent with previous reports and suggest a potential role for lead exposure in the etiology of ALS. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, Box 122233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 NR 56 TC 95 Z9 99 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 BP 311 EP 319 DI 10.1097/00001648-200205000-00012 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 544QF UT WOS:000175170900011 PM 11964933 ER PT J AU Meluh, PB Strunnikov, AV AF Meluh, PB Strunnikov, AV TI Beyond the ABCs of CKC and SCC - Do centromeres orchestrate sister chromatid cohesion or vice versa? SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review DE centromere; kinetochore; CENP-A; histone; methylation; heterochromatin; sister chromatid cohesion; cohesin; chromatin immunoprecipitation ID ALPHA-SATELLITE DNA; REDUCTIONAL CHROMOSOME SEGREGATION; FISSION YEAST CENTROMERES; INNER KINETOCHORE PLATE; CELL-CYCLE PROGRESSION; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CENP-A; S-PHASE; NUCLEAR DIVISION AB The centromere-kinetochore complex is a highly specialized chromatin domain that both mediates and monitors chromosome-spindle interactions responsible for accurate partitioning of sister chromatids to daughter cells. Centromeres are distinguished from adjacent chromatin by specific patterns of histone modification and the presence of a centromere-specific histone H3 variant (e.g. CENP-A). Centromere-proximal regions usually correspond to sites of avid and persistent sister chromatid cohesion mediated by the conserved cohesin complex. In budding yeast, there is a substantial body of evidence indicating centromeres direct formation and/or stabilization of centromere-proximal cohesion. In other organisms, the dependency of cohesion on centromere function is not as clear. Indeed, it appears that pericentromeric heterochromatin recruits cohesion proteins independent of centromere function. Nonetheless, aspects of centromere function are impaired in the absence of sister chromatid cohesion, suggesting the two are interdependent. Here we review the nature of centromeric chromatin, the dynamics and regulation of sister chromatid cohesion, and the relationship between the two. C1 Mem Sloan Kettering Canc Ctr, Program Mol Biol, Lab Mech & Regulat Mitosis, New York, NY 10021 USA. NICHHD, Unit Chromosome Struct & Funct, NIH, Lab Gene Regulat & Dev, Bethesda, MD USA. RP Meluh, PB (reprint author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, Lab Mech & Regulat Mitosis, 1275 York Ave, New York, NY 10021 USA. OI Strunnikov, Alexander/0000-0002-9058-2256 NR 159 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY PY 2002 VL 269 IS 9 BP 2300 EP 2314 DI 10.1046/j.1432-1033.2002.02886.x PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 549HH UT WOS:000175438100007 PM 11985612 ER PT J AU Levy, N De Sandre-Giovannoli, A Chaouch, M Kozlov, S Vallat, J Tazir, M Kassouri, N Szepetowski, P Hammadouche, T Boccaccio, I Grid, D Stewart, CL AF Levy, N De Sandre-Giovannoli, A Chaouch, M Kozlov, S Vallat, J Tazir, M Kassouri, N Szepetowski, P Hammadouche, T Boccaccio, I Grid, D Stewart, CL TI Lamin A/C mutations in Charcot-Marie-Tooth disorder identify a novel laminopathy in human and mouse SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjuction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 Fac Med La Timone, INSERM U491, Marseille, France. CHU Ben Aknoun, Serv Neurol, Algiers, Algeria. NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. CHU Dupuytren, Serv Neuropathol, Limoges, France. CHU Mustapha, Serv Neurol, Algiers, Algeria. Inst Pasteur, Algiers, Algeria. Genethon 3, Evry, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 70 EP 71 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166100079 ER PT J AU Kozma, C Slavotinek, AA Meck, JM AF Kozma, C Slavotinek, AA Meck, JM TI Segregation of a t(1 : 3)(q42.3;p25) translocation resulting in different recombinant chromosomes in multiple family members SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjuction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 Georgetown Univ, Washington, DC 20057 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 118 EP 118 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166100294 ER PT J AU Fogli, A Pierre, EE Rodriguez, D Bertini, E Pineda, M Surtees, R Uziel, G Malaspina, E Shiffmann, R Tanguy, OB AF Fogli, A Pierre, EE Rodriguez, D Bertini, E Pineda, M Surtees, R Uziel, G Malaspina, E Shiffmann, R Tanguy, OB TI Detection of mutations in the translation initiation factor eIF2B in a restricted white matter disorder, the CACH/VWM syndrome SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjunction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 INSERM U384, Clermont Ferrand, France. Hop Trousseau, F-75571 Paris, France. INSERM U546, F-75571 Paris, France. Bambino Gesu Pediat Hosp, Dept Neurosci, Rome, Italy. Hosp San Joan de Deu, Barcelona, Spain. UCL, Inst Child Hlth, London, England. Carlo Basta Inst, Milan, Italy. Inst Clin Padiat, Bologna, Italy. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Fed Auvergne Genet Humaine, Clermont Ferrand, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 253 EP 253 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166100933 ER PT J AU Noorian, AR Pasalar, P Moghimi, B Jannati, A Soltanzadeh, A Krefft, T Crook, R Najmabadi, H Hardy, J AF Noorian, AR Pasalar, P Moghimi, B Jannati, A Soltanzadeh, A Krefft, T Crook, R Najmabadi, H Hardy, J TI A family with Alzheimer's disease caused by a novel APP mutation (Thr714Ala) SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjunction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 Univ Tehran Med Sci, Tehran, Iran. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. Social Welfare & Rehabil Univ, Genet Res Ctr, Tehran, Iran. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Jannati, Ali/J-6453-2012 NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 271 EP 271 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166101014 ER PT J AU Gollust, S Thompson, R Biesecker, BB AF Gollust, S Thompson, R Biesecker, BB TI Living with achondroplasia in an average-sized world SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjuction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 306 EP 306 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166101176 ER PT J AU Peters, KF Hanslo, M Kong, F Biesecker, BB AF Peters, KF Hanslo, M Kong, F Biesecker, BB TI Adults with Marfan syndrome: Sexual functioning and reproduction SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjuction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 Penn State Univ, State Coll, PA USA. Westat Res Inst, Rockville, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 316 EP 316 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166101221 ER PT J AU Biesecker, BB McInerney-Leo, A Thompson, RE Hadley, D Kase, R Giambarresi, T Lerman, C Struewing, J AF Biesecker, BB McInerney-Leo, A Thompson, RE Hadley, D Kase, R Giambarresi, T Lerman, C Struewing, J TI BRCA1/2 testing in hereditary breast and ovarian cancer families: Impact on relationships SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjuction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Ctr Biostat, Baltimore, MD 21218 USA. Westat Res Inc, Rockville, MD USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 319 EP 319 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166101233 ER PT J AU Gooding, HC Wilfond, B Boehm-Frassrand, K Biesecker, BB AF Gooding, HC Wilfond, B Boehm-Frassrand, K Biesecker, BB TI Unintended messages: the ethics of teaching genetic dilemmas SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT European-Society-of-Human-Genetics European Human Genetics Conference in Conjuction With European Meeting on Psychosocial Aspects of Genetics CY MAY 25-28, 2002 CL STRASBOURG, FRANCE SP European Soc Human Genet C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2002 VL 10 SU 1 BP 322 EP 322 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 752MW UT WOS:000187166101248 ER PT J AU Noben-Trauth, N Hu-Li, J Paul, WE AF Noben-Trauth, N Hu-Li, J Paul, WE TI IL-4 secreted from individual naive CD4(+) T cells acts in an autocrine manner to induce Th2 differentiation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE IL-4; IL-4 receptor; Th2 cell ID PRODUCE INTERLEUKIN-4; IL-4-PRODUCING CELLS; IN-VITRO; MICE; RESPONSES; STAT6; GENE; LYMPHOCYTES; CYTOKINES; PHENOTYPE AB Naive CD4(+) T cell populations rapidly produce small amounts of IL-4 in response to T cell receptor-mediated stimulation and may undergo Th2 differentiation without exogenous IL-4. Whether this is due to autocrine IL-4-stimulation or the production of IL-4 by an infrequent naive cell has not been determined. Here we show that single CD4(+) T cells from RAG2-/- T cells receptor transgenic mice primed with their cognate antigen give rise to IL-4-producing cells at a similar frequency whether primed with or without added IL-4, but not if anti-IL-4 is added to the culture. Thus, each founder cell or one or more of its early daughters can produce sufficient IL-4 to drive Th2 differentiation. This indicates that autocrine IL-4 production by naive CD4 T cells can drive the appearance of Th2 cells. C1 George Washington Univ, Dept Immunol, Washington, DC 20037 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Noben-Trauth, N (reprint author), George Washington Univ, Dept Immunol, 2300 Eye St NW, Washington, DC 20037 USA. NR 29 TC 49 Z9 51 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2002 VL 32 IS 5 BP 1428 EP 1433 AR UNSP I 22846 DI 10.1002/1521-4141(200205)32:5<1428::AID-IMMU1428>3.0.CO;2-0 PG 6 WC Immunology SC Immunology GA 553VD UT WOS:000175695700025 PM 11981831 ER PT J AU Eybalin, M Renard, N Aure, F Safieddine, S AF Eybalin, M Renard, N Aure, F Safieddine, S TI Cysteine-string protein in inner hair cells of the organ of Corti: synaptic expression and upregulation at the onset of hearing SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlea; glutamatergic neurotransmission; maturation of hearing; SNARE; synaptic vesicle proteins ID SPIRAL GANGLION NEURONS; GUINEA-PIG COCHLEA; DEVELOPING RAT COCHLEA; GENE-RELATED PEPTIDE; MAMMALIAN COCHLEA; CA2+ CHANNELS; POSTNATAL-DEVELOPMENT; NEUROTRANSMITTER EXOCYTOSIS; FREQUENCY-SELECTIVITY; EFFERENT INNERVATION AB Cysteine-string protein is a vesicle-associated protein that plays a vital function in neurotransmitter release. We have studied its expression and regulation during cochlear maturation. Both the mRNA and the protein were found in primary auditory neurons and the sensory inner hair cells. More importantly, cysteine-string protein was localized on synaptic vesicles associated with the synaptic ribbon in inner hair cells and with presynaptic differentiations in lateral and medial olivocochlear terminals - the cell bodies of which lie in the auditory brainstem. No cysteine-string protein was expressed by the sensory outer hair cells suggesting that the distinct functions of the two cochlear hair cell types imply different mechanisms of neurotransmitter release. In developmental studies in the rat, we observed that cysteine-string protein was present beneath the inner hair cells at birth and beneath outer hair cells by postnatal day 2 only. We found no expression in the inner hair cells before about postnatal day 12, which corresponds to the period during which the first cochlear action potentials could be recorded. In conclusion, the close association of cysteine-string protein with synaptic vesicles tethered to synaptic ribbons in inner hair cells and its synchronized expression with the appearance and maturation of the cochlear potentials strongly suggest that this protein plays a fundamental role in sound-evoked glutamate release by inner hair cells. This also suggests that this role may be common to ribbon synapses and conventional central nervous system synapses. C1 INSERM, UR254, F-34090 Montpellier, France. Univ Montpellier 1, F-34090 Montpellier, France. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Eybalin, M (reprint author), INSERM, UR254, 71 Rue Navacelles, F-34090 Montpellier, France. RI EYBALIN, Michel/A-9895-2011 OI EYBALIN, Michel/0000-0001-9086-1856 NR 87 TC 26 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2002 VL 15 IS 9 BP 1409 EP 1420 DI 10.1046/j.1460-9568.2002.01978.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 554QP UT WOS:000175748900001 PM 12028351 ER PT J AU Hampel, H Burger, K Zinkowski, R Teipel, SJ Kohnken, R Kerkman, D DeBernardis, J Kahle, P Rapoport, SI Sunderland, T Arai, H Tapiola, T Hoffmann-Kiefer, K Andreasen, N Blennow, K Moller, HJ Davies, P AF Hampel, H Burger, K Zinkowski, R Teipel, SJ Kohnken, R Kerkman, D DeBernardis, J Kahle, P Rapoport, SI Sunderland, T Arai, H Tapiola, T Hoffmann-Kiefer, K Andreasen, N Blennow, K Moller, HJ Davies, P TI CSF tau phosphorylated at threonine 231, total tau and neuronal thread protein in the diagnosis of Alzheimer's disease SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract ID CEREBROSPINAL-FLUID C1 Mol Geriatr Corp, Vernon Hills, IL USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Sendai, Miyagi 980, Japan. Univ Kuopio, FIN-70211 Kuopio, Finland. Dept Rehabil, Pitea, Sweden. Gothenburg Univ, S-41124 Gothenburg, Sweden. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD MAY PY 2002 VL 17 SU 1 BP 77S EP 77S PG 1 WC Psychiatry SC Psychiatry GA 581CM UT WOS:000177273600289 ER PT J AU Tohen, M Baker, RW Altshuler, L Zarate, CA Suppes, T Ketter, TA Risser, RC Brown, E Luther, MF Gilmore, JA Schuh, L AF Tohen, M Baker, RW Altshuler, L Zarate, CA Suppes, T Ketter, TA Risser, RC Brown, E Luther, MF Gilmore, JA Schuh, L TI Olanzapine versus divalproex sodium for bipolar mania: a 47-week study SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. NIMH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD MAY PY 2002 VL 17 SU 1 BP 109S EP 109S PG 1 WC Psychiatry SC Psychiatry GA 581CM UT WOS:000177273600416 ER PT J AU Botos, J Smith, R Kochevar, DT AF Botos, J Smith, R Kochevar, DT TI Retinoblastoma function is a better indicator of cellular phenotype in cultured breast adenocarcinoma cells than retinoblastoma expression SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE breast adenocarcinoma; cell cycle; gene expression; gene regulation; retinoblastoma ID E2F FAMILY MEMBERS; HISTONE DEACETYLASE; GENE-EXPRESSION; REPRESS TRANSCRIPTION; ESTROGEN-RECEPTOR; REDUNDANT CYCLIN; TUMOR-CELLS; CANCER; PROTEIN; LINES AB Loss of or lowered retinoblastoma (Rb) expression has been included as a prognostic indicator in breast cancer. Low or no Rb expression is seen most commonly in high-grade breast adenocarcinomas, suggesting that a relationship may exist between loss of Rb and a less differentiated state, high proliferation rate, and high metastatic potential. In this study, we compared Rb function in two established breast adenocarcinoma cell lines, MCF-7 and MDA-MB-231, and in an established immortalized mammary epithelial cell line, MCF10A. Cells were synchronized in G0/G1 and were released for several durations, at which time total Rb protein, mRNA, and Rb/ E2F/DNA complex formation were evaluated. Rb protein was significantly higher in the tumor cells than in MCF10A cells. However, Rb function was high for a longer duration in MCF10A cells as compared with MCF-7 and MDA-MB-231 cells. Our data support the general conclusion that Rb function, but not necessarily Rb protein, is lower in highly malignant breast adenocarcinoma cells as compared with lower grade tumor cells. These results emphasize the relevance of assessing Rb function over Rb protein. This is particularly important if Rb is to be used as a prognostic indicator for breast adenocarcinoma. C1 Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. RP Botos, J (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr,Room C310, Bethesda, MD 20892 USA. RI Smith III, Roger/C-8685-2013; OI Smith, Roger/0000-0001-5645-8422 NR 55 TC 11 Z9 13 U1 0 U2 2 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAY PY 2002 VL 227 IS 5 BP 354 EP 362 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 545RW UT WOS:000175232200008 PM 11976406 ER PT J AU Jackson, SH Alicea, C Owens, JW Eigsti, CL Malech, HL AF Jackson, SH Alicea, C Owens, JW Eigsti, CL Malech, HL TI Characterization of an early dendritic cell precursor derived from murine lineage-negative hematopoietic progenitor cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; LIGAND-TREATED MICE; NECROSIS-FACTOR-ALPHA; IN-VIVO; GM-CSF; GROWTH-FACTOR; IFN-GAMMA; IMMUNE-RESPONSE; CULTURE METHOD AB Objective. We define characteristics of a dendritic cell (DC) precursor generated from murine lineage-negative (Lin(-)) Sca1(+) hematopoietic progenitor cells (HPC). Materials and Methods. Lin(-)Sca1(+) HPC cultured 9 days in 100 ng/mL stem cell factor (SCF), 20 ng/mL interleukin-3 (IL-3), 50 ng/mL monocyte colony-stimulating factor (M-CSF), 5 ng/mL granulocyte-monocyte colony-stimulating factor (GM-CSF), and 25 ng/mL FLT3-ligand (FLT3-L) proliferate 387-fold and differentiate into DC precursors. Switch to greater than or equal to100 ng/mL GM-CSF + 1500 U/mL IL-4 or 500 U/mL tumor necrosis factor-alpha (TNF-alpha) for 3 days induces development into immature DC that are responsive to bacterial lipopolysaccharide (LPS)-induced maturation. Results. Lin(-)Sca1(+) HPC in the first 9 days of culture differentiate into DC precursors expressing surface CD11b(bright), CD11c(mod), CD86(low-mod), major histocompatibility class 11 antigen (MHC) IIlow, DEC 205(low), but are surface CD40(-) and contain high levels of intracellular MHC II Unlike immature DC described by others, these DC precursors are refractory to maturation with LPS and minimally stimulate allogeneic T lymphocytes in mixed leukocyte reactions (MLR). Switch to high-dose GM-CSF alone with IL-4 or TNF-alpha. differentiates these DC precursors into immature DC. LPS treatment of the immature DC results in mature DC that express surface CD40(high) and CD86(high), secrete IL-1beta and IL-12, and strongly stimulate MLR. Conclusions. These studies define a distinct DC precursor derived from murine HPC that precedes development of immature and mature DC. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NIAID, NIH, Flow Cytometry Unit, Off Sci Director, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD USA. Natl Ctr Res Resources, Vet Pathol Lab, Off Director, NIH, Bethesda, MD USA. RP Jackson, SH (reprint author), NIAID, NIH, Flow Cytometry Unit, Off Sci Director, 10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 53 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 2002 VL 30 IS 5 BP 430 EP 439 AR PII S0301-472X(02)00792-0 DI 10.1016/S0301-472X(02)00792-0 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 548HR UT WOS:000175383000007 PM 12031649 ER PT J AU Lee, J Chan, SL Lu, CB Lane, MA Mattson, MP AF Lee, J Chan, SL Lu, CB Lane, MA Mattson, MP TI Phenformin suppresses calcium responses to glutamate and protects hippocampal neurons against excitotoxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article DE AMPA; biguanide; diabetes; glutamate; ischemic stroke; NMDA; oxidative stress; patch clamp ID OXIDATIVE STRESS; DIETARY RESTRICTION; SUBUNIT EXPRESSION; BRAIN-DAMAGE; NMDA; INJURY; APOPTOSIS; MECHANISM; METFORMIN; HOMEOSTASIS AB Phenformin is a biguanide compound that can modulate glucose metabolism and promote weight loss and is therefore used to treat patients with type-2 diabetes. While phenformin may indirectly affect neurons by changing peripheral energy metabolism, the possibility that it directly affects neurons has not been examined. We now report that phenformin suppresses responses of hippocampal neurons to glutamate and decreases their vulnerability to excitotoxicity. Pretreatment of embryonic rat hippocampal cell cultures with phenformin protected neurons against glutamate-induced death, which was correlated with reduced calcium responses to glutamate. Immunoblot analyses showed that levels of the N-methyl-D-aspartate (NMDA) subunits NR1. and NR2A were significantly decreased in neurons exposed to phenformin, whereas levels of the AMPA receptor subunit GluR1 were unchanged. Whole-cell patch clamp analyses revealed that NMDA-induced currents were decreased, and AMPA-induced currents were unchanged in neurons pretreated with phenformin. Our data demonstrate that phenformin can protect neurons against excitotoxicity by differentially modulating levels of NMDA receptor subunits in a manner that decreases glutamate-induced calcium influx. These findings show that phenformin can modulate neuronal responses to glutamate, and suggest possible use of phenformin and related compounds in the prevention and/or treatment of neurodegenerative conditions. (C) 2002 Elsevier Science (USA). C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Lee, J (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 35 TC 13 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2002 VL 175 IS 1 BP 161 EP 167 DI 10.1006/exnr.2002.7864 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 550YN UT WOS:000175532800014 PM 12009768 ER PT J AU Ferreira, CAS Vaz, ID da Silva, SS Haag, KL Valenzuela, JG Masuda, A AF Ferreira, CAS Vaz, ID da Silva, SS Haag, KL Valenzuela, JG Masuda, A TI Cloning and partial characterization of a Boophilus microplus (Acari : Ixodidae) calreticulin SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID CALCIUM-BINDING PROTEIN; AMBLYOMMA-AMERICANUM; ESCHERICHIA-COLI; ANTIGEN; GENE; QUANTITATION; CONSERVATION; AUTOANTIGEN; EXPRESSION; ANTIBODIES AB We report the cloning, sequence characterization and expression analysis of a calreticulin (CRT) coding cDNA of Boophilus microplus. CRT is a calcium-binding protein involved in multiple cell functions and possibly implicated in parasites host immune system evasion. The CRT cDNA sequence and its molecular characterization are described. Sequence similarity and phylogenetic analyses indicate a close relationship to other arthropod CRT sequences. The CRT cDNA was also expressed in a procariotic system and the recombinant protein (rBmCRT) was used to raise antibodies in a rabbit. Expression analyses of the corresponding gene in different developmental stages and tissues were performed by RT-PCR and Western-blot, which indicated a ubiquitous expression of the B. microplus calreticulin gene and demonstrated its presence in saliva. Sera of tick-infested bovines suggested that this protein may not be able to induce an IgG-based humoral response in its natural host. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Fed Rio Grande Sul, Ctr Biotecnol Estado Rio Grande Sul, Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Fac Vet, Porto Alegre, RS, Brazil. Univ Fed Pelotas, Fac Vet, Dept Vet Prevent, Capao Do Leao, RS, Brazil. Univ Fed Rio Grande Sul, Inst Biociencias, Dept Genet, BR-90049 Porto Alegre, RS, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Fed Rio Grande Sul, Inst Biociencias, Dept Biol Mol & Biotecnol, BR-90049 Porto Alegre, RS, Brazil. RP Masuda, A (reprint author), Univ Fed Rio Grande Sul, Ctr Biotecnol Estado Rio Grande Sul, Caixa Postal 15005,Campus Vale, Porto Alegre, RS, Brazil. RI da Silva Vaz Jr, Itabajara/A-5943-2009; Ferreira, Carlos /J-3672-2015 OI da Silva Vaz Jr, Itabajara/0000-0003-0309-9328; Ferreira, Carlos /0000-0002-3727-5097 NR 41 TC 43 Z9 43 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 2002 VL 101 IS 1 BP 25 EP 34 AR PII S0014-4894(02)00032-2 PG 10 WC Parasitology SC Parasitology GA 599HH UT WOS:000178327700004 PM 12243735 ER PT J AU Ameye, L Aria, D Jepsen, K Oldberg, A Xu, TS Young, MF AF Ameye, L Aria, D Jepsen, K Oldberg, A Xu, TS Young, MF TI Abnormal collagen fibrils in tendons of biglycan/fibromodulin-deficient mice lead to gait impairment, ectopic ossification, and osteoarthritis SO FASEB JOURNAL LA English DT Article DE leucine-rich; proteoglycans; cartilage; bone; matrix ID DEGENERATIVE JOINT DISEASE; PROTEOGLYCANS BIGLYCAN; TARGETED DISRUPTION; SKIN FRAGILITY; KNEE-JOINT; FIBROMODULIN; DECORIN; LUMICAN; GENE; EXPRESSION AB Small leucine-rich proteoglycans (SLRPs) regulate extracellular matrix organization, a process essential in development, tissue repair, and metastasis. In vivo interactions of biglycan and fibromodulin, two SLRPs highly expressed in tendons and bones, were investigated by generating biglycan/fibromodulin double-deficient mice. Here we show that collagen fibrils in tendons from mice deficient in biglycan and/or fibromodulin are structurally and mechanically altered resulting in unstable joints. As a result, the mice develop successively and progressively 1) gait impairment, 2) ectopic tendon ossification, and 3) severe premature osteoarthritis. Forced use of the joints increases ectopic ossification and osteoarthritis in the double-deficient mice, further indicating that structurally weak tendons cause the phenotype. The study shows that mutations in SLRPs may predispose to osteoarthritis and offers a valuable and unique animal model for spontaneous osteoarthritis characterized by early onset and a rapid progression of the disease. C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. CUNY Mt Sinai Sch Med, Dept Orthopaed, New York, NY 10029 USA. Lund Univ, Dept Cell & Mol Biol, Lund, Sweden. RP Ameye, L (reprint author), Nestle Res Ctr, Dept Nutr, G35 Vers Chez Blanc,POB 44, CH-1000 Lausanne 26, Switzerland. EM Laurent.Ameye@rdls.nestle.com NR 30 TC 186 Z9 197 U1 2 U2 9 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 MAY PY 2002 VL 16 IS 7 AR UNSP 0892-6638/02/0016-0673 DI 10.1096/fj.01-0848com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 558NR UT WOS:000175973900021 PM 11978731 ER PT J AU Levine, RL AF Levine, RL TI Carbonyl modified proteins in cellular regulation, aging, and disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE aging; carbonyl; carbonylated proteins; free radical; protein oxidation ID METAL-CATALYZED OXIDATION; GLUTAMINE-SYNTHETASE; OXIDIZED PROTEINS; ESCHERICHIA-COLI; PROLYL HYDROXYLATION; HIF-ALPHA; DEGRADATION; PLASMA; DAMAGE; CELLS AB The oxidative modification of proteins by reactive species is implicated in the etiology or progression of a panoply of disorders and diseases. The level of these modified molecules can be quantitated by measurement of the protein carbonyl content, which has been shown to increase in a variety of diseases and processes, notably during aging, For the most part, oxidatively modified proteins are not repaired and must be removed by proteolytic degradation, a process which normally proceeds very efficiently, from microorganisms to mammals. In eukaryotes, removal is usually carried out by the proteosome, which selectively degrades oxidatively modified proteins, whether they be damaged by reactive oxygen species or specifically oxidized by cellular regulatory processes. The molecular deficiencies that cause accumulation of oxidatively modified proteins are not identified, but regardless of cause, the accumulation is likely to disrupt normal cellular function. Published by Elsevier Science Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 54 TC 405 Z9 416 U1 11 U2 49 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 MAY 1 PY 2002 VL 32 IS 9 BP 790 EP 796 AR PII S0891-5849(02)00765-7 DI 10.1016/S0891-5849(02)00765-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 546TV UT WOS:000175291200002 PM 11978480 ER PT J AU Bohr, VA AF Bohr, VA TI Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE free radical; DNA repair; mitochondria; base excision repair; aging ID BASE-EXCISION-REPAIR; HAMSTER OVARY CELLS; POLYMERASE-BETA; THYMINE GLYCOL; ABASIC SITES; RAT-LIVER; LESIONS; PATHWAY; GENE; RECONSTITUTION AB Exposure to exogenous and endogenous sources cause oxidative damage to cellular macromolecules, including DNA. This results in gradual accumulation of oxidative DNA base lesions, and in order to maintain genomic stability we must have effective systems to repair this kind of damage. The accumulation of lesions is most dramatic in the mitochondrial DNA. and this may cause dysfunction and loss of cellular energy production. Base excision DNA repair (BER) is the major pathway that removes oxidative DNA base lesions, and while we know much about its mechanism in the nuclear DNA, little is yet known about this pathway in mitochondria. While nuclear BER decreases with age, the mitochondrial DNA repair may increase with age. This increase is not enough to prevent the gradual accumulation of lesions in the mitochondrial DNA with age. Accumulation of DNA lesions with age may be the underlying cause for age-associated diseases including cancer. Published by Elsevier Science Inc. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 54 TC 239 Z9 244 U1 1 U2 22 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 MAY 1 PY 2002 VL 32 IS 9 BP 804 EP 812 AR PII S0891-5849(02)00787-6 DI 10.1016/S0891-5849(02)00787-6 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 546TV UT WOS:000175291200004 PM 11978482 ER PT J AU Kim, KS Baek, SJ Flake, GP Loftin, CD Calvo, BF Eling, TE AF Kim, KS Baek, SJ Flake, GP Loftin, CD Calvo, BF Eling, TE TI Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue SO GASTROENTEROLOGY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; TGF-BETA SUPERFAMILY; GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEIN; MURINE MODEL; CYTOKINE-1 GDF-15/MIC-1; COLON-CARCINOMA; PREVENTS TUMORS; HUMAN PROSTATE; MIN MOUSE AB Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) induce NSAID-activated gene I (NAG-1), which has proapoptotic and antitumorigenic activities. However, NAG-1 expression and its relationship with apoptosis in human and mouse intestinal tract have not been determined. Methods: NAG-1 expression in human and mouse tissue was determined by immunohistochemistry, and apoptosis was estimated by in situ apoptosis detection. Apoptosis in NAG-1 overexpressing HCT-116 cells was examined with flow cytometry after cell sorting by green fluorescence protein. NAG-1 regulation in mouse cells was examined by Northern blot analysis, comparing sulindac-treated and nontreated mice. Results: Apoptosis was higher in NAG-1 overexpressing cells compared with controls. Human NAG-1 protein was localized to the colonic surface epithelium where cells undergo apoptosis, and higher expression was observed in the normal surface epithelium than in most of the tumors. This localization and lower expression in tumors was similar to that in the Min mouse, in which NSAIDs were also shown to regulate the expression of NAG-1 in mouse cells. Sulindac treatment of mice increased the NAG-1 expression in the colon and liver. Conclusions: Based on these results, we propose that NAG-1 acts as a mediator of apoptosis in intestinal cells and may contribute to cancer chemoprevention by NSAIDs. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Environm Carcinogenesis Mutagenesis, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Baek, Seung/0000-0001-7866-7778 NR 37 TC 80 Z9 83 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2002 VL 122 IS 5 BP 1388 EP 1398 DI 10.1053/gast.2002.32972 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546YW UT WOS:000175305500024 PM 11984525 ER PT J AU Sandler, RS Everhart, JE Donowitz, M Adams, E Cronin, K Goodman, C Gemmen, E Shah, S Avdic, A Rubin, R AF Sandler, RS Everhart, JE Donowitz, M Adams, E Cronin, K Goodman, C Gemmen, E Shah, S Avdic, A Rubin, R TI The burden of selected digestive diseases in the United States SO GASTROENTEROLOGY LA English DT Review ID OLMSTED COUNTY; PEPTIC-ULCER; PREVALENCE; HEALTH; MINNESOTA; SURVIVAL AB Background & Aims: Gastrointestinal (GI) and liver diseases Inflict a heavy economic burden. Although the burden is considerable, current and accessible information on the prevalence, morbidity, and cost is sparse. This study was undertaken to estimate the economic burden of GI and liver disease in the United States for use by policy makers, health care providers, and the public. Methods: Data were extracted from a number of publicly available and proprietary national databases to determine the prevalence, direct costs, and indirect costs for :17 selected GI and liver diseases. Indirect cost calculations were purposefully very conservative. These costs were compared with National Institutes of Health (NIH) research expenditures for selected GI and liver diseases. Results: The most prevalent diseases were non-food-borne gastroenteritis (135 million cases/year), food-borne illness (76 million), gastroesophageal reflux disease (GERD; :19 million), and irritable bowel syndrome (IBS; 15 million). The disease with the highest annual direct costs in the United States was GERD ($9.3 billion), followed by gallbladder disease ($5.8 billion), colorectal cancer ($4.8 billion), and peptic ulcer disease ($3.1 billion). The estimated direct costs for these 17 diseases in 1998 dollars were $36.0 billion, with estimated indirect costs of $22.8 billion. The estimated direct costs for all digestive diseases were $85.5 billion. Total NIH research expenditures were $676 million in 2000. Conclusions: GI and liver diseases exact heavy economic and social costs in the United States, Understanding the prevalence and costs of these diseases is important to help set priorities to reduce the burden of illness. C1 Univ N Carolina, Chapel Hill, NC 27599 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Amer Gastroenterol Assoc, Bethesda, MD USA. Lewin Grp, Falls Church, VA USA. Georgetown Univ, Sch Med, Div Nephrol & Hypertens, Washington, DC USA. RP Sandler, RS (reprint author), Univ N Carolina, CB 7080,719 Burnett Womack Bldg, Chapel Hill, NC 27599 USA. NR 12 TC 750 Z9 765 U1 1 U2 26 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2002 VL 122 IS 5 BP 1500 EP 1511 DI 10.1053/gast.2002.32978 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546YW UT WOS:000175305500033 PM 11984534 ER PT J AU Bream, JH Ping, A Zhang, X Winkler, C Young, HA AF Bream, JH Ping, A Zhang, X Winkler, C Young, HA TI A single nucleotide polymorphism in the proximal IFN-gamma promoter alters control of gene transcription SO GENES AND IMMUNITY LA English DT Article DE single nucleotide polymorphism; proximal IFN-gamma promoter; gene transcription ID IMMUNODEFICIENCY-VIRUS TYPE-1; CANDIDATE GENE; KAPPA-B; AIDS; ACTIVATION; PROGRESSION; EXPRESSION; INFECTION; MUTATION; BINDING AB Interferon-gamma (IFN-gamma) is an important cytokine that regulates cellular immune responses to intracellular pathogens and neoplasia. Regulation of IFN-gamma expression is stringently controlled at the transcriptional level. In this report we describe two novel single nucleotide polymorphisms (SNPs); one, at -179 in the promoter, occurs in 4% of African Americans. This SNP represents a guanidine to thymidine transition and creates a potential AP-1 binding element. Electrophoretic mobility shift analysis reveals a unique complex binding to an oligonucleotide containing the variant -179T but not to the -179G using nuclear extracts from human peripheral blood T cells. In reporter gene assays, T cell lines transfected with the variant -204(179T) IFN-gamma promoter show a six to 13-fold induction of luciferase activity in response to TNF-alpha over the common -204(179G) construct. The -179T allele identified in the proximal IFN-gamma promoter confers TNF-alpha inducibility and may prove important in human immune disorders and responsiveness to pathogens. C1 NCI, Cellular & Mol Immunol Sect, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Cellular & Mol Immunol Sect, Expt Immunol Lab, SAIC Frederick, Bldg 560,Room 31-23, Frederick, MD 21702 USA. RI Young, Howard/A-6350-2008; Zhang, Xia/B-8152-2008 OI Young, Howard/0000-0002-3118-5111; Zhang, Xia/0000-0002-9040-1486 FU NCI NIH HHS [N01-CO-12400] NR 31 TC 49 Z9 55 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAY PY 2002 VL 3 IS 3 BP 165 EP 169 DI 10.1038/sj/gene.6363870 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 552HA UT WOS:000175612800008 PM 12070781 ER PT J AU Williams, RW Dubnau, J Enoch, MA Flaherty, L Sluyter, F Gannon, KS Maxson, SC Riedl, CAL Williams, KD Holmes, A Bolivar, VJ Crusio, WE AF Williams, RW Dubnau, J Enoch, MA Flaherty, L Sluyter, F Gannon, KS Maxson, SC Riedl, CAL Williams, KD Holmes, A Bolivar, VJ Crusio, WE TI Hot topics in behavioral and neural genetics SO GENES BRAIN AND BEHAVIOR LA English DT Article DE behavioral phenotyping; caenorhabditis elegans; DNA microarrays; drosophila melanogaster; history; intelligence; knockout; mouse; psychiatric disorders; QTL; transgenics C1 Univ Massachusetts, Sch Med, Dept Psychiat, Brudnick Neuropsychiat Res Inst, Worcester, MA 01604 USA. Univ Tennessee, Ctr Hlth Sci, Ctr Genomics & Bioinformat, Memphis, TN 38163 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Wadsworth Ctr, Genomics Inst, Albany, NY USA. Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London, England. Eli Lilly & Co, Lilly Res Labs, Neurosci Discovery Res, Indianapolis, IN 46285 USA. Univ Connecticut, Dept Psychol & Biobehav Sci, Grad Degree Program, Storrs, CT USA. Univ Toronto, Dept Zool, Mississauga, ON L5L 1C6, Canada. Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA. NIMH, Sect Behav Genomics, Bethesda, MD 20892 USA. RP Crusio, WE (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, Brudnick Neuropsychiat Res Inst, 303 Belmont St, Worcester, MA 01604 USA. RI Crusio, Wim/A-7070-2008; OI Crusio, Wim/0000-0001-6638-202X; Dubnau, Josh/0000-0002-9285-7444; Williams, Robert/0000-0001-8924-4447 NR 0 TC 2 Z9 3 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD MAY PY 2002 VL 1 IS 2 BP 117 EP 130 DI 10.1034/j.1601-183X.2002.10207.x PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 609UJ UT WOS:000178922700007 PM 12884982 ER PT J AU Ashcroft, N Golden, A AF Ashcroft, N Golden, A TI CDC-25.1 regulates germline proliferation in Caenorhabditis elegans SO GENESIS LA English DT Article DE cdc-25.1; germline; proliferation; C. elegans ID CELL-CYCLE PROGRESSION; C-ELEGANS; CDC25 HOMOLOG; DEVELOPMENTAL REGULATION; GENETIC-CONTROL; DROSOPHILA; INTERFERENCE; EXPRESSION; SURVIVAL; MEIOSIS AB The cell cycles in C. elegans are tightly controlled but appear to use the same regulators found in other organisms. Four homologues of the dual-specificity phosphatase Cdc25 are present in the C. elegans genome. In our study, we have characterized a deletion mutant for one of these orthologues. We show that embryonic defects are absent in cdc-25.1 homozygous mutants, presumably because of maternally contributed CDC-25.1 product. These embryos hatch and develop into sterile adults. The adults do not appear to have any somatic defects. The sterility results from inadequate germline proliferation. Germline precursors divide slowly and produce abnormally sized daughter cells. Only three to four rounds of germ-cell division occur before they die during the L3 and L4 larval stages. genesis 33:1-7, 2002. (C) 2002 Wiley-Liss, Inc. C1 Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. RP Ashcroft, N (reprint author), Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England. NR 27 TC 27 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD MAY PY 2002 VL 33 IS 1 BP 1 EP 7 DI 10.1002/gene.10083 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 558JZ UT WOS:000175963700001 PM 12001064 ER PT J AU Wenstrup, RJ Meyer, RA Lyle, JS Hoechstetter, L Rose, PS Levy, HP Francomano, CA AF Wenstrup, RJ Meyer, RA Lyle, JS Hoechstetter, L Rose, PS Levy, HP Francomano, CA TI Prevalence of aortic root dilation in the Ehlers-Danlos syndrome SO GENETICS IN MEDICINE LA English DT Article DE Ehlers-Danlos; echocardiogram; aorta; aortic dilation ID SYNDROME TYPE-II; SYNDROME TYPE-IV; SYNDROME TYPE-VI; MARFAN-SYNDROME; COL5A1 GENE; CROSS-LINKS; MUTATION; DILATATION; NOSOLOGY; FAMILIES AB Purpose: To determine the prevalence of proximal aortic abnormalities in patients with Ehlers-Danlos syndrome (EDS). Methods: In a prospective cohort study, aortic measurements by two-dimensional echocardiography were performed on consecutive EDS patients. Results: Twenty-eight percent (20 of 71) had aortic root dilation (ARD) (> + 2 SD above population based norms). Fourteen of 42 individuals with the classical form of EDS (types I/II) and 6 of 29 individuals with the hypermobile form (type 111) had ARD, with no gender differences. Conclusion: ARD is a common finding in EDS. Longitudinal studies are indicated to determine progression of ARD and its clinical significance. C1 Childrens Hosp Med Fdn, Div Cardiol, Cincinnati, OH 45229 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Wenstrup, RJ (reprint author), Childrens Hosp Res Fdn, Div Human Genet, Cincinnati, OH 45229 USA. NR 28 TC 45 Z9 45 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 2002 VL 4 IS 3 BP 112 EP 117 DI 10.1097/00125817-200205000-00003 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 553LN UT WOS:000175676800003 PM 12180144 ER PT J AU Smith, ACM Gropman, AL Bailey-Wilson, JE Goker-Alpan, O Elsea, SH Blancato, J Lupski, JR Potocki, L AF Smith, ACM Gropman, AL Bailey-Wilson, JE Goker-Alpan, O Elsea, SH Blancato, J Lupski, JR Potocki, L TI Hypercholesterolemia in children with Smith-Magenis syndrome: del (17)(p11.2p11.2) SO GENETICS IN MEDICINE LA English DT Article DE Smith-Magenis syndrome; hypercholesterolemia; SREBP1; SREBF1; chromosome 17p11.2; haploinsufficiency; hemizygosity ID INTERSTITIAL DELETION; CIRCADIAN-RHYTHM; GENE; ADOLESCENTS; 17P11.2; CHROMOSOMES; MELATONIN; PATHWAY; SREBP-1 AB Purpose: Smith-Magenis syndrome (SMS), a probable contiguous gene syndrome due to an interstitial deletion of chromosome 17 band p11.2, is associated with a distinct and complex phenotype, including physical, developmental, and neurobehavioral features. The majority of SMS patients are deleted for a common similar to4 Mb interval that includes the gene SREBF1, a transmembrane transcription factor that regulates the low density lipoprotein (LDL) receptor and plays a crucial role in cholesterol homeostasis. A systematic study of fasting lipid profiles of patients with SMS was conducted to determine the frequency of cholesterol abnormalities. Methods: Fasting lipid profiles were examined in 49 children (27F/22M) between the ages of 0.6 years to 17.6 years (mean, 6.9 years) with a cytogenetically confirmed diagnosis of SMS. Observed values for serum total cholesterol (TC), triglycerides (TG), LDL cholesterol, and high density lipoprotein cholesterol were compared with published norms. The body mass index (BMI) was used as a measure of nutritional status. Results: Mean TC was significantly higher than published NHANES III pediatric norms (P < 0.0008). Overall 28 of 49 (57%) SMS subjects had lipid values greater than the 95th percentile for age and gender for at least one or more of the following: TC, TG, and/or LDL. Only 16 SMS subjects (32%) were within normal limits for all three of these variables. BMI values showed minimal positive correlation to SMS lipid values; however, no consistent effect was found. Thus BMI values alone do not explain the marked trend in increased TC, TG, and/or ILDL observed in the SMS group. Based on the American Academy of Pediatrics recommended lipid levels for children and adolescents, only one third of SMS subjects fall within normal range for TC and LDL; an additional one third each measure "borderline" or "high" for these values. Conclusion: Hypercholesterolemia is common in SMS and may serve as a useful early clinical biochemical marker of the syndrome. C1 NHGRI, Off Clin Director, NIH, Med Genet Branch, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20007 USA. NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Dept Pediat, E Lansing, MI 48824 USA. Michigan State Univ, Dept Human Genet, E Lansing, MI 48824 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA. Baylor Coll Med, Dept Pediat, Houston, TX USA. RP Smith, ACM (reprint author), NHGRI, Off Clin Director, NIH, Med Genet Branch, Bldg 10,Room 10C103,M5S 1875, Bethesda, MD 20892 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [P01CA75719]; NCRR NIH HHS [M01RR00188]; NICHD NIH HHS [HD94021, HD 08010, HD 38534, HD2406402, K08HD01149] NR 40 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 2002 VL 4 IS 3 BP 118 EP 125 DI 10.1097/00125817-200205000-00004 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 553LN UT WOS:000175676800004 PM 12180145 ER PT J AU Gaines, JM Talbot, LA Metter, EJ AF Gaines, JM Talbot, LA Metter, EJ TI The relationship of arthritis self-efficacy to functional performance in older men and women with osteoarthritis of the knee SO GERIATRIC NURSING LA English DT Article ID COMMUNITY-LIVING ELDERS; MANAGEMENT; DISABILITY; PAIN AB The objective of this study was to examine the relationship between arthritis self-efficacy (ie, the confidence a person has in the ability to perform a specific task) and self-reported functional performance among older men and women with osteoarthritis (OA) of the knee. The findings suggest that the relationship between arthritis self-efficacy and functional performance varies with gender. An older woman's confidence in her ability to perform tasks affects her perceived functional performance. However, this perception may not be true for older men with CA of the knee. C1 Erickson Fdn, Baltimore, MD USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. RP Gaines, JM (reprint author), Erickson Fdn, Baltimore, MD USA. NR 15 TC 20 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0197-4572 J9 GERIATR NURS JI Geriatr. Nurs. PD MAY-JUN PY 2002 VL 23 IS 3 BP 167 EP 170 DI 10.1067/mgn.2002.125420 PG 4 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 573MP UT WOS:000176834100021 PM 12075283 ER PT J AU Barbero, S Bajetto, A Bonavia, R Pirani, P Florio, T Schettini, G AF Barbero, S Bajetto, A Bonavia, R Pirani, P Florio, T Schettini, G TI The chemokine SDF1 alpha induces glioblastoma cells proliferation through the activation of ERK1/2 pathway SO GLIA LA English DT Meeting Abstract C1 Univ Genoa, Pharmacol Sect, Dept Oncol, Genoa, Italy. Adv Biotechnol Ctr, Natl Canc Inst, Genoa, Italy. Univ Chieti, Sch Med, Sect Pharmacol & Toxicol, Chieti, Italy. RI Florio, Tullio/A-2211-2012 OI Florio, Tullio/0000-0002-2394-996X NR 0 TC 0 Z9 0 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 0894-1491 J9 GLIA JI Glia PD MAY PY 2002 SU 1 MA P81 BP S30 EP S30 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 551WL UT WOS:000175586100131 ER PT J AU Fields, RD AF Fields, RD TI Regulation of myelination in PNS and CNS by neural impulses SO GLIA LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0894-1491 J9 GLIA JI Glia PD MAY PY 2002 SU 1 MA W72 BP S8 EP S8 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 551WL UT WOS:000175586100035 ER PT J AU Young, MF Bi, YM Ameye, L Chen, XD AF Young, MF Bi, YM Ameye, L Chen, XD TI Biglycan knockout mice: New models for musculoskeletal diseases SO GLYCOCONJUGATE JOURNAL LA English DT Article DE biglycan; skeleton; SLRPs; compensation ID LEUCINE-RICH PROTEOGLYCANS; INTRON-EXON JUNCTIONS; CHROMOSOMAL LOCALIZATION; EXTRACELLULAR-MATRIX; TARGETED DISRUPTION; DEFICIENT MICE; DECORIN; GENE; BONE; OSTEOPOROSIS AB Biglycan is a Class I Small Leucine Rich Proteoglycans (SLRP) that is localized on human chromosome Xq28-ter. The conserved nature of its intron-exon structure and protein coding sequence compared to decorin (another Class I SLRP) indicates the two genes may have arisen from gene duplication. Biglycan contains two chondroitin sulfate glycosaminoglycan (GAG) chains attached near its NH2 terminus making it different from decorin that has only one GAG chain. To determine the functions of biglycan in vivo, transgenic mice were developed that were deficient in the production of the protein (knockout). These mice acquire diminished bone mass progressively with age. Double tetracycline-calcein labeling revealed that the biglycan deficient mice are defective in their capacity to form bone. Based on this observation, we tested the hypothesis that the osteoporosis-like phenotype is due to defects in cells critical to the process of bone formation. Our data shows that biglycan deficient mice have diminished capacity to produce marrow stromal cells, the bone cell precursors, and that this deficiency increases with age. The cells also have reduced response to tranforming growth factor-beta (TGF-beta), reduced collagen synthesis and relatively more apoptosis than cells from normal littermates. In addition, calvaria cells isolated from biglycan deficient mice have reduced expression of late differentiation markers such as bone sialoprotein and osteocalcin and diminished ability to accumulate calcium judged by alizerin red staining. We propose that any one of these defects in osteogenic cells alone, or in combination, could contribute to the osteoporosis observed in the biglycan knockout mice. Other data suggests there is a functional relationship between biglycan and bone morphogenic protein-2/4 (BMP 2/4) action in controlling skeletal cell differentiation. In order to test the hypothesis that functional compensation can occur between SLRPs, we created mice deficient in biglycan and decorin. Decorin deficient mice have normal bone mass while the double biglycan/decorin knockout mice have more severe osteopenia than the single biglycan indicating redundancy in SLRP function in bone tissue. To further determine whether compensation could occur between different classes of SLRPs, mice were generated that are deficient in both biglycan (class 1) and fibromodulin, a class 11 SLRP highly expressed in mineralizing tissue. These doubly deficient mice had an impaired gait, ectopic calcification of tendons and premature osteoarthritis. Transmission electron microscopy analysis showed that like the decorin and biglycan knockouts, they have severely disturbed collagen fibril structures. Biomechanical analysis of the affected tendons showed they were weaker compared to control animals leading to the conclusion that instability of the joints could be the primary cause of all the skeletal defects observed in the fibromodulin/biglycan knockout mice. These studies present important new animal models for musculoskeletal diseases and provide the opportunity to characterize the network of signals that control tissue integrity and function through SLRP activity. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Young, MF (reprint author), Bldg 30,Room 225,MSC 4320, Bethesda, MD 20892 USA. NR 31 TC 103 Z9 105 U1 2 U2 13 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD MAY-JUN PY 2002 VL 19 IS 4-5 BP 257 EP 262 DI 10.1023/A:1025336114352 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 713EU UT WOS:000184844600005 PM 12975603 ER PT J AU Hassell, J Yamada, Y Arikawa-Hirasawa, E AF Hassell, J Yamada, Y Arikawa-Hirasawa, E TI Role of perlecan in skeletal development and diseases SO GLYCOCONJUGATE JOURNAL LA English DT Article DE heparan sulfate proteoglycan; cartilage development; mutations; chondrodysplasia; myotonia ID HEPARAN-SULFATE PROTEOGLYCAN; FIBROBLAST-GROWTH-FACTOR; SCHWARTZ-JAMPEL-SYNDROME; DENSITY-LIPOPROTEIN-RECEPTOR; SILVERMAN-HANDMAKER TYPE; BASEMENT-MEMBRANE; CELL-ADHESION; DYSSEGMENTAL DYSPLASIA; CAENORHABDITIS-ELEGANS; CHAIN INITIATION AB Perlecan, a large heparan sulfate proteoglycan (HSPG), is present in the basement membrane and other extracellular matrices. Its protein core is 400 kDa in size and consists of five distinct structural domains. A number of in vitro studies suggest multiple functions of perlecan in cell growth and differentiation and tissue organization. Recent studies with gene knockout mice and human diseases revealed critical in vivo roles of perlecan in cartilage development and neuromuscular junction activity. C1 Shriners Hosp Children, Res Dept, Ctr Res Skeletal Dev & Pediat Orthopaed, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Tampa, FL 33612 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Res Inst Dis Old Ages, Tokyo 1138421, Japan. RP Hassell, J (reprint author), Shriners Hosp Children, Res Dept, Ctr Res Skeletal Dev & Pediat Orthopaed, 12502 N Pine Dr, Tampa, FL 33612 USA. NR 65 TC 31 Z9 31 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD MAY-JUN PY 2002 VL 19 IS 4-5 BP 263 EP 267 DI 10.1023/A:1025340215261 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 713EU UT WOS:000184844600006 PM 12975604 ER PT J AU Watanabe, H Yamada, Y AF Watanabe, H Yamada, Y TI Chondrodysplasia of gene knockout mice for aggrecan and link protein SO GLYCOCONJUGATE JOURNAL LA English DT Article DE aggrecan; proteoglycan; link protein; gene defects; knockout mouse ID MATRIX DEFICIENCY CMD; CHONDROITIN SULFATE; INDIAN HEDGEHOG; CARTILAGE; PROTEOGLYCAN; BINDING; MOUSE; DOMAIN; HYALURONAN; EXPRESSION AB The proteoglycan aggregate of the cartilage is composed of aggrecan, link protein, and hyaluronan and forms a unique gel-like moiety that provides resistance to compression in joints and a foundational cartilage structure critical for growth plate formation. Aggrecan, a large chondroitin sulfate proteoglycan, is one of the major structural macromolecules in cartilage and binds both hyaluronan and link protein through its N-terminal domain G1. Link protein, a small glycoprotein, is homologous to the G1 domain of aggrecan. Mouse cartilage matrix deficiency (cmd) is caused by a functional null mutation of the aggrecan gene and is characterized by perinatal lethal dwarfism and craniofacial abnormalities. Link protein knockout mice show chondrodysplasia similar to but milder than cmd mice, suggesting a supporting role of link protein for the aggregate structure. Analysis of these mice revealed that the proteoglycan aggregate plays an important role in cartilage development and maintenance of cartilage tissue and may provide a clue to the identification of human genetic disorders caused by mutations in these genes. C1 Aichi Med Univ, Inst Mol Sci Med, Aichi 4801195, Japan. Natl Inst Dent & Craniofacial Res, Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Watanabe, H (reprint author), Aichi Med Univ, Inst Mol Sci Med, Aichi 4801195, Japan. NR 24 TC 26 Z9 28 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD MAY-JUN PY 2002 VL 19 IS 4-5 BP 269 EP 273 DI 10.1023/A:1025344332099 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 713EU UT WOS:000184844600007 PM 12975605 ER PT J AU Zuvekas, SH Regler, DA Rae, DS Rupp, A Narrow, WE AF Zuvekas, SH Regler, DA Rae, DS Rupp, A Narrow, WE TI The impacts of mental health parity and managed care in one large employer group SO HEALTH AFFAIRS LA English DT Article ID SERVICES; EPISODES AB We examine the impacts of a state mental health parity mandate on a large employer group, which simultaneously introduced a managed behavioral health care carve-out. Overall, we find that mental health/substance abuse (MH/SA) costs dropped 39 percent from the year prior to three years after parity, with managed care offsetting increases in demand induced by parity coverage. Managed care was most effective in reducing very high inpatient use among adolescents and children. The effect of the parity mandate on access was ambiguous: While treatment prevalence rose nearly 50 percent, similar increases were observed for groups not subject to the mandate. C1 Amer Psychiat Assoc, Div Res, Washington, DC 20005 USA. NIMH, Mental Hlth Econ Res Program, Bethesda, MD USA. NR 14 TC 18 Z9 18 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2002 VL 21 IS 3 BP 148 EP 159 DI 10.1377/hlthaff.21.3.148 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 551WG UT WOS:000175585700033 PM 12025978 ER PT J AU Anspaugh, LR Simon, SL Gordeev, KI Likhtarev, IA Maxwell, RM Shinkarev, SM AF Anspaugh, LR Simon, SL Gordeev, KI Likhtarev, IA Maxwell, RM Shinkarev, SM TI Movement of radionuclides in terrestrial ecosystems by physical processes SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY APR 04-05, 2001 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements DE fallout; radionuclide; radioactivity; environmental; National Council on Radiation Protection and Measurements ID FOOD-CHAIN MODEL; INITIAL RETENTION; RESUSPENSION; INTERCEPTION; VEGETATION; FALLOUT; CONTAMINANTS; INGESTION; PATHWAY; RAIN AB Physical processes that effect the movement of radionuclides in the temperate environments post-deposition are considered in this paper. The physical processes considered include the interception of radionuclides by vegetation, resuspension, and vertical migration in soil. United States and Russian results on the interception of radionuclides are reviewed and defined in terms of models that are currently undergoing evaluation and revision. New results on resuspension are evaluated, and a preliminary new model for the time-dependent resuspension factor is proposed. Chernobyl-related results on the movement of radionuclides into the soil column are presented, as is a revised model for this process based upon recent results from Ukraine. C1 Univ Utah, Dept Radiol, Div Radiobiol, Salt Lake City, UT 84108 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. State Res Ctr, Inst Biophys, Minist Hlth, Moscow 123182, Russia. Ukrainian Acad Technol Sci, Radiat Protect Inst, UA-04050 Kiev, Ukraine. Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. RP Anspaugh, LR (reprint author), Univ Utah, Dept Radiol, Div Radiobiol, Salt Lake City, UT 84108 USA. EM LAnspaugh@aol.com RI Maxwell, Reed/D-7980-2013; Shinkarev, Sergey /B-3254-2017 OI Maxwell, Reed/0000-0002-1364-4441; NR 53 TC 31 Z9 33 U1 4 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2002 VL 82 IS 5 BP 669 EP 679 DI 10.1097/00004032-200205000-00013 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 544MN UT WOS:000175164300013 PM 12003017 ER PT J AU Bouville, A Simon, SL Miller, CW Beck, HL Anspaugh, LR Bennett, BG AF Bouville, A Simon, SL Miller, CW Beck, HL Anspaugh, LR Bennett, BG TI Estimates of doses from global fallout SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY APR 04-05, 2001 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements DE fallout; radionuclide; dose; population; National Council on Radiation Protection and Measurements ID RADIONUCLIDE AB This paper summarizes information about external and internal doses resulting from global fallout and presents preliminary estimates of doses resulting from intermediate fallout in the contiguous United States. Most of the data on global fallout were extracted from the reports of the United Nations Scientific Committee on the Effects of Atomic Radiation, in which the radiation exposures from fallout have been extensively reviewed at regular intervals. United Nations Scientific Committee on the Effects of Atomic Radiation estimated the average effective doses received by the world's population before 2000 to be about 0.4 mSv from external irradiation and 0.6 mSv from internal irradiation, the main radionuclide contributing to the effective dose being Cs-137. Effective doses received beyond 2000 result mainly from the environmentally mobile, long-lived C-14 and amount to about 2.5 mSv summed over present and future generations. Specific information about the doses from fallout received by the United States population is based on the preliminary results of a study requested by the U.S. Congress and conducted jointly by the Centers for Disease Control and Prevention and the National Cancer Institute. Separate calculations were made for the tests conducted at the Nevada Test Site and for the high-yield tests conducted mainly by the United States and the former Soviet Union at sites far away from the contiguous United States (global tests). The estimated average doses from external irradiation received by the United States population were about 0.5 mGy for Nevada Test Site fallout and about 0.7 mGy for global fallout. These values vary little from one organ or tissue of the body to another. In contrast, the average doses from internal irradiation vary markedly from one organ or tissue to another; estimated average thyroid doses to children born in 1951 were about 30 mGy from Nevada Test Site fallout and about 2 mGy from global fallout. C1 NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Univ Utah, Dept Radiol, Div Radiobiol, Salt Lake City, UT 84108 USA. Radiat Effects Res Fdn, Hiroshima, Japan. RP Bouville, A (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. EM bouvilla@epndce.nei.nih.gov NR 31 TC 20 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2002 VL 82 IS 5 BP 690 EP 705 DI 10.1097/00004032-200205000-00015 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 544MN UT WOS:000175164300015 PM 12003019 ER PT J AU Simon, SL Bouville, A AF Simon, SL Bouville, A TI Radiation doses to local populations near nuclear weapons test sites worldwide SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY APR 04-05, 2001 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements DE fallout; radionuclide; dose; population; National Council on Radiation Protection and Measurements ID NEVADA TEST SITE; CONTINENTAL UNITED-STATES; EXTERNAL GAMMA-EXPOSURE; MARSHALL ISLANDS; RADIOACTIVE FALLOUT; HARDTACK-II; TEST SERIES; UTAH; INGESTION; LEUKEMIA AB Nuclear weapons testing was conducted in the atmosphere at numerous sites worldwide between 1946 and 1980, which resulted in exposures to local populations as a consequence of fallout of radioactive debris. The nuclear tests were conducted by five nations (United States. Soviet Union, United Kingdom, France, and China) primarily at 16 sites. The 16 testing sites, located in nine different countries on five continents (plus Oceania) contributed nearly all of the radioactive materials released to the environment by atmospheric testing; only small amounts were released at a few other minor testing sites. The 16 sites discussed here are Nevada Test Site, USA (North American continent), Bikini and Enewetak, Marshall Islands (Oceania); Johnston Island, USA (Oceania), Christmas and Malden Island, Kiribati (Oceania); Emu Field, Maralinga, and Monte Bello Islands, Australia (Australian continent); Mururoa and Fangataufa, French Polynesia (Oceania), Reggane, Algeria (Africa), Novaya Zemlya and Kapustin Yar, Russia (Europe), Semipalatinsk, Kazakhstan (Asia), and Lop Nor, China (Asia). There were Large differences in the numbers of tests conducted at each location and in the total explosive yields. Those factors, as well as differences in population density, lifestyle, environment, and climate at each site, led to large differences in the doses received by local populations. In general, the tests conducted earliest led to the highest individual and population exposures, although the amount of information available for a few of these sites is insufficient to provide any detailed evaluation of radiation exposures. The most comprehensive information for any site is for the Nevada Test Site. The disparities in available information add difficulty to determining the radiation exposures of local populations at each site. It is the goal of this paper to summarize the available information on external and internal doses received by the public living in the regions near each of the mentioned nuclear test sites as a consequence of local fallout deposition. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7238, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 107 TC 21 Z9 21 U1 6 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2002 VL 82 IS 5 BP 706 EP 725 DI 10.1097/00004032-200205000-00016 PG 20 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 544MN UT WOS:000175164300016 PM 12003020 ER PT J AU Gilbert, ES Land, CE Simon, SL AF Gilbert, ES Land, CE Simon, SL TI Health effects from fallout SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY APR 04-05, 2001 CL ARLINGTON, VA SP Natl Council Radiat Protect & Measurements DE fallout; dose; population; health effects; National Council on Radiation Protection and Measurements ID ATOMIC-BOMB SURVIVORS; THYROID-CANCER RISK; IONIZING-RADIATION; CHERNOBYL ACCIDENT; MARSHALL-ISLANDS; UNITED-KINGDOM; FOLLOW-UP; MORTALITY; WORKERS; POPULATION AB This paper primarily discusses health effects that have resulted from exposures received as a result of above-ground nuclear tests, with emphasis on thyroid disease from exposure to I-131 and leukemia and solid cancers from low dose rate external and internal exposure. Results of epidemiological studies of fallout exposures in the Marshall Islands and from the Nevada Test Site are summarized, and studies of persons with exposures similar to those from fallout are briefly reviewed (including patients exposed to I-131 for medical reasons and workers exposed externally at low doses and low dose rates). Promising new studies of populations exposed in countries of the former Soviet Union are also discussed and include persons living near the Semipalatinsk Test Site in Kazakhstan, persons exposed as a result of the Chernobyl accident, and persons exposed as a result of operations of the Mayak Nuclear Plant in the Russian Federation. Very preliminary estimates of cancer risks from fallout doses received by the United States population are presented. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Gilbert, ES (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC-7238, Rockville, MD 20852 USA. EM gilberte@mail.nih.gov NR 67 TC 25 Z9 28 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAY PY 2002 VL 82 IS 5 BP 726 EP 735 DI 10.1097/00004032-200205000-00017 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 544MN UT WOS:000175164300017 PM 12003021 ER PT J AU Philpott, CC AF Philpott, CC TI Molecular aspects of iron absorption: Insights into the role of HFE in hemochromatosis SO HEPATOLOGY LA English DT Review ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; DIVALENT METAL TRANSPORTER; CELL-SURFACE EXPRESSION; HEREDITARY HEMOCHROMATOSIS; TRANSFERRIN RECEPTOR; PROTEIN HFE; NEURODEGENERATIVE DISEASE; CERULOPLASMIN GENE; CRYSTAL-STRUCTURE; MOUSE-LIVER AB Hereditary hemochromatosis is the most common genetic disorder occurring in persons of northern European descent, and the clinical hallmark of the disease is the gradual accumulation of iron in internal organs, especially the liver, heart, and pancreas, which ultimately leads to organ failure. HFE, the gene that is defective in the majority of cases, was identified in 1996 and, although the exact role that HFE plays in the uptake and utilization of iron is not yet Clear, important aspects of HFE function are emerging. Identification and studies of new proteins involved in the absorption of iron in the gut and in somatic cells has led to a clearer picture of how humans absorb iron from the diet and regulate this absorption to meet metabolic needs and to balance body iron stores. This review focuses on the molecular aspects of iron absorption and the role that HFE may play in these processes. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Philpott, CC (reprint author), NIDDK, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. NR 62 TC 37 Z9 37 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2002 VL 35 IS 5 BP 993 EP 1001 DI 10.1053/jhep.2002.33466 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546YZ UT WOS:000175305800001 PM 11981749 ER PT J AU Lau, JYN Tam, RC Liang, TJ Hong, Z AF Lau, JYN Tam, RC Liang, TJ Hong, Z TI Mechanism of action of ribavirin in the combination treatment of chronic HCV infection SO HEPATOLOGY LA English DT Editorial Material ID HEPATITIS-C-VIRUS; SPECTRUM ANTIVIRAL ACTIVITY; BLOOD MONONUCLEAR-CELLS; INTERFERON-ALPHA; NONTRANSLATED REGION; CYTOKINE SECRETION; POSITIVE PATIENTS; IMMUNE-RESPONSES; REPLICATION; PROLIFERATION C1 ICN Pharmaceut Inc, Res & Dev, Costa Mesa, CA 92626 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. RP Lau, JYN (reprint author), ICN Pharmaceut Inc, Res & Dev, 3300 Hyland Ave, Costa Mesa, CA 92626 USA. NR 50 TC 242 Z9 250 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2002 VL 35 IS 5 BP 1002 EP 1009 DI 10.1053/jhep.2002.32672 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546YZ UT WOS:000175305800002 PM 11981750 ER PT J AU Lee, JS Thorgeirsson, SS AF Lee, JS Thorgeirsson, SS TI Functional and genomic implications of global gene expression profiles in cell lines from human hepatocellular cancer SO HEPATOLOGY LA English DT Article ID ALPHA-FETOPROTEIN; CDNA MICROARRAY; CARCINOMA CELLS; MOLECULAR CLASSIFICATION; IDENTIFICATION; CARCINOGENESIS; HYBRIDIZATION; PATTERNS; PROTEIN; CLONING AB Global gene expression profiles in cancer have impacted both classification of tumors and definition of molecular pathways in neoplasia. To explore the possibility of employing human tumor cell lines to obtain information on the functional genomics of the early stages of tumorigenesis, we have characterized variation in gene-expression patterns in a cytogenetically well-defined series of cell lines derived from human hepatocellular carcinoma (HCC). Microarrays containing 6,720 sequence-verified human cDNAs were used in this study. Nineteen well-characterized HCC cell fines were analyzed, and a nontumorigenic fiver-derived epithelial cell line (Chang) was used as a reference. Each sample was examined at least twice by switching fluorescent dyes, Cy-5 and Cy-3, and average values of 2 experiments on each sample were used for further analysis. Analysis of the clustered data revealed 2 distinctive subtypes of gene-expression patterns among the 19 cell lines, suggesting a degree of heterogeneity among the gene-expression profiles of cell lines. Remarkably, expression of a-fetoprotein (AFP) was highly correlated with the molecular subtypes of HCC. Although the 3 most distinctive gene-expression modules represented the signatures of 2 different subgroups of HCC, most of the cell lines shared many coexpressed genes. However, sets of coexpressed genes that are specific for the subtypes of HCC were identified. Furthermore, our results indicate that the comparison between gene-expression patterns and structural alterations in chromosomes is potentially useful in identifying genes critical in early stages of tumorigenesis. In conclusion, these results not only identified unrecognized subtypes of HCC, but also provided potential molecular markers for each subtype that can be useful for diagnostic and/or therapeutic purposes. C1 NCI, Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Carcinogenesis Lab, Canc Res Ctr, NIH, 37 Convent Dr,MSC 4258,Bldg 37,room 3C28, Bethesda, MD 20892 USA. NR 45 TC 84 Z9 88 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2002 VL 35 IS 5 BP 1134 EP 1143 DI 10.1053/jhep.2002.33165 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546YZ UT WOS:000175305800015 PM 11981763 ER PT J AU Nomura, M Durbak, L Chan, J Smithies, O Gustafsson, JA Korach, KS Pfaff, DW Ogawa, S AF Nomura, M Durbak, L Chan, J Smithies, O Gustafsson, JA Korach, KS Pfaff, DW Ogawa, S TI Genotype/age interactions on aggressive behavior in gonadally intact estrogen receptor beta knockout (beta ERKO) male mice SO HORMONES AND BEHAVIOR LA English DT Article DE estrogen receptor alpha; estrogen receptor beta; androgen receptor; testosterone; estrogen; sexual behavior; aggression; resident-intruder test ID PLASMA TESTOSTERONE; GENE DISRUPTION; MESSENGER-RNA; MALE RHESUS; RAT-BRAIN; ALPHA; BINDING; MOUSE; FOREBRAIN; ANDROGEN AB Estrogen, as an aromatized metabolite of testosterone, has a facilitatory effect on male aggressive behavior in mice. Two subtypes of estrogen receptors, alpha (ER-alpha) and beta (ER-beta), in the brain are known to bind estrogen. Previous studies revealed that the lack of ER-alpha gene severely reduced the induction of male aggressive behavior. In contrast, mice that lacked the ER-beta gene tended to be more aggressive than wild type (WT) control mice, although the behavioral effects of ER-beta gene disruption were dependent on their social experience. These findings lead us to hypothesize that estrogen may facilitate aggression via ER-alpha whereas it may inhibit aggression via ER-beta. In the present study, we further investigated the role of ER-beta in the regulation of aggressive behavior by examining developmental changes starting at the time of first onset, around the age of puberty. Aggressive behaviors of ER-beta gene knockout (betaERKO) mice were examined in three different age groups, puberty, young-adult, and adult. Each mouse was tested every other day for three times in a resident-intruder paradigm against olfactory bulbectomized intruder mice and their trunk blood was collected for measurements of serum testosterone after the completion of the study. Overall, betaERKO mice were significantly more aggressive than WT. These genotype differences were more pronounced in puberty and young adult age groups, but not apparent in the adult age group, in which betaERKO mice were less aggressive than those in two younger age groups. Serum testosterone levels of betaERKO mice were significantly higher than those of WT mice only in the pubertal age group, but not in young adult (when betaERKO mice were still significantly more aggressive than WT mice) and adult (when no genotype differences in aggression were found) age groups. These results suggest that ER-beta mediated actions of gonadal steroids may more profoundly be involved in the inhibitory regulation of aggressive behavior in pubertal and young adult mice. (C) 2002 Elsevier Science (USA). C1 Rockefeller Univ, Lab Neurobiol & Behav, New York, NY 10021 USA. Univ N Carolina, Dept Pathol & Lab Med, Res Triangle Pk, NC 27709 USA. Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden. NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Ogawa, S (reprint author), Rockefeller Univ, Lab Neurobiol & Behav, 1230 York Ave, New York, NY 10021 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NIMH NIH HHS [NIMH 62147] NR 41 TC 93 Z9 96 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD MAY PY 2002 VL 41 IS 3 BP 288 EP 296 DI 10.1006/hbeh.2002.1773 PG 9 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 551JC UT WOS:000175556300005 PM 11971662 ER PT J AU Gruber, JD Colligan, PB Wolford, JK AF Gruber, JD Colligan, PB Wolford, JK TI Estimation of single nucleotide polymorphism allele frequency in DNA pools by using Pyrosequencing SO HUMAN GENETICS LA English DT Article ID CROHNS-DISEASE; PIMA-INDIANS; SUSCEPTIBILITY; ASSOCIATION; LINKAGE AB Positional cloning of genes underlying complex diseases, such as type 2 diabetes mellitus (T2DM), typically follows a two-tiered process in which a chromosomal region is first identified by genome-wide linkage scanning, followed by association analyses using densely spaced single nucleotide polymorphic markers to identify the causal variant(s). The success of genome-wide single nucleotide polymorphism (SNP) detection has resulted in a vast number of potential markers available for use in the construction of such dense SNP maps. However, the cost of genotyping large numbers of SNPs in appropriately sized samples is nearly prohibitive. We have explored pooled DNA genotyping as a means of identifying differences in allele frequency between pools of individuals with T2DM and unaffected controls by using Pyrosequencing technology. We found that allele frequencies in pooled DNA were strongly correlated with those in individuals (r=0.99, P<0.0001) across a wide range of allele frequencies (0.02-0.50). We further investigated the sensitivity of this method to detect allele frequency differences between contrived pools, also over a wide range of allele frequencies. We found that Pyrosequencing was able to detect an allele frequency difference of less than 2% between pools, indicating that this method may be sensitive enough for use in association studies involving complex diseases where a small difference in allele frequency between cases and controls is expected. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Wolford, JK (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 14 TC 88 Z9 93 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2002 VL 110 IS 5 BP 395 EP 401 DI 10.1007/s00439-002-0722-6 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 562HQ UT WOS:000176191700002 PM 12073008 ER PT J AU de la Cruz, JM Bamford, RN Burdine, RD Roessler, E Barkovich, AJ Donnai, D Schier, AF Muenke, M AF de la Cruz, JM Bamford, RN Burdine, RD Roessler, E Barkovich, AJ Donnai, D Schier, AF Muenke, M TI A loss-of-function mutation in the CFC domain of TDGF1 is associated with human forebrain defects SO HUMAN GENETICS LA English DT Article ID ONE-EYED PINHEAD; RIGHT AXIS FORMATION; VERTEBRATE DEVELOPMENT; ZEBRAFISH ORGANIZER; LATERALITY DEFECTS; GENE; MOUSE; GASTRULATION; CRIPTO; REQUIREMENT AB TDGF1 (CRIPTO) is an EGF-CFC family member and an obligate co-receptor involved in NODAL signaling, a developmental program implicated in midline, forebrain, and left-right axis development in model organisms. Previous studies of CFC1 (CRYPTIC), another member of the EGF-CFC family, demonstrated that normal function of this protein is required for proper laterality development in humans. Here we identify a mutation in the conserved CFC domain of TDGF1 in a patient with midtine anomalies of the forebrain. The mutant protein is inactive in a zebrafish rescue assay, indicating a role for TDGF1 in human midline and forebrain development. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Cell Biol, Skirball Inst Biomol Med,Dev Genet Program, New York, NY 10016 USA. Univ Calif San Francisco, Dept Neuroradiol, San Francisco, CA 94143 USA. St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C 103, Bethesda, MD 20892 USA. OI Burdine, Rebecca/0000-0001-6620-5015 NR 23 TC 67 Z9 68 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2002 VL 110 IS 5 BP 422 EP 428 DI 10.1007/s00439-002-0709-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 562HQ UT WOS:000176191700006 PM 12073012 ER PT J AU Lindsay, RS Kobes, S Knowler, WC Hanson, RL AF Lindsay, RS Kobes, S Knowler, WC Hanson, RL TI Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of birth weight SO HUMAN GENETICS LA English DT Article ID QUANTITATIVE-TRAIT LOCI; PIMA-INDIANS; THRIFTY PHENOTYPE; INSULIN; GENES; TWINS; ASSOCIATION; GLUCOKINASE; HYPOTHESIS; MUTATIONS AB Family studies suggest that genetic variation may influence birth weight. We have assessed linkage of birth weight in a genome-wide scan in 269 Pima Indian siblings (334 sibling pairs, 92 families). As imprinting (expression of only a single copy of a gene depending on parent-of-origin), is commonly found in genes that affect fetal growth, we used a recently described modification of standard multipoint variance-component methods of linkage analysis of quantitative traits. This technique allows for comparison of linkage models that incorporate imprinting effects (in which the strength of linkage is expressed as LODIMP) and models where parent-of-origin effects are not included (LODEQ). Where significant evidence of linkage was present, separate contributions of alleles derived from father (LODFA) or mother (LODMO) to the imprinting model were estimated. Significant evidence of linkage was found on chromosome 11 (at map position 88 cM, LODIMP=3.4) with evidence for imprinting (imprinting model superior, P<0.001). In this region, birth weight was linked predominantly to paternally derived alleles (LODFA=4.1, LODMO=0.0). An imprinted gene on chromosome 11 may influence birth weight in the Pima population. This chromosome contains one of the two major known clusters of imprinted genes in the human genome, lending biological plausibility to our findings. C1 NIDDK, NIH, Phoenix, AZ 85014 USA. RP Lindsay, RS (reprint author), NIDDK, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 40 TC 37 Z9 38 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2002 VL 110 IS 5 BP 503 EP 509 DI 10.1007/s00439-002-0718-2 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 562HQ UT WOS:000176191700016 PM 12073022 ER PT J AU O'Leary, T Berman, JJ AF O'Leary, T Berman, JJ TI Gastrointestinal stromal tumors: Answers and questions SO HUMAN PATHOLOGY LA English DT Editorial Material ID TYROSINE KINASE INHIBITOR; CHRONIC MYELOGENOUS LEUKEMIA; COPY NUMBER CHANGES; MUSCLE TUMORS; C-KIT; CHROMOSOMAL-ABNORMALITIES; POOR-PROGNOSIS; LEIOMYOSARCOMAS; LEIOMYOMAS; MUTATIONS C1 Armed Forces Inst Pathol, Dept Cellular Pathol & Genet, Washington, DC 20306 USA. NCI, Canc Diag Program, NIH, Rockville, MD USA. RP O'Leary, T (reprint author), Armed Forces Inst Pathol, Dept Cellular Pathol & Genet, Washington, DC 20306 USA. NR 31 TC 28 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2002 VL 33 IS 5 BP 456 EP 458 DI 10.1053/hupa.2002.124120 PG 3 WC Pathology SC Pathology GA 567QB UT WOS:000176494700002 PM 12094369 ER PT J AU Fletcher, CDM Berman, JJ Corless, C Gorstein, F Lasota, J Longley, BJ Miettinen, M O'Leary, TJ Remotti, H Rubin, BP Shmookler, B Sobin, LH Weiss, SW AF Fletcher, CDM Berman, JJ Corless, C Gorstein, F Lasota, J Longley, BJ Miettinen, M O'Leary, TJ Remotti, H Rubin, BP Shmookler, B Sobin, LH Weiss, SW TI Diagnosis of gastrointestinal stromal tumors: A consensus approach SO HUMAN PATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; sarcoma; diagnosis; guidelines; KIT; CD117 ID SMOOTH-MUSCLE TUMORS; INTERSTITIAL-CELLS; DIFFERENTIAL-DIAGNOSIS; TRACT; KIT; FEATURES; CAJAL; CD34; HISTOGENESIS; EXPRESSION AB As a result of major recent advances in understanding the biology of gastrointestinal stromal tumors (GISTs), specifically recognition of the central role of activating KIT mutations and associated KIT protein expression in these lesions, and the development of novel and effective therapy for GISTs using the receptor tyrosine kinase inhibitor STI-571, these tumors have become the focus of considerable attention by pathologists, clinicians, and patients. Stromal/mesenchymal tumors of the gastrointestinal tract have long been a source of confusion and controversy with regard to classification, line(s) of differentiation, and prognostication. Characterization of the KIT pathway and its phenotypic implications has helped to resolve some but not all of these issues. Given the now critical role of accurate and reproducible pathologic diagnosis in ensuring appropriate treatment for patients with GIST, the National Institutes of Health convened a GIST workshop in April 2001 with the goal of developing a consensus approach to diagnosis and morphologic prognostication. Key elements of the consensus, as described herein, are the defining role of KIT immunopositivity in diagnosis and a proposed scheme for estimating metastatic risk in these lesions, based on tumor size and mitotic count, recognizing that it is probably unwise to use the definitive term "benign" for any GIST, at least at the present time. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA. Armed Forces Inst Pathol, Dept Soft Tissue Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Dept Cellular Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Dept Genet & Gastrointestinal Pathol, Washington, DC 20306 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Suburban Hosp, Dept Pathol, Bethesda, MD USA. Emory Univ Hosp, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP Fletcher, CDM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 38 TC 1629 Z9 1938 U1 6 U2 49 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2002 VL 33 IS 5 BP 459 EP 465 DI 10.1053/hupa.2002.123545 PG 7 WC Pathology SC Pathology GA 567QB UT WOS:000176494700003 PM 12094370 ER PT J AU Dunson, DB Colombo, B Baird, DD AF Dunson, DB Colombo, B Baird, DD TI Changes with age in the level and duration of fertility in the menstrual cycle SO HUMAN REPRODUCTION LA English DT Article DE Bayesian; fertile interval; ovulation; menstrual cycle; pregnancy probabilities ID INCREASING PATERNAL AGE; DELAYED CONCEPTION; OVULATION; MEN; SPERM; PROBABILITIES; FECUNDABILITY; FECUNDITY; MODEL AB BACKGROUND: Most analyses of age-related changes in fertility cannot separate effects due to reduced frequency of sexual intercourse from effects directly related to ageing. Information on intercourse collected daily through each menstrual cycle provides the data for estimating day-specific probabilities of pregnancy for specific days relative to ovulation, and these estimates allow unconfounded analysis of ageing effects. METHODS: A total of 782 healthy couples using natural family planning methods contributed prospective data on 5860 menstrual cycles. Day of ovulation was based on basal body temperature measurements. Estimates of day-specific probabilities of pregnancy and the length of the fertile window were compared across age groups. RESULTS: Nearly all pregnancies occurred within a 6 day fertile window. There was no evidence for a shorter fertile window in older men or women. On average, the day-specific probabilities of pregnancy declined with age for women from the late 20s onward, with probabilities of pregnancy twice as high for women aged 19-26 years compared with women aged 35-39 years. Controlling for age of the woman, fertility was significantly reduced for men aged >35 years. CONCLUSIONS: Women's fertility begins to decline in the late 20s with substantial decreases by the late 30s. Fertility for men is less affected by age, but shows significant decline by the late 30s. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Padua, Dipartimento Sci Stat, Padua, Italy. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 38 TC 216 Z9 223 U1 0 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2002 VL 17 IS 5 BP 1399 EP 1403 DI 10.1093/humrep/17.5.1399 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 548KT UT WOS:000175387700045 PM 11980771 ER PT J AU Sugita, M Cao, XC Watts, GFM Rogers, RA Bonifacino, JS Brenner, MB AF Sugita, M Cao, XC Watts, GFM Rogers, RA Bonifacino, JS Brenner, MB TI Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells SO IMMUNITY LA English DT Article ID MHC CLASS-II; HERMANSKY-PUDLAK-SYNDROME; BACTERIAL LIPID ANTIGENS; T-CELLS; CYTOPLASMIC TAIL; INVARIANT CHAIN; LIPOGLYCAN ANTIGENS; DENDRITIC CELLS; SORTING SIGNALS; INTRACELLULAR-TRANSPORT AB Endocytosed microbial antigens are primarily delivered to lysosomal compartments where antigen binding to MHC and CD1 molecules occurs in an acidic and proteolytically active environment. Signal-dependent delivery to lysosomes has been suggested for these antigen-presenting molecules, but molecular interactions with vesicular coat proteins and adaptors that direct their lysosomal sorting are poorly understood. Here CD1b but not other CD1 isoforms bound the AP-3 adaptor protein complex. In AP-3-deficient cells derived from patients with Hermansky-Pudlak syndrome type 2 (HPS-2), CD1b failed to efficiently gain access to lysosomes, resulting in a profound defect in antigen presentation. Since MHC class 11 traffics normally in AP-3-deficient cells, defects in CD1b antigen presentation may account for recurrent bacterial infections in HPS-2 patients. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lymphocyte Biol Sect,Div Rheumatol Immunol & Alle, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Brenner, MB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lymphocyte Biol Sect,Div Rheumatol Immunol & Alle, Boston, MA 02115 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 64 TC 121 Z9 124 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2002 VL 16 IS 5 BP 697 EP 706 DI 10.1016/S1074-7613(02)00311-4 PG 10 WC Immunology SC Immunology GA 555YJ UT WOS:000175820400008 PM 12049721 ER PT J AU Zhu, JF Guo, LY Min, BK Watson, CJ Hu-Li, J Young, HA Tsichlis, PN Paul, WE AF Zhu, JF Guo, LY Min, BK Watson, CJ Hu-Li, J Young, HA Tsichlis, PN Paul, WE TI Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation SO IMMUNITY LA English DT Article ID ZINC-FINGER PROTEIN; TRANSCRIPTION FACTOR; IN-VIVO; T-CELLS; GENE-EXPRESSION; TRANSGENIC MICE; GATA-3; GFI-1; STAT6; COMMITMENT AB IL-4 is important in Th2 differentiation and in cell expansion. Stat6 is necessary and sufficient for both functions. Although Gata3 is critical for Th2 polarization, it is not sufficient to mediate IL-4-driven cell expansion. We report that growth factor independent-1 (Gfi-1), a Stat6-dependent transcriptional repressor, strikingly increases Th2 cell expansion by promoting proliferation and preventing apoptosis. Cells infected with a Gfi-1 retrovirus show striking enhancement of IL-2-induced Stat5 phosphorylation and repression of p27(Kip-1) expression, suggesting a potential mechanism for the Gfi-1 growth effect. The synergy of Gfi-1 and Gata3 provides a mechanism through which IL-4 could selectively promote Th2 cell expansion. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Zhu, Jinfang/B-7574-2012 NR 42 TC 134 Z9 140 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2002 VL 16 IS 5 BP 733 EP 744 DI 10.1016/S1074-7613(02)00317-5 PG 12 WC Immunology SC Immunology GA 555YJ UT WOS:000175820400011 PM 12049724 ER PT J AU Schwebach, JR Glatman-Freedman, A Gunther-Cummins, L Dai, ZD Robbins, JB Schneerson, R Casadevall, A AF Schwebach, JR Glatman-Freedman, A Gunther-Cummins, L Dai, ZD Robbins, JB Schneerson, R Casadevall, A TI Glucan is a component of the Mycobacterium tuberculosis surface that is expressed in vitro and in vivo SO INFECTION AND IMMUNITY LA English DT Article ID MONOCLONAL-ANTIBODIES; POLYSACCHARIDES; LIPOARABINOMANNAN; MACROPHAGES; ENVELOPE; ANTIGENS; SURVIVAL; BINDING; BACILLI AB The outermost layer of Mycobacterium tuberculosis is composed primarily of two polysaccharides, glucan (GC) and arabinomannan. To analyze the surface polysaccharide composition of At. tuberculosis, we generated a monoclonal antibody (MAb) that binds At. tuberculosis GC and is known as MAb 24c5. Immunofluorescence and whole-mount immunoelectron microscopy indicated that GC is on the outermost portion of the bacteria. At. tuberculosis strains Erdman and CDC 1551 were analyzed for their ability to bind MAb 24c5 after in vitro growth in media with and without the detergent Tween 80. MAb 24c5 bound to Erdman and CDC][551 at all culture times with only slightly greater apparent affinity after extended culture in the absence of Tween 80, indicating that a stable amount of GC polysaccharide antigen is associated with the cell surface of M. tuberculosis. An enzyme-linked immunosorbent assay indicated that GC is antigenically similar to glycogen, and the amount of GC antigen increased in the media of At. tuberculosis cultures grown either with or without the detergent Tween 80. Other nontuberculosis mycobacteria have antigenically similar GCs on their surfaces after in vitro growth. Inoculation of mice with live bacilli but not inoculation with dead bacilli elicited a strong antibody response to GC consistent with production of this antigen in vivo. Our results provide a more comprehensive picture of the At. tuberculosis cell envelope and the conditions that allow expression of M. tuberculosis GC. C1 Childrens Hosp Montefiore, Dept Pediat, Albert Einstein Coll Med, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Immunol & Microbiol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Analyt Imaging Facil, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Natl Inst Child Hlth, NIH, Bethesda, MD 20892 USA. NIH, Human Dev Biotechnol Unit, Bethesda, MD 20892 USA. RP Glatman-Freedman, A (reprint author), 702 Golding Bldg,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [CA 13330, P30 CA013330]; NHLBI NIH HHS [HL59842, R01 HL059842]; NIAID NIH HHS [AI33142, 1K08AI01691, 5T32AI07501, AI33774, K08 AI001691, N01-AI-75320, R01 AI033142, R01 AI033774, R37 AI033142, T32 AI007501] NR 34 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2002 VL 70 IS 5 BP 2566 EP 2575 DI 10.1128/IAI.70.5.2566-2575.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 543NH UT WOS:000175107700042 PM 11953397 ER PT J AU van Diepen, A van der Straaten, T Holland, SM Janssen, R van Dissel, JT AF van Diepen, A van der Straaten, T Holland, SM Janssen, R van Dissel, JT TI A superoxide-hypersusceptible Salmonella enterica serovar Typhimurium mutant is attenuated but regains virulence in p47(phox-/-) mice SO INFECTION AND IMMUNITY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CHRONIC GRANULOMATOUS-DISEASE; PHAGOCYTE NADPH-OXIDASE; OXIDATIVE STRESS; ANTIMICROBIAL ACTIONS; MURINE MACROPHAGES; PATHOGENICITY; RESISTANT; PRODUCTS; SURVIVAL AB Salmonella enterica serovar Typhimurium is a gram-negative, facultative intracellular pathogen that predominantly invades mononuclear phagocytes and is able to establish persistent infections. One of the innate defense mechanisms of phagocytic cells is the production of reactive oxygen species, including superoxide. S. enterica serovar Typhimurium has evolved mechanisms to resist such radicals, and these mechanisms could be decisive in its ability to survive and replicate within macrophages. Recently, we described a superoxide-hypersusceptible S. enterica serovar Typhimurium mutant strain, DLG294, that carries a transposon in sspJ, resulting in the lack of expression of SspJ, which is necessary for resistance against superoxide and replication within macrophages. Here we show that DLG294, which is a 14028s derivative, hardly induced any granulomatous lesions in the livers upon subcutaneous infection of C3H/HeN (Ity(r)) mice with 3 X 104 bacteria and that its bacterial counts were reduced by 3 log units compared to those of wild-type S. enterica serovar Typhimurium 14028s on day 5 after infection. In contrast, DLG294 replicated like wild-type S. enterica serovar Typhimurium 14028s and induced a phenotypically similar liver pathology in p47(phox-/-) mice, which are deficient in the P47(phox) subunit of the NADPH oxidase complex and which do not produce superoxide. Consistent with these results, DLG294 reached bacterial counts identical to those of wild-type S. enterica serovar Typhimurium 14028s in bone marrow-derived macrophages from p47(phox-/-) mice and in X-CGD PLB-985 cells at 24 h after challenge. These results indicate that SspJ plays a role in the bacterium's resistance to oxidative stress and in the survival and replication of S. enterica serovar Typhimurium both in vitro and in vivo. C1 Leiden Univ, Med Ctr, Dept Infect Dis, NL-2300 RC Leiden, Netherlands. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP van Dissel, JT (reprint author), Leiden Univ, Med Ctr, Dept Infect Dis, POB 9600, NL-2300 RC Leiden, Netherlands. NR 29 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2002 VL 70 IS 5 BP 2614 EP 2621 DI 10.1128/IAI.70.5.2614-2621.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 543NH UT WOS:000175107700048 PM 11953403 ER PT J AU Takahara, K Omatsu, Y Yashima, Y Maeda, Y Tanaka, S Iyoda, T Clausen, BE Matsubara, K Letterio, J Steinman, RM Matsuda, Y Inaba, K AF Takahara, K Omatsu, Y Yashima, Y Maeda, Y Tanaka, S Iyoda, T Clausen, BE Matsubara, K Letterio, J Steinman, RM Matsuda, Y Inaba, K TI Identification and expression of mouse Langerin (CD207) in dendritic cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE Birbeck granules; C-type lectin; gene mapping; Langerhans cells; multimer; transforming growth factor-beta 1 ID COLONY-STIMULATING FACTOR; C-TYPE LECTINS; LYMPH-NODES; TRANSFORMING GROWTH-FACTOR-BETA-1; MONOCLONAL-ANTIBODY; BIRBECK GRANULES; NULL MICE; IN-VITRO; DC-SIGN; RECEPTOR AB We have cloned the mouse homologue of human Langerin (h-Langerin), a type II transmembrane protein with a single external C-type lectin domain. Mouse Langerin (m-Langerin) displays 65 and 74% homologies in total amino acid and lectin domains with those of h-Langerin. The cognate mouse and rat genes were assigned to chromosome 6D1-D2 and chromosome 4q33 distal-q34.1 proximal respectively, syntenic to the h-Langerin gene on chromosome 2p13. With RT-PCR, m-Langerin transcripts were as expected detected in MHC class II(+), but not MHC class II(-), cells from epidermis and the expression level was reduced by culture. However, m-Langerin transcripts were also expressed in spleen, lymph nodes (LN), thymus, liver, lung and even heart, but not gut-associated lymphoid tissues. In single-cell lymphoid suspensions, m-Langerin transcripts were mainly detected in the CD11c(+) dendritic cells (DC), especially the CD11b(low)/CD8(high) fraction of spleen and LN. DC generated from bone marrow precursors by granulocyte macrophage colony stimulating factor (GM-CSF) expressed m-Langerin, but this was shut down during maturation with CD40 ligand or lipopolysaccharide. DC derived from blood monocytes by GM-CSF + IL-4 lacked m-Langerin unless the cultures were supplemented with transforming growth factor (TGF)-beta1. Unexpectedly, significant amounts of m-Langerin transcripts were detected in skin and LN of TGF-beta1-deficient mice, although in much lower amounts than littermate controls. Recombinant m-Langerin could form multimers and bind to mannan-agarose. These findings indicate that Langerin expression is regulated at several levels: by TGF-beta1, DC subsets, DC maturation and the tissue environment. C1 Kyoto Univ, Grad Sch Biostudies, Div Syst Life Sci, Dept Anim Dev & Physiol,Lab Immunobiol, Kyoto 6068502, Japan. Kyoto Univ, Grad Sch Sci, Dept Zool, Kyoto 6068502, Japan. Hokkaido Univ, Fac Sci, Chromosome Res Unit, Sapporo, Hokkaido 0600810, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Div Biosci, Lab Cytogenet, Sapporo, Hokkaido 0600810, Japan. Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands. NCI, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA. RP Inaba, K (reprint author), Kyoto Univ, Grad Sch Biostudies, Div Syst Life Sci, Dept Anim Dev & Physiol,Lab Immunobiol, Kyoto 6068502, Japan. EM kayo@lif.kyoto-u.ac.jp RI CLAUSEN, Bjorn/A-8229-2010; Steinman, Ralph/F-7729-2012; OI CLAUSEN, Bjorn/0000-0002-2484-7842; Matsubara, Kazumi/0000-0002-6680-1084 FU NIAID NIH HHS [AI13013] NR 47 TC 80 Z9 81 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 2002 VL 14 IS 5 BP 433 EP 444 DI 10.1093/intimm/14.5.433 PG 12 WC Immunology SC Immunology GA 548KB UT WOS:000175386200001 PM 11978773 ER PT J AU Olasz, EB Linton, J Katz, SI AF Olasz, EB Linton, J Katz, SI TI Soluble proteins and haptens on bone marrow-derived dendritic cells are presented to host CD4 T cells in an MHC-restricted manner SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigen presentation; contact sensitivity; cross-presentation; delayed-type hypersensitivity; dendritic cell; MHC ID RESPONSES IN-VITRO; CROSS-PRESENTATION; LANGERHANS CELLS; APOPTOTIC CELLS; CONTACT HYPERSENSITIVITY; ANTITUMOR IMMUNITY; ANTIGENS; VIVO; PEPTIDE; LYMPHOCYTES AB Because of their potent antigen-presenting capacity, dendritic cells (DC) have been used extensively in immunotherapy protocols. Our purpose was to functionally characterize mouse bone marrow-derived DC (BMDC) in vitro (in protein antigen- and hapten-specific assays) and in vivo (injecting soluble protein- and hapten-pulsed DC) to determine their suitability for the generation of T-h cell responses. Furthermore, we determined whether there is cross-presentation on MHC class II molecules during in vivo protein and hapten sensitization. Co-culture of protein-pulsed [with hen egg lysozyme (HEL) or with pigeon cytochrome c (CYT)] DC with T cells from HEL- or CYT- sensitized mice induced antigen-specific T cell proliferation, but compared to cultured Langerhans cells (LC), BMDC required higher protein antigen-pulsing concentrations (100 mug and 1 mg/ml). In contrast, at low protein concentrations (10 mug/ml), BMDC stimulated an HEL-specific hybridoma very efficiently. Using an in vitro T cell proliferation assay and in vivo delayed-type hypersensitivity and contact sensitivity assays, we found that protein- and hapten-pulsed BMDC were able to sensitize syngeneic but not allogeneic hosts. Furthermore, if we injected BALB/c- and C57BL/6-derived HEL-pulsed BMDC into F-1 mice, specific secondary proliferation of primed T cells occurred only when antigen-pulsed stimulator cells syngeneic to the injected BMDC were used. Using this model system we found that soluble proteins and haptens are presented by injected BMDC to host T cells in an MHC-restricted manner in vivo. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 42 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 2002 VL 14 IS 5 BP 493 EP 502 DI 10.1093/intimm/14.5.493 PG 10 WC Immunology SC Immunology GA 548KB UT WOS:000175386200007 PM 11978779 ER PT J AU Leyendecker, B Lamb, ME Harwood, RL Scholmerich, A AF Leyendecker, B Lamb, ME Harwood, RL Scholmerich, A TI Mothers' socialisation goals and evaluations of desirable and undesirable everyday situations in two diverse cultural groups SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID PUERTO-RICAN MOTHERS; MEXICAN-AMERICAN; FAMILIES; BELIEFS; VALUES; INDIVIDUALISM; ACHIEVEMENT; CHILDREN; BEHAVIOR; ANGLO AB Long-term socialisation goals and evaluations of infant behaviour in a variety of everyday contexts were studied among 45 mothers who had immigrated from Central America to the United States, and 41 mothers from European American backgrounds. In accord with expectations based on broad cultural constructs, mothers from Central America emphasised long-term socialisation goals related to Proper Demeanour. In addition, when describing and evaluating everyday situations, they were likely to attribute the desirability or undesirability of these situations to the child's own appropriate and cooperative behaviour, and were likely to highlight mutual enjoyment when describing preferred play situations. In contrast, Euro-American mothers emphasised long-term socialisation goals related to Self-Maximisation, and when describing undesirable everyday situations, stressed the role of external factors not under the child's control, presumably to preserve the child's self-esteem. However, it was also found that the Central American mothers endorse selected aspects of individualism related to promoting their children's economic and personal potential in the United States. These findings point not only to the multidimensional nature of individualism, but also to the heterogeneity of beliefs among Latino populations. The importance of studying within-group variation with regard to the individualism/sociocentrism construct is highlighted. C1 Ruhr Univ Bochum, Fak Psychol, D-44780 Bochum, Germany. NICHHD, Bethesda, MD 20892 USA. Univ Connecticut, Storrs, CT USA. RP Leyendecker, B (reprint author), Ruhr Univ Bochum, Fak Psychol, D-44780 Bochum, Germany. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 58 TC 39 Z9 48 U1 2 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD MAY PY 2002 VL 26 IS 3 BP 248 EP 258 DI 10.1080/01650250143000030 PG 11 WC Psychology, Developmental SC Psychology GA 542LV UT WOS:000175046100006 ER PT J AU Kehrl, JH Sinnarajah, S AF Kehrl, JH Sinnarajah, S TI RGS2: a multifunctional regulator of G-protein signaling SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE RGS; G-protein; adenylyl cyclases; olfaction; GTPase ID MESSENGER-RNA; DYNAMIC REGULATION; RECEPTOR; CELLS; MECHANISMS; ACTIVATION; EXPRESSION; GENE AB Regulators of G-protein signaling (RGS) proteins enhance the intrinsic rate at which certain heterotrimeric G-protein alpha-subunits hydrolyze GTP to GDP, thereby limiting the duration that alpha-subunits activate downstream effectors. This activity defines them as GTPase activating proteins (GAPs'). As do other RGS proteins RGS2 possesses a 120 ammo acid RGS domain, which mediates its GAP activity. In addition, RGS2 shares an N-terminal membrane targeting domain with RGS4 and RGS16. Found in many cell types. RGS2 expression is highly regulated. Functionally. RGS2 blocks Gqalpha-mediated signaling, a finding consistent with its potent Gqalpha GAP activity. Surprisingly, RGS2 inhibits Gs signaling to certain adenylyl cyclases. Like other RGS proteins, RGS2 lacks Gsalpha GAP activity, however it directly inhibits the activity of several adenylyl cyclase isoforms. Targeted mutation of RGS2 in mice impairs anti-viral immunity, increases anxiety levels, and alters synaptic development in hippocampal CA1 neurons. RGS2 has emerged as a multifunctional RGS protein that regulates multiple G-protein linked signaling pathways. Published by Elsevier Science Ltd. C1 NIAID, Immunoregulat Lab, B cell Mol Biol Sect, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, B cell Mol Biol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X NR 26 TC 92 Z9 92 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD MAY PY 2002 VL 34 IS 5 BP 432 EP 438 AR PII S1357-2725(01)00141-8 DI 10.1016/S1357-2725(01)00141-8 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 544UL UT WOS:000175180000002 PM 11906816 ER PT J AU Chen, SY Wang, LY Lunn, RM Tsai, WY Lee, PH Lee, CS Ahsan, H Zhang, YJ Chen, CJ Santella, RM AF Chen, SY Wang, LY Lunn, RM Tsai, WY Lee, PH Lee, CS Ahsan, H Zhang, YJ Chen, CJ Santella, RM TI Polycyclic aromatic hydrocarbon-DNA adducts in liver tissues of hepatocellular carcinoma patients and controls SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE PAH-DNA adduct; hepatocellular carcinoma; HbsAg; GSTM1; GSTP1 ID S-TRANSFERASE M1; WHITE BLOOD-CELLS; HEPATITIS-B VIRUS; AFLATOXIN EXPOSURE; INCREASED RISK; C VIRUS; GLUTATHIONE; POLYMORPHISMS; CANCER; ASSOCIATION AB HCC is a common cancer and HBV and AFB(1) are well-documented, major risk factors. Epidemiologic studies have documented that cigarette smoking also contributes to the development of HCC. PAHs are ubiquitous environmental pollutants and products of incomplete combustion. They are present in both mainstream and sidestream cigarette smoke. PAHs are metabolically activated by phase I enzymes, including CYP1A1, into electrophilic reactants (diol epoxides), which covalently bind to DNA to form adducts. Diol epoxides re also substrates for phase II detoxifying enzymes, including GSTM and GSTP. To examine the association between PAH-DNA adducts and HCC, adduct levels were determined in liver tissue by relative staining intensity with an immuno-peroxidase method using a polyclonal antiserum against BPDE-modified DNA. Subjects were also genotyped for polymorphism in several genes involved in the metabolism of PAH, including GSTM1 and GSTP1. Liver tissue was collected from patients with histologically confirmed HCC (n = 105) and from non-HCC controls (n = 37). There was a significant positive correlation (r = 0.3, p < 0.01) between adducts in tumor and adjacent nontumor tissues among HCC cases. The risk of HCC was higher after adjustment for age, sex and HBsAg in the group with the highest tertile tissue levels of PAH-DNA adducts (mean relative nuclear staining intensity of tumor and nontumor tissue >344) than in the group with the lowest tertile (staining < 241, OR = 3.9, 95% Cl = 1.0-14.9). Among non-HCC controls, there were no significant associations between adduct levels and cigarette smoking, GSTM1 null genotype and HBsAg positivity. A strikingly increased HCC risk was observed (OR = 20.3, 95% Cl = 5.0-81.8) among HBsAg-positive subjects whose PAH-DNA adduct levels were high (mean relative nuclear staining intensity of tumor and nontumor tissue >301, median of control tissues) compared to HBsAg-negative subjects who had low PAH-DNA adduct levels. 4-ABP- and AFB(1)-DNA adducts had been measured previously in these same tissues. Subjects with elevated DNA adduct levels of PAH, 4-ABP and AFB(1) had a significantly higher HCC risk with an OR of 36.7 (95% Cl 7.2-187.2) compared to those who had low DNA adduct levels. These results suggest that PAHs may play a role in human hepatocarcinogenesis in conjunction with HB-sAg carrier status, GSTM I and GSTP I genotypes and exposure to 4-ABP and AFB(1). (C) 2002 Wiley-Liss, Inc. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. Tzu Chi Univ, Inst Aboriginal Hlth, Hualien, Taiwan. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. RP Santella, RM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, Rm 505,701 W 168th St, New York, NY 10032 USA. RI Chen, Chien-Jen/C-6976-2008; 王, 豊裕/C-1460-2010; OI LEE, PO-HUANG/0000-0001-5831-035X FU NCI NIH HHS [P30 CA013696]; NIEHS NIH HHS [ES05116, P30 ES009089, P30ES09089, R01 ES005116] NR 44 TC 73 Z9 80 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2002 VL 99 IS 1 BP 14 EP 21 DI 10.1002/ijc.10291 PG 8 WC Oncology SC Oncology GA 546XD UT WOS:000175300900003 PM 11948486 ER PT J AU Feldman, AL Friedl, J Lans, TE Libutti, SK Lorang, D Miller, MS Turner, EM Hewitt, SM Alexander, HR AF Feldman, AL Friedl, J Lans, TE Libutti, SK Lorang, D Miller, MS Turner, EM Hewitt, SM Alexander, HR TI Retroviral gene transfer of interferon-inducible protein 10 inhibits growth of human melanoma xenografts SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE angiogenesis; chemokine; cancer; gene therapy; endothelium ID ESTABLISHED INTRACRANIAL TUMORS; IN-VIVO; THERAPY; LYMPHOCYTES; CHEMOKINE; CANCER; CELLS AB Interferon-inducible protein 10 (IP-10) is an immunomodulatory chemokine recently recognized to have potent antiangiogenic activity in vivo. Due to difficulties in the stability, manufacture and chronic administration of recombinant forms of endogenous antiangiogenic proteins, antiangiogenic gene therapy has emerged as a promising new form of cancer treatment. We retrovirally transduced A375 human melanoma cells with the human IP-10 gene and injected cells subcutaneously into nude mice. IP-10-transduced cells also were mixed with null-transduced cells in varying proportions before injection. In vivo growth of IP-10-transduced melanoma cells was markedly diminished compared to parental or null-transduced cells (p = 0.0002, Kruskal-Wallis test)This growth inhibition was associated with a marked reduction in microvessel density. The degree of growth inhibition of tumors following injection of a mixed population of null- and IP-10-transduced cells was directly associated with the fraction of IP-10-transduced cells present. We conclude that retroviral transduction of human melanoma cells with the IP-10 gene leads to sufficient protein secretion to inhibit angiogenesis and tumor growth. These findings suggest that IP-10 gene therapy might be an effective therapy in patients with cancer. Published 2002 Wiley-Liss, Inc.(dagger) C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012; OI Hewitt, Stephen/0000-0001-8283-1788 NR 19 TC 50 Z9 55 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2002 VL 99 IS 1 BP 149 EP 153 DI 10.1002/ijc.10292 PG 5 WC Oncology SC Oncology GA 546XD UT WOS:000175300900023 PM 11948506 ER PT J AU Morgan, CM Yanovski, SZ Nguyen, TT McDuffie, J Sebring, NG Jorge, MR Keil, M Yanovski, JA AF Morgan, CM Yanovski, SZ Nguyen, TT McDuffie, J Sebring, NG Jorge, MR Keil, M Yanovski, JA TI Loss of control over eating, adiposity, and psychopathology in overweight children SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE binge eating; obesity; child; race; psychopathology ID OBESE BINGE EATERS; DIETARY RESTRAINT; ADOLESCENT GIRLS; COMMUNITY SAMPLE; BODY-IMAGE; DISORDER; BEHAVIOR; QUESTIONNAIRE; POPULATION; PREVALENCE AB Objective: To investigate the relationship between loss of control over eating, adiposity, and psychological distress in a nontreatment sample of overweight children. Method: Based on self-reports of eating episodes, 172 overweight children, 6-10 years old, were categorized using the Questionnaire of Eating and Weight Patterns-Adolescent Version into those describing episodes of loss of control over eating (LC), and those with no loss of control (NoLC). Croups were compared on measures of adiposity, dieting, and eating behavior, and associated psychological distress. Results: LC children (33.1%) were heavier and had greater amounts of body fat than NoLC children. They also had higher anxiety, more depressive symptoms, and more body dissatisfaction. 5.3% met questionnaire criteria for BED. Episodes of loss of control occurred infrequently, were often contextual, and involved usual meal foods. Discussion: As in adults, overweight children reporting loss of control over eating have greater severity of obesity and more psychological distress than those with no such symptoms. It remains unknown whether children who endorse loss of control over eating before adolescence will be those who develop the greatest difficulties with binge eating or obesity in adulthood. (C) 2002 by Wiley Periodicals, Inc. C1 NIH, NICHD, Unit Growth & Obes, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Nutr, Bethesda, MD 20892 USA. Univ Fed Sao Paulo, Dept Psiquiatria, Sao Paulo, Brazil. RP Yanovski, JA (reprint author), NIH, NICHD, Unit Growth & Obes, Dev Endocrinol Branch, 10 Ctr Dr,Bldg 10,Room 10N262,MSC 1862, Bethesda, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 FU NICHD NIH HHS [Z-01-HD-04-00641] NR 47 TC 95 Z9 97 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2002 VL 31 IS 4 BP 430 EP 441 DI 10.1002/eat.10038 PG 12 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 538MX UT WOS:000174820700008 PM 11948648 ER PT J AU Sevostianov, A Fromm, S Nechaev, V Horwitz, B Braun, A AF Sevostianov, A Fromm, S Nechaev, V Horwitz, B Braun, A TI Effect of attention on central auditory processing: An fMRI study SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE auditory cortex; fMRI; mismatch negativity; selective attention; superior temporal sulcus; temporal lobes ID POSITRON-EMISSION-TOMOGRAPHY; EVENT-RELATED FMRI; INTRACEREBRAL POTENTIALS; VISUAL-STIMULI; RARE TARGET; MISMATCH NEGATIVITY; SELECTIVE ATTENTION; CORTEX ACTIVATION; PERCEPTION; MODULATION AB Functional magnetic resonance imaging was used to investigate preattentive and attentional processing of auditory stimuli in 18 right-handed normal volunteers. Responses to trains of 1000-Hz pure tones and infrequent (15%) deviant 1300-Hz tones were characterized while subjects ignored all tones; listened for deviants in the left ear; or listened for deviants in the right ear. Preattentive detection of deviants, associated with the mismatch negativity in electrophysiology, was associated with bilateral temporal lobe activation, with a rightward predominance. Processing of deviant stimuli while attending to either ear produced a more robust and widespread activation of these temporal regions, again with a rightward predominance. Thus, preattentive tone processing appears to be linked to asymmetric activation of a core set of temporal regions in which activity is significantly amplified by selective attention. Extratemporal regions activated by attending to targets in either ear included the anterior cingulate cortex, supramarginal gyrus, and dorsolateral prefrontal cortex. C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Braun, A (reprint author), NIH, 10-5N118A, Bethesda, MD 20892 USA. NR 42 TC 18 Z9 18 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PD MAY PY 2002 VL 112 IS 5 BP 587 EP 606 DI 10.1080/00207450290025671 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 558AX UT WOS:000175943200007 PM 12325392 ER PT J AU Figg, WD Kruger, EA Price, DK Kim, S Dahut, WD AF Figg, WD Kruger, EA Price, DK Kim, S Dahut, WD TI Inhibition of angiogenesis: Treatment options for patients with metastatic prostate cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE antiangiogenesis; cancer therapy; clinical trials; prostate carcinoma ID ENDOTHELIAL GROWTH-FACTOR; ENDOGENOUS MAMMALIAN METABOLITE; CALCIUM INFLUX INHIBITOR; TUMOR-GROWTH; CELL-LINES; PHASE-I; MICROVESSEL DENSITY; BREAST-CANCER; ANTIANGIOGENIC THERAPY; CARBOXYAMIDO-TRIAZOLE AB Prostate cancer is the most frequently diagnosed malignancy and the second most common cause of cancer-related death in men in the United States. Unfortunately, at the current time, no curative treatments are available for metastatic prostate cancer. As is the case for most solid tumors, the recruitment of blood vessels (angiogenesis) is key for the progression and metastasis of prostate cancer. Inhibition of this process is an attractive approach to treatment. Many antiangiogenic agents are currently in clinical development. The following discussion will outline the importance of angiogenesis in the metastasis and progression of prostate cancer, summarize the current surrogate markers of angiogenesis available for the drug development of antiangiogenic agents, and review examples of investigational agents that target tumor angiogenesis (e.g., TNP-470, Thalidomide, CC5013, Carboxyamido-triazole (CAI), Endostatin, SU5416 , SU6668, Bevacizumab (Anti-VEGF rhuMAb), and 2-Methoxyestradiol). C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Dahut, WD (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Rm 12N226,10 Ctr Dr, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012; Figg Sr, William/M-2411-2016 OI Ain, Kenneth/0000-0002-2668-934X; NR 86 TC 65 Z9 70 U1 0 U2 8 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD MAY PY 2002 VL 20 IS 2 BP 183 EP 194 DI 10.1023/A:1015626410273 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 555NZ UT WOS:000175801300005 PM 12099578 ER PT J AU Kaur, M Reed, E Sartor, O Dahut, W Figg, WD AF Kaur, M Reed, E Sartor, O Dahut, W Figg, WD TI Suramin's development: What did we learn? SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE prostate cancer; suramin ID REFRACTORY PROSTATE-CANCER; FLUTAMIDE WITHDRAWAL; CLINICAL-TRIALS; PHASE-II; CARBOXYAMIDO-TRIAZOLE; ADAPTIVE-CONTROL; TUMOR-MARKERS; WORKING-GROUP; ANTIGEN; HYDROCORTISONE AB Suramin, a polysulphonated napthylurea, has been extensively evaluated over the past 10 years as an anticancer agent, with the most interest in the treatment of prostate cancer. Early clinical results were promising with response rates of up to 70% being reported. However, a recent double-blind study showed only modest palliative effect in patients with androgen independent prostate cancer. In retrospect, it appears those initial reports failed to control for confounding variables such as antiandrogen withdrawal and hydrocortisone. Suramin causes numerous reversible toxicities (lethargy, rash, fatigue, anemia, hyperglycemia, hypocalcemia, coagulopathies, neutropenia, renal and hepatic complications). Neurotoxicity has been the most significant complication and appears to be related to the intensity of the dosing regimen. An optimal therapeutic dose has not been determined, but it is clear that adaptive controls add little benefit. Aside from moderate toxicities and the low therapeutic index in patients with prostate cancer, suramin's development has taught us some valuable lessons (i.e., anti-androgen withdrawal was noted during suramin's development, the use of PSA as an indicator of tumor burden was initiated during the evaluation of suramin). These lessons can be applied to all clinical trials in hormone refractory prostate cancer. Suramin has significantly enhanced the evolution of our knowledge in several areas of prostate cancer biology and treatment. C1 NCI, Mol Pharmacol Sect,Canc Therapeut Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. Louisiana State Univ, Stanley Scott Canc Ctr, New Orleans, LA USA. RP Figg, WD (reprint author), NCI, Med Branch, Canc Res Ctr, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 53 TC 45 Z9 45 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD MAY PY 2002 VL 20 IS 2 BP 209 EP 219 DI 10.1023/A:1015666024386 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 555NZ UT WOS:000175801300008 PM 12099581 ER PT J AU Tuaillon, N Shen, DF Berger, RB Lu, B Rollins, BJ Chan, CC AF Tuaillon, N Shen, DF Berger, RB Lu, B Rollins, BJ Chan, CC TI MCP-1 expression in endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ACUTE SEPTIC PERITONITIS; RECEPTOR-DEFICIENT MICE; NECROSIS-FACTOR-ALPHA; LPS-INDUCED UVEITIS; INTERFERON-GAMMA; MESSENGER-RNA; PROTECTS MICE; LIPOPOLYSACCHARIDE AB PURPOSE. Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with chemoattractant properties for monocytes, memory T cells, natural killer cells, mast cells, and basophils. To delineate the role played by MCP-1 in acute anterior uveitis, a common ocular inflammation, MCP-/- mice and wild-type matched control mice were analyzed for the development of endotoxin-induced uveitis (EIU) in response to subcutaneous injection of a sublethal dose of lipopolysaccharide (LPS). METHODS. EIU was induced in MCP-1(-/-) and wild-type control mice by a single subcutaneous injection of Salmonella typhimurium LPS endotoxin at day 0. Alternatively, MCP-1(-/-) mice were injected subcutaneously with LPS plus recombinant MCP-1 at day 0 and with recombinant MCP-1 6 hours later. Mice were killed at day I or 3 after injection. Serum levels of IL-1alpha, Il-1beta, IL-6, IFN-gamma, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1alpha, MIP-2, regulated on activation normal T-cell expressed and secreted (RANTES), and MCP-1 were determined by ELISA. Eyes were collected and analyzed histologically and by RT-PCR for MCP-1, IFN-gamma, IL-6, TNF-alpha, beta-actin, MCP-5, RANTES, KC, inflammatory protein (IP)-10, and toll-like receptor (TLR)-4. RESULTS. EIU was strongly reduced in MCP-1(-/-) mice compared with wild-type control mice. The number of ocular inflammatory cells was significantly reduced. Moreover, intraocular IFN-gamma transcription was increased. EIU was induced in MCP-1(-/-) mice by co-administration of recombinant rat MCP-1 and LPS. CONCLUSIONS. Data indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a new therapeutic strategy for acute anterior uveitis. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 48 TC 61 Z9 65 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 IS 5 BP 1493 EP 1498 PG 6 WC Ophthalmology SC Ophthalmology GA 548FN UT WOS:000175378100031 PM 11980865 ER PT J AU Espinosa-Heidmann, DG Suner, I Hernandez, EP Frazier, WD Csaky, KG Cousins, SW AF Espinosa-Heidmann, DG Suner, I Hernandez, EP Frazier, WD Csaky, KG Cousins, SW TI Age as an independent risk factor for severity of experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; SMOOTH-MUSCLE-CELLS; EXPERIMENTAL HISTOPLASMIC CHOROIDITIS; EXPERIMENTAL OCULAR HISTOPLASMOSIS; SENILE MACULAR DEGENERATION; ENDOTHELIAL GROWTH-FACTOR; PHOTODYNAMIC THERAPY; SUBRETINAL NEOVASCULARIZATION; EVOLUTIONARY PERSPECTIVE; DELAYED ANGIOGENESIS AB PURPOSE.. For many vascular diseases, aging appears to be an independent risk factor for severity of vascular complications, and blood vessels of aged individuals often demonstrate exaggerated repair responses to injury. This study was undertaken to determine the influence of aging on the severity of neovascularization in a mouse model of laser-induced choroidal neovascularization (CNV). METHODS. CNV was induced in young (2-month-old) and aged (16-month-old) C57BL/6 mice by making four separate choroidal burns in each eye with a diode red laser (650 run). At 1, 2, and 4 weeks, the left eyes were removed for histopathology, and the right eyes were removed for flatmount analysis of CNV surface area, vascularity, and cellularity. RESULTS. Aged mice demonstrated a much larger area of CNV than did young mice (3.81 +/- 1.28 Vs. 1.36 +/- 0.99 disc areas, P < 0.001) at 2 weeks, when the lesions showed maximum growth. Aged mice also demonstrated higher ratios for vascularity and cellularity of the CNV (1.34 +/- 0.06 vs. 1.03 +/- 0.11, P < 0.0001 and 4.66 +/- 1.19 vs. 1.91 +/- 0.81, P < 0.002 at 2 weeks, respectively). Histopathology revealed that CNV in older eyes was larger, thicker, and more cellular than in young eyes. CONCLUSIONS. In mice, age is associated with more severe CNV, defined as larger surface area, greater vascularity, and greater cellularity. Age-related systemic susceptibility factors, independent of local changes in the retina, may contribute to the greater severity of CNV in older than in younger individuals. C1 Miami Univ, Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, William L McKnight Vis Res Ctr,Dept Ophthalmol, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD USA. RP Cousins, SW (reprint author), Univ Miami, Sch Med, Bascom Palmer Eye Inst, William L McKnight Vis Res Ctr,Dept Ophthalmol, 1638 NW 10th Ave, Miami, FL 33136 USA. EM scousins@med.miami.edu FU NEI NIH HHS [EY/AI-13318] NR 76 TC 56 Z9 62 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 IS 5 BP 1567 EP 1573 PG 7 WC Ophthalmology SC Ophthalmology GA 548FN UT WOS:000175378100041 PM 11980875 ER PT J AU Ahmed, FA Brown, KM Dietrich, SA Morrison, J Johnson, E Tomarev, SI AF Ahmed, FA Brown, KM Dietrich, SA Morrison, J Johnson, E Tomarev, SI TI Changes in gene expression in the rat retina after experimentally-induced neuronal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lmdb, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC USA. OHSU, Casey Eye Inst, Portland, OR 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 MAY PY 2002 VL 43 SU 2 MA 3382 BP U959 EP U959 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700532 ER PT J AU Al-Khatib, SQ Suhler, EB Djalilian, AR Sen, HN Nussenblatt, RB Buggage, RR AF Al-Khatib, SQ Suhler, EB Djalilian, AR Sen, HN Nussenblatt, RB Buggage, RR TI The use of mycophenolate mofetil for the treatment of non-infectious uveitis in children SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 2 MA 4278 BP U1208 EP U1208 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701432 ER PT J AU Aleman, TS Scott, ML Chen, RJ Chico, JD Cheung, AY Van Hooser, JP Redmond, TM Palczewski, K Jacobson, SG Cideciyan, AV AF Aleman, TS Scott, ML Chen, RJ Chico, JD Cheung, AY Van Hooser, JP Redmond, TM Palczewski, K Jacobson, SG Cideciyan, AV TI Impairment of the papillary light reflex in Rpe65-/- mice and patients with Leber congenital amaurosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA USA. Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Cideciyan, Artur/A-1075-2007 OI Cideciyan, Artur/0000-0002-2018-0905 NR 0 TC 1 Z9 1 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 MAY PY 2002 VL 43 SU 2 MA 3490 BP U982 EP U982 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700644 ER PT J AU Arango, K Espinosa, DG Monroy, DC Hernandez, E Legra, JM Csaky, KG Cousins, SW AF Arango, K Espinosa, DG Monroy, DC Hernandez, E Legra, JM Csaky, KG Cousins, SW TI Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 1294 BP U293 EP U293 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601249 ER PT J AU Ayres, LM Caruso, RC Gahl, WA Kaiser-Kupfer, MI AF Ayres, LM Caruso, RC Gahl, WA Kaiser-Kupfer, MI TI Diagnosis of optic chiasm decussation anomalies in the Hermansky-Pudlak syndrome using steady-state flash visual evoked potentials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 237 BP U44 EP U44 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600211 ER PT J AU Battelle, B Kempler, KE Yamashita, R Sellers, JR AF Battelle, B Kempler, KE Yamashita, R Sellers, JR TI A photoreceptor-specific unconventional myosin is a protein kinase SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Florida, Whitney Lab, St Augustine, FL 32086 USA. Univ Florida, Dept Neurosci, St Augustine, FL 32086 USA. NHLBI, 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 MAY PY 2002 VL 43 SU 1 MA 1385 BP U311 EP U311 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601343 ER PT J AU Becerra, S Fariss, RN Meyer, C AF Becerra, S Fariss, RN Meyer, C TI Characterization of the pigment epithelium-derived factor and collagen interactions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. LMOD, Nei, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 2407 BP U571 EP U571 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602337 ER PT J AU Bettelheim, FA Lizak, MJ Zigler, SJ AF Bettelheim, FA Lizak, MJ Zigler, SJ TI Relaxographic studies on age dependence of human lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Adelphi Univ, Garden City, NY 11530 USA. NINDS, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, 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 MAY PY 2002 VL 43 SU 1 MA 471 BP U94 EP U94 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600449 ER PT J AU Boyle, DL Takemoto, L Brady, JP Wawrousek, EF AF Boyle, DL Takemoto, L Brady, JP Wawrousek, EF TI Morphological characterization of the alphaA-/alphaB-crystallin double knockout mouse lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD USA. Genet Therapy Inc, Gaithersburg, MD USA. Kansas State Univ, Div Biol, Manhattan, KS 66506 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 MAY PY 2002 VL 43 SU 2 MA 3582 BP U1001 EP U1001 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700736 ER PT J AU Buggage, RR Shen, D Tuaillon, N Levy-Clarke, GA Smith, JA Chan, CC AF Buggage, RR Shen, D Tuaillon, N Levy-Clarke, GA Smith, JA Chan, CC TI Molecular signatures of infectious agents in ocular neoplasms SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, 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 MAY PY 2002 VL 43 SU 1 MA 2591 BP U607 EP U607 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602525 ER PT J AU Byrnes, GA Baffi, J Chan, CC Csaky, KG AF Byrnes, GA Baffi, J Chan, CC Csaky, KG TI Clinicopathologic correlation of progressive atypical fibrovascular proliferation in agerelated macular degeneration (AMD) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 USN, Bethesda, MD 20084 USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 2788 BP U651 EP U651 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602720 ER PT J AU Caruso, RC Lopez, P Ayres, LA Smith, JA Schiffmann, R AF Caruso, RC Lopez, P Ayres, LA Smith, JA Schiffmann, R TI Assessment of visual function in mucolipidosis IV using ERG VEP and TAC SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 1197 BP U275 EP U275 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601155 ER PT J AU Caspi, RR Avichezer, D Chan, CC Lewis, GM Wiggert, B Liou, G AF Caspi, RR Avichezer, D Chan, CC Lewis, GM Wiggert, B Liou, G TI Immunologically privileged expression of the retinal self-antigen IRBP results in tolerance SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 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 MAY PY 2002 VL 43 SU 1 MA 1953 BP U449 EP U449 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601890 ER PT J AU Chan, CC Shen, D Hackett, JJ Buggage, RR Tuaillon, N AF Chan, CC Shen, D Hackett, JJ Buggage, RR Tuaillon, N TI Expression of chemokine receptors CXCR4 and CXCR5 and chemokine BLC in primary intraocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2579 BP U605 EP U605 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602513 ER PT J AU Chen, J Li, ZQ Vistica, BP Su, SB Wawrousek, EF Caspi, RR Gery, I AF Chen, J Li, ZQ Vistica, BP Su, SB Wawrousek, EF Caspi, RR Gery, I TI Features that characterize T-helper (Th) lymphocytes capable of inducing ocular inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1542 BP U343 EP U343 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601499 ER PT J AU Chen, S Samuel, W Fariss, RN Duncan, T Kutty, RK Wiggert, B AF Chen, S Samuel, W Fariss, RN Duncan, T Kutty, RK Wiggert, B TI Differentiation of cultured human retinal pigment epithelial (RPE) cells into neuronal phenotypes induced by feretnide SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, 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 MAY PY 2002 VL 43 SU 2 MA 4556 BP U1299 EP U1299 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701708 ER PT J AU Chen, Z Carper, D AF Chen, Z Carper, D TI The molecular role of estrogen in TGF-beta-induced cataracts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 2 MA 3546 BP U992 EP U992 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700697 ER PT J AU Chew, EY Davis, MD Seddon, JM Clemons, TE Hubbard, LD AF Chew, EY Davis, MD Seddon, JM Clemons, TE Hubbard, LD TI The effect of antioxidant and zinc supplements on change in drusen size/area in the Age-Related Eve Disease Study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EMMES Corp, Rockville, MD 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 MAY PY 2002 VL 43 SU 1 MA 1903 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601846 ER PT J AU Chin, MS Caruso, RC Detrick, B Hooks, JJ AF Chin, MS Caruso, RC Detrick, B Hooks, JJ TI Autoantibodies to transcription coactivators p75/p52 (LEDGF) found in patients with origin retinopathy of unknown SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, Immunol & Virol Sect, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 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 MAY PY 2002 VL 43 SU 1 MA 2213 BP U504 EP U504 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602145 ER PT J AU Christen, WG Glynn, RJ Sperduto, RD Chew, EY Buring, JE AF Christen, WG Glynn, RJ Sperduto, RD Chew, EY Buring, JE TI Age-related cataract in a randomized trial of beta-carotene in women SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1520 BP U339 EP U339 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601474 ER PT J AU Clark, AF Wang, WH MnNatt, LG Hellberg, P Pang, IH Rubin, JS Fingert, JH Sheffield, VC Stone, EM AF Clark, AF Wang, WH MnNatt, LG Hellberg, P Pang, IH Rubin, JS Fingert, JH Sheffield, VC Stone, EM TI Increased expression of sFRP-1 in glaucomatous trabecular meshwork and presence of a functional WNT signaling pathway that regulates IOP SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Alcon Res Ltd, Glaucoma Res, Ft Worth, TX USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA. Univ Iowa, Dept Pediat, HHMI, Iowa City, IA 52242 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2002 VL 43 SU 2 MA 4095 BP U1170 EP U1170 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701246 ER PT J AU Cousins, SW Csaky, KG AF Cousins, SW Csaky, KG TI Macrophage function in age-related macular degeneration (AMD) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Miami, Miami, FL 33152 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2002 VL 43 SU 1 MA 864 BP U187 EP U187 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600838 ER PT J AU Crawford, M Smith, JA Galita, DA Chan, CC AF Crawford, M Smith, JA Galita, DA Chan, CC TI Ultrastructural detection of chlamydia inclusions in epithelial cells using conjunctival swabs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Epidemiol & Clin Res, 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 MAY PY 2002 VL 43 SU 1 MA 1600 BP U354 EP U354 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601556 ER PT J AU Csaky, KG Baffi, J Cousins, S Byrnes, G AF Csaky, KG Baffi, J Cousins, S Byrnes, G TI Identification of choroidal vascular changes in experimental and clinical choroidal Neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD USA. BPEI, Miami, FL USA. Natl Naval Hosp, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 685 BP U149 EP U149 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600663 ER PT J AU Cui, W Tomarev, SI Chepelinsky, AB Duncan, MK AF Cui, W Tomarev, SI Chepelinsky, AB Duncan, MK TI MafB is expressed in developing lens and cooperates with Pax6 and Prox1 to regulate chicken beta B1 crystallin gene expression SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2329 BP U555 EP U555 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602262 ER PT J AU Curcio, CA Bradley, K Guidry, C Kirk, M Wilson, L Barnes, S Kruth, HS Chang, CCY Chang, TY AF Curcio, CA Bradley, K Guidry, C Kirk, M Wilson, L Barnes, S Kruth, HS Chang, CCY Chang, TY TI A local source for esterified cholesterol (EC) in human Bruch's membrane (BrM) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 UAB, Birmingham, AL USA. NHBLI, NIH, Bethesda, MD USA. Dartmouth Coll, Hanover, NH 03755 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 MAY PY 2002 VL 43 SU 1 MA 862 BP U187 EP U187 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600837 ER PT J AU Cusick, M Chew, EY Clemons, TE Klein, R Klein, BEK Hubbard, LD AF Cusick, M Chew, EY Clemons, TE Klein, R Klein, BEK Hubbard, LD TI Effect of antioxidant and zinc supplements on development of diabetic retinopathy in the age-related eye disease study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY PY 2002 VL 43 SU 1 MA 1909 BP U438 EP U438 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601852 ER PT J AU D'Amore, PA Massingham, LJ Smith, SR Roberts, AB Piek, E Darland, DC AF D'Amore, PA Massingham, LJ Smith, SR Roberts, AB Piek, E Darland, DC TI Pericyte production of VEGF is differentiation-dependent and mediates endothelial survival SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. NCI, 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 MAY PY 2002 VL 43 SU 1 MA 1932 BP U443 EP U443 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601869 ER PT J AU Djalilian, AR Koch, CA Nussenblatt, RB Zhuang, Z Holland, EJ Shen, D Chan, CC AF Djalilian, AR Koch, CA Nussenblatt, RB Zhuang, Z Holland, EJ Shen, D Chan, CC TI The use of microsatellite analysis to determine the survival of donor epithelial cells after limbal stem cell transplantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Cincinnati Eye Inst, Cincinnati, OH USA. RI Koch, Christian/A-4699-2008 OI Koch, Christian/0000-0003-3127-5739 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 MAY PY 2002 VL 43 SU 1 MA 2232 BP U507 EP U507 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602166 ER PT J AU Ebong, SJ Chepelinsky, AB Robinson, ML Raz, R Zhao, H Guo, Y Levy, DE Egwuagu, CE AF Ebong, SJ Chepelinsky, AB Robinson, ML Raz, R Zhao, H Guo, Y Levy, DE Egwuagu, CE TI STAT3 is not essential for mouse lens development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Children Res Inst, Columbus, OH USA. NYU, Sch Med, New York, NY 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 MAY PY 2002 VL 43 SU 1 MA 2335 BP U556 EP U556 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602267 ER PT J AU Emmert-Buck, LT Best, CJM Bernstein, SL AF Emmert-Buck, LT Best, CJM Bernstein, SL TI Comparison of human retinal gene expression between cDNA micro- and macroarrays SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Maryland, Baltimore, MD 21201 USA. NCI, Pathol Lab, 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 MAY PY 2002 VL 43 SU 1 MA 1426 BP U321 EP U321 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601382 ER PT J AU Espinosa, DG Marin, ME Hernandez, E Csaky, KG Cousins, SW AF Espinosa, DG Marin, ME Hernandez, E Csaky, KG Cousins, SW TI Estrogen depletion decreases matrix metalloproteinase-2 expression and increases SubRPE deposit accumulation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA. NEI, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 698 BP U151 EP U151 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600673 ER PT J AU Fan, J Donovan, AK Ledee, DR Zelenka, PS Chepelinsky, AB AF Fan, J Donovan, AK Ledee, DR Zelenka, PS Chepelinsky, AB TI Identification of proteins interacting with the lens major intrinsic protein (MIP)/Aquaporin 0 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Med Dev Biol, 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 MAY PY 2002 VL 43 SU 2 MA 4639 BP U1314 EP U1314 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701790 ER PT J AU Fine, HF Wright, ME Csaky, KG Masur, H Polis, MA Robinson, MR AF Fine, HF Wright, ME Csaky, KG Masur, H Polis, MA Robinson, MR TI Peripheral choroidal neovascularization as a late finding in HIV-infected patients with inactive cytomegalovirus retinitis and ocular inflammation from immune recovery uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. NIAID, 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 MAY PY 2002 VL 43 SU 1 MA 2208 BP U503 EP U503 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602142 ER PT J AU Gao, CY Negash, S Zelenka, PS AF Gao, CY Negash, S Zelenka, PS TI Cdk5 regulates corneal epithelial cell adhesion and migration in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, 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 MAY PY 2002 VL 43 SU 2 MA 4211 BP U1195 EP U1195 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701362 ER PT J AU Gao, G Li, Y Fant, J Crosson, CE Becerra, SP Ma, JX AF Gao, G Li, Y Fant, J Crosson, CE Becerra, SP Ma, JX TI Rat strain difference in ischemic regulation of VEGF and PEDF and in susceptibilities to retinal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Storm Eye Inst, Charleston, SC 29425 USA. NEI, Retinal Cell & Mol Biol Lab, 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 MAY PY 2002 VL 43 SU 1 MA 2754 BP U643 EP U643 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602684 ER PT J AU Gensler, GR Sperduto, RD Klein, BEK Klein, R Chew, EY AF Gensler, GR Sperduto, RD Klein, BEK Klein, R Chew, EY TI The seven-year incidence and progression of cataract in the Age-Related Eye Disease Study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Emmes Corp, Rockville, MD USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2002 VL 43 SU 1 MA 1908 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601851 ER PT J AU Gilger, BC Roberge, KA Salmon, JH Cruysburg, LPJ Robinson, MR Kim, H Edelhauser, HF Papich, M AF Gilger, BC Roberge, KA Salmon, JH Cruysburg, LPJ Robinson, MR Kim, H Edelhauser, HF Papich, M TI In vivo and in vitro studies of transscleral diffusion of cyclosporine A through equine sclera SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 N Carolina State Univ, Raleigh, NC 27695 USA. Emory Univ, Atlanta, GA 30322 USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1852 BP U425 EP U425 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601806 ER PT J AU Golestaneh, N Kumar, S Fan, J Chepelinsky, AB AF Golestaneh, N Kumar, S Fan, J Chepelinsky, AB TI Transcription regulatory elements of the lens MIP/aquaporin 0 gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4642 BP U1314 EP U1314 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701794 ER PT J AU Gottsch, JD Bowers, A Margulies, EH Seitzman, GD Kim, SW Saha, S Jun, AS Stark, WJ Liu, SH AF Gottsch, JD Bowers, A Margulies, EH Seitzman, GD Kim, SW Saha, S Jun, AS Stark, WJ Liu, SH TI Serial analysis of gene expression in the corneal endothelium in Fuchs' dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Univ, Wilmer Eye Inst, Ctr Corneal Genet, Baltimore, MD 21218 USA. NHGRI, Genome Technol Branch, NIH, Washington, DC USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Mol Genet Lab, Baltimore, MD 21205 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 MAY PY 2002 VL 43 SU 2 MA 4007 BP U1151 EP U1151 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701158 ER PT J AU Ham, DI Gentleman, S Chan, CC McDowell, JH Redmond, TM Gery, I AF Ham, DI Gentleman, S Chan, CC McDowell, JH Redmond, TM Gery, I TI High uveitogenicity of RPE65 in rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Ophthalmol, Gainesville, FL 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 MAY PY 2002 VL 43 SU 1 MA 1541 BP U343 EP U343 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601496 ER PT J AU Harrison, JM Reitsamer, HA Alvarado-Garcia, MM Roache, JD Elkashef, A Mojsiak, J AF Harrison, JM Reitsamer, HA Alvarado-Garcia, MM Roache, JD Elkashef, A Mojsiak, J TI S-Cone ERG in cocaine-dependent humans and controls SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Vienna, Sch Med, Dept Physiol, Vienna, Austria. NIDA, Div Treat Res & Dev, 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 MAY PY 2002 VL 43 SU 1 MA 1193 BP U274 EP U274 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601150 ER PT J AU Herbort, CP Shen, DF Bovey, E Buggage, RR Egwuagu, CE Chan, CC AF Herbort, CP Shen, DF Bovey, E Buggage, RR Egwuagu, CE Chan, CC TI Primary intraocular lymphoma: Possible role of Toxoplasma gondii in the lymphomagenesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 La Source Eye Ctr, Lausanne, Switzerland. Univ Lausanne, Lausanne, Switzerland. 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4294 BP U1212 EP U1212 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701446 ER PT J AU Hickman, FI Fariss, RN Pagan-Mercado, G Yamamoto, T Wawrousek, EF Yabe-Nishimura, C Tsai, JY AF Hickman, FI Fariss, RN Pagan-Mercado, G Yamamoto, T Wawrousek, EF Yabe-Nishimura, C Tsai, JY TI Characterization of retinal neurons over-expressing human aldose reductase in Smaa-Har mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Intramural Res, Bethesda, MD 20892 USA. NEI, Biol Core Facil, Bethesda, MD 20892 USA. NEI, Transgen Core Facil, Bethesda, MD 20892 USA. Kyoto Prefectural Univ Med, Dept Pharmacol, Kyoto, Japan. 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 MAY PY 2002 VL 43 SU 1 MA 742 BP U160 EP U160 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600717 ER PT J AU Horwitz, J Wawrousek, EF Huang, QL Garland, D Ding, L Brady, JP AF Horwitz, J Wawrousek, EF Huang, QL Garland, D Ding, L Brady, JP TI Gamma-crystallin anomalies in alpha A-crystallin gene knockout mouse lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1921 BP U441 EP U441 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601862 ER PT J AU Hough, RB Avivi, A Davis, J Alma, J Nevo, E Piatigorsky, J AF Hough, RB Avivi, A Davis, J Alma, J Nevo, E Piatigorsky, J TI Adaptive changes of small heat shock protein/alpha B-crystallin promoter activity of the blind mole rat to subterranean life SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Univ Haifa, Inst Evolut, IL-31999 Haifa, Israel. 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 MAY PY 2002 VL 43 SU 2 MA 3598 BP U1003 EP U1003 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700750 ER PT J AU Humphrey, SC Smith, JA Crawford, MA Hackett, JJ Galito, DA Chan, CC AF Humphrey, SC Smith, JA Crawford, MA Hackett, JJ Galito, DA Chan, CC TI Keratinization in the conjunctiva of patients with Keratoconjunctivitis Sicca SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LI, 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 MAY PY 2002 VL 43 SU 1 MA 1098 BP U240 EP U240 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601055 ER PT J AU Izumi, K Zhang, Q Sergeev, Y Mashima, Y Noda, S Imamura, Y Kudoh, J Shimizu, N Tanaka, Y Iwata, T AF Izumi, K Zhang, Q Sergeev, Y Mashima, Y Noda, S Imamura, Y Kudoh, J Shimizu, N Tanaka, Y Iwata, T TI Comparison of retina specific amine oxidase (AOC2) and super family gene vascular adhesion protein 1 (AOC3) tandently located in chromosome 17q21 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Natl Tokyo Med Ctr, Natl Ctr Sensory Organs, Tokyo, Japan. NEI, NIH, Rockville, MD USA. Keio Univ, Sch Med, Dept Biol Mol, Tokyo, Japan. Tokai Univ, Sch Hlth Sci, Dept Nursing, Isehara, Kanagawa, Japan. 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 MAY PY 2002 VL 43 SU 1 MA 1433 BP U322 EP U322 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601391 ER PT J AU John, M Carper, DA Subramanian, S Wang, RR Ma, W Spector, A AF John, M Carper, DA Subramanian, S Wang, RR Ma, W Spector, A TI Differential gene expression of matrix metalloproteinases (MMPs) in an oxidative stress model of cataract SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2357 BP U561 EP U561 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602290 ER PT J AU Kantorow, M Sheets, NL Chauhan, B Wawrousek, E Hejtmancik, J Cvekl, A AF Kantorow, M Sheets, NL Chauhan, B Wawrousek, E Hejtmancik, J Cvekl, A TI Lens-specific up-regulation of the ARK membrane receptor tyrosine kinase in Emory mouse cataract SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 W Virginia Univ, Morgantown, WV 26506 USA. Albert Einstein Coll Med, New York, NY USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1917 BP U441 EP U441 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601860 ER PT J AU Kanungo, J Swamynathan, SK Kozmik, Z Piatigorsky, J AF Kanungo, J Swamynathan, SK Kozmik, Z Piatigorsky, J TI Genomic analyses and relative expression patterns of the genes for cornea/lens-specific and ubiquitous gelsolins in zebrafish SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Lab Mol Dev Biol, Bethesda, MD 20892 USA. RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY PY 2002 VL 43 SU 2 MA 3198 BP U883 EP U883 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700350 ER PT J AU Katz, ML Redmond, TM Narfstrom, K AF Katz, ML Redmond, TM Narfstrom, K TI Adeno-associated viral mediated gene therapy for RPE65 gene defect in a canine model - Partial correction of morphological phenotype SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Missouri, Mason Eye Inst, Sch Med, Columbia, MO USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Missouri, Coll Vet Sci, Columbia, MO 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 MAY PY 2002 VL 43 SU 2 MA 4592 BP U1305 EP U1305 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701744 ER PT J AU Kim, H Baffi, J Collins, N Fronheiser, M Byrnes, G Csaky, KG Yuan, P Lutz, RJ Dedrick, R Robinson, MR AF Kim, H Baffi, J Collins, N Fronheiser, M Byrnes, G Csaky, KG Yuan, P Lutz, RJ Dedrick, R Robinson, MR TI The ocular distribution of a lipophilic fluorescent compound released in the subconjunctival space from a sustain-release device in the rat SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NIH, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 2303 BP U519 EP U519 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602234 ER PT J AU Koretz, JF Wimuttisuk, W Garland, D AF Koretz, JF Wimuttisuk, W Garland, D TI Characterization of alpha-crystallin within adult human lenses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Rensselaer Polytech Inst, Troy, NY USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2002 VL 43 SU 2 MA 3554 BP U995 EP U995 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700705 ER PT J AU Kumar, MV Nagineni, CN Hooks, JJ Detrick, B AF Kumar, MV Nagineni, CN Hooks, JJ Detrick, B TI b > expression of toll-like receptors in human retinal pigment epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1563 BP U347 EP U347 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601519 ER PT J AU Kutty, R Fariss, RN Chen, S Samuel, W Duncan, T Bridges, CC El-Sherbeny, A Smith, SB Wiggert, B AF Kutty, R Fariss, RN Chen, S Samuel, W Duncan, T Bridges, CC El-Sherbeny, A Smith, SB Wiggert, B TI Analysis of the expression of NORPEG protein in retinal pigment epithelium and other ocular tissue SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Cell Biol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Anat, Augusta, GA 30912 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 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 MAY PY 2002 VL 43 SU 2 MA 4551 BP U1299 EP U1299 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701703 ER PT J AU Lane, JT Kadar, PF Toris, CB AF Lane, JT Kadar, PF Toris, CB TI Aqueous flow is reduced in galactose-fed dogs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NEI, Lab Ocular Therapeut, 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 MAY PY 2002 VL 43 SU 2 MA 3276 BP U901 EP U901 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700430 ER PT J AU Ledee, DR Zelenka, PS AF Ledee, DR Zelenka, PS TI Interaction between the CDK5 activating proteins, p39 and p35, and an alternatively spliced zinc-finger protein in lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, 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 MAY PY 2002 VL 43 SU 1 MA 2333 BP U556 EP U556 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602266 ER PT J AU Lindblad, AS Clemons, TE Bressler, SB Chew, EY AF Lindblad, AS Clemons, TE Bressler, SB Chew, EY TI NEI-VFQ in the age-related eye disease study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 EMMES Corp, Rockville, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1905 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601847 ER PT J AU Liu, XZ Ouyang, XM Hejtmancik, JF Jacobson, SG Li, AR Du, LL Newton, VE Nance, WE AF Liu, XZ Ouyang, XM Hejtmancik, JF Jacobson, SG Li, AR Du, LL Newton, VE Nance, WE TI Mutation analysis of USH genes in patients with USH and non-syndromic RP SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Miami, Miami, FL 33152 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. Univ Manchester, Ctr Audiol, Manchester, Lancs, England. Virginia Commonwealth Univ, Richmond, VA 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 MAY PY 2002 VL 43 SU 1 MA 2391 BP U569 EP U569 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602323 ER PT J AU Machida, S Sieving, PA Bush, RA AF Machida, S Sieving, PA Bush, RA TI Contribution of the photopic negative response to the photopic ERG in rats with inherited photoreceptor degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Iwate Med Univ, Dept Ophthalmol, Morioka, Iwate 020, Japan. NEI, 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 MAY PY 2002 VL 43 SU 2 MA 3489 BP U982 EP U982 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700641 ER PT J AU Mahdi, R Gery, I Egwuagu, CE Lee, O Said, S AF Mahdi, R Gery, I Egwuagu, CE Lee, O Said, S TI Expression of suppressors of cytokine signaling (SOCS) genes in the retina correlates with onset if experimental autoimmune uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1543 BP U343 EP U343 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601497 ER PT J AU Martin, DF Gensler, G Klein, BEK Klein, R Chew, EY AF Martin, DF Gensler, G Klein, BEK Klein, R Chew, EY TI The effect of cataract surgery on progression to advanced AMD SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Emory Eye Ctr, Atlanta, GA USA. EMMES Corp, Rockville, MD USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1907 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601848 ER PT J AU Miyamoto, Y Mohri, M Kanayama, A Shimizu, M Hisatsune, T Reinach, PS Moskovitz, J AF Miyamoto, Y Mohri, M Kanayama, A Shimizu, M Hisatsune, T Reinach, PS Moskovitz, J TI Hypochlorite ion suppresses interleukin-1 alpha production via interruption of NF kappa B activation in cultured human corneal epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Tokyo, Dept Integrated Biosci, Tokyo, Chiba, Japan. Dept Appl Biol Chem, Tokyo, Japan. SUNY, Dept Biol Sci, Coll Optometry, New York, NY USA. NHLBI, Biochem Lab, 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 MAY PY 2002 VL 43 SU 1 MA 31 BP U1 EP U1 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600007 ER PT J AU Moiseyev, GP Goletz, P Tsin, ATC Redmond, TM Crouch, RK Ma, JX AF Moiseyev, GP Goletz, P Tsin, ATC Redmond, TM Crouch, RK Ma, JX TI Continuous retinyl ester accumulation in Rpe,65 knockout mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Univ Texas San Antonio, San Antonio, TX 78285 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4559 BP U1300 EP U1300 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701710 ER PT J AU Momma, Y Nagineni, CN Chin, MS Srinivasan, K Detrick, B Hooks, JJ AF Momma, Y Nagineni, CN Chin, MS Srinivasan, K Detrick, B Hooks, JJ TI Infection of HRPE cells with CMV induces the differential expression and secretion of MCP-1, MCP-3 and IL-8 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Tokohu Univ, Div Pediat Dent, Grad Sch Dent, Miyagi, Japan. 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4329 BP U1251 EP U1251 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701481 ER PT J AU Monroy, DC Espinosa, DG Legra, JM Hernandez, E Csaky, KG Cousins, SW AF Monroy, DC Espinosa, DG Legra, JM Hernandez, E Csaky, KG Cousins, SW TI The role of estrogen status and lesion severity in experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Miami, Sch Med, Miami, FL USA. Bascom Palmer Eye Inst, Miami, FL 33136 USA. NEI, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 1295 BP U293 EP U293 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601252 ER PT J AU Murata, M Murata, S Sato, S AF Murata, M Murata, S Sato, S TI The effect of conditioned media of astrocytoma cells on survival/growth of dog retinal capillary pericytes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. Yahaba Eye Clin, Yahaba, Japan. Mitake Eye Clin, Morioka, Iwate, Japan. 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 MAY PY 2002 VL 43 SU 2 MA 3704 BP U1026 EP U1026 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700856 ER PT J AU Narfstrom, K Bragadottir, R Redmond, TM Katz, ML Lei, B Lai, CM Rakoczy, EP AF Narfstrom, K Bragadottir, R Redmond, TM Katz, ML Lei, B Lai, CM Rakoczy, EP TI Gene therapy in 6 dogs with RPE65 null mutation improves visual function: A short-term study using clinical observations. Electophysiology and morphology SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Missouri, Coll Vet Sci, Dept Med & Surg, Columbia, MO USA. Ullevaal Univ Hosp, Dept Ophthalmol, Oslo, Norway. NEI, NIH, Bethesda, MD USA. Sch Med, Dept Ophthalmol, Columbia, MO USA. Univ Missouri, Dept Ophthalmol, Columbia, MO USA. Univ Missouri, Dept Surg & Med, Coll Vet Med, Columbia, MO USA. Univ Missouri, Sch Med, Columbia, MO USA. Univ Western Australia, Lions Eye Inst, Perth, WA 6009, Australia. 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 MAY PY 2002 VL 43 SU 2 MA 4601 BP U1307 EP U1307 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701752 ER PT J AU Neal, RE Ercal, N Aykin-Burnes, N Zigler, JS AF Neal, RE Ercal, N Aykin-Burnes, N Zigler, JS TI Does Pb2+ exposure alter the structural protein profile in the lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, LMOD, NIH, Bethesda, MD 20892 USA. Univ Missouri, Dept Chem, Rolla, MO 65401 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 MAY PY 2002 VL 43 SU 2 MA 4796 BP U1351 EP U1351 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701948 ER PT J AU Pagan-Mercado, G Yamamoto, T Hickman, FI Fariss, RN Tsai, JY AF Pagan-Mercado, G Yamamoto, T Hickman, FI Fariss, RN Tsai, JY TI Analysis of NG2 as a marker for retinal pericytes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Intramural Res, Bethesda, MD 20892 USA. NEI, Biol Imaging Core Facil, 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 MAY PY 2002 VL 43 SU 2 MA 3700 BP U1025 EP U1025 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700851 ER PT J AU Radu, RA Mata, NL Sieving, PA Travis, GH AF Radu, RA Mata, NL Sieving, PA Travis, GH TI Treatment Of aber-/- mice with iscuretintain inhibits accumulation of lipofuscin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. NEI, 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 MAY PY 2002 VL 43 SU 2 MA 4579 BP U1303 EP U1303 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701729 ER PT J AU Rao, PV Maddala, RL Deng, PF Costello, MJ Wawrousek, E Zigler, JS AF Rao, PV Maddala, RL Deng, PF Costello, MJ Wawrousek, E Zigler, JS TI Cytoskeletal and morphological changes in Rho GTPase inactivated transgenic mouse lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27515 USA. NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1923 BP U442 EP U442 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601866 ER PT J AU Robinson, MR Kim, H Collins, N Fronheiser, M Lee, S Sullivan, J Yuan, P Byrnes, G Baffi, J Csaky, K AF Robinson, MR Kim, H Collins, N Fronheiser, M Lee, S Sullivan, J Yuan, P Byrnes, G Baffi, J Csaky, K TI One-piece silicone intravitreal implants for sustained drug release SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. NIH, Mech Instrument Design & Fabricat Sect, Bethesda, MD 20892 USA. NIH, Fabricat Sect, Bethesda, MD 20892 USA. NIH, Dept Pharm, Ctr Clin, 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 MAY PY 2002 VL 43 SU 1 MA 2297 BP U518 EP U518 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602228 ER PT J AU SanGiovanni, JP Beck, RW Moke, PS Turpin, AH Johnson, CA Ferris, FL Birch, EE Kraker, RT Cox, TA AF SanGiovanni, JP Beck, RW Moke, PS Turpin, AH Johnson, CA Ferris, FL Birch, EE Kraker, RT Cox, TA TI A new PC-based method of measuring visual acuity in clinical trials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. Jaeb Ctr Hlth Res, Tampa, FL USA. Curtin Univ Technol, Perth, WA 6001, Australia. Devers Eye Inst, Portland, OR USA. Retina Fdn SW, Dallas, TX USA. RI SanGiovanni, John Paul/A-7605-2008 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 MAY PY 2002 VL 43 SU 1 MA 874 BP U191 EP U191 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600850 ER PT J AU Seddon, JM Chew, EY Klein, R Clemons, TE AF Seddon, JM Chew, EY Klein, R Clemons, TE TI Is cholesterol a risk factor for progression to advanced AMD? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2002 VL 43 SU 1 MA 1904 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601849 ER PT J AU Seeliger, MW Grimm, C Jaissle, GB Zrenner, E Reme, CE Humphries, P Biel, M Fariss, RN Redmond, TM Wenzef, A AF Seeliger, MW Grimm, C Jaissle, GB Zrenner, E Reme, CE Humphries, P Biel, M Fariss, RN Redmond, TM Wenzef, A TI Genetic separation of rod and cone-driven activity in RPE65 knockout mice identifies the rods as the source of vision in a form of lebers congenital amaurosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Retinal Electrodiagnost Res Grp, Dept Ophthalmol 2, Tubingen, Germany. Univ Zurich, Lab Retinal Cell Biol, Zurich, Switzerland. Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland. Univ Munich, Dept Pharm, Zentrum Pharmaforsch, Munich, Germany. NEI, Lab Mech Ocular Dis, Bethesda, MD 20892 USA. NEI, Lab Retinal Cell & Mol Biol, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2002 VL 43 SU 2 MA 3682 BP U1020 EP U1020 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700832 ER PT J AU Seitzman, GD Gottisch, JD Margulies, EH Bowers, AL Kim, SW Saha, S Jun, AS Stark, WJ Liu, SH AF Seitzman, GD Gottisch, JD Margulies, EH Bowers, AL Kim, SW Saha, S Jun, AS Stark, WJ Liu, SH TI Gene expression in donor cornea endothelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21287 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Sch, Oncol Ctr Mol Genet Lab, Baltimore, MD 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 MAY PY 2002 VL 43 SU 2 MA 4005 BP U1151 EP U1151 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701157 ER PT J AU Shen, D Tuaillon, N Buggage, RR Chan, CC AF Shen, D Tuaillon, N Buggage, RR Chan, CC TI The effect of a secretory phospholipase A2 inhibitor, 12-epi-scalaradial, on Toxoplasma gondii infection SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, NIH, Bethlehem, PA 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 MAY PY 2002 VL 43 SU 2 MA 4297 BP U1212 EP U1212 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701450 ER PT J AU Silver, PB Agarwal, RK Su, SB Chan, CC Caspi, R AF Silver, PB Agarwal, RK Su, SB Chan, CC Caspi, R TI Vaccination with a plasmid encoding retinal interphotoreceptor retinoid-binding protein (IRBP) protects mice against experimental autoimmune uveitis (EAU) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1539 BP U343 EP U343 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601495 ER PT J AU Smith, JA Reed, GF Grieshaber, S Goodman, L Vanderhoof, VH Nelson, LN AF Smith, JA Reed, GF Grieshaber, S Goodman, L Vanderhoof, VH Nelson, LN TI Dry eye in patients with karyotypically normal spontaneous premature ovarian failure SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, DECR, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NICHD, Bethesda, MD 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 MAY PY 2002 VL 43 SU 2 MA 3890 BP U1117 EP U1117 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701040 ER PT J AU Srinivasan, K Detrick, B Hooks, JJ AF Srinivasan, K Detrick, B Hooks, JJ TI Differential regulation of transcription of chemokine receptors in human corneal and retinal pigment epithelial cell lines during Herpes Simplex virus-1 (HSV-1) infection SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4307 BP U1214 EP U1214 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701461 ER PT J AU Suhler, EB Djalilian, AR Khoshnevisan, MA Al-Khatib, SQ Sen, HN Nussenblatt, RB Buggage, RR AF Suhler, EB Djalilian, AR Khoshnevisan, MA Al-Khatib, SQ Sen, HN Nussenblatt, RB Buggage, RR TI Efficacy of mycophenolate mofetil in treatment of ocular inflammatory disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Immunol Lab, 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 MAY PY 2002 VL 43 SU 2 MA 4279 BP U1208 EP U1208 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701430 ER PT J AU Suner, IJ Tafur, CM Espinosa-Heidmann, DG Legra, JM Arango, K Hernandez, E Monroy, D Csaky, KG Cousins, SW AF Suner, IJ Tafur, CM Espinosa-Heidmann, DG Legra, JM Arango, K Hernandez, E Monroy, D Csaky, KG Cousins, SW TI Nicotine increases severity of choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Bascom Palmer Eye Inst, Miami, FL 33136 USA. Miami Vet Affairs Med Ctr, Miami, FL USA. NEI, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 1292 BP U293 EP U293 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601248 ER PT J AU Swamynathan, SK Piatigorsky, J AF Swamynathan, SK Piatigorsky, J TI Orientation-dependency and silencing of an inter-genic enhancer in the divergently transcribed mouse alpha beta-crystallin and MKBP/HSPB2 genes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2442 BP U577 EP U577 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602372 ER PT J AU Takase, H Sugita, S Rhee, DJ Imai, Y Taguchi, C Sugamoto, Y Tagawa, Y Nishihira, J Russell, P Mochizuki, M AF Takase, H Sugita, S Rhee, DJ Imai, Y Taguchi, C Sugamoto, Y Tagawa, Y Nishihira, J Russell, P Mochizuki, M TI Macrophage migration inhibitory factor (MIF) enhances Th1 type cytokine in the human eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Grad Sch, Tokyo, Japan. NEI, Lab Mech & Ocular Dis, NIH, Bethesda, MD 20892 USA. Kurume Univ, Sch Med, Dept Ophthalmol, Fukuoka, Japan. Hokkaido Univ, Sch Med, Dept Ophthalmol, Sapporo, Hokkaido 060, Japan. Hokkaido Univ, Sch Med, Cent Res Inst, Sapporo, Hokkaido 060, Japan. 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 MAY PY 2002 VL 43 SU 1 MA 1564 BP U347 EP U347 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601522 ER PT J AU Tomarev, SI Torrado, M Trivedi, R Karavanova, I AF Tomarev, SI Torrado, M Trivedi, R Karavanova, I TI Optimedin, a new olfactomedin-related protein, interacts with myocilin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. RI Torrado, Mario/A-4889-2010 OI Torrado, Mario/0000-0001-9762-7018 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 MAY PY 2002 VL 43 SU 2 MA 3011 BP U847 EP U847 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700165 ER PT J AU Tsai, JYY Yamamoto, T Fariss, RN Hickman, FI Pagan-Mercado, G AF Tsai, JYY Yamamoto, T Fariss, RN Hickman, FI Pagan-Mercado, G TI Using SMAA-GFP mice to study pericyte coverage of retinal vessels SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Intramural Res, Bethesda, MD 20892 USA. NEI, Biol Imaging Core Facil, 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 MAY PY 2002 VL 43 SU 1 MA 1929 BP U443 EP U443 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601870 ER PT J AU Tsilou, ET Rubin, BI Reed, G McCain, L Gahl, W Kaiser-Kupfer, MI AF Tsilou, ET Rubin, BI Reed, G McCain, L Gahl, W Kaiser-Kupfer, MI TI Ophthalmic heterogeneity in the Hemansky-Pudlak syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Ophthalm Genet & Visual Funct Branch, Bethesda, MD USA. Biometry Branch, Bethesda, MD USA. NEI, NIH, Bethesda, MD USA. NICHD, Sect Human Biochem Genet, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 343 BP U68 EP U68 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600319 ER PT J AU Tsina, E Koutalos, Y Chen, C Crouch, RK Wiggert, B Cornwall, MC AF Tsina, E Koutalos, Y Chen, C Crouch, RK Wiggert, B Cornwall, MC TI Transport of retinal from salamander rod photoreceptors by IRBP and serum albumin following bleaching SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02215 USA. Univ Colorado, Sch Med, Dept Physiol & Biophys, Denver, CO 80202 USA. Med Univ S Carolina, Dept Ophthalmol, 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3746 BP U1034 EP U1034 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700899 ER PT J AU Velez, G Silk, W Csaky, KG AF Velez, G Silk, W Csaky, KG TI Correlation of in vivo fluorescein angriography findings with in vitro fluorescein uptake by monocytes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2002 VL 43 SU 1 MA 516 BP U103 EP U103 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600494 ER PT J AU Voronina, VA Koslov, SV Mathers, PH Lewandoski, M AF Voronina, VA Koslov, SV Mathers, PH Lewandoski, M TI Conditional inactivation of the Rx homeobox gene results in viable anoplithalmic animals SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 W Virginia Univ, Sensory Neurosci Res Ctr, Morgantown, WV 26506 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 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 MAY PY 2002 VL 43 SU 1 MA 2003 BP U461 EP U461 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601935 ER PT J AU Wesolowska, A Nelson, RF Connaughton, VP AF Wesolowska, A Nelson, RF Connaughton, VP TI Glutamate mechanisms involved in the OFF pathway of zebrafish retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. American Univ, Dept Biol, Washington, DC 20016 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 MAY PY 2002 VL 43 SU 1 MA 1826 BP U417 EP U417 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601782 ER PT J AU Wheelock, RH Russell, P AF Wheelock, RH Russell, P TI Assessment of primary cell cultures isolated from human trabecular meshwork as a model for studying glucocorticoid-mediated gene expression changes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, 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 MAY PY 2002 VL 43 SU 1 MA 1026 BP U226 EP U226 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600984 ER PT J AU Wiggert, BN Duncan, T Kutty, RK Darrow, RM Organisciak, DT AF Wiggert, BN Duncan, T Kutty, RK Darrow, RM Organisciak, DT TI The role of reftnoids genetics and age in retinal light damage SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Bethesda, MD 20892 USA. Wright State Univ, Dayton, OH 45435 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 MAY PY 2002 VL 43 SU 2 MA 4575 BP U1303 EP U1303 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701727 ER PT J AU Wolf, LA Reed, GF Buggage, RR Nussenblatt, RB Chan, CC AF Wolf, LA Reed, GF Buggage, RR Nussenblatt, RB Chan, CC TI Levels of IL-10 and IL-6 in the vitreous are helpful for differential diagnosis of primary intraocular lymphoma and ocular inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Biometry Branch, Bethesda, MD 20892 USA. NEI, Immunol Lab, 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 MAY PY 2002 VL 43 SU 1 MA 2221 BP U505 EP U505 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602152 ER PT J AU Xiao, WH Zimmermann, R Wawrousek, E Vinores, SA AF Xiao, WH Zimmermann, R Wawrousek, E Vinores, SA TI Upregulation of vascular endothelial growth factor (VEGF) associated with interleukin-1 beta (IL-1 beta) expression and retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 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 MAY PY 2002 VL 43 SU 1 MA 1267 BP U289 EP U289 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601224 ER PT J AU Yamamoto, T Fariss, RN Hickman, FI Pagan-Mercado, G Sato, S Tsai, JY AF Yamamoto, T Fariss, RN Hickman, FI Pagan-Mercado, G Sato, S Tsai, JY TI Pericyte recruitment in silver nitrate-induced corneal angiogenesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Intramural Res, 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 MAY PY 2002 VL 43 SU 1 MA 1754 BP U401 EP U401 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601709 ER PT J AU Yang, D FitzGibbon, EJ Miles, FA AF Yang, D FitzGibbon, EJ Miles, FA TI Effects of real and simulated tropias on human short-latency disparity vergence SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 962 BP U211 EP U211 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600922 ER PT J AU Yang, GS Lindbloom, J Yan, Z Engelhardt, J Schmidt, M Kotin, R Davidson, B AF Yang, GS Lindbloom, J Yan, Z Engelhardt, J Schmidt, M Kotin, R Davidson, B TI Viral mediated transduction of murine retina with AAV2 and AAV5 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NHLBI, 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 MAY PY 2002 VL 43 SU 2 MA 4619 BP U1310 EP U1310 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701770 ER PT J AU Yu, C Lin, M Ebong, S Egwuagu, CE AF Yu, C Lin, M Ebong, S Egwuagu, CE TI Interferon regulatory transcription factors regulate cell cycle and growth inhibitory genes in the mammalian lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol 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 ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2326 BP U555 EP U555 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602258 ER PT J AU Zhang, C Strunnikova, N Baffi, J Cousins, S Csaky, K AF Zhang, C Strunnikova, N Baffi, J Cousins, S Csaky, K TI Ratio of caspase-8 to c-Flip determines the susceptibility of human retinal pigment epithelium (hRPE) to tumor necrosis factor-a (TNF-a) induced cell death SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Ocular Gene Therapy Grp, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33152 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 MAY PY 2002 VL 43 SU 1 MA 686 BP U149 EP U149 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600661 ER PT J AU Zhang, M Foxman, EF Hurst, S Muchamuel, T Shen, DF Wawrousek, EF Chan, CC Gery, I AF Zhang, M Foxman, EF Hurst, S Muchamuel, T Shen, DF Wawrousek, EF Chan, CC Gery, I TI Differential expression of cytokines, chemokines and chemokine receptors in Th1- vs Th2-mediated ocular inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA 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 MAY PY 2002 VL 43 SU 1 MA 884 BP U193 EP U193 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600861 ER PT J AU Zhao, X Xu, L Zhang, R Ma, Y AF Zhao, X Xu, L Zhang, R Ma, Y TI The ability of frequency doubling technology perimetry in the diagnosis of glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 LMOD, NEI, NIH, Bethesda, MD USA. Beijing Inst Ophthalmol, Beijing, Peoples R China. 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 MAY PY 2002 VL 43 SU 1 MA 2148 BP U491 EP U491 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602081 ER PT J AU Crane, L Crowe, R Fine, S Gold, M Gorosh, K Gourevitch, M Hellinger, J Jovanovich, J Kalkut, G Keiser, P Matthews, C Nadler, J Nemechek, P Post, J Goldberg, B Rutstein, R Sharp, V Hollinger, F Fleishman, J Frazer, I Conviser, R Dilonardo, J Gaist, P Moore, R Keruly, J Gebo, K Reilly, E Zhao, M AF Crane, L Crowe, R Fine, S Gold, M Gorosh, K Gourevitch, M Hellinger, J Jovanovich, J Kalkut, G Keiser, P Matthews, C Nadler, J Nemechek, P Post, J Goldberg, B Rutstein, R Sharp, V Hollinger, F Fleishman, J Frazer, I Conviser, R Dilonardo, J Gaist, P Moore, R Keruly, J Gebo, K Reilly, E Zhao, M CA HIV Res Network TI Hospital and outpatient health services utilization among HIV-infected patients in care in 1999 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE resource use; health services; cost of care; hospital admission; antiretroviral therapy ID COMBINATION ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG USERS; MEDICAL-CARE; ERA; MORTALITY; DISEASE; COSTS; AIDS AB Background: The evolving epidemiology and therapeutic management of HIV disease has important implications for health care resource utilization in HIV-infected patients, and health care resource use data are also needed to support policy and financial decision making. Methods: Demographic, clinical, and resource utilization data were collected from 9 U.S. HIV primary and specialty care sites in calendar year 1999. Rates of resource use were calculated for hospital admission, length of hospital stay, and outpatient clinic/office visits. Results: The sample included 5255 patients from HIV primary care sites in 3 eastern, 3 midwestern, arid 3 western areas of the United States. Hospital admissions accounted for an annual mean of 297 days per 100 persons/y in 1999. Hospital days ranged from a low of 165 per 100 persons/mo for a CD4 > 500 cells/mm(3) to 840 per 100 persons/mo for a CD4 < 50 cells/mm(3) (p < .01). Mean annual outpatient clinic/office visits were 10.7 per person in 1999. A declining CD4 level and an increasing HIV-1 RNA level were both associated with higher hospital and outpatient utilization. HAART use was associated with fewer hospital days, and a higher outpatient visit rate. Injecting drug use risk was associated with an increase in hospital days. African American race was associated with a higher number of hospital days, but a lower outpatient visit rate. Female gender was associated with higher outpatient utilization. Mean monthly inpatient and outpatient expenditures in 1999 were $423 and $168, respectively. Conclusion: As HIV care continues to evolve, data from our network of HIV providers will be useful in quantifying changes in HIV health services utilization makers, as well as HIV care payers and providers. C1 Wayne State Univ, Detroit, MI USA. Alameda Cty Med Ctr, Oakland, CA USA. Community Hlth Network, Rochester, NY USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. CORE Fdn, Chicago, IL USA. Montefiore Med Grp, Bronx, NY USA. Community Med Alliance, Boston, MA USA. Henry Ford Hosp, Detroit, MI 48202 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Parkland Hlth & Hosp Syst, Dallas, TX USA. Univ Calif San Diego, Owen Clin, San Diego, CA 92103 USA. Tampa Gen Hlth Care, Tampa, FL USA. Nemechek Hlth Renewal, Kansas City, MO USA. MIHS McDowell Healthcare Ctr, Phoenix, AZ USA. Care Oregon, Portland, OR USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. St Lukes Roosevelt Hosp, New York, NY USA. Agcy Healthcare Res & Qual, Rockville, MD USA. US Hlth Resources & Serv Adm, Rockville, MD USA. Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. NIH, Off AIDS Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Moore, R (reprint author), Johns Hopkins Univ, Sch Med, 1830 E Monument St,Room 8059, Baltimore, MD 21205 USA. RI Gebo, Kelly/B-9223-2009 NR 19 TC 46 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAY 1 PY 2002 VL 30 IS 1 BP 21 EP 26 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 548QY UT WOS:000175401600003 ER PT J AU Hibbeln, JR AF Hibbeln, JR TI Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: a cross-national, ecological analysis SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE postpartum depression; cross-national; omega-3 fatty acids; docosahexaenoic acid; arachidonic acid; nutrition; seafood; meta-analysis; ecological; epidemiology ID FATTY-ACID COMPOSITION; FISH-OIL SUPPLEMENTATION; RANDOMIZED CONTROLLED TRIAL; SELF-REPORT QUESTIONNAIRES; PLACEBO-CONTROLLED TRIAL; BLOOD-CELL MEMBRANES; POSTNATAL-DEPRESSION; BREAST-MILK; PRETERM INFANTS; RISK-FACTORS AB Background: Mothers selectively transfer docosahexaenoic acid (DHA) to their fetuses to support optimal neurological development during pregnancy. Without sufficient dietary intake, mothers become depleted of DHA and may increase their risk of suffering major depressive symptoms in the postpartum period. We postulated that the DHA content of mothers' milk and seafood consumption would both predict prevalence rates of postpartum depression across countries. Methods: Published prevalence data for postpartum depression were included that used the Edinburgh Postpartum Depression Scale (n = 14 532 subjects in 41 studies). These data were compared to the DHA, eicosapentaenoic acid (EPA) and arachidonic acid (AA) content in mothers' milk and to seafood consumption rates in published reports from 23 countries. Results: Higher concentrations of DHA in mothers' milk (r = -0.84, p < 0.0001, n = 16 countries) and greater seafood consumption (r = -0.81, p < 0.0001, n = 22 countries) both predicted lower prevalence rates of postpartum depression in simple and logarithmic models, respectively. The AA and EPA content of mothers' milk were unrelated to postpartum depression prevalence. Limitations: These findings do not prove that higher omega-3 status cause lower prevalence rates of postpartum depression. Data on potentially confounding factors were not uniformly available for all countries. Conclusions: Both lower DHA content in mothers' milk and lower seafood consumption were associated with higher rates of postpartum depression. These results do not appear to be an artifact of cross-national differences in well-established risk factors for postpartum depression. Interventional studies are needed to determine if omega-3 fatty acids can reduce major postpartum depressive symptoms. Published by Elsevier Science B.V. C1 NIAAA, Lab Membrane Biophys & Biochem, NIH, Rockville, MD 20892 USA. RP Hibbeln, JR (reprint author), NIAAA, Lab Membrane Biophys & Biochem, NIH, Pk 5,Room 150,12420 Parklawn Dr, Rockville, MD 20892 USA. NR 124 TC 269 Z9 282 U1 6 U2 45 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2002 VL 69 IS 1-3 BP 15 EP 29 AR PII S0165-0327(01)00374-3 DI 10.1016/S0165-0327(01)00374-3 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 575EK UT WOS:000176933500002 PM 12103448 ER PT J AU Devouassoux, G Saxon, A Metcalfe, DD Prussin, C Colomb, MG Brambilla, C Diaz-Sanchez, D AF Devouassoux, G Saxon, A Metcalfe, DD Prussin, C Colomb, MG Brambilla, C Diaz-Sanchez, D TI Chemical constituents of diesel exhaust particles induce IL-4 production and histamine release by human basophils SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE basophil; IL-4; histamine; diesel exhaust particles; allergy; pollution ID BRONCHIAL EPITHELIAL-CELLS; NF-KAPPA-B; IN-VIVO; AIRWAY INFLAMMATION; PERIPHERAL-BLOOD; CYTOKINE EXPRESSION; NASAL CHALLENGE; EXPOSURE; IGE; ACTIVATION AB Background: An epidemiologic relationship between airway allergic diseases and exposure to atmospheric pollutants has been demonstrated and suggested to be one factor in the increasing prevalence of asthma. Diesel exhaust particles (DEPs) have been shown to participate in the development of allergic airway inflammation, in which the targets include macrophages, B and T cells, epithelial cells, and mast cells. In addition to the adjuvant effect of DEPs on total and allergen-specific IgE production, DEPs also act to induce chemokines and cytokines and may play a key role in primary sensitization. Objective: DEPs have been shown to increase local IL-4-containing Kit(+) cells soon after in vivo nasal challenge. The aim of this study was to examine the effects of DEPs on human basophils, a key source of IL-4. Methods: Peripheral blood leukocytes from allergic and control subjects were cultured in the presence of organic extracts of DEP (DEPex) with or without allergen. The cultures were analyzed for IL-4-containing cells by using multiparameter flow cytometry, IL-4 secretion with ELISA, and histamine release. Results: Basophils, when exposed in vitro to DEPex, expressed IL-4 and released histamine significantly (P < .01) more than with antigen activation. DEPex did not synergize with allergen in cytokine production and histamine release. DEPex-induced basophil IL-4 expression peaked at 2 hours and persisted through 20 hours, in contrast to allergen-induced IL-4, which was transient. The effect of DEPex on basophil cytokine expression and histamine release was dose dependent and occurred with cells from both allergic and nonallergic subjects. DEPex induced IL-4 expression and histamine release in highly enriched basophil populations, suggesting it acts directly on basophils. Other peripheral blood leukocytes, including T cells, did not contribute to this cytokine expression. Preincubation with N-acetylcysteine completely abrogated DEPex-driven basophil IL-4 expression. Conclusions: Basophils are a direct target for DEPex, inducing IL-4 expression and histamine release in an IgE-allergen independent fashion. N-acetyleysteine inhibition of DEPex-driven IL-4 expression provides evidence that generation of reactive oxygen species is required for the effects observed. The capability of DEPex to activate basophils in both allergic and nonallergic subjects suggests a potential role of this pollutant in the increasing prevalence of allergic diseases. C1 CHU Grenoble, Hop A Michallon, Dept Immunol, F-38043 Grenoble 09, France. INSERM, EMI 9924, Grenoble, France. Dept Resp Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Div Clin Immunol, Los Angeles, CA 90024 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, Inst A Bonniot, Grenoble, France. RP Devouassoux, G (reprint author), CHU Grenoble, Hop A Michallon, DMAS, Dept Resp Med, BP 217, F-38043 Grenoble 09, France. RI BRAMBILLA, CHRISTIAN/K-2285-2013; OI Prussin, Calman/0000-0002-3917-3326 FU NIAID NIH HHS [AI-50495] NR 36 TC 61 Z9 62 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2002 VL 109 IS 5 BP 847 EP 853 DI 10.1067/mai.2002.122843 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 553QW UT WOS:000175687800016 PM 11994710 ER PT J AU Goering, PL Morgan, DL Ali, SF AF Goering, PL Morgan, DL Ali, SF TI Effects of mercury vapor inhalation on reactive oxygen species and antioxidant enzymes in rat brain and kidney are minimal SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE mercury vapor; reactive oxygen species; kidney; brain; neurotoxicity; nephrotoxicity ID ASTROCYTE CULTURES; DIFFERENT REGIONS; TRANSGENIC MICE; FREE-RADICALS; NULL MICE; METALLOTHIONEIN; EXPOSURE; TOXICITY; NEUROTOXICITY; MANGANESE AB Metals are known to induce the formation of reactive oxygen species (ROS) that initiate oxidative stress, an important mechanism of cell injury. The brain is particularly sensitive to oxidative attack because of its high level of unsaturated lipids and high rate of oxidative metabolism. The objective of this study was to determine if elemental mercury (Hg-0) vapor inhalation increases ROS production and affects activities or levels of antioxidant-related bioniolecules in the rat brain and kidney. Adult female Sprague-Dawley rats were exposed for 2 h per day for 11 consecutive days to Hg-0 vapor (1, 2, and 4 mg Hg-0 m(-3)). Brain regions (frontal cortex, cerebellum, brain stem) and kidney were assayed for total Hg, ROS and glutathione (GSH) levels, and for enzyme activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Marked exposure-related increases (2500-5600-fold) in total Hg were detected in the brain regions and in kidney. A statistically significant increase in ROS production (ca. 30% above controls) was observed only in the cortex of rats exposed to 1 mg m(-3) Hg vapor, but no significant changes were apparent at other exposures. Although a trend towards increasing ROS production was observed in the kidney, these effects were not statistically significant. Mercury vapor exposure had no significant effects on GSH levels or GPx activity in the three brain regions, however, statistically significant decreases in GSH and GPx activity were detected in the kidneys of rats exposed to 2 mg m(-3). Mercury exposure did not cause significant effects on SOD activity in the brain or kidney. The data indicate that oxidative stress and changes in GSH and activities of antioxidant enzymes do not play a major role in Hg-0 vapor toxicity in brain and kidney. Published in 2002 by John Wiley Sons, Ltd. C1 US FDA, Ctr Devices & Radiol Hlth HFZ112, Rockville, MD 20852 USA. NIEHS, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth HFZ112, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 29 TC 26 Z9 33 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 2002 VL 22 IS 3 BP 167 EP 172 DI 10.1002/jat.844 PG 6 WC Toxicology SC Toxicology GA 557JB UT WOS:000175904500005 PM 12015796 ER PT J AU Miyamoto, T Hasuike, S Jinno, Y Soejima, H Yun, K Miura, K Ishikawa, M Niikawa, N AF Miyamoto, T Hasuike, S Jinno, Y Soejima, H Yun, K Miura, K Ishikawa, M Niikawa, N TI The human ASCL2 gene escaping genomic imprinting and its expression pattern SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE ASCL2; imprinting; expression; placenta ID LOCALIZATION; DELETION; REGION; MASH2; MOUSE; IGF2; H19 AB The mouse achaete-scute homolog-2 gene (Ascl2 or Mash2) encodes a transcription factor playing a role in the development of the trophoblast. The Ascl2 is an imprinted gene with maternal expression and assigned to an imprinting gene cluster region (ICR) at a distal region of mouse chromosome 7. We previously isolated a phage clone carrying the human homolog, ASCL2, and mapped it to human chromosome 11p15.5, a human ICR. In the present study, we demonstrate the expression patterns of the human ASCL2 in the fetus at a stage between first and second trimesters and in the placental tissues. In addition, it has been shown that the human ASCL2 gene escapes genomic imprinting. C1 Nagasaki Univ, Sch Med, Dept Human Genet, Nagasaki 852, Japan. RP Miyamoto, T (reprint author), NICHHD, LMGD, NIH, Bldg 6B Room 2B211,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 24 Z9 25 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD MAY PY 2002 VL 19 IS 5 BP 240 EP 244 DI 10.1023/A:1015362903486 PG 5 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 547WK UT WOS:000175355600006 PM 12099555 ER PT J AU Sawitzke, JA Li, YF Sergueev, K Youngren, B Brendler, T Jones, K Austin, S AF Sawitzke, JA Li, YF Sergueev, K Youngren, B Brendler, T Jones, K Austin, S TI Transcriptional interference by a complex formed at the centromere-like partition site of plasmid P1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; PARB PROTEIN; HOST FACTOR; SYSTEM; GENES; SEGREGATION; REPLICATION; SPECIFICITY; CHROMOSOME; BINDING AB The partition site,parS, promotes accurate segregation of the replicated P1 plasmid to daughter cells when the P1-encoded ParA and ParB proteins are supplied. The parS site was inserted into the Escherichia coli chromosome between the promoter and the structural gene for beta-galactosidase, lacZ. There was little interference with lacZ expression when ParA and ParB were supplied in trans. However, when a mutant ParA protein, ParAM314I, was supplied along with ParB, expression of lacZ was shut down. ParAM314I, ParB, and parS appear to form a nucleoprotein complex that blocks transcription. Mutations in parA and parB that relieved the parAM314I-dependent block were found. In addition, new mutations which impose the block were selected. Five of the latter mapped to parA and one to parB; all had a propagation-defective phenotype (Par(PD)) similar to that of parAM314I. Thus, whereas a null par mutant P1 plasmid segregates its DNA randomly, these mutants prevent even random distribution of the plasmid. We propose that ParA protein normally interacts transiently with the ParB-parS complex for partition to proceed but that the mutations block ParA dissociation. This "permanent" ParA-ParB-parS complex acts as a transcription block. Consistent with this hypothesis, we found that three of the seven blocking mutations lie within regions of ParA and ParB that are known to interact with each other. When the transcription block is imposed, regional silencing of nearby genes occurs. However, the requirement for ParA and a mutant parA or parB allele distinguishes the transcription block from the regional ParB-dependent gene silencing previously described. C1 NCI, Frederick, MD 21702 USA. RP Austin, S (reprint author), NCI, POB B, Frederick, MD 21702 USA. EM austin@ncifcrf.gov FU NIGMS NIH HHS [5 F32 GM16971, F32 GM016971] NR 30 TC 8 Z9 8 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2002 VL 184 IS 9 BP 2447 EP + DI 10.1128/JB.184.9.2447-2454.2002 PG 9 WC Microbiology SC Microbiology GA 541TK UT WOS:000175000400014 PM 11948158 ER PT J AU Borden, A O'Grady, PI Vandewiele, D de Henestrosa, ARF Lawrence, CW Woodgate, R AF Borden, A O'Grady, PI Vandewiele, D de Henestrosa, ARF Lawrence, CW Woodgate, R TI Escherichia coli DNA polymerase III can replicate efficiently past a T-T cis-syn cyclobutane dimer if DNA polymerase v and the 3 ' to 5 ' exonuclease proofreading function encoded by dnaQ are inactivated SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; POL-IV; TRANSLESION REPLICATION; INDUCED MUTAGENESIS; GENE-EXPRESSION; ERROR-PRONE; Y-FAMILY; BYPASS; MUTATIONS; LESION AB Although very little replication past a T-T cis-syn cyclobutane dimer normally takes place in Escherichia coli in the absence of DNA polymerase V (Pol V), we previously observed as much as half of the wild-type bypass frequency in Pol V-deficient (DeltaumuDC) strains if the 3' to 5' exonuclease proofreading activity of the Pol III e subunit was also disabled by mutD5. This observation might be explained in at least two ways. In the absence of Pol V, wild-type Pol III might bind preferentially to the blocked primer terminus but be incapable of bypass, whereas the proofreading-deficient enzyme might dissociate more readily, providing access to bypass polymerases. Alternatively, even though wild-type Pol III is generally regarded as being incapable of lesion bypass, proofreading-impaired Poll III might itself perform this function. We have investigated this issue by examining dimer bypass frequencies in AumuDC mutD5 strains that were also deficient for Pol I, Pol II, and Pol IV, both singly and in all combinations. Dimer bypass frequencies were not decreased in any of these strains and indeed in some were increased to levels approaching those found in strains containing Pol V. Efficient dimer bypass was, however, entirely dependent on the proofreading deficiency imparted by mutD5, indicating the surprising conclusion that bypass was probably performed by the mutD5 Pol III enzyme itself. This mutant polymerase does not replicate past the much more distorted T-T (6-4) photoadduct, however, suggesting that it may only replicate past lesions, like the T-T dimer, that form base pairs normally. C1 Univ Rochester, Med Ctr, Dept Biochem & Biophys, Sch Med & Dent, Rochester, NY 14642 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Lawrence, CW (reprint author), Univ Rochester, Med Ctr, Dept Biochem & Biophys, Sch Med & Dent, Rochester, NY 14642 USA. FU NIGMS NIH HHS [GM 32885] NR 40 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2002 VL 184 IS 10 BP 2674 EP 2681 DI 10.1128/JB.184.10.2674-2681.2002 PG 8 WC Microbiology SC Microbiology GA 548XU UT WOS:000175415800013 PM 11976296 ER PT J AU Scholl, D Adhya, S Merril, CR AF Scholl, D Adhya, S Merril, CR TI Bacteriophage SP6 is closely related to phages K1-5, K5, and K1E but encodes a tail protein very similar to that of the distantly related P22 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; TAILSPIKE PROTEIN; RNA-POLYMERASE; GENE; RECOGNITION; EXPRESSION; FIBER AB The lytic salmonella phage SP6 encodes a tail protein with a high degree of sequence similarity to the tail protein of the biologically unrelated lysogenic salmonella phage P22. The SP6 tail gene is flanked by an upstream region that contains a promoter and a downstream region that contains a putative Rho-independent transcription terminator, giving it a cassette or modular structure almost identical to the structure of the tail genes of coliphages K1E, K5, and K1-5. It now appears that SP6, K1-5, K5, and K1E are very closely related but have different tail fiber proteins, giving them different host specificities. C1 NIMH, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NCI, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. RP Merril, CR (reprint author), NIMH, Lab Biochem Genet, NIH, Bldg 10,Room 2D54,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 18 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2002 VL 184 IS 10 BP 2833 EP 2836 DI 10.1128/JB.184.10.2833-2836.2002 PG 4 WC Microbiology SC Microbiology GA 548XU UT WOS:000175415800030 PM 11976314 ER PT J AU Sen, HN Uusitalo, R Laatikainen, L AF Sen, HN Uusitalo, R Laatikainen, L TI Subclinical inflammation after laser in situ keratomileusis in corneal grafts SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT 18th Congress of the European-Society-of-Cataract-and-Refractive-Surgeons CY SEP, 2000 CL BRUSSELS, BELGIUM SP European Soc Cataract & Refract Surgeons ID FLARE-CELL METER; PHOTOREFRACTIVE KERATECTOMY; PENETRATING KERATOPLASTY; EXCIMER-LASER; REFRACTIVE SURGERY; PHOTOTHERAPEUTIC KERATECTOMY; REJECTION EPISODE; TREAT MYOPIA; ASTIGMATISM; KERATOTOMY AB Purpose: To evaluate postoperative inflammatory reaction in the eye after laser in situ keratomileusis (LASIK) in corneal grafts. Setting. Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. Methods: Ten eyes of 9 patients with penetrating keratoplasty (PKP) and significant postoperative refractive errors and astigmatism had LASIK 22 months or more after the PKP. All patients were treated with the VISX Star excimer laser and the Bausch & Lomb Hansatome(R) microkeratome. Preoperative and early postoperative inflammation was evaluated by quantifying the aqueous flare intensity with a laser flare photometer (Kowa FM-500). A full ophthalmic assessment was also performed before LASIK and up to 6 months postoperatively. Results: The inflammatory response was mild and limited to the first postoperative hour. The mean anterior chamber flare increased from 6.0 photons/millisecond (ph/ms) preoperatively to 14.0 ph/ms at 1 hour and then decreased to 6.7 ph/ms (hour 3), 6.8 ph/ms (day 1), and 8.2 ph/ms (day 7). The mean spherical equivalent (SE) refraction decreased from -3.81 diopters (D) (range -9.63 to - 0.25 D) to - 0.46 D (range -1.13 to +0.38 D), and the mean preoperative astigmatism decreased from 3.0 D (range 6.5 to 0.5 D) to 0.7 D (range 0.0 to 2.0 D). At the last examination, 9 eyes were within +/-1.0 D (6 within +/-0.5 D) and all were within +/-1.5 D of the intended SE refraction. Three eyes achieved full cylinder correction, and 7 were within +/-1.0 D of the intended correction. Eight eyes had a best corrected visual acuity of 20/40 or better (unchanged or gain of 1 to 4 lines [6], loss of 1 line [1], and loss of 3 lines [1]), and 8 had an uncorrected visual acuity of 20/50 or better. Conclusions: Uneventful LASIK induced subtle, short-lasting anterior chamber flare when measured by the laser flare meter. In corneal grafts, LASIK appeared to be a safe and effective procedure for residual refractive errors. C1 Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki, Finland. RP Sen, HN (reprint author), NEI, 9000 Rockville Pike,Bldg 10,Room 10N112, Bethesda, MD 20892 USA. NR 40 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAY PY 2002 VL 28 IS 5 BP 782 EP 787 DI 10.1016/S0886-3350(02)01239-7 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 546NW UT WOS:000175281000016 PM 11978455 ER PT J AU Yamazaki, T Zaal, K Hailey, D Presley, J Lippincott-Schwartz, J Samelson, LE AF Yamazaki, T Zaal, K Hailey, D Presley, J Lippincott-Schwartz, J Samelson, LE TI Role of Grb2 in EGF-stimulated EGFR internalization SO JOURNAL OF CELL SCIENCE LA English DT Article DE Grb2; EGFR; SH3 domain; endocytosis; GFP ID EPIDERMAL GROWTH-FACTOR; LIGAND-INDUCED INTERNALIZATION; NUCLEOTIDE EXCHANGE FACTOR; RECEPTOR TYROSINE KINASES; ALDRICH SYNDROME PROTEIN; SH3 DOMAINS; SH2-CONTAINING PROTEINS; SIGNAL-TRANSDUCTION; ADAPTER PROTEIN; DYNAMIN GTPASE AB Grb2 is an adaptor molecule that couples membrane receptors such as the epidermal growth factor receptor (EGFR) to intracellular signaling pathways. To gain insight into the trafficking pathways followed by these molecules after activation by EGF, we visualized Grb2 and EGFR fused to GFP spectral variants in single live cells. In nonstimulated cells, Grb2-YFP was primarily localized diffusely in the cytoplasm, whereas EGFR-CFP was found on the plasma membrane and in endocytic structures localized in the perinuclear area. Within I minute of EGF stimulation, Grb2 redistributed to the plasma membrane where it bound EGFR-CFP in an SH2 dependent manner. The plasma membrane then began to dynamically ruffle, and Grb2-YFP and EGFR-CFP were found to internalize together in large macropinocytic structures. These structures were morphologically distinct from conventional, clathrin-derived endosomes and did not label with transferrin, AP-2 or clathrin heavy chain. Evidence that these structures did not require clathrin for internalization came from experiments showing that expression of the C-terminus of AP-180, which inhibited transferrin uptake, had no effect on EGF-induced internalization of EGFR. YFP-tagged Grb2 containing an inhibitory mutation in either N- or C-SH3 domain redistributed to the plasma membrane upon EGF stimulation, but the macropinocytic structures containing Grb2-YFP and EGFR-CFP did not translocate inward and appeared to remain tethered to the plasma membrane. This suggested that the Grb2 SH3 domain was responsible for coupling the membranes containing EGFR with downstream effectors involved in internalization of these membranes. Transferrin uptake was unaffected in the presence of all of the SH3 domain mutants, consistent with the EGF-stimulated EGFR internalization pathway being clathrin-independent. These results demonstrate a role for Grb2 in events associated with a macropinocytic internalization pathway for EGFR in activated cells. C1 NCI, Mol & Cellular Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Mol & Cellular Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NR 45 TC 79 Z9 80 U1 1 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2002 VL 115 IS 9 BP 1791 EP 1802 PG 12 WC Cell Biology SC Cell Biology GA 555NX UT WOS:000175801100003 PM 11956311 ER PT J AU Weise, M Merke, DP Pacak, K Walther, MM Eisenhofer, G AF Weise, M Merke, DP Pacak, K Walther, MM Eisenhofer, G TI Utility of plasma free metanephrines for detecting childhood pheochromocytoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-2; URINARY CREATININE EXCRETION; LIQUID-CHROMATOGRAPHY; LINDAU-DISEASE; MENTAL STRESS; CATECHOLAMINE; CHILDREN; DIAGNOSIS; OVERWEIGHT; PREVALENCE AB Measurements of plasma free metanephrines, normetanephrine (NMN) and metanephrine (MN), provide a sensitive test for diagnosis of pheochromocytoma in adults but have not been evaluated in children. We therefore established reference ranges for plasma and urinary metanephrines and the catecholamines, norepinephrine (NE) and epinephrine (E), in 86 healthy children (age 5-17). A group of 158 healthy adults (age 18-72) served as a comparison group. Pediatric reference ranges were applied to examine the diagnostic utility of the various tests in 45 children evaluated for pheochromocytoma (age 8-17; 38 with von Hippel-Lindau syndrome), with tumors found on 12 occasions. Upper reference limits for E and MN were higher and those for NE and NMN lower in children than in adults. Boys had higher plasma levels of E and MN and higher urinary excretion of all four amines than girls. Plasma free metanephrines provided a diagnostic test with values for sensitivity (100%) and specificity (94%) that were equal to or higher than those of other tests. In two children screened for pheochromocytoma on multiple occasions, use of pediatric reference ranges for plasma free metanephrines indicated the tumor a year earlier than indicated using adult reference ranges. The findings indicate that plasma free metanephrines provide a sensitive tool for detection of pheochromocytoma in children. Age appropriate reference ranges should be used and gender differences should be considered. C1 NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NINCDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 6N252,10 Ctr Dr,MSC 1620, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov NR 28 TC 46 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 1955 EP 1960 DI 10.1210/jc.87.5.1955 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100007 PM 11994324 ER PT J AU Rapuri, PB Kinyamu, HK Gallagher, JC Haynatzka, V AF Rapuri, PB Kinyamu, HK Gallagher, JC Haynatzka, V TI Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VITAMIN-D STATUS; HEALTHY POSTMENOPAUSAL WOMEN; PARATHYROID-HORMONE; BIOCHEMICAL MARKERS; D METABOLITES; SERUM CONCENTRATIONS; RELATIVE CONTRIBUTIONS; SUNLIGHT EXPOSURE; TURNOVER; 25-HYDROXYVITAMIN-D AB Seasonal variation of serum vitamin D metabolites, PTH, bone turnover markers, and bone mineral density (BMD), adjusted for confounding variables, was studied in a cross-sectional population of 251 ambulatory elderly women aged 65-77 yr. A significant (P < 0.05) seasonal change was observed in serum 25 hydroxyvitamin D (25OHD), bone resorption marker (urine N-telopeptide), and BMD of the spine, total body, and midradius. Serum 25ORD was significantly lower (P < 0.05) in winter (December, January, February, March) compared with summer (June, July, August, September), with the nadir in February (68.4 +/- 6.74 nmol/liter) and the zenith in August (85.6 +/- 5.12 nmol/liter). Mean serum PTH levels were higher in winter when serum 25OHD was low, and mean serum PTH was lower in summer when serum 25OHD was high, although the seasonal change in serum PTH was not significant. The change in serum 1,25-dihydroxy vitamin D. paralleled that of serum 25OHD levels, but the seasonal effect was not significant. Mean 24-h urine N-telopeptide showed a significant seasonal change (P < 0.05); it was about 24% higher in February (zenith) compared with that in August (nadir). The zenith month of urine N-telopeptide levels corresponded to the nadir month of serum 25OHD levels and vice versa. A significant (P < 0.05) inverse correlation was observed between 24-h urine N-telopeptides and serum 25OHD levels. There was a significant (P < 0.05) seasonal change in mean BMD of spine, total body, and mid-radius. These changes paralleled those in serum 25OHD levels. Spine BMD was 8.4% higher in August (zenith) compared with that in February (nadir), whereas total body BMD and mid-radius BMD were 6.1 and 7.6% higher, respectively, in July (zenith) compared with that in January (nadir). There was a nonsignificant increase of 3.6% in total hip BMD. In summary (see Fig. 5), the seasonal changes in vitamin D metabolism in elderly women are closely associated with small changes in serum PTH, changes in bone resorption, and BMD. C1 Creighton Univ, Sch Med, Bone Metab Unit, Omaha, NE 68131 USA. Creighton Univ, Sch Med, Dept Prevent Med, Omaha, NE 68131 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Rapuri, PB (reprint author), Creighton Univ, Sch Med, Bone Metab Unit, 601 N 30th St,Room 6718, Omaha, NE 68131 USA. EM thiyyari@creighton.edu FU NIA NIH HHS [R01-AG10358, UO1-AG10373] NR 60 TC 89 Z9 92 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 2024 EP 2032 DI 10.1210/jc.87.5.2024 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100020 PM 11994336 ER PT J AU Charmandari, E Weise, M Bornstein, SR Eisenhofer, G Keil, MF Chrousos, GP Merke, DP AF Charmandari, E Weise, M Bornstein, SR Eisenhofer, G Keil, MF Chrousos, GP Merke, DP TI Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: Potential clinical implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OB GENE-EXPRESSION; MESSENGER-RIBONUCLEIC-ACID; POLYCYSTIC-OVARY-SYNDROME; BODY-MASS INDEX; PLASMA LEPTIN; OBESE GENE; 21-HYDROXYLASE DEFICIENCY; CIRCULATING LEPTIN; PUBERTAL STAGE; ADIPOSE-TISSUE AB Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied IS children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 muU/ml, P < 0.001) and testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dI, P = 0.003) concentrations. Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear regression analysis indicated that serum leptin concentrations were best predicted by BMI in both patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients with CAH may further enhance adrenal and ovarian androgen production, decrease the therapeutic efficacy of glucocorticoids, and contribute to later development of polycystic ovary syndrome and/or the metabolic syndrome and their complications. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Endocrinol, D-40001 Dusseldorf, Germany. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 65 TC 86 Z9 88 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 2114 EP 2120 DI 10.1210/jc.87.5.2114 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100033 PM 11994350 ER PT J AU Charmandari, E Pincus, SM Matthews, DR Johnston, A Brook, CGD Hindmarsh, PC AF Charmandari, E Pincus, SM Matthews, DR Johnston, A Brook, CGD Hindmarsh, PC TI Oral hydrocortisone administration in children with classic 21-hydroxylase deficiency leads to more synchronous joint GH and cortisol secretion SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; GROWTH-HORMONE-SECRETION; CORTICOTROPIN-RELEASING HORMONE; FOLLICLE-STIMULATING-HORMONE; CUSHINGS-DISEASE; LUTEINIZING-HORMONE; (GH)-RELEASING HORMONE; APPROXIMATE ENTROPY; PUBERTAL CHANGES; PULSE FREQUENCY AB In humans, GH and cortisol are secreted in a pulsatile fashion and a mutual bidirectional interaction between the GH/IGF-I axis and hypothalamic-pituitary-adrenal axis has been established. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in the synthesis of glucocorticoids and often mineralocorticoids, and adrenal hyperandrogenism. Substitution therapy is given to prevent adrenal crises and to suppress the abnormal secretion of androgens and steroid precursors from the adrenal cortex. However, treatment with twice or three times daily oral hydrocortisone does not mimic physiological adrenal rhythms and may influence the activity of the GH/IGF-I axis. We investigated the pattern of GH and cortisol secretion and the synchrony of joint GH-cortisol secretory dynamics in 15 children with classic 21-hydroxylase deficiency (5 males and 10 females; median age 9.5 yr, range 6.1-11.0 yr) and 28 short normal children (23 males and 5 females; median age 7.7 yr, range 4.9-9.3 yr). All subjects were prepubertal. Serum GH and cortisol concentrations were determined at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol secretory patterns was computed at various time lags covering the 24-h period. Children with CAH had significantly lower mean 24-h serum cortisol concentrations (6.4 +/- 2.2 vs. 10.4 +/- 2.6 mug/dl, P < 0.001), ApEn (GH) (0.64 +/- 0.13 vs. 0.74 +/- 0.17, P = 0.04), ApEn (cortisol) (0.54 +/- 0.13 vs, 1.08 +/- 0.18, P < 0.001) and cross-ApEn values of paired GH-cortisol secretion (0.78 +/- 0.19 vs. 1.05 +/- 0.12, P < 0.001) than normal children. There was no difference in mean 24-h GH concentrations between the two groups (4.5 +/- 2.9 vs. 4.5 +/- 1.9 mU/liter). In children with CAH, a significant positive correlation between GH and cortisol was noted at lag time 0 min (r = 0.299, P < 0.01), peaking at 20 min (r = 0.406, P < 0.0001), whereas in normal children, a significant negative correlation between the two hormones was noted at lag time 0 min (r = -0.312, P < 0.01). The above findings suggest that children with classic CAH have a more regular pattern of GH secretion and a more synchronous joint GH-cortisol secretory dynamics than their normal counterparts. These differences reflect bidirectional interactions between the GH/IGF-I axis and hypothalamic-pituitary-adrenal axis in humans, and are likely to evolve as a result of the exogenous administration of hydrocortisone at fixed doses and at specific time intervals, which leads to a more regular pattern in circulating cortisol concentrations, independent of variations in CRH and ACTH concentrations. C1 UCL, London Ctr Pediat Endocrinol, London W1T 3AA, England. Radcliffe Infirm, Diabet Res Labs, Oxford OX2 6HE, England. St Bartholomews Sch Med & Dent, London EC1M 6BQ, England. RP Charmandari, E (reprint author), NICHHD, NIH, Pediat & Reprod Endocrinol Branch, 10 Ctr Dr,Bldg 10,Suite 9D42, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011 NR 49 TC 20 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 2238 EP 2244 DI 10.1210/jc.87.5.2238 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100052 PM 11994370 ER PT J AU Schechter, AN Gladwin, MT Cannon, RO AF Schechter, AN Gladwin, MT Cannon, RO TI NO solutions? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID NITRIC-OXIDE; ERYTHROCYTES; THERAPY C1 NIDDKD, Lab Chem Biol, NIH, Bethesda, MD 20892 USA. NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDKD, Lab Chem Biol, NIH, Bldg 10,Room 9N-307, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 16 TC 16 Z9 17 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 9 BP 1149 EP 1151 DI 10.1172/JCI200215637 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 550DH UT WOS:000175488000005 PM 11994403 ER PT J AU Mizukami, H Mi, YD Wada, R Kono, M Yamashita, T Liu, YJ Werth, N Sandhoff, R Sandhoff, K Proia, RL AF Mizukami, H Mi, YD Wada, R Kono, M Yamashita, T Liu, YJ Werth, N Sandhoff, R Sandhoff, K Proia, RL TI Systemic inflammation in glucocerebrosidase-deficient mice with minimal glucosylceramide storage SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INHERITED ENZYME DEFICIENCY; GAUCHERS-DISEASE; REPLACEMENT THERAPY; GLYCOSPHINGOLIPID SYNTHESIS; RECEPTOR G2A; PATHOGENESIS; ASSOCIATION; LIPOPROTEIN; CYTOKINES; LACKING AB Gaucher disease, the most common lysosomal storage disease, is caused by a deficiency of glucocerebrosidase resulting in the impairment of glucosylceramide degradation. The hallmark of the disease is the presence of the Gaucher cell, a macrophage containing much of the stored glucosylceramide found in tissues, which is believed to cause many of the clinical manifestations of the disease. We have developed adult mice carrying the Gaucher disease L444P point mutation in the glucocerebrosidase (Gba) gene and exhibiting a partial enzyme deficiency. The mutant mice demonstrate multisystem inflammation, including evidence of B cell hyperproliferation, an aspect of the disease found in some patients. However, the mutant mice do not accumulate large amounts of glucosylceramide or exhibit classic Gaucher cells in tissues. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Hirosaki Univ, Sch Med, Dept Pathol, Hirosaki, Aomori 036, Japan. Univ Bonn, Kekule Inst Organ Chem & Biochem, D-5300 Bonn, Germany. Deutsch Krebsforschungszentrum, Abt Zellulare & Mol Pathol, D-6900 Heidelberg, Germany. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg 10,Room 9N-314,10 Ctr DR MS 1821, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 36 TC 79 Z9 83 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 9 BP 1215 EP 1221 DI 10.1172/JCI200214530 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 550DH UT WOS:000175488000012 PM 11994410 ER PT J AU Candotti, F Notarangelo, L Visconti, R O'Shea, J AF Candotti, F Notarangelo, L Visconti, R O'Shea, J TI Molecular aspects of primary immunodeficiencies: lessons from cytokine and other signaling pathways SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; IN-VIVO REVERSION; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; LEUKOCYTE ADHESION DEFICIENCY; ATAXIA-TELANGIECTASIA GENE; COMBINED IMMUNE-DEFICIENCY; AUTOSOMAL RECESSIVE FORM; GAMMA CHAIN MUTATION; HYPER-IGM SYNDROME; B-CELL DEVELOPMENT C1 Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Univ Brescia, Dept Pediat, Brescia, Italy. Univ Frederico 2, Dept Pathol, Naples, Italy. RP O'Shea, J (reprint author), Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Immunol & Inflammat Branch, 10 Ctr Dr Bldg 10 Rm 9N262, Bethesda, MD 20892 USA. RI Visconti, Roberta/C-5299-2009; Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 64 TC 26 Z9 28 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 10 BP 1261 EP 1269 DI 10.1172/JCI200215769 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 554WL UT WOS:000175760100001 PM 12021239 ER PT J AU Petersen, KF Oral, EA Dufour, S Befroy, D Ariyan, C Yu, CL Cline, GW DePaoli, AM Taylor, SI Gorden, P Shulman, GI AF Petersen, KF Oral, EA Dufour, S Befroy, D Ariyan, C Yu, CL Cline, GW DePaoli, AM Taylor, SI Gorden, P Shulman, GI TI Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FREE FATTY-ACIDS; DIABETES-MELLITUS; IN-VIVO; GLUCOSE; TROGLITAZONE; SPECTROSCOPY; THERAPY; HUMANS AB Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism. It has recently been shown that chronic leptin treatment ameliorates these abnormalities. Here we show that chronic leptin treatment improves insulin-stimulated hepatic and peripheral glucose metabolism in severely insulin-resistant lipodystrophic patients. This improvement in insulin action was associated with a marked reduction in hepatic and muscle triglyceride content. These data suggest that leptin may represent an important new therapy to reverse the severe hepatic and muscle insulin resistance and associated hepatic steatosis in patients with lipodystrophy. C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. NIDDK, NIH, Bethesda, MD USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. RP Petersen, KF (reprint author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St,Fitkin Mem Pavil 1,POB 208020, New Haven, CT 06520 USA. OI Oral, Elif/0000-0002-9171-1144 FU NCRR NIH HHS [M01 RR000125, M01 RR-00125]; NIDDK NIH HHS [K23 DK-02347, P30 DK-45735, P30 DK045735, R01 DK-42930] NR 27 TC 426 Z9 437 U1 2 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 10 BP 1345 EP 1350 DI 10.1172/JCI200215001 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 554WL UT WOS:000175760100012 PM 12021250 ER PT J AU O'Sullivan, CE Miller, DR Schneider, PS Roberts, GD AF O'Sullivan, CE Miller, DR Schneider, PS Roberts, GD TI Evaluation of Gen-Probe Amplified Mycobacterium Tuberculosis Direct test by using respiratory and nonrespiratory specimens in a tertiary care center laboratory SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID EXTRAPULMONARY SPECIMENS; COMPLEX; ASSAY AB The performance of the Amplified Mycobacterium Tuberculosis Direct (AMTD) test (Gen-Probe Inc., San Diego, Calif.) was assessed in a large tertiary care mycobacteriology laboratory. Both acid-fast smear-positive and smear-negative respiratory and nonrespiratory clinical specimens were analyzed. From February 1998 to 4 October 2001, AMTD assays were performed on 391 respiratory specimens and 164 nonrespiratory specimens. The AMTD assay was compared to the "gold standard" of combined culture and clinical diagnosis. The overall sensitivity for all specimens, including those for which no smear result was available, was 91.2%. The overall sensitivities of the assay, including acid-fast smear-positive and -negative specimens, were 97.8 and 77.3% for respiratory and nonrespiratory specimens, respectively. The corresponding specificities for respiratory and nonrespiratory specimens were 99.1 and 98.5%, respectively. The overall specificity for all specimens was 98.9%. Positive and negative predictive values were 93.9 and 99.7% and 91.7 and 96.4% for respiratory and nonrespiratory specimens, respectively. The time saved by using the AMTD test for making a diagnosis of tuberculosis instead of using culture was 8.99 days. Inhibitors to the AMTD assay were found in 3.1% of respiratory specimens and 3.1% of nonrespiratory specimens. The assay, used in a general mycobacteriology laboratory setting, represents an important advance in improving the speed and accuracy of diagnosis in the management of patients with tuberculosis. C1 Mayo Clin & Mayo Fdn, Div Clin Microbiol, Dept Lab Med & Pathol, Rochester, MN 55905 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Roberts, GD (reprint author), Mayo Clin & Mayo Fdn, Div Clin Microbiol, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. NR 13 TC 46 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2002 VL 40 IS 5 BP 1723 EP 1727 DI 10.1128/JCM.40.5.1723-1727.2002 PG 5 WC Microbiology SC Microbiology GA 549DA UT WOS:000175428200027 PM 11980950 ER PT J AU Studentsov, YY Schiffman, M Strickler, HD Ho, GYF Pang, YYS Schiller, J Herrero, R Burk, RD AF Studentsov, YY Schiffman, M Strickler, HD Ho, GYF Pang, YYS Schiller, J Herrero, R Burk, RD TI Enhanced enzyme-linked immunosorbent assay for detection of antibodies to virus-like particles of human papillomavirus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SERUM ANTIBODIES; BLOCKING-AGENT; POLYVINYL-ALCOHOL; NATURAL-HISTORY; RISK-FACTORS; YOUNG-WOMEN; L1 PROTEIN; IN-VITRO; TYPE-16; CAPSIDS AB Measurement of antibodies to human papillomavirus (HPV) is complicated by many factors. Although enzyme-linked immunosorbent assays (ELISAs) that use virus-like particles (VLPs) have proved useful, the assays have, in general, had moderate sensitivities and low signal-to-noise ratios. To enhance the performance of the assay, a systematic investigation was undertaken to examine key variables used in ELISAs for the detection of antibodies to VLPs of HPV. Incorporation of two vinyl polymers, polyvinyl alcohol (molecular weight, 50,000) (PVA-50) and poly-vinylpyrrolidone (molecular weight, 360,000) (PVP-360), was found to increase the sensitivity as well as the specificity of the assay for the detection of antibodies to VLPs of HPV. In particular, the addition of PVA-50 to the blocking solution reduced the amount of nonspecific binding of antibodies to VLPs and the microplate surface, whereas the addition of PVP-360 increased the sensitivity of antibody detection. The new ELISA demonstrated increased sensitivity and specificity for the detection of cervical HPV type 16 infection compared to those of a prototype assay with coded clinical serum samples from women with known cervicovaginal HPV infection status. It is anticipated that the enhanced ELISA conditions will have wide application to a large number of clinical diagnostic assays. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY 10461 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Burk, RD (reprint author), Yeshiva Univ Albert Einstein Coll Med, Ctr Canc Res, Ullmann Bldg,Rm 515, Bronx, NY 10461 USA. NR 43 TC 54 Z9 57 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2002 VL 40 IS 5 BP 1755 EP 1760 DI 10.1128/JCM.40.5.177-1760.2002 PG 6 WC Microbiology SC Microbiology GA 549DA UT WOS:000175428200033 PM 11980956 ER PT J AU Smoot, JC Korgenski, EK Daly, JA Veasy, LG Musser, JM AF Smoot, JC Korgenski, EK Daly, JA Veasy, LG Musser, JM TI Molecular analysis of group A Streptococcus type emm18 isolates temporally associated with acute rheumatic fever outbreaks in Salt Lake City, Utah SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GROUP-A STREPTOCOCCUS; 2-COMPONENT REGULATORY SYSTEM; HYALURONIC-ACID CAPSULE; M-PROTEIN; INTERMOUNTAIN AREA; UNITED-STATES; PYOGENES; VIRULENCE; IDENTIFICATION; INFECTION AB Acute rheumatic fever (ARF) and subsequent rheumatic heart disease are rare but serious sequelae of group A Streptococcus (GAS) infections in most western countries. Salt Lake City (SLC), Utah, and the surrounding intermountain region experienced a resurgence of ARF in 1985 which has persisted. The largest numbers of cases were encountered in 1985-1986 and in 1997-1998. Organisms with a mucoid colony phenotype when grown on blood agar plates were temporally associated with the higher incidence of ARF. To develop an understanding of the molecular population genetic structure of GAS strains associated with ARF in the SLC region, 964 mucoid and nonmucoid pharyngeal isolates recovered in SLC from 1984 to 1999 were studied by sequencing the emm gene. Isolates with an emm 18 allele were further characterized by sequencing the spa, covR, and covS genes. Peak periods of ARF were associated with GAS isolates possessing an emm18 allele encoding the protein found in serotype M18 isolates. Among the serotype M18 isolates, the difference in the number of C repeats produced three size variants. Variation was limited in spa, a gene that encodes a streptococcal protective antigen, and covR and covS, genes that encode a two-component regulatory system that, when inactivated, results in a mucoid phenotype and enhanced virulence in mouse infection models. Pulsed-field gel electrophoresis showed a single restriction profile for serotype M18 organisms isolated during both peak periods of ARF. In SLC, the incidence of ARF coresurged with the occurrence of GAS serotype M18 isolates that have very restricted genetic variation. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Primary Childrens Med Ctr, Salt Lake City, UT 84123 USA. RP Musser, JM (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 31 TC 42 Z9 43 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2002 VL 40 IS 5 BP 1805 EP 1810 DI 10.1128/JCM.40.5.1805-1810.2002 PG 6 WC Microbiology SC Microbiology GA 549DA UT WOS:000175428200040 PM 11980963 ER PT J AU Quinn, JA Pluda, J Dolan, ME Delaney, S Kaplan, R Rich, JN Friedman, AH Reardon, DA Sampson, JH Colvin, OM Haglund, MM Pegg, AE Moschel, RC McLendon, RE Provenzale, JM Gururangan, S Tourt-Uhlig, S Herndon, JE Bigner, DD Friedman, HS AF Quinn, JA Pluda, J Dolan, ME Delaney, S Kaplan, R Rich, JN Friedman, AH Reardon, DA Sampson, JH Colvin, OM Haglund, MM Pegg, AE Moschel, RC McLendon, RE Provenzale, JM Gururangan, S Tourt-Uhlig, S Herndon, JE Bigner, DD Friedman, HS TI Phase II trial of carmustine plus O-6-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; BRAIN-TUMOR XENOGRAFTS; ALKYLATING-AGENTS; CYTO-TOXICITY; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; CELLULAR-RESISTANCE; ONCOLOGY-GROUP; HELA-CELLS; DNA; SENSITIVITY AB Purpose : We conducted a phase 11 trial of carmustine (BCNU) plus the O-6-alkylguanine-DNA alkyltransferase inhibitor O-6-benzylguanine (O-6-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent malignant glioma resistant to nitrosoureas. Patients and Methods: Patients were treated with O-6-BG at an intravenous dose of 120 m/m(2) followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week intervals. Results: Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hemaopoietic toxicity. Twelve patients experienced reversible greater than or equal to grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/- 1.7 mug/mL/h v 5.0 +/- 1.3 mug/mL/h) of O-6-BG for patients receiving phenytoin and those not treated with this drug. Conclusion: These results indicate that O-6-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection. (C) 2002 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Brain Tumor Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol & Pharmacol, Sch Med, Hershey, PA 17033 USA. NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Adv Biosci Labs, Frederick, MD USA. NCI, Invest Drug Branch, NIH, Bethesda, MD 20892 USA. RP Quinn, JA (reprint author), Duke Univ, Med Ctr, Brain Tumor Ctr, Dept Surg, Box 3624, Durham, NC 27710 USA. FU NINDS NIH HHS [1K23NS41737-01, NS20023, NS30245] NR 49 TC 139 Z9 143 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2002 VL 20 IS 9 BP 2277 EP 2283 DI 10.1200/JCO.2002.09.084 PG 7 WC Oncology SC Oncology GA 548CG UT WOS:000175370500010 PM 11980998 ER PT J AU Albandar, JM DeNardin, AM Adesanya, MR Winn, DM Diehl, SR AF Albandar, JM DeNardin, AM Adesanya, MR Winn, DM Diehl, SR TI Associations of serum concentrations of IgG, IgA, IgM and interleukin-1 beta with early-onset periodontitis classification and race SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE adolescents; cytokines; periodontal diseases/pathogenesis; periodontal diseases/early-onset; periodontitis/immunology; antibodies ID G SUBCLASS CONCENTRATIONS; JUVENILE PERIODONTITIS; NEUTROPHIL CHEMOTAXIS; YOUNG-ADULTS; CYTOKINES; ANTIBODY; SMOKING; TISSUE; DISEASE; ALPHA AB Background: The significance of serum concentrations of various antibodies and cytokines in the pathogenesis of early-onset periodontitis (EOP) is not well understood. Recent reports suggest differences between young blacks and whites in certain humoral responses, regardless of periodontal status. This study was undertaken to compare the serum concentrations of IgG, IgA, IgM, and IL-1beta in EOP subjects with that of healthy controls, and to study the effect of race on these levels. Material and Methods: This case-control study included 228 individuals, 19-25 years old who were selected from a larger population examined in the National Survey of Oral Health of United States Children in 1986/1987. The subjects were classified by their EOP status and they included 166 subjects with EOP and 62 healthy controls. Blood samples were used to assess the serum concentrations of IgG, IgM, IgA, IgG subclass, and IL-1beta. Results: The serum concentrations of IgG, IgG subclasses, IgA, and IgM in blacks were not significantly different in the generalized, localized and incidental EOP groups as compared to the healthy controls. The serum IL-1beta concentration was slightly and uniformly lower in the EOP groups than in the control group, although not statistically significant. Blacks had significantly higher serum concentrations of total IgG, and of IgG1, IgG2 and IgG3 than whites and Hispanics. Hispanics had significantly higher serum concentrations of IgM and IgG4 than whites and blacks. Hispanics also had a significantly higher serum concentration of IL-1beta than blacks. Conclusions: Total antibody response in blacks is not associated with EOP classification. Race has a significant effect on serum antibody concentrations irrespective of disease classification, with blacks having significantly higher serum concentrations of IgG1, IgG2 and IgG3 than whites and Hispanics. C1 Temple Univ, Sch Dent, Dept Periodontol, Philadelphia, PA 19140 USA. SUNY Buffalo, Dept Oral Biol, Buffalo, NY USA. Natl Inst Dent & Craniofacial Res, Div Intramural Res, Bethesda, MD USA. RP Albandar, JM (reprint author), Temple Univ, Sch Dent, Dept Periodontol, 3223 N Broad St, Philadelphia, PA 19140 USA. OI Albandar, Jasim M./0000-0001-7801-3811 FU NIDCR NIH HHS [H19 DE13102] NR 27 TC 15 Z9 17 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAY PY 2002 VL 29 IS 5 BP 421 EP 426 DI 10.1034/j.1600-051X.2002.290506.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 571EP UT WOS:000176702100006 PM 12060424 ER PT J AU Wienecke, R Klemm, E Karparti, S Swanson, NA Green, AJ DeClue, JE AF Wienecke, R Klemm, E Karparti, S Swanson, NA Green, AJ DeClue, JE TI Reduction of expression of tuberin, the tuberous-sclerosis-complex-gene-2 product in tuberous sclerosis complex associated connective tissue nevi and sporadic squamous and basal cell carcinomas SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID GENE-PRODUCT; ALLELIC LOSS; TARGET RAP1; LESIONS; HAMARTOMAS; MUTATION AB Background: Patients affected with tuberous sclerosis complex (TSC) are prone to the development of multiple benign tumors of the skin and other organs. Tuberin, the protein product of the tuberous-sclerosis-complex-2 tumor suppressor gene (TSC2) has been shown to inhibit cell proliferation. In TSC associated kidney tumors and sporadic brain tumors the loss/reduction of tuberin has been shown. Methods: Specimens of nine squamous cell carcinomas (SCC) and five basal cell carcinomas (BCC) from patients without TSC and six biopsies of connective tissue nevi (CTN) of patients with TSC were obtained. Specimens were analyzed by immunoblotting for the expression of tuberin. Results: Absent or reduced levels of tuberin were detected in the dermal parts of three of six shagreen patches, two of five BCC, and four of nine SCC. Conclusions: In tumors/hamartomas of patients with TSC the complete loss of TSC2 and tuberin is a mechanism which could be shown for CTN, thereby excluding the possibility of haploinsufficiency of TSC2. In a substantial number of cutaneous BCC and SCC the loss or downregulation of tuberin seems to be epigenetic, as alterations of TSC2 are not known in these tumors. The absence or reduction of tuberin might contribute to their proliferation. C1 Univ Munich, Dept Dermatol & Allergol, D-80337 Munich, Germany. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Dermatol, Budapest, Hungary. Oregon Hlth Sci Univ, Dept Dermatol, Portland, OR 97201 USA. Univ Coll Dublin, Dept Med Genet, Dublin, Ireland. Univ Coll Dublin, Conway Inst, Dublin, Ireland. RP Wienecke, R (reprint author), Univ Munich, Dept Dermatol & Allergol, Frauerichstr 9-11, D-80337 Munich, Germany. NR 17 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2002 VL 29 IS 5 BP 287 EP 290 DI 10.1034/j.1600-0560.2002.290505.x PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 570CR UT WOS:000176641100005 PM 12100629 ER PT J AU Song, YS Park, EH Hur, GM Ryu, YS Kim, YM Jin, C AF Song, YS Park, EH Hur, GM Ryu, YS Kim, YM Jin, C TI Ethanol extract of propolis inhibits nitric oxide synthase gene expression and enzyme activity SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE ethanol extract of propolis; nitric oxides; inducible nitric oxide synthase; promoter activity; NF-kappa B ID NF-KAPPA-B; INTERFERON-GAMMA; KINASE COMPLEX; DIFFERENTIAL REGULATION; IKK-ALPHA; ACTIVATION; LIPOPOLYSACCHARIDE; ANTIBACTERIAL; CELLS; BETA AB Propolis obtained from honeybee hives has been used in Oriental folk medicine as an anti-inflammatory. anti-carcinogenic, or immunomodulatory agent. However, the molecular basis for anti-inflammatory properties of propolis has not yet been established, Since nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been known to be involved in inflammatory and autoimmune-mediated tissue destruction, modulation of NO synthesis or action represents a new approach to the treatment of inflammatory and autoimmune diseases. The present study, therefore, examined effects of ethanol extract of propolis (EEP) on iNOS expression and activity of iNOS enzyme itself. Treatment of RAW 264.7 cells with EEP significantly inhibited NO production and iNOS protein expression induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). EEP also inhibited iNOS mRNA expression and nuclear factor-kappa B (NF-kappaB) binding activity in a concentration-dependent manner. Furthermore, transfection of RAW 264.7 cells with iNOS promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene, revealed that EEP inhibited the iNOS promoter activity induced by LPS plus IFN-gamma through the NF-kappaB sites of the iNOS promoter. In addition, EEP directly interfered with the catalytic activity of murine recombinant iNOS enzyme. These results suggest that EEP may exert its anti-inflammatory effect by inhibiting the iNOS gene expression via action on the NF-kappaB sites in the iNOS promoter and by directly inhibiting the catalytic activity of iNOS. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Korea Inst Sci & Technol, Bioanal & Biotransformat Res Ctr, Seoul 130650, South Korea. Chungnam Natl Univ, Coll Med, Dept Pharmacol, Taejon 301131, South Korea. NINCDS, Genet Pharmacol Unit, NIH, Bethesda, MD 20892 USA. Sookmyung Womens Univ, Coll Pharm, Seoul 140742, South Korea. RP Jin, C (reprint author), Korea Inst Sci & Technol, Bioanal & Biotransformat Res Ctr, POB 131, Seoul 130650, South Korea. NR 35 TC 35 Z9 42 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD MAY PY 2002 VL 80 IS 2-3 BP 155 EP 161 AR PII S0378-8741(02)00023-5 DI 10.1016/S0378-8741(02)00023-5 PG 7 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 555KQ UT WOS:000175793600008 PM 12007705 ER PT J AU Pimenta, PEP Diamond, LS Mirelman, D AF Pimenta, PEP Diamond, LS Mirelman, D TI Entamoeba histolytica Schaudinn, 1903 and Entamoeba dispar Brumpt, 1925: Differences in their cell surfaces and in the bacteria-containing vacuoles SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE fracture-flip; freeze-fracture; intra-membranous particles; trophozoites; ultrastructure ID TRYPANOSOMA-CRUZI; FRACTURE-FLIP; LIPOPHOSPHOGLYCAN; PHAGOCYTOSIS; VIRULENCE; ULTRASTRUCTURE; CULTIVATION; MIDGUT AB Entamoeba histolytica Schaudinn, 1903 and Entamoeba dispar Brumpt, 1925 are two of eight species of Entamoeba that sometimes inhabit the human colon, The former is an invasive organism capable of causing life-threatening intestinal and extra-intestinal disease: the latter appears not to be invasive. Because the two species. when viewed by light microscopy appear morphologically similar. they were long regarded as a single species. However. recent biochemical, immunological, and genetic studies provided convincing evidence that they belong tu separate species. Our ultrastructural studies revealed distinct differences in at least two features of the trophozoites. 1) The cell surfaces of the trophozoites of each species differ with regard to structures exposed on the surface, and the distribution and arrangement of intra-membranous proteins. 2) The phagocytosis of bacteria differs in respect to the formation of the phagocytic vacuoles. Loose vacuoles containing several bacteria were in E. histolytica whereas tight vacuoles containing a single bacterium were observed in E. dispar. Furthermore, bacteria were found only within vacuoles in L histolytica. in E. dispar, bacteria were found within vacuoles and some were found free in the cytoplasm. C1 Fdn Oswaldo Cruz, Lab Med Entomol, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. RP Pimenta, PEP (reprint author), Fdn Oswaldo Cruz, Lab Med Entomol, Ctr Pesquisas Rene Rachou, Av Augusto Lima 1715, BR-30190002 Belo Horizonte, MG, Brazil. NR 28 TC 24 Z9 24 U1 1 U2 2 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 2002 VL 49 IS 3 BP 209 EP 219 DI 10.1111/j.1550-7408.2002.tb00525.x PG 11 WC Microbiology SC Microbiology GA 571WU UT WOS:000176742800005 PM 12120986 ER PT J AU Kington, RA AF Kington, RA TI Internal medicine and alcohol - Time to move forward SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 NIAAA, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Kington, RA (reprint author), NIAAA, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2002 VL 17 IS 5 BP 400 EP 401 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 556ZU UT WOS:000175882000014 PM 12047740 ER PT J AU Rossouw, JE AF Rossouw, JE TI Effect of postmenopausal hormone therapy on cardiovascular risk SO JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT International Symposium on Cardiovascular Risk in Special Populations: Hypertensive Disease in Women CY SEP 22-23, 2000 CL BOLOGNA, ITALY DE estrogen; hormone replacement therapy; coronary heart disease; stroke ID DENSITY LIPOPROTEIN CHOLESTEROL; RANDOMIZED CONTROLLED TRIAL; CORONARY HEART-DISEASE; REPLACEMENT THERAPY; WOMEN; ESTROGEN; ESTRADIOL AB The role of postmenopausal hormone therapy for the prevention and treatment of coronary heart disease remains an important unanswered question. Clinical trials have not yet produced evidence of benefit and at least one trial has suggested initial harm after initiation of therapy. The data from observational epidemiology remain supportive of benefit however these data are subject to various biases and interpretations. Mechanistic studies support either potential benefit or potential harm. Postmenopausal hormone therapy should not be recommended for the prevention of coronary heart disease until the potential early harm has been explained, methods of screening out women at high risk have been devised, and long-term benefit has been demonstrated in randomized controlled clinical trials. (C) 2002 Lippincott Williams Wilkins. C1 NHLBI, Womens Hlth Initiat, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, 1 Rockledge Dr, Bethesda, MD 20892 USA. NR 25 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD MAY PY 2002 VL 20 SU 2 BP S62 EP S65 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 562FE UT WOS:000176186100015 PM 12183856 ER PT J AU Dasso, J Lee, J Bach, H Mage, RG AF Dasso, J Lee, J Bach, H Mage, RG TI A comparison of ELISA and flow micro sphere-based assays for quantification of immunoglobulins SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ELISA; flow cytometry; multiplex assay; FlowMetrix (TM); fecal immunoglobulins ID NUCLEOTIDE POLYMORPHISM ANALYSIS; MICROSPHERE IMMUNOASSAY; FLOWMETRIX(TM) SYSTEM; MULTIPLEXED ANALYSIS; BLOOD; QUANTITATION; ANTIBODIES; CYTOKINES AB An automated microsphere-based flow cytometric assay (FlowMetrix(TM) system) was compared with a conventional enzyme-linked immunosorbent assay (ELISA) for quantifying Ig classes in serum and stool samples. The reproducibility of the process of coupling capture antibodies to microspheres was tested, The use of independently coupled microspheres did not increase the variation of assay results relative to using the same bead set in repeated assays. However, it is necessary to ensure quality control of the coupling process since slight variations in the coupling procedures can profoundly affect the density of capture reagents coupled to the microspheres and consequently adversely affect assay precision. Although the ELISA was more sensitive and did not have the problems with instrument performance encountered with the FlowMetrix(TM) assay, the latter was more reproducible, had a greater dynamic range of measurement, and took considerably less preparation time than the ELISA. Greater reproducibility is especially important for measurement of fecal Ig. which is typically highly variable. Thus, in addition to its multi-analyte capability, the FlowMetrix(TM) assay system has definite advantages over a conventional ELISA. Mechanical problems such as microspheres settling to the bottom of wells during analysis by an automated plate reader will likely be overcome, and sensitivity improved as this technology develops. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Dasso, J (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,MSC-1892, Bethesda, MD 20892 USA. NR 16 TC 54 Z9 62 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 1 PY 2002 VL 263 IS 1-2 BP 23 EP 33 AR PII S0022-1759(02)00028-5 DI 10.1016/S0022-1759(02)00028-5 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 560HH UT WOS:000176076300003 PM 12009201 ER PT J AU Xie, ZH Ambudkar, I Siraganian, RP AF Xie, ZH Ambudkar, I Siraganian, RP TI The adapter molecule Gab2 regulates Fc epsilon RI-mediated signal transduction in mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; AFFINITY IGE RECEPTOR; PHOSPHOLIPASE C-GAMMA; GROWTH-FACTOR RECEPTORS; HISTAMINE-RELEASE; IMMUNOGLOBULIN-E; PHOSPHATIDYLINOSITOL 3-KINASE; ANTIGEN RECEPTORS; T-CELL; ACTIVATION AB The recently cloned scaffolding molecule Gab2 can assemble multiple molecules involved in signaling pathways. Bone marrow-derived mast cells isolated from Gab2(-/-) mice have defective signaling probably due to the lack of the activation of phosphatidylinositol-3 kinase (P13-kinase). In this study, we investigated the role of Gab2 using the rat basophilic leukemia 2H3 cell line mast cells. FcepsilonRI aggregation induced the tyrosine phosphorylation of Gab2 and translocation of a significant fraction of it from the cytosol to the plasma membrane. As in other cells, Gab2 was found to associate with several signaling molecules including Src homology 2-containing protein tyrosine phosphatase 2, Grb2, Lyn, and phospholipase Cgamma (PLCgamma). The association of Gab2 with Lyn and PLCgamma were enhanced after receptor aggregation. Overexpression of Gab2 in rat basophilic leukemia 2H3 cell line cells inhibited the FcepsilonRI-induced tyrosine phosphorylation of the subunits of the receptor, and the phosphorylation and/or activation of Syk and mitogen-activated protein kinase. Downstream events such as calcium mobilization, degranulation, and induction of TNF-alpha and IL-6 gene transcripts were decreased in Gab2 overexpressing cells, although Akt phosphorylation as a measure of P13-kinase activation was unaffected. These results suggest that in addition to the positive effects mediated by P13-kinase that are apparent in Gab2(-/-) mast cells, Gab2 by interacting with Lyn and PLCgamma may have negative regulatory effects on FcepsilonRI-induced mast cell signaling and functions. C1 Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Siraganian, RP (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, Dept Hlth & Human Serv,NIH, Bldg 10,Room 1N106, Bethesda, MD 20892 USA. NR 58 TC 39 Z9 39 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 MAY 1 PY 2002 VL 168 IS 9 BP 4682 EP 4691 PG 10 WC Immunology SC Immunology GA 546FP UT WOS:000175263000056 PM 11971018 ER PT J AU Janabi, N AF Janabi, N TI Selective inhibition of cyclooxygenase-2 expression by 15-deoxy-Delta(12),(14)-prostaglandin J(2) in activated human astrocytes, but not in human brain macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; HUMAN FETAL ASTROCYTES; CENTRAL-NERVOUS-SYSTEM; HUMAN MICROGLIAL CELLS; PPAR-GAMMA AGONISTS; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); RECEPTOR-GAMMA; INFLAMMATION CONTROL; ALZHEIMERS-DISEASE AB Overexpression of the inducible cyclooxygenase (COX-2) and inducible NO synthase (iNOS) in activated brain macrophages (microglia) and astrocytes appears central to many neuroinflammatory conditions. 15-Deoxy-Delta(12.14)-PGJ(2) (15d-PGJ(2)) is a ligand for the peroxisome proliferator-activated receptor (PPAR)gamma. It has been proposed as an inhibitor of microglial activation, based on the study of iNOS down-regulation in rodent microglia. Because iNOS induction after cytokine activation remains controversial in human microglia, we examined the effect of 15d-PGJ2 and other PPAR agonists on human microglia and astrocytes, using COX-2 induction as an index of activation. We found that PPARalpha ligands (clofibrate and WY14643) enhanced IL-1beta-induced COX-2 expression in human astrocytes and microglia, while inhibiting IL-1beta plus IFN-gamma induction of iNOS in astrocytes. This is the first description of an inhibition of iNOS uncoupled from that of COX-2. 15d-PGJ2 suppressed COX-2 induction in human astrocytes. It prevented NF-kappaB binding to the COX-2 promoter through a new pathway that is the repression of NF-kappaBp50 induction by IL-1beta. In contrast, 15d-PGJ(2) increased c-Jun and c-Fos DNA-binding activity in astrocytes, which may result in the activation of other inflammatory pathways. In human microglia, no effect of 15d-PGJ2 on COX-2 and NF-kappaBp65/p50 induction was observed. However, the entry of 15d-PGJ2 occurred in microglia because STAT-1 and c-Jun expression was modulated. Our data suggest the existence of novel pathways mediated by 15d-PGJ2 in human astrocytes. They also demonstrate that, unlike astrocytes and peripheral macrophages or rodent brain macrophages, human microglia are not subject to the anti-inflammatory effect of 15d-PGJ(2) in terms of COX-2 inhibition. C1 NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Janabi, N (reprint author), Ecole Natl Vet Toulouse, UMR960 INRA, Mol Microbiol Lab, 23 Chemin Capelles, F-31076 Toulouse, France. NR 48 TC 55 Z9 57 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 MAY 1 PY 2002 VL 168 IS 9 BP 4747 EP 4755 PG 9 WC Immunology SC Immunology GA 546FP UT WOS:000175263000063 PM 11971025 ER PT J AU Melo, MEF Qian, JH El-Amine, M Agarwal, RK Soukhareva, N Kang, YB Scott, DW AF Melo, MEF Qian, JH El-Amine, M Agarwal, RK Soukhareva, N Kang, YB Scott, DW TI Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; TOLERANCE INDUCTION; ORAL TOLERANCE; MULTIPLE-SCLEROSIS; ENCEPHALOMYELITIS; MECHANISMS; PEPTIDE; ANTIGENS; SELF; IMMUNOGLOBULIN AB Based on the tolerogenic properties of IgG carriers and B cell Ag presentation, we developed a retrovirally mediated gene expression approach for treatment of autoimmune conditions. In this study, we show that the IgG-Ag retroviral constructs, expressing myelin basic protein (MBP) or glutamic acid decarboxylase in B cells, can be used for the treatment of murine models for multiple sclerosis and diabetes. Transduction of syngeneic B cells with MBP-IgG leads to the amelioration of ongoing experimental allergic encephalomyelitis induced by the transfer of primed cells from PLxSJL F-1 mice with ongoing disease and could be effective even after symptoms appeared. This effect is specific and does not involve bystander suppression because treatment with MBP-IgG does not affect disease induced after immunization with proteolipid protein immunodominant peptide plus MBP. Interestingly, if donor B cells are derived from g/d mice (Fas ligand-negative), then tolerance is not induced with a model Ag although there was no evidence for Fas ligand-mediated deletion of target T cells. In spontaneous diabetes in nonobese diabetic mice, we were able to stop the ongoing autoimmune process by treatment at 7-10 wk with glutamic acid decarboxylase-IgG retrovirally transduced B cells, or attenuate it with B cells transduced with an insulin B chain (B9-23) epitope IgG fusion protein. Furthermore, IgG fusion protein gene therapy can also protect primed recipients from Ag-induced anaphylactic shock, and thus does not cause immune deviation. These results demonstrate proof of principle for future efforts to develop this approach in a clinical setting. C1 Amer Red Cross, Holland Lab, Dept Immunol, Rockville, MD 20855 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Scott, DW (reprint author), Amer Red Cross, Holland Lab, Dept Immunol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NIAID NIH HHS [R01 AI35622, K08 AI01509]; NIDDK NIH HHS [DK61327] NR 30 TC 87 Z9 89 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 MAY 1 PY 2002 VL 168 IS 9 BP 4788 EP 4795 PG 8 WC Immunology SC Immunology GA 546FP UT WOS:000175263000068 PM 11971030 ER PT J AU Hwu, P Freedman, RS AF Hwu, P Freedman, RS TI The immunotherapy of patients with ovarian cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE ovarian cancer; immunotherapy; T-cells; vaccine; tumor antigens ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOTOXIC T-LYMPHOCYTES; RECOMBINANT INTERFERON-GAMMA; GYNECOLOGIC-ONCOLOGY-GROUP; TRANSFORMING GROWTH-FACTOR; MINIMAL RESIDUAL-DISEASE; PHASE-II; MALIGNANT ASCITES; DENDRITIC CELLS; INTRAPERITONEAL CISPLATIN AB Ovarian cancer is a leading cause of cancer mortality. Chemotherapy is effective in reducing tumor burden in a majority of patients, however, only approximately 20% of advanced disease patients will ultimately survive tumor free, and further treatment options are needed. Continuing advances in immunology make immunotherapy a promising area for future research. The design of immunotherapy strategies for ovarian cancer requires an understanding of the immune microenvironment of the peritoneal cavity, which is frequently involved with ovarian cancer metastases and is the site of its most devastating effects. Immunotherapy approaches for ovarian cancer include locoregional and systemic cytokine therapies, prophylactic and therapeutic vaccines, and adoptive immunotherapy strategies. This review will summarize previous clinical trials as well as future directions for research. Further progress in T-cell specific immune responses will require the identification of specific ovarian cancer antigens that are processed and presented on the surface of tumor cells in the context of specific HLA molecules. In addition, a more detailed understanding of functional relations between the peritoneal microenvironment and the metastatic process is required. C1 NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Obstet Gynecol, Houston, TX 77030 USA. RP Hwu, P (reprint author), Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 88 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2002 VL 25 IS 3 BP 189 EP 201 DI 10.1097/00002371-200205000-00001 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 552ZQ UT WOS:000175650800001 PM 12000860 ER PT J AU Antony, PA Restifo, NP AF Antony, PA Restifo, NP TI Do CD4(+)CD25(+) immunoregulatory T cells hinder tumor immunotherapy? SO JOURNAL OF IMMUNOTHERAPY LA English DT Editorial Material DE T regulatory cells; autoimmunity; B16 melanoma; self tolerance; tumor immunotherapy ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; SELF-TOLERANCE; REGULATORY CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; EFFECTOR FUNCTION; TRANSGENIC MICE; IN-VIVO; INDUCTION; COSTIMULATION; ELIMINATION AB After years of banishment from mainstream immunology, the notion that one subset of T cells can exert regulatory effects on other T lymphocytes is back in fashion. Recent work in knockout and transgenic mice has begun to bring molecular definition to our understanding of immunoregulatory CD4(+)CD25(+) T cells (Treg/Th3/Tr1). The identification of the glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18) expressed on T regulatory cells might afford new therapeutic opportunities. Another possible therapeutic intervention could be the blockade of signaling through the molecular pair of tumor necrosis factor-related activation induced cytokine (TRANCE) and receptor activator of NF-kappaB (RANK). Based on the available evidence from experimental mouse tumor models, however, it seems that simply blocking or even eliminating T regulatory function will not be enough to manage established tumors. The challenge for immunotherapists now is to overcome immunosuppression using the knowledge gained through the understanding of T regulatory cell function. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP Antony, PA (reprint author), NCI, NIH, Surg Branch, Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 37 TC 57 Z9 61 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2002 VL 25 IS 3 BP 202 EP 206 DI 10.1097/00002371-200205000-00002 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 552ZQ UT WOS:000175650800002 PM 12000861 ER PT J AU Rosenberg, SA Spiess, PJ Kleiner, DE AF Rosenberg, SA Spiess, PJ Kleiner, DE TI Antitumor effects in mice of the intravenous injection of attenuated Salmonella typhimurium SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cancer; Salmonella; therapy; mice ID CANCER; AGENT AB Salmonella typhimurium genetically modified at the purI and msbB genes to increase dependence on adenine and decrease stimulation of tumor necrosis factor-alpha production were injected intravenously into C57BL/6 mice bearing subcutaneous tumor or lung metastases. Decreased tumor growth and prolonged survival were seen in some, but not all of nine transplantable tumors. Salmonella increased in number in the tumor and reached levels 10,000 times higher than in the normal liver reservoir of these bacteria. Histologic studies revealed Salmonella growth in areas of the tumor although, in all cases, a viable rim of tumor survived and ultimately resulted in progressive tumor growth in all mice. These studies demonstrate that Salmonella can localize to transplantable murine tumors and partially inhibit tumor growth; however, additional modifications of the bacteria may be necessary if this approach is to develop into an effective treatment for patients with cancer. C1 Natl Canc Inst, Ctr Canc Res, Inst Hlth, Surg Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Ctr Canc Res, Inst Hlth, Pathol Lab, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), Natl Canc Inst, Ctr Canc Res, Inst Hlth, Surg Branch, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS [Z01 SC003811-33] NR 9 TC 42 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2002 VL 25 IS 3 BP 218 EP 225 DI 10.1097/00002371-200205000-00004 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 552ZQ UT WOS:000175650800004 PM 12000863 ER PT J AU Dudley, ME Wunderlich, JR Yang, JC Hwu, P Schwartzentruber, DJ Topalian, SL Sherry, RM Marincola, FM Leitman, SF Seipp, CA Rogers-Freezer, L Morton, KE Nahvi, A Mavroukakis, SA White, DE Rosenberg, SA AF Dudley, ME Wunderlich, JR Yang, JC Hwu, P Schwartzentruber, DJ Topalian, SL Sherry, RM Marincola, FM Leitman, SF Seipp, CA Rogers-Freezer, L Morton, KE Nahvi, A Mavroukakis, SA White, DE Rosenberg, SA TI A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE adoptive transfer therapy; nonmyeloablative chemotherapy; T cell clones; interleukin-2 therapy; melanoma ID STEM-CELL TRANSPLANTATION; INFILTRATING LYMPHOCYTES; PERIPHERAL-BLOOD; REGULATORY PROPERTIES; VITRO STIMULATION; IMMUNOTHERAPY; INTERLEUKIN-2; REGRESSION; RECIPIENTS; CLONES AB This report describes a phase I clinical trial using nonmyeloablative, lympho-depleting chemotherapy in combination with adoptive imununotherapy in patients with metastatic melanoma. The chemotherapy-conditioning schedule that induced transient lymphopenia consisted of cyclophosphamide (30 or 60 mg/kg per day for 2 days) followed by fludarabine (25 mg/m(2) per day for 5 days). Immunotherapy for all patients consisted of in vitro expanded, tumor-reactive, autologous T-cell clones selected for high avidity recognition of melanoma antigens. Cohorts of three to six patients each received either no interleukin (IL)-2, low-dose IL-2 (72,000 IU/kg intravenously three times a day to a maximum of 15 doses), or high-dose IL-2 (720,000 IU/kg intravenously three times a day for a maximum of 12 doses). The toxicities associated with this treatment were transient and included neutropenia and thrombocytopenia that resolved in all patients. High dose intravenous IL-2 was better tolerated by patients after chemotherapy than during previous immunotherapy cycles without chemotherapy. No patient exhibited an objective clinical response to treatment, although five patients demonstrated mixed responses or transient shrinkage of metastatic deposits. This study established a nonmyeloablative-conditioning regimen that could be safely administered in conjunction with adoptive T-cell transfer and IL-2 in patients with metastatic melanoma. C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, NIH, Surg Branch, Bldg 10,Room 2B-08,10 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 32 TC 211 Z9 218 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2002 VL 25 IS 3 BP 243 EP 251 DI 10.1097/00002371-200205000-00007 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 552ZQ UT WOS:000175650800007 PM 12000866 ER PT J AU Seiter, S Monsurro, V Nielsen, MB Wang, E Provenzano, M Wunderlich, JR Rosenberg, SA Marincola, FM AF Seiter, S Monsurro, V Nielsen, MB Wang, E Provenzano, M Wunderlich, JR Rosenberg, SA Marincola, FM TI Frequency of MART-1/MelanA and gp100/PMe117-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma antigens; immunotherapy; tumor-specific antigens ID MELANOMA-ASSOCIATED ANTIGENS; IN-VITRO STIMULATION; PERIPHERAL-BLOOD; IMMUNE SURVEILLANCE; HLA-A; PEPTIDE; VIVO; VACCINATION; RECOGNITION; MART-1 AB Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17, frequently are observed as targets of tumor infiltrating lymphocytes (TIL) originated from HLA-A*0201-expressing patients with melanoma. Furthermore, particular clinical relevance was attributed to gp100/pMel17 based on the impression that the adoptive transfer of gp100-recognizing TIL was associated with clinical responses in a small group of patients. However, the actual frequency of specific T cells for these melanoma differentiation antigens has never been directly enumerated in ex vivo or in vitro expanded TIL cultures. Here, we enumerated melanoma differentiation antigen-specific T-cell precursor frequency in TIL using tetrameric HLA/epitope complexes, functionally characterizing their responsiveness to cognate epitope by cytokine release assay. T-cell precursor frequencies were enumerated in I I fresh-tumor preparations and 17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100-specific T cells could be detected respectively in 5 and 2 of the I I fresh preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one exception, melanoma differentiation antigen-specific T-cell precursor frequency in fresh material and TIL ranged between 5,000 to 21,000/10(6) CD8(+) T cells. T-cell precursor frequency was not significantly higher in TIL whose administration was associated with clinical response. These data provide direct enumeration of MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of HLA-A*0201. C1 NCI, NIH, Div Clin Sci, Surg Branch, Bethesda, MD 20892 USA. Ctr Clin, Dept Transfus Med, Bethesda, MD USA. RP Marincola, FM (reprint author), NCI, NIH, Div Clin Sci, Surg Branch, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 43 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2002 VL 25 IS 3 BP 252 EP 263 DI 10.1097/00002371-200205000-00008 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 552ZQ UT WOS:000175650800008 PM 12000867 ER PT J AU Marroquin, CE Westwood, JA Lapointe, R Mixon, A Wunderlich, JR Caron, D Rosenberg, SA Hwu, P AF Marroquin, CE Westwood, JA Lapointe, R Mixon, A Wunderlich, JR Caron, D Rosenberg, SA Hwu, P TI Mobilization of dendritic cell precursors in patients with cancer by Flt3 ligand allows the generation of higher yields of cultured dendritic cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dendritic cells; Flt3 ligand; melanoma cancer; renal cancer ID COLONY-STIMULATING FACTOR; IN-VIVO; METASTATIC MELANOMA; IMMUNE-RESPONSE; PEPTIDE VACCINE; TUMOR-IMMUNITY; TREATED MICE; STEM-CELLS; ANTIGEN; MATURE AB Flt3 ligand (Flt3L) stimulates the proliferation and differentiation of hematopoietic cells. Subcutaneous Flt3L administration has been shown to effectively manage some murine cancers and in humans, to lead to an increase in peripheral blood monocyte and dendritic cell (DC) counts. In the current study, we determined the effects of Flt3L therapy on patients with melanoma and renal cancer, and in particular, if Flt3L could be used either by enhancing the immunization of patients with melanoma to tumor antigen peptides in vivo, or by mobilizing DC precursors to allow the production of larger numbers of cultured DC. Flt3 ligand administration resulted in a 19-fold increase in DC counts in the peripheral blood of patients. The DC generated in vivo appeared only partially activated, expressing increased levels of CD86, CD33, and major histocompatibility complex class H, but no or low levels of CD80 and CD83. This partial activation may account for the lack of enhanced immune responses to melanoma anti-ens and absence of clinical responses in the patients even in combination with antigen immunization. Flt3 ligand administration did result, however, in a 7-fold increased yield of monocytes per liter of blood from leukapheresed patients. Dendritic cells were as readily generated from monocytes collected before and after Flt3L therapy, and they stimulated allogeneic T-cell proliferation in a mixed leukocyte reaction to a similar magnitude. Thus, the use of Flt3L may be an important method to mobilize DC precursors to allow patient therapy with larger numbers of cultured DC. C1 NCI, NIH, Bethesda, MD 20892 USA. Immunex Corp, Seattle, WA USA. RP Hwu, P (reprint author), NCI, NIH, Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 39 TC 41 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2002 VL 25 IS 3 BP 278 EP 288 DI 10.1097/00002371-200205000-00011 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 552ZQ UT WOS:000175650800011 PM 12000870 ER PT J AU Hisada, M Lal, RB Masciotra, S Rudolph, DL Martin, MP Carrington, M Wilks, RJ Manns, A AF Hisada, M Lal, RB Masciotra, S Rudolph, DL Martin, MP Carrington, M Wilks, RJ Manns, A TI Chemokine receptor gene polymorphisms and risk of human T lymphotropic virus type I infection in Jamaica SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th International Conference on Human Retrovirology HTLV and Related Viruses CY JUN 25-29, 2001 CL DUBLIN, IRELAND ID DISEASE PROGRESSION; HIV-1 INFECTION; CCR2; AIDS AB Polymorphisms of some chemokine receptor genes and their ligands are associated with susceptibility and progression of human immunodeficiency virus infection. This study assessed whether these variants are also responsible for susceptibility to infection with human T lymphotropic virus (HTLV) type I. Frequencies of CCR5-Delta32, CCR2-64I, and SDF-1-3'A genotype among 116 HTLV-I-positive and 126 HTLV-I-negative persons of African descent in Jamaica were 1.0%, 14.9%, and 5.4%, respectively. The association of HTLV-I infection with the most common variant, CCR2-64I, was examined in 532 subjects. Thirteen (5.4%) of 241 HTLV-I-negative subjects were homozygous for CCR2-64I, versus 3 (1.0%) of 291 HTLV-I-positive subjects (P = .005). Among HTLV-I carriers, provirus load and antibody titer were not significantly different in persons with CCR2-+/64I or CCR2-+/+. These findings suggest that CCR2-64I, or alleles in linkage disequilibrium with it, may affect the risk of HTLV-I infection in a recessive manner. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Frederick, MD USA. CDCP, HIV Immunol & Diagnost Branch, Div AIDS STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA USA. Univ W Indies, Res Inst Trop Med, Epidemiol Res Unit, Kingston 7, Jamaica. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut B;vd,EPS 8008, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CO-56000] NR 15 TC 5 Z9 5 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2002 VL 185 IS 9 BP 1351 EP 1354 DI 10.1086/340129 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 542FR UT WOS:000175033300020 PM 12001056 ER PT J AU Wohl, DA Aweeka, FT Schmitz, J Pomerantz, R Cherng, DW Spritzler, J Fox, L Simpson, D Bell, D Holohan, MK Thomas, S Robinson, W Kaplan, G Teppler, H AF Wohl, DA Aweeka, FT Schmitz, J Pomerantz, R Cherng, DW Spritzler, J Fox, L Simpson, D Bell, D Holohan, MK Thomas, S Robinson, W Kaplan, G Teppler, H CA Natl Inst Allergy Infect Dis AIDS TI Safety, tolerability, and pharmacokinetic effects of thalidomide in patients infected with human immunodeficiency virus: AIDS Clinical Trials Group 267 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, ILLINOIS ID APHTHOUS ULCERS AB Thalidomide is used to treat human immunodeficiency virus (HIV)-associated conditions, including aphthous ulcers and wasting syndrome. The safety, tolerability, and pharmacokinetics of a formulation of thalidomide with improved bioavailability in HIV-infected persons was examined in a placebo-controlled, dose-escalating phase 1 study. Subjects with CD4 cell counts of 200-500 cells/mm(3) were enrolled and randomized 3: 1 in groups of 12 to receive 50, 100, or 150 mg of thalidomide or matching placebo. Two subjects who received 150 mg of drug and 2 subjects assigned placebo experienced dose-limiting toxicity. Concentrations of thalidomide in the blood increased with escalating dose, but the time to maximum concentration and clearance did not differ across dose cohorts. Previous suggestions of autoinduction of drug metabolism were not confirmed by this study. At the doses studied, thalidomide was tolerated well and had linear pharmacokinetics. C1 Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA. Thomas Jefferson Sch Med, Div Infect Dis, Philadelphia, PA USA. Merck & Co Inc, W Point, PA USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Social & Sci Syst, Rockville, MD USA. Mt Sinai Sch Med, Sch Med, New York, NY USA. Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10021 USA. Celgene, Warren, NJ USA. RP Wohl, DA (reprint author), Univ N Carolina, Div Infect Dis, 547 Burnett Womack Bldg,CB 7030, Chapel Hill, NC 27599 USA. NR 15 TC 13 Z9 13 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2002 VL 185 IS 9 BP 1359 EP 1363 DI 10.1086/340133 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 542FR UT WOS:000175033300022 PM 12001058 ER PT J AU Bohr, VA AF Bohr, VA TI DNA damage and its processing. Relation to human disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article; Proceedings Paper CT 39th Annual SSIEM Symposium CY 2001 CL PRAGUE, CZECH REPUBLIC ID MITOCHONDRIAL-DNA; EXCISION-REPAIR; CANCER AB We are constantly exposed to sources of agents that directly damage the genetic material. This exposure comes from environmental sources but also from within our own organisms. DNA damage occurs at a high frequency due to metabolic processes and environmental factors such as various exposures and the intake of food and drugs. The stability and correct function of the DNA is necessary for normal cellular functions and there is good evidence that damage to the DNA can lead to cellular dysfunction, cancer and other diseases, or cell death. To avoid or minimize the damage to DNA we have evolved an elaborate set of DNA repair pathways that survey the DNA and fix the errors. There are several human diseases that are known to be defective in these repair pathways, and the accumulation of DNA damage with time in their genome may then be the cause of the associated high incidence of cancer or of an expedited ageing process. The prevention and/or repair of DNA damage thus represent major concerns in biology and medicine. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 14 TC 25 Z9 25 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD MAY PY 2002 VL 25 IS 3 BP 215 EP 222 DI 10.1023/A:1015681929316 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 555GL UT WOS:000175786300008 PM 12137230 ER PT J AU Endo, F Sun, MS AF Endo, F Sun, MS TI Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article; Proceedings Paper CT 39th Annual SSIEM Symposium CY 2001 CL PRAGUE, CZECH REPUBLIC ID TYROSINEMIA TYPE-I; LETHAL ALBINO DELETIONS; HEREDITARY TYROSINEMIA; FUMARYLACETOACETATE HYDROLASE; 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE; HEPATIC-DYSFUNCTION; MOUSE STRAIN; MURINE MODEL; MICE; GENE AB Hereditary tyrosinaemia type I (HT I) (McKusick 276700) is caused by a deficiency of fumarylacetoacetate hydrolase (FAH) activity, the last enzyme in the tyrosine catabolic pathway. Homozygous disruption of the gene encoding FAH in mice (Fah) causes neonatal lethality (i.e. lethal Albino deletion c14CoS mice), which limits the use of this animal as a model for HT I. We developed a new mouse model that carries two genetic defects, Fah and 4-hydroxyphenyl-pyruvate dioxygenase (Hpd). The double mutant Fah-/-Hpd-/- mice grew normally without evidence of liver and renal disease, showing a phenotype similar to Hpd-/- mice. Complete blockage of the tyrosine catabolic pathway at the, step of HPD prevents development of clinical phenotypes. Administration of homogentisate resulted in rapid apoptosis of hepatocytes and renal tubular epithelial cells, a central feature of visceral injury in patients with HT I. Simultaneously, renal tubular function was impaired, resulting in Fanconi syndrome. Apoptosis of hepatocyte and renal tubular cells is prevented by the caspase inhibitors YVAD or DEVD. However, these inhibitors do not prevent the release of cytochrome c or the development of renal tubular dysfunction. Apoptosis of hepatocytes and of renal tubular epithelial cells are characteristic features of this disease and the apoptotic signal in this disease seems to be initiated by fumarylacetoacetate. C1 Kumamoto Univ, Dept Pediat, Kumamoto 8608556, Japan. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Endo, F (reprint author), Kumamoto Univ, Dept Pediat, Honjo 1-1-1, Kumamoto 8608556, Japan. NR 23 TC 12 Z9 13 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD MAY PY 2002 VL 25 IS 3 BP 227 EP 234 DI 10.1023/A:1015646400182 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 555GL UT WOS:000175786300010 PM 12137232 ER PT J AU Kuo, AY Reiss, AL Freund, LS Huffman, LC AF Kuo, AY Reiss, AL Freund, LS Huffman, LC TI Family environment and cognitive abilities in girls with fragile-X syndrome SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE cognition; family environment; fragile-X syndrome; Family Environment Scale; genetic abnormalities ID HOME-ENVIRONMENT; CHILDREN; TEMPERAMENT; INTELLIGENCE; DISABILITIES; MULTICENTER; CHILDHOOD; PHENOTYPE; ADOPTION; BEHAVIOR AB Background There remains some variance in cognitive ability that is unexplained in children with fragile-X syndrome (FXS). Studies in typically developing children suggest that family environment might be one contributor to this unexplained variance. However, the effect of family environment in relation to cognition in atypical children with FXS has been relatively unexplored to date. Methods The present authors examined the putative genetic and environmental factors associated with cognition in a group of age-matched children consisting of 26 females with FXS and 31 typically developing children. All subjects were administered the Wechsler Intelligence Scale for Children - Revised; and the subjects' parents were administered the Wechsler Adult Intelligence Scale - Revised, and completed the Hollingshead Index of Social Status and the Moos & Moos Family Environment Scale. Results Using a multiple regression analytic strategy, the present authors found that family environment contributed significantly to cognitive abilities in typically developing girls, but did not have a unique contribution to cognitive abilities in girls with FXS. There was a suggestion that, for girls with FXS, socio-economic status, a measure of sociocultural environment, was correlated with IQ. Conclusions The present study provides a basis for future research on the environmental contributions to cognitive abilities, particularly work related to verbal cognition. C1 Childrens Hlth Council, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Huffman, LC (reprint author), Childrens Hlth Council, 650 Clark Way, Palo Alto, CA 94304 USA. FU NIMH NIH HHS [MH 01142, MH 50047] NR 29 TC 7 Z9 7 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD MAY PY 2002 VL 46 BP 328 EP 339 DI 10.1046/j.1365-2788.2002.00396.x PN 4 PG 12 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 550XZ UT WOS:000175531500005 PM 12000584 ER PT J AU Mascarucci, P Taub, D Saccani, S Paloma, MA Dawson, H Roth, GS Lane, MA Ingram, DK AF Mascarucci, P Taub, D Saccani, S Paloma, MA Dawson, H Roth, GS Lane, MA Ingram, DK TI Cytokine responses in young and old rhesus monkeys: Effect of caloric restriction SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID BLOOD MONONUCLEAR-CELLS; DIETARY RESTRICTION; IMMUNE-SYSTEM; PERIPHERAL-BLOOD; MACACA-MULATTA; NONHUMAN-PRIMATES; OXIDATIVE STRESS; AGE; INTERLEUKIN-6; FOOD AB Caloric restriction (CR) is the only known intervention demonstrated to retard a great variety of aging processes, extend median and maximum life-span, and decrease the incidence of age-associated diseases in mammals. Paralleling findings from rodent studies, studies in rhesus monkeys (Macaca mulatta) suggest that CR may retard many age-sensitive parameters in primates. A recent study in rhesus monkeys showed age-related dysregulation of cytokine levels. Specifically, age-related increases in interleukin-10 (IL-10) and IL-6 proteins were observed in supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-gamma) protein exhibited an age-related decrease in phytohemagglutinin (PHA)stimulated PBMCs. To investigate effects of CR on age-related changes in cytokine production, we obtained PBMCs from control and CR rhesus monkeys aged 6-7 and 22-25 years. We evaluated IL-10 and IL-6 protein and gene expression after exposure to LPS and IFN-gamma protein and gene expression after PHA stimulation. The results revealed significantly higher levels of IFN-gamma protein and gene expression in aged monkeys on CR for 2 years compared with controls. No significant CR effects were observed on IL-10 and IL-6 protein levels. IFN-gamma plays an important role in the initial defense mechanism against viral and microbial disease and cancer. Altered regulation of IFN-gamma in old CR rhesus monkeys may be a key factor in reducing cancer incidence and other age-associated diseases. C1 NIA, Behav Neurosci Sect, Neurosci Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Behav Neurosci Sect, Neurosci Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Dawson, Harry/H-8242-2013 NR 46 TC 24 Z9 25 U1 2 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD MAY PY 2002 VL 22 IS 5 BP 565 EP 571 DI 10.1089/10799900252982043 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 558EG UT WOS:000175952900007 PM 12060495 ER PT J AU Wahl, SM AF Wahl, SM TI In memoriam - Geertruida Jeanette Thorbecke, MD, Ph.D. - 1929-2001 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Biographical-Item C1 NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIH, Bldg 10, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2002 VL 71 IS 5 BP 905 EP 906 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 550DU UT WOS:000175489000020 ER PT J AU Gonzalez-Navarro, H Nong, ZX Freeman, L Bensadoun, A Peterson, K Santamarina-Fojo, S AF Gonzalez-Navarro, H Nong, ZX Freeman, L Bensadoun, A Peterson, K Santamarina-Fojo, S TI Identification of mouse and human macrophages as a site of synthesis of hepatic lipase SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipoprotein lipase; lipoproteins; RAW 264.7; THP ID IN-VIVO EVIDENCE; HIGH-DENSITY-LIPOPROTEINS; TRIGLYCERIDE LIPASE; TRANSGENIC MICE; DEFICIENT MICE; ATHEROSCLEROSIS; CHOLESTEROL; METABOLISM; LIVER; GENE AB Hepatic lipase (HL) is synthesized by the liver and is also present in steroidogenic tissues. As both a lipolytic enzyme and a ligand that facilitates the cellular uptake of lipoproteins, HL plays a major role in lipoprotein metabolism and may modulate atherogenic risk. However, HL has not been directly implicated in lesion development. In the present study we demonstrate that HL is also synthesized by, mouse and human macrophages. Northern analysis and real time RT-PCR showed that HL mRNA is present in mouse peritoneal macrophages, RAW-264.7, and IC-21 cells. The levels of HL mRNA in mouse peritoneal macrophages were approximately 10-30% that of mouse liver. HL protein was identified by Western blot analyses in human monocyte-derived macrophages, THP, RAW-264.7, and mouse peritoneal macrophages following fractionation by heparin-sepharose affinity chromatography. These combined findings establish that HL is synthesized de novo by macrophages as well as liver, and rates the possibility that HL may have a direct role in the pathogenesis of atherosclerosis. C1 Cornell Univ, Div Nutr Sci, Ithaca, NY 14852 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Gonzalez-Navarro, H (reprint author), Cornell Univ, Div Nutr Sci, Ithaca, NY 14852 USA. NR 35 TC 43 Z9 44 U1 1 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2002 VL 43 IS 5 BP 671 EP 675 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 548PY UT WOS:000175398800002 PM 11971936 ER PT J AU Li, YJ Tsoi, SCM AF Li, YJ Tsoi, SCM TI Phylogenetic analysis of vertebrate lactate dehydrogenase (LDH) multigene families SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE gene duplication; transversion; sequence convergence; molecular clock; phylogeny; vertebrate evolution ID DOGFISH SQUALUS-ACANTHIAS; RELATIVE-RATE TEST; CDNA SEQUENCE; EVOLUTIONARY RELATIONSHIPS; MOLECULAR EVOLUTION; DIVERGENCE DATES; GENE DUPLICATION; NUCLEOTIDE; MAMMALS; TREES AB In this paper we analyzed 49 lactate dehydrogenase (LDH) sequences, mostly from vertebrates. The amino acid sequence differences were found to be larger for a human-killifish pair than a human-lamprey pair. This indicates that some protein sequence convergence may occur and reduce the sequence differences in distantly related species. We also examined transitions and transversions separately for several species pairs and found that the transitions tend to be saturated in the distantly related species pair, while transversions are increasing. We conclude that transversions maintain a conservative rate through the evolutionary time. Kimura's two-parameter model for multiple-hit correction on transversions only was used to derive a distance measure and then construct a neighbor-joining (NJ) tree. Three findings were revealed from the NJ tree:(i) the branching order of the tree is consistent with the common branch pattern of major vertebrates; (ii) Ldh-A and Ldh-B genes were duplicated near the origin of vertebrates; and (iii) Ldh-C and Ldh-A in mammals were produced by an independent gene duplication in early mammalian history. Furthermore, a relative rate test showed that mammalian Ldh-C evolved more rapidly than mammalian Ldh-A. Under a two-rate model, this duplication event was calibrated to be approximately 247 million years ago (mya), dating back to the Triassic period. Other gene duplication events were also discovered in Xenopus, the first duplication occurring approximately 60-70 mya in both Ldh-A and Ldh-B, followed by another recent gene duplication event, approximately 20 mya, in Ldh-B. C1 Grad Univ Adv Studies, Dept Biosyst Sci, Hayama, Kanagawa 2400193, Japan. NIH, Genet Mol Lab, Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Li, YJ (reprint author), Duke Univ, Med Ctr, Ctr Human Genet, Box 3468, Durham, NC 27707 USA. NR 49 TC 14 Z9 18 U1 1 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAY PY 2002 VL 54 IS 5 BP 614 EP 624 DI 10.1007/s00239-001-0058-1 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 541YN UT WOS:000175014700005 PM 11965434 ER PT J AU Chang, LC Otero-Quintero, S Hooper, JNA Bewley, CA AF Chang, LC Otero-Quintero, S Hooper, JNA Bewley, CA TI Batzelline D and isobatzelline E from the Indopacific sponge Zyzzya fuliginosa SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYTOTOXIC PYRROLOIMINOQUINONE; PYRROLOQUINOLINE ALKALOIDS; GENUS LATRUNCULIA; CARIBBEAN SPONGE; PRIANOS-MELANOS; DISCORHABDIN-C; MAKALUVAMINES; INHIBITORS; PIGMENT; FUSION AB Two new pyrroloquinoline alkaloids, isobatzelline E (1) and batzelline D (2), together with the known compounds batzelline C(3 isobatzelline C (4), and makaluvamine D (5), were isolated from an Indopacific collection of the marine sponge Zyzzya fuliginosa; the known compounds makaluvarnines A (9), H (10), J (7), K (8), and P (6) were obtained from Z. fuliginosa collected in Papua New Guinea. The structures were elucidated by interpretation of 1D H-1 and C-13 NMR spectra and 2D HSQC and HSQC-LR Spectra. Compounds 1-10 were isolated because the crude extracts of both Zyzzya species inhibited HIV-1 envelope-mediated cell fusion. However, the inhibition profile observed for the pure compounds 1 - 10 mirrors that reported for the inhibition of topoisomerase H by other pyrroloquinolines, leaving open the possibility that the activity results from interactions with DNA-modifying enzymes. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Queensland Museum, Brisbane, Qld 4101, Australia. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. OI Hooper, John/0000-0003-1722-5954 NR 21 TC 31 Z9 33 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 2002 VL 65 IS 5 BP 776 EP 778 DI 10.1021/np010581l PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 555JG UT WOS:000175790500037 PM 12027767 ER PT J AU Jimenez, CR Eyman, M Lavina, ZS Gioio, A Li, KW van der Schors, RC Geraerts, WPM Giuditta, A Kaplan, BB van Minnen, J AF Jimenez, CR Eyman, M Lavina, ZS Gioio, A Li, KW van der Schors, RC Geraerts, WPM Giuditta, A Kaplan, BB van Minnen, J TI Protein synthesis in synaptosomes: a proteomics analysis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE local protein synthesis; mass-spectrometry; pre-synaptic; proteomics; squid; synaptosomes ID SQUID GIANT-AXON; SHOCK COGNATE PROTEIN; MESSENGER-RNA; ACTIVE POLYSOMES; PLASTICITY; SYNAPSE; BRAIN; LOCALIZATION; TRANSPORT; FRACTION AB A proteomics approach was used to identify the translation products of a unique synaptic model system, squid optic lobe synaptosomes. Unlike its vertebrate counterparts, this preparation is largely free of perikaryal cell fragments and consists predominantly of pre-synaptic terminals derived from retinal photoreceptor neurones. We metabolically labelled synaptosomes with [S-35]methionine and applied two-dimensional gel electrophoresis to resolve newly synthesized proteins at high resolution. Autoradiographs of blotted two-dimensional gels revealed de novo synthesis of about 80 different proteins, 18 of which could be matched to silver-stained gels that were run in parallel. In-gel digestion of the matched spots and mass spectrometric analyses revealed the identities of various cytosolic enzymes, cytoskeletal proteins, molecular chaperones and nuclear-encoded mitochondrial proteins. A number of novel proteins (i.e. not matching with database sequences) were also detected. In situ hybridization was employed to confirm the presence of mRNA and rRNA in synaptosomes. Together, our data show that pre-synaptic endings of squid photoreceptor neurones actively synthesize a wide variety of proteins involved in synaptic functioning, such as transmitter recycling, energy supply and synaptic architecture. C1 Vrije Univ Amsterdam, Grad Sch Neurosci Amsterdam, Neurosci Res Inst, Fac Biol, Amsterdam, Netherlands. NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Naples Federico II, Dipartimento Fisiol Gen & Ambientale, Naples, Italy. RP van Minnen, J (reprint author), Vrije Univ Amsterdam, Grad Sch Neurosci Amsterdam, Neurosci Res Inst, Fac Biol, Amsterdam, Netherlands. NR 31 TC 47 Z9 49 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2002 VL 81 IS 4 BP 735 EP 744 DI 10.1046/j.1471-4159.2002.00873.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 549YL UT WOS:000175475100008 PM 12065633 ER PT J AU Carvelli, L Moron, JA Kahlig, KM Ferrer, JV Sen, N Lechleiter, JD Leeb-Lundberg, LMF Merrill, G Lafer, EM Ballou, LM Shippenberg, TS Javitch, JA Lin, RZ Galli, A AF Carvelli, L Moron, JA Kahlig, KM Ferrer, JV Sen, N Lechleiter, JD Leeb-Lundberg, LMF Merrill, G Lafer, EM Ballou, LM Shippenberg, TS Javitch, JA Lin, RZ Galli, A TI PI 3-kinase regulation of dopamine uptake SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amphetamine; dopamin transporter; insulin; P13-kinase ID PROTEIN-KINASE-C; CELL-SURFACE EXPRESSION; N-SH CELLS; FUNCTIONAL REGULATION; NEUROTRANSMITTER TRANSPORTERS; NOREPINEPHRINE TRANSPORT; RECEPTOR INTERNALIZATION; SEROTONIN TRANSPORTERS; MEMBRANE TRAFFICKING; INSULIN-RECEPTORS AB The magnitude and duration of dopamine (DA) signaling is defined by the amount of vesicular release, DA receptor sensitivity, and the efficiency of DA clearance, which is largely determined by the DA transporter (DAT). DAT uptake capacity is determined by the number of functional transporters on the cell surface as well as by their turnover rate. Here we show that inhibition of phosphatidylinositol (PI) 3-kinase with LY294002 induces internalization of the human DAT (hDAT), thereby reducing transport capacity. Acute treatment with LY294002 reduced the maximal rate of [H-3]DA uptake in rat striatal synaptosomes and in human embryonic kidney (HEK) 293 cells stably expressing the hDAT (hDAT cells). In addition, LY294002 caused a significant redistribution of the hDAT from the plasma membrane to the cytosol. Conversely, insulin, which activates PI 3-kinase, increased [H-3]DA uptake and blocked the amphetamine-induced hDAT intracellular accumulation, as did transient expression of constitutively active PI 3-kinase. The LY294002-induced reduction in [H-3]DA uptake and hDAT cell surface expression was inhibited by expression of a dominant negative mutant of dynamin I, indicating that dynamin-dependent trafficking can modulate transport capacity. These data implicate DAT trafficking in the hormonal regulation of dopaminergic signaling, and suggest that a state of chronic hypoinsulinemia, such as in diabetes, may alter synaptic DA signaling by reducing the available cell surface DATs. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. NIDA, Integrat Neurosci Sect, IRP, Baltimore, MD USA. Columbia Univ, Coll Phys & Surg, Ctr Mol Recognit, New York, NY USA. Brooke Army Med Ctr, Dept Clin Invest, Ft Sam Houston, TX 78234 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Galli, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Mail Code 7764,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Lin, Richard/J-1754-2014 OI Lin, Richard/0000-0002-3473-7276 FU NIDA NIH HHS [DA 13975, DA 11495, DA 14684]; NIMH NIH HHS [MH 57324]; NINDS NIH HHS [R01 NS029051] NR 52 TC 126 Z9 130 U1 2 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2002 VL 81 IS 4 BP 859 EP 869 DI 10.1046/j.1471-4159.2002.00892.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 549YL UT WOS:000175475100020 PM 12065645 ER PT J AU Herman, MM Ghribi, O Savory, J AF Herman, MM Ghribi, O Savory, J TI Endoplasmic reticulum-specific apoptosis in experimental neurodegeneration and reversal by lithium. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH, NIH, IRP, Bethesda, MD 20892 USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 63 BP 458 EP 458 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500070 ER PT J AU Cassarino, DS Quezado, MM Ghatak, NR Duray, PH AF Cassarino, DS Quezado, MM Ghatak, NR Duray, PH TI Lyme-associated striatonigral degeneration: A neuropathological case study. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NCI, NIH, Dept Pathol, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pathol & Neuropathol, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 85 BP 463 EP 463 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500091 ER PT J AU Auerbach, A Cassarino, DS Rushing, EJ AF Auerbach, A Cassarino, DS Rushing, EJ TI Solitary fibrous tumor involving the sphenoid sinus, cavernous sinus, and pituitary fossa: A clinicopathological case study. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NCI, NIH, Dept Pathol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 149 BP 479 EP 479 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500155 ER PT J AU Cruz, LR Hull, KM Wood, GM Chu, W Kastner, DL Sandberg, GD Wong, K AF Cruz, LR Hull, KM Wood, GM Chu, W Kastner, DL Sandberg, GD Wong, K TI Monocytic fasciitis is the cause of myalgia in tumor necrosis factor-receptor associated periodic paralysis syndrome. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Dept Neuropathol, Washington, DC 20306 USA. NIAMSD, Off Clin Director, Bethesda, MD USA. NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD USA. Armed Forces Inst Pathol, Dept Hematopathol, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 175 BP 486 EP 486 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500182 ER PT J AU Feldman, AL Quezado, MM Biesecker, LG Ghatak, NR AF Feldman, AL Quezado, MM Biesecker, LG Ghatak, NR TI Malignant meningioma metastatic to lung associated with Proteus syndrome. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, Bethesda, MD USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Pathol & Neuropathol, Richmond, VA USA. RI Feldman, Andrew/D-5028-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 199 BP 492 EP 492 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500205 ER PT J AU Sun, MK Alkon, DL AF Sun, MK Alkon, DL TI Impairment of hippocampal CA1 heterosynaptic transformation and spatial memory by beta-amyloid(25-35) SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; AMYLOID-BETA-PEPTIDE; GAMMA-AMINOBUTYRIC-ACID; PROTEIN-KINASE-C; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; TRANSGENIC MICE; SYNAPTIC-TRANSMISSION; ACETYLCHOLINE-RELEASE; GABA(A) RECEPTORS AB In Alzheimer's disease, the cholinergic damage (reduced neurotransmission) and cognitive impairment occur long before beta-amyloid (Abeta) plaque formation. It has not been established whether the link between soluble Abeta and cholinergic functions contributes to synaptic dysfunction that underlies the cognitive impairment. Here, we report that Abeta(25-35), an active form of Abeta, inhibited long-term synaptic modification that depends on the associative activation of cholinergic and GABAergic inputs when bilaterally injected intracerebroventricularly (icv; 200 mug/site). The Abeta microinjections did not affect single-pulse-evoked glutamatergic and GABAergic synaptic transmission onto the hippocampal CA1 pyramidal cells, while cholinergic intracellular theta was dramatically reduced by the Abeta(25-35) injection. Spatial memory of the water maze task was also impaired by the bilateral icv Abeta(25-35) injections, while bilateral microinjections of the same dose of Abeta(35-25) was ineffective in affecting the long-term synaptic modification evoked by associative activation of cholinergic and GABAergic inputs, the cholinergic intracellular theta, or producing memory impairments. Thus restoring the synaptic plasticity involved in this associative activation of cholinergic and GABAergic inputs may offer an important therapeutic target in the treatment of early Abeta-induced memory decline. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. NINCDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Sun, MK (reprint author), Blanchette Rockefeller Neurosci Inst, Johns Hopkins Acad & res Bldg,Rm 319,9601 Med Ctr, Rockville, MD 20850 USA. NR 60 TC 45 Z9 46 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2002 VL 87 IS 5 BP 2441 EP 2449 DI 10.1152/jn.00230.2001 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 548YH UT WOS:000175417100020 PM 11976381 ER PT J AU De Vries, TJ Shippenberg, TS AF De Vries, TJ Shippenberg, TS TI Neural systems underlying opiate addiction SO JOURNAL OF NEUROSCIENCE LA English DT Review ID DELTA-OPIOID RECEPTORS; FREELY MOVING RATS; STRESS-INDUCED RELAPSE; DRUG-SEEKING BEHAVIOR; D2 DOPAMINE-RECEPTORS; NUCLEUS-ACCUMBENS; HEROIN-SEEKING; MORPHINE-WITHDRAWAL; COCAINE-SEEKING; MOTOR SYSTEM C1 Vrije Univ Amsterdam, Med Ctr, Dept Med Pharmacol, Drug Abuse Program,Res Inst Neurosci, NL-1081 BT Amsterdam, Netherlands. NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. RP De Vries, TJ (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Pharmacol, Drug Abuse Program,Res Inst Neurosci, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. RI De Vries, Taco/B-2831-2014; OI De Vries, Taco/0000-0002-0340-4946 NR 68 TC 159 Z9 162 U1 1 U2 19 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2002 VL 22 IS 9 BP 3321 EP 3325 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 546VN UT WOS:000175296200007 PM 11978806 ER PT J AU Bowie, D Lange, GD AF Bowie, D Lange, GD TI Functional stoichiometry of glutamate receptor desensitization SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate; AMPA; kainate; desensitization; stoichiometry; gating ID C-TYPE INACTIVATION; POTASSIUM CHANNEL INACTIVATION; NATIVE AMPA RECEPTORS; LIGAND-BINDING CORE; KAINATE RECEPTORS; THALAMOCORTICAL SYNAPSES; SUBUNIT INTERACTIONS; HIPPOCAMPAL-NEURONS; K+ CHANNELS; ACTIVATION AB Potassium (K+) channels and ionotropic glutamate receptors (iGluRs) fulfill divergent roles in vertebrate nervous systems. Despite this, however, recent work suggests that these ion channels are structurally homologous, sharing an ancestral protein, architectural design, and tetrameric subunit stoichiometry. Their gating mechanisms also are speculated to have overlapping features. Here we show that the mechanism of iGluR desensitization is unique. Unlike K+ channels, AMPA- and kainate-type iGluR subunits desensitize in several ordered conformational steps. AMPA receptors operate as dimers, whereas the functional stoichiometry of kainate receptor desensitization is dependent on external ions. Contrary to conventional understanding, kinetic models suggest that partially desensitized AMPA and kainate receptors conduct ions and are likely participants in synaptic signaling. Although sharing many structural correlates with K+ channels, iGluRs have evolved unique subunit-subunit interactions, tailoring their gating behavior to fulfill distinct roles in neuronal signaling. C1 Emory Univ, Sch Med, Rollins Res Ctr, Dept Pharmacol, Atlanta, GA 30322 USA. NINCDS, Instrumentat & Comp Sect, NIH, Bethesda, MD 20892 USA. RP Bowie, D (reprint author), Emory Univ, Sch Med, Rollins Res Ctr, Dept Pharmacol, 1510 Clifton Rd, Atlanta, GA 30322 USA. FU NIMH NIH HHS [R01 MH62144]; NINDS NIH HHS [R01 NS36654] NR 60 TC 57 Z9 59 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2002 VL 22 IS 9 BP 3392 EP 3403 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 546VN UT WOS:000175296200017 PM 11978816 ER PT J AU Reddy, DS Rogawski, MA AF Reddy, DS Rogawski, MA TI Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility SO JOURNAL OF NEUROSCIENCE LA English DT Article DE stress; seizure; pentylenetetrazol; kindling; neurosteroid; deoxycorticosterone; 5 alpha-dihydrodeoxycorticosterone; 5 alpha,3 alpha-tetrahydrodeoxycorticosterone (3 alpha,21-dihydroxy-5 alpha-pregnan-20-one); finasteride; indomethacin; GABA(A) receptor ID ENHANCED ANTICONVULSANT ACTIVITY; AMINOBUTYRIC ACID(A) RECEPTOR; TEMPORAL-LOBE EPILEPSY; RAT-BRAIN; STEROID 5-ALPHA-REDUCTASE; NEUROACTIVE STEROIDS; CATAMENIAL EPILEPSY; SWIM STRESS; 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE; HIPPOCAMPAL-NEURONS AB Stress affects seizure susceptibility in animals and humans, but the underlying mechanisms are obscure. Here, we provide evidence that GABA(A) receptor-modulating neurosteroids derived from deoxycorticosterone (DOC) play a role in stress-related changes in seizure control. DOC, an adrenal steroid whose synthesis is enhanced during stress, undergoes sequential metabolic reduction by 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase to form 5alpha-dihydrodeoxycorticosterone (DHDOC) and allotetrahydrodeoxycorticosterone (THDOC), a GABA(A) receptor-modulating neurosteroid with anticonvulsant properties. Acute swim stress in rats significantly elevated plasma THDOC concentrations and raised the pentylenetetrazol (PTZ) seizure threshold. Small systemic doses of DOC produced comparable increases in THDOC and PTZ seizure threshold. Pretreatment with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of DOC to DHDOC, reversed the antiseizure effects of stress. DOC also elevated plasma THDOC levels and protected mice against PTZ, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, picrotoxin, and amygdala-kindled seizures in mice (ED50 values, 84-97 mg/kg). Finasteride reversed the antiseizure activity of DOC (ED50, 7.2 mg/kg); partial antagonism was also obtained with indomethacin (100 mg/kg), an inhibitor of 3alpha-hydroxysteroid oxidoreductase. Finasteride had no effect on seizure protection by DHDOC and THDOC, whereas indomethacin partially reversed DHDOC but not THDOC. DHDOC, like THDOC, potentiated GABA-activated Cl- currents in cultured hippocampal neurons (less than or equal to1 muM) and directly activated GABA(A) receptor currents (greater than or equal to1 muM), compatible with a role for DHDOC in the antiseizure activity of DOC. DOC is a mediator of the physiological effects of acute stress that could contribute to stress-induced changes in seizure susceptibility through its conversion to neurosteroids with modulatory actions on GABA(A) receptors including THDOC and possibly also DHDOC. C1 NINCDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RP NINCDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Marion-Poll, Frederic/D-8882-2011; OI Marion-Poll, Frederic/0000-0001-6824-0180; Reddy, Samba/0000-0003-2735-9550 NR 69 TC 150 Z9 155 U1 1 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2002 VL 22 IS 9 BP 3795 EP 3805 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 546VN UT WOS:000175296200056 PM 11978855 ER PT J AU Toman, RE Movsesyan, V Murthy, SK Milstien, S Spiegel, S Faden, AI AF Toman, RE Movsesyan, V Murthy, SK Milstien, S Spiegel, S Faden, AI TI Ceramide-induced cell death in primary neuronal cultures: Upregulation of ceramide levels during neuronal apoptosis SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE apoptosis; ceramide; cerebellar granule cells; cortical neurons; sphingolipid ID CEREBELLAR GRANULE CELLS; ACTIVATED PROTEIN-KINASE; NERVE GROWTH-FACTOR; PC12 CELLS; SPHINGOMYELIN CYCLE; KAPPA-B; STRESS; SYSTEM; INHIBITION; SURVIVAL AB Ceramide is a sphingolipid that has been implicated both in apoptosis and protection from cell death. We show that in both rat cerebellar granule cells and cortical neuronal cultures application of C-2-ceramide causes cell death in a dose- and time-dependent manner. Similar effects were observed with the exogenous application of bacterial sphingomyelinase, which hydrolyzes sphingomyelin located on the outer leaflet of the plasma membrane and leads to endogenous ceramide accumulation. Furthermore, endogenous ceramide levels were increased during apoptosis induced by nutrient deprivation or etoposide treatment. These findings suggest that upregulation of ceramide levels, which may be generated through activation of sphingomyelinase, contributes to neuronal apoptosis. (C)2002 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIMH, Lab Cellular & Mol Commun, Bethesda, MD 20892 USA. RP Faden, AI (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, 3970 Reservoir Rd NW,Room EP-12, Washington, DC 20007 USA. NR 60 TC 58 Z9 58 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 2002 VL 68 IS 3 BP 323 EP 330 DI 10.1002/jnr.10190 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 548XX UT WOS:000175416100008 PM 12111862 ER PT J AU Watson, JC Gorbach, AM Pluta, RM Rak, R Heiss, JD Oldfield, EH AF Watson, JC Gorbach, AM Pluta, RM Rak, R Heiss, JD Oldfield, EH TI Real-time detection of vascular occlusion and reperfusion of the brain during surgery by using infrared imaging SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebrovascular system; collateral blood flow; brain temperature; brain metabolism; ischemia; infrared imaging; cynomolgus monkey ID INTRAOPERATIVE ANGIOGRAPHY; INTRACRANIAL ANEURYSMS; FLOW AB Object. Application of sensitive infrared imaging is ideally suited to observe blood vessels and blood flow in exposed organs, including the brain. Temporary vascular occlusion is an important part of neurosurgery, but the capacity to monitor the effects of these occlusions in real time is limited. In surgical procedures that require vascular manipulation, such as those involving aneurysms, arteriovenous malformations (AVMs), or tumors, the ability to visualize blood flow in vessels and their distribution beds would be beneficial. The authors recount their experience in the use of a sensitive (0.02degreesC). high-resolution (up to 50 mum/pixel) infrared camera with a rapid shutter speed (up to 2 msec/frame) for localizing cortical function intraoperatively. They observed high-resolution images of cerebral arteries and veins. The authors hypothesized that infrared imaging of cerebral arteries. performed using a sensitive, high-resolution camera during surgery, would permit changes in arterial flow to be be seen immediately, thus providing real-time assessment of brain perfusion in the involved vascular territory. Methods. Cynomolgus monkeys underwent extensive craniectomies. exposing the frontal, parietal. and temporal lobes. Temporary occlusions of the internal carotid artery and middle cerebral artery branches (30 events) were performed serially and were visualized with the aid of an infrared camera. Arteries and veins of the monkey brain were clearly visualized due to cooling of the exposed brain, which contrasted with blood within the vessels that remained at core temperature. Blood flow changes in vessels were seen immediately (< 1 second) in real time during occlusion and reopening of the vessels. regardless of the duration of the occlusion. Areas of decreased cortical blood flow rapidly cooled (-0.3 to 1.3degreesC) and reheated in response to reperfusion. Rewarming occurred faster in arteries than in the cortex (for a 20-minute occlusion. the change in temperature per second was 2 x 10(-2degrees)C in the artery and 7 x 10(-3degrees)C in the brain). Collateral flow could be evaluated by intraoperative observations and data processing. Conclusions. Use of high-resolution, digital infrared imaging permits real-time visualization of arterial flow. It has the potential to provide the surgeon with a means to assess collateral flow during temporary vessel occlusion and to visualize directly the flow in parent arteries or persistent filling of an aneurysm after clipping. During surgery for AVMs, the technique may provide a new way to assess arterial inflow. venous outflow, results of embolization, collateral flow, steal, and normal perfusion pressure breakthrough. C1 NINCDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINCDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. NR 29 TC 29 Z9 34 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 2002 VL 96 IS 5 BP 918 EP 923 DI 10.3171/jns.2002.96.5.0918 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 547VT UT WOS:000175353700014 PM 12005400 ER PT J AU Narayan, RK Michel, ME AF Narayan, RK Michel, ME CA The Clin Trials Head Injury Study TI Clinical trials in head injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE clinical trials; head injury; intracranial pressure; outcome measures; traumatic brain injury; trial design; uniformed consent ID TRAUMATIC BRAIN-INJURY; GLASGOW OUTCOME SCALE; RANDOMIZED CONTROLLED-TRIALS; ACUTE ISCHEMIC STROKE; MULTICENTER TRIAL; ANTAGONIST; DEXAMETHASONE; HU-211; NEUROPROTECTANT; HYDROPEROXIDES AB Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical,, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research. C1 Temple Univ Hosp & Med Sch, Dept Neurosurg, Philadelphia, PA 19140 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NIH NCMRR, Bethesda, MD USA. Univ Munich, Munich, Germany. Lawrence Berkeley Natl Lab, Berkeley, CA USA. Yale Univ, Sch Med, New Haven, CT USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Texas HSC, Houston, TX USA. Baylor Coll Med, Houston, TX USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Miami, Sch Med, Miami, FL USA. Brain Trauma Fdn, New York, NY USA. Hosp Univ Penn, Philadelphia, PA USA. Pfizer Global R&D, Ann Arbor, MI USA. NIH, NINDS, Bethesda, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Temple Univ, Sch Med, Philadelphia, PA USA. Food & Drug Adv, Rockville, MD USA. Sheba Med Ctr, Tel Hashomer, Israel. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Acad Hosp, Rotterdam, Netherlands. Off Naval Res, Arlington, VA USA. Univ Calif San Diego, La Jolla, CA USA. Parke Davis Pharmaceut Res, Ann Arbor, MI USA. Univ Calif Davis, Med Ctr, Sacramento, CA USA. Univ Calif San Francisco, San Francisco, CA USA. Pharmos Corp, Iselin, NJ USA. Temple Univ, Sch Med, Philadelphia, PA USA. So Gen Hosp, Glasgow, Lanark, Scotland. Univ Washington, Seattle, WA USA. Allegheny Gen Hosp, Pittsburgh, PA USA. Univ Kentucky, Chandler Med Ctr, Lexington, KY USA. Pfizer Pharmaceut Inc, Groton, CT USA. RP Narayan, RK (reprint author), Temple Univ Hosp & Med Sch, Dept Neurosurg, 3401 N Broad St, Philadelphia, PA 19140 USA. EM Narayan@nimbus.temple.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [R01 NS038654, R01 NS038654-02] NR 50 TC 489 Z9 503 U1 0 U2 22 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD MAY PY 2002 VL 19 IS 5 BP 503 EP 557 DI 10.1089/089771502753754037 PG 55 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 557PA UT WOS:000175915900001 PM 12042091 ER PT J AU Carson, RE Toczek, MT Lang, LX Fraser, C Spanaki, MV Ma, Y Der, MG Theodore, WH Eckelman, WC AF Carson, RE Toczek, MT Lang, LX Fraser, C Spanaki, MV Ma, Y Der, MG Theodore, WH Eckelman, WC TI Human functional imaging with the 5-HT1A ligand F-18-FCway. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 198 BP 55P EP 55P AR UNSP 200903 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800199 ER PT J AU Weber, S Bruyndonckx, P Chatziioannou, AF Clark, JC Daube-Witherspoon, ME Di Domenico, G Zavattini, G Honer, M Huber, J Karp, JS Laforest, R Muehllehner, G Pichler, BJ Seidel, J Siegel, S Spinks, T Tai, YC Vaquero, JJ AF Weber, S Bruyndonckx, P Chatziioannou, AF Clark, JC Daube-Witherspoon, ME Di Domenico, G Zavattini, G Honer, M Huber, J Karp, JS Laforest, R Muehllehner, G Pichler, BJ Seidel, J Siegel, S Spinks, T Tai, YC Vaquero, JJ TI Performance measurements of small animal positron emission tomographs. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Forschungszentrum Julich, Cent Elect Lab, Julich, Germany. Free Univ Brussels, IIHE, Brussels, Belgium. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Cambridge, Wolfson Brain Imaging Ctr, Cambridge CB2 1TN, England. Univ Penn, Fairfax Stn, VA USA. Univ Ferrara, Dipartimento Fis, I-44100 Ferrara, Italy. Paul Scherrer Inst, Ctr Radiopharmaceut Sci, Villigen, Switzerland. Univ Hosp, Villigen, Switzerland. Lawrence Berkeley Natl Lab, Berkeley, CA USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA. Med Syst, Philadelphia, PA USA. Tech Univ Munich, Klinikum Rechts Isar, Nukl Med Klin & Poliklin, D-8000 Munich, Germany. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. Concorde Microsyst, Knoxville, TN USA. Imaging Res Solut Ltd, Hammersmith Hosp, London, England. Hosp Gen Univ Gregorio Maranon, Unidad Med & Circugia Expt, Madrid, Spain. RI Vaquero, Juan Jose/D-3033-2009; Beer, Simone/E-1486-2017 OI Vaquero, Juan Jose/0000-0001-9200-361X; Beer, Simone/0000-0003-4290-4051 NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 212 BP 59P EP 59P AR UNSP 200314 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800213 ER PT J AU Daftary, A Gottschalk, C Zoghbi, SS Fujita, M Innis, RB Seibyl, JP AF Daftary, A Gottschalk, C Zoghbi, SS Fujita, M Innis, RB Seibyl, JP TI Age related changes in distribution of I-123-Iomazenil in healthy human subjects. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. NIMH, Bethesda, MD 20892 USA. Inst Neurodegenerat Disorders, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 237 BP 65P EP 66P AR UNSP 201262 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800238 ER PT J AU Liow, J Zaini, M Rehm, K Strother, S Anderson, J Schaper, K Rottenberg, D AF Liow, J Zaini, M Rehm, K Strother, S Anderson, J Schaper, K Rottenberg, D TI Evaluation of an MRI-based partial volume correction for PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN USA. Donnish LLC, Savage, MN USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 358 BP 100P EP 100P AR UNSP 201471 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800359 ER PT J AU Freedman, N Sundaram, SK Carson, JM Libutti, SK Whatley, M Sellers, D Carrasquillo, JA Bacharach, SL AF Freedman, N Sundaram, SK Carson, JM Libutti, SK Whatley, M Sellers, D Carrasquillo, JA Bacharach, SL TI Patlak tumor images revisited. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Sundaram, Senthil/B-3905-2013 OI Sundaram, Senthil/0000-0002-0382-0536 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 365 BP 102P EP 102P AR UNSP 202444 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800366 ER PT J AU Fujita, M van Dyck, CH Ichise, M Zoghbi, SS Tamagnan, G Bozkurt, A Seneca, N Mukhin, AG Vaupel, DB Horti, AG Koren, AO Kimes, AS London, ED Seibyl, JP Baldwin, RM Innis, RB AF Fujita, M van Dyck, CH Ichise, M Zoghbi, SS Tamagnan, G Bozkurt, A Seneca, N Mukhin, AG Vaupel, DB Horti, AG Koren, AO Kimes, AS London, ED Seibyl, JP Baldwin, RM Innis, RB TI Quantification of brain nicotinic acetylcholine receptors in humans using I-123-5-I-A-85380. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. Yale Univ, Sch Med, New Haven, MD USA. Natl Inst Drug Abuse, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Inst Neurodegenerat Disorders, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 395 BP 110P EP 110P AR UNSP 201336 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800396 ER PT J AU Jagoda, EM Kiesewetter, DO Shimoji, K Ravasi, L Duttaroy, A Gomeza, J Wess, J Eckelman, WC AF Jagoda, EM Kiesewetter, DO Shimoji, K Ravasi, L Duttaroy, A Gomeza, J Wess, J Eckelman, WC TI Regional brain uptake of F-18-FP-TZTP is not decreased in mice lacking functional M1 receptors (M1KO) vs wildtypes (WT). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 399 BP 111P EP 111P AR UNSP 200586 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800400 ER PT J AU Heeger, SW Moldenhauer, G Egerer, G Wesch, H Eisenmenger, A Nikula, T Apostolidis, C Janssens, W Brechbiel, M Haberkorn, U Ho, AD Haas, R AF Heeger, SW Moldenhauer, G Egerer, G Wesch, H Eisenmenger, A Nikula, T Apostolidis, C Janssens, W Brechbiel, M Haberkorn, U Ho, AD Haas, R TI Treatment of B-lineage non-Hodgkin's lymphoma using a Bi-213-labeled anti-CD20-CHX-A-DTPA antibody conjugate. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Heidelberg Hosp, Heidelberg, Germany. Commiss European Communities, Joint Res Ctr, Inst Transuranium Elements, D-7500 Karlsruhe, Germany. NCI, Bethesda, MD 20892 USA. Univ Hosp Dusseldorf, Dusseldorf, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 418 BP 116P EP 116P AR UNSP 202429 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800419 ER PT J AU Kobayashi, H Shirakawa, K Kawamoto, S Saga, T Togashi, K Konishi, J Brechbiel, MW Waldmann, TA Wakasugi, H AF Kobayashi, H Shirakawa, K Kawamoto, S Saga, T Togashi, K Konishi, J Brechbiel, MW Waldmann, TA Wakasugi, H TI Rapid accumulation of radiolabeled herceptin in an inflammatory breast cancer xenograft with an new type of vasculogenesis "vasculogenic mimicry", which is advantageous for radioimmunotherapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Japan Natl Canc Ctr, Tokyo, Japan. Johns Hopkins Univ, Baltimore, MD 21218 USA. Kyoto Univ Hosp, Kyoto 606, Japan. Kyoto Univ, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 554 BP 152P EP 153P AR UNSP 200730 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800555 ER PT J AU Mattes, MJ Michel, RB Brechbiel, MW AF Mattes, MJ Michel, RB Brechbiel, MW TI Cytotoxicity of B-lymphoma cells with conjugates of antibodies to radionuclides emitting electrons of various energies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Ctr Mol Med & Immunol, Belleville, NJ USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 560 BP 154P EP 154P AR UNSP 201311 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800561 ER PT J AU Sundaram, SK Freedman, N Carrasquillo, JA Carson, JA Libutti, SK Whatley, M Sellers, D Bacharach, SL AF Sundaram, SK Freedman, N Carrasquillo, JA Carson, JA Libutti, SK Whatley, M Sellers, D Bacharach, SL TI Can simplified kinetic Patlak analysis be used to monitor tumor therapy? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. RI Carrasquillo, Jorge/E-7120-2010; Sundaram, Senthil/B-3905-2013 OI Sundaram, Senthil/0000-0002-0382-0536 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 565 BP 155P EP 155P AR UNSP 202155 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800566 ER PT J AU Garg, PK Hou, YK Al-Tikriti, M Garg, S Korde, A Fu, X Kula, NS Seibyl, JP Innis, RB Baldessarini, R Baldwin, RM Tamagnan, G AF Garg, PK Hou, YK Al-Tikriti, M Garg, S Korde, A Fu, X Kula, NS Seibyl, JP Innis, RB Baldessarini, R Baldwin, RM Tamagnan, G TI C-11 labeled 2B-carbomethoxy-3B-(3 ' methoxypyridyl) phenyltropane: Synthesis and bio-logical evaluation. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Yale Univ, Sch Med, West Haven, CT 06516 USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. Inst Neurodegenerat Disorders, New Haven, CT USA. NIMH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 598 BP 164P EP 164P AR UNSP 202464 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800599 ER PT J AU Pavlova, OA Koren, AO Chefer, SI Horti, AG Kimes, AS Mukhin, AG AF Pavlova, OA Koren, AO Chefer, SI Horti, AG Kimes, AS Mukhin, AG TI Inhibition of cytochrome P-450 improves pharmacokinetics of 5-I-123-iodo-A-85380 and 2-F-18-fluoro-A-85380, radioligands for in vivo imaging of brain nicotinic receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 607 BP 167P EP 167P AR UNSP 202604 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800608 ER PT J AU Ichise, M Carson, RE Toyama, H Innis, RB AF Ichise, M Carson, RE Toyama, H Innis, RB TI Linear methods to reduce the bias in estimating reversible neuroreceptor parameters. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 843 BP 205P EP 205P AR UNSP 201187 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800753 ER PT J AU Kim, KM Watabe, H Varrone, A Fujita, M Innis, RB Iida, H AF Kim, KM Watabe, H Varrone, A Fujita, M Innis, RB Iida, H TI Comparison of FBP and OSEM in quantitative dopamine SPECT with scatter correction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 565, Japan. Natl Res, Ctr Nucl Med, Naples, Italy. Yale Univ, Sch Med, New Haven, CT 06520 USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 883 BP 215P EP 216P AR UNSP 201360 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800792 ER PT J AU Wu, Y Lang, L Ma, Y Der, MG Herscovitch, P Eckelman, WC Carson, RE AF Wu, Y Lang, L Ma, Y Der, MG Herscovitch, P Eckelman, WC Carson, RE TI Uptake of radiolabeled acid metabolites into monkey brain. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 960 BP 236P EP 236P AR UNSP 200165 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800870 ER PT J AU Giovacchini, G Mason, A Toczek, M Der, MG Channing, MA Ma, Y Vuong, BK Fraser, C Hallett, M Chang, MC Herscovitch, P Eckelman, WC Rapoport, SI Carson, RE AF Giovacchini, G Mason, A Toczek, M Der, MG Channing, MA Ma, Y Vuong, BK Fraser, C Hallett, M Chang, MC Herscovitch, P Eckelman, WC Rapoport, SI Carson, RE TI Effect of partial volume correction on measurements of brain incorporation of [1-C-11]arachidonic acid. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 969 BP 238P EP 238P AR UNSP 201967 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800879 ER PT J AU Fujita, M Al-Tikriti, MS Tamagnan, G Zoghbi, SS Baldwin, RM Innis, RB AF Fujita, M Al-Tikriti, MS Tamagnan, G Zoghbi, SS Baldwin, RM Innis, RB TI Influence of acetylcholine levels on the binding of a SPECT nicotinic acetylcholine receptor tracer I-123-5-I-A-85380. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, West Haven, CT 06516 USA. Yale Univ, Sch Med, W Haven, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 978 BP 240P EP 241P AR UNSP 200524 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800888 ER PT J AU Ravasi, L Shimoji, K Jagoda, EM Kiesewetter, KO Eckelman, WC AF Ravasi, L Shimoji, K Jagoda, EM Kiesewetter, KO Eckelman, WC TI Is internalization the answer to M2 selectivity to FP-TZTP? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 977 BP 240P EP 240P AR UNSP 200522 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800887 ER PT J AU Lee, KS Zhang, L Jones, DW Gorey, JG Weinberger, DR AF Lee, KS Zhang, L Jones, DW Gorey, JG Weinberger, DR TI Estrogen upregulates muscarinic receptor binding activity in the hippocampus and thalamus of rat. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 979 BP 241P EP 241P AR UNSP 202570 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800889 ER PT J AU Mamede, M Saga, T Ishimori, T Higashi, T Kobayashi, H Konishi, J Brechbiel, MW AF Mamede, M Saga, T Ishimori, T Higashi, T Kobayashi, H Konishi, J Brechbiel, MW TI Radiolabeling of Avidin with very high specific activity for internal radiation therapy of intraperitoneally disseminated tumors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Kyoto Univ, Kyoto, Japan. Kyoto Univ Hosp, Kyoto 606, Japan. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1090 BP 270P EP 270P AR UNSP 201090 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801000 ER PT J AU Jagoda, EM Kiesewetter, DO Shimoji, K Ravasi, L Eckelman, WC AF Jagoda, EM Kiesewetter, DO Shimoji, K Ravasi, L Eckelman, WC TI Comparison of the biodistributions of fluorinated and tritiated paclitaxel (PAC) in mdr1a(-)/1b(-) knockout vs wildtype mice. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1118 BP 277P EP 277P AR UNSP 200366 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801028 ER PT J AU Kimes, AS Horti, AG Contoreggi, C Chefer, SI Kurian, V Friello, P Vaupel, DB Koren, AO Ernst, M Matochik, JA Pavlova, OA London, ED Mukhin, AG AF Kimes, AS Horti, AG Contoreggi, C Chefer, SI Kurian, V Friello, P Vaupel, DB Koren, AO Ernst, M Matochik, JA Pavlova, OA London, ED Mukhin, AG TI Imaging human alpha 4 beta 2 nicotinic receptors with PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1433 BP 356P EP 357P AR UNSP 201021 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801344 ER PT J AU Katoch-Rouse, R Chefer, SI Pavlova, OA Vaupel, DB Matochik, JA Kimes, AS Mukhin, AG Horti, AG AF Katoch-Rouse, R Chefer, SI Pavlova, OA Vaupel, DB Matochik, JA Kimes, AS Mukhin, AG Horti, AG TI Synthesis and evaluation of C-11-NIDA-41020, a radiotracer for studying cerebral cannabinoid (CB1) receptors by PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA, IRP, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1443 BP 359P EP 359P AR UNSP 200262 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801354 ER PT J AU Pike, V Tarkiainen, J Marchais, S McCarron, J Halldin, C Sovago, J Gulyas, B Truong, P Wikstrom, H Farde, L AF Pike, V Tarkiainen, J Marchais, S McCarron, J Halldin, C Sovago, J Gulyas, B Truong, P Wikstrom, H Farde, L TI Evaluation of two C-methyl derivatives of C-11-WAY-100635 as potential radioligands for 5-HT1A receptors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Karolinska Inst, Stockholm, Sweden. Univ Groningen, Groningen, Netherlands. IRSL, London, England. RI Sovago, Judit/G-7961-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1445 BP 359P EP 360P AR UNSP 200687 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801356 ER PT J AU Lang, L Eckelman, WC AF Lang, L Eckelman, WC TI One step radiosynthesis of F-18 FCWAY. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1449 BP 360P EP 360P AR UNSP 202202 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801360 ER PT J AU Szajek, LP Kao, CK Kiesewetter, DO Sassaman, MB Eckelman, WC AF Szajek, LP Kao, CK Kiesewetter, DO Sassaman, MB Eckelman, WC TI Preparation of high specific activity Br-76 compounds. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1501 BP 373P EP 374P AR UNSP 201919 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801412 ER PT J AU Han, ES Sato, N Wong, KJ Park, LS Yu, S Vanderheyden, JL Carrasquillo, JA Paik, CH AF Han, ES Sato, N Wong, KJ Park, LS Yu, S Vanderheyden, JL Carrasquillo, JA Paik, CH TI Labeling Annexin V with Tc-99m-tricarbonyl PADA improved its organ clearance property. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1504 BP 374P EP 374P AR UNSP 202214 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801415 ER PT J AU Park, LS Szajek, LP Wong, KJ Plascjak, PS Garmestani, K Googins, S Eckelman, WC Carrasquillo, JA Paik, CH AF Park, LS Szajek, LP Wong, KJ Plascjak, PS Garmestani, K Googins, S Eckelman, WC Carrasquillo, JA Paik, CH TI Optimization of a semi-automated Y-86 purification method for clinical use. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1525 BP 379P EP 380P AR UNSP 201218 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801436 ER PT J AU Zheng, TZ Blair, A Zhang, YW Weisenburger, DD Zahm, SH AF Zheng, TZ Blair, A Zhang, YW Weisenburger, DD Zahm, SH TI Occupation and risk of non-Hodgkin's lymphoma and chronic lymphocytic leukemia SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ANIMAL BREEDING WORKERS; POPULATION CASE-CONTROL; UNITED-STATES; HISTOLOGICAL TYPE; MAGNETIC-FIELDS; MORTALITY; CANCER; EXPOSURE; FARMERS; COHORT AB To investigate the association between occupation and the risk of non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), and to test whether the associations may vary by histological type of NHL, we analyzed data from two population-based, case-control studies of NHL performed in Kansas and Nebraska. A total of 555 incident NHL cases, 56 CLL cases, and 2380 population-based controls were included in the analysis. Information on occupation and other confounding factors was collected through telephone interviews. Study pathologists reviewed slides of tumor tissues in all cases. In men, we found an increased risk of NHL and CLL for those working in agricultural, forestry, and logging industries (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2 to 2.1). The OR was 1.9 (95% CI, 1.4 to 2.6) for those producing crops. An increased risk was also observed for industries involving metalworking machinery and equipment (OR, 8.4; 95% CI, 1.4 to 50.6), motor vehicles and motor vehicle equipment (OR, 4.2; 95% CI, 1.3 to 13.9), and telephone communications (OR, 3.1; 95% CI, 1.2 to 8.0), and for teachers (OR, 2.5; 95% CI, 1.0 to 6.5), farmers (OR, 2.0; 95% CI, 1.5 to 2.8), and welders and solderers (OR, 2.9; 95% CI, 1.2 to 6.9). The risks for these associations increased by duration of employment and seem to vary by histological type. Work in the printing and publishing industry was also associated with an increased risk of NHL among women. These data suggest that the workers employed in these industries or occupations experienced an increased risk of NHL and CLL, and the risks associated with these industries or occupations may vary by histological type of NHL. C1 Yale Univ, Sch Publ Hlth, Div Environm Hlth Sci, New Haven, CT 06520 USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Lincoln, NE 68583 USA. RP Zheng, TZ (reprint author), 129 Church St,Suite 700, New Haven, CT 06510 USA. RI Zahm, Shelia/B-5025-2015 NR 37 TC 41 Z9 42 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2002 VL 44 IS 5 BP 469 EP 474 DI 10.1097/00043764-200205000-00015 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 551PT UT WOS:000175570600015 PM 12024692 ER PT J AU Mittendorf, R Dambrosia, J Dammann, O Pryde, PG Lee, KS Ben-Ami, TE Yousefzadeh, D AF Mittendorf, R Dambrosia, J Dammann, O Pryde, PG Lee, KS Ben-Ami, TE Yousefzadeh, D TI Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage SO JOURNAL OF PEDIATRICS LA English DT Article ID CRANIAL ULTRASOUND ABNORMALITIES; TRANSIENT HYPOXIA-ISCHEMIA; TOTAL PEDIATRIC MORTALITY; BIRTH-WEIGHT CHILDREN; CEREBRAL-PALSY; BRAIN INJURY; SULFATE EXPOSURE; PRETERM INFANTS; NEWBORN PIGLET; CORD BLOOD AB Objectives: To determine whether magnesium sulfate (MgSO4) exposure is associated with a reduced risk for neonatal intraventricular hemorrhage (IVH). Study design: In a randomized, controlled trial, women in preterm labor were randomly assigned to receive MgSO4 "other" tocolytic, or saline control. At delivery, we collected maternal antecubital and umbilical cord blood for determination of serum ionized magnesium levels. Neonatal lVH was diagnosed by cranial ultrasonogram. Results: Among 144 infants, 24 were diagnosed with IVH. Using crude intention-to-treat analysis, we found that 18% (13174) of survivors exposed after birth to MgSO4 had IVH compared with 16% (11/70) of babies who were not exposed. Infants who had IVH were more likely to have been delivered by mothers with higher serum ionized magnesium (Mg) levels (0.75 vs 0.56 mmol/L) (P =.01). Using multivarlable logistic regression, we confirmed that higher Mg levels are a significant predictor of neonatal IVH (adjusted odds ratio, 15.8; 95% CI, 1.4-175.0) even when adjusted for birth weight, gestational age, antenatal hemorrhage, and neonatal glucocorticoid exposure. Conclusions: In mothers with preterm labor, our data indicate that antenatal MgSO4 exposure may be associated with an increased risk for IVH among their newborns. C1 Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. NINCDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol,Neuroepidemiol Unit, Boston, MA 02115 USA. Univ Wisconsin, Dept Obstet & Gynecol, Div Maternal Fetal Med, Madison, WI 53706 USA. Univ Chicago, Dept Radiol, Sect Pediat Radiol, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Sect Neonatal, Chicago, IL 60637 USA. RP Mittendorf, R (reprint author), Loyola Univ, Med Ctr, Dept Obstet & Gynecol, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 40 TC 37 Z9 37 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2002 VL 140 IS 5 BP 540 EP 546 DI 10.1067/mpd.2002.123283 PG 7 WC Pediatrics SC Pediatrics GA 561MF UT WOS:000176144000012 PM 12032519 ER PT J AU Franklin, SL Eisenhofer, G Geffner, ME AF Franklin, SL Eisenhofer, G Geffner, ME TI Simultaneous development of pheochromocytomas in prepubertal siblings with von Hippel-Lindau syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-2; DISEASE; PLASMA AB We report 2 siblings with a known von Hippel-Lindau mutation who simultaneously, developed asymptomatic pheochromocytomas at significantly younger ages than are typically seen in this setting. C1 Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Endocrinol, Los Angeles, CA 90095 USA. NINCDS, NIH, Bethesda, MD 20892 USA. RP Franklin, SL (reprint author), Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Pediat, Div Endocrinol, 10833 Le Conte Ave,MDCC 22-315, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK07688-08] NR 13 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2002 VL 140 IS 5 BP 625 EP 628 DI 10.1067/mpd.2002.123279 PG 4 WC Pediatrics SC Pediatrics GA 561MF UT WOS:000176144000027 PM 12032534 ER PT J AU Terlouw, SA Graeff, C Smeets, PHE Fricker, G Russel, FGM Masereeuw, R Miller, DS AF Terlouw, SA Graeff, C Smeets, PHE Fricker, G Russel, FGM Masereeuw, R Miller, DS TI Short- and long-term influences of heavy metals on anionic drug efflux from renal proximal tubule SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID P-GLYCOPROTEIN; ORGANIC-ANIONS; DEPENDENT TRANSPORT; CADMIUM UPTAKE; KIDNEY-CELLS; NITRIC-OXIDE; INSECT CELLS; ENDOTHELIN; SECRETION; EXPRESSION AB We recently demonstrated in isolated killifish renal proximal tubules that two classes of nephrotoxicants, aminoglycoside antibiotics and radiocontrast agents, rapidly decrease transport mediated by multidrug resistance protein 2 (Mrp2) by causing endothelin (ET) release and signaling through an ETB receptor and protein kinase C (PKC) (Masereeuw et al., 2000; Terlouw et al., 2001). In the present study, we used killifish proximal tubules, fluorescein methotrexate, a fluorescent model substrate for Mrp2, and confocal microscopy to examine the effects of two heavy metal salts (CdCl2 and HgCl2) on Mrp2 function. Three patterns of effects were seen. First, exposing tubules to 10 muM CdCl2 or 100 nM HgCl2 for 30 min reduced Mrp2-mediated transport. This reduction was abolished by the ETB receptor antagonist, RES-701-1, and by the PKC-selective inhibitor, bis-indolylmaleimide I; neither of these pharmacological tools by itself affected transport. As with aminoglycoside antibiotics and radiocontrast agents, the acute effects of 10 muM CdCl2 or 100 nM HgCl2 on transport were also blocked by nifedipine, suggesting that Ca2+ also initiated cadmium and mercury action. Second, exposure to higher concentrations of CdCl2 and HgCl2 appeared to be toxic. Third, exposing tubules for 6 to 24 h to lower levels of CdCl2 increased Mrp2-mediated transport and Mrp2 immunostaining at the luminal membrane of the proximal tubule cells. Together, these findings indicate that exposure of renal proximal tubules to heavy metals initially leads to reduced Mrp2 function but is followed by an induction in Mrp2-mediated transport after long-term exposure. C1 Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol 233, NL-6500 HB Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Inst Pharmazeut Technol & Biopharm, Heidelberg, Germany. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. RP Masereeuw, R (reprint author), Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol 233, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014; OI Russel, Frans/0000-0002-7959-2314; Masereeuw, Rosalinde/0000-0002-1560-1074 NR 43 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2002 VL 301 IS 2 BP 578 EP 585 DI 10.1124/jpet.301.2.578 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543ZB UT WOS:000175132800023 PM 11961059 ER PT J AU Gupman, AE Svikis, D McCaul, ME Anderson, J Santora, PB AF Gupman, AE Svikis, D McCaul, ME Anderson, J Santora, PB TI Detection of alcohol and drug problems in an urban gynecology clinic SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE alcohol abuse; drug abuse; urban population ID RISK-DRINKING; WOMEN; CAGE; NEEDS AB OBJECTIVE: To compare screening instuments for their utility to detect substance use problems in women seeking gynecologic care, to assess the likelihood that alcohol/drug problems mill be detected by physicians during a routine office visit and to examine the relationship between regular alcohol and/or drug use and the patient's presenting gynecologic complaints. STUDY DESIGN: Women (N = 360) attending a hospital-based gynecology clinic were screened prior to physician visit using the Michigan Alcoholism Screening Test, CAGE and T-ACE. After the visit, information on presenting complaint and physician's documentation of the patient's tobacco, alcohol and other drug use was abstracted from the medical record. RESULTS: The rates of alcohol and illicit drug use varied across assessment instruments; physician documentation, however, yielded the lowest prevalence estimates, Regular alcohol and drug users were more likely to present with chronic and acute medical problems than patients who were not regular users of these substances CONCLUSION: The gynecology clinic offers an opportunity for early identification of women with substance problems, Mid alternative strategies are needed to encourage gynecologists to routinely screen for such problems at each medical visit. C1 Johns Hopkins Univ, Sch Med, NIDA, IRP,Treatment Sect, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21224 USA. Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. RP Gupman, AE (reprint author), Johns Hopkins Univ, Sch Med, NIDA, IRP,Treatment Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 19 TC 6 Z9 7 U1 1 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 2002 VL 47 IS 5 BP 404 EP 410 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 555RE UT WOS:000175806400012 PM 12063880 ER PT J AU Carroll, NM Alexander, HR AF Carroll, NM Alexander, HR TI Hyperthermic isolated hepatic perfusion for the treatment of unresectable cancers confined to the liver SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Letter ID TUMOR-NECROSIS-FACTOR; MELPHALAN C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Carroll, NM (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B01,10 Ctr Dr, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAY PY 2002 VL 80 IS 1 BP 64 EP 65 DI 10.1002/jso.10097 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 548XH UT WOS:000175414800014 PM 11967911 ER PT J AU Iwasa, KH Ehrenstein, G AF Iwasa, KH Ehrenstein, G TI Cooperative interaction as the physical basis of the negative stiffness in hair cell stereocilia SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MECHANOELECTRICAL TRANSDUCTION; ADAPTATION; CHANNELS; MODELS; AMPLIFICATION AB A recent report confirmed that stiffness of the stereocilia can be negative, as predicted by the Howard-Hudspeth model. According to this model, the mechanotransducer channel's gating not only reduces the stereociliary stiffness, but can alter its sign as well. The basic assumptions of this model do not include cooperativity in channel gating. Here we consider two possible explanations for the observed negative stiffness. If the stereocilia have a special structure so that microscopic displacement can be imposed on each channel by controlling the bending of the bundle, negative stiffness can occur without channel cooperativity. If such a microscopic condition cannot be imposed by a macroscopic manipulation, an additional physical process, such as cooperativity in channel gating, is required to explain negative stiffness. C1 Natl Inst Deafness & Other Commun Disorders, Sect Biophys, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Biophys, NIH, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 18 TC 15 Z9 16 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2002 VL 111 IS 5 BP 2208 EP 2212 DI 10.1121/1.1466864 PN 1 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 552RC UT WOS:000175632500026 PM 12051440 ER PT J AU Egan, CA Yee, C Zillikens, D Yancey, KB AF Egan, CA Yee, C Zillikens, D Yancey, KB TI Anti-p200 pemphigoid: Diagnosis and treatment of a case presenting as an inflammatory subepidermal blistering disease SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; LAMINA-LUCIDA; VII COLLAGEN; SKIN; AUTOANTIBODIES; ANTIGEN; IDENTIFICATION; IMMUNOFLUORESCENCE; AUTOIMMUNE; EPILIGRIN AB Anti-p200 pemphigoid is a recently defined subepidermal immunobullous disease. It is characterized by the binding of circulating IgG autoantibodies to the dermal side of I M NaCl split skin and by reactivity of these autoantibodies to a unique 200-kd antigen on immunoblot of dermal extract. On immunoelectron microscopic examination, these autoantibodies deposit at the lamina lucida-lamina densa interface. We describe the clinical, histologic, and immunopathologic features in a patient with anti-p200 pemphigoid, as well as his favorable response to treatment with systemic glucocorticosteroids and dapsone. C1 NCI, Div Clin Sci, Dermatol Branch, NIH, Bethesda, MD USA. Univ Wurzburg, Dept Dermatol, D-97070 Wurzburg, Germany. RP Egan, CA (reprint author), Beaumont Hosp, Dept Dermatol, Dublin 9, Ireland. RI Zillikens, Detlef/C-8572-2011 NR 18 TC 18 Z9 20 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2002 VL 46 IS 5 BP 786 EP 789 DI 10.1067/mjd.2002.120923 PG 4 WC Dermatology SC Dermatology GA 557NN UT WOS:000175914800024 PM 12004326 ER PT J AU Visser, M Kritchevsky, SB Goodpaster, BH Newman, AB Nevitt, M Stamm, E Harris, TB AF Visser, M Kritchevsky, SB Goodpaster, BH Newman, AB Nevitt, M Stamm, E Harris, TB TI Leg muscle mass and composition in relation to lower extremity performance in men and women aged 70 to 79: The health, aging and body composition study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; body composition; computed tomography; fat infiltration; functional status; human; obesity; race; sarcopenia; skeletal muscle ID SKELETAL-MUSCLE; COMPUTED-TOMOGRAPHY; PHYSICAL-DISABILITY; LIPID-CONTENT; ELDERLY MEN; FAT; STRENGTH; SARCOPENIA; ATTENUATION; ASSOCIATION AB OBJECTIVES: The loss of muscle mass with aging, or sarcopenia, is hypothesized to be associated with the deterioration of physical function. Our aim was to determine whether low leg muscle mass and greater fat infiltration in the muscle were associated with poor lower extremity performance (LEP). DESIGN: A cross-sectional study, using baseline data of the Health, Aging and Body Composition study (1997/98). SETTING: Medicare beneficiaries residing in ZIP codes from the metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Three thousand seventy-five well-functioning black and white men and women aged 70 to 79. MEASUREMENTS: Two timed tests (6-meter walk and repeated chair stands) were used to measure LEP. Muscle cross-sectional area and muscle tissue attenuation (indicative of fat infiltration) were obtained from computed tomography scans at the midthigh. Body fat was assessed using dual-energy x-ray absorptiometry. RESULTS: Blacks had greater muscle mass and poorer LEP than whites. Black women had greater fat infiltration into the muscle than white women. After adjustment for clinic site, age, height, and total body fat, smaller muscle area was associated with poorer LEP in all four race-gender groups. Regression coefficients, expressed per standard deviation (+/-55 cm(2)) of muscle area, were 0.658 and 0.519 in white and black men and 0.547 and 0.435 in white and black women, respectively, P < .01.) in addition, reduced muscle attenuation-indicative of greater fat infiltration into the muscle-was associated with poorer LEP, independent of total body fat and muscle area. (Regression coefficients per standard deviation (= 7 Hounsfield Units) of muscle attenuation were 0.292 and 0.224 in white and black men, and 0.193 and 0.159 in white and black women, respectively, (P < .05). The most important body composition components related to LEP were muscle area in men and total body fat in women. Results were similar after additional adjustment for lifestyle factors and health status. No interactions between race and muscle area (P > .7) or between race and muscle attenuation (P > .2) were observed. CONCLUSION: Smaller midthigh muscle area and greater fat infiltration in the muscle arc associated with poorer LEP in well-functioning older men and women. C1 Vrije Univ Amsterdam, Fac Med, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Sch Med, Denver, CO 80262 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Visser, M (reprint author), Vrije Univ Amsterdam, Fac Med, Inst Res Extramural Med, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 31 TC 347 Z9 357 U1 6 U2 26 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2002 VL 50 IS 5 BP 897 EP 904 DI 10.1046/j.1532-5415.2002.50217.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 549GE UT WOS:000175435500017 PM 12028178 ER PT J AU Verreault, R Semba, RD Volpato, S Ferrucci, L Fried, LP Guralnik, JM AF Verreault, R Semba, RD Volpato, S Ferrucci, L Fried, LP Guralnik, JM TI Low serum vitamin D does not predict new disability or loss of muscle strength in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE vitamin D; 25-hydroxyvitamin D; parathyroid hormone; muscle strength; disability; aging; older women ID D DEFICIENCY; PARATHYROID-HORMONE; NURSING-HOME; ADULTS; FRAIL; 1,25-DIHYDROXYVITAMIN-D3; METABOLITES; EXERCISE; PEOPLE; HEALTH AB OBJECTIVES: To determine whether serum levels of 25-hydroxyvitamin D (25(011)D) and parathyroid hormone (PTH) predict accelerated decline in muscular strength or onset of new disability m mobility and upper extremity functioning over a 3-year follow-up. DESIGN: A community-based prospective cohort study. PARTICIPANTS: Six hundred twenty-eight moderately to severely disabled women aged 65 and older living in the community. MEASUREMENTS: Subjects were divided into three groups of baseline 25(OH)D serum levels (deficiency: <25 nmol/L; low normal: 25-52 nmol/L; high normal: greater than or equal to53 nmol/L) and into tertiles of PTH levels. Objective performance measures (hip flexor, knee extensor, and grip strengths; walking speed; and time for repeated chair stands) and disability in activities involving mobility and upper extremity function were assessed at baseline and every 6 months for 3 years. Decline in performance measures and onset of new disability were compared between 25(011)D and PTH groups using random effects models and proportional hazards models, respectively, while adjusting for age, race, education, body mass index,, baseline performance, and chronic conditions. RESULTS: The annual rate of decline over 3 years in muscular strength, walking speed, and time to perform repeated chair stands was similar across 25(OH)D groups. We observed a nonsignificantly faster decline in proximal muscle strength and walking speed with increasing PTH levels. There was no association for either measure between serum level,, and the risk of incident disability in activities relating to mobility and upper extremity function. CONCLUSION: This Study does not support the hypothesis that vitamin D deficiency is associated with loss in muscular strength and decline in mobility and upper extremity functioning over time in older women who were moderately to severely disabled at baseline. C1 Univ Laval, Fac Med, Dept Social & Prevent Med, Quebec City, PQ G1K 7P4, Canada. Johns Hopkins Sch Med, Baltimore, MD USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. RP Verreault, R (reprint author), Univ Laval, Geriatr Res Unit, Ctr St Augustin, 2135 Terrasse Cadieux, Beauport, PQ G1C 1Z2, Canada. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01-AG-2112] NR 28 TC 66 Z9 68 U1 2 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2002 VL 50 IS 5 BP 912 EP 917 DI 10.1046/j.1532-5415.2002.50219.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 549GE UT WOS:000175435500019 PM 12028180 ER PT J AU Knepper, MA AF Knepper, MA TI Proteomics and the kidney SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NA-CL COTRANSPORTER; PROTEIN-PROTEIN INTERACTIONS; TANDEM MASS-SPECTROMETRY; CODED AFFINITY TAGS; RAT-KIDNEY; TARGETED PROTEOMICS; GEL-ELECTROPHORESIS; MEDIATED REGULATION; ALTERED EXPRESSION; TRANSPORTERS AB Proteomics can be defined as "the systematic analysis of proteins for their identity, quantity, and function." The central concept is "multiplexing," i.e., simultaneous analysis of all proteins in a defined protein population. rather than investigation of one protein at a time, as in traditional biochemistry. Two major approaches have been described: (1) mass spectrometry-based approaches and (2) protein micro-array approaches. The purpose of this Science Watch article is to describe the fundamental features of these two approaches and to speculate on how proteomics will be useful in nephrology and nephrology research in the coming years. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282-KE] NR 54 TC 82 Z9 87 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2002 VL 13 IS 5 AR UNSP 1046-6673/1305-1398 DI 10.1097/01.ASN.0000014782.37591.C7 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 545HG UT WOS:000175210800032 PM 11961030 ER PT J AU Hjalgrim, H Rostgaard, K Askling, J Madsen, M Storm, HH Rabkin, CS Melbye, M AF Hjalgrim, H Rostgaard, K Askling, J Madsen, M Storm, HH Rabkin, CS Melbye, M TI Hematopoietic and lymphatic cancers in relatives of patients with infectious mononucleosis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EPSTEIN-BARR-VIRUS; HODGKINS-DISEASE; RISK-FACTORS; EBV AB Background. Young adults with a history of Epstein-Barr virus (EBV)-related infectious mononucleosis have an increased risk for Hodgkin's lymphoma. EBV is detected in Hodgkin's lymphoma Reed-Sternberg cells from some patients, but in young adult patients, it is detected at a relatively low frequency in these cells. Hodgkin's lymphoma and infectious mononucleosis are both associated with high social class, and unknown confounding factors that are also associated with socioeconomic status might explain or contribute to the apparent association between these diseases. To indirectly assess the importance of socioeconomic status on the association between these diseases, we determined the risk for hematopoietic and lymphatic cancers in first-degree relatives of patients with confirmed EBV-related infectious mononucleosis. Methods: We identified parents, siblings, and offspring of 17 045 persons with serologically confirmed EBV-related infectious mononucleosis. Subjects in these cohorts were linked with the population-based Danish Cancer Register to identify those developing hematopoietic/lymphatic cancers after the index patient was diagnosed with infectious mononucleosis. The relative risk for cancer in the infectious mononucleosis family members was expressed as standardized incidence ratios (SIRs; i.e., the ratio between the number of cancers observed and the number of cancers expected, obtained from age-specific, sex-specific, and period-specific incidence rates). Results: We identified 8052 parents, 5264 siblings, and 28 605 offspring of patients with EBV-related infectious mononucleosis who were followed for a total of 892 213 person-years at risk. The risk for Hodgkin's lymphoma was unaltered in the combined group of first-degree relatives of these patients (SIR = 0.99; 95% confidence interval [95% CI] = 0.62 to 1.59; number of cases [n] = 17), in the group of parents (SIR = 0.83; 95% CI = 0.31 to 2.22; n = 4), in the group of siblings (SIR = 0.96; 95% CI = 0.31 to 2.97; n = 3), and in the group of offspring (SIR = 1.08; 95% CI = 0.58 to 2.02; n = 10). Conclusion: The unremarkable risk for Hodgkin's lymphoma in family members of patients with EBV-related infectious mononucleosis indicates that socioeconomic confounding is an unlikely explanation for the association between EBV-related infectious mononucleosis and Hodgkin's lymphoma. C1 Statens Serum Inst, Dept Epidemiol Res, Danish Epidemiol Sci Ctr, DK-2300 Copenhagen S, Denmark. Karolinska Hosp & Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden. Natl Inst Publ Hlth, Copenhagen, Denmark. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Hjalgrim, H (reprint author), Statens Serum Inst, Dept Epidemiol Res, Danish Epidemiol Sci Ctr, Artillerivej 5, DK-2300 Copenhagen S, Denmark. RI Madsen, Mette/B-4341-2008; OI Rostgaard, Klaus/0000-0001-6220-9414 NR 21 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 1 PY 2002 VL 94 IS 9 BP 678 EP 681 PG 4 WC Oncology SC Oncology GA 547QN UT WOS:000175343400009 PM 11983756 ER PT J AU Nnadi, CU Better, W Tate, K Herning, RI Cadet, JL AF Nnadi, CU Better, W Tate, K Herning, RI Cadet, JL TI Contribution of substance abuse and HIV infection to psychiatric distress in an inner-city African-American population SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE psychiatric distress; Symptom Checklist 90; drug abuse; dual diagnosis; HIV ID ADDICTION SEVERITY INDEX; DSM-III-R; PSYCHOLOGICAL DISTRESS; EMOTIONAL DISTRESS; COCAINE ABUSERS; DRUG-USE; ALCOHOL; WOMEN; PSYCHOPATHOLOGY; SYMPTOMATOLOGY AB We used Symptom Checklist 90-Revised (SCL90-R) to investigate psychiatric symptom severity in African-American drug-abusing individuals. Three hundred and seventeen African-American volunteers (52 control subjects; 265 drug users) were recruited, 19.2% of whom were HIV-positive, The impact of drug of choice or HIV status on mental distress was assessed. Symptomatic HIV-positive participants were excluded. The intake SCL90-R, Addiction Severity index, and demographic data were subjected to regression analyses. Drug-abusing African Americans reported increased global distress, a finding that remained robust after we adjusted for HIV status, gender, age, and education. Drug of choice had no influence on the severity of global mental distress in our sample. Asymptomatic HIV-positive African Americans who abused drugs reported more distress than the HIV-negative drug users. Levels of global distress were similar in the HIV-negative and the HIV-positive controls. Subscales of the SCL90-R showed more symptom severity among drug-using, compared with nonusing, African Americans, Except for paranoia, anxiety, and obsessive-compulsive subscales, other symptom dimensions were significantly elevated in HIV-positive, compared with HIV-negative, drug abusers. When taken together, these findings suggest that drug abuse can exacerbate the severity of mental distress in HIV-positive patients. Treatment of these patients may be more successful if both sets of needs are addressed with matched interventions. C1 NIDA, Mol Neuropsychiat Sect, NIH, IRP, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 6 Z9 6 U1 1 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAY PY 2002 VL 94 IS 5 BP 336 EP 343 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 560GB UT WOS:000176073400020 PM 12069213 ER PT J AU Finkelstein, SE Summers, RM Nguyen, DM Stewart, JH Tretler, JA Schrump, DS AF Finkelstein, SE Summers, RM Nguyen, DM Stewart, JH Tretler, JA Schrump, DS TI Virtual bronchoscopy for evaluation of malignant tumors of the thorax SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID FIBEROPTIC BRONCHOSCOPY; CT; TOMOGRAPHY; CARCINOMA AB Objective: Virtual bronchoscopy is a novel technique making use of 3-dimensional reconstruction of 2-dimensional helical computed tomographic images for noninvasive evaluation of the tracheobronchial tree. This study was undertaken to evaluate the diagnostic potential of virtual bronchoscopy by comparing virtual bronchoscopic images with fiberaptic bronchoscopic findings in patients with thoracic malignant disease. Methods: Thirty-two consecutive patients with thoracic malignant tumors underwent virtual bronchoscopy for evaluation of suspected tracheobronchial lesions. For each virtual bronchoscopic examination, 200 to 300 contiguous 1.25-mm images of the thorax were obtained in only one or two 17-second breath holds by using a multislice computed tomographic scanner. Virtual bronchoscopy images were reconstructed and interpreted blind to the actual endoscopic findings. Results of virtual bronchoscopy were compared with fiberoptic bronchoscopic findings in 20 patients. Results: Anatomic computer simulation of the bronchial tree was successfully created in all patients. In 7 (35%) of 20 patients, results of fiberoptic bronchoscopy were found to be within normal limits. In all patients with normal anatomy, virtual bronchoscopy accurately correlated with the fiberoptic findings. Thirteen (6511) patients had a total of 22 abnormal findings on fiberoptic bronchoscopy. Virtual bronchoscopy detected 18 of 22 abnormal fiberoptic bronchoscopic findings: 13 of 13 obstructive lesions, 5 of 6 endoluminal lesions, and 0 of 3 mucosal lesions. The sensitivity of virtual bronchoscopy was 100% for obstructive lesions, 83% for endoluminal lesions, 0 71 for mucosal lesions, and 82% for all abnormalities; the specificity of virtual bronchoscopy was 100%. Conclusions: Preliminary evaluation indicates that virtual bronchoscopy may be a promising and noninvasive modality for identifying bronchial obstructions and endoluminal lesions, as well as for assessing the tracheobronchial tree beyond stenoses. However, at present, virtual bronchoscopy does not enable the detection of subtle mucosal lesions, and as such, this modality may not be appropriate for identifying premalignant lesions in the respiratory tract. Although fiberoptic bronchoscopy remains the standard modality for evaluating airway patency and mucosal lesions, virtual bronchoscopy may provide additional information that may be useful in the management of pulmonary malignant tumors. C1 NIH, Ctr Canc Res, Thorac Oncol Sect, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [K08 CA131482] NR 14 TC 40 Z9 42 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2002 VL 123 IS 5 BP 967 EP 972 DI 10.1067/mtc.2002.121495 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 556CY UT WOS:000175832800019 PM 12019383 ER PT J AU Zampino, R Marrone, A Cirillo, G del Giudice, EM Utili, R Karayiannis, P Liang, TJ Ruggiero, G AF Zampino, R Marrone, A Cirillo, G del Giudice, EM Utili, R Karayiannis, P Liang, TJ Ruggiero, G TI Sequential analysis of hepatitis B virus core promoter and precore regions in cancer survivor patients with chronic hepatitis B before, during and after interferon treatment SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE anti-HBe seroconversion; cancer survivors; chronic hepatitis B; core promoter/precore mutations ID E-ANTIGEN; FULMINANT-HEPATITIS; VIRAL REPLICATION; LIVER-DAMAGE; WILD-TYPE; MUTATIONS; CARRIERS; INFECTION; GENE; SEROCONVERSION AB We analysed the hepatitis B virus (HBV) core-promoter (CP) and precore (PC) regions before, during and after interferon treatment in young Caucasian cancer survivors who had acquired HBV infection during chemotherapy for malignancies. Fourteen patients with chronic hepatitis B [hepatitis B e antigen (HBeAg) /HBV-DNA positive] received alpha-2a interferon (IFN), 5 MU/m(2) t.i.w. for 12 months. HBV CP and PC region sequences were analysed following polymerase chain reaction (PCR) amplification. Sera from responders were studied at: T-0 (before starting IFN), T-1 [at alanine aminotransferase (ALT) peak preceding HBeAg seroconversion], T-2 (at ALT normalization), T-3 (at end of IFN) and T-4 (at one year after IFN) and in nonresponders at time points T-0 , T-3 and T-4. Amplified HBV-DNA was cloned and sequenced automatically. Six of 14 patients (43%) responded to IFN treatment. Five of the six (83%) responders displayed the double CP mutation A1762T/G1764A always in association with a T1753C change. None of the nonresponders showed these mutations at any time point. The G1896A change creating the PC stop codon mutation was never detected in any of the patients. In our cancer survivors, IFN-induced HBeAg/anti-HBe seroconversion appeared to correlate with CP mutations and was not influenced by previous chemotherapy. These mutations in addition to low HBV DNA levels and elevated ALT can be considered favourable factors of response to IFN-induced anti-HBe seroconversion. C1 Univ Naples 2, Inst Med Therapy, Naples, Italy. Univ Naples 2, Dept Pediat, Naples, Italy. St Marys Hosp, Imperial Coll, London, England. NIH, Liver Dis Sect, Bethesda, MD 20892 USA. RP Zampino, R (reprint author), Univ Naples 2, Osped Gesu & Maria, Ist Terapia Med, Via Cotugno 1, I-80135 Naples, Italy. OI ZAMPINO, Rosa/0000-0003-2804-186X NR 40 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAY PY 2002 VL 9 IS 3 BP 183 EP 188 DI 10.1046/j.1365-2893.2002.00347.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 550YX UT WOS:000175533600003 PM 12010505 ER PT J AU Farrell, KB Ting, YT Eiden, MV AF Farrell, KB Ting, YT Eiden, MV TI Fusion-defective gibbon ape leukemia virus vectors can be rescued by homologous but not heterologous soluble envelope proteins SO JOURNAL OF VIROLOGY LA English DT Article ID SARCOMA-ASSOCIATED VIRUS; RECEPTOR-BINDING DOMAIN; SUBGROUP-B; PHOSPHATE TRANSPORTERS; MUTATIONAL ANALYSIS; HAMSTER-CELLS; GLYCOPROTEINS; INFECTION; IDENTIFICATION; PEPTIDE AB Murine leukemia virus (MLV)-derived envelope proteins containing alterations in or adjacent to the highly conserved PHQ motif present at the N terminus of the envelope surface subunit (SU) are incorporated into vector particles but are not infectious due to a postbinding block to viral entry. These mutants can be rendered infectious by the addition of soluble receptor-binding domain (RBD) proteins in the culture medium. The RBD proteins that rescue the infectivity of these defective MLV vectors can be derived from the same MLV or from other MLVs that use distinct receptors to mediate entry. We have now constructed functional immunologically reactive gibbon ape leukemia virus (GALV) envelope proteins, tagged with a feline leukemia virus (FeLV)derived epitope tag, which are efficiently incorporated into infectious particles. Tagged GALV envelope proteins bind specifically to cells expressing the phosphate transporter protein Pit1, demonstrating for the first time that Pit1 is the binding receptor for GALV and not a coreceptor or another type of GALV entry factor. We have also determined that GALV particles bearing SU proteins with an insertion C-terminal to the PHQ motif (GALV I-10) bind Pit1 but fail to infect cells. Incubation with soluble GALV RED renders GALV I-10 particles infectious, whereas incubation with soluble RBDs from MLV or FeLV-B does not. This finding is consistent with the results obtained by Lauring et al. using FeLV-T, a virus that employs Pit1 as a receptor but requires soluble FeLV RBD for entry. MLV and GALV RBDs are not able to render FeLV-T infectious (A. S. Lauring, M. M. Anderson, and J. Overbaugh, J. Virol. 75:8888-8898, 2001). Together, these results suggest that fusion-defective FeLV-T and GALV are restricted to homologous RBD rescue of infectivity. C1 NIMH, Unit Mol Virol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIMH, Unit Mol Virol, Lab Cellular & Mol Regulat, 36 Convent Dr,MSC 4068, Bethesda, MD 20892 USA. NR 46 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4267 EP 4274 DI 10.1128/JVI.76.9.4267-4274.2002 PG 8 WC Virology SC Virology GA 541CB UT WOS:000174966700013 PM 11932392 ER PT J AU Tam, W Hughes, SH Hayward, WS Besmer, P AF Tam, W Hughes, SH Hayward, WS Besmer, P TI Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID E-MU-MYC; TRUNCATED EGF RECEPTOR; B-CELL DEVELOPMENT; TRANSGENIC MICE; INDUCED ERYTHROBLASTOSIS; V-ABL; ONCOGENE COOPERATION; PROMOTER INSERTION; ERBB ACTIVATION; MOLECULAR-BASIS AB bic is a novel gene identified at a common retroviral integration site in avian leukosis virus-induced lymphomas and has been implicated as a collaborator with c-myc in B lymphomagenesis. It lacks an extensive open reading frame and is believed to function as an untranslated RNA (W. Tam, Gene 274:157-167, 2001; W. Tam, D. Ben-Yehuda, and W. S. Hayward, Mol. Cell. Biol. 17:1490-1502, 1997). The oncogenic potential of bic, particularly its ability to cooperate with c-myc in oncogenesis, was tested directly by expressing c-myc and bic, either singly or in pairwise combination, in cultured chicken embryo fibroblasts (CEFs) and in chickens using replication-competent retrovirus vectors. Coexpression of c-myc and bic in CEFs caused growth enhancement of cells. Most importantly, chick oncogenicity assays demonstrated that bic can cooperate with c-myc in lymphomagenesis and erythroleukemogenesis. The present study provides direct evidence for the involvement of untranslated RNAs in oncogenesis and provides further support for the role of noncoding RNAs as riboregulators. C1 Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pathol, New York, NY 10021 USA. Cornell Univ, JOan & Sanford I Weill Med Coll, Grad Program Mol Biol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Canc Res, Program Mol Biol, New York, NY 10021 USA. NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Tam, W (reprint author), Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pathol, K-508,25 E 68th St, New York, NY 10021 USA. FU NCI NIH HHS [CA16599, R37 CA32926] NR 60 TC 112 Z9 118 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4275 EP 4286 DI 10.1128/JVI.76.9.4275-4286.2002 PG 12 WC Virology SC Virology GA 541CB UT WOS:000174966700014 PM 11932393 ER PT J AU Johnson, TR Hong, SM Van Kaer, L Koezuka, Y Graham, BS AF Johnson, TR Hong, SM Van Kaer, L Koezuka, Y Graham, BS TI NK T cells contribute to expansion of CD8(+) T cells and amplification of antiviral immune responses to respiratory syncytial virus SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-KILLER-CELLS; RECOMBINANT VACCINIA VIRUS; MARROW TRANSPLANT RECIPIENTS; IFN-GAMMA PRODUCTION; VIRAL-INFECTION; CYTOKINE EXPRESSION; IN-VIVO; INTERFERON-GAMMA; CUTTING EDGE; BALB/C MICE AB CD1d-deficient mice have normal numbers of T lymphocytes and natural killer cells but lack Valpha14(+) natural killer T cells. Respiratory syncytial virus (RSV) immunopathogenesis was evaluated in 129xC57BL/6, C57BL/6, and BALB/c CD1d(-/-) mice. CD8(+) T lymphocytes were reduced in CD1d(-/-) mice of all strains, as shown by cell surface staining and major histocompatibility complex class I tetramer analysis, and resulted in strain-specific alterations in illness, viral clearance, and gamma interferon (IFN-gamma) production. Transient activation of NK T cells in CD1d(+/+) mice by alpha-GalCer resulted in reduced illness and delayed viral clearance. These data suggest that early IFN-gamma production and efficient induction of CD8(+)-T-cell responses during primary RSV infection require CD1d-dependent events. We also tested the ability of alpha-GalCer as an adjuvant to modulate the type 2 immune responses induced by RSV glycoprotein G or formalin-inactivated RSV immunization. However, immunized CD1-deficient or alpha-GalCer-treated wild-type mice did not exhibit diminished disease following RSV challenge. Rather, some disease parameters, including cytokine production, eosinophilia, and viral clearance, were increased. These findings indicate that CD1d-dependent NK T cells play a role in expansion of CD8(+) T cells and amplification of antiviral responses to RSV. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. Kirin Brewery Co Ltd, Pharmaceut Res Lab, Takasaki, Gumma, Japan. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3017,Bldg 40,Rm 2504, Bethesda, MD 20892 USA. RI Van Kaer, Luc/H-1033-2015 OI Van Kaer, Luc/0000-0001-5275-2309 NR 86 TC 119 Z9 122 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4294 EP 4303 DI 10.1128/JVI.76.9.4294-4303.2002 PG 10 WC Virology SC Virology GA 541CB UT WOS:000174966700016 PM 11932395 ER PT J AU Oldstone, MBA Race, R Thomas, D Lewicki, H Homann, D Smelt, S Holz, A Koni, P Lo, D Chesebro, B Flavell, R AF Oldstone, MBA Race, R Thomas, D Lewicki, H Homann, D Smelt, S Holz, A Koni, P Lo, D Chesebro, B Flavell, R TI Lymphotoxin-alpha- and lymphotoxin-beta-deficient mice differ in susceptibility to scrapie: Evidence against dendritic cell involvement in neuroinvasion SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-INDUCED IMMUNOSUPPRESSION; PRION PROTEIN; LYMPHOID-TISSUES; ABNORMAL-DEVELOPMENT; FOLLICLE STRUCTURE; VIRAL PERSISTENCE; INFECTED MICE; EXPRESSION; PATHOGENESIS; SPLEENS AB Transmissible spongiform encephalopathy or prion diseases are fatal neurodegenerative disorders of humans and animals often initiated by oral intake of an infectious agent. Current evidence suggests that infection occurs initially in the lymphoid tissues and subsequently in the central nervous system (CNS). The identity of infected lymphoid cells remains controversial, but recent studies point to the involvement of both follicular dendritic cells (FDC) and CD11c(+) lymphoid dendritic cells. FDC generation and maintenance in germinal centers is dependent on lymphotoxin alpha (LT-alpha) and LT-beta signaling components. We report here that by the oral route, LT-alpha -/- mice developed scrapie while LT-beta -/- mice did not. Furthermore, LT-alpha -/- mice had a higher incidence and shorter incubation period for developing disease following inoculation than did LT-beta -/- mice. Transplantation of lymphoid tissues from LT-beta -/- mice, which have cervical and mesenteric lymph nodes, into LT-alpha -/- mice, which do not, did not alter the incidence of CNS scrapie. In other studies, a virus that is tropic for and alters functions of CD11c(+) cells did not alter the kinetics of neuroinvasion of scrapie. Our results suggest that neither FDC nor CD11c(+) cells are essential for neuroinvasion after high doses of RML scrapie. Further, it is possible that an as yet unidentified cell found more abundantly in LT-alpha -/- than in LT-beta -/- mice may assist in the amplification of scrapie infection in the periphery and favor susceptibility to CNS disease following peripheral routes of infection. C1 Scripps Res Inst, Res Inst, Dept Neuropharmacol, Div Virol, La Jolla, CA 92037 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA. Digital Gene Technol Inc, La Jolla, CA 92037 USA. RP Oldstone, MBA (reprint author), Scripps Res Inst, Res Inst, Dept Neuropharmacol, Div Virol, IMM-6,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Koni, Pandelakis/A-3349-2008 FU NIA NIH HHS [P01 AG004342, AG04342] NR 40 TC 47 Z9 48 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4357 EP 4363 DI 10.1128/JVI.76.9.4357-4363.2002 PG 7 WC Virology SC Virology GA 541CB UT WOS:000174966700023 PM 11932402 ER PT J AU Guo, JH Wu, TY Kane, BF Johnson, DG Henderson, LE Gorelick, RJ Levin, JG AF Guo, JH Wu, TY Kane, BF Johnson, DG Henderson, LE Gorelick, RJ Levin, JG TI Subtle alterations of the native zinc finger structures have dramatic effects on the nucleic acid chaperone activity of human immunodeficiency virus type 1 nucleocapsid protein SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; PLUS-STRAND TRANSFER; STRONG-STOP DNA; HIV-1 REVERSE TRANSCRIPTION; RNA PACKAGING SIGNAL; STEM-LOOP SL2; MINUS-STRAND; IN-VITRO; POSTTRANSLATIONAL MODIFICATIONS; SHORT OLIGONUCLEOTIDES AB The nucleocapsid protein (NC) of human immunodeficiency virus type 1 has two zinc fingers, each containing the invariant CCHC zinc-binding motif, however, the surrounding amino acid context is not identical in the two fingers. Recently, we demonstrated that zinc coordination is required when NC unfolds complex secondary structures in RNA and DNA minus- and plus-strand transfer intermediates; this property of NC reflects its nucleic acid chaperone activity. Here we have analyzed the chaperone activities of mutants having substitutions of alternative zinc-coordinating residues, i.e., CCHH or CCCC, for the wild-type CCHC motif. We also investigated the activities of mutants that retain the CCHC motifs but have mutations that exchange or duplicate the zinc fingers (mutants 1-1, 2-1, and 2-2); these changes affect amino acid context. Our results indicate that in general, for optimal activity in an assay that measures stimulation of minus-strand transfer and inhibition of nonspecific self-priming, the CCHC motif in the zinc fingers cannot be replaced by CCHH or CCCC and the amino acid context of the fingers must be conserved. Context changes also reduce the ability of NC to facilitate primer removal in plus-strand transfer. In addition, we found that the first finger is a more crucial determinant of nucleic acid chaperone activity than the second finger. Interestingly, comparison of the in vitro results with earlier in vivo replication data raises the possibility that NC may adopt multiple conformations that are responsible for different NC functions during virus replication. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Levin, JG (reprint author), NICHHD, Genet Mol Lab, NIH, Bldg 6B,Room 216, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 73 TC 83 Z9 85 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4370 EP 4378 DI 10.1128/JVI.76.9.4370-4378.2002 PG 9 WC Virology SC Virology GA 541CB UT WOS:000174966700025 PM 11932404 ER PT J AU Dehghani, H Brown, CR Plishka, R Buckler-White, A Hirsch, VM AF Dehghani, H Brown, CR Plishka, R Buckler-White, A Hirsch, VM TI The ITAM in Nef influences acute pathogenesis of AIDS-inducing simian immunodeficiency viruses SIVsm and SIVagm without altering kinetics or extent of viremia SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVATION MOTIF; ACUTE PATHOGENICITY; IN-VIVO; SIVSMMPBJ14; MACAQUES; IDENTIFICATION; REPLICATION; VARIANT; DETERMINANTS; LYMPHOCYTES AB The role of the immunoreceptor tyrosine-based activation motif (ITAM) that is unique to the Nef protein of the acutely pathogenic simian immunodeficiency virus SIVsmPBj was studied in the context of two AIDS-inducing simian immunodeficiency virus molecular clones. NefY(+) variants of SIVagm9063-2 and SIVsmE543-3 replicated in and induced proliferation of unstimulated pig-tailed macaque PBMC. The pathogenesis of the NefY(+) and NefY(-) clones of SIVagm9063-2, SIVsmE543-3, and PBj6.6 were evaluated by intravenous inoculation of pig-tailed macaques (Macaca nemestrina). Introduction of the ITAM did not increase plasma viral RNA levels nor alter the kinetics of viremia compared with the NefY(-) versions of each clone. Clinical symptoms were not observed in animals inoculated with the NefY- variants. In contrast, characteristic PBj symptoms were observed in animals inoculated with any of the three NefY(+) clones. Blunting and fusion of intestinal AM and multifocal infiltration of mononuclear cells were observed in the gastrointestinal tracts of macaques inoculated with the NefY(+) versions. Lesions were associated with active viral replication, as demonstrated by simian immunodeficiency virus-specific in situ hybridization. However, only the macaque inoculated with wild-type NefY(+) SIVsmPBj developed fatal disease; lesions were more widespread and severe in this animal. A switch to macrophages as a viral reservoir and the presence of interleukin-6 in plasma was unique to the macaque infected with PBj6.6. Overall, these data suggest that the ITAM in SIV Nef alters the pathogenesis of simian immunodeficiency virus regardless of the viral background. The change in pathogenesis occurs without enhancement of viral replication. However, NefY(+) variants of SIVagm and SIVsm did not fully recapitulate the virulence of SIVsmPBj, implicating additional viral factors in this unique virus pathogenesis. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. RP Hirsch, VM (reprint author), Twinbrook 2 Facil,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 31 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4379 EP 4389 DI 10.1128/JVI.76.9.4379-4389.2002 PG 11 WC Virology SC Virology GA 541CB UT WOS:000174966700026 PM 11932405 ER PT J AU Yang, XZ Lee, J Mahony, EM Kwong, PD Wyatt, R Sodroski, J AF Yang, XZ Lee, J Mahony, EM Kwong, PD Wyatt, R Sodroski, J TI Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; HIV-1 GP41; NEUTRALIZING ANTIBODIES; GP120 GLYCOPROTEIN; IMMUNE-RESPONSES; ATOMIC-STRUCTURE; RECEPTOR; PROTEIN; DOMAIN; IMMUNIZATION AB The envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) function as a trimer composed of three gp120 exterior glycoproteins and three gp41 transmembrane proteins. Soluble gp140 glycoproteins composed of the uncleaved ectodomains of gp120 and gp41 form unstable, heterogeneous oligomers, but soluble gp140 trimers can be stabilized by fusion with a C-terminal, trimeric GCN4 motif (X. Yang et al., J. Virol 74:5716-5725, 2000). To understand the influence of the C-terminal trimerization domain on the properties of soluble HIV-1 envelope glycoprotein trimers, uncleaved, soluble gp140 glycoproteins were stabilized by fusion with another trimeric motif derived from T4 bacteriophage fibritin. The fibritin construct was more stable to heat and reducing conditions than the GCN4 construct. Both GCN4- and fibritin-stabilized soluble gp140 glycoproteins exhibited patterns of neutralizing and nonneutralizing antibody binding expected for the functional envelope gIycoprotein spike. Of note, two potently neutralizing antibodies, immunoglobulin G1b12 and 2G12, exhibited the greatest recognition of the stabilized, soluble trimers, relative to recognition of the gp120 monomer. The observed similarities between the GCN4 and fibritin constructs indicate that the HIV-1 envelope glycoprotein ectodomains dictate many of the antigenic and structural features of these fusion proteins. The melting temperatures and ligand recognition properties of the GCN4- and fibritin-stabilized soluble gp140 glycoproteins suggest that these molecules assume conformations distinct from that of the fusion-active, six-helix bundle. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NIAID, Struct Biol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Lab Struct Virol, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St JFB824, Boston, MA 02115 USA. FU NIAID NIH HHS [P30 AI028691, AI24755, AI28691, AI31783, AI39420, R01 AI031783, R01 AI039420, R37 AI024755] NR 52 TC 203 Z9 208 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4634 EP 4642 DI 10.1128/JVI.76.9.4634-4642.2002 PG 9 WC Virology SC Virology GA 541CB UT WOS:000174966700050 PM 11932429 ER PT J AU Freed, EO AF Freed, EO TI Viral late domains SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; VESICULAR STOMATITIS-VIRUS; ROUS-SARCOMA VIRUS; MURINE LEUKEMIA-VIRUS; LATE ASSEMBLY DOMAIN; GROWTH-HORMONE RECEPTOR; PFIZER MONKEY VIRUS; TYPE-1 GAG PROTEIN; PROLINE-RICH MOTIF; PARTICLE-PRODUCTION C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. NR 87 TC 309 Z9 319 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4679 EP 4687 DI 10.1128/JVI.76.10.4679-4687.2002 PG 9 WC Virology SC Virology GA 546DK UT WOS:000175256500001 PM 11967285 ER PT J AU Thio, CL Gao, XJ Goedert, JJ Vlahov, D Nelson, KE Hilgartner, MW O'Brien, SJ Karacki, P Astemborski, J Carrington, M Thomas, DL AF Thio, CL Gao, XJ Goedert, JJ Vlahov, D Nelson, KE Hilgartner, MW O'Brien, SJ Karacki, P Astemborski, J Carrington, M Thomas, DL TI HLA-Cw*04 and hepatitis C virus persistence SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-HISTORY; NK CELLS; B VIRUS; INFECTION; HLA; HIV-1; ASSOCIATION; HEMOPHILIA; CLEARANCE; OUTCOMES AB In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% Cl, 0.39 to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A*2301 (OF, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but only HLA-B*53 (OR, 1.70, 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B*53 has similar, but not necessarily identical, binding specificity to some HLA-B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA*04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance. C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. Cornell Med Ctr, New York Presbyterian Hosp, Dept Pediat, New York, NY USA. New York Acad Med, New York, NY USA. RP Thio, CL (reprint author), Johns Hopkins Univ, Dept Med, 424 N Bond St, Baltimore, MD 21231 USA. RI Yang, Chen/G-1379-2010 FU NCI NIH HHS [N01-CO-56000, N01-CP-33002]; NCRR NIH HHS [M01 RR000059, M01 RR000071, M01 RR002558, M01-RR00059, M01-RR00071, M01-RR02558, M01-RR06020]; NICHD NIH HHS [N01-HD-4-3200]; NIDA NIH HHS [DA00441, DA04334, DA13324, K08 DA000441, R01 DA004334, R01 DA013324, R37 DA004334, R56 DA004334]; PHS HHS [MCJ-060570] NR 28 TC 126 Z9 133 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4792 EP 4797 DI 10.1128/JVI.76.10.4792-4797.2002 PG 6 WC Virology SC Virology GA 546DK UT WOS:000175256500012 PM 11967296 ER PT J AU Mascola, JR Louder, MK Winter, C Prabhakara, R De Rosa, SC Douek, DC Hill, BJ Gabuzda, D Roederer, M AF Mascola, JR Louder, MK Winter, C Prabhakara, R De Rosa, SC Douek, DC Hill, BJ Gabuzda, D Roederer, M TI Human immunodeficiency virus type 1 neutralization measured by flow cytometric quantitation of single-round infection of primary human T cells SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1/SIV CHIMERIC VIRUS; BLOOD MONONUCLEAR-CELLS; HIV-INFECTION; ENVELOPE GLYCOPROTEINS; MONOCLONAL-ANTIBODIES; REPLICATIVE CAPACITY; ANTIGEN-DETECTION; P24 ANTIGEN; IN-VITRO; ASSAYS AB There is currently intensive research on the design of novel human immunodeficiency virus type I (HIV-1) vaccine immunogens that can elicit potent neutralizing antibodies. A prerequisite for comparing and optimizing these strategies is the ability to precisely measure neutralizing antibody responses. To this end, we sought to develop an assay that directly quantifies single-round HIV-1 infection of peripheral blood mononuclear cells (PBMC). Initial experiments demonstrated that essentially all productively infected PBMC could be identified by flow cytometric detection of intracellular p24 antigen (p24-Ag). After infection of PBMC with HIV-1, p24(+) lymphocytes could be distinguished beginning 1 day postinfection, and the majority of CD8(-) T cells were p24-Ag positive by 3 to 4 days postinfection. To directly quantify first-round infection, we included a protease inhibitor in PBMC cultures. The resulting 2-day assay was highly sensitive and specific for the detection of HIV-1-infected PBMC. Serial dilutions of virus stocks demonstrated that the number of target cells infected was directly related to the amount of infectious virus input into the assay. In neutralization assays, the flow cytometric enumeration of first-round infection of PBMC provided quantitative data on the number of target calls infected and on the inactivation of infectious virus due to reaction with antibody. We also used this single-round assay to compare the percentage of cells expressing p24-Ag to the number of copies of HIV-1 gag per 100 PBMC. The precision and reproducibility of this assay will facilitate the measurement of HIV-1 neutralization, particularly incrementally improved neutralizing antibody responses generated by new candidate vaccines. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. RI Roederer, Mario/G-1887-2011 FU NINDS NIH HHS [NS37277, R01 NS037277] NR 78 TC 93 Z9 99 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4810 EP 4821 DI 10.1128/JVI.76.10.4810-4821.2002 PG 12 WC Virology SC Virology GA 546DK UT WOS:000175256500014 PM 11967298 ER PT J AU Beasley, BE Hu, WS AF Beasley, BE Hu, WS TI cis-acting elements important for retroviral RNA packaging specificity SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA VIRUS; SPLEEN NECROSIS VIRUS; DEPENDENT DNA POLYMERASE; HELPER-CELL LINE; NUCLEOCAPSID PROTEIN; GENOMIC RNA; GAG POLYPROTEIN; VIRAL-RNA; DEFECTIVE RETROVIRUS AB Spleen necrosis virus (SNN) proteins can package RNA from distantly related murine leukemia virus (MLV), whereas MLV proteins cannot package SNV RNA efficiently. We used this nonreciprocal recognition to investigate regions of packaging signals that influence viral RNA encapsidation specificity. Although the MLV and SNV packaging signals (T and E, respectively) do not contain significant sequence homology, they both contain a pair of hairpins. This hairpin pair was previously proposed to be the core element in MLV Psi. In the present study, MLV-based vectors were generated to contain chimeric SNV/MLV packaging signals in which the hairpins were replaced with the heterologous counterpart. The interactions between these chimeras and MLV or SNV proteins were examined by virus replication and RNA analyses. SNV proteins recognized all of the chimeras, indicating that these chimeras were functional. We found that replacing the hairpin pair did not drastically alter the ability of MLV proteins to package these chimeras. These results indicate that, despite the important role of the hairpin pair in RNA packaging, it is not the major motif responsible for the ability of MLV proteins to discriminate between the MLV and SNV packaging signals. To determine the role of sequences flanking the hairpins in RNA packaging specificity, vectors with swapped flanking regions were generated and evaluated. SNV proteins packaged all of these chimeras efficiently. In contrast, MLV proteins strongly favored chimeras with the MLV 5'-flanking regions. These data indicated that MU Gag recognizes multiple elements in the viral packaging signal, including the hairpin structure and flanking regions. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. NR 68 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4950 EP 4960 DI 10.1128/JVI.76.10.4950-4960.2002 PG 11 WC Virology SC Virology GA 546DK UT WOS:000175256500028 PM 11967312 ER PT J AU Lenardo, MJ Angleman, SB Bounkeua, V Dimas, J Duvall, MG Graubard, MB Hornung, F Selkirk, MC Speirs, CK Trageser, C Orenstein, JO Bolton, DL AF Lenardo, MJ Angleman, SB Bounkeua, V Dimas, J Duvall, MG Graubard, MB Hornung, F Selkirk, MC Speirs, CK Trageser, C Orenstein, JO Bolton, DL TI Cytopathic killing of peripheral blood CD4(+) T lymphocytes by human immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not require env SO JOURNAL OF VIROLOGY LA English DT Article ID FAS-MEDIATED APOPTOSIS; PROGRAMMED CELL-DEATH; ACTIVATION-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; HIV-1 TAT PROTEIN; INFECTED-CELLS; LIGAND EXPRESSION; MONONUCLEAR-CELLS; LYMPH-NODES; IN-VITRO AB An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4(+) T-lymphocyte destruction. We show here that HIV type I (HIV-1) exerts a profound cytopathic effect upon peripheral blood CD4(+) T lymphocytes that resembles necrosis rather than apoptosis. necrotic cytopathology was found with both laboratory-adapted strains and primary isolates of HIV-1. We carefully investigated the role of env, which has been previously implicated in HIV cytopathicity. HIV-1 stocks with equivalent infectivity were prepared from constructs with either an intact or mutated env coding region and pseudotyped with the glycoprotein of vesicular stomatitis virus (VSV-G) so that the HIV envelope was not rate-limiting for infection. Infected Jurkat T cells died whether or not env was intact; however, the expression of env accelerated death significantly. The accelerated death was blocked by protease inhibitors, indicating that it was due to reinfection by newly produced virus in env(+) cultures. Accordingly, we found no disparity in kinetics in CD4(lo) Jurkat cells. In highly infected peripheral blood T cells, profound necrosis occurred equivalently with both env(+) and env(-) stocks of HIV-1. We also found that HIV-1 cytopathicity was undiminished by the absence of nef. However, viral stocks made by complementation or packaging of HIV-1 genomes with the natural protein-coding sequences replaced by the green fluorescent protein were highly infectious but not cytopathic. Thus, env can accelerate cell death chiefly as an entry function, but one or more viral functions other than env or nef is essential for necrosis of CD4(+) T cells induced by HIV-1. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC 20052 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. OI Angleman, Sara/0000-0002-9520-5716 NR 92 TC 67 Z9 72 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 5082 EP 5093 DI 10.1128/JVI.76.10.5082-5093.2002 PG 12 WC Virology SC Virology GA 546DK UT WOS:000175256500040 PM 11967324 ER PT J AU Bolton, DL Hahn, BI Park, EA Lehnhoff, LL Hornung, F Lenardo, MJ AF Bolton, DL Hahn, BI Park, EA Lehnhoff, LL Hornung, F Lenardo, MJ TI Death of CD4(+) T-cell lines caused by human immunodeficiency virus type 1 does not depend on caspases or apoptosis SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; CD4(+) T-CELLS; HIV-1 INFECTION; MONOCLONAL-ANTIBODY; THYMOCYTE APOPTOSIS; TRIGGER APOPTOSIS; LYMPH-NODES; ANNEXIN-V; IN-VITRO; ACTIVATION AB A critical aspect of AIDS pathogenesis that remains unclear is the mechanism by which human immunodeficiency virus type I (HIV-1) induces death in CD4(+) T lymphocytes. A better understanding of the death process occurring in infected cells may pro-tide valuable insight into the viral component responsible for cytopathicity. This would aid the design of preventive treatments against the rapid decline of CD4(+) T cells that results in AIDS. Previously, apoptotic cell death has been reported in HIV-1 infections in cultured T cells, and it has been suggested that this could affect both infected and uninfected cells. To evaluate the mechanism of this effect, we have studied HIV-1-induced cell death extensively by infecting several T-cell lines and assessing the level of apoptosis by using various biochemical and flow cytometric assays. Contrary to the prevailing view that apoptosis plays a prominent role in HIV-1-mediated T-cell death, we found that Jurkat and H9 cells dying from HIV-1 infection fail to exhibit the collective hallmarks of apoptosis. Among the parameters investigated,. in V display, caspase activity and cleavage of caspase substrates, TUNEL (terminal deoxynucleotidyl-Annexin transferase-mediated dUTP-biotin nick end labeling) signal, and APO2.7 display were detected at low to negligible levels. Neither peptide caspase inhibitors nor the antiapoptotic proteins Bel-x, or v-FLIP could prevent cell death in HIV-1-infected cultures. Furthermore, Jurkat cell lines deficient in RIP, caspase-8, or FADD were as susceptible as wild-type Jurkat cells to HIV-1 cytopathicity. These results suggest that the primary mode of cytopathicity by laboratory-adapted molecular clones of HIV-1 in cultured cell lines is not via apoptosis. Rather, cell death occurs most likely via a necrotic or lytic form of death independent of caspase activation in directly infected cells. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM lenardo@nih.gov NR 66 TC 49 Z9 52 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 5094 EP 5107 DI 10.1128/JVI.76.10.5094-5107.2002 PG 14 WC Virology SC Virology GA 546DK UT WOS:000175256500041 PM 11967325 ER PT J AU Vende, P Taraporewala, ZF Patton, JT AF Vende, P Taraporewala, ZF Patton, JT TI RNA-binding activity of the rotavirus phosphoprotein NSP5 includes affinity for double-stranded RNA SO JOURNAL OF VIROLOGY LA English DT Article ID NONSTRUCTURAL PROTEIN NSP2; IN-VIVO; GENOME REPLICATION; READING FRAMES; MESSENGER-RNA; KINASE PKR; OPEN CORES; PHOSPHORYLATION; IDENTIFICATION; MULTIMERS AB Phosphoprotein NSP5 is a component of replication intermediates that catalyze the synthesis of the segmented double-stranded RNA (dsRNA) rotavirus genome. To study the role of the protein in viral replication, His-tagged NSP5 was expressed in bacteria and purified by affinity chromatography. In vitro phosphorylation assays showed that NSP5 alone contains minimal autokinase activity but undergoes hyperphosphorylation when combined with the NTPase and helix-destabilizing protein NSP2. Hence, NSP2 mediates the hyperphosphorylation of NSP5 in the absence of other viral or cellular proteins. RNA-binding assays demonstrated that NSP5 has unique nonspecific RNA-binding activity, recognizing single-stranded RNA and dsRNA with similar affinities. The possible functions of the RNA-binding activities of NSP5 are to cooperate with NSP2 in the destabilization of RNA secondary structures and in the packaging of RNA and/or to prevent the interferon-induced dsRNA-dependent activation of the protein kinase PKR. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. INRA, CRJJ, Lab Virol & Immunol Mol, F-78352 Jouy En Josas, France. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr MSC 8026, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 52 TC 39 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 5291 EP 5299 DI 10.1128/JVI.76.10.5291-5299.2002 PG 9 WC Virology SC Virology GA 546DK UT WOS:000175256500061 PM 11967345 ER PT J AU Lan, TY Melzer, D Tom, BDM Guralnik, JM AF Lan, TY Melzer, D Tom, BDM Guralnik, JM TI Performance tests and disability: Developing an objective index of mobility-related limitation in older populations SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID UNITED-STATES; FUNCTIONAL LIMITATIONS; SUBSEQUENT DISABILITY; OXYGEN-UPTAKE; HEALTH; TRENDS; WOMEN; ASSOCIATION; AMERICANS; ADULTS AB Background. Disability reflects physiological limitations. social and environmental barriers. and "sickness" behavior. Being able to measure these influences separately would greatly assist interpretation of disability comparisons over time or between populations. This study aimed to identify an index of mobility-related limitations composed of physiological measures that are most closely associated with reported mobility disability in elders. Methods. Data from the Third National Health and Nutrition Examination Survey (NHANES 111) were Used. Participants aged 60 and older were included in this analysis. participants included 6596 respondents who were interviewed in their homes. and 5724 (87%) of these attended a further examination. Domains of measurements included body measurements, bone densitometry, physical examination. spirometry. fundus photography, and physical performance measures. Multivariate models were developed oil a random half subsample of the data and were validated oil the other half. Receiver operating characteristic (ROC) areas and logit rank slopes Were Used to evaluate Sets 01 measures. Results. In weighted logistic regression models, six and five measures Were significantly associated with difficulty and inability in walking a quarter of a mile. respectively. These mainly included measures of lower extremity and lung function. A relatively minimal loss of sensitivity and specificity occurred from more economical models. employing a Subset of the identified measures. Conclusions. Subsets Of measures associated with reported mobility disability could provide objective indices of mobility-related limitation for comparing populations or long-term population health monitoring. C1 Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Forv Site,Robinson Way, Cambridge CB2 2SR, England. RI Lan, Tzuo-Yun /E-3844-2010 NR 40 TC 45 Z9 46 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2002 VL 57 IS 5 BP M294 EP M301 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 548XT UT WOS:000175415700010 PM 11983723 ER PT J AU Onder, G Penninx, BWJH Lapuerta, P Fried, LP Ostir, GV Guralnik, JM Pahor, M AF Onder, G Penninx, BWJH Lapuerta, P Fried, LP Ostir, GV Guralnik, JM Pahor, M TI Change in physical performance over time in older women: The Women's Health and Aging Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; SUBSEQUENT DISABILITY; PREDICTOR; VALIDATION; ADULTS AB Background. Although lower and upper extremity performance measures are widely used and represent validated physical function measures in older adults, there is limited information regarding the magnitude of changes ill these measures over time. This study (i) assesses prospective changes in physical performance measures, (ii) defines a summary score that demonstrates a significant amount of change over time, and (iii) examines rates of decline according to age and baseline performance levels. Methods. Data from the Women's Health and Aging Study (WHAS) were analyzed to assess change in the one third most disabled older women living in the community. Lower extremity function was assessed using walking speed, balance, and chair stands tests. The putting-on-blouse test, the lock and key test, the Purdue Pegboard test, and grip strength were used to gauge upper extremity function. Continuous and categorical summary performance scores were calculated using continuous and categorical data of lower and upper performance measures. Results. After 3 years, lower extremity performance measures declined by 16%-27%, while upper extremity performance measures declined less (7%-24%). For lower extremity function, the continuous summary performance score showed a slightly greater 3-year decline from baseline (decline vs baseline mean: 23%; decline vs SD of the baseline mean: 59%) than the categorical score (22% and 41%, respectively). Older age and intermediate level of baseline performance were associated with the greatest decline, especially for lower extremity function. Conclusions. In moderately to severely disabled women aged 65 or older, lower extremity measures show more change over 3 years than upper extremity measures. Among the lower extremity summary scores, the continuous score changes more over time than the categorical score with respect to the baseline SD. The lower extremity Continuous summary performance score may be a useful outcome measure for clinical studies of physical performance in older women. C1 Wake Forest Univ, Sch Med, Dept Internal Med, Sect Gerontol & Geriatr,Sticht Ctr Aging, Winston Salem, NC 27109 USA. Univ Sacred Heart, Dept Gerontol & Geriatr, I-00168 Rome, Italy. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. Johns Hopkins Med Inst, Dept Med & Epidemiol, Baltimore, MD 21205 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Onder, G (reprint author), Wake Forest Univ, Baptist Med Ctr, Sect Gerontol & Geriatr, Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NIA NIH HHS [5P60 AG 10484-07, N01AG12112] NR 19 TC 109 Z9 111 U1 1 U2 12 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2002 VL 57 IS 5 BP M289 EP M293 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 548XT UT WOS:000175415700009 PM 11983722 ER PT J AU Visser, M Pahor, M Taaffe, DR Goodpaster, BH Simonsick, EM Newman, AB Nevitt, M Harris, TB AF Visser, M Pahor, M Taaffe, DR Goodpaster, BH Simonsick, EM Newman, AB Nevitt, M Harris, TB TI Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: The health ABC study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID C-REACTIVE PROTEIN; SUBCUTANEOUS ADIPOSE-TISSUE; SKELETAL-MUSCLE; PLASMA IL-6; CARDIOVASCULAR-DISEASE; BODY-COMPOSITION; OLDER PERSONS; RISK-FACTORS; IN-VIVO; DISABILITY AB Background. A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show it relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers, of inflammation are associated with muscle mass and strength in well-functioning elderly persons. Methods. We Used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray ab absorptiometry). isokinetic knee extensor strength (KinCom). and isometric inip strength were measured. plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA). Results. Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p < .05) after adjustment for age, clinic Site. health status, medications, physical activity. smoking. height. and body fat. Ail overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-alpha. With the exception of white men, elderly persons having high levels of IL-6 (> 1.80 pg/ml) as well as high levels of TNF-alpha (> 3.20 pg/ml) had a smaller muscle area, less appendicular mass. a lower knee extensor strength. and a lower grip strength compared to those with low levels of both cytokines. Conclusions. Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels. as often observed in healthy older persons. may contribute to the loss Of muscle mass and strength that accompanies aging. C1 VU Univ, Ctr Med, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. Univ Queensland, Sch Human Movement Studies, Brisbane, Qld, Australia. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. RP Visser, M (reprint author), VU Univ, Ctr Med, Inst Res Extramural Med, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. FU NIA NIH HHS [N01-AG-6-2103, K01-AG-00851, N01-AG-6-2101, N01-AG-6-2106, P60-AG-10484] NR 35 TC 439 Z9 447 U1 2 U2 18 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2002 VL 57 IS 5 BP M326 EP M332 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 548XT UT WOS:000175415700015 PM 11983728 ER PT J AU Le, SY Liu, WM Maizel, JV AF Le, SY Liu, WM Maizel, JV TI A data mining approach to discover unusual folding regions in genome sequences SO KNOWLEDGE-BASED SYSTEMS LA English DT Article DE data mining; statistical model; RNA/DNA folding; UFR ID RNA SECONDARY STRUCTURE; MESSENGER-RNA; STATISTICAL SIGNIFICANCE; THERMODYNAMIC STABILITY; VIRUS; SITES AB Numerous experiments and analyses of RNA structures have revealed that the local distinct structure closely correlates with the biological function. In this study, we present a data mining approach to discover such unusual folding regions (UFRs) in genome sequences. Our approach is a three-step procedure. During the first step, the quality of a local structure different from a random folding in a genomic sequence is evaluated by two z-scores, significance score (SIGSCR) and stability score (STBSCR) of the local segment. The two scores are computed by sliding a fixed window stepped a base along the sequence from the start to end position. Next, based on the non-central Student's t distribution theory we derive a linearly transformed non-central Student's t distribution (LTNSTD) to describe the distribution of SIGSCR and STBSCR computed in the sequence. In the third step, we extract these significant UFRs from the sequence whose SIGSCR and/or STBSCR are greater or less than a given threshold calculated from the derived LTNSTD. Our data mining approach is successfully applied to the complete genome of Mycoplasma genitalium (M. gen) and discovers these statistical extremes in the genome. By comparisons with the two scores computed from randomly shuffled sequences of the entire M. gen genome, our results demonstrate that the UFRs in the M. gen sequence are not selected by chance. These UFRs may imply an important structure role involved in their sequence information. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Frederick, MD 21702 USA. Indiana Univ, Dept Comp & Informat Sci, Indianapolis, IN 46202 USA. RP Le, SY (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Bldg 469,Room 151, Frederick, MD 21702 USA. NR 21 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0950-7051 J9 KNOWL-BASED SYST JI Knowledge-Based Syst. PD MAY PY 2002 VL 15 IS 4 SI SI BP 243 EP 250 AR PII S0950-7051(01)00146-0 DI 10.1016/S0950-7051(01)00146-0 PG 8 WC Computer Science, Artificial Intelligence SC Computer Science GA 545WH UT WOS:000175240200005 ER PT J AU Priola, SA AF Priola, SA TI Therapeutic potential of prion protein peptides in the transmissible spongiform encephalopathies SO LABORATORY MEDICINE LA English DT Editorial Material ID CREUTZFELDT-JAKOB-DISEASE; DOMINANT-NEGATIVE INHIBITION; MOUSE NEUROBLASTOMA-CELLS; SYNTHETIC PEPTIDES; TRANSGENIC MICE; PRP ACCUMULATION; RESISTANT PRP; VARIANT CJD; HAMSTER PRP; IN-VITRO C1 NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, Lab Persistent Viral Dis,NIH, Hamilton, MT USA. RP Priola, SA (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, Lab Persistent Viral Dis,NIH, Hamilton, MT USA. NR 54 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD MAY PY 2002 VL 33 IS 5 BP 369 EP 373 DI 10.1309/J7YV-8VA1-R6YC-0T5Q PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 545VL UT WOS:000175238200014 ER PT J AU Hursey, M Newton, DL Hansen, HJ Ruby, D Goldenberg, DM Rybak, SM AF Hursey, M Newton, DL Hansen, HJ Ruby, D Goldenberg, DM Rybak, SM TI Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents: A new generation of therapeutics SO LEUKEMIA & LYMPHOMA LA English DT Review DE antibody; ribonuclease; cancer; immunotoxin; apoptosis; CD22 ID ANTI-CD22 MONOCLONAL-ANTIBODY; CYTOTOXIC RIBONUCLEASE; P-30 PROTEIN; ANTITUMOR RIBONUCLEASE; N-TERMINUS; SCID MICE; PHASE-I; IMMUNOTOXINS; CHEMOTHERAPY; ONCONASE AB Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA-damaging chemotherapeutics. A second generation construct with an improved recombinant cytotoxic RNAse is described. Targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin-containing immunoconjugates. C1 NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Rybak, SM (reprint author), NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 47 TC 33 Z9 35 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAY PY 2002 VL 43 IS 5 BP 953 EP 959 DI 10.1080/10428190290021380 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 559EE UT WOS:000176012000003 PM 12148905 ER PT J AU Rosenberger, TA Hovda, JT Peters, JM AF Rosenberger, TA Hovda, JT Peters, JM TI Targeted disruption of peroxisomal proliferator-activated receptor beta (delta) results in distinct gender differences in mouse brain phospholipid and esterified FA levels SO LIPIDS LA English DT Article ID ACID-BINDING-PROTEIN; FATTY-ACID; SEX-DIFFERENCES; RAT-LIVER; METABOLISM; CHAIN; RAFTS; BIOSYNTHESIS; PLASMALOGENS; TRANSPORT AB The peroxisomal proliferator-activated receptor (5) (PPARbeta) is a nuclear hormone receptor that is ubiquitously expressed and that regulates the transcription of genes involved in lipid metabolism. A homozygous PPARbeta-null mouse has been developed in which the ligand-binding domain of the PPAR receptor is disrupted, Analysis of brains from these animals show's that female null mice have 24 and 17(1,) increases in plasmenylethanolamine and phosphatidylserine and a 9% decrease in the level of phosphatidylinositol when compared to controls. The phospholipid changes found in female null mice were associated with increased levels of esterified 18:1 n-9, 20:1 n-9, 20:4n-6, and 22:5n-3 FA in plasmenylethanolamine, 20:1 n-9 in phosphatidylinositol, and 18:0, 18:1 n-9, 18:3n-6, 20:1 n-9, and 20:4n-6 in phosphatidylserine. Increased levels of esterified 18:1 n-9, 18:2n-6. 18:3n-6, and 20:1 n-9 were also found in the phosphatidylethanolamine fraction despite its cellular content remaining unchanged. Brain phospholipid content in male PPARbeta-null mice did not differ from controls, but increased levels of 20:1 n-9 in the phosphatidylinositol and 18:1 n-9 in the phosphatidylserine fractions were observed. No changes were found in the content of brain cholesterol, TAG, and FFA in either female or male PPARbeta-null mice. These data suggest that PPARbeta is involved in maintaining FA and phospholipid levels in adult female mouse brain and provide strong evidence that suggests a role for PPARbeta in brain peroxisomal acyl-CoA utilization. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. RP Rosenberger, TA (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6N202, Bethesda, MD 20892 USA. RI Peters, Jeffrey/D-8847-2011 NR 37 TC 16 Z9 16 U1 0 U2 2 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD MAY PY 2002 VL 37 IS 5 BP 495 EP 500 DI 10.1007/s11745-002-0923-1 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 554NY UT WOS:000175743300009 PM 12056592 ER PT J AU Subramanian, S Yamada, K Irie, A Murugesan, R Cook, JA Devasahayam, N Van Dam, GM Mitchell, JB Krishna, MC AF Subramanian, S Yamada, K Irie, A Murugesan, R Cook, JA Devasahayam, N Van Dam, GM Mitchell, JB Krishna, MC TI Noninvasive in vivo oximetric imaging by radiofrequency FT EPR SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE RF FT-EPR; in vivo imaging; oximetry; EPR imaging ID ELECTRON-PARAMAGNETIC-RESONANCE; MAGNETIC-RESONANCE; RAPID QUANTITATION; TUMOR OXYGENATION; SPIN-RESONANCE; TISSUE; OXYMETRY; SPECTRA; SPECTROSCOPY; TOMOGRAPHY AB A novel method, called relaxo-oximetry, for rapid spatially resolved in vivo measurements of oxygen concentration using time-domain radiofrequency (RF) electron paramagnetic resonance (EPR) is described. Time-domain data from triaryl methyl (TAM)-based single-electron contrast agents were processed by systematic deletion of the initial time points to arrive at T-2*-weighted discrimination of signal amplitudes. In experiments involving phantoms, the line widths [similar to (T-2*)(-1)] increased as a function of oxygen, and the slope (line width/pO(2)) was the same for both absorption- and magnitude-mode line shapes. Line widths derived from T-2* weighting and the computed pO(2) values agreed favorably With the measured ones from phantoms of known oxygen tension. In vivo relaxo-oximetry was performed on C3H mice, and it was found that the liver was more hypoxic than the kidneys. For tumors, 2D oxygen maps were generated while the animal breathed room air or Carbogen(R) (95% O-2/5% CO2). Carbogen(R) enhanced oxygen concentration within the tumor, and the pO(2) histograms showed considerable heterogeneity. Clark electrode oxygen measurements on organs and tumors were in good agreement with tissue oxygen measurements done by relaxo-oximetry. Thus, from a single spatial image data set, pO(2) measurements can be done noninvasively by relaxo-oximetry, and 3D imaging can be performed in less than 3 min. (C) 2002 Wiley-Liss, Inc. C1 NCI, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Groningen Hosp, Dept Surg, Groningen, Netherlands. RP Krishna, MC (reprint author), NIH, Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. RI Yamada, Ken-ichi/E-6318-2012 NR 31 TC 38 Z9 38 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 2002 VL 47 IS 5 BP 1001 EP 1008 DI 10.1002/mrm.10133 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 547RT UT WOS:000175346100021 PM 11979580 ER PT J AU Sloan, JA Aaronson, N Cappelleri, JC Fairclough, DL Varricchio, C AF Sloan, JA Aaronson, N Cappelleri, JC Fairclough, DL Varricchio, C CA Clinical Significance Consensus Me TI Assessing the clinical significance of single items relative to summated scores SO MAYO CLINIC PROCEEDINGS LA English DT Article ID QUALITY-OF-LIFE; CANCER-PATIENTS; SHORT-FORM; HEALTH SURVEY; INSTRUMENT; ITEM; VALIDATION; INDEX; ONCOLOGY; PROFILE AB How many items are needed to measure an individual's quality of life (QOL)? This article describes the strengths and weaknesses of single items and summated scores (from multiple items) as QOL measures. We also address the use of single global measures vs multiple subindices as measures of QOL. The primary themes that recur throughout this article are the relationships between well-defined research objectives, the research setting, and the choice single item vs summated scores to measure QOL. The conceptual framework of the study, the conceptual fit with the measure, and the purpose of the assessment should all be considered when choosing a measure of QOL. No "gold standard" QOL measure can be recommended because no "one size fits all." Single items have the advantage of simplicity at the cost of detail. Multiple-item indices have the advantage of providing a complete profile of QOL component constructs at the cost of increased burden and of asking potentially irrelevant questions. The 2 types of indices are not mutually exclusive and can be used together in a single research study or in the clinical setting. C1 Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA. Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. Pfizer Inc, Global Res & Dev, Groton, CT USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes, Denver, CO USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Sloan, JA (reprint author), Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA35101, CA35415, CA35113, CA35448, CA35272, CA15083, CA63849, CA35269, CA35195, CA25224, CA35103, CA37404, CA52352, CA37417] NR 29 TC 147 Z9 149 U1 1 U2 5 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAY PY 2002 VL 77 IS 5 BP 479 EP 487 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 548FB UT WOS:000175377000012 PM 12004998 ER PT J AU Carroll, RE Matkowskyj, K Saunthararajah, Y Sekosan, M Battey, JF Benya, RV AF Carroll, RE Matkowskyj, K Saunthararajah, Y Sekosan, M Battey, JF Benya, RV TI Contribution of gastrin-releasing peptide and its receptor to villus development in the murine and human gastrointestinal tract SO MECHANISMS OF DEVELOPMENT LA English DT Article ID HUMAN COLON-CANCER; CELL-LINES; BOMBESIN; LUNG; EXPRESSION; MORPHOGEN; MECHANISM; CLONING; BINDING AB Recent studies ha re shown that aberrantly expressed gastrin-releasing peptide (GRP) and its receptor (GRP-R) criticall regulate tumor cell differentiation in colon cancers developing in humans and mice. This finding suggested that the ability of GRP/GRP-R to promote a well-differentiated phenotype in colon cancer might reflect a re-capitulation of a normal role in regulating intestinal organogenesis. To deter-mine if this was the case, we compared and contrasted intestinal development in GRPR(-/-) mice with their wild type littermates. GRP/GRP-R coexpression in wild type mice was only observed in villous enterocytes between N-1 and N-12. During this time frame villous growth was completely attenuated in GRPR(-/-) mice. The contribution of GRP/GRP-R to villous growth was due to their act in increasing enterocyte proliferation prior to N-8 but increasing enterocyte size thereafter. Front N-12 onwards, small intestinal villous growth in GRPR(-/-) mice resumed such that no difference in this structure could be detected at adulthood between mice of either genotype. We next studied GRP/GRP-R expression in human abortuses. These proteins were co-expressed by villous enterocytes only, between weeks 14 and 20 post-conception, a time frame analogous to when they are expressed in the murine intestine. Thus, this study shows for the first time that GRP/GRP-R play a transient and non-critical role in intestinal development, yet prod ides a rationale for their re-appearance in colon cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Illinois, Dept Med, Vet Adm Med Ctr, W Side Div, Chicago, IL 60612 USA. Univ Illinois, Dept Pathol, Chicago, IL 60612 USA. NIDCD, NIH, Bethesda, MD USA. RP Benya, RV (reprint author), Univ Illinois, Dept Med, Vet Adm Med Ctr, W Side Div, 840,S Wood St,M-C 787, Chicago, IL 60612 USA. FU NCI NIH HHS [CA-80360]; NIDDK NIH HHS [DK-51168] NR 36 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAY PY 2002 VL 113 IS 2 BP 121 EP 130 AR PII S0925-4773(02)00032-1 DI 10.1016/S0925-4773(02)00032-1 PG 10 WC Developmental Biology SC Developmental Biology GA 553KY UT WOS:000175675400002 PM 11960700 ER PT J AU Potosky, AL AF Potosky, AL TI Comparing health care systems - The importance and limitations of outcome measures SO MEDICAL CARE LA English DT Editorial Material ID COLORECTAL-CANCER; MORTALITY; TRENDS C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. RP Potosky, AL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, EPN Room 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2002 VL 40 IS 5 BP 359 EP 361 DI 10.1097/00005650-200205000-00001 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 548EJ UT WOS:000175375400001 PM 11961470 ER PT J AU Pinto, NX Torres-Hillera, MA Mendoza, E Leon-Sarmiento, FE AF Pinto, NX Torres-Hillera, MA Mendoza, E Leon-Sarmiento, FE TI Immune response, nitric oxide, autonomic dysfunction and stroke: a puzzling linkage on Trypanosoma cruzi infection SO MEDICAL HYPOTHESES LA English DT Article ID MACROPHAGES; EXPRESSION; SYNTHASE; MICE AB Trypanosoma cruzi (T. cruzi) is a tissue parasite causing American trypanosomiasis or Chagas' disease (ChD) affecting, mostly, the cardiovascular and gastrointestinal systems. We have recently found that people infected by T. cruzi are also more prone to developing ischemic strokes than the general population, even without heart complications; the pathomechanism of it is not yet well understood. However, after infection occurs, immune response induces endothelial dysfunction due to an endothelial nitric oxide synthase (eNOS) inhibition and increased activity of inducible nitric oxide synthase (iNOS). These factors are active in inducing vasoconstriction and cerebral microvascular spasms, leading to ischemic stroke. In addition, patients with ChD, regardless of cardiopathy, also have autonomic dysfunction, all of which may enhance the risk of developing ischemic stroke. Moreover, the possibility that these neuroimmunomodulatory pathways are disturbed in patients with other types of stroke seems possible, and is worthy of investigation. (C) 2002 Published by Elsevier Science Ltd. C1 Colombian Inst Clin & Restorat Neurol, Lab Neuromuscular Dis & Motor Control, Bucaramanga, Colombia. UIS Santander Univ, Sch Med, Dept Basic Sci, Bucaramanga, Colombia. Young Researchers Program, Bogota, Colombia. UIS Santander Univ, Sch Med, Dept Internal Med, Bucaramanga, Colombia. RP Leon-Sarmiento, FE (reprint author), Natl Inst Nuerol Disorders & Stroke, Brain Stimulat Unit, NIH, Bldg 10,Room 5N234, Bethesda, MD 20892 USA. NR 17 TC 7 Z9 7 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 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD MAY PY 2002 VL 58 IS 5 BP 374 EP 377 DI 10.1054/mehy.2001.1401 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 579FT UT WOS:000177168500005 PM 12056871 ER PT J AU Dagan, T Sable, C Bray, J Gerschenson, M AF Dagan, T Sable, C Bray, J Gerschenson, M TI Mitochondrial dysfunction and antiretroviral nucleoside analog toxicities: what is the evidence? SO MITOCHONDRION LA English DT Review DE cardiovascular; hepatic; human immunodeficiency virus; lactic acidosis; lipodystrophy; myopathies; neuropathy; nucleoside analog reverse transcriptase inhibitors; pancreatitis ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; HIV-INFECTED PATIENTS; ZIDOVUDINE-ASSOCIATED MYOPATHY; SKELETAL-MUSCLE MITOCHONDRIA; SEVERE LACTIC-ACIDOSIS; TERM RHESUS MACAQUES; EXPOSED IN-UTERO; PERIPHERAL NEUROPATHY; HEPATIC STEATOSIS AB Mitochondrial dysfunction has been associated with long-term toxicities of human immunodeficiency virus (HIV) therapy, particularly with the nucleoside analog reverse transcriptase inhibitors (NRTIs). Lactic acidosis, hepatic steatosis, myopathies, cardiomyopathies, neuropathies, and lipodystrophy are frequently attributed to mitochondrial toxicity. Since mitochondrial toxicity could pose a major threat to the long-term success of HIV therapy, the scientific evidence underlying an association between mitochondrial toxicity and antiretroviral therapies, must be carefully examined. There is some data to support the association between NRTIs and mitochondria dysfunction. In this review, we examine human, animal, and in vitro data implicating mitochondrial dysfunction as the causal mechanism of NRTI-associated toxicity in HIV-infected patients. Published by Elsevier Science B.V. and Mitochondria Research Society. C1 NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Ctr Hlth Serv Res & Policy, Forum Collaborat HIV Res, Washington, DC 20006 USA. RP Gerschenson, M (reprint author), NHLBI, Div Heart & Vasc Dis, NIH, Rockledge 2,Room 9180,6701 Rockledge Drive, Bethesda, MD 20892 USA. NR 133 TC 65 Z9 65 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD MAY PY 2002 VL 1 IS 5 BP 397 EP 412 AR PII S1567-7249(02)00003-X DI 10.1016/S1567-7249(02)00003-X PG 16 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 561NL UT WOS:000176147300001 PM 16120293 ER PT J AU Kaneko, O Mu, JB Tsuboi, T Su, XZ Torii, M AF Kaneko, O Mu, JB Tsuboi, T Su, XZ Torii, M TI Gene structure and expression of a Plasmodium falciparum 220-kDa protein homologous to the Plasmodium vivax reticulocyte binding proteins SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; Plasmodium falciparum; merozoite; rhoptry ID YOELII ADHESIVE PROTEINS; RHOPTRY PROTEIN; INVASION; IDENTIFICATION; MEROZOITES C1 Ehime Univ, Sch Med, Dept Mol Parasitol, Shigenobu, Ehime 7910295, Japan. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kaneko, O (reprint author), Ehime Univ, Sch Med, Dept Mol Parasitol, Shigenobu, Ehime 7910295, Japan. OI Su, Xinzhuan/0000-0003-3246-3248 NR 17 TC 62 Z9 62 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAY PY 2002 VL 121 IS 2 BP 275 EP 278 AR PII S0166-6851(02)00042-7 DI 10.1016/S0166-6851(02)00042-7 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 560MR UT WOS:000176086300013 PM 12034462 ER PT J AU Stadtman, ER Moskovitz, J Berlett, BS Levine, RL AF Stadtman, ER Moskovitz, J Berlett, BS Levine, RL TI Cyclic oxidation and reduction of protein methionine residues is an important antioxidant mechanism SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE methionine sulfoxide reductase; antioxidants; oxidative stress ID INTERCONVERTIBLE ENZYME CASCADES; RADICAL-CATION COMPLEXES; SULFOXIDE REDUCTASE; METABOLIC-REGULATION; ALZHEIMERS-DISEASE; SYSTEMS; SUPERIORITY; SUPEROXIDE; PEPTIDES; MSRA AB Almost all forms of reactive oxygen species (ROS) oxidize methionine residues of proteins to a mixture of the R- and S-isomers of methionine sulfoxide. Because organisms contain methionine sulfoxide reductases (Msr's) that can catalyze the thioredoxin-dependent reduction of the sulfoxides back to methionine, it was proposed that the cyclic oxidation/reduction of methionine residues might serve as antioxidants to scavenge ROS, and also to facilitate the regulation of critical enzyme activities. We summarize here results of studies showing that organisms possess two different forms of Msr - namely, MsrA that catalyzes reduction of the S-isomer and MsrB that catalyzes the reduction of the R-isomer. Deletion of the msrA gene in mice leads to increased sensitivity to oxidative stress and to a decrease (40%) in the maximum lifespan. This suggests that elimination of both Msr's would have more serious consequences. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 24 TC 157 Z9 162 U1 0 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY-JUN PY 2002 VL 234 IS 1 BP 3 EP 9 DI 10.1023/A:1015916831583 PG 7 WC Cell Biology SC Cell Biology GA 564VW UT WOS:000176335100002 PM 12162447 ER PT J AU Dhar, A Young, MR Colburn, NH AF Dhar, A Young, MR Colburn, NH TI The role of AP-1, NF-kappa B and ROS/NOS in skin carcinogenesis: The JB6 model is predictive SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE AP-1; NF-kappa B; ROS; JB6 cells; transformation ID MOUSE EPIDERMAL-CELLS; ACTIVATOR PROTEIN-1 ACTIVATION; NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE SYNTHASE; PROMOTER-INDUCED TRANSFORMATION; CONTAINING SUPEROXIDE-DISMUTASE; MOBILITY GROUP-I(Y) PROTEIN; ACID RESPONSE ELEMENT; BREAST-CANCER CELLS; NEOPLASTIC TRANSFORMATION AB Generation of reactive oxygen species (ROS) stimulates transcription by activating transcription factors activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB). The mouse epidermal JB6 cells constitute a model system that has significantly contributed to the understanding of these events. Clonal variants of JB6 cells are differentially responsive to transformation induced by tumor promoters such as phorbol esters (TPA), epidermal growth factor (EGF) and tumor necrosis factor alpha (TNF-alpha), as well as oxidative stress. TPA and EGF, acting through the MAP kinase pathway, activate AP-1 and subsequently NF-kappaB proteins and downstream transcription processes that are involved in the transformation response in transformation-sensitive (P+) JB6 cells. The effect of TNF-alpha is primarily on the NF-kappaB pathway. ROS and other free radicals can activate AP-1 and NF-kappaB transcription coordinately. In JB6 cells, both ERK/Fra-1 and NF-kappaB activity is essential for the transformation response. Inhibition of NF-kappaB and AP-1 activity abrogates transformation in JB6 cells as well as in transgenic mice and human keratinocytes. A similar effect is seen with antioxidants, which inhibit NF-kappaB and AP-1 activity as well as transformation in JB6 cells. The JB6 model is therefore valuable for monitoring early events in oxidative stress related signaling leading to carcinogenesis, and for identifying molecular targets for cancer chemoprevention. C1 NCI Frederick, Gene Regulat Sect, Frederick, MD 21702 USA. RP Dhar, A (reprint author), NCI Frederick, Gene Regulat Sect, Bldg 567,Room 180,POB B, Frederick, MD 21702 USA. NR 123 TC 127 Z9 132 U1 3 U2 12 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY-JUN PY 2002 VL 234 IS 1 BP 185 EP 193 DI 10.1023/A:1015948505117 PG 9 WC Cell Biology SC Cell Biology GA 564VW UT WOS:000176335100022 PM 12162432 ER PT J AU Samuni, AM DeGraff, W Krishna, MC Mitchell, JB AF Samuni, AM DeGraff, W Krishna, MC Mitchell, JB TI Nitroxides as antioxidants: Tempol protects against EO9 cytotoxicity SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE EPR; mitomycin C; redox cycling; quinone; bioreductive ID DT-DIAPHORASE ACTIVITY; HUMAN TUMOR-CELLS; INDOLOQUINONE EO9; PHASE-II; RELATIVE IMPORTANCE; LIPID-PEROXIDATION; SPIN PROBES; MITOMYCIN-C; SUPEROXIDE; RADICALS AB Nitroxide free radicals have been shown to be potent antioxidants in a variety of experimental models using diverse means of insults. Among other insults, nitroxides have been shown effective in inhibiting cytotoxicity of quinone-based drugs such as streptonigrin and mitomycin C. These drugs and other chemotherapeutic agents have the potential to undergo bioreductive activation by the normal reducing enzymes within a cell. In the present work we studied the effect of the nitroxide Tempol on the cytotoxicity induced by EO9, a mitomycin C analogue, in HT29 cells under aerobic and hypoxic conditions. The study was aimed to better understand the mechanism of EO9 cytotoxicity and the molecular level of the nitroxide's mode of protection. The reactions of Tempol with activated EO9, and the reactive species formed during EO9 activation were studied in a cell-free solution, using spin-trapping, and electron paramagnetic resonance (EPR) spectrometry. Our results indicate that EO9 induced similar cytotoxicity in HT29 cells under aerobic and hypoxic conditions while Tempol provided similar and almost complete protection to both aerobic and hypoxic cells. The results indicate that EO9 cytotoxicity is due to both 1- and 2-electron reductive activation processes, with aerobic toxicity caused by back-oxidation of the hydroquinone to the semiquinone, EO9(.)-. Tempol serves both as a useful tool in the study of the mechanisms of quinone-mediated cytotoxicity and as a potent antioxidant against the damaging effects of redox cycling quinones and semiquinones by scavenging of EO9(.)- or detoxification of O(2)(.-) and H(2)O(2). C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3b69, Bethesda, MD 20892 USA. EM jbm@helix.nih.gov NR 44 TC 23 Z9 23 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY-JUN PY 2002 VL 234 IS 1 BP 327 EP 333 DI 10.1023/A:1015974126615 PG 7 WC Cell Biology SC Cell Biology GA 564VW UT WOS:000176335100038 PM 12162451 ER PT J AU Nguyen, A Burack, WR Stock, JL Kortum, R Chaika, OV Afkarian, M Muller, WJ Murphy, KM Morrison, DK Lewis, RE McNeish, J Shaw, AS AF Nguyen, A Burack, WR Stock, JL Kortum, R Chaika, OV Afkarian, M Muller, WJ Murphy, KM Morrison, DK Lewis, RE McNeish, J Shaw, AS TI Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID T-CELL ACTIVATION; MAP-KINASE; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; THYMOCYTE DIFFERENTIATION; NEGATIVE SELECTION; POSITIVE SELECTION; GENE ENCODES; C-ELEGANS; PHOSPHORYLATION AB While scaffold proteins are thought to be key components of signaling pathways, their exact function is unknown. By preassembling multiple components of signaling cascades, scaffolds are predicted to influence the efficiency and/or specificity of signaling events. Here we analyze a potential scaffold of the Ras/mitogenactivated protein kinase (MAPK) pathway, kinase suppressor of Ras (KSR), by generating KSR-deficient mice. KSR-deficient mice were grossly normal even though ERK kinase activation was attenuated to a degree sufficient to block T-cell activation and inhibit tumor development. Consistent with its role as a scaffold, high-molecular-weight complexes containing KSR, MEK, and ERK were lost in the absence of KSR. This demonstrates that KSR is a bona fide scaffold that is not required for but enhances signaling via the Ras/MAPK signaling pathway. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol & Immunol, St Louis, MO 63110 USA. Pfizer Inc, Cent Res, Dept Exploratory Med Sci, Groton, CT 06340 USA. Eppley Inst Res Canc & Allied Dis, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. McMaster Univ, Dept Biol, Inst Mol Biol & Biotechnol, Hamilton, ON L8S 4K1, Canada. NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Shaw, AS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave,Box 8118, St Louis, MO 63110 USA. FU NCI NIH HHS [CA90400, R01 CA090400]; NIDDK NIH HHS [DK52809, R01 DK052809] NR 73 TC 175 Z9 177 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 9 BP 3035 EP 3045 DI 10.1128/MCB.22.9.3035-3045.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541EQ UT WOS:000174972600015 PM 11940661 ER PT J AU Zhao, M Gold, L Ginsberg, AM Liang, LF Dean, J AF Zhao, M Gold, L Ginsberg, AM Liang, LF Dean, J TI Conserved furin cleavage site not essential for secretion and integration of ZP3 into the extracellular egg coat of transgenic mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOUSE ZONA-PELLUCIDA; SPERM-BINDING; MONOCLONAL-ANTIBODIES; SURFACE-PROTEINS; FEMALE MICE; GLYCOPROTEINS; RECEPTOR; CELLS; GENE; ENVELOPE AB The extracellular zona pellucida surrounding mammalian eggs is formed by interactions of the ZP1, ZP2, and ZP3 glycoproteins. Female mice lacking ZP2 or ZP3 do not form a stable zona matrix and are sterile. The three zona proteins are synthesized in growing oocytes and secreted prior to incorporation into the zona pellucida. A well-conserved furin site upstream of a transmembrane domain near the carboxyl terminus of each has been implicated in the release of the zona ectodomains from oocytes. However, mutation of the furin site (RNRR --> ANAA) does not affect the intracellular tracking or secretion of an enhanced green fluorescent protein (EGFP)-ZP3 fusion protein in heterologous somatic cells. After transient expression in growing oocytes, normal EGFP-ZP3 and mutant EGFP-ZP3 associate with the inner aspect of the zona pellucida, which is distinct from the plasma membrane. These in vitro results are confirmed in transgenic mice expressing EGFP-ZP3 with or without the mutant furin site. In each case, EGFP-ZP3 is incorporated throughout the width of the zona pellucida and the transgenic mice are fertile. These results indicate that the zona matrix accrues from the inside out and, unexpectedly, suggest that cleavage at the furin site is not required for formation of the extracellular zona pellucida surrounding mouse eggs. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3134, Bethesda, MD 20892 USA. NR 45 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 9 BP 3111 EP 3120 DI 10.1128/MCB.22.9.3111-3120.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541EQ UT WOS:000174972600022 PM 11940668 ER PT J AU Petiniot, LK Weaver, Z Vacchio, M Shen, R Wangsa, D Barlow, C Eckhaus, M Steinberg, SM Wynshaw-Boris, A Ried, T Hodes, RJ AF Petiniot, LK Weaver, Z Vacchio, M Shen, R Wangsa, D Barlow, C Eckhaus, M Steinberg, SM Wynshaw-Boris, A Ried, T Hodes, RJ TI RAG-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ATAXIA-TELANGIECTASIA; THYMIC LYMPHOMA; DEFECTS; GENE; REARRANGEMENT AB Atm-deficient mice die of malignant thymic lymphomas characterized by translocations within the Tcralpha/8 locus, suggesting that tumorigenesis is secondary to aberrant responses to double-stranded DNA (dsDNA) breaks that occur during RAG-dependent V(D)J recombination. We recently demonstrated that development of thymic lymphoma in Atm(-/-) mice was not prevented by loss of RAG-2. Thymic lymphomas that developed in Rag2(-/-) Atm(-/-) mice contained multiple chromosomal abnormalities, but none of these involved the Tcralpha/delta locus. These findings indicated that tumorigenesis in Atm(-/-) mice is mediated by chromosomal translocations secondary to aberrant responses to dsDNA breaks and that V(D)J recombination is an important, but not essential, event in susceptibility. In contrast to these findings, it was recently reported that Ragl(-/-) Atm(-/-) mice do not develop thymic lymphomas, a finding that was interpreted as demonstrating a requirement for RAG-dependent recombination in the susceptibility to tumors in Atm-deficient mice. To test the possibility that RAG-1 and RAG-2 differ in their roles in tumorigenesis, we studied Rag1(-/-) Atm(-/-) mice in parallel to our previous Rag2(-/-) Atm(-/-) study. We found that thymic lymphomas occur at high frequency in Rag1(-/-) Atm(-/-) mice and resemble those that occur in Rag2(-/-) Atm(-/-) mice. These results indicate that both RAG-1 and RAG-2 are necessary for tumorigenesis involving translocation in the Tcralpha/delta locus but that Atm deficiency leads to tumors through a broader RAG-independent predisposition to translocation, related to a generalized defect in dsDNA break repair. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Off Director, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Howard Hughes Med Inst, NIH Res Scholars Program, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Vet Resources Program, Off Res Serv, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 13,Room 5C35, Bethesda, MD 20892 USA. NR 22 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 9 BP 3174 EP 3177 DI 10.1128/MCB.22.9.3174-3177.2002 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541EQ UT WOS:000174972600028 PM 11940674 ER PT J AU Fletcher, TM Xiao, NQ Mautino, G Baumann, CT Wolford, R Warren, BS Hager, GL AF Fletcher, TM Xiao, NQ Mautino, G Baumann, CT Wolford, R Warren, BS Hager, GL TI ATP-dependent mobilization of the glucocorticoid receptor during chromatin remodeling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; DNA-BINDING DOMAIN; MMTV PROMOTER; IN-VIVO; POSITIONED NUCLEOSOMES; TRANSCRIPTION FACTORS; HORMONE RECEPTORS; NUCLEAR FACTOR-1; COMPLEX AB Chromatin remodeling by the glucocorticoid receptor (GR) is associated with activation of transcription at the mouse mammary tumor virus (MMTV) promoter. We reconstituted this nucleoprotein transition with chromatin assembled on MMTV DNA. The remodeling event was ATP dependent and required either a nuclear extract from HeLa cells or purified human Swi/Snf. Through the use of a direct interaction assay (magnetic bead pull-down), we demonstrated recruitment of human Swi/Snf to MMTV chromatin by GR. Unexpectedly, we found that GR is actively displaced from the chromatin template during the remodeling process. ATP-dependent GR displacement was reversed by the addition of apyrase and was specific to chromatin templates. The disengagement reaction could also be induced with purified human Swi/Snf. Although GR apparently dissociated during chromatin remodeling by Swi/Snf, it participated in binding of the secondary transcription factor, nuclear factor 1. These results are paralleled by a recent discovery that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment in living cells. Both the in vitro and in vivo results are consistent with a dynamic model (hit and run) in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, facilitates transcription factor binding, and is simultaneously lost from the template. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, B602 41 Lib Dr, Bethesda, MD 20892 USA. NR 58 TC 98 Z9 102 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3255 EP 3263 DI 10.1128/MCB.22.10.3255-3263.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900005 PM 11971959 ER PT J AU Haller, K Wu, YL Derow, E Schmitt, I Jeang, KT Grassmann, R AF Haller, K Wu, YL Derow, E Schmitt, I Jeang, KT Grassmann, R TI Physical interaction of human T-cell leukemia virus type 1 Tax with cyclin-dependent kinase 4 stimulates the phosphorylation of retinoblastoma protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HTLV-I TAX; PRIMARY HUMAN-LYMPHOCYTES; ONCOGENE PRODUCT TAX; OLIGOCLONAL EXPANSION; HERPESVIRUS-SAIMIRI; GENE-EXPRESSION; ONCOPROTEIN TAX; D2 GENE; ACTIVATION; CDK AB The Tax oncoprotein of human T-cell leukemia virus type 1 (HTLV-1) induces leukemia in transgenic mice and permanent T-cell growth in vitro. In transformed lymphocytes, it acts as an essential growth factor. Tax stimulates the cell cycle in the G, phase by activating the cyclin-dependent kinase (CDK) CDK4 and CDK6 holoenzyme complexes. Here we show that Tax directly interacts with CDK4. This binding to CDK4 was specific, since Tax did not bind to either CDK2 or CDK1. The interaction with CDK4/cyclin D complexes was observed in vitro, in transfected fibroblasts, in HTLV-1-infected T cells, and in adult T-cell leukemia-derived cultures. Binding studies with several point and deletion mutants indicated that the N terminus of Tax mediates the interaction with CDK4. The Tax/CDK complex represented an active holoenzyme which capably phosphorylates the Rb protein in vitro and is resistant to repression by the inhibitor p21(CIP). Binding-deficient Tax mutants failed to activate CDK4, indicating that direct association with Tax is required for enhanced kinase activity. Tax also increased the association of CDK4 with its positive cyclin regulatory subunit. Thus, protein-protein contact between Tax and the components of the cyclin D/CDK complexes provides a further mechanistic explanation for the mitogenic and immortalizing effects of this HTLV-1 oncoprotein. C1 Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-91054 Erlangen, Germany. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Grassmann, R (reprint author), Univ Erlangen Nurnberg, Inst Klin & Mol Virol, Schlossgarten 4, D-91054 Erlangen, Germany. RI Jeang, Kuan-Teh/A-2424-2008 NR 52 TC 105 Z9 106 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3327 EP 3338 DI 10.1128/MCB.22.10.3327-3338.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900012 PM 11971966 ER PT J AU Kanduri, M Kanduri, C Mariano, P Vostrov, AA Quitschke, W Lobanenkov, V Ohlsson, R AF Kanduri, M Kanduri, C Mariano, P Vostrov, AA Quitschke, W Lobanenkov, V Ohlsson, R TI Multiple nucleosome positioning sites regulate the CTCF-mediated insulator function of the H19 imprinting control region SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; CHROMATIN CONFORMATION; MOUSE H19; METHYLATION; GENE; EXPRESSION; PROMOTER; SEQUENCES; UPSTREAM; ELEMENT AB The 5' region of the H19 gene harbors a methylation-sensitive chromatin insulator within an imprinting control region (ICR). Insertional mutagenesis in combination with episomal assays identified nucleosome positioning sequences (NPSs) that set the stage for the remarkably precise distribution of the four target sites for the chromatin insulator protein CTCF to nucleosome linker sequences in the H19 ICR. Changing positions of the NPSs resulted in loss of both CTCF target site occupancy and insulator function, suggesting that the NPSs optimize the fidelity of the insulator function. We propose that the NPSs ensure the fidelity of the repressed status of the maternal Igf2 allele during development by constitutively maintaining availability of the CTCF target sites. C1 Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, S-75236 Uppsala, Sweden. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Ohlsson, R (reprint author), Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, Norbyvagen 18A, S-75236 Uppsala, Sweden. NR 22 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3339 EP 3344 DI 10.1128/MCB.22.10.3339-3344.2002 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900013 PM 11971967 ER PT J AU Park, EK Warner, N Mood, K Pawson, T Daar, IO AF Park, EK Warner, N Mood, K Pawson, T Daar, IO TI Low-molecular-weight protein tyrosine phosphatase is a positive component of the fibroblast growth factor receptor signaling pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID XENOPUS MESODERM INDUCTION; MAP KINASE; PHOSPHOTYROSINE PHOSPHATASE; ACID-PHOSPHATASE; PDGF RECEPTOR; BINDING-SITE; NEURAL CREST; ANIMAL CAPS; CELL FATE; C-SRC AB Low-molecular-weight protein tyrosine phosphatase (LMW-PTP) has been implicated in the regulation of cell growth and actin rearrangement mediated by several receptor tyrosine kinases, including platelet-derived growth factor and epidermal growth factor. Here we identify the Xenopus laevis homolog of LMW-PTP1 (XLPTP1) as an additional positive regulator in the fibroblast growth factor (FGF) signaling pathway during Xenopus development. XLPTP1 has an expression pattern that displays substantial overlap with FGF receptor 1 (FGFR1) during Xenopus development. Using morpholino antisense technology, we show that inhibition of endogenous XLPTP1 expression dramatically restricts anterior and posterior structure development and inhibits mesoderm formation. In ectodermal explants, loss of XLPTP1 expression dramatically blocks the induction of the early mesoderm gene, Xbrachyury (Xbra), by FGF and partially blocks Xbra induction by Activin. Moreover, FGF-induced activation of mitogen-activated protein (MAP) kinase is also inhibited by XLPTP1 morpholino antisense oligonucleotides; however, introduction of RNA encoding XLPTP1 is able to rescue morphological and biochemical effects of antisense inhibition. Inhibition of FGF-induced MAP kinase activity due to loss of XLPTP1 is also rescued by an active Ras, implying that XLPTP1 may act upstream of or parallel to Ras. Finally, XLPTP1 physically associates only with an activated FGFR1, and this interaction requires the presence of SNT1/FRS-2 (FGFR substrate 2). Although LMW-PTP1 has been shown to participate in other receptor systems, the data presented here also reveal XLPTP1 as a new and important component of the FGF signaling pathway. C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada. RP Daar, IO (reprint author), NCI, Regulat Cell Growth Lab, Bldg 560,Room 22-3, Frederick, MD 21702 USA. RI Pawson, Tony/E-4578-2013; OI Daar, Ira/0000-0003-2657-526X NR 89 TC 24 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3404 EP 3414 DI 10.1128/MCB.22.10.3404-3414.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900018 PM 11971972 ER PT J AU Wang, W Fan, J Yang, X Furer-Galban, S de Silanes, IL von Kobbe, C Guo, J Georas, SN Foufelle, F Hardie, DG Carling, D Gorospe, M AF Wang, W Fan, J Yang, X Furer-Galban, S de Silanes, IL von Kobbe, C Guo, J Georas, SN Foufelle, F Hardie, DG Carling, D Gorospe, M TI AMP-activated kinase regulates cytoplasmic HuR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MESSENGER-RNA STABILITY; AU-RICH ELEMENT; PROTEIN-KINASE; BINDING PROTEIN; HEAT-SHOCK; CARCINOMA CELLS; CYCLIN KINASES; UP-REGULATION; ELAV PROTEIN; EXPRESSION AB While transport of RNA-binding protein HuR from nucleus to cytoplasm is emerging as a key regulatory step for HuR function, the mechanisms underlying this process remain poorly understood. Here, we report that the AMP-activated kinase (AMPK), an enzyme involved in responding to metabolic stresses, potently regulates the levels of cytoplasmic HuR. Inhibition of AMPK, accomplished either through cell treatment or by adenovirus infection to express dominant-negative AMPK, was found to increase the level of HuR in the cytoplasm and to enhance the binding of HuR to p21, cyclin 131, and cyclin A mRNA transcripts and elevate their expression and half-lives. Conversely, AMPK activation, achieved by means including infection to express constitutively active AMPK, resulted in reduced cytoplasmic HuR; decreased levels and half-lives of mRNAs encoding p21, cyclin A, and cyclin B1; and diminished HuR association with the corresponding transcripts. We therefore propose a novel function for AMPK as a regulator of cytoplasmic HuR levels, which in turn influences the mRNA-stabilizing function of HuR and the expression of HuR target transcripts. C1 NIA, LCMB, NIH, Baltimore, MD 21224 USA. NIA, Lab Mol Gerontol, Internal Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Asthma & Allergy Ctr, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. INSERM, Ctr Rech Biomed Cordeliers, U465, F-75270 Paris 06, France. Univ Dundee, Sch Life Sci, Dundee DD1 5EH, Scotland. Univ Dundee, Wellcome Trust Bioctr, Dundee DD1 5EH, Scotland. Univ London Imperial Coll Sci Technol & Med, Sch Med, MRC, Ctr Clin Sci, London W12 0NN, England. RP Gorospe, M (reprint author), NIA, LCMB, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Carling, David/F-1943-2014; Lopez de Silanes, Isabel/K-4962-2015; OI Carling, David/0000-0002-2316-1830; Lopez de Silanes, Isabel/0000-0001-6762-9792; Hardie, Grahame/0000-0002-8373-7379 NR 64 TC 162 Z9 166 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3425 EP 3436 DI 10.1128/MCB.22.10.3425-3436.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900020 PM 11971974 ER PT J AU Shabalina, SA AF Shabalina, SA TI Regions of intermolecular complementarity in Escherichia coli 16S rRNA, mRNA, and tRNA molecules SO MOLECULAR BIOLOGY LA English DT Article DE RNA-RNA interactions; computer analysis; pattern of complementarity; E. coli 16S rRNA ID RIBOSOMAL-RNA-COMPLEMENTARITY; DIRECTED CROSS-LINKING; MESSENGER-RNA; 5'-UNTRANSLATED REGION; ENTRY SITE; TRANSLATION; PROTEIN; INITIATION; BINDING; MODEL AB The results of computer analysis of complementarity regions in the sequences of E. coli 16S rRNA, mRNAs and tRNAs are reported in this article. The potential regions of intermolecular RNA-RNA hybridization, or clinger fragments, in 16S rRNA, which are complementary to the sites frequently occurring in mRNAs and tRNAs, were found. Major clinger fragments on 16S rRNA are universal for genes that belong to different functional groups. Our results show there are adaptations of the structural organization of the 16S rRNA molecule to messenger and transport RNA sequences. RNA interaction with clinger fragments may contribute to upregulation of the translation process through increasing the local concentration of mRNAs and tRNAs in the vicinity of the ribosome and their proper positioning, as well as decrease the efficiency of translation through nonspecific mRNA-16SrRNA interactions. C1 NIH, NCBI, NLM, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Math Problems Biol, Pushchino 142292, Moscow Region, Russia. RP Shabalina, SA (reprint author), NIH, NCBI, NLM, Rockville Pike, Bethesda, MD 20894 USA. RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 NR 22 TC 2 Z9 2 U1 0 U2 0 PU MAIK NAUKA/INTERPERIODICA PI NEW YORK PA C/O KLUWER ACADEMIC-PLENUM PUBLISHERS, 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD MAY-JUN PY 2002 VL 36 IS 3 BP 359 EP 364 AR UNSP UDC 577.21 DI 10.1023/A:1016003228275 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 567CX UT WOS:000176468800012 ER PT J AU Iglesias, JM Morgan, RO Jenkins, NA Copeland, NG Gilbert, DJ Fernandez, MP AF Iglesias, JM Morgan, RO Jenkins, NA Copeland, NG Gilbert, DJ Fernandez, MP TI Comparative genetics and evolution of annexin A13 as the founder gene of vertebrate annexins SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE annexin gene family; gene duplication; gene organization; genetic mapping; molecular evolution; phylogenetic analysis ID GENOME DUPLICATIONS; MOUSE GENOME; LINKAGE MAP; EXPRESSION; XIIIB; IDENTIFICATION; SEQUENCE; DNA; CHROMOSOMES; MEMBRANE AB Annexin A 13 (ANXA13) is believed to be the original founder gene of the 12-member vertebrate annexin A family, and it has acquired an intestine-specific expression associated with a highly differentiated intracellular transport function. Molecular characterization of this subfamily in a range of vertebrate species was undertaken to assess coding region conservation, gene organization, chromosomal linkage, and phylogenetic relationships relevant to its progenitor role in the structure-function evolution of the annexin gene superfamily. Protein diagnostic features peculiar to this subfamily include an alternate isoform containing a KGD motif, an elevated basic amino acid content with polyhistidine expansion in the 5'-translated region, and the conservation of 15% core tetrad residues specific to annexin A13 members. The 12 coding exons comprising the 58-kb human ANXA13 gene were deduced from BAC clone sequencing, whereas internal repetitive elements and neighboring genes in chromosome 8q24.12 were identified by contig analysis of the draft sequence from the human genome project. A unique exon splicing pattern in the annexin A13 gene was corroborated by coanalysis of mouse, rat, zebrafish, and pufferfish genomic DNA and determined to be the most distinct of all vertebrate annexins. The putative promoter region was identified by phylogenetic footprinting of potential binding sites for intestine-specific transcription factors. Mouse annexin A13 cDNA was used to map the gene to an orthologous linkage group in mouse chromosome 15 (between Sdc2 and Myc by backcross analysis), and the zebrafish cDNA permitted its localization to linkage group 24. Comparative analysis of annexin A 13 from nine species traced this gene's speciation history and assessed coding region variation, whereas phylogenetic analysis showed it to be the deepest-branching vertebrate annexin, and computational analysis estimated the gene age and divergence rate. The unique, conserved aspects of annexin A13 primary structure, gene organization, and genetic maps identify it as the probable common ancestor of all vertebrate annexins, beginning with the sequential duplication to annexins A7 and All approximately 700 MYA. before the emergence of chordates. C1 Univ Oviedo, Dept Biochem & Mol Biol, E-33006 Oviedo, Spain. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Fernandez, MP (reprint author), Univ Oviedo, Dept Biochem & Mol Biol, Edificio Santiago Gascon, E-33006 Oviedo, Spain. EM pfernandez@bioquimica.uniovi.es OI Fernandez-Fernandez, Maria Pilar/0000-0001-6552-409X NR 47 TC 23 Z9 27 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAY PY 2002 VL 19 IS 5 BP 608 EP 618 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 552EJ UT WOS:000175605900003 PM 11961095 ER PT J AU Wu, XF Wang, F Rao, K Sellers, JR Hammer, JA AF Wu, XF Wang, F Rao, K Sellers, JR Hammer, JA TI Rab27a is an essential component of melanosome receptor for myosin Va SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID KINESIN-LIKE PROTEIN; UNCONVENTIONAL MYOSIN; NUCLEOTIDE EXCHANGE; DILUTE MELANOCYTES; LIGHT-CHAINS; WILD-TYPE; MUTATIONS; TRANSPORT; FAMILY; IDENTIFICATION AB Melanocytes that lack the GTPase Rab27a (ashen) are disabled in myosin Va-dependent melanosome capture because the association of the myosin with the melanosome surface depends on the presence of this resident melanosomal membrane protein. One interpretation of these observations is that Rab27a functions wholly or in part as the melanosome receptor for myosin Va (Myo5a). Herein, we show that the ability of the myosin Va tail domain to localise to the melanosome and generate a myosin Va null (dilute) phenotype in wild-type melanocytes is absolutely dependent on the presence of exon F, one of two alternatively spliced exons present in the tail of the melanocyte-spliced isoform of myosin Va but not the brain-spliced isoform. Exon D, the other melanocyte-specific tail exon, is not required. Similarly, the ability of full-length myosin Va to colocalize with melanosomes and to rescue their distribution in dilute melanocytes requires exon F but not exon D. These results predict that an interaction between myosin Va and Rab27a should be exon F dependent. Consistent with this, Rab27a present in detergent lysates of melanocytes binds to beads coated with purified, full-length melanocyte myosin Va and melanocyte myosin Va lacking exon D, but not to beads coated with melanocyte myosin Va lacking exon F or brain myosin Va. Moreover, the preparation of melanocyte lysates in the presence of GDP rather than guanosine-5'-O-(3-thio)triphosphate reduces the amount of Rab27a bound to melanocyte myosin Va-coated beads by approximately fourfold. Finally, pure Rab27a does not bind to myosin Va-coated beads, suggesting that these two proteins interact indirectly. Together, these results argue that Rab27a is an essential component of a protein complex that serves as the melanosome receptor for myosin Va, suggest that this complex contains at least one additional protein capable of bridging the indirect interaction between Rab27a and myosin Va, and imply that the recruitment of myosin Va to the melanosome surface in vivo should be regulated by factors controlling the nucleotide state of Rab27a. C1 NHLBI, Lab Cell Biol & Mol Cardiol, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Lab Cell Biol & Mol Cardiol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 44 TC 110 Z9 110 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2002 VL 13 IS 5 BP 1735 EP 1749 DI 10.1091/mbc.01-12-0595 PG 15 WC Cell Biology SC Cell Biology GA 555VA UT WOS:000175812900024 PM 12006666 ER PT J AU Egland, KA Kumar, V Duray, P Pastan, I AF Egland, KA Kumar, V Duray, P Pastan, I TI Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancers SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-ANTIGENS; HUMAN-MELANOMA; GENE; CELLS; PROSTATE; FAMILY; IDENTIFICATION; IMMUNOTHERAPY; INHIBITION AB Cancer testis (CT) antigens have an expression pattern that is predominantly restricted to testis in normal tissues, yet they are expressed in many different histological types of cancers. One previously described member of the CT antigen family, XAGE-1, was shown to be expressed in Ewing's sarcomas and rhabdomyosarcomas. Here we show that XAGE-1 is also expressed in breast cancer, prostate cancer, and different types of lung cancers, including lung squamous cell carcinoma, adenocarcinoma, small cell lung carcinoma, and non-small cell lung carcinoma. In addition, XAGE-1 mRNA was present in ovarian cancer, melanoma, glioblastoma, T-cell lymphoma, chronic myelogenous leukemia, and histiocytic lymphoma cell lines. We also characterized the XAGE-1 transcript by primer extension analysis and found that transcription of the XAGE-1 gene is initiated from two distinct start sites, resulting in two overlapping transcripts, XAGE-1a and XAGE-1b. XAGE-1a contains two in-frame ATG translational start codons; whereas XAGE-1b initiates downstream of the first ATG start codon. Our results suggest that XAGE-1b is the dominant transcript, and that translation begins with the second ATG start codon, producing a 9 kDa protein. Because XAGE-1 is expressed in such a diverse range of cancers, it has potential to be used as a target for many cancer immunotherapies. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr MSC 4264,Room 5106, Bethesda, MD 20892 USA. NR 26 TC 31 Z9 40 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2002 VL 1 IS 7 BP 441 EP 450 PG 10 WC Oncology SC Oncology GA 607BK UT WOS:000178770400001 PM 12479262 ER PT J AU Greene, EC Mizuchi, K AF Greene, EC Mizuchi, K TI Direct observation of single MuB polymers: Evidence for a DNA-dependent conformational change for generating an active target complex SO MOLECULAR CELL LA English DT Article ID BACTERIOPHAGE-MU; RETROVIRAL INTEGRATION; TRANSPOSITION PATHWAY; V(D)J RECOMBINATION; STRAND-TRANSFER; SITE SELECTION; B-PROTEIN; MOLECULES; IMMUNITY; TETRAMER AB MuB, an ATIP-dependent DNA binding protein, is critical for selection of target sites on the host chromosome during Mu transposition. We have developed a system for observing the behavior of single MuB polymers bound to an immobilized molecule of DNA. We show that the individual polymers display a broad distribution of disassembly rates and exhibit regional variations in DNA binding. Additionally, ATIP hydrolysis was obligatorily coupled to dissociation of MuB sub-units from the DNA during polymer disassembly. We propose a model in which the formation of an active target complex is mediated by a conformational change within the MuB polymer that is influenced by the sequence of the DNA. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 33 TC 32 Z9 33 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY PY 2002 VL 9 IS 5 BP 1079 EP 1089 DI 10.1016/S1097-2765(02)00514-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 558LD UT WOS:000175967100018 PM 12049743 ER PT J AU Intine, RV Dundr, M Mistelli, T Maraia, RJ AF Intine, RV Dundr, M Mistelli, T Maraia, RJ TI Aberrant nuclear trafficking of La protein leads to disordered processing of associated precursor tRNAs SO MOLECULAR CELL LA English DT Article ID TRANSFER-RNA PRECURSORS; SPLICED TRANSFER-RNA; SACCHAROMYCES-CEREVISIAE; POLYMERASE-III; SCHIZOSACCHAROMYCES-POMBE; SUBNUCLEAR LOCALIZATION; INTERVENING SEQUENCES; NASCENT RNA; EXPORT; YEAST AB Eukaryotic precursor tRNAs undergo extensive processing prior to nuclear export. The first of multiple factors to interact with pre-tRNAs and other nascent transcripts is the La protein. Using suppressor and wild-type tRNAs, we demonstrate that the normal distribution of cellular end-processed and spliced tRNA species is disordered by La proteins that lack a conserved nuclear retention element. Fission yeast or human La mutants that lack this element enter nuclei and stabilize nascent pre-tRNA but are aberrantly exported and fail to support normal tRNA processing. Instead, anomalous 5' and 3' end-containing, spliced tRNAs accumulate, complexed with the mutant La protein. Thus, appropriate nuclear trafficking by La affects the normal order of pre-tRNA processing. C1 NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NR 43 TC 50 Z9 50 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY PY 2002 VL 9 IS 5 BP 1113 EP 1123 DI 10.1016/S1097-2765(02)00533-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 558LD UT WOS:000175967100021 PM 12049746 ER PT J AU Prufer, K Schroder, C Hegyi, K Barsony, J AF Prufer, K Schroder, C Hegyi, K Barsony, J TI Degradation of RXRs influences sensitivity of rat osteosarcoma cells to the antiproliferative effects of calcitriol SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; VITAMIN-D-RECEPTOR; ACUTE PROMYELOCYTIC LEUKEMIA; BREAST-CANCER CELLS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ACID RECEPTOR; 1,25-DIHYDROXYVITAMIN D-3; THYROID-HORMONE; DEPENDENT DEGRADATION; MEDIATED DEGRADATION AB Several cell lines, including ROS17/2.8 rat osteosarcoma (ROS) cells, contain functional VDRs and RXRs but are resistant to the anti proliferative effects of calcitriol and retinoids. We explored the role of receptor degradation in this hormone resistance. Results of transactivation assays indicated that ROS cells contain insufficient amounts of RXR to activate a DR-1 reporter, and Western blot analyses of cell extracts showed that the degradation of RXR is accelerated and produces an aberrant 45-kDa RXR. We stably expressed functional fluorescent chimeras of VDR and RXR [green fluorescent protein (GFP)-VDR; yellow fluorescent protein (YFP)-RXR] to evaluate degradation mechanisms and the impact of excess receptor expression on antiproliferative effects. Microscopy showed a diminished expression of YFP-RXR in ROS cells compared with the expression in CV-1 cells. Treatment with inhibitors of proteasomal degradation (lactacystin and MG132) selectively enhanced GFP-VDR and YFP-RXR expression and also increased the endogenous levels of VDR and RXR. Expression of GFP-VDR had no effect on the sensitivity of ROS cells to calcitriol. Increases of RXR levels by YFP-RXR expression, drug treatments, or the combination of the two, however, restored the growth-inhibitory effects of calcitriol and 9-cis-RA and restored p21 induction by calcitriol. These studies revealed that an accelerated and aberrant RXR degradation could cause resistance to the antiproliferative effects of calcitriol and retinoids in ROS cells. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Barsony, J (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, 8 Ctr Dr,Room 422, Bethesda, MD 20892 USA. RI Hegyi, Krisztina/A-1778-2011 NR 57 TC 22 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2002 VL 16 IS 5 BP 961 EP 976 DI 10.1210/me.16.5.961 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 546UP UT WOS:000175293500006 PM 11981032 ER PT J AU Ferrand, PE Parry, S Sammel, M Macones, GA Kuivaniemi, H Romero, R Strauss, JF AF Ferrand, PE Parry, S Sammel, M Macones, GA Kuivaniemi, H Romero, R Strauss, JF TI A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE amnion epithelial cells; extracellular matrix; genetic association; PPROM; transcriptional control ID FETAL MEMBRANES; IV COLLAGENASE; GENE; MATRIX-METALLOPROTEINASE-9; EXPRESSION; CELLS; LABOR; SUSCEPTIBILITY; DISEASE AB Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macropliage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans. C1 Univ Penn, Med Ctr, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Biostat & Clin Epidemiol, Philadelphia, PA 19104 USA. Hutzel Hosp, Natl Inst Child Hlth & Human Dev, Perinatol Res Branch, Detroit, MI 48201 USA. RP Strauss, JF (reprint author), 421 Curie Blvd 1354 BRB 2, Philadelphia, PA 19104 USA. OI Kuivaniemi, Helena/0000-0001-5753-8766 FU FIC NIH HHS [D43/TW01272]; NICHD NIH HHS [HD34612] NR 30 TC 103 Z9 107 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAY PY 2002 VL 8 IS 5 BP 494 EP 501 DI 10.1093/molehr/8.5.494 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 554TY UT WOS:000175754300011 PM 11994547 ER PT J AU Aliberti, J Sher, A AF Aliberti, J Sher, A TI Positive and negative regulation of pathogen induced dendritic cell function by G-protein coupled receptors SO MOLECULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 2nd Al Ain Immunology Meeting on Immunoregulation CY MAR 11, 2001-MAR 14, 2002 CL AL AIN, U ARAB EMIRATES DE Toxoplasma gondii; IL-12; CCR5; dendritic cell; lipoxin ID INTERLEUKIN-12; INFECTION; CCR5; RESISTANCE; ACTIVATION; INDUCTION; INNATE; IL-12; GAMMA; MICE AB The induction of IL-12 from dendritic cells (DC) is a major initiating step in host resistance to intracellular pathogens. We have studied the regulation of this response using an in vivo model in which IL-12 production by splenic CD8alpha(+) DC is followed after injection of a soluble extract (STAB) of the protozoan parasite Toxoplasma gondii. Our findings indicate that the potent IL-12 response observed is highly dependent on both the chemokine receptor CCR5 and G(i)-protein coupled signaling. In addition, we have examined the basis of the unresponsiveness of DC to secondary STAB injection which occurs following primary exposure to this parasite stimulus. Our results demonstrate that this refractory state correlates with the down-regulation of CCR5 expression on DC which, in turn, appears to depend on the induction of endogenous lipoxin A(4) (LXA(4)), a product of arachidonic acid metabolism. Since LXA(4) is known to also signal through a G-protein coupled receptor pathway, these findings taken together support a major role for G-protein signaling in the regulation of microbial-induced DC function. Published by Elsevier Science Ltd. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD USA. RP Sher, A (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 15 TC 7 Z9 8 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 MAY PY 2002 VL 38 IS 12-13 BP 891 EP 893 AR PII S0161-5890(02)00015-9 DI 10.1016/S0161-5890(02)00015-9 PG 3 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 552QU UT WOS:000175631700004 PM 12009566 ER PT J AU Sun, PD AF Sun, PD TI To kill or not to kill SO MOLECULAR IMMUNOLOGY LA English DT Editorial Material C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2002 VL 38 IS 14 SI SI BP 1005 EP 1006 AR PII S0161-5890(02)00029-9 DI 10.1016/S0161-5890(02)00029-9 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 558VC UT WOS:000175986600001 ER PT J AU Boyington, JC Sun, PD AF Boyington, JC Sun, PD TI A structural perspective on MHC class I recognition by killer cell immunoglobulin-like receptors SO MOLECULAR IMMUNOLOGY LA English DT Review DE NK cell receptors; receptor recognition; allotype specificity; KIR; HLA-C ID COMPLEX CLASS-I; HLA-B ALLOTYPES; INHIBITORY RECEPTOR; CRYSTAL-STRUCTURE; DIRECT BINDING; MOLECULAR-CLONING; MEDIATED LYSIS; NK CLONES; FUNCTIONAL TRANSFER; ANTIGEN EXPRESSION AB Killer cell immunoglobulin-like receptors (KIR) play a critical role in the regulation of natural killer (NK) cell activity through their recognition of class I MHC Molecules expressed on target cells. KIR recognition provides vital information to NK cells about whether a target cell should be lysed or spared. Understanding the molecular mechanism of this recognition has remained a strong focus of investigation. This has resulted in the crystal structures of several members of the KIR family and more recently the determinations of the three dimensional structures of KlR2DL2 and KIR2DL1 complexed with their respective ligands. HLA-Cw3 and HLA-Cw4. A strong structural conservation has been revealed both in the receptor design and in the overall mode of KIR binding to class I molecules. Nevertheless, distinct differences in the receptor binding sites allow for high specificity between ligands. Furthermore, unexpected similarities with T-cell receptor (TCR) recognition of MHC molecules are also observed. The detailed interactions between KIR and HLA-C Molecules and their functional implications will be reviewed here. Published by Elsevier Science Ltd. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 84 TC 97 Z9 99 U1 0 U2 2 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 MAY PY 2002 VL 38 IS 14 SI SI BP 1007 EP 1021 AR PII S0161-5890(02)00030-5 DI 10.1016/S0161-5890(02)00030-5 PG 15 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 558VC UT WOS:000175986600002 PM 11955593 ER PT J AU Natarajan, K Dimasi, N Wang, J Margulies, DH Mariuzza, RA AF Natarajan, K Dimasi, N Wang, J Margulies, DH Mariuzza, RA TI MHC class I recognition by Ly49 natural killer cell receptors SO MOLECULAR IMMUNOLOGY LA English DT Review DE natural killer (NK) cells; NK receptors; Ly49; MHC ID CRYSTAL-STRUCTURE; COMPLEX; LIGAND; CD8-ALPHA-ALPHA; DOMAINS; NKG2D; SITE AB Natural killer (NK) cell function is regulated by NK receptors that bind either classical MHC class I (MHC-1) molecules or their structural relatives (MICA. RAE-I and H-60). Two distinct families of NK receptors have been identified: the C-type lectin-like family (Ly49, NKG2D and CD94/NKG2) and the immunoglobulin-like family (KIRs and LIRs). Here, we e describe the crystal structure of the C-type lectin-like NK receptor (Ly49A), bound to its MHC-1 ligand (H-2D(d)). We also discuss results from recent mutagenesis studies of the Ly49A/H-2D(d) interaction in the context of the complex structure. (C) 2002 Published by Elsevier Science Ltd. C1 NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 24 TC 21 Z9 22 U1 0 U2 3 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 MAY PY 2002 VL 38 IS 14 SI SI BP 1023 EP 1027 AR PII S0161-5890(02)00031-7 DI 10.1016/S0161-5890(02)00031-7 PG 5 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 558VC UT WOS:000175986600003 PM 11955594 ER PT J AU Allison, TJ Garboczi, DN AF Allison, TJ Garboczi, DN TI Structure of gamma delta T cell receptors and their recognition of non-peptide antigens SO MOLECULAR IMMUNOLOGY LA English DT Review DE gamma delta T lymphocytes; T cell receptors; non-peptide antigens ID HEAT-SHOCK PROTEIN; MYCOBACTERIUM-TUBERCULOSIS; PERIPHERAL-BLOOD; ALPHA-BETA; IN-VITRO; ISOPENTENYL PYROPHOSPHATE; ISOPRENOID BIOSYNTHESIS; LISTERIA-MONOCYTOGENES; LYMPHOCYTES-T; FAB FRAGMENT AB The gammadelta T cell receptors (TCRs) and alphabeta TCRs are similar in both sequence and structure: however gammadelta(+) and alphabeta(+) T cells are not merely similar lymphocytes with Subtly different receptors. These cell types differ in several ways. including the types of antigens recognized, the mechanism of antigen presentation and recognition and the mechanism and kinetics of downstream signaling events. gammadelta TCRs can directly recognize antigens in the form of intact proteins or non-peptidic compounds, unlike alphabeta TCRs which recognize peptide antigens bound to major histocompatibility complex molecules (MHC). One of the major classes of human gammadelta(+) T cells expresses Vgamma9Vdelta2 TCRs which recognize pyrophosphomonoester. alkylamine and aminobisphosphonate antigens, This review focuses on the recently determined structure of a Vgamma9Vdelta2 TCR, with emphasis on antigen recognition and receptor signaling. (C) 2002 Published by Elsevier Science Ltd. C1 NIAID, Struct Biol Sect, Immunogenet Lab, Rockville, MD 20852 USA. RP Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM garboczi@nih.gov NR 91 TC 27 Z9 32 U1 1 U2 4 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 MAY PY 2002 VL 38 IS 14 SI SI BP 1051 EP 1061 AR PII S0161-5890(02)00034-2 DI 10.1016/S0161-5890(02)00034-2 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 558VC UT WOS:000175986600006 PM 11955597 ER PT J AU Radaev, S Sun, P AF Radaev, S Sun, P TI Recognition of immunoglobulins by Fc gamma receptors SO MOLECULAR IMMUNOLOGY LA English DT Review DE Fc receptors; immunoglobulins; immune complexes; crystal structures; Fc gamma RIII ID AFFINITY IGE RECEPTOR; EPSILON-RI-ALPHA; CRYSTAL-STRUCTURE; BINDING-SITE; EFFECTOR FUNCTIONS; RHEUMATOID-FACTOR; CELL ACTIVATION; MOLECULAR-BASIS; COMPLEX; FRAGMENT AB Fc receptors mediate antibody dependent inflammatory response and cytotoxicity as well as certain autoimmune dysfunctions. Fcgamma receptors interact with IgG antibodies by binding the Fc portion of the antibody in asymmetric fashion creating a 1:1 receptor-ligand stoichiometry. Regions of the C-terminal domain of Fc receptors including the BC. C'E. FG loops. and the C' beta-strand interact with immunoglobulins. The lower hinge region of the antibody contribute most of the binding to the low affinity Fcgamma receptors. Carbohydrates, attached to the conserved glycoslation site on Fc portion of an antibody are critical to the recognition of immunoglobulins by the affinity Fcgamma receptor. They are likely to function as a substitution for the hydrophobic core to preserve an optimal lower hinge conformation for the receptor binding. Subtype specificities of FcgammaRIII receptor probably are determined by the length of the lower hinge regions of immunoglobulins, but not their amino acid composition as revealed by the binding study of the lower hinge peptides. These studies also paved a new way for designing of novel therapeutic compounds in fighting autoimmune diseases. Published by Elsevier Science Ltd. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, P (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 51 TC 74 Z9 74 U1 0 U2 2 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 MAY PY 2002 VL 38 IS 14 SI SI BP 1073 EP 1083 AR PII S0161-5890(02)00036-6 DI 10.1016/S0161-5890(02)00036-6 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 558VC UT WOS:000175986600008 PM 11955599 ER PT J AU Jayanthi, S McCoy, MT Ladenheim, B Cadet, JL AF Jayanthi, S McCoy, MT Ladenheim, B Cadet, JL TI Methamphetamine causes coordinate regulation of Src, Cas, Crk, and the Jun N-terminal kinase-Jun pathway SO MOLECULAR PHARMACOLOGY LA English DT Article ID DISMUTASE TRANSGENIC MICE; ACTIVATED PROTEIN-KINASE; C-JUN; INDUCED NEUROTOXICITY; TRANSCRIPTION FACTORS; LIPID-PEROXIDATION; INDUCED APOPTOSIS; MAP KINASE; KAPPA-B; IN-VIVO AB The clinical abuse of methamphetamine (METH) is a major concern because it can cause long-lasting neurodegenerative effects in humans. Current concepts of the molecular mechanisms underlying these complications have centered on the formation of reactive oxygen species. Herein, we provide cDNA microarray evidence that METH administration caused the induction of c-Jun and of other members involved in the pathway leading to c-Jun activation [stress-activated protein kinase/Jun N-terminal kinase (JNK3), Crk-associated substrate-Cas and c-Src] after environmental stresses or cytokine stimulation. Reverse transcription-polymerase chain reaction analysis confirmed these increases and also showed that the expression of JNK1 and JNK3 but not JNK2 was also increased in the METH-treated mice. Western blot analysis showed that METH increased the expression of c-Jun phosphorylated at serine-63 and serine-73 residues. Other upstream members of the JNK pathway, including phosphorylated JNKs, mitogen-activated protein kinase kinase 4, mitogen-activated protein kinase kinase 7, Crk II, Cas, and c-Src were also increased at the protein level. These values returned to baseline by 1 week after drug treatment. These results are discussed in terms of their support for a possible role of the activation of the JNK/Jun pathway in the pathophysiological effects of METH. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, 5500 Nathan Shock Drive, Baltimore, MD 21224 USA. NR 55 TC 49 Z9 51 U1 1 U2 4 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 MAY PY 2002 VL 61 IS 5 BP 1124 EP 1131 DI 10.1124/mol.61.5.1124 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543ZL UT WOS:000175133700020 PM 11961130 ER PT J AU Fraites, TJ Schleissing, MR Shanely, RA Walter, GA Cloutier, DA Zolotukhin, I Pauly, DF Raben, N Plotz, PH Powers, SK Kessler, PD Byrne, BJ AF Fraites, TJ Schleissing, MR Shanely, RA Walter, GA Cloutier, DA Zolotukhin, I Pauly, DF Raben, N Plotz, PH Powers, SK Kessler, PD Byrne, BJ TI Correction of the enzymatic and functional deficits in a model of Pompe disease using adeno-associated virus vectors SO MOLECULAR THERAPY LA English DT Article DE glycogen storage disease type II; gene therapy; cardiovascular diseases; lysosomal storage diseases; musculoskeletal diseases ID ACID-ALPHA-GLUCOSIDASE; GENERALIZED GLYCOGEN-STORAGE; SKELETAL-MUSCLE; GENE-TRANSFER; INTRAMUSCULAR INJECTION; CULTURED FIBROBLASTS; IMMUNOCOMPETENT MICE; MALTASE DEFICIENCY; LYSOSOMAL GLYCOGEN; SEROTYPE VECTORS AB Pompe disease is a lysosomal storage disease caused by the absence of acid alpha-1,4 glucosidase (GAA). The pathophysiology of Pompe disease includes generalized myopathy of both cardiac and skeletal muscle. We sought to use recombinant adeno-associated virus (rAAV) vectors to deliver functional GAA genes in vitro and in vivo. Myotubes and fibroblasts from Pompe patients were transduced in vitro with rAAV2-GAA. At 14 days postinfection, GAA activities were at least fourfold higher than in their respective untransduced controls, with a 10-fold increase observed in GAA-deficient myotubes. BALB/c and Gaa(-/-) mice were also treated with rAAV vectors. Persistent expression of vector-derived human GAA was observed in BALB/c mice up to 6 months after treatment. In Gaa(-/-) mice, intramuscular and intramyocardial delivery of rAAV2-Gaa (carrying the mouse Gaa cDNA) resulted in near-normal enzyme activities. Skeletal muscle contractility was partially restored in the soleus muscles of treated Gaa(-/-) mice, indicating the potential for vector-mediated restoration of both enzymatic activity and muscle function. Furthermore, intramuscular treatment with a recombinant AAV serotype 1 vector (rAAV1-Gaa) led to nearly eight times normal enzymatic activity in Gaa(-/-) mice, with concomitant glycogen clearance as assessed in vitro and by proton magnetic resonance spectroscopy. C1 Johns Hopkins Univ, Sch Med, Div Cardiol, Dept Med,Peter Belfer Cardiac Lab, Baltimore, MD 21287 USA. Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA. Univ Florida, Coll Hlth & Human Performance, Ctr Exercise Sci, Gainesville, FL 32610 USA. NIH, NIAMSD, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. RP Byrne, BJ (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Dept Med,Peter Belfer Cardiac Lab, Baltimore, MD 21287 USA. EM bbyrne@ufl.edu FU NHLBI NIH HHS [P0-HL59412A] NR 52 TC 78 Z9 81 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2002 VL 5 IS 5 BP 571 EP 578 DI 10.1006/mthe.2002.0580 PN 1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 550BC UT WOS:000175482600012 PM 11991748 ER PT J AU Palacio, LG Rivera, D Builes, JJ Jimenez, ME Salgar, M Anaya, JM Jimenez, I Camargo, M Arcos-Burgos, M Sanchez, JL AF Palacio, LG Rivera, D Builes, JJ Jimenez, ME Salgar, M Anaya, JM Jimenez, I Camargo, M Arcos-Burgos, M Sanchez, JL TI Multiple sclerosis in the tropics: genetic association to STR's loci spanning the HLA and TNF SO MULTIPLE SCLEROSIS LA English DT Article DE Colombia; D6S265; D6S273; D6S276; D6S291; genetics; HLA; linkage disequilibrium; microsatellites; multiple sclerosis; STR's; TNF-1 ID NECROSIS-FACTOR-ALPHA; LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY LOCI; CLINICAL-FEATURES; IFN-GAMMA; DQ-ALPHA; POPULATION; COLOMBIA; POLYMORPHISM; HAPLOTYPE AB Clear evidence has been presented correlating gene polymorphisms at 6p21.3-21.4 (containing HLA and TNF) and the predisposition to acquire multiple sclerosis (MS). In a previous study, we found that polymorphisms at HLA DQA1 were associated with being or not being predisposed to MS in individuals inhabiting the tropics, where the prevalence of MS is significantly lower than in subtropical areas. Here, we tested the hypothesis that polymorphisms at D6S276, D6S265, D6S273 and D6S291 microsatellite loci are in strong linkage disequilibrium with a major genetic factor Predisposing to MS. These microsatellites span the 6p21.3 region with intervals of 5 cM establishing particular landmarks for the HLA and TNF loci. Thirty-five MS patients and 35 controls, age, sex, social, ethnically and geographically matched healthy individuals, were studied. After testing the fit of gene frequencies to the normal distribution and performing the correlation for multiple comparisons, we found significant differences among the case and the control frequencies for the allele 202 belonging to the marker D6S276 (Pc = 0.00455) and for the allele 114 belonging to the marker D6S265 (Pc = 0.0084). For these two alleles at different loci, we found higher frequencies in the cases than in the controls. A nonsignificant p value was found in testing the existence of linkage disequilibrium among the studied loci in the cases and in the controls. In conclusion, the current study adds evidence to the established association among polymorphisms of genes located at 6p21.3-21.4 and MS. Furthermore, because of the distribution of the tested microsatellite loci, the more probable critical region could be correlated with the TNF neighborhood. C1 Neurol Inst Antioquia, Medellin 46 36, Colombia. Univ Antioquia, Inst Biol, Populat Genet Mutacarcinogenesis & Genet Epidemio, Calle Barranquilla 1229, Medellin, Colombia. Corp Biol Res, Medellin, Colombia. RP Arcos-Burgos, M (reprint author), NHGRI, NIH, Med Genet Branch, 10 Ctr Dr MSG 1852, Bethesda, MD 20892 USA. RI Anaya, Juan-Manuel/J-1960-2016; OI Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario, Biblioteca/0000-0003-3491-9392; Builes Gomez, Juan Jose/0000-0001-8403-6809 NR 56 TC 16 Z9 17 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD MAY PY 2002 VL 8 IS 3 BP 249 EP 255 DI 10.1191/1352458502ms804oa PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 561NV UT WOS:000176148300011 PM 12120698 ER PT J AU McKay, R AF McKay, R TI A more astonishing hypothesis SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID IN-VIVO; CELLS; MYOCARDIUM C1 NINCDS, NIH, Bethesda, MD 20892 USA. RP McKay, R (reprint author), NINCDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 11 TC 18 Z9 19 U1 0 U2 0 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 MAY PY 2002 VL 20 IS 5 BP 426 EP 427 DI 10.1038/nbt0502-426 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 548AE UT WOS:000175364800009 PM 11981544 ER PT J AU Pan, Z Yang, DM Nararaj, RY Nosek, TA Nishi, M Takeshima, H Cheng, HP Ma, JJ AF Pan, Z Yang, DM Nararaj, RY Nosek, TA Nishi, M Takeshima, H Cheng, HP Ma, JJ TI Dysfunction of store-operated calcium channel in muscle cells lacking mg29 SO NATURE CELL BIOLOGY LA English DT Article ID MUTANT MICE LACKING; SKELETAL-MUSCLE; RYANODINE-RECEPTOR; CA2+ ENTRY; MAST-CELLS; RELEASE; INHIBITION; DEPLETION; FIBERS; SK-AND-F-96365 AB The store-operated calcium channel (SOC) located in the plasma membrane (PM) mediates capacitative entry of extracellular calcium after depletion of intracellular calcium stores in the endoplasmic or sarcoplasmic reticulum (ER/SR)(1,2). An intimate interaction between the PM and the ER/SR is essential for the operation of this calcium signalling pathway(3-5). Mitsugumin 29 (MG29) is a synaptophysin-family-related protein located in the junction between the PM and SR of skeletal muscle(6,7). Here, we identify SOC in skeletal muscle and characterise its regulation by MG29 and the ryanodine receptor (RyR) located in the SR. Targeted deletion of mg29 alters the junctional membrane structure, causes severe dysfunction of SOC and SR calcium homeostasis and increases the susceptibility of muscle to fatigue stimulation(8). Severe dysfunction of SOC is also identified in muscle cells lacking both type 1 and type 3 RyRs, indicating that SOC activation requires an intact interaction between the PM and the SR, and is linked to conformational changes of RyRs. Whereas defective SOC seems to be inconsequential to short-term excitation contraction coupling, the slow cumulative calcium entry through SOC is crucial for long-term calcium homeostasis, such that reduced SOC activity exaggerates muscle fatigue under conditions of intensive exercise. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Tohoku Univ, Grad Sch Med, Dept Biochem, Sendai, Miyagi 9808575, Japan. Japan Sci & Technol Corp, CREST, Sendai, Miyagi 9808575, Japan. RP Pan, Z (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, 675 Hoes Lane, Piscataway, NJ 08854 USA. NR 28 TC 115 Z9 120 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2002 VL 4 IS 5 BP 379 EP 383 DI 10.1038/ncb788 PG 5 WC Cell Biology SC Cell Biology GA 547GR UT WOS:000175325100020 PM 11988740 ER PT J AU Brody, LC AF Brody, LC TI CHEKs and balances: accounting for breast cancer SO NATURE GENETICS LA English DT Editorial Material ID CHK2 AB Two highly penetrant loci have been linked to familial breast cancer (BRCA1 and BRCA2), but do not explain most breast cancer familial aggregation. A new study suggests that a variant in a gene involved in DNA repair may account for some of this unexplained risk. C1 NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Brody, LC (reprint author), NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NR 13 TC 6 Z9 6 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 MAY PY 2002 VL 31 IS 1 BP 3 EP 4 DI 10.1038/ng0502-3 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 547ZF UT WOS:000175362500002 PM 11984555 ER PT J AU Agarwal, AK Arioglu, E de Almeida, S Akkoc, N Taylor, SI Bowcock, AM Barnes, RI Garg, A AF Agarwal, AK Arioglu, E de Almeida, S Akkoc, N Taylor, SI Bowcock, AM Barnes, RI Garg, A TI AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34 SO NATURE GENETICS LA English DT Article ID LYSOPHOSPHATIDIC ACID ACYLTRANSFERASES; CDNA CLONING; EXPRESSION; LOCALIZATION; GENE AB Congenital generalized lipodystrophy is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. We report several different mutations of the gene (AGPAT2) encoding 1-acylglycerol-3-phosphate O-acyltransferase 2 in 20 affected individuals from 11 pedigrees of diverse ethnicities showing linkage to chromosome 9q34. The AGPAT2 enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, a key intermediate in the biosynthesis of triacylglycerol and glycerophospholipids. AGPAT2 mRNA is highly expressed in adipose tissue. We conclude that mutations in AGPAT2 may cause congenital generalized lipodystrophy by inhibiting triacylglycerol synthesis and storage in adipocytes. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Div Nutr & Metab Dis, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, McDermott Ctr Human Growth & Dev, Ctr Human Nutr, Dallas, TX 75390 USA. NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. Hosp Dona Estefania, Serv Genet Med, Lisbon, Portugal. Dokuz Eylul Univ, Sch Med, Dept Internal Med, Izmir, Turkey. Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Univ Texas, SW Med Ctr, McDermott Ctr Human Growth & Dev, Dallas, TX USA. RP Garg, A (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Div Nutr & Metab Dis, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Akkoc, Nurullah/D-9870-2011; OI Akkoc, Nurullah/0000-0002-3718-171X; Oral, Elif/0000-0002-9171-1144; Bowcock, Anne/0000-0001-8691-9090 NR 15 TC 259 Z9 269 U1 2 U2 9 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 MAY PY 2002 VL 31 IS 1 BP 21 EP 23 DI 10.1038/ng880 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 547ZF UT WOS:000175362500009 PM 11967537 ER PT J AU Sehnert, AJ Huq, A Weinstein, BM Walker, C Fishman, M Stainier, DYR AF Sehnert, AJ Huq, A Weinstein, BM Walker, C Fishman, M Stainier, DYR TI Cardiac troponin T is essential in sarcomere assembly and cardiac contractility SO NATURE GENETICS LA English DT Article ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; SUDDEN-DEATH; CARDIOVASCULAR-SYSTEM; MUTATIONS; ZEBRAFISH; TROPOMYOSIN; DISEASE; CHAIN; GENES AB Mutations of the gene (TNNT2) encoding the thin-filament contractile protein cardiac troponin T are responsible for 15% of all cases of familial hypertrophic cardiomyopathy, the leading cause of sudden death in young athletes(1,2). Mutant proteins are thought to act through a dominant-negative mode that impairs function of heart muscle(3). TNNT2 mutations can also lead to dilated cardiomyopathy, a leading cause of heart failure(4). Despite the importance of cardiac troponin T in human disease, its loss-of-function phenotype has not been described. We show that the zebrafish silent heart (sih) mutation affects the gene tnnt2. We characterize two mutated alleles of sih that severely reduce tnnt2 expression: one affects mRNA splicing, and the other affects gene transcription. Tnnt2, together with alpha-tropomyosin (Tpma) and cardiac troponins C and I (Tnni3), forms a calcium-sensitive regulatory complex within sarcomeres(5). Unexpectedly, in addition to loss of Tnnt2 expression in sih mutant hearts, we observed a significant reduction in Tpma and Tnni3, and consequently, severe sarcomere defects. This interdependence of thin-filament protein expression led us to postulate that some mutations in tnnt2 may trigger misregulation of thin-filament protein expression, resulting in sarcomere loss and myocyte disarray, the life-threatening hallmarks of TNNT2 mutations in mice and humans(6,7). C1 Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Genet Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Program Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Stainier, DYR (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, 513 Parnassus Ave,Box 0448, San Francisco, CA 94143 USA. NR 25 TC 307 Z9 314 U1 0 U2 25 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 MAY PY 2002 VL 31 IS 1 BP 106 EP 110 DI 10.1038/ng875 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 547ZF UT WOS:000175362500024 PM 11967535 ER PT J AU Moody, DB Briken, V Cheng, TY Roura-Mir, C Guy, MR Geho, DH Tykocinski, ML Besra, GS Porcelli, SA AF Moody, DB Briken, V Cheng, TY Roura-Mir, C Guy, MR Geho, DH Tykocinski, ML Besra, GS Porcelli, SA TI Lipid length controls antigen entry into endosomal and nonendosomal pathways for CDIb presentation SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL RECOGNITION; PRESENTING MOLECULES; LIPOGLYCAN ANTIGENS; STRUCTURAL REQUIREMENTS; CYTOPLASMIC TAIL; SELF-GLYCOLIPIDS; HUMAN CD1B; MOUSE CD1; BINDING; LYMPHOCYTES AB CD I proteins present various glycolipid antigens to T cells, but the cellular mechanisms that control which particular glycolipids generate T cell responses are not understood. We show here that T cell recognition of glucose monomycolate antigens with long (C-80) alkyl chains involves the delivery of CD Ib proteins and antigens to late endosomes in a process that takes several hours. In contrast, analogs of the same antigen with shorter (C-32) alkyl chains are rapidly, but inefficiently, presented by cell surface CD Ib proteins. Dendritic cells (DCs) preferentially present long-chain glycolipids, which results, in part, from their rapid internalization and selective delivery of antigens to endosomal compartments. Nonprofessional antigen-presenting cells, however, preferentially present short-chain glycolipids because of their lack of prominent endosomal presentation pathways. Because long alkyl chain length distinguishes certain microbial glycolipids from common mammalian glycolipids, these findings suggest that DCs use a specialized endosomal-loading pathway to promote preferential recognition of glycolipids with a more intrinsically foreign structure. C1 Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Univ Newcastle Upon Tyne, Sch Med, Dept Microbiol & Immunol, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Moody, DB (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Smith Bldg Room 514,1 Jimmy Fund Way, Boston, MA 02115 USA. RI Roura-Mir, Carme/D-4538-2013 OI Roura-Mir, Carme/0000-0003-0514-337X FU NCI NIH HHS [CA74958]; NIAID NIH HHS [AI48933, AI 31044, AI 38960, AI45889, AI49313]; NIAMS NIH HHS [ARO1988] NR 45 TC 114 Z9 115 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2002 VL 3 IS 5 BP 435 EP 442 DI 10.1038/ni780 PG 8 WC Immunology SC Immunology GA 548VU UT WOS:000175411200011 PM 11938350 ER PT J AU Sotiriou, S Gispert, S Cheng, J Wang, YH Chen, A Hoogstraten-Miller, S Miller, GF Kwon, O Levine, M Guttentag, SH Nussbaum, RL AF Sotiriou, S Gispert, S Cheng, J Wang, YH Chen, A Hoogstraten-Miller, S Miller, GF Kwon, O Levine, M Guttentag, SH Nussbaum, RL TI Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival SO NATURE MEDICINE LA English DT Article ID DEHYDROASCORBIC ACID; PREMATURE-INFANT; CLONING; PLASMA; CELLS AB The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy(1,2), presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen(3). We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts from homozygous Slc23a1(-/-) mice had less than 5% of normal ascorbic-acid uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1(-/-) mice. Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1(-/-) fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport. Slc23a1(-/-) mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1(-/-) mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period. C1 NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Director, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Neonatol, Philadelphia, PA 19104 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RI Guttentag, Susan/D-8705-2013 OI Guttentag, Susan/0000-0003-4420-5879 NR 25 TC 192 Z9 198 U1 1 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2002 VL 8 IS 5 BP 514 EP 517 DI 10.1038/nm0502-514 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 547ZW UT WOS:000175336800038 PM 11984597 ER PT J AU Gerdeman, GL Ronesi, J Lovinger, DM AF Gerdeman, GL Ronesi, J Lovinger, DM TI Postsynaptic endocannabinoid release is critical to long-term depression in the striatum SO NATURE NEUROSCIENCE LA English DT Article ID CB1 CANNABINOID RECEPTOR; EXCITATORY SYNAPTIC TRANSMISSION; ACID AMIDE HYDROLASE; ENDOGENOUS CANNABINOIDS; KNOCKOUT MICE; DORSAL STRIATUM; PURKINJE-CELLS; BASAL GANGLIA; RAT; NEURONS AB The striatum functions critically in movement control and habit formation. The development and function of cortical input to the striatum are thought to be regulated by activity-dependent plasticity of corticostriatal glutamatergic synapses. Here we show that the induction of a form of striatal synaptic plasticity, long-term depression (LTD), is dependent on activation of the CB1 cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic depression. The endocannabinoid necessary for striatal LTD is thus likely to be released postsynaptically as a retrograde messenger. These findings demonstrate a new role for endocannabinoids in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control. C1 Vanderbilt Univ, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN 37232 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, 158H Pk 5 Bldg, Rockville, MD 20852 USA. FU NIDA NIH HHS [DA05923]; NINDS NIH HHS [NS30470] NR 48 TC 414 Z9 426 U1 1 U2 11 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 MAY PY 2002 VL 5 IS 5 BP 446 EP 451 DI 10.1038/nn832 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 546JY UT WOS:000175272000015 PM 11976704 ER PT J AU Thomas, OM Cumming, BG Parker, AJ AF Thomas, OM Cumming, BG Parker, AJ TI A specialization for relative disparity in V2 SO NATURE NEUROSCIENCE LA English DT Article ID RANDOM-DOT STEREOGRAMS; INFERIOR TEMPORAL CORTEX; VISUAL-CORTEX; DEPTH DISCRIMINATION; BINOCULAR DISPARITY; V1; RESPONSES; NEURONS; MOTION; REPRESENTATION AB Stereoscopic depth perception relies on binocular disparities, or small geometric differences between the retinal images of each eye. The most reliable binocular depth judgments are those that are based on relative disparities between two simultaneously visible features in a scene. Many cortical areas contain neurons that are sensitive to disparity, but it is unclear whether any areas show a specific sensitivity to relative disparity. We recorded from neurons in the early cortical visual area V2 of the awake macaque during presentation of random-dot patterns. The depth of a central region ('center'), and that of an annular surrounding region ('surround'), were manipulated independently in these stimuli. Some cells were fully selective for the resulting relative disparities. Most showed partial selectivity, which nonetheless indicated a sensitivity for the depth relationship between center and surround. Both types of neural response could support psychophysical judgments of relative depth. C1 Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Thomas, OM (reprint author), Univ Oxford, Physiol Lab, Parks Rd, Oxford OX1 3PT, England. RI Parker, Andrew/I-7867-2013 OI Parker, Andrew/0000-0001-5800-0407 NR 23 TC 108 Z9 111 U1 0 U2 8 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 MAY PY 2002 VL 5 IS 5 BP 472 EP 478 DI 10.1038/nn837 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 546JY UT WOS:000175272000019 PM 11967544 ER PT J AU Germain, RN AF Germain, RN TI T-cell development and the CD4-CD8 lineage decision SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID THYMOCYTE POSITIVE SELECTION; ACTIVATED PROTEIN-KINASE; TCR SIGNALING THRESHOLDS; ANTIGEN-PRESENTING CELL; CD4 GENE-EXPRESSION; TYROSINE-PHOSPHATASE; TRANSGENIC MICE; IMMATURE THYMOCYTES; NEGATIVE SELECTION; MHC CLASS AB Cell-fate decisions are controlled typically by conserved receptors that interact with co-evolved ligands. Therefore, the lineage-specific differentiation of immature CD4(+)CD8(+) T cells into CD4(+) or CD8(+) mature T cells is unusual in that it is regulated by clonally expressed, somatically generated T-cell receptors (TCRs) of unpredictable fine specificity. Yet, each mature T cell generally retains expression of the co-receptor molecule (CD4 or CD8) that has an MHC-binding property that matches that of its TCR. Two models were proposed initially to explain this remarkable outcome - 'instruction' of lineage choice by initial signalling events or `selection' after a stochastic fate decision that limits further development to cells with coordinated TCR and co-receptor specificities. Aspects of both models now appear to be correct; mistake-prone instruction of lineage choice precedes a subsequent selection step that filters out most incorrect decisions. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bldg 10,Room 11N311 MSC-1892,10 Ctr Dr, Bethesda, MD 20892 USA. NR 138 TC 288 Z9 296 U1 7 U2 61 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAY PY 2002 VL 2 IS 5 BP 309 EP 322 DI 10.1038/nri798 PG 14 WC Immunology SC Immunology GA 636DD UT WOS:000180438500017 PM 12033737 ER PT J AU Oz, M Dinc, M Tchugunova, Y Dunn, SMJ AF Oz, M Dinc, M Tchugunova, Y Dunn, SMJ TI Comparison of the effects of xenon and halothane on voltage-dependent Ca2+ fluxes in rabbit T-tubule membranes SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE calcium channels; xenon; halothane; skeletal muscle ID SKELETAL-MUSCLE; GENERAL-ANESTHETICS; CALCIUM CHANNELS; ISOFLURANE; CONTRACTILITY; INHIBITION; DOGS AB The effects of xenon and halothane on depolarization-induced Ca-45(2+) fluxes mediated by voltage-dependent Ca2+ channels were investigated in transverse tubule membrane vesicles from rabbit skeletal muscle. Halothane, in the concentration range of 0.5-2 mM, caused a significant inhibition of Ca-45(2+) fluxes. Xenon tested in the range of 60%-100% did not affect the Ca-45(2+) fluxes. Radioligand binding studies indicated that xenon and halothane have different effects on the specific binding of [H-3]Isradipine to transverse tubule membranes. Halothane caused a significant inhibition on the specific binding of [H-3]Isradipine. In controls and in presence of 0.5 mM halothane, B-max values were 26.9 pmole/mg and 15.1 pmole/mg, and K-D values were 238 pM and 247 pM, respectively. On the other hand, there was no effect of xenon (60%-100%) on the characteristics of [H-3]Isradipine binding. In conclusion, results indicate that xenon and halothane differ in their effects on the function of voltage-dependent Ca2+ channels and on the specific binding of [H-3]Isradipine in skeletal muscle membranes. C1 NIDA, IRP, Cellular Neurobiol Sect, Baltimore, MD 21224 USA. Oncol Hosp, Dept Pulm Disorders, TR-06514 Ankara, Turkey. Univ Alberta, Dept Pharmacol, Edmonton, AB T6G 2H7, Canada. RP Oz, M (reprint author), NIDA, IRP, Cellular Neurobiol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Oz, Murat/E-2148-2012 NR 21 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAY PY 2002 VL 365 IS 5 BP 413 EP 417 DI 10.1007/s00210-002-0541-2 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 560EN UT WOS:000176069900011 PM 12012028 ER PT J AU Oh, JS Kucab, JE Bushel, PR Martin, K Bennett, L Collins, J DiAugustine, RP Barrett, JC Afshari, CA Dunn, SE AF Oh, JS Kucab, JE Bushel, PR Martin, K Bennett, L Collins, J DiAugustine, RP Barrett, JC Afshari, CA Dunn, SE TI Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells SO NEOPLASIA LA English DT Article DE microarray; insulin-like growth factor-1 receptor; AKT; transcription factors; breast cancer ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; ELEMENT-BINDING PROTEIN; TRANSFERASE P1 GENE; CARCINOMA IN-SITU; TRANSCRIPTION FACTOR; RECEPTOR EXPRESSION; FACTOR (IGF)-I; MYC REPRESSES; PLASMA-LEVELS AB Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P450 1A1, cytochrome P450 1B1, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s) whereby some of these changes occur. C1 British Columbia Inst Childrens & Womens Hlth, Dept Pediat, Vancouver, BC V5Z 4H4, Canada. NIEHS, Lab Mol Carcinogenesis Hormones & Canc Grp, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Funct Genom Program, Raleigh, NC 27695 USA. NIEHS, Mol Carcinogenesis Lab, Microarray Grp, Bethesda, MD USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Dunn, SE (reprint author), British Columbia Inst Childrens & Womens Hlth, Dept Pediat, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. FU NIEHS NIH HHS [5K22 ES 00337-02] NR 67 TC 45 Z9 48 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2002 VL 4 IS 3 BP 204 EP 217 DI 10.1038/sj/neo/7900229 PG 14 WC Oncology SC Oncology GA 550WR UT WOS:000175528000004 PM 11988840 ER PT J AU Bosetti, F Brizzi, F Barogi, S Mancuso, M Siciliano, G Tendi, EA Murri, L Rapoport, SI Solaini, G AF Bosetti, F Brizzi, F Barogi, S Mancuso, M Siciliano, G Tendi, EA Murri, L Rapoport, SI Solaini, G TI Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer; mitochondria; F1F0-ATPase; cytochrome c oxidase; platelets; brain ID AMYLOID PRECURSOR PROTEIN; OXIDATIVE-PHOSPHORYLATION; NEUROFIBRILLARY TANGLES; LIPID-PEROXIDATION; IN-VIVO; DEMENTIA; STRESS; METABOLISM; ACROLEIN; RETAIN AB Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F1F0-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS). and lead to neuronal death. fit the present study, cytochrome c oxidase (COX) and F1F0-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%. P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F1F0-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F1F0-ATPase is a mitochondrial target in AD. in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability. Abbreviations: Abeta: amyloid betas AD: Alzheimer's disease; COX: cytochrome oxidase OS-ATPase: oligomycin-sensitive ATPase: ROS: reactive oxygen species. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Scuola Super Sant Anna, I-56127 Pisa, Italy. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dipartimneto Neurosci, Neurol Clin, Pisa, Italy. RP Solaini, G (reprint author), Scuola Super Sant Anna, Via G Carducci 40, I-56127 Pisa, Italy. EM gsolaini@sssup.it RI Siciliano, Gabriele/K-7259-2016; OI Siciliano, Gabriele/0000-0002-6142-2384; SOLAINI, GIANCARLO/0000-0001-7825-0446 NR 60 TC 188 Z9 197 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 2002 VL 23 IS 3 BP 371 EP 376 AR PII S0197-4580(01)00314-1 DI 10.1016/S0197-4580(01)00314-1 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 544TA UT WOS:000175175600005 PM 11959398 ER PT J AU Atack, JR Schapiro, MB AF Atack, JR Schapiro, MB TI Inositol monophosphatase activity in normal, Down syndrome and dementia of the Alzheimer type CSF SO NEUROBIOLOGY OF AGING LA English DT Article DE cerebrospinal fluid; inositol monophosphatase; Down syndrome; aging; dementia of the Alzheimer type; acetylcholinesterase; butyrylcholinesterase ID CEREBROSPINAL-FLUID PRODUCTION; LITHIUM TREATMENT; TS65DN MOUSE; MYOINOSITOL; BRAIN; DISEASE; SCHIZOPHRENIA; MODEL; H-1 AB Inositol monophosphatase (IMPase), a cytoplasmic enzyme that hydrolyses inositol monophosphates to produce inositol is also found in the cerebrospinal fluid (CSF). Since levels of inositol have been previously reported to be elevated in Down syndrome (DS) CSF. IMPase activity A as measured in CSF of DS subjects to establish whether altered inositol levels may be related to changes in IMPase activity. In addition. and to better understand the regulation of IMPase expression in the CSF, enzyme activity was measured in normal aging. patients with Alzheimer-type or multi-infarct dementia (DAT and MID, respectively) and in CSF obtained by repeat lumbar puncture or front sequential aliquots of CSF from along the rostro-caudal axis. IMPase activity,vas relatively constant in CSF obtained front repeated lumbar puncture and there was no significant rostro-caudal gradient of activity in either normal or DS subjects. indicating that the enzyme originates from both brain and spinal cord. Compared to respective age-matched normal subjects, CSF IMPase activity A as unaltered in DS, DAT and MID. However. in normal volunteers there was a significant positive correlation between age and CSF IMPase activity. Furthermore, there were significant correlations between CSF IMPase activity and acetylcholinesterase and butyrylcholinesterase activities and total protein. suggesting co-regulation of these parameters within the CSF. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Merck Sharp & Dohme Ltd, Res Lab, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Atack, JR (reprint author), Merck Sharp & Dohme Ltd, Res Lab, Neurosci Res Ctr, Terlings Pk,Eastwick Rd, Harlow CM20 2QR, Essex, England. NR 28 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 2002 VL 23 IS 3 BP 389 EP 396 AR PII S0197-4580(01)00335-9 DI 10.1016/S0197-4580(01)00335-9 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 544TA UT WOS:000175175600008 PM 11959401 ER PT J AU LaFontaine, MA Mattson, MP Butterfield, DA AF LaFontaine, MA Mattson, MP Butterfield, DA TI Oxidative stress in synaptosomal proteins from mutant presenilin-1 knock-in mice: Implications for familial Alzheimer's disease SO NEUROCHEMICAL RESEARCH LA English DT Article DE Alzheimer's disease; presenilin-1; reactive oxygen species; electron paramagnetic resonance; oxidative stress; protein carbonyls; synaptosomes ID AMYLOID BETA-PEPTIDE; BRAIN; NEUROTOXICITY; LOCALIZATION; ASSOCIATION; MEMBRANES; DAMAGE AB Presenilin-1 (PS-1) is a transmembrane protein that may be involved in the processing of amyloid precursor protein (APP). Mutations in PS-1 are the major cause of familial Alzheimer's disease (AD). AD brain is under significant oxidative stress, including protein oxidation. In the present study, protein oxidation was compared in synaptosomes from knock-in mice expressing mutant human PS-1 (M146V mutation) and from wild-type mice expressing non-mutant human PS-1. Synaptosomal membrane protein conformational alterations associated with oxidative stress were measured using electron paramagnetic resonance (EPR) in conjunction with a protein-specific spin-label. Direct synaptosomal protein oxidation was assessed by a carbonyl detection assay. Synaptosomal proteins from PS-1 mutant mice displayed increased oxidative stress as measured by both techniques, compared with synaptosomal proteins from wild type mice. These data suggest that PS-1 mutations cause oxidative alterations in synaptosomal membrane protein structure and oxidative modification of synaptosomal proteins. Our findings suggest that familial AD may be associated with oxidative stress that may play a pivotal role in neuronal dysfunction and death. C1 Univ Kentucky, Dept Chem, Ctr Membrane Sci, Lexington, KY 40506 USA. Cent Connecticut State Univ, Dept Chem, New Britain, CT 06050 USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40506 USA. RP Butterfield, DA (reprint author), Univ Kentucky, Dept Chem, Ctr Membrane Sci, Lexington, KY 40506 USA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG-12423, AG-05119, AG-10836] NR 27 TC 22 Z9 26 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 MAY PY 2002 VL 27 IS 5 BP 417 EP 421 AR UNSP 0364-3190/02/0500-0417/0 DI 10.1023/A:1015560116208 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 554TX UT WOS:000175754200010 PM 12064358 ER PT J AU Basile, AS AF Basile, AS TI Special issue: Role of mitochondria in neurological disease - Preface SO NEUROCHEMISTRY INTERNATIONAL LA English DT Editorial Material C1 NIH, Neurosci Lab, Bethesda, MD 20892 USA. RP Basile, AS (reprint author), NIH, Neurosci Lab, Bldg 8,Room 111,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY PY 2002 VL 40 IS 6 BP 467 EP 467 AR PII S0197-0186(01)00116-4 DI 10.1016/S0197-0186(01)00116-4 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 537EW UT WOS:000174746500001 ER PT J AU Casellas, P Galiegue, S Basile, AS AF Casellas, P Galiegue, S Basile, AS TI Peripheral benzodiazepine receptors and mitochondrial function SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review DE peripheral benzodiazepine receptors; mitochondria; neurosteroids; mitochondrial permeability transition; PK11195 : Ro5-4864 ID POSITRON-EMISSION-TOMOGRAPHY; DIAZEPAM-BINDING INHIBITOR; RO 5-4864 BINDING; HUMAN BREAST-CANCER; RAT ADRENAL-GLAND; CHOLESTEROL TRANSPORT; CELL-PROLIFERATION; HUMAN-BRAIN; AUTORADIOGRAPHIC LOCALIZATION; QUANTITATIVE AUTORADIOGRAPHY AB For over 20 years, numerous investigations have focused on elucidating the function of the peripheral benzodiazepine receptor (PBR). This relatively small protein (18 kDa) arouses great interest because of its association with numerous biological functions, including the regulation of cellular proliferation, immunomodulation, porphyrin transport and heme biosynthesis, anion transport, regulation of steroidogenesis and apoptosis. Although the receptor was first identified as a binding site for the benzodiazepine, diazepam, in peripheral organ systems, the PBR was subsequently found to be distinct from the central benzodiazepine receptor (CBR) in terms of its pharmacological profile, structure, subcellular localization, tissue distribution and physiological functions. The PBR is widely expressed throughout the body, with high densities found in steroid-producing tissues. In contrast, its expression in the CNS is restricted to ependymal cells and glia. The benzodiazepine Ro5-4864 and the isoquinoline carboxamide PK11195 exhibit nanomolar affinity for the PBR, and are the archtypic pharmacological tools for characterizing the receptor and its function. Primary among these functions are its regulation of steroidogenesis and apoptosis, which reflect its mitochondrial localization and involvement in oxidative processes. This review will evaluate the basic pharmacology and molecular biology of the PBR, and highlight its role in regulating mitochondrial function, the mitochondrial transmembrane potential and its sensitivity to reactive oxygen species (ROS), and neurosteroid synthesis, processes relevant to the pathogenesis of a number of neurological and neuropsychiatric disorders. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Sanofi Rech, SYNTHELABO, Dept Immunol Oncol, Montpellier, France. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Casellas, P (reprint author), 371 Rue Prof Joseph Blayac, F-34184 Montpellier 04, France. NR 113 TC 298 Z9 318 U1 4 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY PY 2002 VL 40 IS 6 BP 475 EP 486 AR PII S0197-0186(01)00118-8 DI 10.1016/S0197-0186(01)00118-8 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 537EW UT WOS:000174746500003 PM 11850104 ER PT J AU Blumenthal, JD Zijdenbos, A Molloy, E Giedd, JN AF Blumenthal, JD Zijdenbos, A Molloy, E Giedd, JN TI Motion artifact in magnetic resonance imaging: Implications for automated analysis SO NEUROIMAGE LA English DT Article DE brain; magnetic resonance imaging; motion artifact; segmentation ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BRAIN-DEVELOPMENT; ADOLESCENCE; CHILDHOOD; MRI AB Automated measures of cerebral magnetic resonance images (MRI) often provide greater speed and reliability compared to manual techniques but can be particularly sensitive to motion artifact. This study employed an automatic MRI analysis program that quantified regional gray matter volume and created images for verification and quality control. Motion artifact was assessed on each image and assigned a rating of none, mild, moderate, or severe. Greater motion artifact was associated with smaller gray matter volumes. Severity of motion artifact is an important, but often overlooked, consideration in the interpretation of automated MRI measures. (C) 2002 Elsevier Science (USA). C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. RP Blumenthal, JD (reprint author), NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 13 TC 34 Z9 34 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2002 VL 16 IS 1 BP 89 EP 92 DI 10.1006/nimg.2002.1076 PG 4 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 569WD UT WOS:000176624700009 PM 11969320 ER PT J AU Deng, XL Cai, NS McCoy, MT Chen, WG Trush, MA Cadet, JL AF Deng, XL Cai, NS McCoy, MT Chen, WG Trush, MA Cadet, JL TI Methamphetamine induces apoptosis in an immortalized rat striatal cell line by activating the mitochondrial cell death pathway SO NEUROPHARMACOLOGY LA English DT Article DE methamphetamine; apoptosis; bax; mitochondria; caspases; DFF40 ID DISMUTASE TRANSGENIC MICE; TUMOR-NECROSIS-FACTOR; CYTOCHROME-C RELEASE; 3-NITROPROPIONIC ACID; PERMEABILITY TRANSITION; CASPASE ACTIVATION; DNA FRAGMENTATION; INDUCED NEUROTOXICITY; BRAIN DOPAMINE; PROTEIN-KINASE AB Methamphetamine is a neurotoxic drug of abuse known to cause cell death both in vitro and in vivo. Nevertheless, the molecular and cellular mechanisms involved in this process remain to be clarified. Herein, we show that methamphetamine-induced apoptosis is associated with early (2 h) overexpression of bax, decreases of mitochondrial membrane potential and oxygen consumption as well as release of cytochrotne c from mitochondria. In addition, activated caspase-9 was detected at 4 h post-METH exposure. Cell death was detectable by annexin V and propidium iodide staining after 8 h of methamphetamine exposure. At that time, the majority of the cells were stained by annexin V alone, with some cells being stained for both annexin V and propidium iodide. Moreover, cleavage of caspase-3, poly (ADP-ribose) polymerase and DNA fragmentation-related factor 45 was detected at 8 h post drug treatment. These results indicate that methamphetamine-induced apoptotic cell death results from early overexpression of bax, reduction of mitochondrial respiration and membrane potential and release of mitochondrial cytochrotne c with subsequent activation of the caspase cascade. Published by Elsevier Science Ltd. C1 NIDA, IRP, Mol Neuropsychiat Sect, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Div Toxicol Sci, Baltimore, MD 21205 USA. RP Cadet, JL (reprint author), NIDA, IRP, Mol Neuropsychiat Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 53 TC 68 Z9 77 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAY PY 2002 VL 42 IS 6 BP 837 EP 845 AR PII S0028-3908(02)00034-5 DI 10.1016/S0028-3908(02)00034-5 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 568CF UT WOS:000176524300011 PM 12015210 ER PT J AU Ernst, M Bolla, K Mouratidis, M Contoreggi, C Matochik, JA Kurian, V Cadet, JL Kimes, AS London, ED AF Ernst, M Bolla, K Mouratidis, M Contoreggi, C Matochik, JA Kurian, V Cadet, JL Kimes, AS London, ED TI Decision-making in a risk-taking task: A PET study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE reward; punishment; guessing; informed decision; orbital frontal cortex; cognitive task; neuroimaging ID VENTROMEDIAL PREFRONTAL CORTEX; POSITRON EMISSION TOMOGRAPHY; DIFFERENTIAL NEURAL RESPONSE; CEREBRAL BLOOD-FLOW; ORBITOFRONTAL CORTEX; HUMAN AMYGDALA; INTRAVENOUS (H2O)-O-15; WORKING-MEMORY; BASAL GANGLIA; FMRI AB As decision-making is central to motivated behavior, understanding its neural substrates car? help elucidate the deficits that characterize various maladaptive behaviors. Twenty healthy adults performed a risk-taking task during positron emission tomography with O-15-labeled water. The task, a computerized card game, tests the ability to weigh short-term rewards against long-terra losses. A control task matched cell components of the risk-taking task except for decision-making and the difference between responses to contingent and non-contingent reward and punishment. Decision-making (2 runs of file active task minus 2 runs of the control task) activated orbital clad dorsolateral prefrontal cortex, anterior cingulate, insula, inferior parietal cortex and thalamus predominantly on the right side, and cerebellum predominantly on the left silo. In an exploratory analysis, guessing (run 1 minus run 2 of the active task) accompanied activation of sensory-motor associative areas, and amygdala on the left side, whereas informed decision-making (curt 2 minus run 1) activated areas that subserve memory (hippocampus, posterior cingulate) and motor control (striatum, cerebellum). The findings provide a framework for future investigations of decision-making in maladaptive behaviors. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Johns Hopkins Univ, Sch Med, Intramural Res Program, Natl Inst Drug Abuse, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Ernst, M (reprint author), NIMH, MAP, Room 118,MSC 2670,15K N Dr, Bethesda, MD 20892 USA. FU NCRR NIH HHS [M01 RR 02719]; NIDA NIH HHS [DA 11426] NR 47 TC 256 Z9 260 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2002 VL 26 IS 5 BP 682 EP 691 AR PII S0893-133X(01)00414-6 DI 10.1016/S0893-133X(01)00414-6 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 538AJ UT WOS:000174791600013 PM 11927193 ER PT J AU Eells, JB Yeung, SK Nikodem, VM AF Eells, JB Yeung, SK Nikodem, VM TI Dopamine neurons heterozygous for the Nurr1-null allele have reduced survival in vitro SO NEUROSCIENCE RESEARCH COMMUNICATIONS LA English DT Article DE Nurr1; postnatal mesencephalic cultures; tyrosine hydroxylase; dopamine ID ORPHAN NUCLEAR RECEPTOR; PARKINSONS-DISEASE; TYROSINE-HYDROXYLASE; SUPEROXIDE-DISMUTASE; SUBSTANTIA-NIGRA; MIDBRAIN NEURONS; PROGENITOR CELLS; RAT-BRAIN; 2 PARTS; EXPRESSION AB Although Nurr1 is essential for the differentiation of midbrain dopamine neurons, its function in mature dopamine neurons has not been determined. In order to investigate the role of Nurr1 in the survival of dopamine neurons, neurons from the mesencephalon of newborn pups heterozygous for the Nurr1-null mutation (+/-) or wild-type (+/+) littermates were grown in culture. Postnatal cultures revealed a significant reduction in the survival and growth of tyrosine hydroxylase immunoreactive (TH-IR) neurons from Nurr1 +/- pups as early as 1 day in culture despite having normal TH-IR neuron numbers in vivo. The Nurr1 +/+ and +/- TH-IR neurons responded to treatment with forskolin, glia cell-line derived neurotrophic factor and brain-derived neurotrophic factor, although significantly fewer Nurr1 +/- TH-IR neurons survived. These data suggest that the loss of a single allele of Nurr1 significantly reduces the survival capacity of postnatal dopamine neurons in vitro without affecting normal development or differentiation. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Eells, JB (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. OI Eells, Jeffrey/0000-0002-6381-1666 NR 33 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0893-6609 J9 NEUROSCI RES COMMUN JI Neurosci. Res. Commun. PD MAY-JUN PY 2002 VL 30 IS 3 BP 173 EP 183 DI 10.1002/nrc.10029 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 569VB UT WOS:000176622100005 ER PT J AU Ma, W Shaffer, KM Pancrazio, JJ O'Shaughnessy, TJ Stenger, DA Zhang, L Barker, JL Maric, D AF Ma, W Shaffer, KM Pancrazio, JJ O'Shaughnessy, TJ Stenger, DA Zhang, L Barker, JL Maric, D TI Toluene inhibits muscarinic receptor-mediated cytosolic Ca2+ responses in neural precursor cells SO NEUROTOXICOLOGY LA English DT Article DE neural stem cell; Ca2+ imaging; muscarinic acetylcholine receptor; 5-bromo-2 '-deoxyuridine; toluene ID ABUSE EMBRYOPATHY; PRENATAL EXPOSURE; IN-VITRO; RAT; CALCIUM; DELINEATION; EXPRESSION; ACTIVATION; CHANNELS; ETHANOL AB Toluene is widely used as a component in industrial solvents and many toluene-containing products are abused via inhalation. While many studies have demonstrated its inhibitory effects on neuronal activity, the effects of toluene on receptor signaling in proliferating and differentiating neural precursor cells are presently unclear. Here, using digital video microscopy and Ca2+ imaging, we investigated the effects of acute exposure to toluene on the function of muscarinic acetylcholine receptors (mAChRs) expressed in neural precursor cells. The neural precursor cells were isolated from embryonic day 13 (E13) rat cortex and expanded in serum-free medium containing basic fibroblast growth factor (bFGF). We found that the acetylcholine (ACh) analog carbachol (CCh) induced a dose-dependent increase in cytosolic Ca2+ which was blocked by the muscarinic receptor antagonist atropine in a reversible manner Toluene was added to the perfusion medium and concentrations of toluene in the medium were determined by gas chromatographic analysis. Following imaging, the cells were fixed and processed for 5-bromo-2'-deoxyuridine (BrdU, cell proliferation marker) and beta-tubulin (TuJ1, neuronal marker) immunostaining. In the 5 day culture, most cells continued to divide (BrdU(+)), while a few cells differentiated into young neurons (TuJ1(+)). The CCh-induced Ca2+ elevations in proliferating (BrdU(+)TuJ1(-)) neural precursor cells were significantly reduced by acute exposure to 0.15 mM toluene and completely blocked by 10 mM toluene. Toluene's inhibition of muscarinic receptor-mediated Ca2+ signaling was rapid, reversible and dose-dependent with an IC50 value 0.5 mM. Since muscarinic receptors mediate cell proliferation and differentiation during neural precursor cell development, these results suggest that depression of muscarinic signaling may play a role in toluene's teratogenic effect on the developing nervous system. (C) 2002 Elsevier Science Inc. All rights reserved. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Ma, W (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6910,4555Overlook Ave SW, Washington, DC 20375 USA. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 23 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2002 VL 23 IS 1 BP 61 EP 68 AR PII S0161-813X(01)00084-5 DI 10.1016/S0161-813X(01)00084-5 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 576XU UT WOS:000177033100006 ER PT J AU Flynn, KM Newbold, RR Ferguson, SA AF Flynn, KM Newbold, RR Ferguson, SA TI Multigenerational exposure to dietary nonylphenol has no severe effects on spatial learning in female rats SO NEUROTOXICOLOGY LA English DT Article DE estrogen; endocrine disrupter; memory; water maze; age-related; nonylphenol ID WATER MAZE PERFORMANCE; RECEPTOR CONCENTRATIONS; OVARIECTOMIZED RATS; PITUITARY-GLAND; SEXUAL-BEHAVIOR; PREOPTIC AREA; AGED RATS; ESTRADIOL; ESTROGEN; MEMORY AB Nonylphenol is a common intermediate in the production of many consumer compounds and reportedly acts as an estrogen mimic. Because estrogen affects the spatial learning and memory in rats, the effects of nonylphenol exposure on the performance of female rats in the Morris water maze were investigated. Here, Sprague-Dawley rats (170) consumed soy-free diets containing 0, 25, 200 or 750 ppm nonylphenol (0, 2, 16 or 60 mg/kg per day) beginning on postnatal day (PND) 42 and continuing for two generations (171 and 172) with breeding occurring within treatments. Females to be behaviorally tested (n = 7-8 per treatment per generation) were ovariectomized at adulthood and assessed for spatial learning and memory between PND 125-150 (young adult age). Each rat was tested for four consecutive days (three trials per day) in the Morris water maze with the platform in a fixed location. One week later, each subject was primed with estrogen and progesterone and assessed on a single day (three trials). The F, rats continued on the same diets until PND 380-395 (middle aged) when they were re-tested as above (four consecutive days followed I week later with hormonal priming and a single test day). Latency to find the platform, path length and swim speed were averaged over the three trials per day and analyzed using repeated measures analyses of variance. There were no consistent effects of dietary nonylphenol exposure and no interactions of nonylphenol exposure on any measure of performance in either generation at the young age nor at the middle age in the F, generation. When tested at the young adult age, however hormone priming resulted in latencies and path lengths that were significantly shorter than in those exhibited during the unprimed test days, and there was no such effect when tested at middle age. Middle aged rats exhibited better performance than the same animals tested at a young age, likely as a result of familiarity and practice with the test paradigm. These data suggest that multigenerational dietary nonylphenol exposure does not cause gross alterations in, Morris water maze performance in young adult or middle aged ovariectomized female rats. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-93-0001] NR 42 TC 6 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2002 VL 23 IS 1 BP 87 EP 94 AR PII S0161-813X(02)00007-4 DI 10.1016/S0161-813X(02)00007-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 576XU UT WOS:000177033100009 PM 12164552 ER PT J AU Milenic, DE Garmestani, K Chappell, LL Dadachova, E Yordanov, A Ma, DS Schlom, J Brechbiel, MW AF Milenic, DE Garmestani, K Chappell, LL Dadachova, E Yordanov, A Ma, DS Schlom, J Brechbiel, MW TI In vivo comparison of macrocyclic and acyclic ligands for radiolabeling of monoclonal antibodies with Lu-177 for radioimmunotherapeutic applications SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE radioimmunotherapy; Lu-177; DOTA; PA-DOTA; CHX-A '' ID BIFUNCTIONAL CHELATING AGENT; IN-VIVO; CARCINOMA XENOGRAFTS; DTPA LIGAND; CHX-DTPA; COMPLEXES; CANCER; B72.3; BIODISTRIBUTION; STABILITY AB The studies reported herein present the first in vitro and in vivo comparison of radioimmunoconjugates (RIC) radiolabeled with Lu-177 using the acyclic CHX-A"-DTPA ligand and the macrocyclic ligands, C-DOTA and PA-DOTA. The in vivo studies include pharmacokinetics and biodistribution of the formed Lu-177-labeled immunoconjugates in a tumor bearing murine model with engineered monoclonal antibody HuCC49DeltaCH2. The in vitro analysis indicated that the CHX-A" RIC was superior with respect to immunoreactiviry, radiolabeling with Lu-177, and specific activity. The in vivo pharmacokinetic data by itself indicated that the Lu(III)-PA-DOTA complex may not be as stable as Lu(III) complexes with CHX-A" or C-DOTA. All three RICs demonstrated tumor targeting of human colon carcinoma xenografts in athymic mice. In these biodistribution studies, there appears to be no overall pattern or trend of one RIC over the other two. Based on these in vitro and in vivo studies, the CHX-A" DTPA ligand should be considered a suitable bifunctional chelate for the radiolabeling of monoclonal antibodies with Lu-177 for radioimmunotherapy applications. Published by Elsevier Science Inc. C1 NCI, Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 59 TC 70 Z9 70 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2002 VL 29 IS 4 BP 431 EP 442 AR PII S0969-8051(02)00294-9 DI 10.1016/S0969-8051(02)00294-9 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 555KZ UT WOS:000175794400007 PM 12031878 ER PT J AU Phillips, J Grady, PA AF Phillips, J Grady, PA TI Reducing health disparities in the twenty-first century: Opportunities for nursing research SO NURSING OUTLOOK LA English DT Article AB This article highlights selected components of the National Institute of Nursing Research's (NINR) Strategic Plan on Reducing Health Disparities. Building on its long history of supporting research devoted to improving minority health, NINR has expanded its opportunities and efforts related to health disparities and enhancing the research career development of minority investigators. Given the increased emphasis on reducing and, ultimately, eliminating health disparities, nurse researchers are encouraged to explore the various opportunities provided by NINR when addressing health inequalities. C1 Natl Inst Nursing Res, NIH, Bethesda, MD 20892 USA. RP Phillips, J (reprint author), Natl Inst Nursing Res, NIH, 45 Ctr Dr,MSC 6300, Bethesda, MD 20892 USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD MAY-JUN PY 2002 VL 50 IS 3 BP 117 EP 120 DI 10.1067/mno.2002.123529 PG 4 WC Nursing SC Nursing GA 568BA UT WOS:000176521500009 PM 12085025 ER PT J AU Johnson, CD Zhang, J AF Johnson, CD Zhang, J TI Survival of other fetuses after a fetal death in twin or triplet pregnancies SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRAUTERINE DEATH; MULTIPLE GESTATION; VANISHING TWIN; DEMISE; MANAGEMENT AB OBJECTIVE: To estimate the frequency of fetal death in multifetal pregnancies and the probability of survival to age 1 year for twins or triplets in which at least one fetal death occurred at 20 weeks' gestation or more. METHODS: We used the Matched Multiple Birth File from the US National Center for Health Statistics, which included 152,233 sets of twins and 5356 sets of triplets registered from 1995 to 1997. The Cox proportional hazards model was used to estimate the adjusted relative risk of death before age 1 year for remaining twins and triplets. RESULTS: Fetal death at 20 weeks' gestation or later was uncommon, occurring in 2.6% of twin and 4.3% of triplet gestations. After adjustment for confounders, the survival of the remaining fetuses was inversely related to the time of the first fetal demise. Same-sex twins were two times more likely than opposite-sex twins to die after an intrauterine demise at 25-32 weeks' gestation and were more than three times more likely to die after a death at 33 weeks' gestation or more. CONCLUSION: After a fetal death in a multifetal pregnancy at 20 weeks' gestation or later, the survival of the remaining fetuses is inversely related to the time the death occurred. Among twins, survival also depends on sex concordance, with opposite-sex twins more likely than same-sex twins to survive. (Obstet Gynecol 2002;99:698-703. (C) 2002 by the American College of Obstetricians and Gynecologists). C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 24 TC 13 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2002 VL 99 IS 5 BP 698 EP 703 AR PII S0029-7844(02)01960-9 DI 10.1016/S0029-7844(02)01960-9 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 548BU UT WOS:000175369000005 PM 11978275 ER PT J AU Alzubaidi, NH Chapin, HL Vanderhoof, VH Calis, KA Nelson, LM AF Alzubaidi, NH Chapin, HL Vanderhoof, VH Calis, KA Nelson, LM TI Meeting the needs of young women with secondary amenorrhea and spontaneous premature ovarian failure SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FRACTURE RISK; BONE LOSS; PREVALENCE; POPULATION; PATTERNS AB OBJECTIVE: To investigate the experiences of young women with spontaneous premature ovarian failure with regard to the initial presenting symptom, promptness of diagnosis, and patient education. METHODS: We asked 50 patients previously diagnosed with spontaneous premature ovarian failure to participate in a structured interview survey consisting of 38 true-or-false, multiple-choice, and open-ended questions. RESULTS: Disturbance in menstrual pattern was the most common initial symptom in the 48 women who completed the interview (44 of 48, 92%). Over half of the 44 women who presented with this complaint reported visiting a clinician's office three or more times before laboratory testing was performed to determine the diagnosis. Over half of them reported seeing three or more different clinicians before diagnosis. In 25% of women it took longer than 5 years for the diagnosis of premature ovarian failure to be established. Patients who spent more than 5 minutes with the clinician discussing the diagnosis were significantly more likely to be satisfied with the manner in which they were informed (P<.001). Ninety percent of participants were college graduates, and 40% had graduate degrees. CONCLUSION: Women with spontaneous premature ovarian failure perceived a need for more aggressive evaluation of secondary amenorrhea and oligomenorrhea, Loss of menstrual regularity can be a sign of ovarian insufficiency, and the associated estrogen deficiency is a well-established risk factor for osteoporosis. (Obstet Gynecol 2002;99: 720-5. (C) 2002 by the American College of Obstetricians and Gynecologists). C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 29 TC 54 Z9 58 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2002 VL 99 IS 5 BP 720 EP 725 AR PII S0029-7844(02)01962-2 DI 10.1016/S0029-7844(02)01962-2 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 548BU UT WOS:000175369000008 PM 11978278 ER PT J AU Anzick, SL Trent, JM AF Anzick, SL Trent, JM TI Role of genomics in identifying new targets for cancer therapy SO ONCOLOGY-NEW YORK LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENE-EXPRESSION PATTERNS; HUMAN PROSTATE-CANCER; MOLECULAR CLASSIFICATION; BREAST-CANCER; LINKAGE DISEQUILIBRIUM; SEQUENCE VARIATION; COMPLEMENTARY-DNA; CDNA MICROARRAYS; DRUG-THERAPY AB The detailed map of the human genome can potentially transform future cancer therapy by merging genomics with pharmacology, thereby identifying which patients will benefit from specific therapeutic agents. Single-nucleotide polymorphisms (SNPs) provide a valuable tool for this pharmacogenetic approach to cancer therapy. The discovery of SNPs as disease markers may facilitate identification of populations at increased risk for certain cancers. In addition, SNP genetic screening may facilitate administration of appropriate treatment modalities or reveal specific genetic profiles that have importance in drug efficacy and toxicity. In addition to SNP analysis, DNA and tissue microarray analyses have the potential to transform the future of cancer therapy. For example, DNA microarrays may improve tumor classification systems as well as provide a molecular level dissection of global gene expression changes that occur in carcinogenesis. Tissue microarrays would allow one to verify, candidate genes, identified from DNA microarrays, against archival tumor specimens with known clinical outcome. In addition, both microarray technologies may be combined to rapidly validate gene targets. We will review and discuss these state-of-the-art technologies including data suggesting that the combined use of these high throughput technologies will facilitate our understanding of the genetic complexities inherent in cancer and will revolutionize cancer therapy. C1 Natl Human Genome Res Inst, NIH, Div Intramural Res, Canc Genet Branch, Bethesda, MD 20892 USA. RP Trent, JM (reprint author), Natl Human Genome Res Inst, NIH, Div Intramural Res, Canc Genet Branch, 50 South Dr, Bethesda, MD 20892 USA. EM jtrent@nhgri.nih.gov NR 58 TC 17 Z9 18 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 MAY PY 2002 VL 16 IS 5 SU 4 BP 7 EP 13 PG 7 WC Oncology SC Oncology GA 555ZP UT WOS:000175823200002 PM 12102580 ER PT J AU Longo, DL AF Longo, DL TI Controversies in early-stage Hodgkin's disease - The Ng/Mauch article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BREAST-CANCER; MORTALITY; RADIOTHERAPY; NEOPLASMS; INFANCY; COHORT; WOMEN; RISK C1 NIA, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Baltimore, MD 21224 USA. NR 12 TC 1 Z9 1 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 MAY PY 2002 VL 16 IS 5 BP 610 EP + PG 3 WC Oncology SC Oncology GA 554HR UT WOS:000175730200010 ER PT J AU Conley, BA Enos, RA Cheson, BD AF Conley, BA Enos, RA Cheson, BD TI Clinical Trials Reference Resource - Targeted therapy in squamous cell cancers of the head and neck SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR; MICROVESSEL DENSITY; IONIZING-RADIATION; CYCLIN D1; EXPRESSION; CARCINOMAS; ANGIOGENESIS; SURVIVAL; CHEMORADIOTHERAPY C1 NCI, Bethesda, MD 20892 USA. RP Conley, BA (reprint author), NCI, Bethesda, MD 20892 USA. NR 22 TC 1 Z9 1 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 MAY PY 2002 VL 16 IS 5 BP 621 EP + PG 4 WC Oncology SC Oncology GA 554HR UT WOS:000175730200012 PM 12108889 ER PT J AU Yarchoan, R Little, RF AF Yarchoan, R Little, RF TI AIDS malignancies in the era of highly active antiretroviral therapy - Part 2 - The Gates/Kaplan article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID LYMPHOMA; INFECTION C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 9 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 MAY PY 2002 VL 16 IS 5 BP 669 EP 670 PG 2 WC Oncology SC Oncology GA 554HR UT WOS:000175730200021 ER PT J AU Cope, MB Steele, VE Eto, I Juliana, MM Hill, DL Grubbs, CJ AF Cope, MB Steele, VE Eto, I Juliana, MM Hill, DL Grubbs, CJ TI Prevention of methylnitrosourea-induced mammary cancers by 9-cis-retinoic acid and/or vitamin D3 SO ONCOLOGY REPORTS LA English DT Article DE 9-cis-retinoic acid; vitamin D3; chemoprevention; mammary cancer ID 9-CIS RETINOIC ACID; X-RECEPTOR-ALPHA; BREAST-CANCER; CELL-GROWTH; 1,25-DIHYDROXYVITAMIN D-3; ANALOGS RETINOIDS; TUMOR-INCIDENCE; DIFFERENTIATION; RAT; CARCINOGENESIS AB Two cancer chemopreventive agents, vitamin D3 and 9-cis-retinoic acid (9-cis-RA), were evaluated alone and in combination in the methylnitrosourea (MNU)-induced mammary cancer model. In this study, female Sprague-Dawley rats received MNU (50 mg/kg BW) at 50 days of age. Vitamin D3 and 9-cis-RA were administered in the diet beginning three days later. The groups were: Group 1, vehicle only; Group 2, 9-cis-RA (60 mg/kg diet); Group 3, vitamin D3 (10 mug/kg diet); Group 4, vitamin D3 (3.3 mug/kg diet); Group 5, 9-cis-RA (60 mg/kg diet) plus vitamin D3 (10 mug/kg diet); and Group 6, 9-cis-RA (60 mg/kg diet) plus vitamin D3 (3.3 mug/kg diet). Animals were observed daily for signs of toxicity and were palpated 2x/week for mammary tumors. The study was terminated 150 days after treatment with MNU. The average number of mammary cancers was 6.7 in the animals receiving only the carcinogen. 9-cis-RA alone caused a 23% decrease in mammary cancer multiplicity, while vitamin D3 alone actually caused slight increases of 17 and 16%, at 10 and 3.3 mug/kg diet dose levels, respectively. When the agents were given in combination, however, the 9-cis-RA plus the high dose of vitamin D caused a statistically significant decrease (44%) in mammary cancer number, while the 9-cis-RA plus the low dose resulted in a 37% decrease. Thus, low doses of these agents that were not effective in preventing mammary cancer when given alone appeared to be active when given in combinations. Possible interactions between the retinoic acid receptors and vitamin D receptor may be responsible for the observed inhibition of mammary carcinogenesis. C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Univ Alabama, Dept Genom & Pathobiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Cope, MB (reprint author), Univ Alabama, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA. NR 41 TC 9 Z9 9 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAY-JUN PY 2002 VL 9 IS 3 BP 533 EP 537 PG 5 WC Oncology SC Oncology GA 545BR UT WOS:000175196800015 PM 11956623 ER PT J AU Arora, NK Johnson, P Gustafson, DH McTavish, F Hawkins, RP Pingree, S AF Arora, NK Johnson, P Gustafson, DH McTavish, F Hawkins, RP Pingree, S TI Barriers to information access, perceived health competence, and psychosocial health outcomes: test of a mediation model in a breast cancer sample SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE information needs; barriers to access; self-efficacy; health competence; quality of life ID QUALITY-OF-LIFE; SELF-EFFICACY; FUNCTIONAL ASSESSMENT; IMPROVING COMMUNICATION; RADIATION-THERAPY; COMPUTER SUPPORT; PHYSICAL ILLNESS; FOLLOW-UP; NEEDS; WOMEN AB This study examined the relationship between breast cancer patients' experience of barriers to accessing health information and their psychosocial health outcomes and explored the extent to which this relationship was mediated by patient perceptions of competence in dealing with health-related issues. Study sample consisted of 225 women surveyed within 6 months of diagnosis. Regression analyses suggested that patients who reported greater difficulty in accessing needed information experienced lower emotional (P = 0.05), functional (P < 0.05), and social/family (P < 0.05) well-being as well as lower perceptions of health competence (P < 0.001). Also, patient perceptions of health competence mediated the relationship between barriers to accessing information and patient outcomes (emotional well-being, P < 0.05; functional well-being. P < 0.01; social/family well-being, P = 0.01). Breast cancer patients often report dissatisfaction with the extent to which their information needs are addressed by their health care providers. Our findings underscore the need for designing and implementing interventions that would aid providers in better meeting the information needs of their patients. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, DCCPS, ARP, Outcomes Res Branch, Bethesda, MD 20892 USA. Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI 53705 USA. RP Arora, NK (reprint author), NCI, DCCPS, ARP, Outcomes Res Branch, 6130 Execut Blvd,MSC 7344,EPN Room 4005, Bethesda, MD 20892 USA. FU NICHD NIH HHS [5R01HD32922] NR 74 TC 76 Z9 78 U1 3 U2 10 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 MAY PY 2002 VL 47 IS 1 BP 37 EP 46 AR PII S0738-3991(01)00170-7 DI 10.1016/S0738-3991(01)00170-7 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 578LJ UT WOS:000177118800006 PM 12023099 ER PT J AU Chiou, CC Groll, AH Mavrogiorgos, N Wood, LV Walsh, TJ AF Chiou, CC Groll, AH Mavrogiorgos, N Wood, LV Walsh, TJ TI Esophageal candidiasis in human immunodeficiency virus-infected pediatric patients after the introduction of highly active antiretroviral therapy SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Candida; esophagitis; children; acquired immunodeficiency syndrome; highly active antiretroviral therapy ID FLUCONAZOLE-RESISTANT OROPHARYNGEAL; PROTEASE INHIBITORS; COMBINATION THERAPY; HIV-1-INFECTED CHILDREN; PHASE I/II; IN-VITRO; TYPE-1; MORTALITY; HIV; RESPONSES AB Objective. To investigate epidemiologic trends, clinical features and outcome of esophageal candidiasis in the era of highly active antiretroviral therapy in a prospectively monitored population of HIV-infected children and adolescents followed at the National Cancer Institute. Patients and methods. The records of all HIV-infected pediatric patients (n = 266) followed between 1995 and 2000 were reviewed for a history of esophageal candidiasis. Proven esophageal candidiasis was defined as clinical plus radiographic and/or endoscopic findings of esophageal candidiasis. Probable esophageal candidiasis was defined as esophageal symptoms that responded promptly to appropriate antifungal therapy. The medical records of all patients fulfilling these criteria were reviewed for demographic, clinical and laboratory features at presentation, as well as therapeutic interventions and outcome. Results. Of the 266 patients 9 (3.4%) had 18 documented episodes of proven (n = 16) or probable (n = 2) esophageal candidiasis. A history of prior mucosal candidiasis was present in 94% of all episodes. The median CD4(+) count at the time of diagnosis was 7/mul (range, 0 to 550), and the median viral load was 98 000 copies/ml (range, 22 916 to 1278 933). Concurrent oropharyngeal candidiasis was the most common clinical presentation (72%) followed by fever (55%), odynophagia (50%) and nausea or vomiting (39%). Treatment consisted of antifungal triazoles (61%) or amphotericin B (39%). Clinical cure was achieved in 15 cases, including all patients receiving triazoles. Conclusion. Esophageal candidiasis persists in the subgroup of patients not responding to highly active antiretroviral therapy and in that setting may present without concomitant oropharyngeal. candidiasis or typical clinical symptoms, thus underscoring the need for a high index of suspicion in children with very low CD4(+) counts. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Taipei 112, Taiwan. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 32 TC 6 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 2002 VL 21 IS 5 BP 388 EP 392 DI 10.1097/01.inf.0000012554.19241.80 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 552GL UT WOS:000175611200007 PM 12150174 ER PT J AU Gaughan, DM Mofenson, LM Hughes, MD Seage, GR Ciupak, GL Oleske, JM AF Gaughan, DM Mofenson, LM Hughes, MD Seage, GR Ciupak, GL Oleske, JM CA Pediat AIDS Clin Trials Grp Proto TI Osteonecrosis of the hip (Legg-Calve-Perthes disease) in human immunodeficiency virus-infected children SO PEDIATRICS LA English DT Article DE osteonecrosis; Legg-Calve-Perthes disease; perinatal human immunodeficiency virus infection ID PROTEIN-S DEFICIENCY; ACTIVE ANTIRETROVIRAL THERAPY; AVASCULAR NECROSIS; FEMORAL-HEAD; BONE; GROWTH; MEN; THROMBOPHILIA; OSTEOPENIA; BORN AB Objective. Osteonecrosis of the hip has been reported in human immunodeficiency virus (HIV) infected adults; whether this is related to HIV infection or its treatment is unknown. There has been 1 report of osteonecrosis among HIV-infected children. Specifically, avascular necrosis of the hip consistent with Legg-Calve-Perthes disease (LCPD) was reported in 3 HIV-infected children with AIDS from Spain in 1992. We evaluated the prevalence and incidence of LCPD, the pediatric equivalent of adult osteonecrosis of the hip, in HIV-infected children participating in a prospective cohort study of long-term outcomes in HIV-infected and HIV-exposed children-Pediatric AIDS Clinical Trials Group (PACTG) protocol 219. Methods. PACTG 219 enrolled 2014 HIV-infected and 849 HIV-exposed, uninfected children between April 1993 and September 2000. Children had periodic examinations with collection of clinical and laboratory data. The database was reviewed for reports of LCPD and other bone disorders. A prevalent case was defined as LCPD diagnosis preceding PACTG 219 enrollment and an incident case had to have occurred between enrollment and September 2000. A case-control study (matching on age, gender, and race/ethnicity, which are known to be associated with risk of LCPD and HIV infection status) was performed to investigate factors possibly associated with LCPD. Results. Six cases of LCPD (4 prevalent cases reported at study entry; 2 diagnosed during 5837 person-years of follow-up) were observed; LCPD was seen only in children with perinatal HIV infection. LCPD prevalence was 199 per 100 000 compared with an estimated general pediatric population prevalence of 23 per 100 000. Based on age-adjusted general population rates, the expected number of prevalent cases at PACTG 219 study entry would have been 0.44; the age-adjusted LCPD prevalence rate ratio was 9.0 (95% confidence interval [CI]: 8.3-9.7) for HIV-infected children compared with the general population. LCPD incidence was 34 per 100 000 person-years (95% CI: 0.42-124) compared with the estimated general population incidence of 6 per 100 000 person-years (95% CI: 5-7). Based on age-adjusted general population rates, the expected incidence of LCPD in PACTG 219 would have been 0.42; the age-adjusted relative risk of LCPD in HIV-infected PACTG 219 children was 4.8 (95% CI: 0.56-10.4). No cases were observed in uninfected children during 1919 person-years of follow-up on PACTG 219; the age-adjusted expected number of cases was 0.09. Median onset age was 7 years; 67% were of Hispanic or black race/ethnicity and 33% were female. Four of the 6 LCPD cases had received antiretroviral therapy before diagnosis; treatment was primarily with nucleoside reverse transcriptase inhibitors, and 2 had received protease inhibitors. Three of the LCPD cases had corticosteroid exposure before the diagnosis, but only 1 child had systemic exposure and the remaining 2 had topical exposure exclusively. In the case-control study, antiretroviral and corticosteroid therapy, CD4 cell percentage, birth weight, height for age and gender percentile, and triglyceride levels were not significantly associated with LCPD. However, the case-control study had limited power to evaluate possible associations. Conclusion. Similar to HIV-infected adults, children with perinatal HIV infection have an increased risk for osteonecrosis of the hip, and clinicians should be alert to this diagnosis when HIV-infected children present with limp or hip pain. Whether LCPD is attributable to HIV infection itself, HIV-associated complications that could predispose to hypercoagulopathy, HIV-related therapies, or to the growth abnormalities in HIV-infected children is unknown and deserves additional evaluation. C1 NICHHD, NIH, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. RP Mofenson, LM (reprint author), NICHHD, NIH, Pediat Adolescent & Maternal AIDS Branch, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 FU NIAID NIH HHS [AI-41110] NR 54 TC 17 Z9 17 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2002 VL 109 IS 5 AR e74 DI 10.1542/peds.109.5.e74 PG 8 WC Pediatrics SC Pediatrics GA 547EZ UT WOS:000175321200005 PM 11986480 ER PT J AU Little, RE Northstone, K Golding, J AF Little, RE Northstone, K Golding, J CA ALSPAC Study Team TI Alcohol, breastfeeding, and development at 18 months SO PEDIATRICS LA English DT Article DE alcohol; lactation; child development ID PREGNANCY; CHILDREN AB Objective. We aimed to replicate a previous study of 1-year-olds that reported a deficit in motor development associated with moderate alcohol use during lactation, using a different but comparable population. Methodology. The mental development of 915 18-month-old toddlers from a random sample of a longitudinal population-based study in the United Kingdom was measured using the Griffiths Developmental Scales. Frequent self-administered questionnaires during and after pregnancy provided maternal data. The dose of alcohol available to the lactating infant was obtained by multiplying the alcohol intake of the mother by the proportion of breast milk in the infant's diet. We compared this dose with the Griffiths Scales of Mental Development, taking into account potentially confounding variables. Result. Three of the Griffiths scales increased slightly but significantly with increasing infant alcohol exposure; there was no association in the remaining 2 or average of the scales. Discussion. We were unable to replicate the earlier deficit in motor skills associated with lactation alcohol use. One reason may be that the dose of alcohol reaching the lactating infant is small, and tests of infants and toddlers have limited ability to pick up small effects. Studies of older children may resolve the question of the safety of drinking while nursing. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Bristol, Dept Child Hlth, Bristol, Avon, England. RP Little, RE (reprint author), NIEHS, Epidemiol Branch, NIH, A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. RI Northstone, Kate/A-8165-2011 OI Northstone, Kate/0000-0002-0602-1983 FU NIAAA NIH HHS [AA09342] NR 14 TC 19 Z9 20 U1 3 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2002 VL 109 IS 5 AR e72 DI 10.1542/peds.109.5.e72 PG 6 WC Pediatrics SC Pediatrics GA 547EZ UT WOS:000175321200003 PM 11986478 ER PT J AU Hoare, SRJ Usdin, TB AF Hoare, SRJ Usdin, TB TI Specificity and stability of a new PTH1 receptor antagonist, mouse TIP(7-39) SO PEPTIDES LA English DT Article DE hypercalcemia; parathyroid hormone; tuberoinfundibular peptide; hyperparathyroidism; plasma pharmacokinetics ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; TUBEROINFUNDIBULAR PEPTIDE; IN-VIVO; PRIMARY HYPERPARATHYROIDISM; CALCIUM-RECEPTOR; PLASMA-LEVELS; 39 RESIDUES; PROTEIN; HYPERCALCEMIA AB Parathyroidhormone 1 (PTH 1) receptor antagonists might be of benefit in hypercalcemia of malignancy (HHM) and hyperparathyroidism. We previously identified bovine tuberoinfundibular peptide (7-39) (bTIP(7-39)) as a high-affinity PTH1 receptor antagonist. Mouse TIP(7-39) is an antagonist (rPTH1 K-B = 44 nM, rPTH2 = 940 nM) that is more potent than other known PTH1 receptor antagonists: bTIP(7-39) (210 nM), PTH-related protein (PTHrP)(7-34) (640 nM), and bPTH(7-34) (>3000 nM). Plasma proteases Slowly (t(1/2) = 81 min) inactivated [I-125]mTIP(7-39). Intravenous plasma [I-125]mTIP(7-39) was bi-phasically cleared (radioactivity t(1/2) = 2.9 min (70%) and 120 min (30%), binding activity t(1/2) = 3.6 min (92%), and t1/2 = 21 min (8%)). Loss of unlabeled mTIP(7-39) (250 mug/kg i.v.) receptor binding was similar. mTIP(7-39)'s high-affinity should facilitate animal evaluation of effects of PTH1 receptor antagonism. Published by Elsevier Science Inc. C1 Natl Inst Mental Hlth, Unit Cell Biol, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), Natl Inst Mental Hlth, Unit Cell Biol, Rm 3D06,Bld 36,36 Convent Dr, Bethesda, MD 20892 USA. NR 42 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2002 VL 23 IS 5 BP 989 EP 998 AR PII S0196-9781(02)00023-2 DI 10.1016/S0196-9781(02)00023-2 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 583ZV UT WOS:000177442800022 PM 12084532 ER PT J AU Moody, TW Tuthill, C Badamchian, M Goldstein, AL AF Moody, TW Tuthill, C Badamchian, M Goldstein, AL TI Thymosin alpha(1) inhibits mammary carcinogenesis in Fisher rats SO PEPTIDES LA English DT Article DE thymosin alpha(1); mammary carcinoma; chemoprevention; Fisher rats ID CELL LUNG-CANCER; BREAST-CANCER; CHEMOIMMUNOTHERAPY; INTERLEUKIN-2; EFFICACY; TRIAL AB The effects of thymosin alpha(1) (Talpha(1)) on mammary carcinogenesis was investigated in Fisher rats. Mammary carcinomas were observed 3 months after N-nitrosomethylurea (NMU) injection (10 mg, i.p.) into Fisher rats. Daily administration of Talpha(1) (10 mug, s.c.) reduced mammary carcinoma incidence and prolonged survival time. Animals treated with exogenous Talpha(1) had a significantly greater blood white cell density than control Fisher rats. These results suggest that Talpha(1) prevents mammary carcinoma incidence as a result of stimulation of the immune system. (C) 2002 Published by Elsevier Science Inc. C1 Cell & Canc Biol Branch, NCI, Rockville, MD 20850 USA. SciClone Pharmaceut, San Mateo, CA 94404 USA. George Washington Univ, Ctr Med, Dept Biochem & Mol Biol, Washington, DC 20037 USA. RP Moody, TW (reprint author), Cell & Canc Biol Branch, NCI, 9610 Med Ctr Dr,Bldg KWC,Rm 300, Rockville, MD 20850 USA. NR 26 TC 17 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2002 VL 23 IS 5 BP 1011 EP 1014 AR PII S0196-9781(02)00025-6 DI 10.1016/S0196-9781(02)00025-6 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 583ZV UT WOS:000177442800024 PM 12084534 ER PT J AU Van Ess, PJ Poloyac, S Mattson, MP Blouin, RA AF Van Ess, PJ Poloyac, S Mattson, MP Blouin, RA TI Blunted induction of hepatic CYP4A in TNF (p55(-/-/)p75(-/-)) double receptor knockout mice following clofibrate treatment SO PHARMACEUTICAL RESEARCH LA English DT Article DE catalase; clofibrate; cytochrome; P450 4A; cytokines; lauric acid hydroxylase; tumor necrosis factor-alpha ID PROLIFERATOR-ACTIVATED RECEPTOR; FETAL-RAT HEPATOCYTES; TUMOR-NECROSIS-FACTOR; CYTOCHROME-P-450 EXPRESSION; PPAR-ALPHA; PEROXISOME; INTERLEUKIN-6; SUPPRESSION; APOPTOSIS; ENDOTOXIN C1 Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY 40536 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. RP Blouin, RA (reprint author), Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012 NR 26 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAY PY 2002 VL 19 IS 5 BP 709 EP 713 AR UNSP 0724-8741/02/0500-0709-0 DI 10.1023/A:1015326717522 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 550AV UT WOS:000175481900021 ER PT J AU Ringner, M Peterson, C Khan, J AF Ringner, M Peterson, C Khan, J TI Analyzing array data using supervised methods SO PHARMACOGENOMICS LA English DT Article DE artificial neural networks; bioinformatics; diagnostic classification; diagnostic prediction; DNA chip; drug targets; genes; machine learning microarray; support vector machines; target identification ID GENE-EXPRESSION PROFILES; ARTIFICIAL NEURAL NETWORKS; CDNA MICROARRAYS; MOLECULAR CLASSIFICATION; BREAST-CANCER; OLIGONUCLEOTIDE ARRAYS; GENOMIC HYBRIDIZATION; CLUSTER-ANALYSIS; DNA MICROARRAYS; PREDICTION AB Pharmacogenomics is the application of genomic technologies to drug discovery and development, as well as for the elucidation of the mechanisms of drug action on cells and organisms. DNA microarrays measure genome-wide gene expression patterns and are an important tool for pharmacogenomic applications, such as the identification of molecular targets for drugs, toxicological studies and molecular diagnostics. Genome-wide investigations generate vast amounts of data and there is a need for computational methods to manage and analyze this information. Recently, several supervised methods, in which other information is utilized together with gene expression data, have been used to characterize genes and samples. The choice of analysis methods will influence the results and their interpretation, therefore it is important to be familiar with each method, its scope and limitations. Here, methods with special reference to applications for pharmacogenomics are reviewed. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Lund Univ, Dept Theoret Phys, Complex Syst Div, SE-22362 Lund, Sweden. NCI, Ctr Adv Technol, NIH, Gaithersburg, MD 20877 USA. RP Ringner, M (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 50,Room 5142,50 S Dr MSC 8000, Bethesda, MD 20892 USA. EM mringner@nhgri.nih.gov RI Ringner, Markus/G-3641-2011; Khan, Javed/P-9157-2014 OI Ringner, Markus/0000-0001-5469-8940; Khan, Javed/0000-0002-5858-0488 NR 55 TC 42 Z9 43 U1 0 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD MAY PY 2002 VL 3 IS 3 BP 403 EP 415 DI 10.1517/14622416.3.3.403 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 557BX UT WOS:000175888400017 PM 12052147 ER PT J AU Malson, JL Pickworth, WB AF Malson, JL Pickworth, WB TI Bidis - hand-rolled, Indian cigarettes: Effects on physiological, biochemical and subjective measures SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE bidis; beedies; adolescent; smoking ID NICOTINE DEPENDENCE; SMOKERS; SMOKING; CANCER; ADOLESCENTS; RISK AB Bidis, hand-rolled cigarettes imported from India, have become increasingly popular among US teenagers. These cigarettes are perceived as a safer, more natural alternative to conventional cigarette smoking. The present study was conducted to determine whether the acute effects of bidis and conventional cigarettes are similar. Undergraduate cigarette smokers with a history of bidi smoking were tested in two experimental sessions, using a within-subject design. Subjects smoked both a bidi and a conventional cigarette. Physiological and biochemical measures, subjective evaluations an smoking behavior characteristics were obtained before, during, and after smoking each experimental cigarette. Although time to smoke and puffs per cigarette were significantly higher after the bidi, physiological and biochemical effects of bidi smoking were similar to those of smoking conventional cigarettes. Bidis were rated less satisfying than the conventional cigarette. However, there were no significant differences between the cigarettes in other subjective measures. Our results do not support the belief that bidis are a safe alternative to conventional cigarettes. Furthermore, bidi smoking, like conventional cigarette smoking, may lead to nicotine dependence. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Coll Notre Dame Maryland, Baltimore, MD USA. RP Malson, JL (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 13 Z9 13 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2002 VL 72 IS 1-2 BP 443 EP 447 AR PII S0091-3057(02)00709-8 DI 10.1016/S0091-3057(02)00709-8 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 577MQ UT WOS:000177065200057 PM 11900818 ER PT J AU Piscitelli, SC Formentini, E Burstein, AH Alfaro, R Jagannatha, S Falloon, J AF Piscitelli, SC Formentini, E Burstein, AH Alfaro, R Jagannatha, S Falloon, J TI Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers SO PHARMACOTHERAPY LA English DT Article ID ST JOHNS WORT; SILYBUM-MARIANUM; ENZYMES AB Study Objective. To characterize the pharmacokinetics of indinavir in the presence and absence of milk thistle and to determine the offset of any effect of milk thistle on indinavir disposition. Design. Prospective open-label drug interaction study Setting. Outpatient clinic. Subjects. Ten healthy volunteers. Intervention. Blood samples were collected over 8 hours after the volunteers took four doses of indinavir 800 mg every 8 hours on an empty stomach for baseline pharmacokinetics. This dosing and sampling were repeated after the subjects took milk thistle 175 mg (confirmed to contain silymarin 153 mg, the active ingredient) 3 times/day for 3 weeks. After an 11-day washout, indinavir dosing and blood sampling were repeated to evaluate the offset of any potential interaction. Measurements and Main Results. Indinavir concentrations were measured by using a validated high-performance liquid chromatography method. The following pharmacokinetic parameters were determined: highest concentration (C-max), hour-0 concentration, hour-8 concentration (CS), time to reach C-max, and area under the plasma concentration-time curve over the 8-hour dosing interval (AUC(8)). Milk thistle did not alter significantly the overall exposure of indinavir, as evidenced by a 9% reduction in the indinavir AUC(8) after 3 weeks of dosing with milk thistle, although the least squares mean trough level (C-8) was significantly decreased by 25%. Conclusion. Milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Pharm, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. RP Falloon, J (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11C103, Bethesda, MD 20892 USA. NR 12 TC 90 Z9 96 U1 1 U2 3 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2002 VL 22 IS 5 BP 551 EP 556 DI 10.1592/phco.22.8.551.33205 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 547HL UT WOS:000175326900001 PM 12013352 ER PT J AU Chen, X Yang, L Oppenheim, JJ Howard, OMZ AF Chen, X Yang, L Oppenheim, JJ Howard, OMZ TI Cellular pharmacology studies of shikonin derivatives SO PHYTOTHERAPY RESEARCH LA English DT Review DE shikonin; Zicao; cellular pharmacology; anti tumour; antiinflammatory ID ANTI-TUMOR ACTIVITY; LITHOSPERMUM-ERYTHRORHIZON; GRANULATION-TISSUE; ANTICANCER DRUGS; ARNEBIA-EUCHROMA; TOPOISOMERASE-I; NAPHTHOQUINONE DERIVATIVES; DNA TOPOISOMERASE; PLANT-EXTRACTS; LEUKEMIA-CELLS AB The naphthoquinone pigment, shikonin, isolated from Lithospermum erythrorhizon Sieb. et Zucc.(Boraginaceae) and its derivatives are the active components isolated from the Chinese herbal therapeutic, Zicao. Historically, Zicao root extracts have been used to treat macular eruption, measles, sore-throat, carbuncles and burns. Multiple pharmacological actions have been attributed to shikonin, e.g. antiinflammatory, antigonadotropic and anti-HIV-1 activity. In this review, several therapeutic applications of shikonin will be summarized including its pleiotropic, antiinflammatory and antitumour effects. Widely diverse and sometimes conflicting activities have been attributed to shikonin, e.g. wound healing, enhanced granuloma formation, suppression of local acute inflammatory reactions, inhibition of angiogenesis, inhibition of select chemokine ligands, inhibition of DNA topoisomerase activity, inhibition of platelet activation and antimicrobial activity. Comparison of the various reported mechanisms of action for shikonin lead us to hypothesize that shikonin is an effective inhibitor of protein-protein interaction with multiple targets in both the intracellular and extracellular compartments. This general inhibitory effect can account for the broad spectrum of shikonin biological and pharmacological activities. Published in 2002 by John Wiley Sons, Ltd. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Howard, OMZ (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. RI Chen, Xin/I-6601-2015; Howard, O M Zack/B-6117-2012 OI Chen, Xin/0000-0002-2628-4027; Howard, O M Zack/0000-0002-0505-7052 FU NCCIH NIH HHS [Y2-AT-9002] NR 73 TC 197 Z9 212 U1 3 U2 49 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD MAY PY 2002 VL 16 IS 3 BP 199 EP 209 DI 10.1002/ptr.1100 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 554VP UT WOS:000175758100001 PM 12164262 ER PT J AU Kalache, KD Lehmann, K Chaoui, R Kivelitz, DE Mundlos, S Bollmann, R AF Kalache, KD Lehmann, K Chaoui, R Kivelitz, DE Mundlos, S Bollmann, R TI Prenatal diagnosis of partial agenesis of the corpus callosum in a fetus with thanatophoric dysplasia type 2 SO PRENATAL DIAGNOSIS LA English DT Article DE thanatophoric dysplasia type 2; corpus callosum abnormalities; ultrasonography; magnetic resonance imaging ID MUTATIONS; ABNORMALITIES; MICE AB A fetus with thanatophoric dysplasia type 2 (TD2) associated with cloverleaf skull and abnormal development of the corpus callosum is reported. This case represent,, the first prenatal direct visualization a partial agenesis of the corpus callosum (ACC) using high-resolution ultrasonography and colour power Doppler. which was confirmed by post-mortem magnetic resonance imaging (MRI). The causal link between cloverleaf skull in TD and partial ACC is discussed. Copyright (C) 2002 John Wiley Sons. Ltd. C1 Humboldt Univ, Fac Med, Univ Hosp, Dept Radiol, Berlin, Germany. Humboldt Univ, Fac Med, Dept Med Genet, Berlin, Germany. Humboldt Univ, Fac Med, Dept Obstet & Gynaecol, Fetal Med Unit, Berlin, Germany. RP Kalache, KD (reprint author), Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,NIH, 4707 St Antoine Blvd, Detroit, MI 48201 USA. OI Dathe, Katarina/0000-0002-8674-5817 NR 24 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAY PY 2002 VL 22 IS 5 BP 404 EP 407 DI 10.1002/pd.327 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 554LR UT WOS:000175737500014 PM 12001196 ER PT J AU Troy, JB Shou, T AF Troy, JB Shou, T TI The receptive fields of cat retinal ganglion cells in physiological and pathological states: where we are after half a century of research SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID LATERAL GENICULATE-NUCLEUS; OPTIC-NERVE-FIBERS; INTRAOCULAR-PRESSURE ELEVATION; CONTRAST GAIN-CONTROL; MEDIAL INTERLAMINAR NUCLEUS; LINEAR SPATIAL SUMMATION; STARBURST AMACRINE CELLS; GAMMA-AMINOBUTYRIC ACID; PUPILLARY LIGHT REFLEX; GATED CALCIUM CURRENTS AB Studies on the receptive field properties of cat retinal ganglion cells over the past half-century are reviewed within the context of the role played by the receptive field in visual information processing. Emphasis is placed on the work conducted within the past 20 years, but a summary of key contributions from the 1950s to 1970s is provided. We have sought to review aspects of the ganglion cell receptive field that have not been featured prominently in previous review articles. Our review of the receptive field properties of X- and Y-cells focuses on quantitative studies and includes consideration of the function of the receptive field in visual signal processing. We discuss the non-classical as well as the classical receptive field. Attention is also given to the receptive field properties of the less well-studied cat ganglion cells-the W-cells-and the effect of pathology on cat ganglion cell properties. Although work from our laboratories is highlighted, we hope that we have given a reasonably balanced view of the current state of the field. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Fudan Univ, Sch Life Sci, Ctr Brain Sci Res, Shanghai 200433, Peoples R China. NIMH, Sect Neural Coding & Computat, Neuropsychol Lab, Bethesda, MD USA. Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. Chinese Acad Sci, Lab Visual Informat Proc, Beijing, Peoples R China. RP Shou, T (reprint author), Fudan Univ, Sch Life Sci, Ctr Brain Sci Res, Shanghai 200433, Peoples R China. RI Troy, John/B-7635-2009 FU NEI NIH HHS [R01 EY06669] NR 392 TC 50 Z9 51 U1 3 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD MAY PY 2002 VL 21 IS 3 BP 263 EP 302 AR PII S1350-9462(02)00002-2 DI 10.1016/S1350-9462(02)00002-2 PG 40 WC Ophthalmology SC Ophthalmology GA 578ZM UT WOS:000177151000001 PM 12052385 ER PT J AU Kajava, AV Kobe, B AF Kajava, AV Kobe, B TI Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information SO PROTEIN SCIENCE LA English DT Article DE crystal structure; leucine-rich repeat; molecular modeling; solenoid-like proteins; structural bioinformatics ID CRYSTAL-STRUCTURE; MOLECULAR CHARACTERIZATION; CHORIONIC-GONADOTROPIN; SIGNAL-TRANSDUCTION; BINDING PROTEIN; DOMAIN; MOTIF; SEQUENCE; RECEPTOR; EXPRESSION AB The three-dimensional structures of leucine-rich repeat (LRR) -containing proteins from five different families were previously predicted based on the crystal structure of the ribonuclease inhibitor. using an approach that combined homology-based modeling, structure-based sequence alignment of LRRs, and several rational assumptions. The structural models have been produced based on very limited sequence similarity, which, in general. cannot yield trustworthy predictions. Recently, the protein structures from three of these five families have been determined. In this report we estimate the quality of the modeling approach by comparing the models with the experimentally determined structures. The comparison suggests that the general architecture, curvature, "interior/exterior" orientations of side chains. and backbone conformation of the LRR structures can be predicted correctly. On the other hand. the analysis revealed that, in some cases. it is difficult to predict correctly the twist of the overall super-helical structure. Taking into consideration the conclusions from these comparisons, we identified a new family of bacterial LRR proteins and present its structural model. The reliability of the LRR protein modeling suggests that it would be informative to apply similar modeling approaches to other classes of solenoid proteins. C1 NIH, Ctr Informat Technol, Ctr Mol Modeling, Bethesda, MD 20892 USA. Univ Queensland, Dept Biochem & Mol Biol, Brisbane, Qld 4072, Australia. Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. RP Kajava, AV (reprint author), NIH, Ctr Informat Technol, Ctr Mol Modeling, Bldg 12A,Room 2047, Bethesda, MD 20892 USA. RI Kobe, Bostjan/D-1292-2009; Kajava, Andrey/E-1107-2014 OI Kobe, Bostjan/0000-0001-9413-9166; Kajava, Andrey/0000-0002-2342-6886 NR 45 TC 85 Z9 88 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2002 VL 11 IS 5 BP 1082 EP 1090 DI 10.1110/ps.4010102 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 544DA UT WOS:000175141900009 PM 11967365 ER PT J CA NICHD Early Child Care Res Network TI Child-care structure -> process -> outcome: Direct and indirect effects of child-care quality on young children's development SO PSYCHOLOGICAL SCIENCE LA English DT Article ID LANGUAGE-DEVELOPMENT; SOCIAL-DEVELOPMENT; CRITERIA; POLICY AB With data front the NICHD Study of Early Child Care, we used structural equation modeling to test paths from structural indicators of child-care quality, specifically caregiver training and child-staff ratio, through a process indicator to child outcomes. There were three main findings: (a) Quality, of maternal caregiving was the strongest predictor of cognitive competence, as well as caregivers' ratings of social competence; (b) quality, of nonmaternal caregiving was associated with cognitive competence and caregivers' ratings of social competence; and (c) there was a mediated path from both caregiver training and child-staff ratio through quality of nonmaternal caregiving to cognitive competence, as well as to caregivers' ratings of social competence, that was not accounted for entirely by family, v variables. These findings provide empirical support for policies that improve state regulations for caregiver training and child-staff ratios. C1 NICHHD, CRMC, Rockville, MD 20852 USA. RP NICHHD, CRMC, 6100 Execut Blvd 4B05, Rockville, MD 20852 USA. NR 42 TC 8 Z9 8 U1 8 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0956-7976 EI 1467-9280 J9 PSYCHOL SCI JI Psychol. Sci. PD MAY PY 2002 VL 13 IS 3 BP 199 EP 206 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 544EE UT WOS:000175144600001 ER PT J AU Senior, C AF Senior, C TI Not a hit through the covers SO PSYCHOLOGIST LA English DT Letter C1 NIMH, Lab Brain & Cognit, Sect Cognit Neuropsychol, Bethesda, MD 20892 USA. RP Senior, C (reprint author), NIMH, Lab Brain & Cognit, Sect Cognit Neuropsychol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0952-8229 J9 PSYCHOLOGIST JI Psychologist PD MAY PY 2002 VL 15 IS 5 BP 222 EP 222 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 553ZN UT WOS:000175708400010 ER PT J AU Holmes, A Murphy, DL Crawley, JN AF Holmes, A Murphy, DL Crawley, JN TI Reduced aggression in mice lacking the serotonin transporter SO PSYCHOPHARMACOLOGY LA English DT Article DE serotonin transporter; knockout mouse; aggression; resident-intruder; RU24969; locomotor activity ID KNOCK-OUT MICE; NITRIC-OXIDE SYNTHASE; 5-HT TRANSPORTER; BRAIN-SEROTONIN; BINDING-SITES; MONOAMINE-OXIDASE; MUTANT MICE; RECEPTOR; BEHAVIOR; ASSOCIATION AB Rationale: Dysregulation of the brain serotonergic system has been implicated in the pathophysiology of violence and aggression. As a key regulator of central serotonergic activity, dysfunction of the serotonin transporter (5-HTT) represents a potential mechanism mediating pathological aggression. Objectives: To assess aggressive behavior in 5-HTT knockout (KO) mice. To examine home cage activity and 5-HT1A/1B receptor function in 5-HTT KO mice as factors contributing to an aggressive phenotype. Methods: Isolated male 5-HTT KO mice were compared to +/+ control mice using the resident-intruder test for aggression over two encounters. Locomotor activity was measured in the home cage over a 24-h period. 5-HT1A/1B receptor function was assessed via the pharmacological effects of the 5-HT1A/1B receptor agonist, RU24969, on locomotion. Results: 5-HTT -/- mice were slower to attack the intruder and attacked with less frequency than +/+ littermates, but showed equivalent social investigation. 5-HTT +/- mice were as quick to attack, but made fewer overall attacks, as compared to +/+ controls. Aggression increased with repeated exposure to an intruder in 5-HTT +/- and +/+ mice, but not in 5-HTT -/- mice. 5-HTT -/- mice showed a normal circadian pattern of home cage activity, but less activity overall, as compared to 5-HTT +/- and +/+ mice. RU24969 (5 mg/kg) produced hyperlocomotor effects in 5-HT +/- and +/+, but not 5-HTT -/- mice. Conclusions: Deletion of the 5-HTT gene produces a reduction in aggressive behavior and home cage activity. Desensitization of 5-HT1A/1B receptor function may contribute to reduced aggression in 5-HTT KO mice. C1 NIMH, Sect Behav Genom, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Holmes, A (reprint author), NIMH, Sect Behav Genom, Bldg 10 Room 4D11, Bethesda, MD 20892 USA. NR 71 TC 157 Z9 161 U1 1 U2 16 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2002 VL 161 IS 2 BP 160 EP 167 DI 10.1007/s00213-002-1024-3 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 557CH UT WOS:000175889400007 PM 11981596 ER PT J AU Baas, JMP Grillon, C Bocker, KBE Brack, AA Morgan, CA Kenemans, JL Verbaten, MN AF Baas, JMP Grillon, C Bocker, KBE Brack, AA Morgan, CA Kenemans, JL Verbaten, MN TI Benzodiazepines have no effect on fear-potentiated startle in humans SO PSYCHOPHARMACOLOGY LA English DT Article DE fear; anxiety; benzodiazepine; oxazepam; diazepam; startle reflex ID POSTTRAUMATIC-STRESS-DISORDER; ACOUSTIC STARTLE; CONDITIONED FEAR; ANTICIPATORY ANXIETY; ANIMAL-MODELS; BASE-LINE; REFLEX; DIAZEPAM; AMYGDALA; PARADIGM AB Rationale: Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. Objective: The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. Methods: Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cuespecific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. Results: None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. Conclusions: At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders. C1 Univ Utrecht, Fac Pharm, Dept Psychopharmacol, NL-3508 TB Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Connecticut VA Med Ctr, Dept Psychiat, West Haven, CT 06516 USA. RP Baas, JMP (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K N Dr MSC 2670, Bethesda, MD 20892 USA. OI Baas, Johanna/0000-0001-6267-8712 NR 46 TC 77 Z9 77 U1 3 U2 11 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2002 VL 161 IS 3 BP 233 EP 247 DI 10.1007/s00213-002-1011-8 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 562JG UT WOS:000176193200003 PM 12021826 ER PT J AU Powell, LH Lovallo, WR Matthews, KA Meyer, P Midgley, AR Baum, A Stone, AA Underwood, L McCann, JJ Herro, KJ Ory, MG AF Powell, LH Lovallo, WR Matthews, KA Meyer, P Midgley, AR Baum, A Stone, AA Underwood, L McCann, JJ Herro, KJ Ory, MG TI Physiologic markers of chronic stress in premenopausal, middle-aged women SO PSYCHOSOMATIC MEDICINE LA English DT Article DE cortisol; catecholamines; testosterone; divorce; chronic stress; women's health; aging ID PLASMA TESTOSTERONE LEVELS; SALIVARY CORTISOL; PSYCHOLOGICAL STRESS; SERUM TESTOSTERONE; PERCEIVED STRESS; SEX-DIFFERENCES; SOCIAL SUPPORT; EMPLOYED WOMEN; JOB STRAIN; RESPONSES AB Objective: The purpose of this study was to identify physiological markers of chronic stress in middle-aged women that can be assessed simply and are thus feasible for introduction into large-scale, epidemiologic studies of aging. Methods: Subjects were 40 nonsmoking, premenopausal women between the ages of 42 and 52 years, 20 of whom were chronically stressed because of undergoing a divorce or separation and 20 of whom were nonstressed because of being in stable marriages. Stressed and nonstressed women were matched for age, ethnicity, and education. Hypotheses focused on morning and evening salivary cortisol, overnight urinary catecholamines, cortisol, and testosterone, and platelet catecholamines. Results: Relative to the nonstressed control subjects, the stressed women had elevated evening (9 PM) salivary cortisols, a finding that was observed on both days (mixed effects model: effect = 0.44; se = 0.14, p = .003). Support for the importance of the HPA axis was provided by the observation that the stressed women had less suppression of salivary cortisol in response to low-dose dexamethasone. Contrary to our hypothesis that stressed women would have lower overnight urinary testosterone, they had higher testosterone on day 2 (stressed = 0.76 ng/mg, nonstressed = 0.55 ng/mg; p = .04). Post hoc repeated measures analysis revealed a significant group effect over all time periods of observation (F = 5.48, p = .03, df = 1,18). Stressed women had a nonsignificant trend toward elevated platelet catecholamines. No association was found for overnight urinary catecholamines or cortisol. Conclusions: Promising markers of marital upheaval in middle-aged women are evening salivary cortisol and urinary testosterone from a first morning void. Replication of these findings with the same and different chronic stressors and with women of older ages is needed. The low cost and minimal burden of these potential markers makes it feasible to introduce them into large-scale epidemiologic studies of health in aging women. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Inst Healthy Aging, Chicago, IL 60612 USA. Univ Oklahoma, Hlth Sci Ctr, VA Med Ctr, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Oklahoma City, OK USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Michigan, Reprod Sci Program, Ann Arbor, MI 48109 USA. SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. Fetzer Inst, Kalamazoo, MI USA. NIA, Behav & Social Sci Res Program, NIH, Bethesda, MD 20892 USA. RP Powell, LH (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, 1700 W Van Buren St,Suite 470, Chicago, IL 60612 USA. EM lpowell@rush.edu NR 49 TC 81 Z9 81 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 2002 VL 64 IS 3 BP 502 EP 509 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 555JV UT WOS:000175791700015 PM 12021424 ER PT J AU Wasserman, BA Smith, WI Trout, HH Cannon, RO Balaban, RS Arai, AE AF Wasserman, BA Smith, WI Trout, HH Cannon, RO Balaban, RS Arai, AE TI Carotid artery atherosclerosis: In vivo morphologic characterization with gadolinium-enhanced double-oblique MR imaging - Initial results SO RADIOLOGY LA English DT Article DE arteriosclerosis; magnetic resonance (MR), high-resolution; magnetic resonance (MR), tissue characterization; magnetic resonance (MR), vascular studies ID PLAQUE RUPTURE; IN-VITRO; MECHANISMS; COMPONENTS; STENOSIS; CONTRAST; IMAGES; WALL AB In nine subjects With carotid atherosclerosis, double-oblique, contrast material-enhanced, double inversion-recovery, fast spin-echo magnetic resonance (MR) images were acquired through atheroma in the proximal internal carotid artery. Fibrocellular tissue within atheroma selectively enhanced 29% after administration of gadolinium-based contrast agent. Contrast enhancement helped discriminate fibrous cap from lipid core with a contrast-to-noise ratio as good as or better than that with T2-weighted MR images but With approximately twice the signal-to-noise ratio (postcontrast images, 36.6 +/- 3.6; T2-weighted images, 17.5 +/- 2.1; P < .001). (C) RSNA, 2002. C1 Johns Hopkins Univ Hosp, Dept Radiol Neuroradiol, Baltimore, MD 21287 USA. Natl Heart Lung & Blood Inst, Lab Cardiac Energet, NIH, Bethesda, MD USA. Natl Heart Lung & Blood Inst, Cardiol Branch, NIH, Bethesda, MD USA. Suburban Hosp, Dept Pathol, Bethesda, MD USA. Suburban Hosp, Dept Surg, Bethesda, MD USA. RP Wasserman, BA (reprint author), Johns Hopkins Univ Hosp, Dept Radiol Neuroradiol, 600 N Wolfe St Phipps B-100, Baltimore, MD 21287 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 FU PHS HHS [98-H-0157] NR 24 TC 188 Z9 196 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2002 VL 223 IS 2 BP 566 EP 573 DI 10.1148/radiol.2232010659 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 546JB UT WOS:000175270000042 PM 11997569 ER PT J AU Cheng, RYS Alvord, WG Powell, D Kasprzak, KS Anderson, LM AF Cheng, RYS Alvord, WG Powell, D Kasprzak, KS Anderson, LM TI Microarray analysis of altered gene expression in the TM4 Sertoli-like cell line exposed to chromium(III) chloride SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Sertoli-like cell; chromium(III); microarray; gene expression; Bach2 ID ACYL-COA SYNTHETASE; BINDING-PROTEIN; MESSENGER-RNA; ASPARAGINE SYNTHETASE; TRANSCRIPTION FACTORS; RAT TESTIS; STATISTICAL-ANALYSIS; DENSITY-LIPOPROTEIN; CDNA MICROARRAY; GERM-CELLS AB Chromium(III) chloride is a common human exposure metal that is a preconceptional carcinogen in mice, although it enters cells poorly, and is non-toxic and non-carcinogenic in most biologic systems. An indirect effect on sperm is postulated, and this effect might be mediated through the testicular Sertoli cells that influence spermatogenesis. To test this possibility, we exposed mouse TM4 Sertoli-like cultured cells to 1 mM CrCl3.6H(2)O, a non-toxic dose, for 7 days and then extracted mRNA for microarray analysis. The chromium(III) chloride had modest effects on the expression of many genes, in the range of 1.5-2.3-fold. These effects provided an opportunity for development of statistical approaches for sifting microarray data in a situation where differences were small. Data were winnowed by screening for those ratios that fell outside the 99% confidence limits and/or represented a greater than or equal to50% change in expression in the three comparison pairs. Fifty-two genes/clones were significant after the Bonferroni adjustment for multiple comparisons. The largest average increase was observed for the transcription factor Bach2, and this increase was confirmed by RT-PCR. The results show that Cr(III) has significant effects on gene expression in a Sertoli-like cell line. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Data Management Serv Inc, Frederick, MD USA. RP Cheng, RYS (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Box B,Bldg 538,Ft Detrick, Frederick, MD 21702 USA. OI Cheng, Robert/0000-0003-0287-6439 NR 69 TC 18 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 2002 VL 16 IS 3 BP 223 EP 236 AR PII S0890-6238(02)00016-3 DI 10.1016/S0890-6238(02)00016-3 PG 14 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 597CZ UT WOS:000178205700003 PM 12128095 ER PT J AU Dodd, SJ Williams, DS Olson, C Silva, AC Koretsky, AP Ho, C AF Dodd, SJ Williams, DS Olson, C Silva, AC Koretsky, AP Ho, C TI An open transverse z-gradient coil design for magnetic resonance imaging SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article AB A method for designing open gradient coils for magnetic resonance imaging using a simulated annealing optimization algorithm is described. The algorithm allows the current density toward the open end to be increased, compensating for the "missing" coil section. A semicylindrical transverse z gradient has been designed and built providing a gradient efficiency of 0.82 mT/m/A. The prototype provided good agreement with the theory over the central imaging region. (C) 2002 American Institute of Physics. C1 Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78229 USA. Carnegie Mellon Univ, Pittsburgh NMR Ctr Biomed Res, Pittsburgh, PA 15213 USA. NINCDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Dodd, SJ (reprint author), Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Silva, Afonso/A-7129-2009; Koretsky, Alan/C-7940-2015; Ho, Chien/O-6112-2016 OI Koretsky, Alan/0000-0002-8085-4756; Ho, Chien/0000-0002-4094-9232 NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD MAY PY 2002 VL 73 IS 5 BP 2208 EP 2210 DI 10.1063/1.1470709 PG 3 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 545AN UT WOS:000175194200040 ER PT J AU Moriuchi, M Moriuchi, H AF Moriuchi, M Moriuchi, H TI In vitro reactivation of HIV-1 by stimulation with herpes simplex virus infection SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS; TRANSMISSION; REPLICATION C1 Nagasaki Univ, Grad Sch Med Sci, Dept Mol Microbiol & Immunol, Div Med Virol, Nagasaki 8528523, Japan. NIAID, Labs Immunoregulat, NIH, Bethesda, MD 20892 USA. RP Moriuchi, H (reprint author), Nagasaki Univ, Grad Sch Med Sci, Dept Mol Microbiol & Immunol, Div Med Virol, Nagasaki 8528523, Japan. NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAY PY 2002 VL 29 IS 5 BP 308 EP 309 DI 10.1097/00007435-200205000-00010 PG 2 WC Infectious Diseases SC Infectious Diseases GA 549NK UT WOS:000175450200010 PM 11984449 ER PT J AU Bazzano, LA He, J Ogden, LG Loria, C Vupputuri, S Myers, L Whelton, PK AF Bazzano, LA He, J Ogden, LG Loria, C Vupputuri, S Myers, L Whelton, PK TI Dietary intake of folate and risk of stroke in US men and women - NHANES I Epidemiologic Follow-up Study SO STROKE LA English DT Article DE cardiovascular disease; cerebrovascular disorders; diet; folic acid; prospective studies ID CORONARY HEART-DISEASE; NUTRITION EXAMINATION SURVEY; FOLIC-ACID; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; NATIONAL-HEALTH; SERUM FOLATE; ATHEROSCLEROSIS; HOMOCYST(E)INE; VITAMIN-B-6 AB Background and Purpose-Few population-based studies have examined the relationship between dietary intake of folate and risk of stroke and cardiovascular disease (CVD). This study examines the association between dietary intake of folate and the subsequent risk of stroke and CVD. Methods-Study participants included 9764 US men and women aged 25 to 74 years who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS) and were free of CVD at baseline. Dietary intake of folate was assessed at baseline using a 24-hour dietary recall and calculated using ESHA software. Incidence data for stroke and CVD were obtained from medical records and death certificates. Results-Over an average of 19 years of follow-up, 926 incident stroke events and 3758 incident CVD events were documented. The relative risk (RR) was 0.79 (95% confidence interval [CI], 0.63 to 0.99, P=0.03 for trend) for incident stroke events and 0.86 (95% CI: 0.78 to 0.95, P<0.001 for trend) for incident CVD events in the highest quartile of dietary folate intake (median, 405.0 μg/day) compared with those in the lowest quartile (median, 99.0 μg/day), after adjustment for established cardiovascular risk factors and dietary factors. Conclusions-Our findings indicate an inverse relationship between dietary intake of folate and subsequent risk of stroke and CVD. Increasing dietary intake of folate from food sources may be an important approach to the prevention of CVD in the US population. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA 70112 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP He, J (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1430 Tulane Ave,SL18, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [R01HL60300, R03 HL61954] NR 45 TC 92 Z9 96 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2002 VL 33 IS 5 BP 1183 EP 1188 DI 10.1161/01.STR.0000014607.90464.88 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 549ML UT WOS:000175447900011 PM 11988588 ER PT J AU Barrientos, LG Louis, JM Botos, I Mori, T Han, ZZ O'Keefe, BR Boyd, MR Wlodawer, A Gronenborn, AM AF Barrientos, LG Louis, JM Botos, I Mori, T Han, ZZ O'Keefe, BR Boyd, MR Wlodawer, A Gronenborn, AM TI The domain-swapped dimer of cyanovirin-N is in a metastable folded state: Reconciliation of X-ray and NMR structures SO STRUCTURE LA English DT Article DE 3D domain swapping; cyanovirin-N; protein folding; NMR; X-ray ID RESIDUAL DIPOLAR COUPLINGS; MACROMOLECULAR STRUCTURE DETERMINATION; BOVINE SEMINAL RIBONUCLEASE; HIV-INACTIVATING PROTEIN; CRYSTAL-STRUCTURE; PROLINE RESIDUES; NEURODEGENERATIVE DISEASES; GLUTAMINE REPEATS; RNASE-A; RESOLUTION AB The structure of the potent HIV-inactivating protein cyanovirin-N was previously found by NMR to be a monomer in solution and a domain-swapped dimer by X-ray crystallography. Here we demonstrate that in solution, CV-N can exist both in monomeric an in domain-swapped dimeric form. The dimer is a metastable, kinetically trapped structure at neutral pH and room temperature. Based on orientational NMR constraints, we show that the domain-swapped solution dimer is similar to structures in two different crystal forms, exhibiting solely a small reorientation around the hinge region. Mutation of the single proline residue in the hinge to glycine significantly stabilizes the protein in both its monomeric and dimeric forms. By contrast, mutation of the neighboring serine to proline results in an exclusively dimeric protein, caused by a drastic destabilization of the monomer. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Mol Targets Drug Discovery Program, Frederick, MD 21702 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 48 TC 94 Z9 96 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2002 VL 10 IS 5 BP 673 EP 686 AR PII S0969-2126(02)00758-X DI 10.1016/S0969-2126(02)00758-X PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 548ZK UT WOS:000175419900010 PM 12015150 ER PT J AU Ashby, CR Paul, M Gardner, EL Gerasimov, MR Dewey, SL Lennon, IC Taylor, SJC AF Ashby, CR Paul, M Gardner, EL Gerasimov, MR Dewey, SL Lennon, IC Taylor, SJC TI Systemic administration of 1R,4S-4-AminoCyclopent-2-Ene-Carboxylic acid, a reversible inhibitor of GABA transaminase, blocks expression of conditioned place preference to cocaine and nicotine in rats SO SYNAPSE LA English DT Article DE conditioned place preference; GABA; nicotine; cocaine ID NUCLEUS-ACCUMBENS DOPAMINE; PROGRESSIVE-RATIO; BACLOFEN; ADDICTION; INCREASES; STRATEGY; BEHAVIOR; HEROIN AB We examined the effect of 1R,4S-4-amino-eyelopent-2-ene-carboxylic acid (ACC), a reversible inhibitor of GABA transaminase, on the expression of conditioned place preference response to cocaine and nicotine in rats. Cocaine (20 mg/kg i.p.) and nicotine (0.4 mg/kg s.c.), but not vehicle or 300 mg/kg i.p. of ACC, produced a significant conditioned place preference response. Pretreatment of animals with 300 and 75 mg(kg i.p. of ACC significantly attenuated the expression of the cocaine- and nicotine-induced conditioned place preference responses, respectively. These results are the first to suggest that reversible inhibition of GABA transaminase may be useful in blocking cue-induced relapse to nicotine and cocaine. (C) 2002 Wiley-Liss, Inc. C1 St Johns Univ, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. Pfizer Res Labs, Brooklyn, NY USA. NIDA, Intramural Res Program, Baltimore, MD USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Chirotech Technol Ltd, Cambridge, England. RP Ashby, CR (reprint author), St Johns Univ, PHS Dept, 8000 Utopia Pkwy, Jamaica, NY 11439 USA. NR 17 TC 29 Z9 29 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 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2002 VL 44 IS 2 BP 61 EP 63 DI 10.1002/syn.10052 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 539GG UT WOS:000174861700001 PM 11891877 ER PT J AU Rothman, RB Carroll, FI Morales, M Rowley, DL Rice, KC Dersch, CM Donovan, DM AF Rothman, RB Carroll, FI Morales, M Rowley, DL Rice, KC Dersch, CM Donovan, DM TI Studies of the biogenic amine transporters. 10. Characterization of a novel cocaine binding site in brain membranes prepared from dopamine transporter knockout mice SO SYNAPSE LA English DT Article DE cocaine; RTI-55; dopamine transporter; dopamine ID HIGH-AFFINITY; I-125 RTI-55; RAT-BRAIN; SEROTONIN; ANALOGS; CAUDATE; NOREPINEPHRINE; AMPHETAMINE; ESTER; ABUSE AB Previous work suggested that the cocaine analog [I-125]RTI-55 labels a novel binding site in rat brain membranes, which is not associated with the dopamine (DA), serotonin (5-HT), or norepinephrine (NE) tran porters [Rothman et al. (1995) J Pharmacol xp Ther 274:385-395]. Here, we tested whether this site is a product of the DA transporter (DAT) gene. We used a T-antigen knock-in at the DAT gene that results in an effective DAT knock-out (KO) confirmed by Southern blot, DAT immunobistochemistry, and [I-125]RTI-55 ligand binding. Brain membranes were prepared from frozen whole brain minus caudate of wild-type (WT) B6/Sv129, +/+ and -/- (KO) mice. KO mice were used at approximately 23 days of age. Binding surface analysis of [I-125]RTI-55 binding to membranes prepared from the brains of WT mice, with 100 nM citalopram to block binding to the 5-HT transporter (SERT), revealed two binding sites: the DAT and a second site, replicating previous studies conducted with rat brains. In the absence of the DAT (-/- mice), binding surface analysis demonstrated that [I-125]RTI-55 labeled two sites: the NET and a second site called site "X." Structure-activity studies of site "X" demonstrated that high-affinity ligands for the DAT, NET, and SERT have low or negligible affinity for site "X" The relatively high density of site "X" in brain membranes and the fact that the K-i values of cocaine and cocaethylene for site "X" are in the range achieved in the brain following cocaine administration suggests that site "X" could contribute to the pharmacological or toxicological effects of cocaine. Further progress in delineating the function of site "X" will depend on developing potent and selective agents for this site. Published 2002 Wiley-Liss, Inc.(dagger) C1 NIDA, IRP, DIR, Baltimore, MD 21224 USA. RTI, Res Triangle Pk, NC USA. NIA, TKFS, RRB, GRC,NIH, Baltimore, MD USA. NIDDK, LMC, NIH, Bethesda, MD USA. RP Rothman, RB (reprint author), NIDA, IRP, DIR, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 15 TC 4 Z9 4 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 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2002 VL 44 IS 2 BP 94 EP 105 DI 10.1002/syn.10060 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 539GG UT WOS:000174861700005 PM 11891881 ER PT J AU Doudet, DJ Jivan, S Ruth, TJ Wyatt, RJ AF Doudet, DJ Jivan, S Ruth, TJ Wyatt, RJ TI In vivo PET studies of the dopamine D1 receptors in rhesus monkeys with long-term MPTP-induced parkinsonism SO SYNAPSE LA English DT Article ID IN-VIVO; STRIATAL DOPAMINE; ENDOGENOUS DOPAMINE; H-3 SCH-23390; HUMAN-BRAIN; D-1; BINDING; DISEASE; NEURONS; SCHIZOPHRENIA C1 Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, Kinsmen Lab Neurol Res, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, TRIUMF, Vancouver, BC V6T 2B5, Canada. NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. RP Doudet, DJ (reprint author), Univ British Columbia, Dept Med, Div Neurol, 2221 Wesbrook Mall,Rm M36,Purdy Pavil, Vancouver, BC V6T 2B5, Canada. NR 30 TC 10 Z9 10 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2002 VL 44 IS 2 BP 111 EP 115 DI 10.1002/syn.10057 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 539GG UT WOS:000174861700007 PM 11891883 ER PT J AU Lucas, R Lijnen, HR Suffredini, AF Pepper, MS Steinberg, KP Martin, TR Pugin, J AF Lucas, R Lijnen, HR Suffredini, AF Pepper, MS Steinberg, KP Martin, TR Pugin, J TI Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE adult respiratory distress syndrome; endothelium; angiostatin; lipopolysaccharide ID RESPIRATORY-DISTRESS-SYNDROME; SOLUBLE FAS LIGAND; MATRIX METALLOPROTEINASES; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; INDUCE APOPTOSIS; PLASMINOGEN; GENERATION; INJURY; ANGIOGENESIS AB Acute respiratory distress syndrome (ARDS) is characterized by a disruption of the alveolar-capillary barrier, due to both an epithelial and an endothelial dysfunction. Whereas epithelial apoptosis seems to be mainly mediated by Fas ligand, the mediators of endothelial damage remain to be identified. Angiostatin, a powerful inhibitor of angiogenesis in vivo, also specifically induces apoptosis in endothelial cells. The concentration of various enzymes that cleave angiostatin from plasminogen was reported to be significantly increased in bronchalveolar lavage (BAL) fluids from patients with ARDS. Therefore, in this study, we investigated whether angiostatin was generated during the pulmonary inflammatory response of both healthy subjects challenged with endobronchial endotoxin and in patients with ARDS, We found significantly elevated angiostatin levels in BAL fluids from patients at risk for and with early ARDS (up to 0.022% and 0.018% of total protein, respectively), as well as in BAL fluids from volunteers treated with endotoxin (up to 1.17% of total protein), as compared to BAL fluids from control patients (<0.005% of total protein). These data suggest that angiostatin may contribute to the endothelial damage observed in ARDS, probably via an increased permeability of the alveolar capillary barrier, allowing for an intra-alveolar processing of its precursor plasminogen. C1 Univ Konstanz, Chair Biochem Pharmacol, Dept Biochem Pharmacol, D-78457 Constance, Germany. Univ Hosp Geneva, Dept Internal Med, Div Med Intens Care, Geneva, Switzerland. Univ Geneva, Fac Med, Dept Morphol, Geneva, Switzerland. Univ Leuven, Ctr Mol & Vasc Biol, Louvain, Belgium. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA USA. VA Puget Sound Med Ctr, Seattle, WA USA. RP Lucas, R (reprint author), Univ Konstanz, Chair Biochem Pharmacol, Dept Biochem Pharmacol, M-667,Univ Str 10, D-78457 Constance, Germany. RI Lucas, Rudolf/G-5197-2012 FU PHS HHS [H230542] NR 42 TC 10 Z9 10 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAY PY 2002 VL 87 IS 6 BP 966 EP 971 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 563AK UT WOS:000176231100007 PM 12083503 ER PT J AU Yu, J Steiner, FA Muench, JP Gourgiotis, L Skarulis, MC Altemus, RM Libutti, SK Merino, MJ Sarlis, NJ AF Yu, J Steiner, FA Muench, JP Gourgiotis, L Skarulis, MC Altemus, RM Libutti, SK Merino, MJ Sarlis, NJ TI Juxtathyroidal neck soft tissue angiosarcoma presenting as an undifferentiated thyroid carcinoma SO THYROID LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; MALIGNANT HEMANGIOENDOTHELIOMA; EPITHELIOID ANGIOSARCOMA; ANGIOMATOID CARCINOMA; PROGNOSTIC FACTORS; HEAD; TUMORS; SARCOMAS; GLAND AB Angiosarcoma is a malignant growth of endothelial origin, uncommon in the head and neck. We present the case of a 38-year-old woman with long-standing goiter who presented with a rapidly growing 6.0-cm neck mass. Fine-needle aspiration biopsy of the tumor showed features of "undifferentiated thyroid carcinoma (ThyrCa)." Total thyroidectomy resulted in extirpation of all gross disease. Pathology revealed a high-grade angiosarcoma of the neck invading the thyroid gland, coexisting with papillary ThyrCa (follicular variant) in the contralateral lobe. Aggressive external electron beam radiotherapy was initiated for local control. Despite the absence of systemic dissemination initially, bulky neck recurrences, and pulmonary metastases developed rapidly, leading to the patient's demise on postoperative day 41. Autopsy showed metastatic disease involving most organs. This case illustrates that neck angiosarcomas need to be considered in the differential diagnosis of "poorly differentiated" thyroid malignancies. These soft tissue neck tumors may complicate postoperative management due to their bleeding tendency and aggressive infiltrative behavior, and carry a dismal prognosis because of the rapidity of development of local recurrence and distant metastases. C1 NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDKD, Div Intramural Res, NIH, Bldg 10,Room 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 1 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 MAY PY 2002 VL 12 IS 5 BP 427 EP 432 DI 10.1089/105072502760043521 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 560LB UT WOS:000176082600013 PM 12097205 ER PT J AU Morton, D Lee, PN Fry, JS Fairweather, WR Haseman, JK Kodell, RL Chen, JJ Roth, AJ Soper, K AF Morton, D Lee, PN Fry, JS Fairweather, WR Haseman, JK Kodell, RL Chen, JJ Roth, AJ Soper, K TI Statistical methods for carcinogenicity studies SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material ID TUMORIGENICITY EXPERIMENTS; ANIMAL CARCINOGENESIS; REGRESSION-ANALYSIS; TUMOR; TESTS; ONSET; TIME; MORTALITY C1 Pharmacia Corp, STP Peto Working Grp, Skokie, IL 60077 USA. PN Lee Stat & Comp Ltd, Surrey SM2 5DA, England. Flower Valley Consulting Inc, Rockville, MD 20853 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Merck Res Labs, W Point, PA 19486 USA. RP Morton, D (reprint author), Pharmacia Corp, STP Peto Working Grp, 4901 Searle Pkwy, Skokie, IL 60077 USA. NR 28 TC 3 Z9 4 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY 1 PY 2002 VL 30 IS 3 BP 403 EP 414 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 558EQ UT WOS:000175953700015 ER PT J AU Harry, GJ Tyler, K d'Hellencourt, CL Tilson, HA Maier, WE AF Harry, GJ Tyler, K d'Hellencourt, CL Tilson, HA Maier, WE TI Morphological alterations and elevations in tumor necrosis factor-alpha, interleukin (IL)-1 alpha, and IL-6 in mixed glia cultures following exposure to trimethyltin: Modulation by proinflammatory cytokine recombinant proteins and neutralizing antibodies SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE trimethyltin; TNF alpha; interleukin 1; interleukin 6; microglia; astrocytes ID CENTRAL-NERVOUS-SYSTEM; FIBRILLARY ACIDIC PROTEIN; RAT-BRAIN; GENE-EXPRESSION; MESSENGER-RNA; NITRIC-OXIDE; IN-VITRO; HIPPOCAMPAL-NEURONS; CELL-CULTURES; ASTROCYTES AB Trimethyltin (TMT), is a hippocampal neurotoxicant characterized by neuronal degeneration, astrogliosis, and microglia reactivity with an associated elevation in proinflammatory cytokine mRNA levels. To examine the role of proinflammatory cytokines in the TMT-induced glia response, mixed cortical glia cultures were exposed to TMT and morphological and cytokine responses were examined. Morphological changes in the glia monolayer, enlarged, rounded cell bodies and retraction of the monolayer into distinct GFAP+ dense processes, displayed a dose (1, 5, and 10 muM TMT) and temporal response (6-48 h), accompanied by clustering of OX-42+ microglia. Tumor necrosis factor-alpha (TNF), interleukin (IL)-1alpha, and IL-6 mRNA levels were elevated by 3 and 6 h of TMT (10 muM) and proteins by 24 h. Recombinant proteins for IL-1alpha (100 pg/ml) and IL-6 (10 ng/ml) exacerbated the morphological response to TMT while those for TNFalpha (150 pg/ml) did not. Neutralizing antibodies (1:100) to IL-la and IL-6 showed a slight decrease in the severity of the morphological response to TMT while, at 24 h, TNFa antibodies (1:100) and an antibody cocktail offered a significant level of protection. At 6 h, the neutralizing antibodies to TNFa or IL-la did not elevate basal cytokine mRNA levels, however, IL-6 and the cocktail of antibodies significantly elevated IL-1alpha, IL-1beta, and IL-6 mRNA levels. The specific elevation in IL-la and IL-6 mRNA levels induced by, TMT remained evident only in cells coexposed to anti-TNFalpha. Similar responses in cytokine mRNA levels were seen in cocultures of hippocampal neurons and glia exposed to TMT. These data suggest a relationship between microglia activation, proinflammatory cytokine release, and glia morphological responses, the significance of which remains to be determined, as well as, the impact on neuronal degeneration. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NHEERL, US EPA, Res Triangle Pk, NC 27711 USA. RP Harry, GJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 62 TC 39 Z9 40 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 1 PY 2002 VL 180 IS 3 BP 205 EP 218 DI 10.1006/taap.2002.9390 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 555TE UT WOS:000175808700007 PM 12009860 ER PT J AU Bons, N Lehmann, S Mestre-Frances, N Dormont, D Brown, P AF Bons, N Lehmann, S Mestre-Frances, N Dormont, D Brown, P TI Brain and buffy coat transmission of bovine spongiform encephalopathy to the primate Microcebus murinus SO TRANSFUSION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; TRANSFUSION; INFECTIVITY; BSE AB BACKGROUND: More than 100 cases of variant CJD resulting from infections with bovine spongiform encephalopathy (BSE) have accumulated in the United Kingdom since 1995. Concern about the possibility of secondary transmissions via blood and blood components donated by infected individuals has prompted a variety of international donor deferral policies that will continue until laboratory and epidemiologic evidence provides a consensus about potential risk. STUDY DESIGN AND METHODS: BSE was passaged through macaque monkeys and then adapted to the prosimian microcebe (Microcebus murinus). Brain homogenate and buffy coat from an affected microcebe were separately inoculated intracerebrally into three healthy microcebes (two animals received brain and one received buffy coat). RESULTS: All three inoculated microcebes became ill after incubation periods of 16 to 18 months. Clinical, histopathologic, and immunocytologic features were similar in each of the recipients. CONCLUSION: Buffy coat from a symptomatic microcebe infected 17 months earlier with BSE contained the infectious agent. This observation represents the first documented transmission of BSE from the blood of an experimentally infected primate, which in view of rodent buffy coat infectivity precedents and the known host range of BSE is neither unexpected nor cause for alarm. C1 NINCDS, NIH, Bethesda, MD 20892 USA. Atom Energy Commiss, Neurovirol Serv, Fontenay Aux Roses, France. Natl Ctr Sci Res, Inst Human Genet, Montpellier, France. Univ Montpellier 2, Sch Adv Studies, Lab Funct Neuropathol, Montpellier, France. RP Brown, P (reprint author), NINCDS, NIH, Room 4 A-19,36 Convent Dr,MSC 4123, Bethesda, MD 20892 USA. NR 10 TC 46 Z9 49 U1 1 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2002 VL 42 IS 5 BP 513 EP 516 DI 10.1046/j.1537-2995.2002.00098.x PG 4 WC Hematology SC Hematology GA 560WL UT WOS:000176104300002 PM 12084158 ER PT J AU Stroncek, DF Matthews, CL Follmann, D Leitman, SF AF Stroncek, DF Matthews, CL Follmann, D Leitman, SF TI Kinetics of G-CSF-induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; NEUTROPHILS; VOLUNTEERS AB BACKGROUND: Granulocyte donors are frequently given G-CSF with or without dexamethasone approximately 18 hours before apheresis to increase cell yields. The purpose of this study was to assess the kinetics of G-CSF plus dexamethasone neutrophil mobilization to determine whether the neutrophils can be mobilized and collected the same day. STUDY DESIGN AND METHODS: Sixteen subjects were given four separate mobilization regimens: IV G-CSF (5 mug/kg), subcutaneous G-CSF (5 mug/kg), IV G-CSF (5 mug/kg) plus oral dexamethasone (8 mg), and subcutaneous G-CSF (5 mug/kg) plus oral dexamethasone (8 mg). Blood cell counts were measured before and after G-CSF administration. RESULTS: Following all four mobilization regimens, neutrophil counts fell 0.5 hour after the mobilizing agents were given, rose above baseline levels at Hour 2, and increased further with each time interval to Hour 8. In the absence of dexamethasone at Hours 2 through 8, there was no difference in neutrophil counts by subcutaneous or IV G-CSF administration routes. The addition of dexamethasone enhanced mobilization of neutrophils from Hours 3 through 24. Through Hour 8, there was no difference in the degree of mobilization among the subcutaneous G-CSF plus dexamethasone and the IV G-CSF plus dexamethasone regimens. However, at Hour 24, neutrophil counts were sustained at higher levels with subcutaneous G-CSF plus dexamethasone than with IV G-CSF plus dexamethasone. CONCLUSIONS: Granulocyte mobilization response to subcutaneous G-CSF plus dexamethasone is sustained at peak levels for 8 to 24 hours after coadministration of the two drugs. There was no advantage to giving G-CSF intravenously. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 8 TC 17 Z9 18 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2002 VL 42 IS 5 BP 597 EP 602 DI 10.1046/j.1537-2995.2002.00091.x PG 6 WC Hematology SC Hematology GA 560WL UT WOS:000176104300012 PM 12084168 ER PT J AU Spiegel, S English, D Milstien, S AF Spiegel, S English, D Milstien, S TI Sphingosine 1-phosphate signaling: providing cells with a direction SO TRENDS IN CELL BIOLOGY LA English DT Review ID ACTIVATED PROTEIN-KINASE; HUMAN ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; SRC FAMILY KINASES; GROWTH-FACTOR; MOLECULAR-CLONING; PDGF-B; FUNCTIONAL-CHARACTERIZATION; LYSOPHOSPHATIDIC ACID; ACTIN REORGANIZATION AB Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite that regulates diverse biological functions. S1P has been identified as a high-affinity ligand for a family of five G-protein-coupled receptors, known as the S1P receptors. The physiological role of the S1P receptor S1P, in vascular maturation was recently revealed by gene disruption in mice. In addition to other cellular processes, the binding of S1P to its receptors regulates motility and directional migration of a variety of cell types, including endothelial cells and vascular smooth muscle cells. This review focuses on the important role of S1P and its receptors in cell migration and describes a new paradigm for receptor cross-communication in which transactivation of S1P(1) by a receptor tyrosine kinase (PDGFR) is crucial for cell motility. C1 Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Richmond, VA 23298 USA. Methodist Res Inst, Expt Cell Res Program, Indianapolis, IN 46202 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Med Coll Virginia Campus, Richmond, VA 23298 USA. FU NCI NIH HHS [CA61774]; NHLBI NIH HHS [HL61751]; NIGMS NIH HHS [GM43880] NR 70 TC 105 Z9 110 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAY PY 2002 VL 12 IS 5 BP 236 EP 242 AR PII S0962-8924(02)02277-8 DI 10.1016/S0962-8924(02)02277-8 PG 7 WC Cell Biology SC Cell Biology GA 542VP UT WOS:000175065200013 PM 12062172 ER PT J AU Jarred, RA McPherson, SJ Bianco, JJ Couse, JF Korach, KS Risbridger, GP AF Jarred, RA McPherson, SJ Bianco, JJ Couse, JF Korach, KS Risbridger, GP TI Prostate phenotypes in estrogen-modulated transgenic mice SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ANDROGEN RECEPTOR EXPRESSION; AROMATASE-DEFICIENT MICE; RAT VENTRAL PROSTATE; REPRODUCTIVE PHENOTYPES; TARGETED DISRUPTION; REGIONAL VARIATION; ANTERIOR PROSTATE; SEMINAL-VESICLE; DUCTAL SYSTEM; CYP19 GENE AB Estrogen-modulated transgenic mice, such as estrogen receptor-knockouts (alphaERKO and betaERKO), aromatase-knockout (ArKO) and aromatase-overexpressing (AROM+) mice, have contributed to our understanding of the roles of estrogens in male reproductive biology, including prostate growth and development. Varying pathological changes of the prostate have been described as being the result of aberrant actions of estrogen, both directly through the estrogen receptors or indirectly by altering the endocrine status of these mice. This article identifies the consequences of aberrant estrogen signaling on prostate growth and development. Further characterization and manipulation of these estrogen-modulated transgenic mice will lead to a more complete understanding of the hormonal regulation of the mammalian prostate gland. C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Risbridger, GP (reprint author), Monash Univ, Monash Inst reprod & Dev, 27-31 Wright St, Clayton, Vic 3168, Australia. RI McPherson, Stephen/A-9490-2009; Taylor, Renea/A-5022-2009; Risbridger, Gail/B-8655-2008; OI Taylor, Renea/0000-0003-2609-2380; Risbridger, Gail/0000-0003-3089-4028; Korach, Kenneth/0000-0002-7765-418X NR 48 TC 37 Z9 38 U1 0 U2 0 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 MAY-JUN PY 2002 VL 13 IS 4 BP 163 EP 168 AR PII S1043-2760(02)00575-1 DI 10.1016/S1043-2760(02)00575-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541HE UT WOS:000174978500006 PM 11943560 ER PT J AU Epifano, O Dean, J AF Epifano, O Dean, J TI Genetic control of early folliculogenesis in mice SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PRIMORDIAL GERM-CELLS; DIFFERENTIATION FACTOR-IX; TRANSCRIPTION FACTOR; ZONA-PELLUCIDA; FOLLICLE DEVELOPMENT; OVARIAN-FUNCTION; MOUSE EMBRYO; LEYDIG-CELLS; STEEL-PANDA; KIT-LIGAND AB Perinatally, granulosa cells encase individual oocytes within the ovary to form primordial follicles. The initial stages of folliculogenesis are independent of gonadotropins and involve cell-autonomous and non-cell-autonomous factors Although still poorly understood at a molecular level, successful follicle formation and initiation of follicle growth must involve genetic networks both in germ and in somatic cells. Mouse models offer useful windows into these essential processes. By investigating phenotypes of mouse lines lacking specific gene products, genetic hierarchies that regulate the initial stages of folliculogenesis are being elucidated. These investigations will provide insight into the regulation of mammalian fertility. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Epifano, O (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 63 TC 48 Z9 50 U1 1 U2 9 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 MAY-JUN PY 2002 VL 13 IS 4 BP 169 EP 173 AR PII S1043-2760(02)00576-3 DI 10.1016/S1043-2760(02)00576-3 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 541HE UT WOS:000174978500007 PM 11943561 ER PT J AU Rogozin, IB Spiridonov, AN Sorokin, AV Wolf, YI Jordan, IK Tatusov, RL Koonin, EV AF Rogozin, IB Spiridonov, AN Sorokin, AV Wolf, YI Jordan, IK Tatusov, RL Koonin, EV TI Purifying and directional selection in overlapping prokaryotic genes SO TRENDS IN GENETICS LA English DT Article ID COG DATABASE; EVOLUTION; ALIGNMENT; GENOMES; VIRUSES AB In overlapping genes,the same DNA sequence codes for two proteins using different reading frames. Analysis of overlapping genes can help in understanding the mode of evolution of a coding region from noncoding DNA. We identified 71 pairs of convergent genes, with overlapping 3' ends longer than 15 nucleotides, that are conserved in at least two prokaryotic genomes. Among the overlap regions, we observed a statistically significant bias towards the 123:132 phase (i.e. the second codon base in one gene facing the degenerate third position in the second gene). This phase ensures the least mutual constraint on nonconservative amino acid replacements in both overlapping coding sequences. The excess of this phase is compatible with directional (positive) selection acting on the overlapping coding regions. This could be a general evolutionary mode for genes emerging from noncoding sequences, in which the protein sequence has not been subject to selection. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 19 TC 81 Z9 84 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 2002 VL 18 IS 5 BP 228 EP 232 AR PII S0168-9525(02)02649-5 DI 10.1016/S0168-9525(02)02649-5 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 545UD UT WOS:000175235200004 PM 12047938 ER PT J AU Taylor, JP Fischbeck, KH AF Taylor, JP Fischbeck, KH TI Altered acetylation in polyglutamine disease: an opportunity for therapeutic intervention? SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material ID HISTONE DEACETYLASE INHIBITORS; CREB-BINDING PROTEIN; HUNTINGTONS-DISEASE; EXPANDED POLYGLUTAMINE; TRANSCRIPTION; DROSOPHILA; GENES; SCA1; NEURODEGENERATION; LOCALIZATION AB Recent investigations into polyglutamine diseases suggest that aberrant transcriptional regulation might be central to the molecular pathogenesis, perhaps because of inappropriate interaction between mutant proteins and important nuclear factors. Several groups have reported an interaction of mutant polyglutamine with histone acetylases, implicating defective acetylation as a cause of abnormal transcription. An important recent observation is that reversal of the acetylation defect with histone deacetylase inhibitors ameliorates polyglutamine toxicity in yeast, mammalian cell culture, and animal models. These encouraging findings suggest that a novel strategy - pharmacological restoration of histone acetylation - could prove effective in treating this group of devastating illnesses. C1 NINCDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Taylor, JP (reprint author), NINCDS, Neurogenet Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3B-14, Bethesda, MD 20892 USA. NR 22 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2002 VL 8 IS 5 BP 195 EP 197 AR PII S1471-4914(02)02332-8 DI 10.1016/S1471-4914(02)02332-8 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 547LU UT WOS:000175334500001 PM 12067622 ER PT J AU Natesan, AK Cassone, VM AF Natesan, AK Cassone, VM TI Melatonin receptor mRNA localization and rhythmicity in the retina of the domestic chick, Gallus domesticus SO VISUAL NEUROSCIENCE LA English DT Article DE circadian; ganglion cells; Photoreceptors; Mel(1A); Mel(1B); Mel(1C) ID SEROTONIN N-ACETYLTRANSFERASE; 2-IODOMELATONIN BINDING-SITES; HYDROXYINDOLE-O-METHYLTRANSFERASE; CIRCADIAN REGULATION; MESSENGER-RNA; PINEAL-GLAND; MOLECULAR REGULATION; GUANINE-NUCLEOTIDES; XENOPUS RETINA; DIURNAL RHYTHM AB The indoleamine hormone melatonin is synthesized and released by photoreceptors during the night within the chick retina, and confers timing information to modulate retinal physiology. Three subtypes of melatonin receptor with nearly identical pharmacological profiles have been described in chickens and are present in the retina. In this study, the spatial localization and temporal pattern of the mRNA for each of these receptors within the retina are described. The localization and rhythmicity of receptor mRNA were analyzed using in situ hybridization and RNase protection assay, respectively, with probes against specific nucleotide sequences encoding these receptors. Mel(1A) and Mel(1C) receptor mRNA have similar patterns of expression, primarily in the inner segments of photoreceptors, vitread portion of the inner nuclear layer, and in the retinal ganglion cell layer. Mel(1B) receptor mRNA is expressed at higher levels in the retina, with expression in photoreceptors, throughout the inner nuclear layer, and in the ganglion cell layer. Mel(1A) receptor mRNA is rhythmic in both light:dark (LD) cycles and in constant darkness (DD); Mel(1A) peaks during midday and mid-subjective day, respectively. Mel(1C) receptor mRNA is also rhythmically expressed in LD, but with a lower amplitude, such that transcript is high during the day and low during the night. In DD, Mel(1C) rhythms become 180 deg out of phase with a slight increase at night. Mel(1B) mRNA expression was highly variable and arrhythmic. C1 Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Natesan, AK (reprint author), NIMH, Lab Cellular & Mol Regulat, 36 Convent Dr, Bethesda, MD 20892 USA. FU NINDS NIH HHS [R01NS 35822] NR 46 TC 44 Z9 46 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 2002 VL 19 IS 3 BP 265 EP 274 DI 10.1017/S0952523802192042 PG 10 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 603UQ UT WOS:000178579300004 PM 12392176 ER PT J AU Kumar, S Tsai, CJ Nussinov, R AF Kumar, S Tsai, CJ Nussinov, R TI Maximal stabilities of reversible two-state proteins SO BIOCHEMISTRY LA English DT Article ID DIFFERENTIAL SCANNING CALORIMETRY; HYDROPHOBIC FOLDING UNITS; HEAT-CAPACITY CHANGES; CONFORMATIONAL STABILITY; GLOBULAR-PROTEINS; COLD DENATURATION; ESCHERICHIA-COLI; BINDING-PROTEIN; THERMODYNAMIC CHARACTERIZATION; LINEAR EXTRAPOLATION AB The hydrophobic effect is the major force driving protein folding. Around room temperature, small organic solutes and hydrophobic amino acids have low solubilities in water and the hydrophobic effect is the strongest. These facts suggest that globular proteins should be maximally stable around room temperature. While this fundamental paradigm has been expected, it has not actually been shown to hold. Toward this goal, we have collected and analyzed experimental thermodynamic data for 31 proteins that show reversible two-state folding reversible arrow unfolding transitions at or near neutral pH. Twenty-six of these are unique, and 20 of the 26 are maximally stable around room temperature irrespective of their structural properties, the melting temperature, or the living temperatures of their source organisms. Their average temperature of maximal stability is 293 +/- 8 K (20 +/- 8 degreesC). These proteins differ in size, fold, and number of domains, hydrophobic folding units, and oligomeric states. They derive from the cold-loving psychrophiles, from mesophiles, and from thermophiles. Analysis of the single-domain proteins present in this set shows that the variations in their thermodynamic parameters are correlated in a way which may explain the adaptation of the proteins to the living temperatures of the organisms from which they derive. The average energetic contribution of the individual amino acids toward protein stability decreases with an increase in protein size, suggesting that there may be an upper limit for protein maximal thermodynamic stability. For the remaining proteins, deviation of the maximal stability temperatures from room temperature may be due to greater uncertainties in their heat capacity change (DeltaC(p)) values, a weaker hydrophobic effect, and/or a stronger electrostatic contribution. C1 NCI, FCRF, Lab Expt & Computat Biol, Ft Detrick, MD 21702 USA. NCI, Lab Expt & Computat Biol, SAIC, Intramural Res Support Program, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, FCRF, Lab Expt & Computat Biol, Bldg 469 Rm 151, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 73 TC 60 Z9 62 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 30 PY 2002 VL 41 IS 17 BP 5359 EP 5374 DI 10.1021/bi012154c PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 548AH UT WOS:000175365100004 PM 11969396 ER PT J AU Sondej, M Weinglass, AB Peterkofsky, A Kaback, HR AF Sondej, M Weinglass, AB Peterkofsky, A Kaback, HR TI Binding of enzyme IIA(Glc), a component of the phosphoenolpyruvate : sugar phosphotransferase system, to the Escherichia coli lactose permease SO BIOCHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCING PROTEIN; CYSTEINE-SCANNING MUTAGENESIS; LAC CARRIER PROTEIN; MEMBRANE-VESICLES; SUBSTRATE-BINDING; SALMONELLA-TYPHIMURIUM; INDUCER EXCLUSION; TERMINAL DOMAIN; HELIX-IV; TRANSPORT AB Enzyme IIA(Glc), encoded by the crr gene of the phosphoenolpyruvate: sugar phosphotransferase system, plays an important role in regulating intermediary metabolism in Escherichia coli ("catabolite repression"). One function involves inhibition of inducible transport systems ("inducer exclusion"), and with lactose permease, a galactoside is required for unphosphorylated IIA(Glc) binding to cytoplasmic loops IV/V and VI/VII [Sondej, M., Sun, J. et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 3525-3530]. With inside-out membrane vesicles containing the permease, [I-125]IIA(Glc) binding promoted by melibiose exhibits an affinity (K-D(IIA)) of approximate to 1 muM and a stoichiometry of one mole of IIA(Glc) per six moles of lactose permease. Both the quantity of [I-125]IIA(Glc) bouynd and the sugar concentration required for half-maximal IIA(Glc) binding (K-0.5(sug)IIA) was measured for eight permease substrates. Differences in maximal IIA(Glc) binding are observed, and the K-0.5(sug)IIA does not correlate with the affinity of LacY for sugar. Furthermore, K-0.5(sug)IIA does not correlate with sugar affinities for various permease mutants. IIA(Glc) does not bind to a mutant (Cys 154 --> Gly), which is locked in an outwardly facing conformation, binds with increased stoichiometry to Mutant Lys131 --> Cys, and binds only weakly to two other mutants which appear to be predominantly in either an outwardly or an inwardly facing conformation. When the latter two mutations are combined, sugar-dependent IIA(Glc) binding returns to near wild-type levels. The findings suggest that binding of various substrates to lactose permease results in a collection of unique conformations, each of which presents a specific surface toward the inner face of the membrane that can interact to varying degrees with IIA(Glc). C1 Univ Calif Los Angeles, HHMI, MacDonald Res Labs 5 748, Dept Physiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Howard Hughes Med Inst, Dept Microbiol & Mol Genet, Inst Mol Biol, Los Angeles, CA 90095 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kaback, HR (reprint author), Univ Calif Los Angeles, HHMI, MacDonald Res Labs 5 748, Dept Physiol, Box 951662, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK51131:06] NR 52 TC 21 Z9 21 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 APR 30 PY 2002 VL 41 IS 17 BP 5556 EP 5565 DI 10.1021/bi011990j PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 548AH UT WOS:000175365100024 PM 11969416 ER PT J AU Larsen, G Hallstrom, A McAnulty, J Pinski, S Olarte, A Sullivan, S Brodsky, M Powell, J Marchant, C Jennings, C Akiyama, T AF Larsen, G Hallstrom, A McAnulty, J Pinski, S Olarte, A Sullivan, S Brodsky, M Powell, J Marchant, C Jennings, C Akiyama, T CA AVID Investigators TI Cost-effectiveness of the implantable cardioverter-defibrillator versus antiarrhythmic drugs in survivors of serious ventricular tachyarrhythmias - Results of the Antiarrhythmics Versus Implantable Defibrillators (AVID) economic analysis substudy SO CIRCULATION LA English DT Article DE cost-benefit analysis; heart arrest; antiarrhythmia agents; defibrillation; tachyarrhythmias ID PREVENTION; AMIODARONE; DISEASE; DEATH; CIDS AB Background-The implantable cardioverter-defibrillator (ICD) is an effective but expensive device. We used prospectively collected data from a large randomized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug (AAD) therapy, largely with amiodarone. Methods and Results-Charges for initial and repeat hospitalizations, emergency room, and day surgery stays and the costs of antiarrhythmic drugs were collected on 1008 patients. Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients. Regression models were then created to attribute these expenses to the rest of the patients. Charges were converted to 1997 costs using standard methods. Costs and life years were discounted at 3% per year. Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness (C/E) ratio. Six-year, twenty-year, and lifetime C/E ratios were also estimated. At 3 years. total costs were $71 421 for a patient taking AADs and $85 522 for a patient using an ICD, and the ICD provided a 0.21-year survival benefit over AAD treatment. The base-case C/E ratio was thus $66 677 per year of life saved by the ICD compared with AAD therapy (95% Cl. $30 761 to $154 768). Six- and 20-year C/E ratios remained stable between $68 000 and $80 000 per year of life saved. Conclusions-The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias, as judged from prospectively collected data in a randomized clinical trial. C1 Portland VA Med Ctr, Cardiol Sect, Portland, OR USA. AVID Clin Trial Ctr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Div Cardiol, Portland, OR 97201 USA. Rush Presbyterian St Lukes Med Ctr, Cardiol Sect, Rush Med Coll, Chicago, IL 60612 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Calif Irvine, Dept Cardiol, Irvine, CA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Rochester, Dept Cardiol, Rochester, NY USA. RP Larsen, G (reprint author), Portland VA Med Ctr, Cardiol Sect, P-3-CARD,3710 SW US Vet Hosp Rd, Portland, OR USA. FU NHLBI NIH HHS [N01-HC-25117] NR 16 TC 77 Z9 78 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 30 PY 2002 VL 105 IS 17 BP 2049 EP 2057 DI 10.1161/01.CIR.0000015504.57641.D0 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 548YR UT WOS:000175418000018 PM 11980684 ER PT J AU Tsodikov, OV Record, MT Sergeev, YV AF Tsodikov, OV Record, MT Sergeev, YV TI Novel computer program for fast exact calculation of accessible and molecular surface areas and average surface curvature SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE accessible surface area; Gauss-Bonnet theorem; molecular surface; average curvature; cavities ID ANALYTICAL SHAPE COMPUTATION; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; PROTEIN INTERACTIONS; REFINED STRUCTURE; RIBONUCLEASE-A; CAVITIES; PACKING; MACROMOLECULES; VOLUME AB New computer programs, SurfRace and FastSurf, perform fast calculations of the solvent accessible and molecular (solvent excluded) surface areas of macromolecules. Program SurfRace also calculates the areas of cavities inaccessible from the outside. We introduce the definition of average curvature of molecular surface and calculate average molecular surface curvatures for each atom in a structure. All surface area and curvature calculations are analytic and therefore yield exact values of these quantities. High calculation speed of this software is achieved primarily by avoiding computationally expensive mathematical procedures wherever possible and by efficient handling of surface data structures. The programs are written initially in the language C for PCs running Windows 2000/98/NT, but their code is portable to other platforms with only minor changes in input-output procedures. The algorithm is robust and does not ignore either multiplicity or degeneracy of atomic overlaps, Fast, memory-efficient and robust execution make this software attractive for applications both in computationally expensive energy minimization algorithms, such as docking or molecular dynamics simulations, and in stand-alone surface area and curvature calculations. (C) 2002 Wiley Periodicals, Inc. C1 Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. NEI, OGCS, NIH, Bethesda, MD 20892 USA. RP Tsodikov, OV (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Bld C-2,Room 226,240 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM23467] NR 51 TC 283 Z9 283 U1 0 U2 18 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD APR 30 PY 2002 VL 23 IS 6 BP 600 EP 609 DI 10.1002/jcc.10061 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 537CH UT WOS:000174739600002 PM 11939594 ER PT J AU Mattson, MP AF Mattson, MP TI Brain evolution and lifespan regulation: conservation of signal transduction pathways that regulate energy metabolism SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Akt; antioxidant; brain-derived neurotrophic factor; glucose; insulin; stress ID CORTICOTROPIN-RELEASING HORMONE; GLUCAGON-LIKE PEPTIDE-1; DIETARY RESTRICTION; NEUROTROPHIC FACTOR; CAENORHABDITIS-ELEGANS; GLUCOSE-METABOLISM; NERVOUS-SYSTEM; NEURODEGENERATIVE DISORDERS; MOLECULAR MECHANISMS; HUNTINGTONS-DISEASE AB Mechanisms for sensing, acquiring, storing and using energy are fundamental to the survival of organisms at all levels of the phylogenetic scale. Single-cell organisms evolved surface receptors that sense an energy source and, via signal transduction pathways that couple the receptors to the cell cytoskeleton move towards the energy source. Mutlicellular organisms evolved under conditions that favored species that developed complex mechanisms for obtaining food, with nervous systems being critical mediators of energy acquisition and regulators of energy metabolism. A conserved signaling system involved in regulating cellular and organismal energy metabolism, and in sensing and responding to energy/food-related environmental signals, involves receptors coupled to the phosphatidylinositol-3-kinase-Akt signaling pathway. Prominent activators of this pathway are insulin, insulin-like growth factors and brain-derived neurotrophic factor (BDNF). Recent studies in diverse organisms including nematodes, flies and rodents have provided evidence that insulin-like signaling in the nervous system can control lifespan, perhaps by modulating stress responses and energy metabolism. Interestingly, the lifespan-extending effect of dietary restriction in rodents is associated with increased BDNF signaling in the brain, and a related increase of peripheral insulin sensitivity, suggesting a mechanism whereby the brain can control lifespan. Thus a prominent evolutionarily conserved function of the nervous system is to regulate food acquisition and energy metabolism, thereby controlling lifespan. Published by Elsevier Science Ireland Ltd. C1 NIA, Neurosci Lab, Gerontol Res Ctr 4F01, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 61 TC 33 Z9 34 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR 30 PY 2002 VL 123 IS 8 BP 947 EP 953 AR PII S0047-6374(02)00032-5 DI 10.1016/S0047-6374(02)00032-5 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 580MN UT WOS:000177238500016 PM 12044943 ER PT J AU Bohr, VA AF Bohr, VA TI Human premature aging syndromes and genomic instability SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE genomic instability; DNA repair; human premature aging diseases ID WERNER-SYNDROME PROTEIN; RNA-POLYMERASE-II; SYNDROME GENE-PRODUCT; TRANSCRIPTION-COUPLED REPAIR; DNA HELICASE ACTIVITY; GROUP-B CELLS; COCKAYNE-SYNDROME; EXCISION-REPAIR; SYNDROME FIBROBLASTS; PUTATIVE HELICASES C1 NIA, Lab Mol Gerontol, GRC, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, GRC, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 46 TC 21 Z9 24 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD APR 30 PY 2002 VL 123 IS 8 BP 987 EP 993 AR PII S0047-6374(02)00039-8 DI 10.1016/S0047-6374(02)00039-8 PG 7 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 580MN UT WOS:000177238500020 PM 12044947 ER PT J AU Hazama, M Watanabe, D Suzuki, M Mizoguchi, A Pastan, I Nakanishi, S AF Hazama, M Watanabe, D Suzuki, M Mizoguchi, A Pastan, I Nakanishi, S TI Different regulatory sequences are required for parvalbumin gene expression in skeletal muscles and neuronal cells of transgenic mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE parvalbumin; skeletal muscle; gene expression; transgenic mouse; bacterial artificial chromosome; immunotoxin-mediated cell targeting ID BINDING PROTEIN PARVALBUMIN; POSITION-EFFECT VARIEGATION; GABAERGIC NEURONS; NERVOUS-SYSTEM; INSITU HYBRIDIZATION; RAT HIPPOCAMPUS; MESSENGER-RNA; CORTEX; INTERNEURONS; LOCALIZATION AB Parvalbumin (PV) is expressed in fast-twitch fibers in skeletal muscles and a subpopulation of inhibitory neurons in the CNS. We generated transgenic mice that expressed the human interleukin-2 receptor a-subunit-green fluorescent fusion protein (hIL-2R-GFP) using two types of PV transgene. One contained the hIL-2R-GFP gene downstream of a 16.5-kb 5'-upstream PV genomic sequence (PV line). The other comprised the hIL-2R-GFP gene in bacterial artificial chromosome (BAC) with either a 180-kb (PA line) or 155-kb (PB line) insert encompassing the PV gene. Independent lines of all transgenic mice showed a faithful hIL-2R-GFP expression in fast-twitch muscle fibers. However, appreciable hIL-2R-GFP expression in the CNS occurred only in the PA transgenic lines. In one line of PA transgenic mice, hIL-2R-GFP was properly expressed in PV-containing neurons in the cerebellum, thalamic reticular nucleus, globus pallidus and cerebral cortex, though ectopic expression was observed in a particular subset of cerebellar astrocytes. Another line of PA transgenic mice showed a selective and mosaic expression of hIL-2R-GFP in PV-containing Purkinje, basket and stellate cells in the cerebellum. These results indicate that the 16.5-kb PV genomic sequence is sufficient for fiber-type-selective transcription but additional regulatory sequences comprised in BAC DNA are required for proper expression in PV-containing neurons. Published by Elsevier Science B.V. C1 Kyoto Univ, Fac Med, Dept Sci Biol, Sakyo Ku, Kyoto 6068501, Japan. Kumamoto Univ, Ctr Anim Resources & Dev, Div Transgen Technol, Kumamoto 8600811, Japan. Kyoto Univ, Fac Med, Dept Anat & Neurobiol, Sakyo Ku, Kyoto 6068501, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Biostudies, Dept Mol & Syst Biol, Sakyo Ku, Kyoto 6068501, Japan. RP Nakanishi, S (reprint author), Kyoto Univ, Fac Med, Dept Sci Biol, Sakyo Ku, Kyoto 6068501, Japan. NR 46 TC 4 Z9 4 U1 0 U2 1 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 APR 30 PY 2002 VL 100 IS 1-2 BP 53 EP 66 AR PII S0169-328X(02)00142-0 DI 10.1016/S0169-328X(02)00142-0 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 559HN UT WOS:000176020900006 ER PT J AU Levens, D AF Levens, D TI Disentangling the MYC web SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID C-MYC; HISTONE ACETYLATION; ESSENTIAL COFACTOR; CELL-CYCLE; N-MYC; GENES; TARGET; BINDING; COMPLEX; GROWTH C1 NCI, Canc Res Ctr, Pathol Lab, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, Canc Res Ctr, Pathol Lab, Bldg 10,Room 2N106, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 40 TC 78 Z9 81 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 2002 VL 99 IS 9 BP 5757 EP 5759 DI 10.1073/pnas.102173199 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 548FK UT WOS:000175377800003 PM 11983876 ER PT J AU Hayashi, N Liu, DC Min, BK Ben-Sasson, SZ Paul, WE AF Hayashi, N Liu, DC Min, BK Ben-Sasson, SZ Paul, WE TI Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tolerance; TH1 cells; anergy; immunologic memory; apoptosis ID RECEPTOR-TRANSGENIC MICE; IN-VIVO; INTERLEUKIN-4; RESPONSES; SURVIVAL; THERAPY; ANERGY; GAMMA AB TH1 memory T cells derived from T cell receptor transgenic mice, in which the T cell antigen receptor is specific for a cytochrome C peptide in association with I-E-k, were transferred into normal B10.A mice and allowed to adopt a resting phenotype. When challenged, 30-60 days after transfer, with i.v. cytochrome C, the transgenic cells rapidly became activated, expressed mRNA for IFNgamma, and began to divide. However, after 48 h, the frequency of the cells fell progressively, reaching levels only slightly above the limit of detection by day 8 and thereafter remain depressed for up to 90 days. The remaining cells were anergic as shown by limitation in proliferation and IFNgamma production in response to in vitro antigen stimulation. Even if challenged with antigen emulsified in complete Freund's adjuvant, the overall pattern was similar, except that in the draining lymph nodes, the surviving antigen-specific cells were not anergic, although spleen cells were still strikingly anergic. Thus, antigenic challenge of mice possessing resting memory TH1 CD4 T cells leads to the unanticipated loss of most of the specific cells and an apparent depletion rather than enhancement of immunologic memory. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Ctr, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 41 Z9 44 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 APR 30 PY 2002 VL 99 IS 9 BP 6187 EP 6191 DI 10.1073/pnas.092129899 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 548FK UT WOS:000175377800080 PM 11959916 ER PT J AU Liu, KB Catalfamo, M Li, Y Henkart, PA Weng, NP AF Liu, KB Catalfamo, M Li, Y Henkart, PA Weng, NP TI IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8(+) memory T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IN-VIVO; LYMPHOCYTE DEVELOPMENT; SIGNAL-TRANSDUCTION; ACTIVATION; NAIVE; STIMULATION; HOMEOSTASIS; PATHWAYS; CYTOKINE; SURVIVAL AB Generation of CD8(+) memory T cells requires antigenic stimulation through T cell receptor (TCR); however, maintenance of CD8+ memory T cells seems to be mediated by cytokines, such as IL-15, in a TCR-independent manner. Compared with the TCR-induced activation, less is known about the mechanisms of IL-15 action. We report here a comparative and kinetic analysis of the responses of memory phenotype CD8(+) T cells to IL-15 or TCR (anti-CD3) stimulation in vitro. These two stimuli induce highly similar responses in memory phenotype CD8(+) T cells as measured by cellular proliferation, gene expression changes, synthesis of effector molecules (IFNgamma, tumor necrosis factor beta, granzyme B, and perforin), and induction of cytotoxicity. From 189 genes/expressed sequence tags (ESTs) whose expression changed in CD8(+) memory T cells after IL-15 and anti-CD3 stimulation identified by cDNA microarray analysis, 77% of the genes/ESTs exhibit a highly similar pattern of expression between IL-15 and anti-CD31-treated cells, and only 16% and 7% of the genes/ESTs are differentially expressed in response to IL-15 and anti-CD3 treatments, respectively. These results show that IL-15 and anti-CD3 stimulation induced remarkably similar gene expression and effector function. Thus, IL-15 acts not only as a crucial growth factor but also as an antigen-independent activator of effector functions for CD8(+) memory T cells. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. OI Liu, Kebin/0000-0003-1965-7240 NR 34 TC 130 Z9 138 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 APR 30 PY 2002 VL 99 IS 9 BP 6192 EP 6197 DI 10.1073/pnas.092675799 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 548FK UT WOS:000175377800081 PM 11972069 ER PT J AU Thorslund, T Sunesen, M Bohr, VA Stevnsner, T AF Thorslund, T Sunesen, M Bohr, VA Stevnsner, T TI Repair of 8-oxoG is slower in endogenous nuclear genes than in mitochondrial DNA and is without strand bias SO DNA REPAIR LA English DT Article DE DNA repair; base excision repair (BER); 8-oxoG; mitochondria; transcription coupled repair (TCR) ID TRANSCRIPTION-COUPLED REPAIR; HAMSTER OVARY CELLS; DIHYDROFOLATE-REDUCTASE GENE; APURINIC APYRIMIDINIC SITES; OXIDATIVE BASE DAMAGE; COCKAYNE-SYNDROME; EXCISION-REPAIR; THYMINE GLYCOL; CROSS-LINKS; RAT-LIVER AB DNA is vulnerable to the attack of certain oxygen radicals and one of the major DNA lesions formed is 7,8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic lesion that can mispair with adenine. The repair of 8-oxoG was studied by measuring the gene specific removal of 8-oxoG after treatment of Chinese hamster ovary (CHO) fibroblasts with the photosensitizer Ro19-8022. This compound introduces 8-oxoG lesions, which can then be detected with the Escherichia coli formamidopyrimidine DNA glycosylase (FPG). In this report we present gene specific repair analysis of endogenous genes situated in different important cellular regions and also the first analysis of strand specific DNA repair of 8-oxoG in an endogenous gene. We were not able to detect any preferential repair of transcribed genes compared to non-transcribed regions and we did not detect any strand-bias in the repair of the housekeeping gene, dihydrofolate reductase (DHFR). In vivo, mitochondrial DNA is highly exposed to reactive oxygen species (ROS), and we find that the repair of 8-oxoG is more efficient in the mitochondrial DNA than in the nuclear DNA. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Aarhus, Danish Ctr Mol Gerontol, Dept Biol Mol & Struct, Aarhus, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Thorslund, Tina/0000-0001-9207-0070 NR 50 TC 55 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 29 PY 2002 VL 1 IS 4 BP 261 EP 273 AR PII S1568-7864(02)00003-4 DI 10.1016/S1568-7864(02)00003-4 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 597YL UT WOS:000178248300001 PM 12509245 ER PT J AU Horton, JK Baker, A Vande Berg, BJ Sobol, RW Wilson, SH AF Horton, JK Baker, A Vande Berg, BJ Sobol, RW Wilson, SH TI Involvement of DNA polymerase beta in protection against the cytotoxicity of oxidative DNA damage SO DNA REPAIR LA English DT Article DE DNA polymerase beta; oxidative DNA damage; DNA repair; hydrogen peroxide; mouse fibroblasts ID BASE EXCISION-REPAIR; TRANSCRIPTION-COUPLED REPAIR; MAMMALIAN-CELL EXTRACTS; POLY(ADP-RIBOSE) POLYMERASE; HYDROGEN-PEROXIDE; APURINIC/APYRIMIDINIC ENDONUCLEASE; 8-OXOGUANINE-DNA GLYCOSYLASE; AP-ENDONUCLEASE; LYASE ACTIVITY; STRAND BREAKS AB We had shown previously that DNA polymerase beta (beta-pol) null mouse fibroblasts, deficient in base excision repair (BER), are hypersensitive to monofunctional methylating agents but not to hydrogen peroxide (H2O2). This is surprising because beta-pol is thought to be involved in BER of oxidative as well as methylated DNA damage. We confirm these findings here in early-passage cells. However, with time in culture, beta-pol null cells become hypersensitive to HO2O2 and other reactive oxygen species-generating agents. Analysis of in vitro BER reveals a strong deficiency in single-nucleotide BER of 8-oxoguanine (8-oxoG) by both early- and late-passage beta-pol null cell extracts. Therefore, in early-passage wild-type and beta-pol null cells, the capacity for single-nucleotide BER of 8-oxoG does not correlate with cellular sensitivity to H2O2. Expression of beta-pol protein in the late-passage null cells almost completely reverses the H-2-O-2-hypersensitivity phenotype. Methoxyamine (MX) treatment sensitizes late-passage wild-type cells to H2O2 as expected for beta-pol-mediated single-nucleotide BER; however in beta-pol null cells, MX has no effect. The data indicate a role(s) of beta-pol-dependent repair in protection against the cytotoxicity of oxidative DNA damage in wild-type cells. Published by Elsevier Science B.V. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 NR 58 TC 66 Z9 67 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 29 PY 2002 VL 1 IS 4 BP 317 EP 333 AR PII S1568-7864(02)00008-3 DI 10.1016/S1568-7864(02)00008-3 PG 17 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 597YL UT WOS:000178248300006 PM 12509250 ER PT J AU Li, ZQ Calzada, MJ Sipes, JM Cashel, JA Krutzsch, HC Annis, DS Mosher, DF Roberts, DD AF Li, ZQ Calzada, MJ Sipes, JM Cashel, JA Krutzsch, HC Annis, DS Mosher, DF Roberts, DD TI Interactions of thrombospondins with alpha 4 beta 1 integrin and CD47 differentially modulate T cell behavior SO JOURNAL OF CELL BIOLOGY LA English DT Article DE thrombospondins; integrins; chemotaxis; T cell antigen receptor; matrix metalloproteinases ID MODEL BASEMENT-MEMBRANE; GELATINASE-B MMP-9; LATE ANTIGEN-4; PROTEIN CD47; TUMOR-GROWTH; A MMP-2; ADHESION; FIBRONECTIN; BINDING; VLA-4 AB Thrombospondin (TSP)-1 has been reported to modulate T cell behavior both positively and negatively. We found that these opposing responses arise from interactions of TSP1 with two different T cell receptors. The integrin alpha4beta1 recognizes an LDVP sequence in the NH2-terminal domain of TSP1 and was required for stimulation of T cell adhesion, chemotaxis, and matrix metalloproteinase gene expression by TSP1. Recognition of TSP1 by T cells depended on the activation state of alpha4beta1 integrin, and TSP1 inhibited interaction of activated alpha4beta1 integrin on T cells with its counter receptor vascular cell adhesion molecule-1. The alpha4beta1 integrin recognition site is conserved in TSP2. A recombinant piece of TSP2 containing this sequence replicated the alpha4beta1 integrin-dependent activities of TSP1. The beta1 integrin recognition sites in TSP1, however, were neither necessary nor sufficient for inhibition of T cell proliferation and T cell antigen receptor signaling by TSP1. A second TSP1 receptor, CD47, was not required for some stimulatory responses to TSPI but played a significant role in its T cell antigen receptor antagonist and antiproliferative activities. Modulating the relative expression or function of these two TSP receptors could therefore alter the direction or magnitude of T cell responses to TSPs. C1 NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Roberts, DD (reprint author), NCI, Lab Pathol, NIH, Bldg 10,Rm 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NHLBI NIH HHS [HL54462, HL56396, R01 HL054462] NR 52 TC 87 Z9 90 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 29 PY 2002 VL 157 IS 3 BP 509 EP 519 DI 10.1083/jcb.200109098 PG 11 WC Cell Biology SC Cell Biology GA 566KH UT WOS:000176427000014 PM 11980922 ER PT J AU Sharma, N Dey, M Satpathy, M Sachar, RC AF Sharma, N Dey, M Satpathy, M Sachar, RC TI Evidence of two forms of poly(A) polymerase in germinated wheat embryos and their regulation by a novel protein kinase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE PAPI; poly(A) polymerase I; PAPII; poly (A) poly merase II; PK; protein kinase; Triticum aestivum ID MESSENGER-RNA; PHOSPHORYLATION; PURIFICATION; ENZYME; CELLS AB Two forms of poly(A) polymerase (PAPI and PAPII) from germinated wheat embryos have been resolved on DEAE-cellulose ion-exchange chromatography by a linear gradient of 0-500 mM (NH4)(2)SO4. Further purification shows that both forms are monomeric in nature with an identical molecular weight, approximately 65 kDa. The phosphoprotein nature of PAPI and PAPII has been established by in vivo labelling with 32 P-orthophosphate. Acid hydrolysis of both P-32-labelled purified PAPI and PAPII has revealed that phosphorylations generally take place in serine and threonine residues. PAPI and PAPII have also been characterised with respect to V-max and K-m for pol(A). The V-max and K-m values of PAPI are 28.57 and 11.37 mug. respectively, whereas 34.48 and 7.04 mug of PAPII In vitro dephosphorylation of the purified enzyme by alkaline phosphatase leads to a significant loss of the enzyme activity, which is regained upon phosphorylation by a 65 kDa protein kinase (PK) purified from wheat embryos. The extent of phosphorylation by protein kinase shows that PK has similar affinity towards both PAPI and PAPII whereas the phosphate incorporation in PAPII is twofold higher than PAPI suggesting their distinct chemical nature. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Optometry, Bloomington, IN 47405 USA. Univ Delhi, Dept Bot, Biochem & Mol Biol Lab, Delhi 110007, India. RP Sharma, N (reprint author), Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA. NR 35 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 26 PY 2002 VL 293 IS 1 BP 403 EP 411 AR PII S0006-291X(02)00231-0 DI 10.1016/S0006-291X(02)00231-0 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 550QX UT WOS:000175514700061 PM 12054614 ER PT J AU Kashlev, M Komissarova, N AF Kashlev, M Komissarova, N TI Transcription termination: Primary intermediates and secondary adducts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLI RNA-POLYMERASE; ESCHERICHIA-COLI; ELONGATION COMPLEX; NASCENT RNA; TERNARY COMPLEXES; CHAIN ELONGATION; CLEAVAGE FACTORS; IN-VIVO; DNA; MECHANISM AB In living organisms, stable elongation complexes of RNA polymerase dissociate at specific template positions in a process of transcription termination. It has been suggested that the dissociation is not the immediate cause of termination but is preceded by catalytic inactivation of the elongation complex. In vitro reducing ionic strength can be used to stabilize very unstable and catalytically inactive complex at the point of termination; the previous biochemical characterization of this complex has led to important conclusions regarding termination mechanism. Here we analyze in detail the complexes formed between DNA template, nascent RNA, and Escherichia coli RNA polymerase during transcription through the tR2 terminator of bacteriophage A. At low ionic strength, the majority of elongation complexes fall apart upon reaching the terminator. Released RNA and DNA efficiently rebind RNA polymerase (RNAP) and form binary RNAP.RNA and RNAP.DNA complexes, which are indistinguishable from binary complexes obtained by direct mixing of the purified nucleic acids and the enzyme. A small fraction of elongation complexes that reach termination point escapes dissociation because RNA polymerase has backtracked from the terminator to an upstream DNA position. Thus, transcription elongation to a terminator site produces no termination intermediates that withstand dissociation in the time scale appropriate for biochemical studies. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kashlev, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, Bldg 539,Rm 222, Frederick, MD 21702 USA. NR 41 TC 25 Z9 29 U1 0 U2 2 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 APR 26 PY 2002 VL 277 IS 17 BP 14501 EP 14508 DI 10.1074/jbc.M200215200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 545EH UT WOS:000175203000021 PM 11856750 ER PT J AU Chay, KO Park, SS Mushinski, JF AF Chay, KO Park, SS Mushinski, JF TI Linkage of caspase-mediated degradation of paxillin to apoptosis in Ba/F3 murine pro-B lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; HEMATOPOIETIC-CELLS; TYROSINE KINASE; LIM DOMAINS; PROTEIN INTERACTIONS; SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; BINDING-SITE; LD MOTIFS; INTEGRIN AB We have cloned the complete cDNA from mouse paxillin, a 68-kDa adapter protein found in focal adhesions. We found that paxillin was degraded by caspases in Ba/F3 cell apoptosis induced by withdrawal of interleukin-3 (IL-3), a survival factor for this cell, and by ionizing radiation. Also, paxillin was degraded in vitro by incubation with recombinant caspase-3. Western blot analyses of degradation products of overexpressed green fluorescence protein-tagged paxillin and site-specific mutants demonstrated that Asp-102 and Asp-301 were early caspase cleavage sites, and Asp-5, Asp-146, Asp-165, and Asp-222 were late cleavage sites. Overexpression of paxillin delayed apoptosis of Ba/F3 after IL-3 withdrawal. Furthermore, this anti-apoptotic effect of paxillin was augmented by a triple mutation in aspartic acids at caspase cleavage sites. These results suggest that paxillin plays a critical role in cell survival signaling and that the cleavage of paxillin by caspases might be an important event for focal adhesion disassembly during cell apoptosis, contributing to detachment, rounding, and death. C1 NCI, Genet Lab, NIH, Bethesda, MD 20852 USA. RP Mushinski, JF (reprint author), NCI, Genet Lab, NIH, Bldg 37,Rm 2B23,9000 Rockville Pike, Bethesda, MD 20852 USA. NR 67 TC 24 Z9 25 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 APR 26 PY 2002 VL 277 IS 17 BP 14521 EP 14529 DI 10.1074/jbc.M111638200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 545EH UT WOS:000175203000024 PM 11825902 ER PT J AU Tang, S Zheng, ZM AF Tang, S Zheng, ZM TI Kaposi's sarcoma-associated herpesvirus K8 Exon 3 contains three 5 '-splice sites and harbors a K8.1 transcription start site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPSTEIN-BARR-VIRUS; PRIMARY EFFUSION LYMPHOMA; MESSENGER-RNA INVITRO; RIBOSOME ENTRY SITE; GENE-EXPRESSION; BZIP PROTEIN; DNA-SEQUENCES; CELL-LINE; NUCLEAR ANTIGEN; LYTIC CYCLE AB Kaposi's sarcoma-associated herpesvirus (KSHV) K8 and K8.1 open reading frames are juxtaposed and span from nucleotide (nt) 74850 to 76695 of the virus genome. A K8 pre-mRNA overlaps the entire K8.1 coding region, and alternative splicing of KSHV K8 and K8.1 pre-mRNAs each produces three isoforms (alpha, beta, and gamma) of the mRNAs. We have mapped the 5' end of the K8.1 RNA in butyrate-induced KSHV-positive JSC-1 cells to nt 75901 in the KSHV genome and have shown that exon 3 of the K8 pre-mRNA in JSC-1 cells covers most part of the intron 3 defined previously and has three 5'-splice sites (ss), respectively, at nt 75838, 76155, and 76338. Selection of the nt 75838 5'-ss dictates the K8 mRNA production and overwhelms the RNA processing. Alternative selection of other two 5'-ss is feasible and leads to production of two additional bicistronic mRNAs, K8/K8.1alpha and -beta. However, the novel bicistronic K8/K8.1 mRNAs translated a little K8 and no detectable K8.1 proteins in 293 cells. Data suggest that production of the K8/K8.1 mRNAs may be an essential way to control K8 mRNAs, especially K8alpha, to a threshold at RNA processing level. C1 NCI, HIV & AIDS malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS malignancy Branch, Ctr Canc Res, NIH, Bldg 10,Rm 10S255,MSC 1868,10 Ctr Dr, Bethesda, MD 20892 USA. RI Tang, Shuang/F-9115-2014 OI Tang, Shuang/0000-0002-3084-0903 NR 71 TC 23 Z9 25 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 APR 26 PY 2002 VL 277 IS 17 BP 14547 EP 14556 DI 10.1074/jbc.M111308200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 545EH UT WOS:000175203000027 PM 11832484 ER EF