FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Helmberg, W Feolo, ML Hoffman, DJ Petersdorf, EW AF Helmberg, W Feolo, ML Hoffman, DJ Petersdorf, EW TI The hematopoietic cell transplantation database at dbMHC SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 18th European Histocompatibility Conference CY MAY 08-11, 2004 CL Sofia, BULGARIA SP European Federat Immunogenet C1 NCBI, NIH, Bethesda, MD USA. Fred Hutchinson Canc Res Inst, Seattle, WA 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 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAY PY 2004 VL 5 SU 1 MA 20 BP S5 EP S5 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 828EI UT WOS:000221955900021 ER PT J AU Helmberg, WMC Dunivin, RJ Feolo, ML AF Helmberg, WMC Dunivin, RJ Feolo, ML TI Use of DBMHC/CN3D to highlight amino acid positions on 3D molecular models SO GENES AND IMMUNITY LA English DT Meeting Abstract CT 18th European Histocompatibility Conference CY MAY 08-11, 2004 CL Sofia, BULGARIA SP European Federat Immunogenet C1 Natl Lib Med, Natl Biotechnol Ctr, 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 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAY PY 2004 VL 5 SU 1 MA 24 BP S6 EP S6 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 828EI UT WOS:000221955900025 ER PT J AU Hallsson, JH Haflidadottir, BS Stivers, C Odenwald, W Arnheiter, H Pignoni, F Steingrimsson, E AF Hallsson, JH Haflidadottir, BS Stivers, C Odenwald, W Arnheiter, H Pignoni, F Steingrimsson, E TI The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development SO GENETICS LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; MOUSE MICROPHTHALMIA LOCUS; NEURAL-CREST; PERIPODIAL CELLS; IMAGINAL DISCS; FACTOR FAMILY; EYELESS GENE; EXPRESSION; DIFFERENTIATION; PROTEIN AB The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) cells of the eye. In Mitf mutant mice, the presumptive RPE cells hyperproliferate, abnormally express the retinal transcriptional regulator Pax6, and form an ectopic neural retina. Here we report the structure of the Mitf gene in Drosophila and demonstrate expression during embryonic development and in the eye-antennal imaginal disc. In vitro, transcriptional regulation by Drosophila Mitf, like its mouse counterpart, is modified by the Eyeless (Drosophila Pax6) transcription factor. In vivo, targeted expression of wild-type or dominant-negative Drosophila Mitf results in developmental abnormalities reminiscent of Mitf function in mouse eye development. Our results suggest that the Mitf gene is the original member of the Mitf-Tfe subfamily of bHLH-Zip proteins and that its developmental function is at least partially conserved between vertebrates and invertebrates. These findings further support the common origin of the vertebrate and invertebrate eyes. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. RP Harvard Univ, Sch Med, Dept Ophthalmol, 507,243 Charles St, Boston, MA 02114 USA. EM francesca_pignoni@meei.harvard.edu OI Hallsson, Jon/0000-0002-9127-2137 FU NEI NIH HHS [R01 EY013167, R01 EY13167] NR 51 TC 30 Z9 32 U1 0 U2 2 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD MAY PY 2004 VL 167 IS 1 BP 233 EP 241 DI 10.1534/genetics.167.1.233 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 826TF UT WOS:000221851100019 PM 15166150 ER PT J AU Bailey, JA Church, DM Ventura, M Rocchi, M Eichler, EE AF Bailey, JA Church, DM Ventura, M Rocchi, M Eichler, EE TI Analysis of segmental duplications and genome assembly in the mouse SO GENOME RESEARCH LA English DT Article ID EVOLUTION; GENE; SHOTGUN; INVERSIONS; SEQUENCE; REGIONS; REARRANGEMENTS; TRANSLOCATION; DISORDERS AB Limited comparative studies suggest that the human genome is particularly enriched for recent segmental duplications. The extent of segmental duplications in other mammalian genomes is unknown and confounded by methodological differences in genome assembly. Here, we present a detailed analysis of recent duplication content within the mouse genome using a whole-genome assembly comparison method and a novel assembly independent method, designed to take advantage of the reduced allelic variation of the C57BL/6J strain. We conservatively estimate that similar to57% of all highly identical segmental duplications ( greater than or equal to90%) were misassembled or collapsed within the working draft WGS assembly. The WGS approach often leaves duplications fragmented and unassigned to a chromosome when compared with the clone-ordered-based approach. Our preliminary analysis suggests that 1.7%-2.0% of the mouse genome is part of recent large segmental duplications (about half of what is observed for the human genome). We have constructed a mouse segmental duplication database to aid in the characterization of these regions and their integration into the final mouse genome assembly. This work suggests significant biological differences in the architecture of recent segmental duplications between human and mouse. In addition, our unique method provides the means for improving whole-genome shotgun sequence assembly of mouse and future mammalian genomes. C1 Case Western Reserve Univ, Sch Med, Ctr Computat Genom, Dept Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Bari, Dipartimento Anat Patol & Genet, Sez Genet, I-70126 Bari, Italy. RP Eichler, EE (reprint author), Case Western Reserve Univ, Sch Med, Ctr Computat Genom, Dept Genet, Cleveland, OH 44106 USA. EM eee@cwru.edu RI Ventura, Mario/E-6420-2011; OI Ventura, Mario/0000-0001-7762-8777; Rocchi, Mariano/0000-0002-9451-5616 FU NCI NIH HHS [CA094816]; NHGRI NIH HHS [HG002385, R01 HG002385]; NIGMS NIH HHS [T32 GM007250, GM58815, R01 GM058815]; Telethon [C.50] NR 51 TC 70 Z9 72 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2004 VL 14 IS 5 BP 789 EP 801 DI 10.1101/gr.2238404 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 817IR UT WOS:000221171700001 PM 15123579 ER PT J AU Castillo-Davis, CI Kondrashov, FA Hartl, DL Kulathinal, RJ AF Castillo-Davis, CI Kondrashov, FA Hartl, DL Kulathinal, RJ TI The functional genomic distribution of protein divergence in two animal phyla: Coevolution, genomic conflict, and constraint SO GENOME RESEARCH LA English DT Article ID NUCLEOTIDE SUBSTITUTION; POSITIVE SELECTION; OVERDOMINANT SELECTION; GENETIC CONFLICTS; RAPID EVOLUTION; SEQUENCE; PREECLAMPSIA; DROSOPHILA; DATABASE; CAENORHABDITIS AB We compare the functional spectrum of protein evolution in two separate animal lineages with respect to two hypotheses: (1) rates of divergence are distributed similarly among functional classes within both lineages, indicating that selective pressure on the proteome is largely independent of organismic-level biological requirements; and (2) rates of divergence are distributed differently among functional classes within each lineage, indicating species-specific selective regimes impact genome-wide substitutional patterns. Integrating comparative genome sequence with data from tissue-specific expressed-sequence-tag (EST) libraries and detailed database annotations, we find a functional genomic signature of rapid evolution and selective constraint shared between mammalian and nematode lineages despite their extensive morphological and ecological differences and distant common ancestry. In both phyla, we find evidence of accelerated evolution among components of molecular systems involved in coevolutionary change. In mammals, lineage-specific fast evolving genes include those involved in reproduction, immunity, and possibly, maternal-fetal conflict. Likelihood ratio tests provide evidence for positive selection in these rapidly evolving functional categories in mammals. In contrast, slowly evolving genes, in terms of amino acid or insertion/deletion (indel) change, in both phyla are involved in core molecular processes such as transcription, translation, and protein transport. Thus, strong purifying selection appears to act on the same core cellular processes in both mammalian and nematode lineages, whereas positive and/or relaxed selection acts on different biological processes in each lineage. C1 Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. EM rkulathinal@oeb.harvard.edu RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 62 TC 63 Z9 63 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAY PY 2004 VL 14 IS 5 BP 802 EP 811 DI 10.1101/gr.2195604 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 817IR UT WOS:000221171700002 PM 15123580 ER PT J AU Crisponi, L Uda, M Deiana, M Loi, A Nagaraja, R Chiappe, F Schlessinger, D Cao, A Pilia, G AF Crisponi, L Uda, M Deiana, M Loi, A Nagaraja, R Chiappe, F Schlessinger, D Cao, A Pilia, G TI FOXL2 inactivation by a translocation 171 kb away: analysis of 500 kb of chromosome 3 for candidate long-range regulatory sequences SO GENOMICS LA English DT Article DE genomic; translocation; transcription; promoter; forkhead protein; enhancer; regulation of gene expression ID EPICANTHUS INVERSUS SYNDROME; SYNDROME BPES; BLEPHAROPHIMOSIS; PTOSIS; MUTATIONS; DELETION; GENE; T(3/4)(Q23,P15.2); IDENTIFICATION; BREAKPOINT AB A translocation breakpoint 171 kb 5' of the transcription start of FOXL2 causes blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) and associated premature ovarian failure. The breakpoint falls within another gene, MRPS22, that has been sequenced in 500 kb of continuous DNA. MRPS22 encodes 20 exons and a number of alternative transcripts. Three CpG islands (>91% identical) are followed by noncoding exons 4-12 and coding exons 13-20. The 3'UTR extends into the 3'UTR of COPB2. Based on the sequence, three reported translocations that cause BPES all fall within intron 6 of MRPS22. Comparisons reveal conserved segments in introns 6, 11, and 12 of human and mouse. Notably intron 11 sequence is also deleted in goat PIS syndrome (which combines craniofacial defects, female infertility, and XX sex reversal). The conserved sequences are candidates for models in which they are distant enhancers or otherwise affect higher order chromatin structure to impose long-range cis regulation of FOXL2 expression. (C) 2004 Elsevier Inc. All rights reserved. C1 CNR, Ist Neurogenet & Neurofarmacol, I-09121 Cagliari, Italy. NIA, Genet Lab, Baltimore, MD 21224 USA. RP Pilia, G (reprint author), CNR, Ist Neurogenet & Neurofarmacol, Via Jenner, I-09121 Cagliari, Italy. EM pilia@unica.it FU Telethon [GP0049Y01] NR 28 TC 37 Z9 38 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2004 VL 83 IS 5 BP 757 EP 764 DI 10.1016/j.ygeno.2003.11.010 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 812JL UT WOS:000220835700002 PM 15081106 ER PT J AU Huang, KM Geunes-Boyer, S Wu, SF Dutra, A Favor, J Stambolian, D AF Huang, KM Geunes-Boyer, S Wu, SF Dutra, A Favor, J Stambolian, D TI Organization and annotation of the Xcat critical region: elimination of seven positional candidate genes SO GENOMICS LA English DT Article ID LINKED CATARACT XCAT; NANCE-HORAN-SYNDROME; CONGENITAL CATARACT; MOUSE; CHROMOSOME; IDENTIFICATION; HYBRIDIZATION; EXCLUSION; MUTATIONS; FAMILY AB Xcat mice display X-linked congenital cataracts and are a mouse model for the human X-Iinked cataract disease Nance Horan syndrome (NHS). The genetic defect in Xcat mice and NHS patients is not known. We isolated and sequenced a BAC contig representing a portion of the Xcat critical region. We combined Our sequencing data with the most recent mouse sequence assemblies from both Celera and public databases. The sequence of the 2.2-Mb Xcat critical region was then analyzed for potential Xcat candidate genes. The coding regions of the seven known genes within this area (Rai2, Rbbp7, Ctps2, Calb3, Grpr Reps2, and Syap1) were sequenced in Xcat mice and no mutations were detected. The expression of Rai2 was quantitatively identical in wild-type and Xcat mutant eyes. These results indicate that the Xcat mutation is within a novel, undiscovered gene. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. GSF Natl Res Ctr Environm & Hlth, Inst Human Genet, D-85764 Neuherberg, Germany. RP Stambolian, D (reprint author), Univ Penn, Sch Med, FM Kirby Ctr Mol Ophthalmol, 422 Curie Blvd, Philadelphia, PA 19104 USA. EM stamboli@mail.med.upenn.edu FU NEI NIH HHS [EY10321, R01 EY13615] NR 22 TC 2 Z9 3 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2004 VL 83 IS 5 BP 893 EP 901 DI 10.1016/j.ygeno.2003.10.010 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 812JL UT WOS:000220835700014 PM 15081118 ER PT J AU Silins, I Wang, XH Tadesse, A Jansen, KU Schiller, JT Avall-Lundqvist, E Frankendal, B Dillner, J AF Silins, I Wang, XH Tadesse, A Jansen, KU Schiller, JT Avall-Lundqvist, E Frankendal, B Dillner, J TI A population-based study of cervical carcinoma and HPV infection in Latvia SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervical cancer; epidemiology; HPV; infections; screening ID HUMAN-PAPILLOMAVIRUS INFECTION; EPIDEMIOLOGIC EVIDENCE; CHLAMYDIA-TRACHOMATIS; ORAL-CONTRACEPTIVES; CANCER WORLDWIDE; RISK-FACTORS; YOUNG-WOMEN; TYPE-16; HYBRIDIZATION; PREVALENCE AB Objectives. We wished to quantify the population-based importance of cervical carcinoma risk factors in Latvia. Methods. Totally, 223 of 224 eligible cases of incident invasive cervical carcinoma were enrolled during July 1998-February 2001 in Latvia. An age-matched sample of 300 healthy control women was selected from the Latvian population registry and 239 of these women (79%) were enrolled. A demographic and life-style questionnaire was completed, cervical brush samples were analyzed for human papillomavirus (HPV) DNA by PCR and serum samples for HPV antibodies. Results. Risk factors for cervical cancer in multivariate analysis were HPV type 16 or 18 DNA positivity (OR = 32.4; CI 95% 16.5-63.6) and living in the capital (OR = 2.4; Cl 95% 1.2-4.7). Oral contraceptive use was not a risk factor (OR = 0.4; CI 95% 0.2-1.1). A strong protective effect was found for having had more than three Pap smears in the last 5 years (OR = 0.07 CI 95% 0.03-0.19). Conclusions. Inadequate population coverage of Pap smears, in spite of excessive smear usage, caused 28.4% of cervical cancers in age groups eligible for screening. HPV type 16 infection was the most important risk factor for cervical cancer in Latvia, with a population-attributable risk percent for all ages of 58.5%. (C) 2004 Elsevier Inc. All rights reserved. C1 MAS Univ Hosp, Dept Med Microbiol, S-20502 Malmo, Sweden. Oncol Ctr Latvia, Riga, Latvia. Karolinska Hosp, Radiumhemmet, Dept Gynecol Oncol, S-10401 Stockholm, Sweden. Merck Sharp & Dohme Ltd, Res Labs, W Point, PA 19486 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Dillner, J (reprint author), MAS Univ Hosp, Dept Med Microbiol, S-20502 Malmo, Sweden. EM joakim.dillner@mikrobiol.mas.lu.se RI Avall-Lundqvist, Elisabeth/C-9292-2009 NR 40 TC 24 Z9 27 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2004 VL 93 IS 2 BP 484 EP 492 DI 10.1016/j.ygyno.2004.01.044 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 816OZ UT WOS:000221120500035 PM 15099967 ER PT J AU Givant-Horwitz, V Davidson, B Goderstad, JM Nesland, JM Trope, CG Reich, R AF Givant-Horwitz, V Davidson, B Goderstad, JM Nesland, JM Trope, CG Reich, R TI The PAC-1 dual specificity phosphatase predicts poor outcome in serous ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE dual specificity phosphatases; mitogen-activated protein kinases; ovarian carcinoma; serous effusions; chemotherapy; survival ID PROTEIN-KINASE PHOSPHATASE-1; SIGNAL-REGULATED KINASE; EPIDERMAL-GROWTH-FACTOR; CANCER-CELLS; MOLECULAR-CLONING; MESSENGER-RNA; EXPRESSION; EFFUSIONS; APOPTOSIS; PATHWAYS AB Objective. Data regarding signal transduction pathways in human tumors are largely confined to cell line studies to date. We have recently reported on the activation and prognostic role of mitogen-activated protein kinases (MAPK) in ovarian carcinoma in effusions. The objective of the present study was to investigate the expression and clinical role of dual-specificity phosphatases (DUSP), inhibitors of MAPK signaling, in ovarian cancer cells at this site. Methods. Thirty-nine fresh frozen malignant effusions from patients diagnosed with serous ovarian carcinoma were studied for mRNA expression of the DUSP MKP-1, MKP-4, MKP-5, and PAG-1 using RT-PCR. DUSP expression was analyzed for possible correlation with patient age, disease stage, tumor grade, histological grade, chemotherapy status, and survival. Results. MKP-1 and PAG-1 mRNA were fund in 36 and 37 effusions, respectively, with expression levels showing considerable variation. MKP-4 and MKP-5 were uniformly absent. MKP-1 showed no association with clinicopathologic parameters. However, PAC-1 expression was significantly higher in effusions obtained be-ore the institution of treatment with both platinum compounds (P = 0.029) and paclitaxel (P = 0.036). In univariate survival analysis, high level of expression of PAC-1 mRNA predicted significantly worse overall survival compared to low expression (mean = 30 vs. 52 months, median = 25 vs. 46 months) (P = 0.007). Conclusions. Despite the limited size of this cohort, our results present the first evidence supporting a clinical role for PAC-1 in ovarian carcinoma. In view of the improved outcome associated with activation of all three MAPK families, as well as their elevated expression and activation in post-chemotherapy specimens presented in our previous work, they also suggest that PAC-1 is a true negative regulator of MAPK in ovarian carcinoma cells in effusions. (C) 2004 Elsevier Inc. All rights reserved. C1 Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Dept Pharmacol & Expt Therapeut, IL-91120 Jerusalem, Israel. Univ Oslo, Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway. Univ Oslo, Norwegian Radium Hosp, Dept Gynecol Oncol, N-0310 Oslo, Norway. Hebrew Univ Jerusalem, David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. RP Davidson, B (reprint author), NIH, Pathol Lab, Bldg 10,Room 4B 1,9000 Rockville Pike, Bethesda, MD 20892 USA. EM davidsob@mail.nih.gov NR 39 TC 28 Z9 30 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2004 VL 93 IS 2 BP 517 EP 523 DI 10.1016/j.ygyno.2004.03.009 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 816OZ UT WOS:000221120500040 PM 15099972 ER PT J AU Bishop, MR AF Bishop, MR TI Allogeneic hematopoietic stem cell transplantation for metastatic breast cancer SO HAEMATOLOGICA LA English DT Article DE graft-versus-tumor; reduced intensity; graft-versus-host disease; chimerism; T cells; adoptive cellular therapy ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST DISEASE; MURINE MAMMARY-CARCINOMA; CHRONIC MYELOID-LEUKEMIA; HIGH-DOSE CHEMOTHERAPY; ADOPTIVE IMMUNOTHERAPY; TUMOR; GRAFT; THERAPY; LYMPHOCYTES AB The prognosis is poor and the options are limited for patients with metastatic breast cancer (MBC), especially for those patients who have previously received taxanes and anthracyclines; treatment strategies are primarily palliative. Murine models have demonstrated that allogeneic T cells are capable of eliciting graft-versus-tumor (GVT) effects against breast cancer, inhibiting growth of breast cancer cell lines in vivo, providing the rationale to pursue allogeneic adoptive cellular therapy as a strategy to treat MBC. However, the clinical application of allogeneic hematopoietic stem cell transplantation (alloHSCT) was limited by concerns over toxicity and unproven efficacy. The development of non-myeloablative (a.k.a. reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T-cell mediated GVT effects, led to increased investigation of alloHSCT in MBC. Early reports of non-myeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses, observed in 20-40% of patients, appear to be associated with the development of complete donor lymphoid chimerism and may be delayed. In its current form, alloHSCT by itself is unlikely to result in complete eradication of MBC; however, it may serve as a therapeutic platform to complement and enhance the effects of existing cytotoxic therapies and immunotherapies (e.g. trastuzumab), as well as therapies under development (e.g. vaccines). Current data on alloHSCT for MBC should be interpreted cautiously and carefully used for the design of future studies to fully determine the clinical efficacy of this form of adoptive cellular therapy in MBC. C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov NR 53 TC 8 Z9 8 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAY PY 2004 VL 89 IS 5 BP 599 EP 605 PG 7 WC Hematology SC Hematology GA 819DC UT WOS:000221292400013 PM 15136224 ER PT J AU Belsky, L Lie, R Mattoo, A Emanuel, EJ Sreenivasan, G AF Belsky, L Lie, R Mattoo, A Emanuel, EJ Sreenivasan, G TI The general agreement on trade in services: Implications for health policymakers SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT Meeting on Globalization, Justice and Health CY NOV 03-04, 2003 CL Washington, DC SP Clin Bioethics, Clin Ctr Dept, NIH, Fogarty Int Ctr AB The General Agreement on Trade in Services (GATS), created under the auspices of the World Trade Organization, aims to regulate measures affecting international trade in services-including health services such as health insurance, hospital services, telemedicine, and acquisition of medical treatment abroad. The agreement has been the subject of great controversy, for it may affect the freedom with which countries can change the shape of their domestic health care systems. We explain the rationale behind the agreement and discuss its scope. We also address the major controversies surrounding the GATS and their implications for the U.S. health care system. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. World Bank, Dev Inst, Washington, DC 20433 USA. World Bank, Washington, DC 20433 USA. Univ Toronto, Dept Philosophy, Canada Res Chair, Toronto, ON, Canada. RP Belsky, L (reprint author), NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. EM gopal.sreenivasan@utoronto.ca NR 12 TC 11 Z9 12 U1 0 U2 2 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 2004 VL 23 IS 3 BP 137 EP 145 DI 10.1377/hlthaff.23.3.137 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 818HX UT WOS:000221237300018 PM 15160811 ER PT J AU Flory, J Young-Xu, Y Gurol, P Levinsky, N Ash, A Emanuel, E AF Flory, J Young-Xu, Y Gurol, P Levinsky, N Ash, A Emanuel, E TI Place of death: US trends since 1980 SO HEALTH AFFAIRS LA English DT Article ID LAST YEAR; PATIENT PREFERENCES; MANAGED CARE; LIFE; SYSTEM; COST; END AB Place of death is one indicator of the state of end-of-life care. We examine trends in national death certificate data on place of death from 1980 to 1998. During these years the percentage of Americans dying as hospital inpatients decreased from approximately 54 percent to 41 percent. About 310,000 fewer people died in the hospital in 1998 than if the proportion of inpatient deaths had not changed since 1980. For certain diseases the change was much greater. In 1980 whites and African Americans died in the hospital in equal proportions, but in 1998 whites died as inpatients less often than African Americans. These racial differences and their implications deserve further study. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA. Bogazici Univ, Dept Econ, TR-80815 Bebek, Turkey. Boston Univ, Sch Med, Dept Med, Boston, MA USA. RP Flory, J (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. EM jflory@cc.nih.gov NR 28 TC 116 Z9 116 U1 1 U2 7 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 2004 VL 23 IS 3 BP 194 EP 200 DI 10.1377/hlthaff.23.3.194 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 818HX UT WOS:000221237300024 PM 15160817 ER PT J AU Wragg, A Mills, P Hall, R AF Wragg, A Mills, P Hall, R TI Case 5: infective endocarditis SO HEART LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. London Chest Hosp, London E2 9JX, England. Univ E Anglia, Norwich NR4 7TJ, Norfolk, England. RP Wragg, A (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAY 1 PY 2004 VL 90 IS 5 BP 580 EP 580 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 812FN UT WOS:000220825500038 PM 17165210 ER PT J AU Adams, PC Arthur, MJ Boyer, TD DeLeve, LD Di Bisceghe, AM Hall, M Levin, TR Provenzale, D Seeff, L AF Adams, PC Arthur, MJ Boyer, TD DeLeve, LD Di Bisceghe, AM Hall, M Levin, TR Provenzale, D Seeff, L TI Screening in liver disease: Report of an AASLD Clinical Workshop SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; CHRONIC VIRAL-HEPATITIS; HEPATOCELLULAR-CARCINOMA; ESOPHAGEAL-VARICES; COST-EFFECTIVENESS; HEREDITARY HEMOCHROMATOSIS; GENETIC DISCRIMINATION; C282Y MUTATION; UNITED-STATES; B VIRUS AB This report summarizes an AASLD Clinical Workshop that was presented at Digestive Diseases Week 2003 on screening in liver diseases. As newer diagnostic tests become available, many liver diseases and complications of liver disease can be detected at an early asymptomatic stage. In many cases, early detection can lead to earlier treatment and an improved outcome. However, screening for liver diseases in asymptomatic persons has the potential for adverse consequences, including discrimination and stigmatization. The cost of screening programs is significant, and access to screening tests varies in different countries. Future screening programs require careful planning and implementation to balance the benefits, risks, and cost-effectiveness. This review outlines the concepts of screening and their application to a broad range of liver diseases. C1 London Hlth Sci Ctr, London, ON N6A 5A5, Canada. Univ Southampton, Southampton, Hants, England. Arizona Liver Res Inst, Tucson, AZ USA. Univ So Calif, Los Angeles, CA USA. St Louis Univ, Sch Med, St Louis, MO USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Kaiser Permanente Med Ctr, Walnut Creek, CA USA. Duke Univ, Med Ctr, Durham, NC USA. NIDDK, NIH, Bethesda, MD USA. RP Adams, PC (reprint author), London Hlth Sci Ctr, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM padams@uwo.ca RI DeLeve, Laurie/F-3549-2012 NR 54 TC 31 Z9 31 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2004 VL 39 IS 5 BP 1204 EP 1212 DI 10.1002/hep.20169 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 815NX UT WOS:000221050100005 PM 15122748 ER PT J AU Radaeva, S Sun, R Pan, HN Hong, F Gao, B AF Radaeva, S Sun, R Pan, HN Hong, F Gao, B TI Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation SO HEPATOLOGY LA English DT Article ID INDUCED LIVER-INJURY; GROWTH-FACTOR; CYCLIN D1; INDUCIBLE FACTOR; FUNCTIONAL-CHARACTERIZATION; NEOPLASTIC DEVELOPMENT; AUTOIMMUNE HEPATITIS; IL-TIF; INHIBITION; PROLIFERATION AB The central role of T cell activation in hepatocellular injury has been well documented. In this article, we provide evidence suggesting that T cells may also play a protective role in liver disease by releasing interleukin-22 (IL-22), a recently identified T cell-derived cytokine whose biological significance is unclear. IL-22 messenger RNA and protein expression are significantly elevated in T cell-mediated hepatitis induced by concanavalin A (ConA) but are less extensively elevated in the carbon tetrachloride-induced liver injury model. Activated CD3(+) T cells are likely responsible for the production of IL-22 in the liver after injection of ConA. The IL-22 receptor is normally expressed at high levels by hepatocytes and further induced after ConA injection. IL-22 blockade with a neutralizing antibody reduces signal transducer and activator of transcription factor 3 (STAT3) activation and worsens liver injury in T cell-mediated hepatitis, whereas injection of recombinant IL-22 attenuates such injury. In vitro treatment with recombinant IL-22 or overexpression of IL-22 promotes cell growth and survival in human hepatocellular carcinoma HepG2 cells. Stable overexpression of IL-22 in HepG2 cells constitutively activates STAT3 and induces expression of a variety of antiapoptotic (e.g., Bcl-2, Bcl-xL, Mcl-1) and mitogenic (e.g., c-myc, cyclin D1, Rb2, CDK4) proteins. Blocking STAT3 activation abolishes the antiapoptotic and mitogenic actions of IL-22 in hepatic cells. In conclusion, the T cell-derived cytokine IL-22 is a survival factor for hepatocytes; this suggests that T cell activation may also prevent and repair liver injury by releasing hepatoprotective cytokine IL-22 in addition to its previously documented central role in hepatocellular injury. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Pk Bldg,Rm 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 47 TC 308 Z9 333 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2004 VL 39 IS 5 BP 1332 EP 1342 DI 10.1002/hep.20184 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 815NX UT WOS:000221050100019 PM 15122762 ER PT J AU Paku, S Nagy, P Kopper, L Thorgeirsson, SS AF Paku, S Nagy, P Kopper, L Thorgeirsson, SS TI 2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: Confocal and electron microscopic studies SO HEPATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; EPITHELIAL-CELLS; GAP-JUNCTIONS; ADHESION MOLECULES; LIVER-REGENERATION; GENE-EXPRESSION; BONE-MARROW; EMBRYOS; HEPATOCARCINOGENESIS; ORGANOGENESIS AB The 2-acetylaminofluorene (AAF)/partial hepatectomy (PH) model is one of the most extensively studied experimental systems for oval cell proliferation and differentiation. We have previously described the oval cells as forming ductular structures surrounded by basement membrane, representing extensions of the canals of Hering. Herein we analyze the differentiation of oval cells into hepatocytes after varying degrees of liver damage induced by AAF. At a low dose of AAF, most oval cells synchronously differentiate into small hepatocytes by 6 days after the PH, resulting in complete restoration of the liver structure in 10 days. Higher doses of AAF delay the differentiation process and the new hepatocytes form foci, in contrast to what is observed at the low dose. Qualitatively, the differentiation process seems to be identical at the cellular level under both conditions. The transition from the expanding oval cell population into hepatocytes was correlated with the upregulation of hepatocyte nuclear factor 4 and the disappearance of the basement membrane. Also, the differentiation of oval cells into hepatocytes coincided with the loss of alpha-fetoprotein and OV-6 staining, and the replacement of the biliary cell-specific alpha6 integrin and connexin 43 with the hepatocyte-specific alpha1 integrin and connexin 32. In addition, bile canaliculi form between the new hepatocytes. In conclusion, these results indicate the rate of oval cell differentiation into hepatocytes is context dependent and suggest that, under favorable conditions, oval cells can complete this process much faster than previously appreciated. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. Hungarian Acad Sci, Joint Res Org, Budapest, Hungary. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 44 TC 77 Z9 83 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2004 VL 39 IS 5 BP 1353 EP 1361 DI 10.1002/hep.20178 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 815NX UT WOS:000221050100021 PM 15122764 ER PT J AU Sangkuhl, K Schulz, A Rompler, H Yun, J Wess, J Schoneberg, T AF Sangkuhl, K Schulz, A Rompler, H Yun, J Wess, J Schoneberg, T TI Aminoglycoside-mediated rescue of a disease-causing nonsense mutation in the V2 vasopressin receptor gene in vitro and in vivo SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; MAMMALIAN TRANSLATION SYSTEM; PREMATURE STOP MUTATIONS; CYSTIC-FIBROSIS; CFTR FUNCTION; SUPPRESSION; GENTAMICIN; EXPRESSION; TERMINATION; DISORDERS AB Many human diseases are caused by inactivating mutations in specific G-protein-coupled receptors (GPCRs). In about 10% of these cases, a premature stop codon leads to the generation of a truncated, functionally inactive receptor protein. In this study, we tested the hypothesis that such GPCR mutations can be functionally rescued in vitro and in vivo by treatment with aminoglycoside antibiotics, which are known for their ability to suppress premature termination codons. As a model system, we studied a mutant V2 vasopressin receptor (AVPR2) containing the inactivating E242X nonsense mutation which mimics human X-linked nephrogenic diabetes insipidus (XNDI) when introduced into mice via gene targeting techniques. Studies with cultured mammalian cells expressing the E242X mutant receptor showed that G418 (geneticin) was by far the most potent aminoglycoside antibiotic capable of suppressing the E242X nonsense codon. Strikingly, G418 treatment increased AVP-mediated cAMP responses in cultured kidney collecting duct cells prepared from E242X mutant mice in vitro, and significantly improved the urine-concentrating ability of E242X mutant mice in vivo. This is the first study demonstrating that G418 (aminoglycosides) can ameliorate the clinical symptoms of a disease-causing premature stop codon in a member of the GPCR superfamily. C1 Univ Leipzig, Fac Med, Dept Mol Biochem, Inst Biochem, D-04103 Leipzig, Germany. Free Univ Berlin, Fac Med, Inst Pharmacol, D-1000 Berlin, Germany. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Schoneberg, T (reprint author), Univ Leipzig, Fac Med, Dept Mol Biochem, Inst Biochem, Deutsch Pl 6, D-04103 Leipzig, Germany. EM schoberg@medizin.uni-leipzig.de RI chen, xuanlan/H-4158-2011 NR 28 TC 49 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2004 VL 13 IS 9 BP 893 EP 903 DI 10.1093/hmg/ddh105 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 813GW UT WOS:000220896600001 PM 14998935 ER PT J AU Booker, DL Berman, JJ AF Booker, DL Berman, JJ TI Dangerous abbreviations SO HUMAN PATHOLOGY LA English DT Editorial Material C1 St Joseph Hosp, Dept Pathol, Med Coll Georgia, Augusta, GA USA. NCI, Canc Diag Program, DCTD, NIH,Pathol Informat, Rockville, MD USA. RP Booker, DL (reprint author), St Joseph Hosp, Dept Pathol, Med Coll Georgia, Augusta, GA USA. NR 7 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2004 VL 35 IS 5 BP 529 EP 531 DI 10.1016/j.humpath.2004.01.007 PG 3 WC Pathology SC Pathology GA 823VS UT WOS:000221642400001 PM 15138924 ER PT J AU Goldstein, DS Eisenhofer, G Flynn, JA Wand, G Pacak, K AF Goldstein, DS Eisenhofer, G Flynn, JA Wand, G Pacak, K TI Diagnosis and localization of pheochromocytoma SO HYPERTENSION LA English DT Article DE pheochromocytoma; norepinephrine ID I-131 METAIODOBENZYLGUANIDINE; DILATED CARDIOMYOPATHY; BIOCHEMICAL-DIAGNOSIS; SCINTIGRAPHY; MANAGEMENT; PET AB This Hypertension Grand Rounds shows how applying new clinical laboratory techniques helped to diagnose pheochromocytoma in a difficult case. In the setting of long-standing, sustained hypertension, the patient had a hypertensive paroxysm during anesthesia induction for surgery, leading to suspicion of a pheochromocytoma. Conventional testing, including CT scanning and fractionated urinary metanephrine test, was not diagnostic. The patient had another hypertensive paroxysm during subsequent anesthesia induction, requiring intensive care. Consistently elevated plasma levels of free normetanephrine provided the first and only biochemical evidence for a pheochromocytoma in this case. 6-[F-18] Fluorodopamine positron emission tomography and I-123-metaiodobenzylguanidine scintigraphy subsequently agreed on the existence of a small left adrenal mass, which when removed surgically proved to be a pheochromocytoma. Postoperatively, plasma levels of normetanephrine normalized, and there were no further hypertensive paroxysms, although the patient remained hypertensive. This case illustrates the superiority of plasma levels of free (unconjugated) metanephrines, compared with other biochemical tests, to detect pheochromocytoma. It also confirms that functional imaging by 6-[F-18] fluorodopamine or I-123-metaiodobenzylguanidine scanning can localize pheochromocytoma in difficult cases in which other imaging tests are not diagnostic. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Natl Inst Child Hlth & Dev, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov NR 21 TC 34 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2004 VL 43 IS 5 BP 907 EP 910 DI 10.1161/01.HYP.0000125014.56023.b8 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816ME UT WOS:000221113200001 PM 15023935 ER PT J AU Vasan, RS Evans, JC Benjamin, EJ Levy, D Larson, MG Sundstrom, J Murabito, JM Sam, F Colucci, WS Wilson, PWF AF Vasan, RS Evans, JC Benjamin, EJ Levy, D Larson, MG Sundstrom, J Murabito, JM Sam, F Colucci, WS Wilson, PWF TI Relations of serum aldosterone to cardiac structure - Gender-related differences in the Framingham Heart Study SO HYPERTENSION LA English DT Article DE echocardiography; aldosterone; hypertrophy; epidemiology ID LEFT-VENTRICULAR HYPERTROPHY; ESSENTIAL-HYPERTENSION; RENOVASCULAR HYPERTENSION; PRESSURE-OVERLOAD; BLOOD-PRESSURE; FAILURE; SPIRONOLACTONE; SYSTEM; MASS; ASSOCIATION AB Aldosterone is associated with myocardial fibrosis in experimental studies and with left ventricular remodeling in heart failure patients. We hypothesized that aldosterone influences ventricular remodeling in people without congestive heart failure in the community. We examined the relations between serum aldosterone and echocardiographic left ventricular measurements in 2820 Framingham Study subjects (mean age 57 years, 58% women, 88% white) free of myocardial infarction and overt heart failure. Serum aldosterone levels were higher in women compared with men. In linear regression models (adjusted for age, systolic blood pressure, weight, height, diabetes, heart rate, hypertension treatment, and ethnicity), left ventricular wall thickness and relative wall thickness were positively related, and left ventricular diastolic dimensions were inversely related to serum aldosterone in women (P<0.05 for all), but not in men (P>0.20 for all). There was no effect modification of the relations observed in women by menopausal status. The gender-related differences in relations of serum aldosterone to relative wall thickness were consistent across subgroups defined on the basis of sex-specific median values of systolic blood pressure and body mass index. Fractional shortening, left ventricular mass, and left atrial dimensions were not related to serum aldosterone in either sex. In conclusion, in our community-based sample of individuals free of myocardial infarction and heart failure, serum aldosterone was positively associated with a left ventricular geometric pattern suggestive of concentric remodeling ( increased left ventricular wall thickness and relative wall thickness but decreased internal dimensions) in women but not in men. Additional investigations are warranted to confirm these findings. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Myocardial Biol Unit, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Preventat Med & Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@fram.nhlbi.nih.gov RI Sundstrom, Johan/A-6286-2009; OI Sundstrom, Johan/0000-0003-2247-8454; Larson, Martin/0000-0002-9631-1254; Murabito, Joanne/0000-0002-0192-7516; Sam, Flora/0000-0001-8442-9362; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, 1K24 HL04334, 1R01HL67288] NR 43 TC 81 Z9 85 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2004 VL 43 IS 5 BP 957 EP 962 DI 10.1161/01.HYP.0000124251.06056.8e PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816ME UT WOS:000221113200013 PM 15007028 ER PT J AU Thadhani, R Ecker, JL Mutter, WP Wolf, M Smirnakis, KV Sukhatme, VP Levine, RJ Karumanchi, SA AF Thadhani, R Ecker, JL Mutter, WP Wolf, M Smirnakis, KV Sukhatme, VP Levine, RJ Karumanchi, SA TI Insulin resistance and alterations in angiogenesis - Additive insults that may lead to preeclampsia SO HYPERTENSION LA English DT Article DE pregnancy; insulin resistance; preeclampsia; clinical trials ID HORMONE-BINDING GLOBULIN; ENDOTHELIAL GROWTH-FACTOR; GESTATIONAL DIABETES-MELLITUS; POSTMENOPAUSAL WOMEN; SIGNAL-TRANSDUCTION; GLUCOSE-TOLERANCE; TYROSINE KINASE-1; PREGNANCY; RISK; HYPERTENSION AB Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208+/-116 versus 256+/-101 nmol/L, P=0.05) and PlGF (16+/-14 versus 67+/-150 pg/mL, P<0.001), and in multivariable analysis, women with serum levels of PlGF&LE;20 pg/mL had an increased risk of developing preeclampsia (odds ratio [OR] 7.6, 95% CI 1.4 to 38.4). Stratified by levels of serum SHBG (&LE;175 versus >175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal testing for interaction (PlGF x SHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PlGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Hosp, Renal Unit, Boston, MA USA. NIDDK, NIH, Bethesda, MD USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Renal Unit, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NICHD NIH HHS [HD39223]; NIDDK NIH HHS [DK02825, DK64255] NR 36 TC 65 Z9 68 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2004 VL 43 IS 5 BP 988 EP 992 DI 10.1161/01.HYP.0000124460.67539.1d PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816ME UT WOS:000221113200018 PM 15023932 ER PT J AU Chobanian, AV Roccella, EJ AF Chobanian, AV Roccella, EJ TI The JNC-7 guidelines and the optimal target for systolic blood pressure - Response SO HYPERTENSION LA English DT Letter ID J-SHAPED RELATIONSHIP C1 Boston Univ, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP Chobanian, AV (reprint author), Boston Univ, Boston, MA 02215 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2004 VL 43 IS 5 BP E31 EP E31 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816ME UT WOS:000221113200047 ER PT J AU Nookala, S Srinivasan, S Kaliraj, P Narayanan, RB Nutman, TB AF Nookala, S Srinivasan, S Kaliraj, P Narayanan, RB Nutman, TB TI Impairment of tetanus-specific cellular and humoral responses following tetanus vaccination in human lymphatic filariasis SO INFECTION AND IMMUNITY LA English DT Article ID IMMUNE-RESPONSES; T-CELL; BANCROFTIAN FILARIASIS; HELMINTH INFECTION; ONCHOCERCIASIS PATIENTS; TRANSMISSION INTENSITY; SCHISTOSOMA-MANSONI; INTERLEUKIN-10; ANTIGENS; IL-10 AB To investigate the consequences of the impaired parasite-specific immune response in lymphatic filariasis, the effect of concurrent Wuchereria bancrofti infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied in 20 asymptomatic microfilaremic (MF) patients, 20 patients with chronic lymphatic obstruction/elephantiasis (chronic pathology [CP]), and 10 endemic normal (EN) control individuals at baseline and at 3 and 6 months after TT vaccination. Peripheral blood mononuclear cell (PBMC) proliferative responses to 17 before vaccination were not significantly different between the EN control and CP groups, but the MF group showed significantly lower baseline proliferative responses to TT compared with either the EN or CP group. Six months following vaccination, the change in proliferative response to TT was significantly greater in the EN and CP groups than in the MF group. This difference in proliferative response was reiterated in the gamma interferon (IFN-gamma) response in the EN group, in that they increased IFN-gamma production by 400% at 6 months, in contrast to that seen in the filaria-infected groups. In contrast to the IFN-gamma responses, PBMCs from the MF group produced significantly increased levels of TT-specific IL-10 compared with PBMCs from the EN group. Although there was significantly greater TT-specific immunoglobulin G (IgG) production at baseline between the EN and MF groups, postvaccination IgG (and IgG1 isotype) responses did not differ among the groups, whereas TT-specific IgG2, IgG3, and IgG4 were all increased in the EN group compared with the filaria-infected groups. These studies indicate that concurrent infection with W. bancrofti can diminish the immune response to an unrelated antigen by a mechanism that is likely to involve IL-10. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India. Directorate Publ Hlth & Prevent Med, Madras 600006, Tamil Nadu, India. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-B1-03, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov NR 36 TC 80 Z9 82 U1 0 U2 4 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 2004 VL 72 IS 5 BP 2598 EP 2604 DI 10.1128/IAI.72.5.2598-2604.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 816OV UT WOS:000221120100018 PM 15102768 ER PT J AU Johnson, AH Leke, RGF Mendell, NR Shon, D Sub, YJ Bomba-Nkolo, D Tchinda, V Kouontchou, S Thuita, LW Van der Wel, AM Thomas, A Stowers, A Saul, A Zhou, AN Taylor, DW Quakyi, IA AF Johnson, AH Leke, RGF Mendell, NR Shon, D Sub, YJ Bomba-Nkolo, D Tchinda, V Kouontchou, S Thuita, LW Van der Wel, AM Thomas, A Stowers, A Saul, A Zhou, AN Taylor, DW Quakyi, IA TI Human leukocyte antigen class II alleles influence levels of antibodies to the Plasmodium falciparum asexual-stage apical membrane antigen 1 but not to merozoite surface antigen 2 and merozoite surface protein 1 SO INFECTION AND IMMUNITY LA English DT Article ID INHIBIT PARASITE GROWTH; HUMORAL IMMUNE-RESPONSE; C-TERMINAL FRAGMENT; MALARIA MORBIDITY; MONOCLONAL-ANTIBODIES; CLINICAL IMMUNITY; CELL INVASION; FULL-LENGTH; HLA-DR; VACCINE AB The apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine for Plasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP1(19)) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP1(19) variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP1(19) but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP1(19) variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated. C1 Georgetown Univ, Sch Med, Dept Pediat, Washington, DC 20057 USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. Univ Yaounde 1, Fac Med & Biomed Sci, Yaounde, Cameroon. Univ Yaounde 1, Ctr Biotechnol, Yaounde, Cameroon. SUNY Stony Brook, Dept Math Appl, Stony Brook, NY 11794 USA. Seoul Natl Univ, Dept Stat, Seoul, South Korea. Seoul Natl Univ, Clin Res Inst, Seoul, South Korea. Biomed Primate Res Ctr, Rijswijk, Netherlands. NIAID, Malaria Vaccine Dev Unit, NIH, Bethesda, MD 20892 USA. Univ Queensland, Queensland Inst Med Res, Brisbane, Qld, Australia. RP Johnson, AH (reprint author), Georgetown Univ, Sch Med, Dept Pediat, PCS Bldg LD8D,3800 Resevoir Rd NW, Washington, DC 20057 USA. EM johnsoa2@georgetown.edu RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU NIAID NIH HHS [U01 AI035839, U01-AI-35839]; NIMH NIH HHS [R01 MH049487, MH49487] NR 52 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2004 VL 72 IS 5 BP 2762 EP 2771 DI 10.1128/IAI.72.5.2762-2771.2004 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 816OV UT WOS:000221120100036 PM 15102786 ER PT J AU Doi, AM Peckham, JC Chou, BJ Dill, JA Renne, RA Grumbein, SL Chhabra, RS AF Doi, AM Peckham, JC Chou, BJ Dill, JA Renne, RA Grumbein, SL Chhabra, RS TI Development of alpha(2u)-globulin nephropathy and adrenal medullary pheochromocytomas in male rats following exposure to Stoddard solvent IIC SO INHALATION TOXICOLOGY LA English DT Article ID DEAROMATIZED WHITE SPIRIT; PETROLEUM HYDROCARBON TOXICITY; DRY-CLEANING WORKERS; ZERO DOSE CONTROL; INHALATION EXPOSURE; ALPHA-2U-GLOBULIN NEPHROPATHY; BODY-WEIGHT; LONG-TERM; CANCER-MORTALITY; TUMOR-INCIDENCE AB Stoddard solvent IIC is widely used as a solvent in paints and varnishes, and for dry cleaning and other grease removal applications. Because concern exists regarding the long-term effects of occupational exposure in industrial settings, the toxicity and carcinogenicity of Stoddard solvent IIC were evaluated in male and female F344/N rats and B6C3F(1) mice. Rats and mice were exposed to 0,138,275,550,1100, or 2200 mg/m(3) Stoddard solvent IIC by whole-body inhalation for 3 mo, and to 0, 138 (male rats), 550, 1100, or 2200 (female rats and male and female mice) mg/m(3) for 2 yr. The kidney, liver, and adrenal medulla were targets of Stoddard solvent IIC toxicity in rats. After 3 mo of exposure, male rats developed lesions characteristic of alpha(2u)-globulin nephropathy. Male and female rats displayed increased liver weights and/or clinical pathology changes suggestive of hepatic injury, although no accompanying histopathologic changes were observed. After 2 yr, increased incidences of adrenal medullary pheochromocytomas provided some evidence of carcinogenicity in male rats. Renal tubule adenomas were slightly increased in male rats after 2 yr, and may have been related to exposure. In mice, there was no chemical-related toxicity after 3 mo, with the exception of increased liver weights in male mice exposed to 2200 mg/m(3). After 2 yr, the incidences of hepatocellular adenomas were increased in female mice exposed to 2200 mg/m(3); however, these increases were marginal and associated with increases in body weight. There was no evidence of Stoddard solvent IIC carcinogenicity in female rats or male mice. In summary, inhalation exposures of Stoddard solvent IIC resulted in renal toxicity and adrenal medullary pheochromocytomas in male rats. The liver also appeared to be a site of toxicity in male and female rats and mice. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Toxicol NW, Richland, WA USA. RP Doi, AM (reprint author), NIEHS, POB 12233,Mail Drop EC-34, Res Triangle Pk, NC 27709 USA. EM doi@niehs.nih.gov NR 46 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD MAY PY 2004 VL 16 IS 5 BP 247 EP 257 DI 10.1080/08958370490427842 PG 11 WC Toxicology SC Toxicology GA 816BE UT WOS:000221084600001 PM 15371178 ER PT J AU Dill, JA Fuciarelli, AF Lee, KM Mellinger, KM Burka, LT Roycroft, JH AF Dill, JA Fuciarelli, AF Lee, KM Mellinger, KM Burka, LT Roycroft, JH TI Toxicokinetics of propylene glycol mono-t-butyl ether following intravenous or inhalation exposure in rats and mice SO INHALATION TOXICOLOGY LA English DT Article ID AGE-RELATED-CHANGES; METABOLISM; ALPHA-2U-GLOBULIN; DISPOSITION; NEPHROPATHY; EXPRESSION AB Propylene glycol mono-t-butyl ether (PGMBE) is a widely used solvent in industry and in consumer products, posing a potential for human exposure via inhalation or dermal routes. Toxicokinetic studies were conducted on F344/N rats and B6C3F1 mice of both sexes to evaluate single or repeated dose, species, and/or sex differences in PGMBE elimination kinetics following intravenous or inhalation exposure. In the first study, rats and mice received a single intravenous dose of 15 or 200 mg PGMBE/kg and serial blood samples were collected and analyzed for PGMBE. In the second study, rats and mice received a single 6-h whole-body inhalation exposure to 75, 300, or 1200 ppm PGMBE and serial blood samples were collected and analyzed for PGMBE. In the third study, rats and mice received whole-body inhalation exposures to 75, 300, or 1200 ppm PGMBE for 6 h/day, 5 days/wk for 14 (rats) or 16 (mice) wk. Serial blood samples were analyzed for PGMBE after 2, 6, 14 (rats), and 16 (mice) wk on study. Urine samples were also collected for 16 It postexposure and analyzed for creatinine and PGMBE sulfate and PGMBE glucuronide conjugates. These studies revealed that: (1) PGMBE was eliminated from blood following concentration-dependent nonlinear kinetics in both species; (2) saturable Michaelis-Menten kinetics were clearly exhibited following a single inhalation exposure at 1200 ppm, but were less obvious following repeated exposures; (3) mice were more efficient in eliminating PG MBE from blood at lower exposure concentrations (i.e.,less than or equal to300 ppm), but at exposure concentrations potentially exceeding their elimination capacity, mice had a greater concentration-dependent decrease in PGMBE elimination than rats; (4) there were minimal but consistent sex differences in PGMBE elimination profiles for rats, with females having higher blood concentrations at all exposure concentrations and sampling times; and (5) sex differences in PGMBE elimination were in part associated with differences in urinary excretion of PGMBE metabolites. C1 Battelle Mem Inst, Toxicol NW, Richland, WA 99352 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dill, JA (reprint author), Battelle Mem Inst, Toxicol NW, MS K4-16,POB 999, Richland, WA 99352 USA. EM dillj@battelle.org FU NIEHS NIH HHS [N01-ES-55392] NR 25 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD MAY PY 2004 VL 16 IS 5 BP 271 EP 290 DI 10.1080/08958370490428319 PG 20 WC Toxicology SC Toxicology GA 816BE UT WOS:000221084600003 PM 15371180 ER PT J AU Chada, S Sutton, RB Ekmekcioglu, S Ellerhorst, J Mumm, JB Leitner, WW Yang, HY Sahin, AA Hunt, KK Fuson, KL Poindexter, N Roth, JA Ramesh, R Grimm, EA Mhashilkar, AM AF Chada, S Sutton, RB Ekmekcioglu, S Ellerhorst, J Mumm, JB Leitner, WW Yang, HY Sahin, AA Hunt, KK Fuson, KL Poindexter, N Roth, JA Ramesh, R Grimm, EA Mhashilkar, AM TI MDA-7/IL-24 is a unique cytokine-tumor suppressor in the IL-10 Family SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE mda-7; IL-24; IL-10; apoptosis; cancer; angiogenesis ID DIFFERENTIATION-ASSOCIATED GENE; HUMAN-MELANOMA DIFFERENTIATION; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; PROTEIN-KINASE CASCADES; CRYSTAL-STRUCTURE; INDUCIBLE FACTOR; INOS EXPRESSION; CANCER CELLS; MDA-7 GENE AB The melanoma differentiation associated gene-7 (mda-7) cDNA was isolated by virtue of being induced during melanoma differentiation. Initial gene transfer studies convincingly demonstrated potent antitumor effects of mda-7. Further studies showed that the mechanism of antitumor activity was due to induction of apoptosis. Most striking was the tumor-selective killing by mda-7 gene transfer-normal cells were unaffected by Adenoviral delivery of mda-7 (Ad-mda7). A variety of molecules implicated in apoptosis and intracellular signaling are regulated by Ad-mda7 transduction. Different apoptosis effector proteins are regulated in different tumor types, suggesting that Ad-mda7 may regulate various signaling pathways. mda-7 encodes a secreted protein, MDA-7, which has now been designated as IL-24, and is a novel member of the IL-10 cytokine family. MDA-7/IL-24 protein is actively secreted from cells after mda-7 gene transfer. In human peripheral blood mononuclear cells (PBMC), STAT3 activation by MDA-7/IL-24 is followed by elaboration of secondary Th1 cytokines, demonstrating that MDA-7/IL-24 is a pro-Th1 cytokine. Furthermore, MDA-7/IL-24 is antagonized by the prototypic Th2 cytokine IL-10. MDA-7/IL-24 protein is endogenously expressed in cultured NK and B-cells and is also expressed in dendritic cells in tissues. MDA-7/IL-24 protein is expressed in nevi and melanoma primary tumors, to varying degrees, but is rarely expressed in malignant melanoma or other human tumors evaluated. Indeed, loss of MDA-7/IL-24 protein expression correlates strongly with melanoma tumor invasion and disease progression. The "bystander" effects proposed for MDA-7/IL-24 protein include immune stimulation, antiangiogenesis and receptor-mediated cytotoxicity. Thus, mda-7 is a unique multifunctional cytokine in the IL-10 family and may have potent antitumor utility in a clinical setting. (C) 2004 Elsevier B.V. All rights reserved. C1 Introgen Therapeut Inc, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA. Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77555 USA. NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. RP Chada, S (reprint author), Introgen Therapeut Inc, 2250 Holcombe Blvd, Houston, TX 77030 USA. EM s.chada@introgen.com RI Ekmekcioglu, Suhendan/A-9686-2009; Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU NCI NIH HHS [R41 CA89778, R43 CA86587, R43 CA97598] NR 56 TC 94 Z9 113 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD MAY PY 2004 VL 4 IS 5 BP 649 EP 667 DI 10.1016/j.intimp.2004.01.017 PG 19 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 820FY UT WOS:000221374000008 PM 15120650 ER PT J AU Gismondi, V Meta, M Bonelli, L Radice, P Sala, P Bertario, L Viel, A Fornasarig, M Arrigoni, A Gentile, M De Leon, MP Anselmi, L Mareni, C Bruzzi, P Varesco, L AF Gismondi, V Meta, M Bonelli, L Radice, P Sala, P Bertario, L Viel, A Fornasarig, M Arrigoni, A Gentile, M De Leon, MP Anselmi, L Mareni, C Bruzzi, P Varesco, L TI Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE MYH; familial adenomatous polyposis coli; colorectal adenomas ID SOMATIC G-C->T-A MUTATIONS; APC VARIANTS; E1317Q; TUMORS AB Biallelic germline mutations in the base excision repair gene MYH have been reported in patients with multiple colorectal adenomas and cancer and in sporadic FAP patients not showing a detectable APC germline mutation. In this study, the prevalence of the common Y165C and G382D germline variants of the MYH gene was examined in 70 FAP/AAPC patients with no detectable APC mutation and a family history compatible with recessive inheritance. In addition, 141 normal-population adenoma patients (mean number of adenomas, 2.8; range, 1-9) and 52 clean colon controls were studied. The entire coding region of the MYH gene was analyzed in Y16SC or G382D heterozygous patients. Since the same second mutational event (a 3 bp deletion in exon 14, 1395delGGA) was detected in 3 patients, the prevalence of this variant was also examined in all groups. In all, 14 of 70 patients in the FAP/AAPC group (20%; 95% CI = 11.7-31.6%) had biallelic germline MYH variants and 3 were heterozygotes (4.3%). None of the 141 normal-population adenoma patients carried biallelic germline MYH variants (95% CI = 0.06-4.1%) and 3 were heterozygotes (2.1%). In the control group, no MYH variants were detected. These results indicated that MYH-associated polyposis (MAP) is present in about 20% of Italian FAP/AAPC patients, in whom no germline APC mutation is detectable and showing a family history compatible with recessive inheritance, and in a small fraction of patients with colorectal adenomas in the general population. In addition, our data suggest that mutation 1395delGGA is a subpolymorphic MYH mutational event in some Caucasian populations. (C) 2004 Wiley-Liss, Inc. C1 Natl Canc Inst, I-16132 Genoa, Italy. Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. Villa Scassi Hosp, Pathol Unit, Genoa, Italy. Univ Modena, Dept Internal Med, I-41100 Modena, Italy. Ist Ricovera Curde De Bellis, Bari, Italy. S Giovanni Hosp, Gastroenterol Unit, Turin, Italy. IRCCS, Ctr Riferimento Oncol, Aviano, Italy. Natl Canc Inst, Italian Registry Hereditary Colorectal Tumors, I-20133 Milan, Italy. Fdn Italiana Ric Canc, Inst Mol Oncol, Milan, Italy. RP Gismondi, V (reprint author), Natl Canc Inst, Largo R Benzi 10, I-16132 Genoa, Italy. EM viviana.gismondi@istge.it RI Radice, Paolo/O-3119-2013; Ponz de Leon, Maurizio/A-9356-2015; OI Ponz de Leon, Maurizio/0000-0003-4465-1043; Bruzzi, Paolo/0000-0002-7874-2077 NR 16 TC 117 Z9 123 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 2004 VL 109 IS 5 BP 680 EP 684 DI 10.1002/ijc.20054 PG 5 WC Oncology SC Oncology GA 807TO UT WOS:000220524000007 PM 14999774 ER PT J AU Tanofsky-Kraff, M Faden, D McDuffie, J Fredricks, A Young-Hyman, D Norman, AC Yanovski, JA AF Tanofsky-Kraff, M Faden, D McDuffie, J Fredricks, A Young-Hyman, D Norman, AC Yanovski, JA TI Eating psychopathology following weight loss treatment in obese adolescents SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 NICHD, Unit Growth & Obes, DEB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2004 VL 35 IS 4 MA 022 BP 380 EP 381 PG 2 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900023 ER PT J AU Morgan, CM Tanofsky-Kraff, M Yanovski, SZ Jorge, MR Yanovski, JA AF Morgan, CM Tanofsky-Kraff, M Yanovski, SZ Jorge, MR Yanovski, JA TI Loss of control over eating, body fat, and psychopathology in normal weight and overweight children SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Univ Fed Sao Paulo, Sao Paulo, Brazil. NICHD, Unit Growth & Obes, NIH, Bethesda, MD USA. Univ Fed Sao Paulo, Sao Paulo, Brazil. NICHD, Unit Growth & Obes, DEB, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 092 BP 421 EP 421 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900092 ER PT J AU Faden, D Tanofsky-Kraff, M McDuffie, J Fredricks, A Mercado, AB Yanovski, JA AF Faden, D Tanofsky-Kraff, M McDuffie, J Fredricks, A Mercado, AB Yanovski, JA TI Loss of control eating & dieting in treatment-seeking overweight adolescents SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 NICHD, Unit Growth & Obes, DEB, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2004 VL 35 IS 4 MA 094 BP 422 EP 423 PG 2 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900094 ER PT J AU Agras, WS Brandt, HA Bulik, CM Dolan-Sewell, R Fairburn, CG Halmi, KA Herzog, DB Jimerson, DC Kaplan, AS Kaye, WH le Grange, D Lock, J Mitchell, JE Rudorfer, MV Street, LL Striegel-Moore, R Vitousek, KM Walsh, BT Wilfley, DE AF Agras, WS Brandt, HA Bulik, CM Dolan-Sewell, R Fairburn, CG Halmi, KA Herzog, DB Jimerson, DC Kaplan, AS Kaye, WH le Grange, D Lock, J Mitchell, JE Rudorfer, MV Street, LL Striegel-Moore, R Vitousek, KM Walsh, BT Wilfley, DE TI Report of the National Institutes of Health Workshop on Overcoming Barriers to Treatment Research in Anorexia Nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE National Institutes of Health; National Institute of Mental Health; workshop; anorexia nervosa; treatment ID EATING-DISORDERS; BULIMIA-NERVOSA; INDIVIDUAL THERAPY; CONTROLLED TRIAL; FOLLOW-UP; FAMILY; ADOLESCENT; RECOVERY; PREDICTORS; RELAPSE AB Objective: Anorexia nervosa (AN) is associated with serious medical morbidity and has the highest mortality rate of all psychiatric disorders. The National Institutes of Health (NIH) Workshop on Overcoming Barriers to Treatment Research in Anorexia Nervosa convened on September 26-27, 2002 to address the dearth of treatment research in this area. The goals of this workshop were to discuss the stages of illness and illness severity, pharmacologic interventions, psychological interventions, and methodologic considerations. Method: The program consisted of a series of brief presentations by moderators, each followed by a discussion of the topic by workshop participants, facilitated by the session chair. Results: This report summarizes the major discussions of these sessions and concludes with a set of recommendations related to the development of treatment research in AN based on these findings. Discussion: It is crucial that treatment research in this area be prioritized. (C) 2004 by Wiley Periodicals, Inc. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychol, St Louis, MO 63110 USA. Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. St Joseph Med Ctr, Ctr Eating Disorders, Baltimore, MD USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. Univ Oxford, Dept Psychiat, Oxford, England. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp Westchester, White Plains, NY USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Toronto, Toronto Gen Hosp, Dept Psychiat, Toronto, ON M5G 1L7, Canada. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ N Dakota, Sch Med & Hlth Sci, Dept Neurosci, Fargo, ND USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Wesleyan Univ, Dept Psychol, Middletown, CT USA. Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Wilfley, DE (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid,Campus Box 8134, St Louis, MO 63110 USA. EM wilfleyd@psychiatry.wustl.edu RI Le Grange, Daniel/A-2649-2011 NR 35 TC 77 Z9 78 U1 0 U2 6 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 2004 VL 35 IS 4 BP 509 EP 521 DI 10.1002/eat.10261 PG 13 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900237 PM 15101067 ER PT J AU Kaye, WH Devlin, B Barbarich, N Bulik, CM Thornton, L Bacanu, SA Fichter, MM Halmi, KA Kaplan, AS Strober, M Woodside, DB Bergen, AW Crow, S Mitchell, J Rotondo, A Mauri, M Cassano, G Keel, P Plonicov, K Pollice, C Klump, KL Lilenfeld, LR Ganjei, JK Quadflieg, N Berrettini, WH AF Kaye, WH Devlin, B Barbarich, N Bulik, CM Thornton, L Bacanu, SA Fichter, MM Halmi, KA Kaplan, AS Strober, M Woodside, DB Bergen, AW Crow, S Mitchell, J Rotondo, A Mauri, M Cassano, G Keel, P Plonicov, K Pollice, C Klump, KL Lilenfeld, LR Ganjei, JK Quadflieg, N Berrettini, WH TI Genetic analysis of bulimia nervosa: Methods and sample description SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE bulimia nervosa; anorexia nervosa; eating disorders; genetics; linkage analysis; affected relative pairs ID ENVIRONMENTAL RISK-FACTORS; TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; FAGERSTROM TOLERANCE QUESTIONNAIRE; 10-YEAR FOLLOW-UP; ANOREXIA-NERVOSA; EATING-DISORDERS; SEROTONIN ACTIVITY; CONTROLLED FAMILY; NICOTINE DEPENDENCE; MAJOR DEPRESSION AB Objective: Twin and family studies suggest that genetic variants contribute to the pathogenesis of bulimia nervosa (BN) and anorexia nervosa (AN). The Price Foundation has supported an international, multisite study of families with these disorders to identify these genetic variations. The current study presents the clinical characteristics of this sample as well as a description of the study methodology, Method: All probands met modified criteria for BN or bulimia nervosa with a history of AN (BAN) as defined in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994). All affected relatives met DSM-IV criteria for BN, AN, BAN, or eating disorders not otherwise specified (EDNOS). Probands and affected relatives were assessed diagnostically using both trained-rater and self-report assessments. DNA samples were collected from probands, affected relatives, and available biologic parents. Results: Assessments were obtained from 163 BN probands and 165 BAN probands. Overall, there were 365 relative pairs available for linkage analysis. Of the affected relatives of BN probands, 62 were diagnosed as BN (34.8%), 49 as BAN (27.5%), 35 as AN (19.7%), and 32 as EDNOS (18.0%). For the relatives of BAN probands, 42 were diagnosed as BN (22.5%), 67 as BAN (35.8%), 48 as AN (25.7%), and 30 as EDNOS (16.0%). Discussion: This study represents the largest genetic study of eating disorders to date. Clinical data indicate that although there are a large number of individuals with BN disorders, a range of eating pathology is represented in the sample, allowing for the examination of several different phenotypes in molecular genetic analyses. (C) 2004 by Wiley Periodicals, Inc. C1 Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Univ Munich, Roseneck Hosp Behav Med, Prien Am Chiemsee, Germany. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, White Plains, NY USA. Toronto Gen Hosp, Program Eating Disorders, Toronto, ON, Canada. Toronto Gen Hosp, Dept Psychiat, Toronto, ON, Canada. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. Univ Pisa, Inst Psychiat, I-56100 Pisa, Italy. Harvard Univ Cambridge, Dept Psychol, Boston, MA USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Kaye, WH (reprint author), Univ Pittsburgh, Med Ctr, Dept Psychiat, Suite 600 Iroquois Bldg,3600 Forbes Ave, Pittsburgh, PA 15213 USA. EM kayewh@msx.upmc.edu OI Bergen, Andrew/0000-0002-1237-7644 NR 74 TC 34 Z9 34 U1 6 U2 16 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 2004 VL 35 IS 4 BP 556 EP 570 DI 10.1002/eat.10271 PG 15 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900241 PM 15101071 ER PT J AU Sina, BJ Molyneux, E AF Sina, BJ Molyneux, E TI Overcoming ethical barriers to childhood tuberculosis research in developing countries SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE bioethics; developing countries; paediatric research AB In 2002, an international Workshop on Tuberculosis in Children was held to determine priority areas for basic, clinical and programmatic research to improve paediatric TB practice. During the workshop, issues related to the ethical treatment of children as research subjects, particularly in resource-poor settings, were identified as major constraints to the goal of expanding paediatric TB research. Based on participation in the workshop discussions, this article proposes concrete activities that can begin to address the ethical barriers. The time and costs associated with creating collaborative scientific and ethical research projects between high and low-income countries should be supported in grants for paediatric TB research studies in developing countries. Paediatric TB researchers in developing countries should be given opportunities to participate in international programmes that develop bioethics expertise. Relevant case studies of paediatric research in developing countries can assist ethical review committees in industrialised countries in understanding the special issues related to paediatric research in resource-limited settings. Paediatricians in developing countries need to be included in childhood TB research studies and ethical review committees. C1 NIH, Div Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA. Malawi Coll Med, Dept Paediat, Blantyre, Malawi. RP Sina, BJ (reprint author), NIH, Div Training & Res, Fogarty Int Ctr, Bldg 31,Room B2C29, Bethesda, MD 20892 USA. EM sinab@mail.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAY PY 2004 VL 8 IS 5 BP 683 EP 686 PG 4 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 818PF UT WOS:000221256300030 PM 15137552 ER PT J AU McHenry, CL Liu, YH Feng, W Nair, AR Feathers, KL Ding, XL Gal, A Vollrath, D Sieving, PA Thompson, DA AF McHenry, CL Liu, YH Feng, W Nair, AR Feathers, KL Ding, XL Gal, A Vollrath, D Sieving, PA Thompson, DA TI MERTK arginine-844-cysteine in a patient with severe rod-cone dystrophy: Loss of mutant protein function in transfected CeRs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RECEPTOR TYROSINE KINASE; INHERITED RETINAL DYSTROPHY; PIGMENT EPITHELIAL-CELLS; PHOTORECEPTOR OUTER SEGMENTS; RCS-RAT; C-MER; RETINITIS-PIGMENTOSA; EXPRESSION ANALYSIS; MANNOSE RECEPTOR; SURVIVAL FACTORS AB Purpose. Mutations in the MERTK gene are responsible for retinal degeneration in the Royal College of Surgeons (RCS) rat and are a cause of human autosomal recessive retinitis pigmentosa (RP). This study reports the identification and functional analysis of novel MERTK mutations to provide information regarding whether they are causative of severe rod-cone degeneration in a young patient. Methods. MERTK missense variants identified by single-strand conformational polymorphism (SSCP) and sequence analysis were introduced into expression constructs and used to transfect HEK293T cells. Recombinant protein expression was assayed with anti-MERTK and anti-phosphotyrosine antibodies. Protein turnover was assayed in pulse-chase studies of 35 S-methionine incorporation. Transcript levels were determined by quantitative RT-PCR. Results. Three MERTK sequence variants were identified in a patient with rod-cone dystrophy: R722X in exon 16 and R865W in exon 19 on the paternal allele and R844C in exon 19 on the maternal allele. The R844C sequence change affects an evolutionarily conserved amino acid residue and was not detected in unaffected individuals. In transfected HEK293Tcells, wild-type (wt) and W865 MERTK were expressed at equivalent levels and present in the plasma membrane, stimulated tyrosine phosphorylation, and induced significant rounding of the cell bodies. In contrast, C844 MERTK was expressed at low levels and did not stimulate tyrosine phosphorylation. In addition, the relative stability of C844 MERTK was significantly less than wt in assays of protein turnover. At age 13, the patient had 20/60 and 20/200 acuities, tunnel vision of 5degrees centrally, and far temporal peripheral crescent bilaterally, and ERGS were nondetectable. The fundi showed bull's-eye macular atrophy and widespread RPE thinning. Conclusions. The present study reports the identification of R844C, the first putative pathogenic MERTK missense mutation that results in severe retinal degeneration with childhood onset when in compound heterozygous form with a R722X allele. The loss of function of C844 MERTK is probably due to decreased protein stability. C1 Univ Michigan, Sch Med, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48105 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Univ Hamburg, Klinikum Eppendorf, Inst Humangenet, Hamburg, Germany. NEI, Bethesda, MD 20892 USA. RP Thompson, DA (reprint author), Univ Michigan, Sch Med, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM dathom@umich.edu FU NCRR NIH HHS [M01-RR00042]; NEI NIH HHS [P30-EY07003, R01-EY12298, R03-EY014650] NR 48 TC 54 Z9 55 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 2004 VL 45 IS 5 BP 1456 EP 1463 DI 10.1167/iovs.03-0909 PG 8 WC Ophthalmology SC Ophthalmology GA 816BF UT WOS:000221084700026 PM 15111602 ER PT J AU Stadtman, TC AF Stadtman, TC TI How I became a biochemist SO IUBMB LIFE LA English DT Editorial Material C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2120,50 S Dr,MSC-8012, Bethesda, MD 20892 USA. EM tcstadtman@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAY PY 2004 VL 56 IS 5 BP 285 EP 286 DI 10.1080/15216540410001277680 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 851AN UT WOS:000223656300007 ER PT J AU Lard-Whiteford, SL Matecka, D O'Rear, JJ Yuen, IS Litterst, C Reichelderfer, P AF Lard-Whiteford, SL Matecka, D O'Rear, JJ Yuen, IS Litterst, C Reichelderfer, P CA The International Working Grp on M TI Recommendations for the nonclinical development of topical microbicides for prevention of HIV transmission: An update SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; topical microbicides; antimicrobial activities; toxicological and chemical testing ID IMMUNODEFICIENCY-VIRUS TYPE-1; SODIUM DODECYL-SULFATE; SPERMICIDE BENZALKONIUM CHLORIDE; GENITAL HERPES INFECTION; CELL-ASSOCIATED HIV-1; IN-VITRO; VAGINAL MICROBICIDES; CHLAMYDIA-TRACHOMATIS; LAURYL SULFATE; BACTERIAL VAGINOSIS AB The development of methods to prevent HIV infection is critical to curbing the rising epidemic. Topical microbicides represent a potential new strategy for reduction of HIV transmission. The purpose of this article is to update and expand upon the nonclinical recommendations of a previously published document on the development of microbicides prepared by the International Working Group on Microbicides. The nonclinical studies discussed here represent general concepts and regulatory considerations that are pertinent to the development of topical microbicides for prevention or reduction of HIV transmission. Essential early steps in product development include the determination of antiviral activity, cytotoxicity, mechanism of action, pathways to resistance, and cross-resistance to approved drugs. Other parameters to consider include activity against vaginal microflora and pathogens that cause sexually transmitted diseases. Before and during clinical trials, nonclinical data on toxicology and pharmacokinetics should be obtained. Finally, product quality issues, including microbicide formulation characteristics, interaction with other products, and stability, should be addressed. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Yuen, IS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, HFD-530,5600 Fisheries Lane, Rockville, MD 20857 USA. EM yueni@cder.fda.gov NR 80 TC 64 Z9 73 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2004 VL 36 IS 1 BP 541 EP 552 DI 10.1097/00126334-200405010-00001 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 817KX UT WOS:000221177500001 PM 15097296 ER PT J AU Chulada, PC Carey, MA Zeldin, DC AF Chulada, PC Carey, MA Zeldin, DC TI Breast-feeding, atopy, and asthma - Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID PROSTAGLANDIN-E2 C1 NIEHS, Off Clin Res, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Chulada, PC (reprint author), NIEHS, Off Clin Res, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 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 2004 VL 113 IS 5 BP 1002 EP 1003 DI 10.1016/j.jaci.2003.12.014 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 818UC UT WOS:000221269000031 ER PT J AU Taft-Benz, SA Schaaper, RM AF Taft-Benz, SA Schaaper, RM TI The theta subunit of Escherichia coli DNA polymerase III: a role in stabilizing the epsilon proofreading subunit SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ALLOW RAPID DETECTION; MISMATCH REPAIR; MUTATOR MUTD5; SALMONELLA-TYPHIMURIUM; RESISTANCE ELEMENTS; LACZ MUTATIONS; REPLICATION; GENE; HOLOENZYME; MUTANTS AB The function of the theta subunit of Escherichia coli DNA polymerase III holoenzyme is not well established. theta is a tightly bound component of the DNA polymerase III core, which contains the alpha subunit (polymerase), the E subunit (3'-->5' exonuclease), and the theta subunit, in the linear order alpha-epsilon-theta. Previous studies have shown that the theta subunit is not essential, as strains carrying a deletion of the holE gene (which encodes theta) proved fully viable. No significant phenotypic effects of the holE deletion could be detected, as the strain displayed normal cell health, morphology, and mutation rates. On the other hand, in vitro experiments have indicated the efficiency of the 3'-exonuclease activity of E to be modestly enhanced by the presence of theta. Here, we report a series of genetic experiments that suggest that theta has a stabilizing role for the E proofreading subunit. The observations include (i) defined DeltaholE mutator effects in mismatch-repair-defective mutL backgrounds, (ii) strong DeltaholE mutator effects in certain proofread i ng- i m paired dnaQ strains, and (iii) yeast two- and three-hybrid experiments demonstrating enhancement of alpha-epsilon interactions by the presence of theta. theta appears conserved among gram-negative organisms which have an exonuclease subunit that exists as a separate protein (i.e., not part of the polymerase polypeptide), and the presence of theta might be uniquely beneficial in those instances where the proofreading 3'-exonuclease is not part of the polymerase polypeptide. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, MD E3-01,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov NR 47 TC 39 Z9 39 U1 2 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 2004 VL 186 IS 9 BP 2774 EP 2780 DI 10.1128/JB.186.9.2774-2780.2004 PG 7 WC Microbiology SC Microbiology GA 816DR UT WOS:000221091100031 PM 15090519 ER PT J AU Kirkley, JE Robey, FA AF Kirkley, JE Robey, FA TI Inhibition of U937 cytokine secretion by HIV-1 gp120 C4-derived peptide constructs SO JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS LA English DT Article DE HIV; CD4; peptomer; lipopolysaccharide; inflammation ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; TUMOR-NECROSIS-FACTOR; HUMAN MONOCYTES; MONONUCLEAR-CELLS; LYMPHOCYTES-T; C4 DOMAIN; CD4; INTERLEUKIN-6; INDUCTION AB Lipopolysaccharide (LPS) stimulation of the human promyelomonocytic cell line U937 results in interleukin 6 and interleukin 10 secretion. Modulation of cytokine secretion in response to LPS may be possible through binding of ligands to surface receptors. A peptomer, containing multiple repeat units of the CD4-binding C4 region of HIV-1 gp120, and the monomeric C4 peptide each were investigated for their ability to affect LPS-induced IL-6 and IL-10 secretion. The peptomer inhibited IL-6 and IL-10 secretion, while the monomer inhibited only IL-6 secretion. Larger CD4-binding proteins, specifically gp120 and Leu3A, a CD4-directed monoclonal antibody, had no effect on the LPS response. PMA differentiation to down-regulate CD4 expression did not reverse the inhibitory effect of the peptomer or peptide, suggesting a CD4-independent effect. Bioactivity changed markedly with different constructs in the presence of IFNgamma with reversal or enhancement of the IL-10 response but not IL-6 production. These results suggest that truncation of a larger polypeptide may result in constructs with novel binding capabilities and bioactivities not seen in parent proteins. C1 Knox Coll, Program Biochem, Galesburg, IL 61401 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Res, NIH, Bethesda, MD 20892 USA. RP Kirkley, JE (reprint author), Knox Coll, Program Biochem, Galesburg, IL 61401 USA. EM jkirkley@knox.edu NR 39 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0883-9115 J9 J BIOACT COMPAT POL JI J. Bioact. Compat. Polym. PD MAY PY 2004 VL 19 IS 3 BP 173 EP 195 DI 10.1177/0883911504044456 PG 23 WC Biotechnology & Applied Microbiology; Materials Science, Biomaterials; Polymer Science SC Biotechnology & Applied Microbiology; Materials Science; Polymer Science GA 830BY UT WOS:000222097800002 ER PT J AU Hilbert, SL Boerboom, LE Livesey, SA Ferrans, VJ AF Hilbert, SL Boerboom, LE Livesey, SA Ferrans, VJ TI Explant pathology study of decellularized carotid artery vascular grafts SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE pathology; decellularized; small-diameter vascular graft ID VEIN BYPASS GRAFTS; SAPHENOUS-VEIN; GASTROEPIPLOIC ARTERY; REVASCULARIZATION; POLYTETRAFLUOROETHYLENE; ASSIST AB The purpose of this study was to evaluate the morphologic findings in small-diameter freeze-dried decellularized carotid artery grafts implanted in goats as carotid artery interposition grafts for 6-7 months. Unimplanted decellularized carotid artery grafts did not contain intact cells; however, remnants of smooth muscle cells were present in the media. The extracellular matrix was well preserved. All decellularized grafts were patent at explant, without significant dimensional changes or aneurysm formation. Their luminal surfaces were lined by a thin neointima, consisting of myofibroblasts, collagen, and a discontinuous layer of endothelial cells. Histologic evidence of calcification within the explants was not observed; however, electron microscopy showed calcification of minute remnants of cell membranes. Inflammatory cells were not present in the graft wall. Host cell migration was greatest in the adventitia along the length of the graft. Migration of host cells into the media was more apparent close to the anastomoses, forming cellular nests rich in extracellular proteoglycans, whereas cell migration into areas subjacent to the lumen was minimal. Ingrowth of host blood vessels was not observed. These results demonstrate satisfactory structural and morphologic features of a decellularized carotid artery small-diameter graft implanted for up to 7 months. (C) 2004 Wiley Periodicals, Inc. C1 US FDA, Off Sci & Technol HFZ150, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. LifeCell Corp, Branchburg, NJ USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Hilbert, SL (reprint author), US FDA, Off Sci & Technol HFZ150, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. EM sxh@cdrh.fda.gov NR 17 TC 16 Z9 23 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAY 1 PY 2004 VL 69A IS 2 BP 197 EP 204 DI 10.1002/jbm.a.10135 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 812ST UT WOS:000220859900001 PM 15057992 ER PT J AU Weber, KL AF Weber, KL TI What's new in musculoskeletal oncology? SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID GUIDED RADIOFREQUENCY ABLATION; METASTASES INVOLVING BONE; SOFT-TISSUE SARCOMAS; TERM FOLLOW-UP; LOWER-LIMB; TUMOR; EMBOLIZATION; CHEMOTHERAPY; OSTEOSARCOMA; MULTICENTER C1 NCI, Amer Canc Soc, Bethesda, MD 20892 USA. RP Weber, KL (reprint author), NCI, Amer Canc Soc, Bethesda, MD 20892 USA. EM kweber6@jhmi.edu NR 19 TC 7 Z9 7 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2004 VL 86A IS 5 BP 1104 EP 1109 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 818SJ UT WOS:000221264500042 PM 15118066 ER PT J AU Whalley, T Timmers, K Coorssen, J Bezrukov, L Kingsley, DH Zimmerberg, J AF Whalley, T Timmers, K Coorssen, J Bezrukov, L Kingsley, DH Zimmerberg, J TI Membrane fusion of secretory vesicles of the sea urchin egg in the absence of NSF SO JOURNAL OF CELL SCIENCE LA English DT Article DE sea urchin; egg; exocytosis; fusion; cortical vesicles ID CORTICAL-GRANULE EXOCYTOSIS; INTRACELLULAR PROTEIN-TRANSPORT; ETHYLMALEIMIDE-SENSITIVE FACTOR; CALCIUM-TRIGGERED FUSION; PLASMA-MEMBRANE; VESICULAR TRANSPORT; IN-VITRO; DEPENDENT EXOCYTOSIS; REGULATED SECRETION; MOLECULAR-MECHANISM AB The role of cytosolic ATPases such as N-ethylmaleimide (NEM)-sensitive fusion protein (NSF) in membrane fusion is controversial. We examined the physiology and biochemistry of ATP and NSF in the cortical system of the echinoderm egg to determine if NSF is an essential factor in membrane fusion during Ca2+-triggered exocytosis. Neither exocytosis in vitro, nor homotypic cortical vesicle (CV) fusion required soluble proteins or nucleotides, and both occurred in the presence of non-hydrolyzable analogs of ATP. While sensitive to thiol-specific reagents, CV exocytosis is not restored by the addition of cytosolic NSF, and fusion and NSF function are differentially sensitive to thiol-specific agents. To test participation of tightly bound, non-exchangeable NSF in CV-CV fusion, we cloned the sea urchin homolog and developed a species-specific antibody for western blots and physiological analysis. This antibody was without effect on CV exocytosis or homotypic fusion, despite being functionally inhibitory. NSF is detectable in intact cortices, cortices from which CVs had been removed and isolated CVs treated with ATP-gamma-S and egg cytosol to reveal NSF binding sites. In contrast, isolated CVs, though all capable of Ca2+-triggered homotypic fusion, contain less than one hexamer of NSF per CV. Thus NSF is not a required component of the CV fusion machinery. C1 NICHHD, Lab Cellular & Mol Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Stirling, Ctr Extracellular Matrix Biol, Dept Biol Sci, Stirling FK9 4LA, Scotland. Univ Calgary, Fac Med, Dept Physiol & Biophys, Cellular & Mol Neurobiol Res Grp, Calgary, AB T2N 4N1, Canada. Delaware State Univ, Agr Res Serv, USDA, Microbial Food Safety Res Unit,WW Baker Ctr, Dover, DE 19901 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov OI Whalley, Tim/0000-0003-3362-0006 NR 76 TC 9 Z9 9 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2004 VL 117 IS 11 BP 2345 EP 2356 DI 10.1242/jcs.01077 PG 12 WC Cell Biology SC Cell Biology GA 830DQ UT WOS:000222102200017 PM 15126634 ER PT J AU Guan, EN Wang, J Norcross, MA AF Guan, EN Wang, J Norcross, MA TI Amino-terminal processing of MIP-1 beta/CCL4 by CD26/dipeptidyl-peptidase IV SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mip-1 beta; CD26/DPPIV; HIV-1 Tat ID DIPEPTIDYL-PEPTIDASE-IV; T-CELL-ACTIVATION; CD26 EXPRESSION; RECEPTOR SPECIFICITY; CHEMOKINE RECEPTORS; ADENOSINE-DEAMINASE; HUMAN-LYMPHOCYTES; BETA-CHEMOKINES; FACTOR 1-ALPHA; HIV-1 TAT AB CD26 is a membrane-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity that has diverse functional properties in T cell physiology and in regulation of bioactive peptides. We have previously reported that activated human peripheral lymphocytes (PBL) secrete an amino-terminal truncated form of macrophage inflammatory protein (MIP)-1 beta/(3-69) with novel functional specificity for CCR1, 2, and 5. In this report, we show that the full length MIP-1 beta is processed by CD26/DPPIV to the truncated form and that cleavage can be blocked by DPPIV inhibitory peptides derived from HIV Tat(1-9) or the thromboxane A2 receptor, TAX2-R(1-9). Addition of Tat(] -9) or TAX2-R(l -9) peptides to PBL cultures partially blocks endogenous MIP-1 beta processing. The kinetics of conversion of MIP-1 beta from intact to MIP-1 beta(3-69) in activated PBLs correlates with cell surface expression of CD26. Our results suggest that NH2-terminal processing of MIP-1 beta and possibly other chemokines may depend on the balance between CD26/DPPIV enzymatic activity and cellular and viral proteins that modulate enzyme function. (C) 2004 Wiley-Liss, Inc. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, NIH, Bethesda, MD 20892 USA. RP Guan, EN (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, NIH, Bldg 29B,Room 4E12,HFM 535,8800 Rockville Pike, Bethesda, MD 20892 USA. EM guan@cber.fda.gov; norcross@cber.fda.gov NR 40 TC 24 Z9 24 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 2004 VL 92 IS 1 BP 53 EP 64 DI 10.1002/jcb.20041 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 818IT UT WOS:000221239500006 PM 15095403 ER PT J AU Vgontzas, AN Zoumakis, E Bixler, EO Lin, HM Follett, H Kales, A Chrousos, GP AF Vgontzas, AN Zoumakis, E Bixler, EO Lin, HM Follett, H Kales, A Chrousos, GP TI Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; CORTISOL-LEVELS; DAYTIME SLEEPINESS; INTERLEUKIN-6; AGE; DEPRIVATION; GENDER; ELEVATION; FATIGUE; ADULTS AB Total sleep restriction in humans is associated with increased daytime sleepiness, decreased performance, and hormonal/metabolic disturbances. The effects of mild chronic sleep restriction that mimic real life are not known. To assess the effects of modest sleep restriction from 8 to 6 h/night for 1 wk, 25 young, healthy, normal sleepers ( 12 men and 13 women) were studied for 12 consecutive nights in the sleep laboratory. After 1 wk of sleep restriction, although subjects' nighttime sleep was deeper, subjects were significantly sleepier ( multiple sleep latency test) and performed worse in four primary variables of psychomotor vigilance test (both P < 0.01). Furthermore, 24-h secretion of IL-6 was increased by 0.8 +/- 0.3 pg/ml (P < 0.05) in both sexes, whereas TNFalpha was increased only in men. Also, the peak cortisol secretion was lower after sleep restriction than at baseline, and this difference was stronger in men (55.18 +/- 24.83 nmol/liter; P < 0.05) than in women (35.87 +/- 24.83 nmol/liter; P < 0.16). We conclude that in young men and women, modest sleep loss is associated with significant sleepiness, impairment of psychomotor performance, and increased secretion of proinflammatory cytokines. Given the potential association of these behavioral and physical alterations with health, well-being, and public safety, the idea that sleep or parts of it are optional should be regarded with caution. C1 Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, H073,500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu FU NHLBI NIH HHS [HL-64415] NR 35 TC 432 Z9 451 U1 4 U2 34 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 2004 VL 89 IS 5 BP 2119 EP 2126 DI 10.1210/jc.2003-031562 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100020 PM 15126529 ER PT J AU Momani, MS Shore-Freedman, E Collins, BJ Lubin, J Ron, E Schneider, AB AF Momani, MS Shore-Freedman, E Collins, BJ Lubin, J Ron, E Schneider, AB TI Familial concordance of thyroid and other head and neck tumors in an irradiated cohort: Analysis of contributing factors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; SALIVARY-GLAND TUMORS; ATOMIC-BOMB SURVIVORS; ATAXIA-TELANGIECTASIA; CANCER; RADIATION; CHILDHOOD; RISK; SUSCEPTIBILITY; HYPERPARATHYROIDISM AB Relatively little is known about variations in susceptibility to the effects of radiation in the general population. We have been studying 4296 individuals exposed as children to head and neck radiation. The present study was designed to evaluate the pattern of thyroid, parathyroid, salivary, and neural tumors in irradiated siblings for evidence of heritable susceptibility factors. We also wanted to determine whether the characteristics of thyroid cancers were influenced by familial factors. The following criteria were met by 251 sibling pairs: both irradiated, both with follow-up (average, 44.3 +/- 9.4 yr; range, 9.4-59.5 yr), and both with organ-dose estimates. For each sibling pair we derived a quantitative score, taking into account the length of follow-up and known risk factors, for their concordance and used the sum of these scores to characterize the population. Whether we used thyroid cancer or all thyroid nodules as an end point, the degree of concordance did not exceed what could be explained by the length of follow-up and known risk factors. For thyroid cancer, neither the presenting characteristics nor their rates of recurrence were influenced by their concordance status. In summary, we were unable to identify familial factors that modify the strong effects of radiation exposure. There is no reason to alter the evaluation or treatment of thyroid cancer in an irradiated patient based on whether another member of the family has radiation-related tumors. C1 Univ Illinois, Sect Endocrinol & Metab, Chicago, IL 60612 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Schneider, AB (reprint author), Univ Illinois, Sect Endocrinol & Metab, 1819 W Polk St,MC 640, Chicago, IL 60612 USA. EM abschnei@uic.edu OI Shore-Freedman, Eileen/0000-0001-6194-1814 FU NCI NIH HHS [CA-21518]; NCRR NIH HHS [M01-RR-13987] NR 22 TC 2 Z9 2 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 2004 VL 89 IS 5 BP 2185 EP 2191 DI 10.1210/jc.2003-031906 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100031 PM 15126540 ER PT J AU Voutetakis, A Argyropoulou, M Sertedaki, A Livadas, S Xekouki, P Maniati-Christidi, M Bossis, I Thalassinos, N Patronas, N Dacou-Voutetakis, C Voutetakis, D AF Voutetakis, A Argyropoulou, M Sertedaki, A Livadas, S Xekouki, P Maniati-Christidi, M Bossis, I Thalassinos, N Patronas, N Dacou-Voutetakis, C Voutetakis, D TI Pituitary magnetic resonance Imaging in 15 patients with Prop1 gene mutations: Pituitary enlargement may originate from the intermediate lobe SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 2-BASE PAIR DELETION; HORMONE DEFICIENCY; ANTERIOR-PITUITARY; MOLECULAR-BASIS; SELLA TURCICA; GLAND; HYPOPITUITARISM; HOMEODOMAIN; CHILDREN; HEIGHT AB Pituitary morphology in patients with Prop1 gene mutations varies. Most patients demonstrate a normal or small pituitary gland. Occasionally, pituitary enlargement of undetermined origin has also been detected. In the present study we use long-term magnetic resonance imagingfindings to characterize the morphological abnormalities of the pituitary gland in 15 patients (aged 2.5-45 yr) with combined pituitary hormone deficiency caused by Prop1 gene mutations (GA296del/GA296del in seven, GA296del/A150del in two, A150del/A150del in five, and GA296del/R73H in one patient) and attempt to uncover the origin and nature of the pituitary enlargement. Small pituitary gland was detected in seven patients (25.2 +/- 14.4 yr of age), normal pituitary size in three patients (10.2 +/- 5.8 yr of age), and pituitary enlargement in five patients (6.5 +/- 2.7 yr of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in three patients. Our data indicate that although a small pituitary gland is usually observed in older subjects, a significant number of young patients with Prop1 gene mutations demonstrate pituitary enlargement with subsequent regression. The distinct magnetic resonance imaging characteristics of the pituitary enlargement in our patients in conjunction with pertinent data from Prop1-deficient mice suggest that the mass causing the pituitary enlargement most likely originates from the intermediate lobe. C1 Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1, GR-11527 Athens, Greece. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Univ Ioannina, Sch Med, Dept Radiol, GR-45110 Ioannina, Greece. Evangelismos Med Ctr, Dept Endocrinol, Ioannina 10676, Greece. RP Dacou-Voutetakis, C (reprint author), Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1, Thivon & Livadias, GR-11527 Athens, Greece. EM adacou@med.uoa.gr OI Livadas, Sarantis/0000-0001-9594-1521 NR 45 TC 54 Z9 56 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 2004 VL 89 IS 5 BP 2200 EP 2206 DI 10.1210/jc.2003-031765 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100033 PM 15126542 ER PT J AU Pacak, K Ilias, I Chen, CC Carrasquillo, JA Whatley, M Nieman, LK AF Pacak, K Ilias, I Chen, CC Carrasquillo, JA Whatley, M Nieman, LK TI The role of [(18)F]fluorodeoxyglucose positron emission tomography and [(111)In]diethylenetriaminepentaacetate-D-Phe-pentetreotide scintigraphy in the localization of ectopic adrenocorticotropin-secreting tumors causing Cushing's syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MEDULLARY-THYROID CARCINOMA; NEUROENDOCRINE TUMORS; OCTREOTIDE SCINTIGRAPHY; DIFFERENTIAL-DIAGNOSIS; ONCOLOGICAL PET; KI-67 ANTIGEN; LUNG-TUMORS; FOLLOW-UP; IN-VITRO AB Conventional imaging modalities cannot localize the source of ACTH in 30-50% of patients with Cushing's syndrome (CS) caused by ectopic ACTH secretion (EAS). We prospectively evaluated whether [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) or [(111)In]-diethylenetriamine-pentaacetate-D-Phe-pentetreotide (OCT) at higher than standard doses of radionuclide (18 mCi; H-OCT), can detect these tumors. Seventeen patients with presumed EAS based on inferior petrosal sinus sampling results underwent routine anatomical imaging studies [computed tomography (CT) and magnetic resonance imaging (MRI)] and OCT scintigraphy with 6 mCi (L-OCT). Research studies included FDG-PET in all patients and H-OCT if L-OCT was negative. ACTH-secreting tumors were localized in 13 patients and were occult in four. Nine of 17 CT, six of 16 MRI, six of 17 FDG-PET, eight of 17 L-OCT, and one of nine H-OCT studies were true positives. The sensitivity of CT and combined H- and L-OCT scintigraphy was higher (both 53%; 95% confidence interval, 29-76%) than that of MRI (37%; 95% confidence interval, 16-64%) or FDG-PET (35%; 95% confidence interval, 15-61%). FDG-PET did not detect tumors that were occult on CT/MRI. L-OCT was a useful complementary modality to CT and MRI. As H-OCT identified a tumor in one patient with otherwise negative imaging, it should be considered only when other imaging modalities fail to localize the ACTH-secreting tumor in patients with EAS. C1 NICHHD, Unit Clin Neuroendocrinol, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Unit Clin Neuroendocrinol, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 55 TC 70 Z9 77 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 2004 VL 89 IS 5 BP 2214 EP 2221 DI 10.1210/jc.2003-031812 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100035 PM 15126544 ER PT J AU Charmandari, E Merke, DP Negro, PJ Keil, MF Martinez, PE Haim, A Gold, PW Chrousos, GP AF Charmandari, E Merke, DP Negro, PJ Keil, MF Martinez, PE Haim, A Gold, PW Chrousos, GP TI Endocrinologic and psychologic evaluation of 21-hydroxylase deficiency carriers and matched normal subjects: Evidence for physical and/or psychologic vulnerability to stress SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; CONGENITAL ADRENAL-HYPERPLASIA; OBSESSIVE-COMPULSIVE DISORDER; AUTONOMIC RESPONSES; MATERNAL-CARE; ANXIETY; HORMONE; NEUROENDOCRINE; DYSREGULATION; DEPRESSION AB Carriers of congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency demonstrate increased secretion of cortisol precursors after ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic CRH secretion. Because both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression, we performed endocrine and psychologic studies in consecutively admitted parents of patients with classic congenital adrenal hyperplasia due to 21-OH deficiency and parents of children with other chronic endocrine disorders. The number of excluded carriers because of pathologic reasons was higher than that of controls (P = 0.05). Carriers of 21-OH deficiency had a lower mean 24-h urinary free cortisol excretion (26.4 +/- 3.4 vs. 42.7 +/- 6.4 mug/ d, P = 0.03) and higher peak ACTH (75.7 +/- 8.1 vs. 54.2 +/- 5.9 pg/ml, P = 0.04) and 17-hydroxyprogesterone (224.2 +/- 28.1 vs. 107.1 +/- 12.5 ng/dl, P < 0.001) concentrations post CRH stimulation than control subjects. Cortisol and androstenedione responses were similar in the two groups. Psychometric assessment performed by administering the State-Anxiety Inventory, Beck Depression Inventory, Profile of Mood States, Symptom Checklist-90R, and Temperament and Character Inventory revealed no differences between the two subject groups. Interestingly, a step-wise multiple linear regression model analysis in each population sample revealed that in carriers of 21-OH deficiency but not in the control subjects, a lower mean 24-h urinary free cortisol excretion and a higher ACTH response to ovine CRH stimulation predicted predisposition to obsessive-compulsive behavior, novelty seeking, reward dependence, and harm avoidance. We conclude that carriers of 21-OH deficiency appear to have mild hypocortisolism and compensatory changes of CRH secretion secondary to lower cortisol concentrations. These changes might predict mild predisposition of these subjects to physical and psychologic pathology, suggesting that larger studies are necessary. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9D42, Bethesda, MD 20892 USA. RI Charmandari, Evangelia/B-6701-2011 NR 47 TC 17 Z9 19 U1 1 U2 2 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 2004 VL 89 IS 5 BP 2228 EP 2236 DI 10.1210/jc.2003-031322 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100037 PM 15126546 ER PT J AU Freedman, RJ Aziz, N Albanes, D Hartman, T Danforth, D Hill, S Sebring, N Reynolds, JC Yanovski, JA AF Freedman, RJ Aziz, N Albanes, D Hartman, T Danforth, D Hill, S Sebring, N Reynolds, JC Yanovski, JA TI Weight and body composition changes during and after adjuvant chemotherapy in women with breast cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GAIN; DIAGNOSIS; TAMOXIFEN; THERAPY AB Uncontrolled trials have reported significant weight gain in women with breast cancer during treatment with adjuvant chemotherapy. We prospectively evaluated body composition before (visit 1), immediately after (visit 2), and 6 months after (visit 3) chemotherapy in 20 women with stages I-IIIA breast cancer [body mass index (BMI): 24.1 +/- 3.9 kg/m(2)]. We compared their weight change to 51 age- and BMI-matched healthy controls (BMI: 25.5 +/- 3.8 kg/m(2)). In women with breast cancer, there was no weight change from visit 1-2, or from visit 1-3, but weight increased from visit 2-3 (+1.09 +/- 2.46 kg; P = 0.05). Weight change was not different from controls during either interval. In the breast cancer group, the percentage of body fat assessed by air displacement plethysmography increased, and fat-free mass decreased from visit 1-2 (-2.3 +/- 4% and -2.2 +/- 4%; P = 0.02) and from visit 1-3 (+4.0 +/- 6% and -3.8 +/- 6%; P = 0.01). By dual energy x-ray absorptiometry, the percentage of body fat increased from visit 2-3 (+0.9 +/- 1.6%; P = 0.02). Bone mineral content decreased from visit 2-3 (-0.02 +/- 0.04 kg; P = 0.02) and from visit 1-3 (-0.04 +/- 0.06 kg; P = 0.005). By computed tomography, the visceral adipose to sc adipose tissue ratio decreased from visit 1-3 (-0.02 +/- 0.05 ml; P = 0.02). We conclude that, compared with controls, women with breast cancer receiving modern adjuvant chemotherapy regimens show no significant changes in weight during the first year of their treatment. They do, however, appear to undergo unfavorable changes in body composition. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Off Canc Survivorship, Div Canc Control Populat Sci, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dept Nutr, Warren Grant Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Freedman, RJ (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM freedmar@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Yanovski, Jack/0000-0001-8542-1637 NR 31 TC 83 Z9 84 U1 0 U2 3 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 2004 VL 89 IS 5 BP 2248 EP 2253 DI 10.1210/jc.2003-031874 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100040 PM 15126549 ER PT J AU Weeraratna, AT Nagel, JE De Mello-Coelho, V Taub, DD AF Weeraratna, AT Nagel, JE De Mello-Coelho, V Taub, DD TI Gene expression profiling: From microarrays to medicine SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE microarray; clinic; gene expression; review ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ACUTE RESPIRATORY SYNDROME; CDNA MICROARRAY; OLIGONUCLEOTIDE MICROARRAYS; MOLECULAR CLASSIFICATION; COMPLEMENTARY-DNA; RESPONSIVE GENES; SKELETAL-MUSCLE; PROSTATE-CANCER; HORMONE-THERAPY AB With the mapping of the human genome comes the ability to identify genes of interest in specific diseases and the pathways involved therein. Laboratory technology has evolved in parallel, providing us with the ability to assay thousands of these genes at once, a technique known as microarray analysis. The main question that this type of technology raises is how we can apply this powerful technology to clinical medicine. Recently, advances in data analysis, as well as standardization of the technology, have allowed us to examine this question, and indeed a few clinical trials currently being performed include microarrays as part of their protocol. In this review we outline the microarray technique and describe these types of studies in further detail. C1 NIA, Clin Immunol Sect, Immunol Lab, Gerontol res Ctr,NIH, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Clin Immunol Sect, Immunol Lab, Gerontol res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM taubd@grc.nia.nih.gov NR 94 TC 26 Z9 28 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 2004 VL 24 IS 3 BP 213 EP 224 DI 10.1023/B:JOCI.0000025443.44833.1d PG 12 WC Immunology SC Immunology GA 815VR UT WOS:000221070300001 PM 15114052 ER PT J AU Karai, L Brown, DC Mannes, AJ Connelly, ST Brown, J Gandal, M Wellisch, OM Neubert, JK Olah, Z Iadarola, MJ AF Karai, L Brown, DC Mannes, AJ Connelly, ST Brown, J Gandal, M Wellisch, OM Neubert, JK Olah, Z Iadarola, MJ TI Deletion of vanilloid receptor 1-expressing primary afferent neurons for pain control SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PRIMARY SENSORY NEURONS; DORSAL-ROOT GANGLION; RAT SPINAL-CORD; CAPSAICIN RECEPTOR; SUBSTANCE-P; NEUROGENIC INFLAMMATION; INTRATHECAL CAPSAICIN; MYELINATED AFFERENTS; TRIGEMINAL GANGLION; RESINIFERATOXIN AB Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member I (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged. increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management. C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, 49 Convent Dr, Bethesda, MD 20892 USA. EM miadarola@dir.nidcr.nih.gov OI Mannes, Andrew/0000-0001-5834-5667 NR 58 TC 175 Z9 179 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 2004 VL 113 IS 9 BP 1344 EP 1352 DI 10.1172/JCI200420449 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818MP UT WOS:000221249500017 PM 15124026 ER PT J AU Sun, LX Lee, JW Fine, HA AF Sun, LX Lee, JW Fine, HA TI Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID C-KIT RECEPTOR; TYROSINE KINASE RECEPTOR; CENTRAL-NERVOUS-SYSTEM; IN-VITRO; SUBVENTRICULAR ZONE; PROGENITOR CELLS; OLFACTORY-BULB; ADULT BRAIN; DIRECTIONAL GUIDANCE; AXON OUTGROWTH AB Neural stem/progenitor cell (NSPC) migration toward sites of damaged central nervous system (CNS) tissue may represent an adaptive response for the purpose of limiting and/or repairing damage. Little is known of the mechanisms responsible for this migratory response. We constructed a cDNA library of injured mouse fore-brain using subtractive suppression hybridization (SSH) to identify genes that were selectively upregulated in the injured hemisphere. We demonstrate that stem cell factor (SCF) mRNA and protein are highly induced in neurons within the zone of injured brain. Additionally, the SCF receptor c-kit is expressed on NSPCs in vitro and in vivo. Finally, we demonstrate that recombinant SCF induces potent NSPC migration in vitro and in vivo through the activation of c-kit on NSPCs. These data suggest that the SCF/c-kit pathway is involved in the migration of NSPCs to sites of brain injury and that SCF may prove useful for inducing progenitor cell recruitment to specific areas of the CNS for cell-based therapeutic strategies. C1 NCI, Neurooncol Branch, NINDS, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, NINDS, NIH, Block Bldg,Room 225,9030 Old Georgetown Rd, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov NR 66 TC 178 Z9 208 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 2004 VL 113 IS 9 BP 1364 EP 1374 DI 10.1172/JCI200420001 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818MP UT WOS:000221249500019 PM 15124028 ER PT J AU Fuss, IJ Heller, F Boirivant, M Leon, F Yoshida, M Fichtner-Feigl, S Yang, ZQ Exley, M Kitani, A Blumberg, RS Mannon, P Strober, W AF Fuss, IJ Heller, F Boirivant, M Leon, F Yoshida, M Fichtner-Feigl, S Yang, ZQ Exley, M Kitani, A Blumberg, RS Mannon, P Strober, W TI Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; OXAZOLONE COLITIS; INTERFERON-GAMMA; CD1D TETRAMERS; MURINE MODEL; IFN-GAMMA; ACTIVATION; MICE; INTERLEUKIN-4 AB While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative colitis (UC), remains enigmatic. Here we show that lamina propria T (LPT) cells from UC patients produce significantly greater amounts of IL-13 (and IL-5) than control cells and little IFN-gamma, whereas comparable cells from CD patients produce large amounts of IFN-gamma and small amounts of IL-13. We then show that stimulation of UC LPT cells bearing an NK marker (CD161) with anti-CD2/ and-CD28 or with B cells expressing transfected CD1d induces substantial IL-13 production. While this provided firm evidence that the IL-13-producing cell is an NK T (NKT) cell, it became clear that this cell does not express invariant NKT cell receptors characteristic of most NKT cells since there was no increase in cells binding alpha-galactosylceramide-loaded tetramers, and alpha-galactosylceramide did not induce IL-13 secretion. Finally, we show that both human NKT cell lines as well as UC CD161(+) LPT cells are cytotoxic for HT-29 epithelial cells and that this cytotoxicity is augmented by IL-13. These studies show that UC is associated with an atypical Th2 response mediated by nonclassical NKT cells producing IL-13 and having cytotoxic potential for epithelial cells. C1 NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. Ist Super Sanita, Immunol Lab, I-00161 Rome, Italy. NIH, Immune Cell Interact Unit, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Biol Program,Hematol Oncol Div, Boston, MA 02115 USA. RP Fuss, IJ (reprint author), NIH, Mucosal Immun Sect, 10 Ctr Dr,Bldg 10,Room 11N238, Bethesda, MD 20892 USA. EM ifuss@niaid.nih.gov RI BOIRIVANT, MONICA/B-9977-2016 FU NIDDK NIH HHS [R01 DK044319, DK-44319, DK-51362, DK-53056, R37 DK044319] NR 51 TC 412 Z9 432 U1 2 U2 12 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 2004 VL 113 IS 10 BP 1490 EP 1497 DI 10.1172/JCI200419836 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 822IA UT WOS:000221531200017 PM 15146247 ER PT J AU Baskar, S Kobrin, CB Kwak, LW AF Baskar, S Kobrin, CB Kwak, LW TI Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NON-HODGKINS-LYMPHOMA; IMMUNOGLOBULIN VARIABLE REGION; COLONY-STIMULATING FACTOR; B-CELL; SURFACE-IMMUNOGLOBULIN; SOMATIC HYPERMUTATION; LYMPHOCYTES RECOGNIZE; MYELOMA PATIENTS; DENDRITIC CELLS; TUMOR-ANTIGENS AB The clonotypic surface Ig receptor expressed by malignant B cells, idiotype, is a tumor-specific antigen and an attractive target for active immunotherapy. While Ab's specific for tumor idiotype have been well described in patients with B cell malignancies, the precise antigenic epitopes in human idiotype recognized by autologous T cells remain largely unknown. We report here that T cell lines generated from lymphoma patients actively immunized with idiotype protein specifically recognized multiple, unique immunodominant epitopes in autologous tumor idiotype. Synthetic peptides corresponding to hypervariable, but not framework, regions of Ig heavy chain specifically stimulated CD4(+) and CD8(+) T cells to proliferate and secrete proinflammatory cytokines in an MHC-associated manner. Detailed analysis revealed a minimal determinant of an immunodominant epitope, comprising critical residues at the amino terminus that may be a product of somatic hypermutation. Association of idiotype-specific T cell responses with previously documented molecular remissions in idiotype-vaccinated patients suggests that the newly identified T cell epitopes may be clinically relevant. Such antigenic epitopes may serve as candidates for novel peptide-vaccine strategies, and as tools to selectively expand tumor antigen-specific T cells for adoptive immunotherapy and for monitoring T cell immunity in vaccinated patients. C1 Natl Canc Inst, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NIH, Expt Transplantat & Immunol Branch, Ctr Canc Res, Frederick, MD USA. RP Baskar, S (reprint author), Natl Canc Inst, Basic Res Program, SAIC Frederick Inc, Bldg 567,Room 203, Frederick, MD 21702 USA. EM baskar@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 49 TC 45 Z9 45 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 2004 VL 113 IS 10 BP 1498 EP 1510 DI 10.1172/JCI200420312 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 822IA UT WOS:000221531200018 PM 15146248 ER PT J AU Sergeev, N Volokhov, D Chizhikov, V Rasooly, A AF Sergeev, N Volokhov, D Chizhikov, V Rasooly, A TI Simultaneous analysis of multiple Staphylococcal enterotoxin genes by an oligonucleotide microarray assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SHOCK-SYNDROME TOXIN-1; ATOPIC-DERMATITIS; PATHOGENICITY ISLANDS; RHEUMATOID-ARTHRITIS; EXFOLIATIVE TOXINS; COMMON ANTIBODIES; AUREUS; SUPERANTIGENS; PCR; DETERMINANTS AB Staphylococcal enterotoxins (SEs) are a family of 17 major serological types of heat-stable enterotoxins that are one of the leading causes of gastroenteritis resulting from consumption of contaminated food. SEs are considered potential bioweapons. Many Staphylococcus aureus isolates contain multiple SEs. Because of the large number of SEs, serological typing and PCR typing are laborious and time-consuming. Furthermore, serological typing may not always be practical because of antigenic similarities among enterotoxins. We report on a microarray-based one-tube assay for the simultaneous detection and identification (genetic typing) of multiple enterotoxin (ent) genes. The proposed typing method is based on PCR amplification of the target region of the ent genes with degenerate primers, followed by characterization of the PCR products by microchip hybridization with oligonucleotide probes specific for each ent gene. We verified the performance of this method by using several other techniques, including PCR amplification with gene-specific primers, followed by gel electrophoresis or microarray hybridization, and sequencing of the enterotoxin genes. The assay was evaluated by analysis of previously characterized staphylococcal isolates containing 16 ent genes. The microarray assay revealed that some of these isolates contained additional previously undetected ent genes. The use of degenerate primers allows the simultaneous amplification and identification of as many as nine different ent genes in one S. aureus strain. The results of this study demonstrate the usefulness of the oligonucleotide microarray assay for the analysis of multitoxigenic strains, which are common among S. aureus strains, and for the analysis of microbial pathogens in general. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US FDA, Ctr Biol Evaluat & Res, College Pk, MD USA. RP Rasooly, A (reprint author), NCI, NIH, EPN, 6130 Execut Blvd,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 42 TC 65 Z9 75 U1 1 U2 4 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 2004 VL 42 IS 5 BP 2134 EP 2143 DI 10.1128/JCM.42.5.2134-2143.2004 PG 10 WC Microbiology SC Microbiology GA 820XU UT WOS:000221424100041 PM 15131181 ER PT J AU Bacon, RM Pilgard, MA Johnson, BJB Raffel, SJ Schwan, TG AF Bacon, RM Pilgard, MA Johnson, BJB Raffel, SJ Schwan, TG TI Glycerophosphodiester phosphodiesterase gene (glpQ) of Borrelia lonestari identified as a target for differentiating Borrelia species associated with hard ticks (Acari : Ixodidae) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMBLYOMMA-AMERICANUM ACARI; LYME-DISEASE; ERYTHEMA MIGRANS; RELAPSING FEVER; RASH ILLNESS; AGENT; DNA AB A glpQ ortholog was identified in DNA from Borrelia lonestari-positive Amblyomma americanum, providing further evidence that B. lonestari is more closely related to the relapsing fever group spirochetes than to borreliae that cause Lyme disease. This finding provides a basis for developing diagnostic assays to differentiate species of borrelia transmitted by hard ticks. C1 CDCP, Natl Ctr Infect Dis, Bacterial Zoonoses Branch, Div Vector Borne Infect Dis, Ft Collins, CO 80521 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Bacon, RM (reprint author), CDC, NCID, DVBID, Bacterial Zoonoses Branch, POB 2087, Ft Collins, CO 80522 USA. EM rbacon@cdc.gov NR 18 TC 20 Z9 22 U1 0 U2 4 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 2004 VL 42 IS 5 BP 2326 EP 2328 DI 10.1128/JCM.42.5.2326-2328.2004 PG 3 WC Microbiology SC Microbiology GA 820XU UT WOS:000221424100085 PM 15131225 ER PT J AU Gould, TD Manji, HK AF Gould, TD Manji, HK TI The molecular medicine revolution and psychiatry: Bridging the gap between basic neuroscience research and clinical psychiatry SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID NEUROPSYCHIATRIC DISORDERS; GENE-EXPRESSION; SCHIZOPHRENIA; BRAIN AB Recent years have witnessed a considerable increase in both fundamental knowledge and available experimental techniques in the basic neurosciences. Unfortunately, clinical translation of these findings vis-A-vis a direct benefit to patients who suffer from psychiatric diseases has not been as rapid. It is likely that this will change in the near future. We discuss some of the knowledge and expanding techniques of basic neuroscience, focusing on those that may be most promising regarding the future impact of the current molecular medicine revolution in psychiatry. Some of the more exciting findings (basic mechanisms, techniques, and clinical methodologies) that are expected to have a major impact on both our understanding of the biological underpinnings of psychiatric diseases and the development of novel and/or improved therapies include genetics, epigenetics, transcriptomics/proteomics, neuroimaging, animal models, and improved psychiatric endophenotypes. C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bldg 49,Room B1EE16, Bethesda, MD 20892 USA. EM manji@nih.gov NR 34 TC 23 Z9 25 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2004 VL 65 IS 5 BP 598 EP 604 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 827GG UT WOS:000221887100002 PM 15163244 ER PT J AU Goel, V Makale, M Grafman, J AF Goel, V Makale, M Grafman, J TI The hippocampal system mediates logical reasoning about familiar spatial environments SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL-ANATOMY; VISUOSPATIAL ATTENTION; WORKING-MEMORY; ACTIVATION; IMAGERY; CORTEX; BELIEF; FACES; FMRI AB It has recently been shown that syllogistic reasoning engages two dissociable neural systems. Reasoning about familiar situations engages a frontal-temporal lobe system, whereas formally identical reasoning tasks involving unfamiliar situations recruit a frontal-parietal visuospatial network. These two systems may correspond to the "heuristic'' and "formal'' methods, respectively, postulated by cognitive theory. To determine if this dissociation generalizes to reasoning about transitive spatial relations, we studied 14 volunteers using event-related fMRI, as they reasoned about landmarks in familiar and unfamiliar environments. Our main finding is a task ( reasoning and baseline) by spatial content ( familiar and unfamiliar) interaction. Modulation of reasoning toward unfamiliar landmarks resulted in bilateral activation of superior and inferior parietal lobules ( BA 7, 40), dorsal superior frontal cortex ( BA 6), and right superior and middle frontal gyri ( BA 8), regions widely implicated in visuospatial processing. By contrast, modulation of the reasoning task toward familiar landmarks, engaged the right inferior/orbital frontal gyrus (BA 11/47), bilateral occipital (BA 18, 19), and temporal lobes. The temporal lobe activation included the right inferior temporal gyrus ( BA 37), posterior hippocampus, and parahippocampal gyrus, regions implicated in spatial memory and navigation tasks. These results provide support for the generalization of dual mechanism theory to transitive reasoning and highlight the importance of the hippocampal system in reasoning about familiar spatial environments. C1 York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. NINDS, Bethesda, MD 20892 USA. RP Goel, V (reprint author), York Univ, Dept Psychol, 4700 Keele St, Toronto, ON M3J 1P3, Canada. EM vgoel@yorku.ca OI Grafman, Jordan H./0000-0001-8645-4457 NR 40 TC 41 Z9 44 U1 0 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY PY 2004 VL 16 IS 4 BP 654 EP 664 DI 10.1162/089892904323057362 PG 11 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 822EY UT WOS:000221521200013 PM 15165354 ER PT J AU Deco, G Rolls, ET Horwitz, B AF Deco, G Rolls, ET Horwitz, B TI "What'' and "where'' in visual working memory: A computational neurodynamical perspective for integrating fMRI and single-neuron data SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID PRIMATE PREFRONTAL CORTEX; INFERIOR TEMPORAL CORTEX; CEREBRAL BLOOD-FLOW; PYRAMIDAL NEURONS; RECEPTOR CHANNELS; SYNAPTIC ACTIVITY; UNIFIED MODEL; ATTENTION; MECHANISMS; CURRENTS AB Single-neuron recordings, functional magnetic resonance imaging ( fMRI) data, and the effects of lesions indicate that the prefrontal cortex (PFC) is involved in some types of working memory and related cognitive processes. Based on these data, two different models of the topographical and functional organization of the PFC have been proposed: organization-by-stimulus-domain, and organization-by-process. In this article, we utilize an integrate-and-fire network to model both single-neuron and fMRI data on short-term memory in order to understand data obtained in topologically different parts of the PFC during working memory tasks. We explicitly model the mechanisms that underlie working-memory-related activity during the execution of delay tasks that have a "what''-then-"where'' design ( with both object and spatial delayed responses within the same trial). The model contains different populations of neurons ( as found experimentally) in attractor networks that respond in the delay period to the stimulus object, the stimulus position, and to combinations of both object and position information. The pools are arranged hierarchically and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current relevant information ( object or location) enables the system to select the correct neuronal populations during the delay period in what is a biased competition model of attention. The processes occurring at the AMPA and NMDA synapses are dynamically modeled in the integrate-and-fire implementation to produce realistic spiking dynamics. It is shown that the fMRI data characteristic of the dorsal PFC and linked to spatial processing and manipulation of items can be reproduced in the model by a high level of inhibition, whereas the fMRI data characteristic of the ventral PFC and linked to object processing can be produced by a lower level of inhibition, even though the network is itself topographically homogeneous with no spatial topology of the neurons. This article, thus, not only presents a model for how spatial versus object short-term memory could be implemented in the PFC, but also shows that the fMRI BOLD signal measured during such tasks from different parts of the PFC could reflect a higher level of inhibition dorsally, without this dorsal region necessarily being primarily spatial and the ventral region object-related. C1 ICREA, Barcelona, Spain. Univ Pompeu Fabra, Barcelona, Spain. Univ Oxford, Oxford OX1 2JD, England. Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. RP Rolls, ET (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. EM Edmund.Rolls@psy.ox.ac.uk RI Bonatti, Luca /E-9048-2011; Brain and Cognition, Center/H-5448-2011; Deco, Gustavo/A-6341-2008; OI Deco, Gustavo/0000-0002-8995-7583; Rolls, Edmund/0000-0003-3025-1292 NR 63 TC 80 Z9 83 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY PY 2004 VL 16 IS 4 BP 683 EP 701 DI 10.1162/089892904323057380 PG 19 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 822EY UT WOS:000221521200015 PM 15165356 ER PT J AU Webster, JI Sternberg, EM AF Webster, JI Sternberg, EM TI Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products SO JOURNAL OF ENDOCRINOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; MIGRATION INHIBITORY FACTOR; HEPATIC PHOSPHOENOLPYRUVATE CARBOXYKINASE; MURINE CYTOMEGALOVIRUS-INFECTION; CORTICOTROPIN-RELEASING HORMONE; STAPHYLOCOCCAL-ENTEROTOXIN-B; GRAM-NEGATIVE BACTERIA; SIMPLEX VIRUS TYPE-1; A-INDUCED ENTERITIS; NF-KAPPA-B AB The hypothalamic-pituitary-adrenal (HPA) axis is activated during many bacterial and viral infections, resulting in an increase in circulating glucocorticoid levels. This HPA axis activation and glucocorticoid response are critical for the survival of the host, as demonstrated by the fact that removal of the HPA axis (by adrenalectomy or hypophysectomy) or glucocorticoid receptor (GR) blockade enhances the severity of the infection and in some cases enhances the mortality rate. Replacement with a synthetic glucocorticoid reverses these effects by reducing the severity of the infection and provides protection against lethal effects. In addition, some bacteria and viral infections have been shown to affect the GR directly. These have been described and the implications of such an effect discussed. C1 NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Dept HHS, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Dept HHS, Bldg 36,Rm 1A23,36 Convent Dr,MSC 4020, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov RI Webster Marketon, Jeanette/H-5613-2011 OI Webster Marketon, Jeanette/0000-0002-3627-1094 NR 149 TC 102 Z9 107 U1 1 U2 5 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAY PY 2004 VL 181 IS 2 BP 207 EP 221 DI 10.1677/joe.0.1810207 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 825NH UT WOS:000221764700001 PM 15128270 ER PT J AU McDonald, MD Walsh, PJ AF McDonald, MD Walsh, PJ TI Dogmas and controversies in the handling of nitrogenous wastes: 5-HT2-like receptors are involved in triggering pulsatile urea excretion in the gulf toadfish, Opsanus beta SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE serotonin; ketinserin; scrotonin receptor; alpha-methyl-5-HT; 8-OH-DPAT ID TROUT ONCORHYNCHUS-MYKISS; LAKE MAGADI TILAPIA; NEUROEPITHELIAL CELLS; ALKALINE ENVIRONMENT; RAINBOW-TROUT; TELEOST FISH; 5-HT1A RECEPTORS; GILL VASCULATURE; COLLECTING DUCT; SEROTONIN AB When injected arterially, serotonin (5-hydroxytryptamine; 5-HT) has been shown to elicit naturally sized urea pulse events in the gulf toadfish, Opsanus beta. The goal of the present study was to determine which 5-HT receptor(s) was involved in mediating this serotonergic stimulation of the pulsatile excretion mechanism. Toadfish were surgically implanted with caudal arterial catheters and intraperitoneal catheters and injected with either 8-OH-DPAT (I mumol kg(-1)), a selective 5-HT1A receptor agonist, (alpha-methyl-5-HT (I mumol kg(-1)), a 5-HT2 receptor agonist, or ketanserin, a 5-HT2 receptor antagonist (0.01, 0.1, 1 and 10 mumol kg(-1)) plus alpha-methyl-5-HT. 8-OH-DPAT injection did not mediate an increase in urea excretion, ruling out the involvement of 5-HT1A receptors in pulsatile excretion. However, within 5 min, a-methyl-5-HT injection caused an increase in the excretion of urea in >95 (N=27) of the fish injected, with an average pulse size of 652+/-102 mumol N kg(-1) (N=26). With alpha-methyl-5-HT injection there was no corresponding increase in ammonia or [H-3]PEG 4000 permeability. Urea pulses elicited by alpha-methyl-5-HT were inhibited in a dose-dependent fashion by the 5-HT2 receptor antagonist ketanserin, which at low doses caused a significant inhibition of pulse size and at higher doses significantly inhibited the occurrence of pulsatile excretion altogether. However, neither 8-OH-DPAT nor alpha-methyl 5-HT injection had an effect on plasma cortisol or plasma urea concentrations. These findings suggest the involvement of a 5-HT2-like receptor in the regulation of pulsatile urea excretion. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP McDonald, MD (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM dmcdonald@rsmas.miami.edu NR 54 TC 26 Z9 27 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD MAY PY 2004 VL 207 IS 12 BP 2003 EP 2010 DI 10.1242/jeb.00957 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 832TD UT WOS:000222289100006 PM 15143134 ER PT J AU White, KE Hoppin, JA AF White, KE Hoppin, JA TI Seed treatment and its implication for fungicide exposure assessment SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE pesticides; fungicides; seed treatment; exposure assessment; agricultural epidemiology ID AGRICULTURAL HEALTH; POTENTIAL EXPOSURE; APPLICATORS AB Farmers may be exposed to fungicides through both personal application and use of treated seed. Most epidemiology studies rely on personal application to assess exposure. We explored the extent of potential exposure via use of treated seed using data from a large cohort of licensed pesticide applicators from Iowa and North Carolina. Potential secondary fungicide exposure due to treated seed was calculated by crop by multiplying the average percent of seed treated by those reporting raising that crop but not applying fungicide. This potential exposure was present for every crop with treated seed ( corn, soybean, wheat, cotton, potato, and peanut), and was highest for corn (71%) and soybean farmers (19%). Potential secondary fungicide exposure was more common in Iowa than in North Carolina since most Iowa farmers plant corn and soybeans and few report applying fungicides. Owing to its widespread use on corn, potential secondary captan exposure may occur among the 90% of the individuals planting corn. The relative intensity of secondary fungicide exposure associated with planting treated seed is anticipated to be lower than actively applying fungicide. Limited data suggest that exposure during planting may be approximately 4% of actively applying fungicide; while seed transfer operations may have similar levels of exposure to personal application (80-200%). Measurement data are necessary to characterize the patterns of exposure related to the use of fungicide-treated seed and to determine whether this route of exposure is an important contributor to fungicide exposure among farmers. C1 NIEHS, US Dept HHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Hoppin, JA (reprint author), NIEHS, US Dept HHS, Epidemiol Branch, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov NR 64 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD MAY PY 2004 VL 14 IS 3 BP 195 EP 203 DI 10.1038/sj.jea.7500312 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 820IS UT WOS:000221382200001 PM 15141148 ER PT J AU Frick, KD Scanlon, DP Bandeen-Roche, K Kasper, JD Simonsick, EM Sullivan, EM AF Frick, KD Scanlon, DP Bandeen-Roche, K Kasper, JD Simonsick, EM Sullivan, EM TI Influenza vaccination by race among disabled community dwelling older women SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article; Proceedings Paper CT 3rd Meeting of the International-Health-Economics-Association CY JUL, 2001 CL York, ENGLAND SP Int Hlth Econom Assoc ID MEDICARE BENEFICIARIES; PREVENTIVE SERVICES; HEALTH; POPULATION; IMMUNIZATION; CARE; MAMMOGRAPHY; VALIDATION; BARRIERS; BENEFITS AB Disabled older adults have been shown to be at risk for underutilization of some preventive services relative to able-bodied individuals. The Women's Health and Aging Study surveyed female Medicare enrollees in Baltimore, Maryland, who were among the most disabled community-dwelling women at the start of the study. Longitudinal survey data from the study were used to test for the existence or emergence of racial variation in influenza vaccination rates, for which racial variation has been shown in the general population. The primary analysis, using data on the same women before and after Medicare flu shot coverage began, suggested that influenza vaccination rates increased after Medicare coverage began and that there was no difference by race. A secondary analysis using data on women who were interviewed only after Medicare flu shot coverage began showed some racial variation, although the difference may have been larger prior to coverage. The utilization rate did not approach the Healthy People 2010 target. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Penn State Univ, Dept Hlth Policy & Adm, University Pk, PA 16802 USA. NIA, Clin Res Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21218 USA. Boston Sci Corp, Boston, MA USA. RP Frick, KD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. FU NIA NIH HHS [N01-AG-1-2112] NR 51 TC 4 Z9 4 U1 2 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2004 VL 15 IS 2 BP 220 EP 236 DI 10.1353/hpu.2004.0023 PG 17 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 824UZ UT WOS:000221713900008 PM 15253375 ER PT J AU Belfer, I Phillips, G Taubman, J Hipp, H Lipsky, RH Enoch, MA Max, MB Goldman, D AF Belfer, I Phillips, G Taubman, J Hipp, H Lipsky, RH Enoch, MA Max, MB Goldman, D TI Haplotype architecture of the norepinephrine transporter gene SLC6A2 in four populations SO JOURNAL OF HUMAN GENETICS LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of American Society of Human Genetics CY NOV, 2003 CL Los Angeles, CA DE single-nucleotide polymorphism; linkage disequilibrium; haplotype; norepinephrine transporter; SLC6A2 ID HUMAN NORADRENALINE TRANSPORTER; PREFRONTAL CORTEX; NEUROTRANSMITTER TRANSPORTERS; ORTHOSTATIC INTOLERANCE; UPTAKE SITES; RAT; POLYMORPHISM; DOPAMINE; COCAINE; ASSOCIATION AB The norepinephrine transporter (NET) regulates levels of monoamine neurotransmitters integral to a variety of behaviors and autonomic functions. Two SLC6A2 polymorphisms have been used in genetic association studies, generating intriguing but nondefinitive results on traits such as hypertension and mood. One of these SLC6A2 variants is functional but rare. The other is common but not informative over the entire 48 kb SLC6A2 region and is insufficient to capture the functional diversity potentially contained within any SLC6A2 region. To elucidate SLC6A2 haplotype structure and define markers sufficient to capture haplotype diversity within detected haplotype blocks, 26 single-nucleotide polymorphisms (SNPs) were genotyped in 384 individuals evenly divided across Finnish Caucasian, US Caucasian, Plains American Indian, and African American populations. Three conserved blocks, 13.6, 12.5, and 25 kb in size and showing little evidence for historical recombination were observed in all populations. Haplotype diversity in block 1 and numbers of common haplotypes were highest in African Americans, among whom 5-6 optimal markers were sufficient to maximize diversity of each block. For other populations, 2-3 markers/block sufficed, but the optimal markers differed across populations. The SLC6A2 haplotype map and 25-marker panel (excluding the monomorphic one) is a comprehensive tool for genetic linkage studies on phenotypes related to NET function. C1 NIAAA, Neurogenet Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, Bethesda, MD USA. RP Belfer, I (reprint author), NIAAA, Neurogenet Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM ibelfer@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473; Hipp, Heather/0000-0002-1089-3928 FU NIAAA NIH HHS [Z01 AA000301]; PHS HHS [Z01] NR 33 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1435-232X J9 J HUM GENET JI J. Hum. Genet. PD MAY PY 2004 VL 49 IS 5 BP 232 EP 245 DI 10.1007/s10038-004-0140-9 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 821FS UT WOS:000221446400002 PM 15362567 ER PT J AU Gauduin, MC Kaur, A Ahmad, S Yilma, T Lifson, JD Johnson, RP AF Gauduin, MC Kaur, A Ahmad, S Yilma, T Lifson, JD Johnson, RP TI Optimization of intracellular cytokine staining for the quantitation of antigen-specific CD4(+) T cell responses in rhesus macaques SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CD4(+) T cell-responses; antigen-specific activation; intracellular cytokine staining; SIV/macaque model ID SIMIAN-IMMUNODEFICIENCY VIRUS; FLOW CYTOMETRIC DETERMINATION; INTERFERON-GAMMA; WHOLE-BLOOD; IFN-GAMMA; ENVELOPE GLYCOPROTEIN; LYMPHOCYTE RESPONSES; ELISPOT ASSAY; SIV VACCINE; EXPRESSION AB Standard proliferation assays used for analysis of CD4(+) T cell function have significant shortcomings, including limited sensitivity, lack of truly quantitative readouts and significant variability. We have optimized an intracellular cytokine staining (ICS) assay in rhesus macaques which allows us to identify virus-specific CD4(+) T cells at the single-cell level with high sensitivity while reducing background staining to a minimum. A variety of parameters were tested to determine the optimal experimental conditions necessary for the detection of antigen-specific CD4(+) T cells in macaques. Central to our optimized protocol was the addition of cross-linked costimulatory anti-CD28 and anti-CD49d Mabs, a modification which resulted in up to threefold enhancement of the frequency of TNF-alpha-secreting CD4(+) T cells following superantigen- or antigen-specific stimulation. The ICS protocol was also optimized with respect to antigen concentration and duration of antigerric stimulation. These modifications resulted in a convenient and highly reproducible assay with intra- and inter-assay variability of less than 10%. Although cryopreservation of PBMC generally led to a 40% to 80% decrease in the frequency of antigen-specific CD4(+) T cells detected by ICS using stimulation with viral proteins, the use of overlapping peptide pools minimized the effects of cryopreservation on ICS responses. The use of more sensitive techniques such as ICS permits delineation of antigen-specific cells at the single cell level and should provide new insights into pathogen-specific immune responses in the rhesus macaque model. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Univ Calif Davis, VM Pathol Microbiol & Immunol, ILMB, Davis, CA 95616 USA. SAIC Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02115 USA. RP Gauduin, MC (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. EM marie-claire_gauduin@hms.harvard.edu FU NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI43890, AI45314] NR 53 TC 27 Z9 28 U1 0 U2 1 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 PY 2004 VL 288 IS 1-2 BP 61 EP 79 DI 10.1016/j.jim.2004.02.007 PG 19 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 831TH UT WOS:000222218500007 PM 15183086 ER PT J AU Popkov, M Jendreyko, N Gonzalez-Sapienza, G Mage, RG Rader, C Barbas, CF AF Popkov, M Jendreyko, N Gonzalez-Sapienza, G Mage, RG Rader, C Barbas, CF TI Human/mouse cross-reactive anti-VEGF receptor 2 recombinant antibodies selected from an immune b9 allotype rabbit antibody library SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE antibody engineering; phage display; angiogenesis; VEGF/KDR/Flk-1; endothelial cells ID ENDOTHELIAL GROWTH-FACTOR; PHAGE DISPLAY LIBRARY; MONOCLONAL-ANTIBODY; TUMOR ANGIOGENESIS; GENERATION; THERAPY; CANCER; INHIBITION; EXPRESSION; REPERTOIRE AB Vascular endothelial growth factor (VEGF) and its receptors have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. Models of murine tumor angiogenesis and receptor-specific antibodies are required to evaluate roles of VEGF receptors in mouse models of human cancer. Human VEGFR2 (also known as KDR) and murine VEGFR2 (or Flk-1) share 85% amino acid sequence identity in their extracellular domain. We describe here the development of antibodies that cross-react with mouse and human VEGFR2. High-affinity, species cross-reactive, Fabs specific for KDR/Flk-1 were selected from an antibody phage display library generated from an immunized rabbit of b9 allotype. The selected chimeric rabbit/human Fabs were found to bind to purified KDR and Flk-1 with nanomolar affinity. Three of the selected Fabs detected KDR expression on human endothelial cells as well as Flk-1 on murine endothelial cells. The availability of anti-VEGFR2 Fab with species cross-reactivity will help to decipher the functional role of KDR/Flk-1 in tumor biology as well as facilitate the preclinical evaluation of the suitability of KDR/Flk-1 for drug targeting. This report underscores our earlier finding that b9 rabbits are excellent sources for high-affinity cross-reactive antibodies with therapeutic potential. (C) 2004 Elsevier B.V. All rights reserved. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Barbas, CF (reprint author), Scripps Res Inst, Dept Mol Biol, BCC-550,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM carlos@scripps.edu FU NCI NIH HHS [R01-CA094966] NR 33 TC 22 Z9 23 U1 0 U2 2 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 PY 2004 VL 288 IS 1-2 BP 149 EP 164 DI 10.1016/j.jim.2004.03.005 PG 16 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 831TH UT WOS:000222218500014 PM 15183093 ER PT J AU Shi, GX Harrison, K Han, SB Moratz, C Kehrl, JH AF Shi, GX Harrison, K Han, SB Moratz, C Kehrl, JH TI Toll-like receptor signaling alters the expression of regulator of G protein signaling proteins in dendritic cells: Implications for G protein-coupled receptor signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; NUCLEOTIDE EXCHANGE FACTOR; ALPHA-SUBUNIT; FAMILY-MEMBERS; B-LYMPHOCYTES; GENE; PHEROMONE; PHOSPHORYLATION; ASSOCIATION; CHEMOTAXIS AB Conserved structural motifs on pathogens trigger pattern recognition receptors present on APCs such as dendritic cells (DCs). An important class of such receptors is the Toll-like receptors (TLRs). TLR signaling triggers a cascade of events in DCs that includes modified chemokine and cytokine production, altered chemokine receptor expression, and changes in signaling through G protein-coupled receptors (GPCRs). One mechanism by which TLR signaling could modify GPCR signaling is by altering the expression of regulator of G protein signaling (RGS) proteins. In this study, we show that human monocyte-derived DCs constitutively express significant amounts of RGS2, RGS10, RGS14, RGS18, and RGS19, and much lower levels of RGS3 and RGS13. Engagement of TLR3 or TLR4 on monocyte-derived DCs induces RGS16 and RGS20, markedly increases RGS1 expression, and potently downregulates RGS18 and RGS14 without modifying other RGS proteins. A similar pattern of Rgs protein expression occurred in immature bone marrow-derived mouse DCs stimulated to mature via TLR4 signaling. The changes in RGS18 and RGS1 expression are likely important for DC function, because both proteins inhibit Galpha(i)- and Galpha(q)-mediated signaling and can reduce CXC chemokine ligand (CXCL)12-, CC chemokine ligand (CCL)19-, or CCL21-induced cell migration. Providing additional evidence, bone marrow-derived DCs from Rgs1(-/-) mice have a heightened migratory response to both CXCL12 and CCL19 when compared with similar DCs prepared from wild-type mice. These results indicate that the level and functional status of RGS proteins in DCs significantly impact their response to GPCR ligands such as chemokines. C1 NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov RI Shi, GengXian/C-4660-2011; OI Kehrl, John/0000-0002-6526-159X NR 49 TC 67 Z9 74 U1 1 U2 4 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 2004 VL 172 IS 9 BP 5175 EP 5184 PG 10 WC Immunology SC Immunology GA 814ZJ UT WOS:000221012300006 PM 15100254 ER PT J AU Sun, R Tian, ZG Kulkarni, S Gao, B AF Sun, R Tian, ZG Kulkarni, S Gao, B TI IL-6 prevents T cell-mediated hepatitis via inhibition of NKT cells in CD4(+) T cell- and STAT3-dependent manners SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED LIVER-INJURY; CONCANAVALIN-A; IN-VITRO; INTERLEUKIN-6-DEFICIENT MICE; INDUCED APOPTOSIS; ACTIVATION; REGENERATION; EXPRESSION; STAT3; PATHWAYS AB The hepatoprotective effect of IL-6 on various forms of liver injury including T cell-mediated hepatitis has been well documented, and it is believed that induction of antiapoptotic proteins is an important mechanism. In this study, we provide evidence suggesting an additional mechanism involved in the protective role of IL-6 in T cell-mediated hepatitis. In NKT cell-depleted mice, Con A-induced liver injury is diminished; this can be restored by the adoptive transfer of liver mononuclear cells or NKT cells from wild-type mice, but not from IL-6-treated mice. In vitro IL-6 treatment inhibits the ability of mononuclear cells to restore Con A-induced liver injury in NKT-depleted mice, whereas the same treatment does not inhibit purified NKT cells from restoring the injury. The addition of CD3(+) T cells or CD4(+) T cells can restore the inhibitory effect of IL-6 on purified NKT cells, whereas the addition of CD3(+) T cells from CD4-deficient mice fails to restore this inhibitory effect. The expression of IL-6R was detected in 52.6% of hepatic CD3(+) T cells and 32.7% of hepatic CD4(+) T cells, but only in 3.9% of hepatic NK and 1.5% of hepatic NKT cells. Finally, treatment with IL-6 induces STAT3 activation in hepatic lymphocytes and hepatic T cells, and blocking such activation abolishes the inhibitory effect of IL-6 on hepatic lymphocytes to restore liver injury. Taken together, these findings suggest that in addition to its antiapoptotic abilities, as previously well documented, IL-6/STAT3 inhibits NKT cells via targeting CD4(+) T cells and consequently prevents T cell-mediated hepatitis. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. Univ Sci & Technol China, Sch Life Sci, Inst Immunol, Hefei 230026, Peoples R China. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Pk Bldg,Room 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI Tian, Zhigang/J-3512-2013 NR 42 TC 66 Z9 68 U1 1 U2 4 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 2004 VL 172 IS 9 BP 5648 EP 5655 PG 8 WC Immunology SC Immunology GA 814ZJ UT WOS:000221012300061 PM 15100309 ER PT J AU Khong, HT Wang, QJ Rosenberg, SA AF Khong, HT Wang, QJ Rosenberg, SA TI Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: Tumor escape by antigen loss and loss of MHC expression SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE tumor-infiltrating lymphocytes; vaccination; melanoma antigens; tumor escape; immunoselection ID WAARDENBURG-SYNDROME; TRANSCRIPTION FACTOR; METASTATIC MELANOMA; DRAMATIC RESPONSE; IMMUNOTHERAPY; CANCER; TYROSINASE; IMMUNITY; NY-ESO-1; SOX10 AB The authors describe a patient who experienced recurrence of metastatic melanoma after an initial dramatic response to immunotherapy using peptides derived from gp100, MART-1, and tyrosinase emulsified in incomplete Freund's adjuvant, and present data to support the hypothesis that the progression of disease in this patient was due to in vivo immunoselection for immunoresistant tumor variants. The authors previously demonstrated the existence of T-cell clones in this patient's peripheral blood and tumor-infiltrating lymphocytes (TILs) reactive against multiple antigens, including gp100, the tyrosinase-related protein (TRP)-2, a novel TRP-2 isoform-TRP-2-6b, SOX10, and the melanoma antigen NY-ESO-1. In addition to the multiple HLA-A2 restricted T-cell clones, the authors have now identified additional HLA-B/C-restricted as well as class 11 (HLA-DP)-restricted anti-melanoma antigen T-cell clones from this patient's TIL. One recurrent tumor showed loss of expression of multiple tumor antigens but retention of HLA class I expression. The other recurrent lesion showed total loss of HLA class I expression even though the tumor cells still expressed many melanoma antigens. This paper thus provides evidence for both the effectiveness of the immune destruction of cancer as well as problems associated with antigen-loss tumor escape mechanisms. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 15 TC 97 Z9 102 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2004 VL 27 IS 3 BP 184 EP 190 DI 10.1097/00002371-200405000-00002 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 818SF UT WOS:000221264100002 PM 15076135 ER PT J AU Heimann, DM Schwartzentruber, DJ AF Heimann, DM Schwartzentruber, DJ TI Gastrointestinal perforations associated with interleukin-2 administration SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE gastrointestinal perforation; interleukin-2; melanoma; renal cell carcinoma ID HIGH-DOSE INTERLEUKIN-2; TUMOR-INFILTRATING LYMPHOCYTES; PROSPECTIVE RANDOMIZED-TRIAL; TERM SURVIVAL UPDATE; METASTATIC MELANOMA; RECOMBINANT INTERLEUKIN-2; MALIGNANT-MELANOMA; THERAPY; CANCER; GUIDELINES AB High-dose interleukin-2 (IL-2) results in objective clinical regression in up to 17% of patients with metastatic melanoma and renal cell carcinoma, with about half of these patients experiencing a complete regression of all lesions. Gastrointestinal (GI) perforation is a rare but potentially serious complication of IL-2 administration. A retrospective review of all patients treated with IL-2 in the Surgery Branch of the National Cancer Institute (NCI) between Nov. 1, 1984, and May 1, 2002, was performed. In addition, a review of the published English literature on GI perforation in conjunction with IL-2 therapy was performed. Among the 1,797 patients treated at the NCI, there were eight (0.44%) cases of GI perforation. Seven of the eight patients were treated with high-dose (720,000 IU/kg every 8 hours) intravenous IL-2 (7/1,680, 0.42%) and one was treated with subcutaneous IL-2 (1/117, 0.85%). These patients developed various signs and symptoms of GI perforation. Six patients developed abdominal pain, yet only two of the eight patients had a fever. All six patients who underwent radiographic evaluation prior to diagnosis had free intraperitoneal air seen on the study. The location of the perforation included the stomach, small bowel, appendix, and colon. All underwent surgical treatment successfully, and four patients received further IL-2 therapy after recovering from the perforation. With the patients presented in this article, there have now been 20 cases reported in the English literature. Two of the patients at the NCI had a ruptured appendix, which has not been previously reported in the literature. The key to early diagnosis of GI perforation during IL-2 therapy is radiographic evaluation. Patients with GI perforation can be safely retreated with IL-2 if they are given adequate time to recover from their surgical intervention and if careful assessment is performed to rule out residual infection. C1 NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Heimann, DM (reprint author), NCI, Ctr Canc Res, Surg Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM David_Heimann@nih.gov NR 20 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2004 VL 27 IS 3 BP 254 EP 258 DI 10.1097/00002371-200405000-00010 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 818SF UT WOS:000221264100010 PM 15076143 ER PT J AU Larsen, HH Huang, L Kovacs, JA Crothers, K Silcott, VA Morris, A Turner, JR Beard, CB Masur, H Fischer, SH AF Larsen, HH Huang, L Kovacs, JA Crothers, K Silcott, VA Morris, A Turner, JR Beard, CB Masur, H Fischer, SH TI A prospective, blinded study of quantitative touch-down polymerase chain reaction using oral-wash samples for diagnosis of Pneumocystis pneumonia in HIV-infected patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 14-17, 2003 CL CHICAGO, IL ID TIME PCR ASSAY; CARINII-PNEUMONIA; SPUTUM AB Oral-wash samples obtained during 113 episodes of suspected Pneumocystis pneumonia (PCP) in human immunodeficiency virus-infected patients were tested by use of a quantitative touch-down PCR (QTD PCR) assay. QTD PCR had a sensitivity of 88% and a specificity of 85%. Treatment for PCP prior to oral wash collection had an impact on the sensitivity, and PCR-positive oral-wash samples obtained within less than or equal to1 day of treatment from patients without PCP had significantly fewer copies per tube than did those from patients with PCP; thus, application of a post hoc cut-off value of 50 copies/tube increased the specificity to 100%. QTD PCR of oral-wash samples can be an accurate and noninvasive method for diagnosis of PCP. C1 Hvidovre Univ Hosp, Copenhagen HIV Programme, Dept 044, DK-2650 Hvidovre, Denmark. Hvidovre Univ Hosp, Dept Clin Microbiol, DK-2650 Hvidovre, Denmark. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Crit Care, Ctr Clin, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA USA. RP Larsen, HH (reprint author), Hvidovre Univ Hosp, Copenhagen HIV Programme, Dept 044, DK-2650 Hvidovre, Denmark. EM hhl@cphiv.dk OI Crothers, Kristina/0000-0001-9702-0371 NR 15 TC 57 Z9 59 U1 0 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 2004 VL 189 IS 9 BP 1679 EP 1683 DI 10.1086/383322 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 814BX UT WOS:000220951300017 PM 15116305 ER PT J AU Higashi, Y Fuda, H Yanai, H Lee, Y Fukushige, T Kanzaki, T Strott, CA AF Higashi, Y Fuda, H Yanai, H Lee, Y Fukushige, T Kanzaki, T Strott, CA TI Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cholesterol; epidermis; keratinocyte; sulfate; sulfotransferase ID STRATUM-CORNEUM LIPIDS; HUMAN CYTOSOLIC SULFOTRANSFERASES; X-LINKED ICHTHYOSIS; SULFATE; DIFFERENTIATION; DESQUAMATION; GENE; CORNIFICATION; PATHOGENESIS; MICROSCOPY AB Cholesterol sulfate is a highly amphipathic molecule that is present in a relatively high concentration in the epidermis of human skin, particularly in the granular layer. The physiologic significance of this finding, however, is not well-understood. Therefore, we examined expression of the gene encoding for the enzyme that sulfonates cholesterol (SULT2B1b). Of the three enzymes known to sulfonate steroids/sterols, only the SULT2B1b isozyme was detected in cultures of normal human epidermal keratinocytes (NHEK) in response to Ca2+-induced terminal differentiation as well as by normal human epidermal tissue. Immunocytochemical analysis of normal skin as well as specific skin disorders was carried out. In normal skin, the expression of SULT2B1b was localized to the granular layer of the epidermis similar to that of filaggrin, an acknowledged late marker of differentiation and in contrast to that of involucrin, an early marker of terminal differentiation, which was expressed throughout the suprabasal region. The confinement of SULT2B1b to the granular layer coincides with this being the area with the highest cholesterol sulfate content suggesting that the physiologic action of cholesterol sulfate is likely carried out in this region of the living epidermis. Additionally, 88% of cholesterol sulfate in NHEK was membrane-associated further suggesting a cellular location for cholesterol sulfate action. C1 NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Fac Med, Dept Dermatol, Kagoshima 890, Japan. RP Strott, CA (reprint author), NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. EM Chastro@mail.nih.gov NR 38 TC 44 Z9 44 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2004 VL 122 IS 5 BP 1207 EP 1213 DI 10.1111/j.0022-202X.2004.22416.x PG 7 WC Dermatology SC Dermatology GA 819FU UT WOS:000221301000026 PM 15140224 ER PT J AU Pascali, G Kiesewetter, DO Salvadori, PA Eckelman, WC AF Pascali, G Kiesewetter, DO Salvadori, PA Eckelman, WC TI Use of 1,8-bis-(dimethylamino)-naphthalene/(HF)-F-18 complex as new radiofluorinating agent SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE proton sponge; nucleophilic fluorination; [F-18]fluoride; PET ID TRIS(HYDROGEN FLUORIDE) SYSTEM; IONIC LIQUIDS; PROTON SPONGE; CHLORODIAZINES; FLUORINATION AB Radiopharmaceuticals containing an F-18 label are of increasing interest due to their utilization in PET imaging. However, the bottleneck in these applications is the limited methods available for introduction of this radionuclide into biologically interesting molecules. In this work, we have evaluated a new radiofluorination method based on the properties of the complex between 1,8-(dimethylamino)-naphthalene (PS) and [F-18]-HF. The results obtained on various model substrates suggest that, in some limited cases, this new procedure can be regarded as a possible alternative to the traditional nucleophilic route using K-222/K2CO3 in CH3CN. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NIH, Bethesda, MD 20892 USA. Univ Lecce, ISUFI, I-73100 Lecce, Italy. NIH, PET & Cyclotron Dept, Ctr Clin, Bethesda, MD 20892 USA. CNR, IFC, Radiofarmacia & Ciclotrone Dept, I-00185 Rome, Italy. RP Pascali, G (reprint author), NIH, Bldg 10,Room 1C401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. EM gp114b@nih.gov RI Salvadori, Piero/B-2342-2012; OI Salvadori, Piero/0000-0001-6114-1059; Pascali, Giancarlo/0000-0001-7919-8416 NR 11 TC 9 Z9 9 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2004 VL 47 IS 6 BP 373 EP 383 DI 10.1002/jlcr.823 PG 11 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 831TE UT WOS:000222218200004 ER PT J AU Zhang, Y Hall, AW Horti, AG AF Zhang, Y Hall, AW Horti, AG TI Efficient synthesis of 6-chloro-3-((2-(S)azetidinyl)methoxy)-5-((E)-2-(2-[F-18]fluoropyridin-4- yl)vinyl)pyridine ([F-18]NIDA 52289), a very high affinity radioligand for nicotinic acetylcholine receptors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE nicotinic acetylcholine receptors; A-85380; positron-emission tomography; F-18 ID HUMAN BRAIN; BIODISTRIBUTION; RADIOTRACER; DISCOVERY; ANALOGS AB 6-Chloro-3-((2-(S)-azetidinyl)methoxy)-5-((E)-2-(2-[F-18]fluoropyridin-4-yl)vinyl)pyridine ([F-18]NIDA 52289), a very high affinity radioligand for studying nicotinic acetylcholine receptors (nAChRs) by positron-emission tomography, was synthesized through Kryptofix 222 assisted no-carrier-added nucleophilic [F-18]fluorination of 6chloro-3-((1-(tert-butoxycarbonyl)-2-(S)-azetidinyl)methoxy)-5-((E)-2-(2-bromopyri- din-4-yl)vinyl)pyridine, followed by acidic deprotection. The overall radiochemical yield of the radiosynthesis was 10% (non-decay-corrected), the specific radioactivity was in the range of 93-326GBq/mumol (2.5-8.8mCi/mumol) and the radiochemical purity was greater than 99%. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Horti, AG (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ahorti@intra.nida.nih.gov NR 20 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2004 VL 47 IS 6 BP 385 EP 392 DI 10.1002/jlcr.824 PG 8 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 831TE UT WOS:000222218200005 ER PT J AU Mazzoni, A Segal, DM AF Mazzoni, A Segal, DM TI Controlling the Toll road to dendritic cell polarization SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE Toll-like receptors; innate immunity; cytokines; infection ID T-HELPER-CELL; COLONY-STIMULATING FACTOR; NF-KAPPA-B; INTERFERON-PRODUCING CELLS; NECROSIS-FACTOR-ALPHA; DOUBLE-STRANDED-RNA; IL-12 P40 PROMOTER; MOUSE LYMPH-NODES; IN-VIVO; CUTTING EDGE AB The activation of dendritic cells (DC) via Toll-like receptors (TLRs) plays a decisive role in shaping the outcome of primary immune responses. Following TLR engagement by microbial products, DC migrate from peripheral tissues to lymphoid organs and up-regulate major histocompatibility complex and costimulatory molecules, acquiring the unique capacity to prime pathogen-specific, naive T cells. In addition, DC determine the character of the ensuing immune response by secreting cytokines that drive the development of T cells into T helper cell type 1 (Th1), Th2, or T regulatory effector cells. Three major factors influence the pattern of cytokines released by DC and accordingly, the Th balance: the lineage to which DC belong; the maturation stimulus; and inflammatory mediators present at the site of infection. A major focus of this review is the capacity of DC to integrate these factors and elicit distinct classes of immune responses. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Mazzoni, A (reprint author), NIH, Expt Immunol Branch, Bldg 10,Room 4B36,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dave_segal@nih.gov NR 123 TC 162 Z9 172 U1 0 U2 8 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 2004 VL 75 IS 5 BP 721 EP 730 DI 10.1189/jlb.1003482 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 817BP UT WOS:000221153300001 PM 14726500 ER PT J AU Worgall, TS Davis-Hayman, SR Magana, MM Oelkers, PM Zapata, F Juliano, RA Osborne, TF Nash, TE Deckelbaum, RJ AF Worgall, TS Davis-Hayman, SR Magana, MM Oelkers, PM Zapata, F Juliano, RA Osborne, TF Nash, TE Deckelbaum, RJ TI Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter: evidence for SREBP as an ancient transcription factor SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cyst-wall protein; encystations; sterol regulatory element binding protein ID ELEMENT-BINDING PROTEIN; MUTANT HAMSTER-CELLS; CYST WALL; GENE FAMILY; EXPRESSION; CHOLESTEROL; METABOLISM; DIFFERENTIATION; IDENTIFICATION; DROSOPHILA AB The sterol regulatory element binding-proteins (SREBPs) are transcription factors that regulate the genes of lipid metabolism. Cholesterol and unsaturated fatty acids regulate SREBPs. Giardia lamblia (GL) is an intestinal parasite and one of the earliest derived members within the eukaryotic lineage. GLs exist as trophozoites and cysts. Growth in cholesterol depletion induces transcription of cyst-wall protein (CWT) genes that are upregulated during encystation. The hypothesis was investigated that SREBP-like pathways have a role in cwp gene transcription. Chinese hamster ovary cells were transfected with a cwp-2 promoter reporter construct. Incubation with cholesterol or oleate reduced cwp-2 mediated gene transcription to about half of the control. Incubation in sterol-depleted media, or in the presence of either an inhibitor of intracellular cholesterol movement or inhibitor of cholesterol synthesis, increased gene expression up to 3-fold. Overexpression of SREBPs increased reporter gene activity 2.5-fold. In the absence of functional SREBPs, cwp-2, was not regulated by cholesterol. Footprint analysis of cwp-2 reveals three novel binding sites for mammalian SREBPs with no homologies in other species or humans. jr The data show that SREBP binds to and can modulate transcription of a regulatory element from an ancient eukaryote and suggest the existence of an SREBP homolog in GL. -Worgall, T S., S. R. Davis-Hayman, M. M. Magana, P. M. Oelkers, F. Zapata, R. A. Juliano, T. F. Osborne T E. Nash, and R. J. Deckelbaum. Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter: evidence for SREBP as an ancient transcription factor.. C1 Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Dept Pediat, New York, NY 10032 USA. Columbia Univ, Inst Human Nutr, New York, NY 10032 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Drexel Univ, Dept Biosci & Biotechnol, Philadelphia, PA 19104 USA. RP Worgall, TS (reprint author), Columbia Univ, Dept Pathol, New York, NY 10032 USA. EM tpw7@columbia.edu FU NHLBI NIH HHS [HL-40404]; NIDDK NIH HHS [T32DK-07715] NR 41 TC 11 Z9 13 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2004 VL 45 IS 5 BP 981 EP 988 DI 10.1194/jlr.M400024-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 814TS UT WOS:000220997600023 PM 14967824 ER PT J AU Devasahayam, N Murugesan, R Matsumoto, K Mitchell, JB Cook, JA Subramanian, S Krishna, MC AF Devasahayam, N Murugesan, R Matsumoto, K Mitchell, JB Cook, JA Subramanian, S Krishna, MC TI Tailored sinc pulses for uniform excitation and artifact-free radio frequency time-domain EPR imaging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; IN-VIVO EPR; 250 MHZ EPR; ESR SPECTROMETER; SPECTROSCOPY; PROBE; MICE; MRI AB A method to generate shaped radiofrequcncy pulses for uniform excitation of electron spins in time-domain radio frequency (RF) electron paramagnetic resonance (EPR) imaging is presented. A commercial waveform generator was integrated with the transmit arm of the existing time-domain RF-EPR spectrometer to generate tailored excitation pulses with sub-nano second resolution for excitation with a 90degrees flip-angle. A truncated sine [sin (x)/x] pulse, tailored to compensate for the Q-profile (RF frequency response) of the resonator, was shown to yield images from phantom objects as well as in vivo images, with minimal distortion. These studies point to the advantages in using shaped sinc pulses to achieve improved Uniform excitation over a relatively wide bandwidth region in time-domain RF-EPR imaging (RF-FT-EPRI). Published by Elsevier Inc. C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM murali@helik.nih.gov NR 35 TC 15 Z9 15 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2004 VL 168 IS 1 BP 110 EP 117 DI 10.1016/j.jmr.2004.01.016 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 814XE UT WOS:000221006600013 PM 15082255 ER PT J AU Petkova, AT Tycko, R AF Petkova, AT Tycko, R TI Rotational resonance in uniformly C-13-labeled solids: effects on high-resolution magic-angle spinning NMR spectra and applications in structural studies of biomolecular systems SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE solid state NMR; magic-angle spinning; rotational resonance; amyloid structure ID NUCLEAR-MAGNETIC-RESONANCE; BETA-AMYLOID PEPTIDE; STATE NMR; INTERNUCLEAR DISTANCES; LABELED MOLECULE; FLOQUET THEORY; C-13; SPECTROSCOPY; ASSIGNMENTS; FIBRILS AB We describe investigations of the effects of rotational resonance (R-2) oil solid state C-13 NMR spectra of uniformly C-13-labeled samples obtained under magic-angle spinning (MAS), and of the utility of R-2 measurements as structural probes of peptides and proteins with multiple uniformly labeled residues. We report results for uniformly C-13-labeled L-alanine and L-valine in polycrystalline form. and for amyloid fibrils formed by the 15-residue peptide Abeta(11-25) with uniform labeling of a four-residue segment. The MAS NMR spectra reveal a novel J-decoupling effect at R-2 conditions that may be useful in spectral assignments for systems with sharp C-13 MAS NMR lines. Pronounced dependences of the apparent isotropic C NMR chemical shifts on MAS frequency near R-2 conditions are also observed. We demonstrate the feasibility of quantitative C-13-C-13 distance determinations in L-valine, and qualitative determinations of inter-residue C-13-C-13 Contacts in Abeta(11-25) fibrils. Finally, we demonstrate a "relayed" R 2 technique that may be useful in structural measurements on systems with poorly resolved C-13 MAS NMR lines. Published by Elsevier Inc. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM tycko@helix.nih.gov NR 33 TC 17 Z9 18 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2004 VL 168 IS 1 BP 137 EP 146 DI 10.1016/j.jmr.2004.02.007 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 814XE UT WOS:000221006600017 PM 15082259 ER PT J AU Longui, CA Lemos-Marini, SHV Figueiredo, B Mendonca, BB Castro, M Liberatore, R Watanabe, C Lancellotti, CLP Rocha, MN Melo, MB Monte, O Calliari, LEP Guerra, G Baptista, MTM Sbragia-Neto, L Latronico, AC Moreira, A Tardelli, AMD Nigri, A Taymans, SE Stratakis, CA AF Longui, CA Lemos-Marini, SHV Figueiredo, B Mendonca, BB Castro, M Liberatore, R Watanabe, C Lancellotti, CLP Rocha, MN Melo, MB Monte, O Calliari, LEP Guerra, G Baptista, MTM Sbragia-Neto, L Latronico, AC Moreira, A Tardelli, AMD Nigri, A Taymans, SE Stratakis, CA TI Inhibin alpha-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CARCINOMA-CELLS; BINDING-PROTEIN; ADRENAL-CORTEX; CARNEY COMPLEX; EXPRESSION; RECEPTOR; P53; SECRETION; CHILDHOOD AB The R337H TP53 mutation is a low-penetrance molecular defect that predisposes to adrenocortical tumour (ACT) formation in Brazilian and possibly other populations. Additional genetic defects may be responsible for the variable expression of ACTs in these cases. The inhibin alpha-subunit gene (INHA) on 2q33-qter has been implicated in mouse adrenocortical tumourigenesis. We studied 46 pediatric patients with ACTs from Brazil for INHA genetic alterations; 39 of these patients were heterozygous carriers of the R337H TP53 mutation. We first mapped the INHA gene by radiation hybrid analysis and determined 10 linked microsatellite markers in an area flanked by D2S1371 and D2S206 on 2q33-qter. These markers were then used for loss of heterozygozity (LOH) studies in nine paired germline and tumour DNA samples. Mapping placed the INHA gene in close proximity to D2S2848 (SHGC11864) with a log of odds (LOD) score of 5.84. LOH for at least one marker in the region was identified in 8/9 tumours (89%). Six patients were heterozygous for three INHA mutations: one in exon 1, 127C>G, and two in exon 2, 3998G>A and 4088G>A, all leading to amino acid substitutions (P43A, G227R, and A257T, respectively). A257T is located in a conserved INHA region, highly homologous to transforming growth factor-beta; both G227R and A257T change polarity, and, in addition, G227R changes the pH. We conclude that these sequence alterations and the detected 2q allelic changes suggest that INHA may be one of the contributing factors needed for ACT formation in pediatric patient carriers of the R337H TP53 mutation. C1 NICHD, Sect Edocrinol & Genet, DEB, NIH, Bethesda, MD 20892 USA. Santa Casa Sao Paulo, Sch Med, Lab Mol Invest, Sao Paulo, Brazil. Santa Casa Sao Paulo, Sch Med, Dept Pathol, Sao Paulo, Brazil. State Univ Campinas, UNICAMP Pediat Endocrinol Unit, Campinas, SP, Brazil. Univ Fed Parana, BR-80060000 Curitiba, Parana, Brazil. Univ Sao Paulo, FMUSP SP Endocrinol Div, Sao Paulo, Brazil. Univ Sao Paulo, Endocrinol Unit, BR-14049 Ribeirao Preto, Brazil. Sch Med, Sao Jose Do Rio Preto, SP, Brazil. Catholic Univ Sorocaba, Sorocaba, SP, Brazil. RP Stratakis, CA (reprint author), NICHD, Sect Edocrinol & Genet, DEB, NIH, Bldg 10,Room 10N262,10 Ctr MSC1862, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Castro, Margaret/A-4918-2009; Guerra-Junior, Gil/C-1609-2012; Mendonca, Berenice/C-2827-2012; Latronico, Ana Claudia/E-1198-2012; Rocha, Mylene/F-4211-2012; Monte, Osmar/G-9063-2012; Liberatore Junior, Raphael/B-5562-2013; Lemos-Marini, Sofia Helena/D-2184-2013; Sbragia, Lourenco/P-7380-2015 OI Guerra-Junior, Gil/0000-0002-2991-7678; Latronico Xavier, Ana Claudia/0000-0001-6782-693X; Monte, Osmar/0000-0002-2549-9237; Sbragia, Lourenco/0000-0002-1881-6345 NR 36 TC 17 Z9 20 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-6244 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2004 VL 41 IS 5 BP 354 EP 359 DI 10.1136/jmg.2004.018978 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 817GI UT WOS:000221165600007 PM 15121773 ER PT J AU Tanaka, Y Pfeiffer, R Yeo, AET Mizokami, M Edlin, BR Castle, P O'Brien, TR Alter, HJ Shih, JWK AF Tanaka, Y Pfeiffer, R Yeo, AET Mizokami, M Edlin, BR Castle, P O'Brien, TR Alter, HJ Shih, JWK TI PCR-probe capture hybridization assay and statistical model for SEN virus prevalence estimation SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE injection drug users; cut-off value; sensitivity; SENV; mixture model ID INFECTION; HEPATITIS AB SEN viruses (SENV) are newly discovered blood-borne single-stranded circular DNA viruses that may play a role in liver disease. To date, no serologic assays are available for the detection of SENV antigens or antibodies. We report on a rapid and sensitive molecular assay for the detection of four SENV strains (SENV-A -C, -D, -H). This method uses PCR with universal primers and microwell capture hybridization with type-specific probes. Cut-off points to define "infected" based on chemiluminescence readings were determined from a statistical mixture model applied to samples from 300 injection drug users (IDUs) in San Francisco. Based on the estimated cut-off points, we examined the prevalence of SENV infection among 232 healthy US blood donors and assessed sensitivity and specificity of the assay in a small validation sample of infected individuals with partial sequence information. (C) 2004 Wiley-Liss, Inc.(dagger) C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Jacobus Pharmaceut Co Inc, Princeton, NJ USA. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi, Japan. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, DHHS, Rockville, MD 20852 USA. RP Pfeiffer, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,Room 8030, Rockville, MD 20852 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Edlin, Brian/0000-0001-8172-8797 NR 16 TC 2 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 2004 VL 73 IS 1 BP 123 EP 130 DI 10.1002/jmv.20067 PG 8 WC Virology SC Virology GA 808PN UT WOS:000220581100020 PM 15042659 ER PT J AU Boheler, K AF Boheler, K TI Embryonic stem cell-derived cardiomyocytes-development of adult phenotype SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 24th Annual Scientific Sessions of the European-Section of the International-Society-for-Heart-Research CY JUN 02-06, 2004 CL Dresden, GERMANY SP Int Soc Heart Res, European Sect C1 NIA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2004 VL 36 IS 5 MA 13 BP 717 EP 717 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 825HQ UT WOS:000221747400023 ER PT J AU Seubert, J Yang, BC Bradbury, A Graves, J Miller, L Murphy, E Zeldin, DC AF Seubert, J Yang, BC Bradbury, A Graves, J Miller, L Murphy, E Zeldin, DC TI Cytochrome P450 enzymes in the heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 24th Annual Scientific Sessions of the European-Section of the International-Society-for-Heart-Research CY JUN 02-06, 2004 CL Dresden, GERMANY SP Int Soc Heart Res, European Sect C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2004 VL 36 IS 5 MA 173 BP 772 EP 772 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 825HQ UT WOS:000221747400183 ER PT J AU Hardick, J Maldeis, N Theodore, M Wood, BJ Yang, S Lin, S Quinn, T Gaydos, C AF Hardick, J Maldeis, N Theodore, M Wood, BJ Yang, S Lin, S Quinn, T Gaydos, C TI Real-time PCR for Chlamydia pneumoniae utilizing the Roche lightcycler and a 16S rRNA gene target SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID ASSAYS; SPECIMENS; DNA; ATHEROSCLEROSIS; PSITTACI AB Chlamydia pneumoniae (CPN) causes pneumonia in humans, and has emerged as an important respiratory pathogen. There are also established links between CPN infection and coronary artery disease. Traditional culture methods for CPN detection can be time consuming and difficult. There are a variety of molecular-based amplification methods for CPN detection. These methods are more sensitive than culture, but have the disadvantage of being inconsistent and non-comparable across studies. In this paper, we describe the adaptation of the existing primer set CPN 90/CPN91 for use in a real-time PCR assay using the Roche Lightcycler and a Taqman probe. This assay had an analytical sensitivity of between 4 and 0.4 infection-forming units (IFUs)/PCR reaction. A total of 355 samples were tested for validation of the assay. Tested samples included two standardized panels of blinded samples from culture (N = 70), archived specimens consisting of a CPN dilution series, CPN-spiked porcine aortal tissue and endarterectomy specimens (N = 87). The third group consisted of prospectively collected PBMCs from clinical samples (N = 198). Results were compared to nested PCR, which targets the ompA gene of CPN; TETR PCR, which targets the 16S rRNA gene of CPN, or the known result for the sample. Overall, the assay had a sensitivity of 88.5% (69 of 78) and a specificity of 99.3% (275 of 277). This method should prove useful for accurate, high throughput detection of CPN. C1 Johns Hopkins Univ, Sch Med, Dept Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Emergency Med, Baltimore, MD USA. RP Gaydos, C (reprint author), Johns Hopkins Univ, Sch Med, Dept Infect Dis, Ross Bldg,Room 1147,720 Rutland Ave, Baltimore, MD 21205 USA. EM cgaydos@jhmi.edu RI Gaydos, Charlotte/E-9937-2010 NR 13 TC 20 Z9 22 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2004 VL 6 IS 2 BP 132 EP 136 DI 10.1016/S1525-1578(10)60501-6 PG 5 WC Pathology SC Pathology GA 814VP UT WOS:000221002500009 PM 15096569 ER PT J AU Cui, XH Wang, JC Deckhut, A Joseph, BC Eberwein, P Cubitt, CL Ryschkewitsch, CF Agostini, HT Stoner, GL AF Cui, XH Wang, JC Deckhut, A Joseph, BC Eberwein, P Cubitt, CL Ryschkewitsch, CF Agostini, HT Stoner, GL TI Chinese strains (Type 7) of JC virus are Afro-Asiatic in origin but are phylogenetically distinct from the Mongolian and Indian strains (Type 2D) and the Korean and Japanese strains (Type 2A) SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE JC virus; polyomavirus; genotypes; viral evolution; phylogenetics; urine; China; India; Korea ID HUMAN POLYOMAVIRUS JC; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; DNA-SEQUENCE ANALYSIS; PAPUA-NEW-GUINEA; POPULATION HISTORY; MODERN HUMANS; MITOCHONDRIAL-DNA; NATIVE-AMERICANS; COMPLETE GENOMES; HUMAN MIGRATIONS AB We have further characterized the Asian genotypes (Types 2 and 7) and subtypes of JC virus (JCV). Urine samples from 224 individuals with Han and Mongolian populations were collected in five regions in eastern China: Kunming, Chengdu, Shenyang, Chifeng, and Manzhouli. Also, 99 urine samples were collected from coastal and hill groups in Kerala, southern India, and 23 urine samples from Seoul, Korea. PCR products of four typing fragments were sequenced, including two in the VP1 gene, as well as one each in the VT intergenic region and regulatory region. It was possible to clone and sequence a total of 42 JCV whole genomes (similar to5120 bp). Five genotypes of JCV (Types 7A, 713, 7C, 2D, and 4) were found in China, four genotypes (Types 2D, 7C, 4, and 113) in southern India, and three genotypes (Types 713, 2A, and 1A) in Korea. Type 7A was most prevalent in South China (59-64%) and Type 713 was predominant in northeast China and Inner Mongolia (67-77%). Type 7C strains were spread throughout North and South China (3-14%), while Type 2D strains were found only in the two Mongolian groups (9-10%). In southern India, Type 2D was predominant in the coastal group (95%), and two major types, Type 7C (50%) and Type 2D (35%), were prevalent in the tribal hill groups. In Korea two major genotypes were found: Type 713 (50%) and Type 2A (43%). Phylogenetic reconstruction places the Chinese genotypes in the Afro-Asiatic supercluster, but distinct from the Mongolian and Indian strains (Type 2D), as well as the Korean and Japanese genotype (Type 2A) that predominates in the Americas. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Dept Ophthalmol, D-79106 Freiburg, Germany. RP Cui, XH (reprint author), NINDS, Neurotoxicol Sect, NIH, MSC-4126,36 Convent Dr, Bethesda, MD 20892 USA. EM cuixh@yahoo.com; agostini@aug.ukl.uni-fi-eiburg.de NR 50 TC 20 Z9 20 U1 0 U2 0 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 2004 VL 58 IS 5 BP 568 EP 583 DI 10.1007/s00239-003-2579-2 PG 16 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 819QB UT WOS:000221328600009 PM 15170260 ER PT J AU Muraro, PA Liberati, L Bonanni, L Pantalone, A Caporale, CM Iarlori, C De Luca, G Farina, D Lugaresi, A Gambi, D AF Muraro, PA Liberati, L Bonanni, L Pantalone, A Caporale, CM Iarlori, C De Luca, G Farina, D Lugaresi, A Gambi, D TI Decreased integrin gene expression in patients with MS responding to interferon-beta treatment SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; interferon-beta; adhesion molecules; VLA-4; LFA-1 ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; RELAPSING MULTIPLE-SCLEROSIS; T-LYMPHOCYTES; LEUKOCYTE MIGRATION; CONTROLLED TRIAL; CELL-ADHESION; REMITTING MS; MRI LESIONS AB Interferon-beta (IFN-beta) ameliorates disease course in a subset of patients with MS. The reasons for heterogeneity of clinical responses, however, are unclear. We assessed possible effects of IFN-beta on the gene expression of the leukocyte adhesion molecules VLA-4 and LFA-1 during the first year of treatment of 50 patients with relapsing-remitting MS who showed differential clinical responses. We observed a significant reduction of VLA-4 (P=0.002) and LFA-1 (P=0.03) mRNA expression compared to baseline in first-year clinical responders (n=22). In contrast, first-year IFN-beta non-responders (n=28) had unchanged levels of VLA-4 and LFA-1. In vitro treatment of PBMC with IFN-beta indicated a direct effect on transcription of the integrins' genes. Transcriptional downmodulation of adhesion molecules during IFN-beta treatment may contribute to its mode of action in MS. (C) 2004 Elsevier B.V. All rights reserved. C1 NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. Univ Annunzio, Med Sch, Dept Oncol & Neurosci, Neuroimmunol Unit, I-66013 Chieti, Italy. RP Muraro, PA (reprint author), NINDS, Neuroimmunol Branch, Bldg 10,Room 5B16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. EM murarop@ninds.nih.gov RI Lugaresi, Alessandra/C-7743-2012; OI Lugaresi, Alessandra/0000-0003-2902-5589; Muraro, Paolo/0000-0002-3822-1218 NR 45 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY PY 2004 VL 150 IS 1-2 BP 123 EP 131 DI 10.1016/j.jneuroim.2004.01.002 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 817CR UT WOS:000221156100015 PM 15081256 ER PT J AU Foltynie, T Goldberg, TE Lewis, SJ Blackwell, AD Kolachana, B Weinberger, DR Robbins, TW Barker, RA AF Foltynie, T Goldberg, TE Lewis, SJ Blackwell, AD Kolachana, B Weinberger, DR Robbins, TW Barker, RA TI Working memory ability in Parkinson's disease is associated with the COMT val(108/158)met polymorphism SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT Autumn Meeting of the Association-of-British-Neurologists CY OCT 01-03, 2003 CL GLASGOW, SCOTLAND SP Assoc British Neurologists C1 Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge, England. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 2004 VL 75 IS 5 MA 076 BP 804 EP 804 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 813DB UT WOS:000220886700080 ER PT J AU Weickert, CS Herman, MM McClintock, BW Halim, N Lipska, BK Hyde, TM Weinberger, DR Straub, RE Kleinman, JE AF Weickert, CS Herman, MM McClintock, BW Halim, N Lipska, BK Hyde, TM Weinberger, DR Straub, RE Kleinman, JE TI Levels of dysbindin, a schizophrenia susceptibility gene, are reduced in the frontal cortex of patients with schizophrenia. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 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 2004 VL 63 IS 5 MA 43 BP 521 EP 521 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400053 ER PT J AU Goebel, HH Nagele, A Fritz, P Sechtem, U Goldfarb, LG AF Goebel, HH Nagele, A Fritz, P Sechtem, U Goldfarb, LG TI Desminopathy - A new mutational form. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Univ Mainz, Ctr Med, Dept Neuropathol, Mainz, Germany. Dept Neurol, Goppingen, Germany. Robert Bosch Krankenhaus, Dept Pathol, Stuttgart, Germany. Robert Bosch Krankenhaus, Dept Internal Med, Stuttgart, Germany. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 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 2004 VL 63 IS 5 MA 88 BP 532 EP 532 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400099 ER PT J AU Quezado, M Santi, M Dilys, P Rushing, E AF Quezado, M Santi, M Dilys, P Rushing, E TI Familial chordomas: A morphologic and immunohistochemical study in relation to sporadic tumors. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 NCI, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC 20010 USA. Armed Forces Inst Pathol, 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 2004 VL 63 IS 5 MA 146 BP 546 EP 546 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400156 ER PT J AU Izquierdo, A Murray, EA AF Izquierdo, A Murray, EA TI Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair affective processing in rhesus monkeys SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BASOLATERAL AMYGDALA; ORBITOFRONTAL CORTEX; NEUROTOXIC LESIONS; FRONTAL-CORTEX; DISSOCIABLE CONTRIBUTIONS; UTILIZATION BEHAVIOR; TEMPORAL LOBECTOMY; NEURONAL-ACTIVITY; MACACA-MULATTA; FEAR AB The amygdala and orbital prefrontal cortex (PFo) interact as part of a system for affective processing. To assess whether there is a hemispheric functional specialization for the processing of emotion or reward or both in nonhuman primates, rhesus monkeys (Macaca mulatta) with combined lesions of the amygdala and PFo in one hemisphere, either left or right, were compared with unoperated controls on a battery of tasks that tax affective processing, including two tasks that tax reward processing and two that assess emotional reactions. Although the two operated groups did not differ from each other, monkeys with unilateral lesions, left and right, showed altered reward-processing abilities as evidenced by attenuated reinforcer devaluation effects and an impairment in object reversal learning relative to controls. In addition, both operated groups showed blunted emotional reactions to a rubber snake. By contrast, monkeys with unilateral lesions did not differ from controls in their responses to an unfamiliar human (human "intruder"). Although the results provide no support for a hemispheric specialization of function, they yield the novel finding that unilateral lesions of the amygdala-orbitofrontal cortical circuit in monkeys are sufficient to significantly disrupt affective processing. C1 NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, Bethesda, MD 20892 USA. RP Izquierdo, A (reprint author), NIMH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM alicia@ln.nimh.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 81 TC 90 Z9 91 U1 0 U2 4 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 2004 VL 91 IS 5 BP 2023 EP 2039 DI 10.1152/jn.00968.2003 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 810GH UT WOS:000220692300015 PM 14711973 ER PT J AU Butefisch, CM Khurana, V Kopylev, L Cohen, LG AF Butefisch, CM Khurana, V Kopylev, L Cohen, LG TI Enhancing encoding of a motor memory in the primary motor cortex by cortical stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-LASTING POTENTIATION; USE-DEPENDENT PLASTICITY; INTERHEMISPHERIC INHIBITION; TERM POTENTIATION; HUMAN-BRAIN; HORIZONTAL CONNECTIONS; SYNAPTIC TRANSMISSION; ADULT-RATS; EXCITABILITY AB Motor training results in encoding of motor memories, a form of use-dependent plasticity. Here we tested the hypothesis that transcranial magnetic stimulation (TMS) synchronously applied to a motor cortex engaged in a motor training task could enhance this plastic process. Healthy volunteers were studied in four sessions: training consisting of performance of directionally specific voluntary thumb movements (Train alone), training with TMS delivered during the execution of the training movement in a strictly temporal relationship to the motor cortex contralateral (Train + TMS synchronous(contra)) and ipsilateral (Train + TMS synchronous (ipsi)) to the training hand, and training with TMS delivered asynchronous to the training movement to the motor cortex contralateral to the training hand (Train + TMS asynchronous(contra)). Train alone, Train + TMS synchronous(contra), and Train + TMS asynchronous(contra) but not Train + TMS synchronous ipsi elicited a clear motor memory. The longevity of the encoded memory was significantly enhanced by Train + TMS synchronous(contra) when compared with Train alone and Train + TMS asynchronous(contra). Therefore use-dependent encoding of a motor memory can be enhanced by synchronous Hebbian stimulation of the motor cortex that drives the training task and reduced by stimulation of the homologous ipsilateral motor cortex, a result relevant for studies of cognitive and physical rehabilitation. C1 NINDS, Human Cort Physiol Sect, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, NIH, Bethesda, MD 20892 USA. RP Butefisch, CM (reprint author), Univ Dusseldorf, Neurol Therapeut Ctr, Hohensandweg 37, D-40591 Dusseldorf, Germany. EM cathrin.buetefisch@uni-duesseldorf.de; cohen@ninds.nih.gov NR 52 TC 128 Z9 130 U1 0 U2 8 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 2004 VL 91 IS 5 BP 2110 EP 2116 DI 10.1152/jn.01038.2003 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 810GH UT WOS:000220692300022 PM 14711974 ER PT J AU Wang, J Cheng, CM Zhou, J Smith, A Weickert, CS Perlman, WR Becker, KG Powell, D Bondy, CA AF Wang, J Cheng, CM Zhou, J Smith, A Weickert, CS Perlman, WR Becker, KG Powell, D Bondy, CA TI Estradiol alters transcription factor gene expression in primate prefrontal cortex SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE estrogen; brain; neuron; c-FOS; E2F1; TFIIB; rhesus monkey; memory; cognition ID ADULT RHESUS-MONKEYS; I IGF-I; POSTMENOPAUSAL WOMEN; WORKING-MEMORY; RAT-BRAIN; ESTROGEN; E2F1; HYDROXYLASE; APOPTOSIS; INDUCTION AB Estrogen protects neurons from a variety of experimental insults in vitro, and is thought to protect from acute and chronic neurodegenerative processes in vivo. Estrogen also enhances higher-level cognitive functions that are centered in the dorsolateral prefrontal cortex (DLPFC) in human and non-human primates. To investigate genomic mechanisms involved in estrogenic effects on the primate brain in vivo, we compared transcription factor mRNA and protein expression in the DLPFC of ovariectomized rhesus monkeys treated with either vehicle or estradiol (E2). c-FOS, E2F1, and general transcription factor IIB (TFIIB) mRNA and protein expression were altered significantly by short-term E2 treatment, as shown by DNA array, in situ hybridization, and immuno-histochemical and immunoblot evaluations. c-FOS expression was increased significantly whereas E2F1 and TFIIB levels were decreased in the DLPFC of E2-treated animals. These transcription factors were concentrated in cortical pyramids, as were estrogen receptors alpha and beta. These data indicate that estrogen may have direct as well as indirect effects on neuronal gene expression in the primate prefrontal cortex. (C) 2004 Wiley-Liss, Inc. C1 NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Natl Inst Child Hlth, Dev Endocrinol Branch, Bethesda, MD USA. RP Bondy, CA (reprint author), NIH, Off Res Serv, Div Vet Resources, Bldg 10,10N262 10 Ctr Dr, Bethesda, MD 20892 USA. EM bondvc@mail.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; OI Becker, Kevin/0000-0002-6794-6656 NR 30 TC 32 Z9 33 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 2004 VL 76 IS 3 BP 306 EP 314 DI 10.1002/jnr.20076 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 817NB UT WOS:000221183100004 PM 15079859 ER PT J AU Newbold, RR Padilla-Banks, E Jefferson, WN AF Newbold, RR Padilla-Banks, E Jefferson, WN TI Neonatal exposure to the soy phytoestrogen genistein alters gene expression in the murine uterus. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract CT 5th International Symposium on the Role of Soy in Preventing and Treating Chronic Disease CY SEP 21-24, 2003 CL Orlando, FL C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. N Carolina State Univ, Raleigh, NC 27695 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2004 VL 134 IS 5 BP 1282S EP 1282S PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 820XK UT WOS:000221423000179 ER PT J AU Desnick, RJ Brady, RO AF Desnick, RJ Brady, RO TI Fabry disease in childhood SO JOURNAL OF PEDIATRICS LA English DT Article ID ENZYME REPLACEMENT THERAPY; ANGIOKERATOMA CORPORIS DIFFUSUM; ALPHA-GALACTOSIDASE; CLINICAL MANIFESTATIONS; ATYPICAL VARIANT; DIAGNOSIS; STORAGE; CARBAMAZEPINE; DISORDER; SYMPTOMS C1 CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Desnick, RJ (reprint author), CUNY Mt Sinai Sch Med, Dept Human Genet, Box 1498,5th Ave & 100th St, New York, NY 10029 USA. EM rjdesnick@mssm.edu NR 34 TC 52 Z9 59 U1 0 U2 2 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 2004 VL 144 IS 5 SU S BP S20 EP S26 DI 10.1016/j.jpeds.2004.01.051 PG 7 WC Pediatrics SC Pediatrics GA 823GW UT WOS:000221599200004 PM 15126980 ER PT J AU Kajava, AV Potekhin, SA Corradin, G Leapman, RD AF Kajava, AV Potekhin, SA Corradin, G Leapman, RD TI Organization of designed nanofibrils assembled from alpha-helical peptides as determined by electron microscopy SO JOURNAL OF PEPTIDE SCIENCE LA English DT Article DE alpha-helical coiled coil; design; fibrils; peptides; self-assembly ID 5-STRANDED COILED-COIL; GCN4 LEUCINE-ZIPPER; HIGH AVIDITY; PROTEIN; FIBRILS; DOMAIN AB Self-assembling peptides present attractive platforms for engineering materials with controlled nanostructures. Recently, an alpha-helical fibril forming peptide (alphaFFP) was designed that self-assembles into nanofibrils at acid pH. Circular dichroism spectroscopy, electron-microscopy and x-ray fibre diffraction data showed that the most likely structure of aFFP fibrils is a five-stranded coiled coil rope. In the present study, scanning transmission electron microscopy (STEM) was used to improve our understanding of the alphaFFP fibril structure. The measurements of fibril mass per length suggest that there are ten alpha-helices in transverse sections of the fibrils. Based on the known data, it. is proposed that a predominant fibrillar structure of aFFP is a dimer of a-helical five-stranded protofilaments wrapped around a common axis. It is shown that these structures have an axial dimension of 58 +/- 16 nm and a width of 4 +/- 1 nm. A small number of thin fibrils is also observed in the negative stained preparation and STEM images. The thin fibrils may correspond to the single protofilament. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd. C1 CIT, Ctr Mol Modeling, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. ORS, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Kajava, AV (reprint author), CRBM, CNRS, FRE 2593, 1919 Route Mende, F-34293 Montpellier 5, France. EM kajava@cnrs-mop.fr RI Potekhin, Sergey/M-8274-2015; Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 22 TC 22 Z9 22 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PD MAY PY 2004 VL 10 IS 5 BP 291 EP 297 DI 10.1002/psc.520 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 820FH UT WOS:000221372300007 PM 15160841 ER PT J AU Katz, JL Kopajtic, TA Agoston, GE Newman, AH AF Katz, JL Kopajtic, TA Agoston, GE Newman, AH TI Effects of N-substituted analogs of benztropine: Diminished cocaine-like effects in dopamine transporter ligands SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SCHEDULE-CONTROLLED BEHAVIOR; UPTAKE INHIBITORS; RHESUS-MONKEYS; SQUIRREL-MONKEYS; IN-VITRO; POTENT; COMBINATION; AMPHETAMINE; RIMCAZOLE; RECEPTOR AB Previous studies demonstrated that analogs of benztropine (BZT) possess high affinity for the dopamine transporter, inhibit dopamine uptake, but generally have behavioral effects different from those of cocaine. One hypothesis is that muscarinic-M-1 receptor actions interfere with cocaine-like effects. Several tropane-nitrogen substitutions of 4', 4"-diF-BZT have reduced M-1 affinity compared with the CH3-analog (AHN 1-055; 3alpha-[bis-(4-fluorophenyl)methoxy]tropane). All of the compounds displaced [H-3]WIN 35,428 (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) binding with affinities ranging from 11 to 108 nM. Affinities at norepinephrine ([H-3] nisoxetine) and serotonin ([H-3] citalopram) transporters ranged from 457 to 4810 and 376 to 3260 nM, respectively, and at muscarinic M-1 receptors ([H-3] pirenzepine) from 11.6 (AHN 1-055) to higher values, reaching 1030 nM for the other BZT-analogs. Cocaine and AHN 1-055 produced dose-related increases in locomotor activity in mice, with AHN 1-055 less effective than cocaine. The other compounds were ineffective in stimulating activity. In rats discriminating cocaine (29 mumol/kg i.p.) from saline, WIN 35,428 fully substituted for cocaine, whereas AHN 1-055 produced a maximal substitution of 79%. None of the other analogs fully substituted for cocaine. WIN 35,428 produced dose-related leftward shifts in the cocaine dose-effect curve, whereas selected BZT analogs produced minimal changes in the effects of cocaine. The results suggest that reducing M-1 affinity of 4', 4"-diF-BZT with N-substitutions reduces effectiveness in potentiating the effects of cocaine. Furthermore, although the BZT-analogs bind with high affinity at the dopamine transporter, their behavioral effects differ from those of cocaine. These compounds have reduced efficacy compared with cocaine, a long duration of action, and may serve as leads for the development of medications to treat cocaine abuse. C1 NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 NR 33 TC 51 Z9 52 U1 1 U2 4 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 1 PY 2004 VL 309 IS 2 BP 650 EP 660 DI 10.1124/jpet.103.060525 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814KF UT WOS:000220972900028 PM 14755006 ER PT J AU Forrest, M Sun, SY Hajdu, R Bergstrom, J Card, D Doherty, G Hale, J Keohane, C Meyers, C Milligan, J Mills, S Nomura, N Rosen, H Rosenbach, M Shei, GJ Singer, II Tian, M West, S White, V Xie, J Proia, RL Mandala, S AF Forrest, M Sun, SY Hajdu, R Bergstrom, J Card, D Doherty, G Hale, J Keohane, C Meyers, C Milligan, J Mills, S Nomura, N Rosen, H Rosenbach, M Shei, GJ Singer, II Tian, M West, S White, V Xie, J Proia, RL Mandala, S TI Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN-COUPLED RECEPTOR; VASCULAR MATURATION; IN-VITRO; T-CELLS; SPHINGOSINE-1-PHOSPHATE; FTY720; RAT; ACTIVATION; EXPRESSION; EDG-1 AB Sphingosine 1-phosphate (S1P) is a bioactive lysolipid with pleiotropic functions mediated through a family of G protein-coupled receptors, S1P(1,2,3,4,5). Physiological effects of S1P receptor agonists include regulation of cardiovascular function and immunosuppression via redistribution of lymphocytes from blood to secondary lymphoid organs. The phosphorylated metabolite of the immunosuppressant agent FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol) and other phosphonate analogs with differential receptor selectivity were investigated. No significant species differences in compound potency or rank order of activity on receptors cloned from human, murine, and rat sources were observed. All synthetic analogs were high-affinity agonists on S1P(1), with IC50 values for ligand binding between 0.3 and 14 nM. The correlation between S1P(1) receptor activation and the ED50 for lymphocyte reduction was highly significant (p < 0.001) and lower for the other receptors. In contrast to S1P(1)-mediated effects on lymphocyte recirculation, three lines of evidence link S1P(3) receptor activity with acute toxicity and cardiovascular regulation: compound potency on S1P(3) correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus bradycardia and hypertension was consistent with affinity for S1P(1) relative to S1P(3); and toxicity, bradycardia, and hypertension were absent in S1P(3)(-/-) mice. Blood pressure effects of agonists in anesthetized rats were complex, whereas hypertension was the predominant effect in conscious rats and mice. Immunolocalization of S1P(3) in rodent heart revealed abundant expression on myocytes and perivascular smooth muscle cells consistent with regulation of bradycardia and hypertension, whereas S1P(1) expression was restricted to the vascular endothelium. C1 Merck Res Labs, Dept Immunol & Rheumatol, Rahway, NJ 07065 USA. Merck Res Labs, Dept Pharmacol, Rahway, NJ 07065 USA. Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA. NIH, Bethesda, MD 20892 USA. RP Mandala, S (reprint author), Merck Res Labs, Dept Immunol & Rheumatol, POB 2000,RY80Y-215, Rahway, NJ 07065 USA. EM Suzanne_mandala@merck.com RI Proia, Richard/A-7908-2012 NR 40 TC 227 Z9 231 U1 0 U2 2 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 1 PY 2004 VL 309 IS 2 BP 758 EP 768 DI 10.1124/jpet.103.062828 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814KF UT WOS:000220972900041 PM 14747617 ER PT J AU Yu, LR Conrads, TP Uo, T Issaq, HJ Morrison, RS Veenstra, TD AF Yu, LR Conrads, TP Uo, T Issaq, HJ Morrison, RS Veenstra, TD TI Evaluation of the acid-cleavable isotope-coded affinity tag reagents: Application to camptothecin-treated cortical neurons SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE isotope-coded affinity tags; quantitative proteomics; mass spectrometry; cortical neurons ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; QUANTITATIVE PROTEOMICS; PEPTIDES; PROTEIN AB The new generation of isotope-coded affinity tag (ICAT) reagents have been evaluated by labeling an equimolar amount of bovine serum albumin (BSA) with ICAT-C-12(9) and ICAT-C-13(9), combining the mixtures, digesting them with trypsin and analyzing the digestate both by muRPLC-tandem MS and by matrix-assisted laser desorption ionization (MALDI) TOF/TOF MS. The use of C-13 in place of H-2 resulted in both of the labeled peptides having identical elution characteristics in a reversed-phase separation. This similarity in elution allows ICAT-labeled peptides to be effectively analyzed using a muRPLC-MALDI-MS strategy as well. All of the cysteinyl-containing tryptic peptides from BSA were identified with only a 10% variation in the relative abundance measurements between the light and heavy versions of each peptide. A facile method for the removal of contaminants that arise from the cleaved biotin moiety that otherwise interfere with downstream separations and MS analysis has also been developed. The new ICAT reagents were then applied to the analysis of a cortical neuron proteome sample to identify proteins regulated by the antitumor drug, camptothecin. C1 NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, POB B,Bldg 469,Rm 160, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400]; NINDS NIH HHS [NS35533] NR 19 TC 44 Z9 48 U1 3 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAY-JUN PY 2004 VL 3 IS 3 BP 469 EP 477 DI 10.1021/pr034090t PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 829UK UT WOS:000222075500015 PM 15253428 ER PT J AU Woods, AS AF Woods, AS TI The mighty arginine, the stable quaternary amines, the powerful aromatics, and the aggressive phosphate: Their role in the noncovalent minuet SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE noncovalent interactions; quaternary amines; phosphate moieties ID ASSISTED-LASER-DESORPTION/IONIZATION; CATION-PI INTERACTIONS; NICOTINIC ACETYLCHOLINE-RECEPTOR; MASS-SPECTROMETRY; GAS-PHASE; LIGAND RECOGNITION; BINDING-ENERGIES; HALIDE-IONS; METAL-IONS; MATRIX AB In the age of proteomics, the role of certain amino acid residues and some post-translational modifications in noncovalent complex formation are gaining in importance, as the understanding of interactions between biological molecules, is at the heart of the structure function relationship puzzle. In this work, mass spectrometry is used to highlight ammonium- or guaniclinium-aromatic interactions through Cation-pi bonds and ammonium- or guanidinium-phosphate interactions through salt bridge formation. Such interactions are crucial factors in certain ligand-receptor interactions and receptor-receptor interactions. In addition, the ability of phosphorylated residues and phosphorylated lipids to form noncovalent complexes with guanidinium and quaternary ammonium (mostly through Coulombic interactions) is demonstrated, and could explain the stability Of Certain membrane embedded protein, or a possible role for phosphorylation in protein-protein interactions. Dougherty's work demonstrates cation-pi interactions in intra-protein interactions and folding, the present work explores inter-peptide interactions, i.e., the formation of noncovalent complexes between peptides' epitopes containing adjacent aromatic residues and ones containing adjacent Arg as a model to better understand the role of cation-pi complexes in protein-protein interaction. Complexes of peptides containing aromatic residues with quaternary amines as well as the interaction of aromatic compounds, with the guanidinium group of Arg are also investigated. Considering that an inordinate number of therapeutic compounds contain aromatic rings and quaternary amines, the above-described interactions could possibly be of great importance in better understanding their mechanism of action. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov NR 44 TC 76 Z9 76 U1 5 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAY-JUN PY 2004 VL 3 IS 3 BP 478 EP 484 DI 10.1021/pr034091I PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 829UK UT WOS:000222075500016 PM 15253429 ER PT J AU Wisniewski, SR Stegman, D Trivedi, M Husain, MM Eng, H Shores-Wilson, K Luther, J Biggs, MM Burroughs, D Ritz, AL Fava, M Quitkin, F Rush, AJ AF Wisniewski, SR Stegman, D Trivedi, M Husain, MM Eng, H Shores-Wilson, K Luther, J Biggs, MM Burroughs, D Ritz, AL Fava, M Quitkin, F Rush, AJ CA STAR D Investigators TI Methods of testing feasibility for sequenced treatment alternatives to relieve depression (STAR*D) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; treatment; trials; feasibility; procedures; functionality ID RATING-SCALE; SYMPTOMATOLOGY IDS; PATIENT; QUESTIONNAIRE; INVENTORY; CLAIMS; HEALTH; WORK; CARE AB In large multi-site trials, a feasibility or pilot study can be crucial to test the functionality of all aspects of conducting the study prior to the initiation of the formal study. A feasibility trial was conducted for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Project, a multi-site, prospective, sequentially randomized, clinical trial of outpatients with nonpsychotic major depressive disorder. From 14 December 2000 to 8 June 2001, 42 patients were screened for enrollment into the STAR*D Feasibility Trial. Twenty-four patients who were eligible and consented to participate were treated with citalopram for up to 12 weeks. During the course of this trial, issues were raised that resulted in modifications to the study procedures. Modifications made as a result of this trial affected four domains: (1) communication, (2) patient and provider burden, (3) data collection forms, and (4) recruitment and retention of subjects. This paper describes what was learned during the STAR*D Feasibility Trial so researchers planning to conduct similar trials can learn the practical issues related to conducting such a research project. While the information gathered was useful, it did delay the initiation of the formal trial. We view this cost as an investment in the development of overall study procedures that should lead to a stronger study. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. NIMH, Bethesda, MD 20892 USA. Healthcare Technol Syst, Madison, WI 53717 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. RP Wisniewski, SR (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM wisniew@edc.pitt.edu RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 28 TC 6 Z9 6 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-JUN PY 2004 VL 38 IS 3 BP 241 EP 248 DI 10.1016/j.jpsychires.2003.06.001 PG 8 WC Psychiatry SC Psychiatry GA 804YU UT WOS:000220334800004 PM 15003429 ER PT J AU Ward, MM AF Ward, MM TI Relative sensitivity to change of the erythrocyte sedimentation rdte and serum C-reactive protein concentration in rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; C-reactive protein; erythrocyte sedimentation rate; sensitivity to change ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; MODIFYING ANTIRHEUMATIC DRUGS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; NECROSIS-FACTOR-ALPHA; LOW-DOSE METHOTREXATE; CYCLOSPORINE-A; DISEASE-ACTIVITY; COMBINATION THERAPY; CLINICAL-TRIALS AB Objective. To compare the sensitivity to change of the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) concentration used as measures of rheumatoid arthritis (RA) activity. Methods. A literature search was conducted to identify all clinical trials and observational studies of disease-modifying medications and corticosteroids in RA that reported results for both ESR and CRP before treatment and 4 weeks to 24 weeks after treatment in the same patients. For each test, effect sizes were computed as the change in the test with treatment divided by the pretreatment standard deviation. A pooled analysis was performed on the paired differences in effect sizes for ESR and CRP within each study. Results. One hundred twenty-three studies with 184 active treatment arms were identified that included measurements of both ESR and CRP Sixty-three studies with 90 active treatment arms provided sufficient data to permit calculation of effect sizes, and were included in the analysis. In the 36 treatment arms that reported results at 12 weeks, the ESR was more sensitive to change than the CRP, with a paired difference in effect sizes of 0.09 units (95% confidence interval 0.03, 0.15; p = 0.005). In the 76 treatment arms that reported results at 24 weeks, the ESR was also more sensitive to change than the CRP, with a paired difference in effect sizes of 0.11 units (95% Cl 0.05, 0.17; p = 0.0004). Conclusion. In these studies of disease-modifying medications in RA, the ESR was more sensitive to change than the CRP at 12 weeks and 24 weeks of treatment. Few studies examined changes in these measures at times earlier than 12 weeks. C1 NIAMSD, Intramural Res Program, UD Dept HHS, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, UD Dept HHS, NIH, Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 75 TC 21 Z9 23 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2004 VL 31 IS 5 BP 884 EP 895 PG 12 WC Rheumatology SC Rheumatology GA 818LJ UT WOS:000221246300010 PM 15124246 ER PT J AU Pianta, RC AF Pianta, RC TI Untitled SO JOURNAL OF SCHOOL PSYCHOLOGY LA English DT Editorial Material C1 Univ Virginia, NICHD Study Early Child Care, Charlottesville, VA 22908 USA. RP Pianta, RC (reprint author), Univ Virginia, NICHD Study Early Child Care, POB 800784, Charlottesville, VA 22908 USA. EM rcp4p@virginia.edu OI Pianta, Robert/0000-0002-6280-8051 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 0022-4405 J9 J SCHOOL PSYCHOL JI J. Sch. Psychol. PD MAY-JUN PY 2004 VL 42 IS 3 BP 177 EP 178 DI 10.1016/j.jsp.2004.03.001 PG 2 WC Psychology, Educational SC Psychology GA 840OZ UT WOS:000222870100001 ER PT J AU Adams, JS Chen, H Chun, R Gacad, MA Encinas, C Ren, SY Nguyen, L Wu, SX Hewison, M Barsony, J AF Adams, JS Chen, H Chun, R Gacad, MA Encinas, C Ren, SY Nguyen, L Wu, SX Hewison, M Barsony, J TI Response element binding proteins and intracellular vitamin D binding proteins: novel regulators of vitamin D trafficking, action and metabolism SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE vitamin D; binding proteins; receptors; transcription; resistance; metabolism; traffic; heat shock proteins; heterogeneous nuclear ribonucleoproteins ID WORLD PRIMATE CELLS; D-DIRECTED TRANSACTIVATION; D-RECEPTOR; FUNCTIONAL-CHARACTERIZATION; 1,25-DIHYDROXYVITAMIN D3; 25-HYDROXYVITAMIN D-3; D RESISTANCE; PLATYRRHINI; CATARRHINI; FAMILY AB Using vitamin D-resistant New World primates as model of natural diversity for sterol/steroid action and metabolism, two families of novel intracellular vitamin D regulatory proteins have been discovered and their human homologs elucidated. The first family of proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs), initially considered to function only as pre-mRNA-interacting proteins, have been demonstrated to be potent cis-acting, trans-dominant regulators of vitamin D hormone-driven gene transactivation. The second group of proteins bind 25-hydroxylated vitamin D metabolites. Their overexpression increases vitamin D receptor (VDR)-directed target gene expression. We found that these intracellular vitamin D binding proteins (IDBPs) are homologous to proteins in the heat shock protein-70 family. Our ongoing studies indicate directly or indirectly through a series of protein interactions that the IDBPs interact with hydroxylated vitamin D metabolites and facilitate their intracellular targeting. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Burns & Allen Res Inst, Los Angeles, CA 90024 USA. Univ Birmingham, Dept Med Sci, Birmingham B15 2TT, W Midlands, England. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Adams, JS (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Burns & Allen Res Inst, B131,8700 Beverly Blvd, Los Angeles, CA 90024 USA. RI Adams, John/I-3365-2013; Chun, Rene/A-9415-2010 OI Adams, John/0000-0001-9607-5020; Chun, Rene/0000-0002-0190-0807 FU NIAMS NIH HHS [AR37399]; NIDDK NIH HHS [DK58891] NR 27 TC 45 Z9 45 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD MAY PY 2004 VL 89-90 IS 1-5 SI SI BP 461 EP 465 DI 10.1016/j.jsbmb.2004.03.016 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 840IS UT WOS:000222852500085 PM 15225821 ER PT J AU Rapuri, PB Gallagher, JC Knezetic, JA Kinyamu, HK Ryschon, KL AF Rapuri, PB Gallagher, JC Knezetic, JA Kinyamu, HK Ryschon, KL TI Association between vitamin D receptor polymorphisms and the rate of bone loss in elderly women - importance of adjusting for dietary and lifestyle factors SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE VDR genotypes; bone loss; dietary; lifestyle; postmenopausal ID POSTMENOPAUSAL CAUCASIAN WOMEN; START CODON POLYMORPHISM; MINERAL DENSITY; GENE POLYMORPHISMS; CALCIUM INTAKE; MASS; OSTEOPOROSIS; GENOTYPES; DETERMINANTS; ALLELES AB The association between the restriction length polymorphisms of the Vitamin D receptor (VDR) gene and the bone mineral density (BMD) or the rate of bone loss is still under debate. In a longitudinal study of untreated postmenopausal elderly women, we evaluated the relationship between the VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and the rate of bone loss over a 3-year period. We also examined the effect of adjustments for dietary and lifestyle factors on these associations. Before adjustments, the rate of femoral neck bone loss was -3.76 +/- 1.58% in women with BB genotype and 0.45 +/- 0.65% in women with bb genotype, which was not significantly different. Upon adjustment for dietary and lifestyle factors, statistically significant (P = 0.03) bone loss was observed at femoral neck in women with BB genotype (-3.66 +/- 2.44%) compared to that of bb genotype (2.39 +/- 1.32%). Similar results were observed with TaqI genotypes. The rates of bone loss at other skeletal sites were not different between VDR genotypes defined by BsmI and TaqI. VDR gene polymorphisms defined by Apal and Fokl were not related to the rate of bone loss. (C) 2004 Elsevier Ltd. All rights reserved. C1 Creighton Univ, Sch Med, Bone Metab Unit, Omaha, NE 68131 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Ryschon Hlth & Technol Serv, Valentine, NE 69201 USA. RP Rapuri, PB (reprint author), Creighton Univ, Sch Med, Bone Metab Unit, Room 6718,601 N 30th St, Omaha, NE 68131 USA. EM thiyyari@creighton.edu FU NIA NIH HHS [UO1-AG10373, R01-AG10358] NR 21 TC 13 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD MAY PY 2004 VL 89-90 IS 1-5 SI SI BP 503 EP 506 DI 10.1016/j.jsbmb.2004.03.060 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 840IS UT WOS:000222852500092 PM 15225828 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Development of effective immunotherapy for the treatment of patients with cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 89th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 19-23, 2003 CL CHICAGO, IL SP Amer Coll Surg ID TUMOR-INFILTRATING LYMPHOCYTES; DOSE RECOMBINANT INTERLEUKIN-2; METASTATIC MELANOMA; GP100 MELANOMA; T-CELLS; GENE-THERAPY; ANTIGEN; RESPONSES; IDENTIFICATION; GENERATION C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [Z01 SC003811-31] NR 38 TC 40 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2004 VL 198 IS 5 BP 685 EP 696 DI 10.1016/j.jamcollsurg.2004.01.025 PG 12 WC Surgery SC Surgery GA 816XK UT WOS:000221142400001 PM 15110801 ER PT J AU Subar, AF AF Subar, AF TI Developing dietary assessment tools SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID CHILDREN C1 NCI, Div Canc Control & Populat Si, Bethesda, MD 20892 USA. RP Subar, AF (reprint author), NCI, Div Canc Control & Populat Si, Bethesda, MD 20892 USA. NR 5 TC 46 Z9 47 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 2004 VL 104 IS 5 BP 769 EP 770 DI 10.1016/j.jada.2004.02.007 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 817WB UT WOS:000221206500012 PM 15127062 ER PT J AU Penninx, BWJH Pahor, M Cesari, M Corsi, AM Woodman, RC Bandinelli, S Guralnik, JM Ferrucci, L AF Penninx, BWJH Pahor, M Cesari, M Corsi, AM Woodman, RC Bandinelli, S Guralnik, JM Ferrucci, L TI Anemia is associated with disability and decreased physical performance and muscle strength in the elderly SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE InCHIANTI; anemia; strength; physical performance; disability; older persons ID OLDER PERSONS; IRON-DEFICIENCY; INFLAMMATION; WOMEN; PREVALENCE; DECLINE; PEOPLE; INTERLEUKIN-6; POPULATION; PREDICTOR AB OBJECTIVES: To examine the association between anemia and disability, physical performance, and muscle strength in older persons. DESIGN: Cross-sectional. SETTING: Community-dwelling older persons in the Chianti area in Italy. PARTICIPANTS: A total of 1,156 persons aged 65 and older participating in the InChianti Study ("Invecchiare in Chianti," i.e., Aging in the Chianti Area). MEASUREMENTS: Anemia was defined according to World Health Organization criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men. Disability in six basic and eight instrumental activities of daily living was assessed. Physical performance was assessed using the short physical performance battery (4-m walk, balance, and chair stands), which yields a summary performance score ranging from 0 to 12 (high). Muscle strength was determined using knee extensor and handgrip strength assessments. RESULTS: Overall, 11.1% of the men and 11.5% of the women had anemia. After adjustment for age, sex, body mass index, Mini-Mental State Examination score, creatinine level, and presence of various comorbid conditions, anemic persons had more disabilities (1.71 vs 1.04, P=.002) and poorer performance (8.8 vs 9.6, P=.003) than persons without anemia. Anemic persons also had significantly lower knee extensor strength (14.1 vs 15.2 kg, P=.02) and lower handgrip strength (25.3 vs 27.1 kg, P=.04) than persons without anemia. Further adjustment for inflammatory markers (interleukin-6, C-reactive protein, tumor necrosis factor-alpha) did not change these associations. CONCLUSION: Anemia is associated with disability, poorer physical performance, and lower muscle strength. Further research should explore whether treating anemia has a beneficial effect on the functional status of older persons. C1 Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. Natl Res Inst, Geriatr Dept I Fraticini, Florence, Italy. Ortho Biotech Prod LP, Bridgewater, NJ USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Penninx, BWJH (reprint author), Vrije Univ Amsterdam, Dept Psychiat, Valeriuspl 9, NL-1075 BG Amsterdam, Netherlands. EM Brendap@ggzba.nl RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 FU NIA NIH HHS [P30AG021332-01] NR 33 TC 205 Z9 213 U1 0 U2 11 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 2004 VL 52 IS 5 BP 719 EP 724 DI 10.1111/j.1532-5415.2004.52208.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812QZ UT WOS:000220855300009 PM 15086651 ER PT J AU Cowell, J Zeng, Q Ngo, L Lacroix, EM AF Cowell, J Zeng, Q Ngo, L Lacroix, EM TI A frequency-based technique to improve the spelling suggestion rank in medical queries SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID UNDETECTED TYPING ERRORS; WORDS AB Objective: There is an abundance of health-related information online, and millions of consumers search for such information. Spell checking is of crucial importance in returning pertinent results, so the authors propose a technique for increasing the effectiveness of spell-checking tools used for health-related information retrieval. Design: A sample of incorrectly spelled medical terms was submitted to two different spell-checking tools, and the resulting suggestions, derived under two different dictionary configurations, were re-sorted according to how frequently each term appeared in log data from a medical search engine. Measurements: Univariable analysis was carried out to assess the effect of each factor (spell-checking tool, dictionary type, re-sort, or no re-sort) on the probability of success. The factors that were statistically significant in the univariable analysis were then used in multivariable analysis to evaluate the independent effect of each of the factors. Results: The re-sorted suggestions proved to be significantly more accurate than the original list returned by the spell-checking tool. The odds of finding the correct suggestion in the number one rank were increased by 63% after re-sorting using the authors' method. This effect was independent of both the dictionary and the spell-checking tools that were used. Conclusion: Using knowledge about the frequency of a given word's occurrence in the medical domain can significantly improve spelling correction for medical queries. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Decis Syst Grp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Natl Lib Med, Publ Serv Div, Bethesda, MD 20209 USA. RP Cowell, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Decis Syst Grp, Boston, MA 02115 USA. EM jcrowell@dsg.bwh.harvard.edu NR 28 TC 0 Z9 0 U1 1 U2 4 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2004 VL 11 IS 3 BP 179 EP 185 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 822NK UT WOS:000221546700004 ER PT J AU Levy, JA Bergeson, J Putnam, K Rosen, V Cohen, R Lalonde, F Mirza, N Linker, G Sunderland, T AF Levy, JA Bergeson, J Putnam, K Rosen, V Cohen, R Lalonde, F Mirza, N Linker, G Sunderland, T TI Context-specific memory and apolipoprotein E (ApoE)epsilon 4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Alzheimer risk; context-specific memory; apolipoprotein E ID E EPSILON-4 ALLELE; ENTORHINAL CORTEX NEURONS; E GENOTYPE; HIPPOCAMPAL-FORMATION; RECALL PERFORMANCE; GLUCOSE-METABOLISM; PRECLINICAL PHASE; BRAIN ACTIVATION; TYPE-4 ALLELE; APOE GENOTYPE AB The aim of the study was to determine whether the epsilon4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the epsilon4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale-Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of epsilon4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an epsilon4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative epsilon4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies. C1 NIMH, Geriatr Psychiat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Levy, JA (reprint author), NIMH, Geriatr Psychiat Branch, NIH, US Dept HHS, 9000 Rockville Pike,Bldg 10 3N228,MSC 1275, Bethesda, MD 20892 USA. EM jameslevy@mail.nih.gov NR 84 TC 28 Z9 31 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2004 VL 10 IS 3 BP 362 EP 370 DI 10.1017/S1355617704103044 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 817MB UT WOS:000221180500006 PM 15147594 ER PT J AU Hwang, JJ Walther, MM Pautler, SE Coleman, JA Hvizda, J Peterson, J Linehan, WM Wood, BJ AF Hwang, JJ Walther, MM Pautler, SE Coleman, JA Hvizda, J Peterson, J Linehan, WM Wood, BJ TI Radio frequency ablation of small renal tumors: Intermediate results SO JOURNAL OF UROLOGY LA English DT Article DE laparoscopy; kidney neoplasms ID CELL CARCINOMA; RADIOFREQUENCY ABLATION; CLINICAL-EXPERIENCE; CANCER; NEPHRECTOMY; MODEL; VIVO AB Purpose: With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA. Materials and Methods: Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals. Results: Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean standard mean of error) were 243 29 minutes and 67 +/- 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair. Conclusions: At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic criteria of successful RFA treatment. RFA treatment of small renal tumors using the Radionics system appears to result in superior treatment outcomes compared to those of earlier series with lower radio frequency power generators. A high wattage generator might attain more consistent energy deposition with subsequent cell death in the targeted tissue due to less convective heat loss. C1 NCI, Urol Oncol Branch, DCT, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, DCT, NIH, Bldg 10,Room 2B47,10 Ctr Dr,MSC 1501, Bethesda, MD 20892 USA. EM macw@nih.gov OI Coleman, Jonathan/0000-0002-6428-7835 FU Intramural NIH HHS [Z99 CL999999] NR 14 TC 103 Z9 108 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2004 VL 171 IS 5 BP 1814 EP 1818 DI 10.1097/01.ju.0000119905.72574.de PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 812XS UT WOS:000220872800010 PM 15076283 ER PT J AU Kim, Y Brown, TP AF Kim, Y Brown, TP TI Development of quantitative competitive-reverse transcriptase-polymerase chain reaction for detection and quantitation of avian leukosis virus subgroup J SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article ID CHICKENS; RNA; GENE; ENV; PCR AB Infection with avian leukosis virus subgroup J (ALV-J) causes severe economic losses in the broiler industry by increasing mortality, producing tumors, and decreasing weight gain in chickens. The quantitation of ALV-J is difficult because of its failure to produce a cytopathic effect in cell culture systems and the nonspecificity of antigen-capture enzyme-linked immunosorbent assay (ELISA) tests. This study was performed to develop a quantitative competitive-reverse transcriptase-polymerase chain reaction (QC-RT-PCR) method based on coamplification of ALV-J genomic RNA and a known amount of a synthesized RNA competitor. The 369 bp RNA competitor was constructed by restriction enzyme treatment of an ALV-J specific 545 bp PCR product, ligation, transformation into Escherichia coli, and in vitro transcription. The competitor contained the same amplification primer annealing sites and sequence as the original viral RNA, except that it had a 176 bp internal deletion. Coamplified RT-PCR products were visualized by electrophoresis and ethidium bromide staining, and fluorescences were quantified using computer-assisted image analysis. The sensitivity of this new QC-RT-PCR method was 25 fg of viral RNA, and 10-fold dilutions were differentiable. This method allowed absolute and relative quantification of ALV-J RNA copy numbers and was simpler than previously published methods for ALV-J quantification. C1 Univ Georgia, Coll Vet Med, Dept Vet Pathol, Athens, GA 30602 USA. Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. RP Kim, Y (reprint author), NIEHS, Lab Expt Pathol, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA. NR 18 TC 7 Z9 10 U1 0 U2 2 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD MAY PY 2004 VL 16 IS 3 BP 191 EP 196 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 873TC UT WOS:000225302900003 PM 15152832 ER PT J AU Montella, M Serraino, D Crispo, A Romano, N Fusco, M Goedert, JJ AF Montella, M Serraino, D Crispo, A Romano, N Fusco, M Goedert, JJ TI Infection with human herpes virus type 8 in an area at high prevalence for hepatitis C virus infection in southern Italy SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE co-infection; hepatitis C virus; human herpesvirus type 8; prevalence; southern Italy ID MOTHER-TO-CHILD; RISK-FACTORS; GENERAL-POPULATION; KAPOSIS-SARCOMA; PREGNANT-WOMEN; BLOOD-BORNE; TRANSMISSION; HUMAN-HERPESVIRUS-8 AB The Campania Region is a geographical area of southern Italy characterized by high incidence rates of hepatocellular carcinoma and of classic Kaposi's sarcoma. Epidemiological investigations carried out among different population groups in this region have found high prevalence rates of both hepatitis C virus (HCV) and human herpesvirus type 8 (HHV-8). To assess co-infection rates of HCV and HHV-8, we carried out a cross-sectional seroepidemiological study prevalence in Pomigliano d'Arco, a Health District of Campania located 20 km away from Naples. The overall rate of HCV/HHV-8 co-infection was 3.1%, 3.5% among men and 2.7% among women. No difference emerged in the HCV/HHV-8 co-infection rates according to seropositivity for HCV infection, either overall (Mantel Haenszel odds ratio = 1.2, 95% CI: 0.6-2.6) or when the analysis was stratified by gender. These findings support the hypothesis that in Campania common routes of transmission are rarely shared by HCV and HHV-8 infections. Local factors may result in different epidemiological patterns for these two viral infections. However. our findings have important public health implications, especially in Mediterranean countries where HCV and HHV-8 infections are endemic. C1 Fdn G Pascale, Ist Nazl Tumori, Serv Epidemiol, Rome, Italy. Canc Registry RTP, Campania Reg, Rome, Italy. IRCCS, Ist Nazl Malattie Infett Lazzaro Spallanzani, Dipartimento Epidemiol, Rome, Italy. Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe DAlessan, Palermo, Italy. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Montella, M (reprint author), Natl Canc Inst, Epidemiol Unit, Via Mariano Semmola, I-80131 Naples, Italy. EM epidemiologia.int@tin.it OI Crispo, Anna/0000-0002-8455-3328 NR 14 TC 5 Z9 5 U1 0 U2 1 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 2004 VL 11 IS 3 BP 268 EP 270 DI 10.1111/j.1365-2893.2004.00499.x PG 3 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 822FX UT WOS:000221525300011 PM 15117330 ER PT J AU Zhang, ZS Protzer, U Hu, ZY Jacob, J Liang, TJ AF Zhang, ZS Protzer, U Hu, ZY Jacob, J Liang, TJ TI Inhibition of cellular proteasome activities enhances hepadnavirus replication in an HBX-dependent manner SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-B-VIRUS; X-GENE PRODUCT; TRANSCRIPTION FACTORS; DNA-BINDING; IN-VIVO; PROTEIN; TRANSACTIVATION; CELLS; INTERFERON; ACTIVATION AB The X protein (HBX) of the hepatitis B virus (HBV) is not essential for the HBV life cycle in vitro but is important for productive infection in vivo. Our previous study suggests that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. With the woodchuck model, we demonstrated that the X-deficient mutants of woodchuck hepatitis virus (WHV) are not completely replication defective, possibly behaving like attenuated viruses. In the present study, we analyzed the effects of the proteasome inhibitors on the replication of wild-type and X-negative HBV and WHV. Recombinant adenoviruses or baculoviruses expressing replicating HBV or WHV genomes have been developed as a robust and convenient system to study viral replication in tissue culture. In cells infected with either the recombinant adenovirus-HBV or baculovirus-WHV, the replication level of the X-negative construct was about 10% of that of the wild-type virus. In the presence of proteasome inhibitors, the replication of the wild-type virus was not affected, while the replication of the X-negative virus of either HBV or WHV was enhanced and restored to the wild-type level. Our data suggest that HBX affects hepadnavirus replication through a proteasome-dependent pathway. C1 Univ Cologne, ZMMK, Inst Med Microbiol, Cologne, Germany. Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. EM JLiang@nih.gov NR 37 TC 63 Z9 70 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 2004 VL 78 IS 9 BP 4566 EP 4572 DI 10.1128/JVI.78.9.4566-4572.2004 PG 7 WC Virology SC Virology GA 813AO UT WOS:000220880200020 PM 15078938 ER PT J AU Rulli, K Yugawa, T Hanson, C Thompson, D Ruscetti, S Nishigaki, K AF Rulli, K Yugawa, T Hanson, C Thompson, D Ruscetti, S Nishigaki, K TI Ex vivo and in vivo biological effects of a truncated form of the receptor tyrosine kinase Stk when activated by interaction with the friend spleen focus-forming virus envelope glycoprotein or by point mutation SO JOURNAL OF VIROLOGY LA English DT Article ID MET HGF RECEPTOR; CONSTITUTIVE ACTIVATION; RESISTANT MICE; ERYTHROPOIETIN; ERYTHROLEUKEMIA; OVEREXPRESSION; CARCINOMAS; PROTEINS; GROWTH; CANCER AB The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope protein, gp55, which interacts with the erythropoietin (Epo) receptor complex, causing proliferation and differentiation of erythroid cells in the absence of Epo. Susceptibility to SFFV-induced erythroleukemia is conferred by the Fv-2 gene, which encodes a short form of the receptor tyrosine kinase Stk/Ron (sf-Stk) only in susceptible strains of mice. We recently demonstrated that sf-Stk becomes activated by forming a strong interaction with SFFV gp55. To examine the biological consequences of activated sf-Stk on erythroid cell growth, we prepared retroviral vectors which express sf-Stk, either in conjunction with gp55 or alone in a constitutively activated mutant form, and tested them for their ability to induce Epo-independent erythroid colonies ex vivo and disease in mice. Our data indicate that both gp55-activated sf-Stk and the constitutively activated mutant of sf-Stk induce erythroid cells from Fv-2-susceptible and Fv-2-resistant (sf-Stk null) mice to form Epo-independent colonies. Mutational analysis of sf-Stk indicated that a functional kinase domain and 8 of its 12 tyrosine residues are required for the induction of Epo-independent colonies. Further studies demonstrated that coexpression of SFFV gp55 with sf-Stk significantly extends the half-life of the kinase. When injected into Fv-2-resistant mice, neither the gp55-activated sf-Stk nor the constitutively activated mutant caused erythroleukemia. Surprisingly, both Fv-2-susceptible and -resistant mice injected with the gp55-sf-Stk vector developed clinical signs not previously associated with SFFV-induced disease. We conclude that sf-Stk, activated by either point mutation or interaction with SFFV gp55, is sufficient to induce Epo-independent erythroid colonies from both Fv-2-susceptible and -resistant mice but is unable to cause erythroleukemia in Fv-2-resistant mice. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Ruscetti, S (reprint author), NCI, Basic Res Lab, Bldg 469,Room 205, Frederick, MD 21702 USA. EM ruscetti@ncifcrf.gov NR 24 TC 17 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 2004 VL 78 IS 9 BP 4573 EP 4581 DI 10.1128/JVI.78.9.4573-4581.2004 PG 9 WC Virology SC Virology GA 813AO UT WOS:000220880200021 PM 15078939 ER PT J AU Men, R Yamashiro, T Goncalvez, AP Wernly, C Schofield, DJ Emerson, SU Purcell, RH Lai, CJ AF Men, R Yamashiro, T Goncalvez, AP Wernly, C Schofield, DJ Emerson, SU Purcell, RH Lai, CJ TI Identification of chimpanzee Fab fragments by repertoire cloning and production of a full-length humanized immunoglobulin G1 antibody that is highly efficient for neutralization of dengue type 4 virus SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE PROTEIN-E; HUMAN GERM-LINE; ANTIGENIC DETERMINANTS; E-GLYCOPROTEIN; PHAGE DISPLAY; YELLOW-FEVER; BINDING-SITE AB A safe and effective dengue vaccine is still not available. Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative for the prevention of dengue virus infection. Fab monoclonal antibodies to dengue type 4 virus (DENV-4) were recovered by repertoire cloning of bone marrow mRNAs from an immune chimpanzee and analyzed for antigen binding specificity, V-H and V-L sequences, and neutralizing activity against DENV-4 in vitro. Fabs 5A7, 3C1, 3E4, and 7G4 were isolated from a library constructed from a chimpanzee following intrahepatic transfection with infectious DENV-4 RNA. Fabs 5H2 and 5D9, which had nearly identical V-H Sequences but varied in their V-L sequences, were recovered from a library constructed from the same chimpanzee after superinfection with a mixture of DENV-1, DENV-2, and DENV-3. In radioimmunoprecipitation, Fab 5A7 precipitated only DENV-4 prM, and Fabs 3E4, 7G4, 5D9, and 5112 precipitated DENV-4 E but little or no prM. Fab 3E4 and Fab 7G4 competed with each other for binding to DENV-4 in an enzyme-linked immunosorbent assay, as did Fab 3C1 and Fab 5A7. Fab 5H2 recognized an epitope on DENV-4 that was separate from the epitope(s) recognized by other Fabs. Both Fab 5H2 and Fab 5D9 neutralized DENV-4 efficiently with a titer of 0.24 to 0.58 mug/ml by plaque reduction neutralization test (PRNT), whereas DENV-4-neutralizing activity of other Fabs was low or not detected. Fab 5H2 was converted to full-length immunoglobulin G1 (IgG1) by combining it with human sequences. The humanized chimpanzee antibody IgG1 5H2 produced in CHO cells neutralized DENV-4 strains from different geographical origins at a similar 50% plaque reduction (PRNT50) titer of 0.03 to 0.05 mug/ml. The DENV-4 binding affinities were 0.42 nM for Fab 5H2 and 0.24 nM for full-length IgG1 5H2. Monoclonal antibody IgG1 5H2 may prove valuable for passive immunoprophylaxis against dengue virus in humans. C1 NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lai, CJ (reprint author), NIAID, Mol Viral Biol Sect, Infect Dis Lab, NIH, 50 South Dr,MSC 8009, Bethesda, MD 20892 USA. EM clai@niaid.nih.gov NR 65 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 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4665 EP 4674 DI 10.1128/JVI.78.9.4665-4674.2004 PG 10 WC Virology SC Virology GA 813AO UT WOS:000220880200031 PM 15078949 ER PT J AU Fernandez-Vega, V Sosnovtsev, SV Belliot, G King, AD Mitra, T Gorbalenya, A Green, KY AF Fernandez-Vega, V Sosnovtsev, SV Belliot, G King, AD Mitra, T Gorbalenya, A Green, KY TI Norwalk virus N-terminal nonstructural protein is associated with disassembly of the Golgi complex in transfected cells SO JOURNAL OF VIROLOGY LA English DT Article ID FELINE CALICIVIRUS GENOME; HEMORRHAGIC-DISEASE VIRUS; GASTROENTERITIS OUTBREAKS; ENTERIC CALICIVIRUSES; ENCODED PROTEINASE; CYTOPLASMIC TAIL; DOWN-REGULATION; CLEAVAGE SITES; INFECTED CELLS; RNA AB Norwalk virus is the prototype strain for members of the genus Norovirus in the family Caliciviridae, which are associated with epidemic gastroenteritis in humans. The nonstructural protein encoded in the N-terminal region of the first open reading frame (ORF1) of the Norwalk virus genome is analogous in gene order to proteins 2A and 2B of the picornaviruses; the latter is known for its membrane-associated activities. Confocal microscopy imaging of cells transfected with a vector plasmid that provided expression of the entire Norwalk virus N-terminal protein (amino acids 1 to 398 of the ORF1 polyprotein) showed colocalization of this protein with cellular proteins of the Golgi apparatus. Furthermore, this colocalization was characteristically associated with a visible disassembly of the Golgi complex into discrete aggregates. Deletion of a predicted hydrophobic region (amino acids 360 to 379) in a potential 2B-like (2BL) region (amino acids 301 to 398) near the C terminus of the Norwalk virus N-terminal protein reduced Golgi colocalization and disassembly. Confocal imaging was conducted to examine the expression characteristics of fusion proteins in which the 2BL region from the N-terminal protein of Norwalk virus (a genogroup I norovirus) or MD145 (a genogroup II norovirus) was fused to the C terminus of enhanced green fluorescent protein. Expression of each fusion protein in cells showed evidence for its colocalization with the Golgi apparatus. These data indicate that the N-terminal protein of Norwalk virus interacts with the Golgi apparatus and may play a 2BL role in the induction of intracellular membrane rearrangements associated with positive-strand RNA virus replication in cells. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Leiden Univ, Ctr Med, Dept Med Microbiol, Leiden, Netherlands. RP Green, KY (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6318,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kgreen@niaid.nih.gov RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 NR 49 TC 42 Z9 43 U1 1 U2 6 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 2004 VL 78 IS 9 BP 4827 EP 4837 DI 10.1128/JVI.78.9.4827-4837.2004 PG 11 WC Virology SC Virology GA 813AO UT WOS:000220880200046 PM 15078964 ER PT J AU Emerson, SU Nguyen, H Graff, J Stephany, DA Brockington, A Purcell, RH AF Emerson, SU Nguyen, H Graff, J Stephany, DA Brockington, A Purcell, RH TI In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein SO JOURNAL OF VIROLOGY LA English DT Article ID ORF3 PROTEIN; UNITED-STATES; CELL-CULTURE; RNA; SWINE; INFECTION; PREVALENCE; STRAINS; IDENTIFICATION; ANTIBODIES AB Hepatitis E virus (HEV) RNA replication occurred in seven of nine primate cell cultures transfected with in vitro transcripts of an infectious cDNA clone. Cell-to-cell spread did not occur in cell cultures, but rhesus monkeys inoculated with lysates of HEV-transfected PLC/PRF/5 and Huh-7 cells became infected with HEV. A replicon with the ORF2 and ORF3 genes deleted and replaced with the green fluorescent protein gene also replicated in the same primate cells that supported the replication of the full-length genome. Fluorescence-activated cell sorter analysis confirmed that the 7mG cap structure was critical for efficient infectivity, although replication could be initiated at a very low level in its absence. HEV virions were also able to infect a limited number of cells of certain lines. C1 NIAID, Mol Hepatitis Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Res Technol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Flow Cytometry Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), Bldg 50,Room 6537,50 South Dr,MSC-8009, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov FU NIAID NIH HHS [1-AO-02733, N01AO02733] NR 33 TC 79 Z9 89 U1 2 U2 8 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 2004 VL 78 IS 9 BP 4838 EP 4846 DI 10.1128/JVI.78.9.4838-4846.2004 PG 9 WC Virology SC Virology GA 813AO UT WOS:000220880200047 PM 15078965 ER PT J AU Seth, P Diaz, F Tao-Cheng, JH Major, EO AF Seth, P Diaz, F Tao-Cheng, JH Major, EO TI JC virus induces nonapoptotic cell death of human central nervous system progenitor cell-derived astrocytes SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HUMAN BRAIN; APOPTOSIS; INFECTION; DISEASE; EXPRESSION; CASPASES; DAMAGE; PATHOGENESIS; LYMPHOCYTES AB JC virus (JCV), a human neurotropic polyomavirus, demonstrates a selective glial cell tropism that causes cell death through lytic infection. Whether these cells die via apoptosis or necrosis following infection with JCV remains unclear. To investigate the mechanism of virus-induced cell death, we used a human central nervous system progenitor-derived astrocyte cell culture model developed in our laboratory. Using in situ DNA hybridization, inummocytochemistry, electron microscopy, and an RNase protection assay, we observed that astrocytes support a progressive JCV infection, which eventually leads to nonapoptotic cell death. Infected astrocyte cell cultures showed no difference from noninfected cells in mRNA expression of the caspase family genes or in any ultrastructural features associated with apoptosis. Infected cells demonstrated striking necrotic features such as cytoplasmic vacuolization, watery cytoplasm, and dissolution of organelles. Furthermore, staining for caspase-3 and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling were not detected in infected astrocyte cultures. Our findings suggest that JCV-induced cell death of these progenitor cell-derived astrocytes does not utilize an apoptosis pathway but exhibits a pattern of cell destruction consistent with necrotic cell death. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. NINDS, Electron Microscopy Facil, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Room 5W21,36 Convent Dr, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov NR 40 TC 20 Z9 21 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 2004 VL 78 IS 9 BP 4884 EP 4891 DI 10.1128/JVI.78.9.4884-4891.2004 PG 8 WC Virology SC Virology GA 813AO UT WOS:000220880200051 PM 15078969 ER PT J AU Mitra, T Sosnovtsev, SV Green, KY AF Mitra, T Sosnovtsev, SV Green, KY TI Mutagenesis of tyrosine 24 in the VPg protein is lethal for feline calicivirus SO JOURNAL OF VIROLOGY LA English DT Article ID GENOME-LINKED PROTEIN; COWPEA MOSAIC-VIRUS; HEMORRHAGIC-DISEASE VIRUS; CLEAVAGE SITES; NONSTRUCTURAL POLYPROTEIN; PHOSPHODIESTER LINKAGE; MUTATIONAL ANALYSIS; POLIOVIRUS RNA; INFECTED-CELLS; VIRAL-RNA AB The genome of feline calicivirus (FCV) is an similar to7.7-kb single-stranded positive-sense RNA molecule that is polyadenylated at its 3' end and covalently linked to a VPg protein (calculated mass, 12.6 kDa) at its 5' end. We performed a mutational analysis of the VPg protein in order to identify amino acids potentially involved in linkage to the genome and replication. The tyrosine residues at positions 12, 24, 76, and 104 were changed to alanines by mutagenesis of an infectious FCV cDNA clone. Viruses were recovered when Tyr-12, Tyr-76, or Tyr-104 of the VPg protein was changed to alanine, but virus was not recovered when Tyr-24 was changed to alanine. Growth properties of the recovered viruses were similar to those of the parental virus. We examined whether the amino acids serine, threonine, and phenylalanine could substitute for the tyrosine at position 24, but these mutations were lethal as well. A tyrosine at this relative position is conserved among all calicivirus VPg proteins examined thus far, suggesting that the VPg protein of caliciviruses, like those of picornaviruses and potyviruses, utilizes tyrosine in the formation of a covalent bond with RNA. C1 NIAID, LID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Green, KY (reprint author), NIAID, LID, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 50,Room 6318, Bethesda, MD 20892 USA. EM kgreen@niaid.nih.gov NR 35 TC 23 Z9 26 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 2004 VL 78 IS 9 BP 4931 EP 4935 DI 10.1128/JVI.78.9.4931-4935.2004 PG 5 WC Virology SC Virology GA 813AO UT WOS:000220880200059 PM 15078978 ER PT J AU Doh-Ura, K Ishikawa, K Murakami-Kubo, I Sasaki, K Mohri, S Race, R Iwaki, T AF Doh-Ura, K Ishikawa, K Murakami-Kubo, I Sasaki, K Mohri, S Race, R Iwaki, T TI Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN PRP; SULFATED GLYCANS; CULTURED-CELLS; SCRAPIE; PROLONG; MICE; SUSCEPTIBILITY; ACCUMULATION; QUINACRINE AB The therapeutic efficacy of direct drug infusion into the brain, the target organ of transmissible spongiform encephalopathies, was assessed in transgenic mice intracerebrally infected with 263K scrapie agent. Pentosan polysulfate (PPS) gave the most dramatic prolongation of the incubation period, and amphotericin B had intermediate effects, but antimalarial drugs such as quinacrine gave no significant prolongation. Treatment with the highest dose of PPS at an early or late stage of the infection prolonged the incubation time by 2.4 or 1.7 times that of the control mice, respectively. PPS infusion decreased not only abnormal prion protein deposition but also neurodegenerative changes and infectivity. These alterations were observed within the brain hemisphere fitted with an intraventricular infusion cannula but not within the contralateral hemisphere, even at the terminal disease stage long after the infusion had ended. Therapeutic effects of PPS were also demonstrated in mice infected with either RML agent or Fukuoka-1 agent. However, at doses higher than that providing the maximal effects, intraventricular PPS infusion caused adverse effects such as hematoma formation in the experimental animals. These findings indicate that intraventricular PPS infusion might be useful for the treatment of transmissible spongiform encephalopathies in humans, providing that the therapeutic dosage is carefully evaluated. C1 Kyushu Univ, Grad Sch Med Sci, Dept Neuropathol, Fukuoka 8128582, Japan. Kyushu Univ, Grad Sch Med Sci, Biomed Res Ctr, Fukuoka 8128582, Japan. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Doh-Ura, K (reprint author), Tohoku Univ, Grad Sch Med, Dept Prion Res, 2-1 Seiryo Cho, Sendai, Miyagi 9808575, Japan. EM doh-ura@mail.tains.tohoku.ac.jp RI U-ID, Kyushu/C-5291-2016 NR 22 TC 121 Z9 133 U1 1 U2 12 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 2004 VL 78 IS 10 BP 4999 EP 5006 DI 10.1128/JVI.78.10.4999-5006.2004 PG 8 WC Virology SC Virology GA 817YF UT WOS:000221212100006 PM 15113880 ER PT J AU Budge, PJ Li, YQ Beeler, JA Graham, BS AF Budge, PJ Li, YQ Beeler, JA Graham, BS TI RhoA-derived peptide dimers share mechanistic properties with other polyanionic inhibitors of respiratory syncytial virus (RSV), including disruption of viral attachment and dependence on RSV G SO JOURNAL OF VIROLOGY LA English DT Article ID REPLICATION IN-VITRO; DEXTRAN SULFATE; FUSION PROTEIN; ANTIVIRAL ACTIVITY; HEPARAN-SULFATE; F-GLYCOPROTEIN; INFECTION; TYPE-1; CELLS; BINDING AB Large polyanionic molecules, such as sulfated polysaccharides (including soluble heparin and dextran sulfate), synthetic polyanionic polymers, and negatively charged proteins, have been shown to broadly inhibit several enveloped viruses. We recently reported the antiviral activity of a peptide derived from amino acids 77 to 95 of a potential binding partner of respiratory syncytial virus F protein (RSV F), the GTPase RhoA. A subsequent study with a truncated peptide (amino acids 80 to 94) revealed that optimal antiviral activity required dimerization via intermolecular disulfide bonds. We report here that the net negative charge of this peptide is also a determining factor for its antiviral activity and that it, like other polyanions, inhibits virus attachment. In a flow cytometry-based binding assay, peptide 80-94, heparin, and dextran sulfate inhibited the attachment of virus to cells at 4degreesC at the same effective concentrations at which they prevent viral infectivity. Interestingly, time-of-addition experiments revealed that peptide 80-94 and soluble heparin were also able to inhibit the infectivity of a virus that had been prebound to cells at 4degreesC, as had previously been shown for dextran sulfate, suggesting a potential role for postattachment effects of polyanions on RSV entry. Neutralization experiments with recombinant viruses showed that the antiviral activities of peptide 80-94 and dextran sulfate were diminished in the absence of the RSV attachment glycoprotein (G). Taken together, these data indicate that the antiviral activity of RhoA-derived peptides is functionally similar to that of other polyanions, is dependent on RSV G, and does not specifically relate to a protein-protein interaction between F and RhoA. C1 NIAID, Vaccine Res Ctr, NIH, Viral Pathogenesis Lab, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Virus Dis, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Viral Pathogenesis Lab, MSC 3017,Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 53 TC 12 Z9 14 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 2004 VL 78 IS 10 BP 5015 EP 5022 DI 10.1128/JVI.78.10.5015-5022.2004 PG 8 WC Virology SC Virology GA 817YF UT WOS:000221212100008 PM 15113882 ER PT J AU Fonteneau, JF Larsson, M Beignon, AS McKenna, K Dasilva, I Amara, A Li, YJ Lifson, JD Littman, DR Bhardwaj, N AF Fonteneau, JF Larsson, M Beignon, AS McKenna, K Dasilva, I Amara, A Li, YJ Lifson, JD Littman, DR Bhardwaj, N TI Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells SO JOURNAL OF VIROLOGY LA English DT Article ID INTERFERON-PRODUCING CELLS; HIV-INFECTED INDIVIDUALS; T-CELLS; INTRAVAGINAL INOCULATION; FUNCTIONAL DEFICIENCIES; ANTIRETROVIRAL THERAPY; ADAPTIVE IMMUNITY; INFLUENZA-VIRUS; HUMAN BLOOD; DC-SIGN AB In this study, we analyzed the phenotypic and physiological consequences of the interaction of plasmacytoid dendritic cells (pDCs) with human immunodeficiency virus type 1 (HIV-1). pDCs are one cellular target of HIV-1 and respond to the virus by producing alpha/beta interferon (IFN-alpha/beta) and chemokines. The outcome of this interaction, notably on the function of bystander myeloid DC (CD11c(+) DCs), remains unclear. We therefore evaluated the effects of HIV-1 exposure on these two DC subsets under various conditions. Blood-purified pDCs and CD11c(+) DCs were exposed in vitro to HIV-1, after which maturation markers, cytokine production, migratory capacity, and CD4 T-cell stimulatory capacity were analyzed. pDCs exposed to different strains of infectious or even chemically inactivated, nonreplicating HIV-1 strongly upregulated the expression of maturation markers, such as CD83 and functional CCR7, analogous to exposure to R-848, a synthetic agonist of toll-like receptor-7 and -8. In addition, HIV-1-activated pDCs produced cytokines (IFN-alpha and tumor necrosis factor alpha), migrated in response to CCL19 and, in coculture, matured CD11c(+) DCs, which are not directly activated by HIV. pDCs also acquired the ability to stimulate naive CD4(+) T cells, albeit less efficiently than CD11c(+) DCs. This HIV-1-induced maturation of both DC subsets may explain their disappearance from the blood of patients with high viral loads and may have important consequences on HIV-1 cellular transmission and HIV-1-specific T-cell responses. C1 NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Med, New York, NY 10016 USA. NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. NYU, Sch Med, Mol Pathogenesis Program, Skirball Inst Biomol Med, New York, NY 10016 USA. NCI, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21701 USA. Univ Texas, MD Anderson Canc Ctr, Ctr Canc Immunol Res, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. INSERM, U463, Inst Biol, Nantes, France. RP Bhardwaj, N (reprint author), NYU, Sch Med, Dept Pathol, MSB507,550 1st Ave, New York, NY 10016 USA. EM bhardn02@med.nyu.edu RI Jean-Francois, Fonteneau/L-4095-2015; OI Jean-Francois, Fonteneau/0000-0002-3284-8319; BEIGNON, Anne-Sophie/0000-0003-0863-983X FU NCI NIH HHS [N01 CO 124000]; NIAID NIH HHS [AI 44628, R01 AI044628, R37 AI044628] NR 51 TC 240 Z9 249 U1 2 U2 12 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 2004 VL 78 IS 10 BP 5223 EP 5232 DI 10.1128/JVI.78.10.5223-5232.2004 PG 10 WC Virology SC Virology GA 817YF UT WOS:000221212100030 PM 15113904 ER PT J AU Liao, HX Alam, SM Mascola, JR Robinson, J Ma, BJ Montefiori, DC Rhein, M Sutherland, LL Scearce, R Haynes, BF AF Liao, HX Alam, SM Mascola, JR Robinson, J Ma, BJ Montefiori, DC Rhein, M Sutherland, LL Scearce, R Haynes, BF TI Immunogenicity of constrained monoclonal antibody A32-human immunodeficiency virus (HIV) env gp120 complexes compared to that of recombinant HIV type 1 gp120 envelope glycoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID CROSS-LINKED COMPLEXES; NEUTRALIZATION SENSITIVITY; CORECEPTOR USAGE; EXPRESSION; CD4; IMMUNIZATION; INFECTION; MACAQUES; ELICITS; PROTEIN AB One strategy for the generation of broadly reactive neutralizing antibodies (NA) against human immunodeficiency virus type 1 (HIV-1) primary isolates is to use immunogens that have constrained HIV-1 envelope gp120 conformations reflective of triggered envelope on the surface of virions. A major change in gp120 following binding to CD4 is the enhanced exposure of the CCR5 binding site. One inducer of CCR5 binding site epitopes on gp120 is the human anti-gp120 monoclonal antibody, A32. We have made cross-linked A32-rgp120(89.6) and A32-rgp120(BaL) complexes and have compared their immunogenicities to those of uncomplexed recombinant gp120(BaL) (rgp120(BaL)) and rgp120(89.6). A32-rgp120(89.6) and A32-rgp120(BaL) complexes had stable induced CCR5 binding site expression compared to that of uncomplexed rgp120s. However, the A32-rgp120 complexes had similar capacities in guinea pigs for induction of NA against HIV-1 primary isolates versus that of rgp120 alone. A32-rgp120(89.6) induced antibodies that neutralized 6 out of 11 HIV-1 isolates, while rgp120(89.6) alone induced antibodies that neutralized 4 out of 11 HIV-1 isolates. A32-rgp120(BaL) complexes induced antibodies that neutralized 4 out of 14 HIV-1 isolates while, surprisingly, non-cross-linked rgp120(BaL) induced antibodies that neutralized 9 out of 14 (64%) HIV-1 isolates. Thus, stable enhanced expression of the coreceptor binding site on constrained gp120 is not sufficient for inducing broadly neutralizing anti-HIV-1 NA. Moreover, the ability of HIV-1 rgp120(BaL) to induce antibodies that neutralized similar to60% of subtype B HIV-1 isolates warrants consideration of using HIV-1 BaL as a starting point for immunogen design for subtype B HIV-1 experimental immunogens. C1 Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Liao, HX (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Box 3258, Durham, NC 27710 USA. EM liao0001@mc.duke.edu FU NIAID NIH HHS [AI 51445, AI 15351, AI 24030, N01 AI 05397, N01AI05397, P01 AI 52816, P01 AI052816, P30 AI051445, R01 AI024030] NR 26 TC 25 Z9 26 U1 1 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 2004 VL 78 IS 10 BP 5270 EP 5278 DI 10.1128/JVI.78.10.5270-5278.2004 PG 9 WC Virology SC Virology GA 817YF UT WOS:000221212100034 PM 15113908 ER PT J AU Li, Y Bao, YM Wei, CH Kang, ZS Zhong, YW Mao, P Wu, G Chen, ZL Schiemann, J Nelson, RS AF Li, Y Bao, YM Wei, CH Kang, ZS Zhong, YW Mao, P Wu, G Chen, ZL Schiemann, J Nelson, RS TI Rice dwarf phytoreovirus segment S6-encoded nonstructural protein has a cell-to-cell movement function SO JOURNAL OF VIROLOGY LA English DT Article ID POTATO-VIRUS-X; TOBACCO-MOSAIC-VIRUS; MAJOR STRUCTURAL PROTEINS; OUTER CAPSID PROTEIN; NICOTIANA-BENTHAMIANA; 183-KDA PROTEINS; VIRAL-PROTEINS; COAT PROTEIN; GENE; PLASMODESMATA AB Rice dwarf virus (RDV) is a member of the genus Phytoreovirus, which is composed of viruses with segmented double-stranded RNA genomes. Proteins that support the intercellular movement of these viruses in the host have not been identified. Microprojectile bombardment was used to determine which open reading frames (ORFs) support intercellular movement of a heterologous virus. A plasmid containing an infectious clone of Potato virus X (PVX) defective in cell-to-cell movement and expressing either beta-glucuronidase or green fluorescent protein (GFP) was used for cobombardment with plasmids containing ORFs from RDV gene segments S1 through S12 onto leaves of Nicotiana benthamiana. Cell-to-cell movement of the movement-defective PVX was restored by cobombardment with a plasmid containing S6. In the absence of S6, no other gene segment supported movement. Identical results were obtained with Nicotiana tabacum, a host that allows fewer viruses to infect and spread within its tissue. S6 supported the cell-to-cell movement of the movement-defective PVX in sink and source leaves of N. benthamiana. A mutant S6 lacking the translation start codon did not complement the cell-to-cell movement of the movement-defective PVX. An S6 protein product (Pns6)-enhanced GFP fusion was observed near or within cell walls of epidermal cells from N. tabacum. By immunocytochemistry, unfused Pns6 was localized to plasmodesmata in rice leaves infected with RDV. S6 thus encodes a protein with characteristics identical to those of other viral proteins required for the cell-to-cell movement of their genome and therefore is likely required for the cell-to-cell movement of RDV. C1 Peking Univ, Peking Yale Joint Ctr Plant Mol Genet & Agrobiote, Natl Lab Prot Engn & Plant Genet Engn, Coll Life Sci, Beijing 100871, Peoples R China. Fede Biol Res Ctr Agr & Forestry, Inst Biochem & Plant Virol, D-38104 Braunschweig, Germany. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Samuel Roberts Noble Fdn Inc, Div Plant Biol, Ardmore, OK 73401 USA. NW Agr & Forestry Univ, Dept Plant Protect, Shaanxi 712100, Yangling, Peoples R China. RP Li, Y (reprint author), Peking Univ, Peking Yale Joint Ctr Plant Mol Genet & Agrobiote, Natl Lab Prot Engn & Plant Genet Engn, Coll Life Sci, Beijing 100871, Peoples R China. EM liyi@pku.edu.cn; rsnelson@noble.org RI Zhong, Yongwang/A-2527-2012 NR 52 TC 42 Z9 54 U1 1 U2 11 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 2004 VL 78 IS 10 BP 5382 EP 5389 DI 10.1128/JVI.78.10.5382-5389.2004 PG 8 WC Virology SC Virology GA 817YF UT WOS:000221212100044 PM 15113917 ER PT J AU Voronin, YA Pathak, VK AF Voronin, YA Pathak, VK TI Frequent dual initiation in human immunodeficiency virus-based vectors containing two primer-binding sites: a quantitative in vivo assay for function of initiation complexes SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; TRANSFER-RNA-PRIMER; ROUS-SARCOMA-VIRUS; HIV-1 REVERSE TRANSCRIPTION; TYPE-1 NUCLEOCAPSID PROTEIN; DEPENDENT DNA POLYMERASE; NUCLEOTIDE-SEQUENCE; VIRAL-DNA; SECONDARY STRUCTURE; LENTIVIRAL VECTOR AB We previously demonstrated that murine leukemia virus (MLV)-based vectors containing two primer-binding sites (PBSs) have the capacity to initiate reverse transcription more than once (Y. A. Voronin and V. K. Pathak, Virology 312:281-294; 2003). To determine whether human immunodeficiency virus (HIV-based vectors also have the capacity to initiate reverse transcription twice, we constructed an HIV type 1 (HIV-1)based vector containing the HIV-1 PBS, a green fluorescent protein reporter gene (GFP), and a second PBS derived from HIV-2 3' of GFP. Simultaneous initiation of reverse transcription at both the 5' HIV-1 PBS and 3' HIV-2 PBS was predicted to result in deletion of GFP. As in the MLV-based vectors, GFP was deleted in approximately 25% of all proviruses, indicating frequent dual initiation in HIV-based vectors containing two PBSs. Quantitative real-time PCR analysis of early reverse transcription products indicated that HIV-1 reverse transcriptase efficiently used the HIV-2 PBS. To investigate tRNA primer-RNA template interactions in vivo, we introduced several mutations in the HIV-2 U5 region. The effects of these mutations on the efficiency of reverse transcription initiation were measured by quantitative real-time PCR analysis of early reverse transcription products, with initiation at the HIV-1 PBS used as an internal control. Disruption of the lower and upper parts of the U5-inverted repeat stem reduced the efficiency of initiation 20- and 6-fold, respectively. in addition, disruption of the proposed interactions between viral RNA and tRNA(Lys3) thymidine-pseudouridine-cytidine and anticodon loops decreased the efficiency of initiation seven- and sixfold, respectively. These results demonstrate the relative influence of various RNA-RNA interactions on the efficiency of initiation in vivo. Furthermore, the two-PBS vector system provides a sensitive and quantitative in vivo assay for analysis of RNA-RNA and protein-RNA interactions that can influence the efficiency of reverse transcription initiation. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. W Virginia Univ, Dept Biochem, Morgantown, WV 25606 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 334, Frederick, MD 21702 USA. EM VPATHAK@ncifcrf.gov NR 77 TC 9 Z9 10 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 2004 VL 78 IS 10 BP 5402 EP 5413 DI 10.1128/JVI.78.10.5402-5413.2004 PG 12 WC Virology SC Virology GA 817YF UT WOS:000221212100046 PM 15113919 ER PT J AU Sadjadpour, R Theodore, TS Igarashi, T Donau, OK Plishka, RJ Buckler-White, A Martin, MA AF Sadjadpour, R Theodore, TS Igarashi, T Donau, OK Plishka, RJ Buckler-White, A Martin, MA TI Induction of disease by a molecularly cloned highly pathogenic simian immunodeficiency virus/human immunodeficiency virus chimera is multigenic SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; RHESUS-MONKEYS; CLINICAL-OUTCOMES; TYPE-1 ISOLATE; IN-VIVO; INFECTION; MACAQUES; AIDS; VACCINE; PREVENTION AB One of three full-length infectious molecular clones of SHIVDH12R, designated SHIVDH12R-CL-7 and obtained from productively infected rhesus monkey peripheral blood mononuclear cells, directed rapid and irreversible loss of CD4(+) T cells within 3 weeks of its inoculation into Indian rhesus monkeys. Induction of complete CD4(+) T-cell depletion by SHIVDH12R-CL-7 was found to be dependent on inoculum size. The acquisition of this pathogenic phenotype was accompanied by the introduction of 42 amino acid substitutions into multiple genes of parental nonpathogenic SHIVDH12. Transfer of the entire SHIVDH12R-CL-7 env gene into the genetic background of nonpathogenic SHIVDH12 failed to confer the rapid CD4(+) T-lymphocyte-depleting syndrome; similarly, the substitution of gag plus pol sequences from SIVsmE543 for analogous SIVmac239 genes in SHIVDH12R-CL-7 attenuated the pathogenic phenotype. Amino acid changes affecting multiple viral genes are necessary, but insufficient by themselves, to confer the prototypically rapid and irreversible CD4(+) T-cell-depleting phenotype exhibited by molecularly cloned SHIVDH12R-CL-7. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM malm@nih.gov NR 26 TC 12 Z9 12 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 2004 VL 78 IS 10 BP 5513 EP 5519 DI 10.1128/JVI.78.10.5513-5519.2004 PG 7 WC Virology SC Virology GA 817YF UT WOS:000221212100058 PM 15113931 ER PT J AU Zhang, L Ribeiro, RM Mascola, JR Lewis, MG Stiegler, G Katinger, H Perelson, AS Davenport, MP AF Zhang, L Ribeiro, RM Mascola, JR Lewis, MG Stiegler, G Katinger, H Perelson, AS Davenport, MP TI Effects of antibody on viral kinetics in simian/human immunodeficiency virus infection: Implications for vaccination SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODIES; TYPE-1 INFECTION; RHESUS-MONKEYS; MACAQUES; TRANSMISSION; PROTECTION; ENVELOPE; SHIV AB Passive antibody treatment of macaques prior to simian/human immunodeficiency virus infection produces "sterilizing immunity" in some animals and long-term reductions in viral loads in others. Analysis of viral kinetics suggests that antibody mediates sterilizing immunity by its effects on the initial viral inoculum. By contrast, reduction in peak viral load later in infection prevents CD4 depletion and contributes to long-term viral control. C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Univ New S Wales, Dept Haematol, Prince Wales Hosp, Kensington, NSW 2052, Australia. Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2052, Australia. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. BIOQUAL Inc, Rockville, MD 20850 USA. Agr Univ Vienna, Inst Appl Microbiol, A-1180 Vienna, Austria. RP Perelson, AS (reprint author), Los Alamos Natl Lab, MS-K710, Los Alamos, NM 87545 USA. EM asp@lanl.gov RI Zhang, Lei/D-4039-2011 FU NCI NIH HHS [CA 50139, R01 CA050139]; NCRR NIH HHS [R01 RR006555, RR 06555]; NIAID NIH HHS [AI 28433, R01 AI028433, R37 AI028433] NR 13 TC 20 Z9 21 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 2004 VL 78 IS 10 BP 5520 EP 5522 DI 10.1128/JVI.78.10.5520-5522.2004 PG 3 WC Virology SC Virology GA 817YF UT WOS:000221212100059 PM 15113932 ER PT J AU Lane, MA Mattison, JA Roth, GS Brant, LJ Ingram, DK AF Lane, MA Mattison, JA Roth, GS Brant, LJ Ingram, DK TI Effects of long-term diet restriction on aging and longevity in primates remain uncertain SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID RHESUS-MONKEYS; CALORIE RESTRICTION; INSULIN-RESISTANCE; DIABETES-MELLITUS; MORBIDITY; MORTALITY; OBESITY; MODELS C1 NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov NR 16 TC 31 Z9 33 U1 1 U2 2 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 2004 VL 59 IS 5 BP 405 EP 407 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 820TB UT WOS:000221411100001 PM 15123747 ER PT J AU Valenti, G Denti, L Maggio, M Ceda, G Volpato, S Bandinelli, S Ceresini, G Cappola, A Guralnik, JM Ferrucci, L AF Valenti, G Denti, L Maggio, M Ceda, G Volpato, S Bandinelli, S Ceresini, G Cappola, A Guralnik, JM Ferrucci, L TI Effect of DHEAS on skeletal muscle over the life span: The InCHIANTI study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID GROWTH-FACTOR-I; DEHYDROEPIANDROSTERONE-SULFATE; BODY-COMPOSITION; ELDERLY-PEOPLE; OLDER MEN; WOMEN; SERUM; TESTOSTERONE; REPLACEMENT; STRENGTH AB Background. It has been suggested that the reduced production of dehydroepiandrosterone sulfate (DHEAS) may be partially responsible for the decline of muscle strength and mass that often occurs with aging. However, this hypothesis has been only tested in small series of normal volunteers, with little consideration for potential confounders. Using data from a representative sample of 558 men (20-95 years) we tested the hypothesis that circulating DHEAS is independently associated with muscle strength and mass. Methods. Data are from InCITIANTI,an epidemiological study conducted in the Chianti geographic area (Tuscany, Italy). DHEAS serum levels were related to lower extremity muscle strength assessed by hand-held dynamometry and calf muscle area estimated from quantitative computerized tomography. Confounders included age, anthropometrics, physical activity, smoking, energy and alcohol intake, albumin, lipids, interleukin-6, comorbidity, depressive symptoms, and disability in activities of daily living. Results. In fully adjusted models predicting lower extremity muscle strength and calf muscle area, we found significant age*log DHEAS interactions, suggesting that the relationship between DHEAS levels and muscle parameters differs across the life span. In age-stratified models adjusted for confounders, serum DHEAS was an independent predictor of muscle strength (p < .02) and mass (p < .01), but only for men between 60 and 79 years of age. After adjusting these models for serum-free or bioavailable testosterone, results were unchanged. Conclusions. In men aged 60-79 years, circulating DHEAS is an independent correlate of muscle strength and calf muscle area. The possible causal role of declining DHEAS in age-related sarcopenia should be further explored in longitudinal studies. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA. Univ Parma, Dept Geriatr, I-43100 Parma, Italy. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. INRCA Geriatr Dept, Lab Clin Epidemiol, Florence, Italy. Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Div Epidemiol, Philadelphia, PA 19104 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, 3001 Hanover St,Rm NM534, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI VOLPATO, STEFANO/H-2977-2014; OI VOLPATO, STEFANO/0000-0003-4335-6034; Ceda, Gian Paolo/0000-0002-9648-8295 FU NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13] NR 29 TC 52 Z9 56 U1 2 U2 3 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 2004 VL 59 IS 5 BP 466 EP 472 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 820TB UT WOS:000221411100011 PM 15123757 ER PT J AU Slebos, RJC Umbach, DM Sommer, CA Horner, GA Choi, JY Taylor, JA AF Slebos, RJC Umbach, DM Sommer, CA Horner, GA Choi, JY Taylor, JA TI Analytical and statistical methods to evaluate microsatellite allelic imbalance in small amounts of DNA SO LABORATORY INVESTIGATION LA English DT Article DE microsatellite; loss of heterozygosity; allelic imbalance; time-release PCR; tissue microdissection ID POLYMERASE-CHAIN-REACTION; LUNG-CANCER; GENOMIC INSTABILITY; BRONCHIAL LAVAGE; K-RAS; MICRODISSECTION; EPITHELIUM; TUMORS; CELLS AB Microsatellite analysis is a powerful tool for the assessment of genetic instability and loss of heterozygosity in cancer cells. However, most human tumors harbor significant numbers of normal cells, which may contribute to false-negative results. Recent techniques based on fluorescently labeled primers and semiautomated capillary ellectrophoresis of pollymerase chain reaction (PCR) products allow a reliable quantitative assessment of (PCR) products while requiring very small numbers of cells. We report a highly sensitive protocol for the semiautomated analysis of allelic imbalance based on time-release PCR and capillary electrophoresis. With this protocol, as few as 100 cells can be used to reliably assess allelic imbalance (Al) in DNA samples. Using a panel of seven microsatellite markers, we determined allelic variation in a large set of heterozygous lymphocyte DNA samples and examined the use of different statistical analysis techniques. Using these statistical approaches, we describe a calibration method to evaluate All from microsatellite results. Using a simple formula, cutoff points at preset confidence levels are used to decide whether allelic imbalance exists in a given sample at the loci under investigation. Our method allows the reliable detection of All with very small amounts of DNA, and is sufficiently quantitative to assess allelic ratios in nonclonal tissue specimens. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, NIH, Maildrop A3-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 NR 23 TC 21 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2004 VL 84 IS 5 BP 649 EP 657 DI 10.1038/labinvest.3700076 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 840CH UT WOS:000222834100015 PM 15048133 ER PT J AU Davidson, B Reich, R Lazarovici, P Florenes, VA Risberg, B Nielsen, S Sert, B Bedrossian, C AF Davidson, B Reich, R Lazarovici, P Florenes, VA Risberg, B Nielsen, S Sert, B Bedrossian, C TI Expression of the nerve growth factor receptors TrkA and p75 in malignant mesothelioma SO LUNG CANCER LA English DT Article DE malignant mesothelioma; neurotrophins; tyrosine kinase receptors; p75; effusions ID SEROUS OVARIAN-CARCINOMA; CELL-LINES; NEUROTROPHIN RECEPTORS; SIGNAL-TRANSDUCTION; TUMORS; TISSUE; NEUROBLASTOMAS; PROGRESSION; INHIBITION; EFFUSIONS AB The objective of the present report was to study the expression of the tow affinity nerve growth factor (NGF) receptor p75 and of the activated high-affinity NGF receptor TrkA in malignant mesothelioma (MM). In addition, to analyze whether expression of these receptors is site-related (pleural. versus peritoneal MM, solid lesions versus effusions). Sections from 81 MM (57 biopsies, 24 effusions) were analyzed. Sixty-one mesotheliomas were of pleural origin, while the remaining 20 were peritoneal Effusion specimens consisted of 6 peritoneal and 18 pleural. effusions, while biopsies consisted of 14 peritonea[ and 43 pleura[ lesions. Specimens were immunohistochemically stained using antibodies against p75 and phospho-TrkA (p-TrkA). Six effusions were additionally analyzed for p-TrkA expression using immunoblotting (113). p-TrkA membrane expression (66/81 specimens; 81%) was by far more frequent than that of p75 (26/81 specimens; 32%). In addition, p-TrkA expression was significantly higher in peritoneal. MM compared to their pleural counterparts (20/20 versus 46/61 positive tumors; P = 0.014). p-TrkA membrane expression was marginally higher in effusions (P = 0.058), while the opposite was true for p75 membrane expression (P = 0.008) and p-TrkA cytoplasmic expression (P = 0.003). In conclusion, our results document for the first time frequent expression of p-TrkA and tower expression of p75 in MM, in agreement with the biological aggressiveness of this tumor. The enhanced expression of p-TrkA in peritoneal. MM, tumors that appear in younger patients, and in effusions as compared to solid tumors, suggest that p-TrkA plays a significant role in the biology of this disease and may aid in defining tumor progression in this setting. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Univ Oslo, Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway. Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Dept Pharmacol & Expt Therapeut, IL-91120 Jerusalem, Israel. Aalborg Hosp, Dept Pathol, DK-9000 Aalborg, Denmark. Univ Oslo, Norwegian Radium Hosp, Dept Gynecol Oncol, N-0310 Oslo, Norway. Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. Hebrew Univ Jerusalem, David R Bloom Ctr Pharm, IL-91905 Jerusalem, Israel. RP Davidson, B (reprint author), NIH, Pathol Lab, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20862 USA. EM bend@ulrik.uio.no RI Risberg, Bjorn/A-6447-2008 NR 33 TC 30 Z9 32 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 2004 VL 44 IS 2 BP 159 EP 165 DI 10.1016/j.lungcan.2003.11.014 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 817CW UT WOS:000221156600003 PM 15084380 ER PT J AU Lavoie, B Basyuk, E Bordonne, R Bertrand, E AF Lavoie, B Basyuk, E Bordonne, R Bertrand, E TI Cell polarity and actin mRNA localization SO M S-MEDECINE SCIENCES LA French DT Review ID IN-SITU HYBRIDIZATION; BINDING PROTEIN; INTRACELLULAR-LOCALIZATION; GROWTH CONES; NEURONS; MOTILITY; OLIGODENDROCYTES; MICROFILAMENTS; TRANSLATION; FIBROBLASTS AB In many species, intracellular mRNA localization is linked to cell polarity. In many cases however, mRNAs become localized as a result of a pre-existing cell-polarity, and they do not modify it. Remarkably, in the case beta actin mRNA in vertebrate, it has been shown that the transport and localization of this RNA is required for the establishment and maintenance of cell polarity. This occurs in fibroblasts, but, very interestingly, in immature neurons as well. This review will describe the functions and mechanisms of actin mRNA localization. C1 NINDS, Mol Plast Sect, Bethesda, MD 20892 USA. Univ Montpellier 2, IGMM, CNRS, UMR 5535, F-34293 Montpellier 5, France. RP Lavoie, B (reprint author), NINDS, Mol Plast Sect, 36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. EM lavoieb@ninds.nih.gov; bertrand@igmn.cnrs-mop.fr NR 36 TC 1 Z9 1 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD MAY PY 2004 VL 20 IS 5 BP 539 EP 543 DI 10.1051/medsci/2004205539 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 819ZX UT WOS:000221356800014 PM 15190471 ER PT J AU Yim, PJ Cebral, JR Weaver, A Lutz, RJ Soto, O Vasbinder, GBC Ho, VB Choyke, PL AF Yim, PJ Cebral, JR Weaver, A Lutz, RJ Soto, O Vasbinder, GBC Ho, VB Choyke, PL TI Estimation of the differential pressure at renal artery stenoses SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE renal artery disease; magnetic resonance angiography; phase contrast magnetic resonance imaging; computational fluid dynamics ID COMPUTATIONAL FLUID-DYNAMICS; BLOOD-FLOW; CAROTID BIFURCATION; RENOVASCULAR HYPERTENSION; BREATH-HOLD; MRI; RECONSTRUCTION; QUANTIFICATION; ANGIOGRAPHY; VELOCITY AB Atherosclerotic disease of the renal artery can lead to reduction in arterial caliber and ultimately to conditions including renovascular hypertension. Renal artery stenosis is conventionally assessed, using angiography, according to the severity of the stenosis. However, the severity of a stenosis is not a reliable indicator of functional significance, or associated differential pressure, of a stenosis. A methodology is proposed for estimation of the renal artery differential pressure (RADP) from MR imaging. Realistic computational fluid dynamics (CFD) models are constructed from MR angiography (MRA) and phase-contrast (PC) MR. The CFD model is constructed in a semiautomated manner from the MR images using the Isosurface Deformable Model (IDM) for surface reconstruction and a Marching Front algorithm for construction of the volumetric CFD mesh. Validation of RADP estimation was performed in a realistic physical flow-through model. Under steady flow, the CFD estimate of the differential pressure across a stenosis in the physical flow-through model differed by an average of 5.5 mmHg from transducer measurements of the pressure differential, for differential pressures less than 60 mmHg. These results demonstrate that accurate estimates of differential pressure at stenoses may be possible based only on structural and flow images. Magn Reson Med 51:969-977, 2004. Published 2004 Wiley-Liss, lnc.(dagger). C1 UMDNJy, Robert Wood Johnson Med Sch, Dept Radiol, New Brunswick, NJ 08903 USA. George Mason Univ, Fairfax, VA 22030 USA. Natl Inst Hlth, Bethesda, MD USA. Maastricht Univ Hosp, Maastricht, Netherlands. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Yim, PJ (reprint author), UMDNJy, Robert Wood Johnson Med Sch, Dept Radiol, Robert Wood Johnson Pl,MEB 404, New Brunswick, NJ 08903 USA. EM yimpj@umdnj.edu NR 34 TC 24 Z9 24 U1 0 U2 5 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 2004 VL 51 IS 5 BP 969 EP 977 DI 10.1002/mrm.20078 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 818IO UT WOS:000221239000013 PM 15122679 ER PT J AU Chen, ZQ Annilo, T Shulenin, S Dean, M AF Chen, ZQ Annilo, T Shulenin, S Dean, M TI Three ATP-binding cassette transporter genes, Abca14, Abca15, and Abca16, form a cluster on mouse Chromosome 7F3 SO MAMMALIAN GENOME LA English DT Article ID FAMILIAL INTRAHEPATIC CHOLESTASIS; TANGIER-DISEASE; MULTIDRUG-RESISTANCE; DIETARY-CHOLESTEROL; MEMBRANE-PROTEIN; II CELLS; IDENTIFICATION; MUTATIONS; SUPERFAMILY; SEQUENCE AB We have identified and cloned three mouse genes that belong to the ABCA subfamily of ATP-binding cassette (ABC) transporters. These three genes are arranged in a tandem head-to-tail cluster spanning about 300 kb on mouse Chromosome (Chr) 7F3. Phylogenetic analysis indicates that although the three genes are related to human and mouse ABCA3, they are not orthologs of any of the current list of 48 human ABC genes and were, therefore, named Abca14, Abca15, and Abca16. The coding region of each gene is split into 31 exons, has an open reading frame of more than 1600 amino acids, and encodes a full transporter molecule with two nucleotide-binding folds (NBF) and two transmembrane domains (TMD). All three genes are predominantly expressed in testis, which suggests that they may perform special functions in testicular development or spermatogenesis. Interestingly, the human genome contains only fragments (less than ten exons) of at least two different ABC genes in the syntenic region on Chromosome 16p12 that are scattered among other, unrelated genes and are not capable of coding functional ABC transporters. C1 NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012; Annilo, Tarmo/J-2900-2013 OI Dean, Michael/0000-0003-2234-0631; Annilo, Tarmo/0000-0002-9588-3058 FU NCI NIH HHS [N01-CO-12400] NR 29 TC 12 Z9 16 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 2004 VL 15 IS 5 BP 335 EP 343 DI 10.1007/s00335-004-2281-8 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 818QH UT WOS:000221259100001 PM 15170222 ER PT J AU Kuznetsova, NV Forlino, A Cabral, WA Marini, JC Leikin, S AF Kuznetsova, NV Forlino, A Cabral, WA Marini, JC Leikin, S TI Structure, stability and interactions of type I collagen with GLY349-CYS substitution in alpha 1(I) chain in a murine Osteogenesis Imperfecta model SO MATRIX BIOLOGY LA English DT Article DE Osteogenesis Imperfecta; collagen-collagen interactions; thermal stability ID FIBRILLAR COLLAGENS; THERMAL-STABILITY; MUTATIONS; DISEASES; FIBRILLOGENESIS; TEMPERATURE; HOMOTRIMER; PHENOTYPE; INVITRO; SYSTEM AB Here we report the structural and functional studies of collagen from the Brt1 mouse, a heterozygous knock-in model for Osteogenesis Imperfecta, which has a G349C substitution introduced in one co11a1 allele. We observed that 25 +/- 5% of alpha1(I) chains in different tissues and in different extracts from matrix deposited by cultured cells were S-S-linked mutant dimers. Apparently mutant and normal molecules are equally well incorporated into the matrix and they form mature covalent crosslinks with the same efficiency. We found different extents of post-translational overmodification of mutant molecules in different tissues. but we found no consistent differences between lethal and non-lethal animals. We did not detect any changes in the thermal stability or rate of thermal denaturation of mutant collagen. We also did not detect any changes in collagen-collagen recognition and interactions except for disruption of quasi-crystalline lateral packing of molecules in tendons from some, mostly prepubertal. mutant animals. In contrast, alpha1(I)(3) collagen from the oim mouse-the only other non-lethal murine OI model studied by similar techniques-has altered stability, fibrillogenesis, collagen-collagen interactions and produces a more consistent and more pronounced disruption of tendon crystallinity. Nevertheless, while the G349C substitution causes moderate or lethal OI, heterozygous oim mice are much less affected. Overall, our results suggest that OI symptoms and phenotype variation in G349C animals are related to abnormal interactions of mutant collagen helices with other matrix molecules or abnormal function of osteoblasts rather than to abnormal structure, physical properties or interactions between mutant collagen helices. (C) 2004 Elsevier B.V./Intemational Society of Matrix Biology. All rights reserved. C1 NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. NICHD, BEMB, Sect Connect Tissue Disorders, NIH, Bethesda, MD 20892 USA. Univ Pavia, Dipartimento Biochem A Castellani, I-27100 Pavia, Italy. RP Leikin, S (reprint author), NICHD, Sect Phys Biochem, NIH, Bldg 9,Rm 1E-127, Bethesda, MD 20892 USA. EM leikins@mail.nih.gov RI Leikin, Sergey/A-5518-2008; Forlino, Antonella/H-5385-2015 OI Leikin, Sergey/0000-0001-7095-0739; Forlino, Antonella/0000-0002-6385-1182 NR 33 TC 22 Z9 23 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAY PY 2004 VL 23 IS 2 BP 101 EP 112 DI 10.1016/j.matbio.2004.03.002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 840JO UT WOS:000222854800004 PM 15246109 ER PT J AU Blumenthal, JA Babyak, MA Carney, RM Huber, M Saab, PG Burg, MM Sheps, D Powell, L Taylor, CB Kaufmann, PG AF Blumenthal, JA Babyak, MA Carney, RM Huber, M Saab, PG Burg, MM Sheps, D Powell, L Taylor, CB Kaufmann, PG TI Exercise, depression, and mortality after myocardial infarction in the ENRICHD trial SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE cardiac rehabilitation; depression; heart disease; morbidity ID CORONARY-HEART-DISEASE; PHYSICAL-ACTIVITY; CARDIAC REHABILITATION; LEISURE-TIME; PREVENTION; INTERVIEW; IMPACT; MEN AB Purpose: The large and well-characterized population of acute myocardial infarction (AMI) patients studied in the recently completed Enhancing Recovery in Coronary Heart Disease (ENRICHD) multicenter clinical trial provides a unique opportunity to examine the importance of self-reported regular physical exercise in a large cohort of patients with a recent AMI who are depressed or report low levels of social support. Methods: We prospectively examined the association between self-reported physical exercise and all-cause mortality and cardiovascular morbidity among 2078 men (N = 1175; 56.5 %) and women (N = 903; 43.5%) with an AMI participating in the ENRICHD Trial. Six months after suffering an AMI, patients were surveyed about their exercise habits and were then followed for up to 4 yr. Results: During an average 2 yr of follow-up, 187 fatal events occurred. Patients reporting regular exercise had less than half the events (5.7%) of those patients reporting they did not regularly exercise (12.0%). After adjustment for medical and demographic variables, the hazard ratio for fatal events was 0.62 (95% CI = 0.44-0.86, P = 0.004). The rate of nonfatal AMI among the exercisers was 6.5% compared with 10.5% who reported no regular exercise. After adjustment for covariates, the hazard ratio for nonfatal AMI was 0.72 (95% Cl = 0.52-0.99, P = 0.044). Conclusions: The present findings demonstrate the potential value of exercise in reducing mortality and nonfatal reinfarction in AMI patients at increased risk for adverse events by virtue of their either being depressed or having low social support. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Washington Univ, St Louis, MO USA. Univ N Carolina, Chapel Hill, NC USA. Univ Miami, Miami, FL 33152 USA. Yale New Haven Vet Adm Hosp, New Haven, CT USA. Univ Florida, Gainesville, FL USA. Rush Presbyterian Hosp, Chicago, IL USA. Stanford Univ, Palo Alto, CA 94304 USA. NHLBI, Bethesda, MD 20892 USA. RP Blumenthal, JA (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3119, Durham, NC 27710 USA. EM Blume003@mc.duke.edu FU NHLBI NIH HHS [N01-HC-55148, N01-HC-55142, N01-HC55140, N01-HC-55143, N01-HC-55145, N01-HC-55146, N01-HC-55144, N01-HC-55141, N01-HC-55147] NR 33 TC 61 Z9 67 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2004 VL 36 IS 5 BP 746 EP 755 DI 10.1249/01.MSS.0000125997.63493.13 PG 10 WC Sport Sciences SC Sport Sciences GA 819LH UT WOS:000221315900002 PM 15126705 ER PT J AU Daves, MG Turner, MJ Kleeberger, SR Lightfoot, JT AF Daves, MG Turner, MJ Kleeberger, SR Lightfoot, JT TI Daily physical activity level in male inbred mouse strains SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Sports-Medicine CY JUN 02-05, 2004 CL Indianapolis, IN SP Amer Coll Sports Med C1 Univ N Carolina, Charlotte, NC 28223 USA. NIEHS, Durham, NC USA. EM mgdaves@email.unce.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2004 VL 36 IS 5 SU S MA 1772 BP S260 EP S260 PG 1 WC Sport Sciences SC Sport Sciences GA 913XG UT WOS:000228188302367 ER PT J AU Martel, G Aiken, B Brill, M Roth, SM Hurley, BF Metter, EJ Rogers, MA AF Martel, G Aiken, B Brill, M Roth, SM Hurley, BF Metter, EJ Rogers, MA TI Short-term strength training does not alter skeletal muscle capillarization in young or older women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Sports-Medicine CY JUN 02-05, 2004 CL Indianapolis, IN SP Amer Coll Sports Med C1 Univ Maryland Eastern Shore, Princess Anne, MD USA. Univ Maryland, College Pk, MD 20742 USA. NIA, Baltimore, MD 21224 USA. EM gfmartel@mail.umes.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2004 VL 36 IS 5 SU S MA 0399 BP S54 EP S54 PG 1 WC Sport Sciences SC Sport Sciences GA 913XG UT WOS:000228188300254 ER PT J AU McKenzie, T Catellier, D Conway, T Webber, L Lytle, L Elder, J Pratt, C Greiser, M AF McKenzie, T Catellier, D Conway, T Webber, L Lytle, L Elder, J Pratt, C Greiser, M TI Girls' physical activity levels and lesson context during middle school physical education: TAAG baseline SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Sports-Medicine CY JUN 02-05, 2004 CL Indianapolis, IN SP Amer Coll Sports Med C1 Univ San Diego, San Diego, CA 92110 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Tulane Univ, New Orleans, LA 70118 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NHLBI, Washington, DC USA. Univ Maryland, Baltimore, MD 20742 USA. EM tmckenzie@sdsu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2004 VL 36 IS 5 SU S MA 0723 BP S101 EP S101 PG 1 WC Sport Sciences SC Sport Sciences GA 913XG UT WOS:000228188301050 ER PT J AU Walsh, S Shea, PR Metter, J Hurley, BF Ferrell, RE Roth, SM AF Walsh, S Shea, PR Metter, J Hurley, BF Ferrell, RE Roth, SM TI Androgen receptor CAG repeat is associated with fat free mass in men but not in women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Sports-Medicine CY JUN 02-05, 2004 CL Indianapolis, IN SP Amer Coll Sports Med C1 Univ Maryland, College Pk, MD 20742 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIA, Baltimore, MD 21224 USA. EM walshs@umd.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2004 VL 36 IS 5 SU S MA 0713 BP S99 EP S99 PG 1 WC Sport Sciences SC Sport Sciences GA 913XG UT WOS:000228188301042 ER PT J AU Deterding, LJ Banks, GC Tomer, KB Archer, TK AF Deterding, LJ Banks, GC Tomer, KB Archer, TK TI Understanding global changes in histone H1 phosphorylation using mass spectrometry SO METHODS LA English DT Article DE histone H1; H1 isoforrns; post-translational modifications; transcription; phosphorylation; electrospray ionization; mass spectrometry; dexamethasone; chromatin; MMTV ID GENE-EXPRESSION; IN-VIVO; TRANSCRIPTION; PROTEOMICS AB Histone post-translational modifications have been implicated in a variety of biological processes such as gene expression, DNA replication, and chromatin assembly. The modifications include methylation, acetylation, phosphorylation, ubiquitination, glycosylation, and ADP-ribosylation. For several years, we have been investigating the role of historic HI phosphorylation in transcription using the hormone inducible mouse mammary tumor virus (MMTV) promoter. When mouse cells were exposed to prolonged treatment with dexamethasone, a significant decrease in the level of histone H1 phosphorylation was observed. Traditionally, Western analyses with anti-histone H1 and phospho-specific H1 antibodies were performed to observe changes in phosphorylation levels of the bulk H1 histories. More recently, we have applied electrospray ionization mass spectrometry to the analysis of histone H1 isoforms. Utilizing this approach, we have investigated the phosphorylation state of the specific H1 isoforms before and after prolonged treatment with dexamethasone. Specifically, we could determine that the relative phosphorylation levels of the histone H1.3, H1.4 and H1.5 isoforms decrease after prolonged hormone exposure. Recent advancements in mass spectrometry have proven invaluable toward the analysis of post-translational modifications on proteins. The continued developments in the area of mass spectrometry should provide new insights into not only the function of proteins but also into the basic regulatory mechanisms that control cellular functions. Published by Elsevier Inc. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 22 TC 11 Z9 12 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 1046-2023 J9 METHODS JI Methods PD MAY PY 2004 VL 33 IS 1 BP 53 EP 58 DI 10.1016/j.ymeth.2003.10.020 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808GD UT WOS:000220556700008 PM 15039087 ER PT J AU Kim, YJ Shen, CH Clark, DJ AF Kim, YJ Shen, CH Clark, DJ TI Purification and nucleosome mapping analysis of native yeast plasmid chromatin SO METHODS LA English DT Article DE yeast; chromatin; nucleosome positions; histories; monomer extension mapping ID MICROCOCCAL NUCLEASE; GLOBIN GENE; IN-VITRO; DNA; SEQUENCES; ACTIVATOR; CHICKEN AB There is much evidence indicating the importance in gene regulation of the positions of nucleosomes with respect to DNA sequence. Low resolution chromatin structures have been described for many genes, but there is a dearth of detailed high resolution chromatin structures. In the cases where they are available, high resolution maps have revealed much more complex chromatin structures, with multiple alternative nucleosome positions. The discovery that ATP-dependent chromatin remodelling machines are recruited to genes.. with their ability to mobilise nucleosomes on DNA and to alter nucleosomal conformation, emphasises the necessity for obtaining high resolution nucleosome maps, so that the details of these remodelling reactions can be defined in vivo. Here, we describe protocols for purifying plasmid chromatin from cells of the yeast Saccharomyces cerevisiae and for mapping nucleosome positions on the plasmid using the monomer extension mapping method. This method requires purified chromatin, but is capable of mapping relatively long stretches of chromatin in great detail. Typically, it reveals very complex chromatin structures. Published by Elsevier Inc. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Clark, DJ (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3148,50 South Dr,MSC 8028, Bethesda, MD 20892 USA. EM djclark@helix.nih.gov NR 20 TC 9 Z9 9 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2004 VL 33 IS 1 BP 59 EP 67 DI 10.1016/j.ymeth.2003.10.021 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808GD UT WOS:000220556700009 PM 15039088 ER PT J AU Murillo, R Crucilla, C Schmittner, J Hotchkiss, E Pickworth, WB AF Murillo, R Crucilla, C Schmittner, J Hotchkiss, E Pickworth, WB TI Pupillometry in the detection of concomitant drug use in opioid-maintained patients SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE drug detection; methadone-maintenance; pupil diameter; pupillometry; saccadic velocity; urinalysis ID LIGHT REFLEX; INTRAVENOUS BUPRENORPHINE; HUMANS; URINE; ABUSE AB Pupillometry and ocular response measures are sensitive to a variety of acutely administered drugs and as such are useful for drug detection and fitness-for-duty applications. The utility of pupillometry to complement urine testing in methadone clinics, where there is considerable non-therapeutic drug use, has not been tested. A video-based pupillometer (FIT 2000) was evaluated in 37 opioid-maintained patients. Three times a week they provided urine samples and pupillometry measures of initial diameter (ID) in mm; constriction amplitude (CA) in mm; constriction latency (CL) in msec; and saccadic velocity (SV) in min/sec. Analysis of the success rates indicated that 92.9% (if subjects obtained an acceptable reading, 59% on the first attempt. Low variability in pupillarly parameters on drug-free days are necessary for effective identification of concomitant drug use. The variability (standard deviation) of ID (0.51 vs. 0.68), CA (0.12 vs. 0.27) and SV (7.2 vs. 11.1) increased on days when the urine was positive for abused drugs compared with drug-free urine days in subjects (n = 6). Subjects who were always drug-free (it = 4) had lower variability than those who always had urine positive for additional drugs (n = 20). These preliminary results suggest that pupillometry may be useful to verify concomitant drug use in a methadone-maintained population. Successful implementation of the methodology could reduce costly and intrusive urine testing. (C) 2004 Prous Science. All rights reserved. C1 NIDA, IRP, Clin Pharmacol & Therapeut Branch, Baltimore, MD 21224 USA. PMI Inc, Rockville, MD USA. RP Pickworth, WB (reprint author), NIDA, IRP, Clin Pharmacol & Therapeut Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wpickwo@intra.nida.nih.gov NR 19 TC 10 Z9 11 U1 0 U2 2 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD MAY PY 2004 VL 26 IS 4 BP 271 EP 275 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 826LQ UT WOS:000221831000005 PM 15319805 ER PT J AU Vestereng, VH Kovacs, JA AF Vestereng, VH Kovacs, JA TI Inability of Pneumocystis organisms to incorporate bromodeoxyuridine suggests the absence of a salvage pathway for thymidine SO MICROBIOLOGY-SGM LA English DT Article; Proceedings Paper CT Joint International Conference on Anaerobic Protists (ICAP)/8th International Workshop on Opportunistic Protists (IWOP) CY JUL 25-29, 2003 CL Hilo, HI ID CARINII DIHYDROPTEROATE SYNTHASE; THYMIDYLATE SYNTHASE; TRIMETHOPRIM-SULFAMETHOXAZOLE; DIAGNOSTIC-TOOL; DIHYDROFOLATE-REDUCTASE; PNEUMONIA; MUTATIONS; GENE; PROPHYLAXIS; MEDICINE AB Because thymidine metabolism is a potential target for therapy of Pneumocystis pneumonia, it was investigated whether Pneumocystis organisms have a salvage pathway for thymidine by administering 5-bromo-2'-deoxyuridine (BrdU) to mice and rats with Pneumocystis pneumonia. Although BrdU incorporation was detected in host cells, no incorporation was seen in Pneumocystis organisms infecting either rats or mice. This suggests that Pneumocystis organisms do not have a salvage pathway for thymidine, and that inhibitors of de novo synthesis, such as thymidylate synthase inhibitors, may be effective drugs for treating Pneumocystis pneumonia. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov NR 35 TC 4 Z9 4 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD MAY PY 2004 VL 150 BP 1179 EP 1182 DI 10.1099/mic.0.26890-0 PN 5 PG 4 WC Microbiology SC Microbiology GA 822KK UT WOS:000221538000013 PM 15133078 ER PT J AU Ravichandran, V Vasquez, GB Srivastava, S Verma, M Petricoin, E Lubell, J Sriram, RD Barker, PE Gilliland, GL AF Ravichandran, V Vasquez, GB Srivastava, S Verma, M Petricoin, E Lubell, J Sriram, RD Barker, PE Gilliland, GL TI Data standards for proteomics: mitochondrial two-dimensional polyacrylamide gel electrophoresis data as a model system SO MITOCHONDRION LA English DT Article DE 2D gel electrophoresis; data standards; interoperability; proteomics; data uniformity ID PROTEIN IDENTIFICATION AB Proteomics has emerged as a major discipline that led to a re-examination of the need for consensus and a nationally sanctioned set of proteomics technology standards. Such standards for databases and data reporting may be applied to two-dimensional polyacrylamide gel electrophoresis (2D PAGE) technology as a pilot project for assessing global and national needs in proteomics, and the role of the National Institute of Standards and Technology (NIST) and other similar standards and measurement organizations. The experience of harmonizing the heterogeneous data included in the Protein Data Bank (PDB) provides a paradigm for technology in an area where significant heterogeneity in technical detail and data storage has evolved. Here we propose an approach toward standardizing mitochondrial 2D PAGE data in support of a globally relevant proteomics consensus. (C) 2004 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, Mfg Syst Integrat Div, Gaithersburg, MD 20899 USA. Natl Canc Inst, Div Canc Prevent, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Ravichandran, V (reprint author), Univ Maryland, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM vravi@nist.gov NR 12 TC 2 Z9 2 U1 0 U2 0 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 2004 VL 3 IS 6 BP 327 EP 336 DI 10.1016/j.mito.2004.02.006 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 823TE UT WOS:000221635300002 PM 16120364 ER PT J AU Florens, L Liu, X Wang, YF Yang, SG Schwartz, O Peglar, M Carucci, DJ Yates, JR Wu, YM AF Florens, L Liu, X Wang, YF Yang, SG Schwartz, O Peglar, M Carucci, DJ Yates, JR Wu, YM TI Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; Plasmodium; erythrocyte; surface; membrane ID MASS-SPECTRAL DATA; RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM; GENOME SEQUENCE; LIFE-CYCLE; PARASITE; MEMBRANE; MODEL; IDENTIFICATION; CYTOADHERENCE AB Proteins on the surface of parasite-infected erythrocytes (PIESPs) have been one of the major focuses of malaria research due to their role in pathogenesis and their potential as targets for immunity and drug intervention. Despite intense scrutiny, only a few surface proteins have been identified and characterized. We report the identification of two novel surface proteins from Plasmodiom falciparum-infected erythrocytes. Surface proteins were fractionated through biotin-streptavidin interaction and analyzed by shotgun proteomics. From a list of 36 candidates, two were selected for further characterization. The surface location of both proteins was confirmed by confocal microscopy using specific antibodies. PIESP1 and PIESP2 are unlikely to be associated with knobs, the protrusions oil the parasite-infected erythrocyte (PIE) surface. In contrast to other known PIESPs, such as PfEMP1 and Rifin, these novel proteins are encoded by single copy genes, highly conserved across Plasmodium ssp., making them good targets for interventions with a broad specificity to various P. falciparum isolates. (C) 2004 Elsevier B.V. All rights reserved. C1 Amer Type Culture Collect, Manassas, VA USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. NIAID, Malaria Vaccine Dev Unit, Rockville, MD 20852 USA. Univ Texas, Dept Biol, San Antonio, TX 78249 USA. Naval Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. RP Wu, YM (reprint author), Amer Type Culture Collect, 10801 Univ Blvd, Manassas, VA USA. EM yiwu@niaid.nih.gov OI Florens, Laurence/0000-0002-9310-6650 FU NIAID NIH HHS [R21AI49300-1] NR 29 TC 110 Z9 119 U1 1 U2 4 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 2004 VL 135 IS 1 BP 1 EP 11 DI 10.1016/j.molbiopara.2003.12.007 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 821UW UT WOS:000221489500001 PM 15287581 ER PT J AU Park, KY Sellars, EA Grinberg, A Huang, SP Pfeifer, K AF Park, KY Sellars, EA Grinberg, A Huang, SP Pfeifer, K TI The H19 differentially methylated region marks the parental origin of a heterologous locus without gametic DNA methylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; IMPRINTING CONTROL REGION; MOUSE H19; CHROMATIN CONFORMATION; ALPHA-FETOPROTEIN; MOLECULAR-BIOLOGY; IGF2/H19 LOCUS; H19/IGF2 LOCUS; GENE; EXPRESSION AB Igf2 and H19 are coordinately regulated imprinted genes physically linked on the distal end of mouse chromosome 7. Genetic analyses demonstrate that the differentially methylated region (DMR) upstream of the H19 gene is necessary for three distinct functions: transcriptional insulation of the maternal Igf2 allele, transcriptional silencing of paternal H19 allele, and marking of the parental origin of the two chromosomes. To test the sufficiency of the DMR for the third function, we inserted DMR at two heterologous positions in the genome, downstream of H19 and at the alpha-fetoprotein locus on chromosome 5. Our results demonstrate that the DMR alone is sufficient to act as a mark of parental origin. Moreover, this activity is not dependent on germ line differences in DMR methylation. Thus, the DMR can mark its parental origin by a mechanism independent of its own DNA methylation. C1 NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), NICHD, Lab Mammalian Genes & Dev, NIH, Bldg 6B,Room 2B206,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kpfeifer@helix.nih.gov OI Pfeifer, Karl/0000-0002-0254-682X NR 47 TC 28 Z9 29 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 2004 VL 24 IS 9 BP 3588 EP 3595 DI 10.1128/MCB.24.9.3588-3595.2004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 813HL UT WOS:000220898100002 PM 15082756 ER PT J AU West, KL Castellini, MA Duncan, MK Bustin, M AF West, KL Castellini, MA Duncan, MK Bustin, M TI Chromosomal proteins HMGN3a and HMGN3b regulate the expression of glycine transporter 1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HIGH-MOBILITY; GENE-EXPRESSION; TRANSCRIPTIONAL COACTIVATOR; TRANSCRIBED GENES; NASCENT CHROMATIN; THYROID-HORMONE; HISTONE CODE; RAT RETINA; IN-VIVO; HMG-17 AB HMGN proteins promote chromatin unfolding, enhance access to nucleosomes, and modulate transcription from chromatin templates. It is not known whether they act indiscriminately as general modulators of transcription or whether they regulate specific gene expression. Here, we investigated the role of HMGN3, a recently discovered HMGN family member, in transcription in vivo. We created cell lines overexpressing HMGN3a or its splice variant, HMGN3b, and analyzed their gene expression profiles using microarrays and reverse transcriptase PCR. We found that ectopic expression of HMGN3a alters the expression of approximately 0.8% of genes. Both HMGN3a and HMGN3b upregulate the expression of the glycine transporter 1 gene (Glyt1). Glyt1 encodes a membrane transporter that regulates the glycine concentration in synaptic junctions. Both GLYT1 and HMGN3 are highly expressed in glia cells and the eye, and we show that both proteins are coexpressed in the retina. Chromatin immunoprecipitation assays showed that HMGN3 protein is recruited to a region of the Glyt1 gene encompassing the Glyt1a transcriptional start site. These results suggest that HMGN3 regulates Glyt1 expression and demonstrate that members of the HMGN family can regulate the transcription of specific genes. C1 Univ Glasgow, Div Canc Sci & Mol Pathol, Glasgow, Lanark, Scotland. Univ Delaware, Dept Biol Sci, Newark, DE USA. NCI, Met Lab, NIH, Bethesda, MD USA. RP West, KL (reprint author), Western Infirm & Associated Hosp, Dept Pathol, Dumbarton Rd, Glasgow G11 6NT, Lanark, Scotland. EM k.west@clinmed.gla.ac.uk RI Bustin, Michael/G-6155-2015; OI Duncan, Melinda/0000-0003-1570-322X NR 54 TC 33 Z9 34 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 2004 VL 24 IS 9 BP 3747 EP 3756 DI 10.1128/MCB.24.9.3747-3756.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 813HL UT WOS:000220898100016 PM 15082770 ER PT J AU Yang, HS Cho, MH Zakowicz, H Hegamyer, G Sonenberg, N Colburn, NH AF Yang, HS Cho, MH Zakowicz, H Hegamyer, G Sonenberg, N Colburn, NH TI A novel function of the MA-3 domains in transformation and translation suppressor Pdcd4 is essential for its binding to eukaryotic translation initiation factor 4A SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BOX RNA HELICASE; INTERNAL RIBOSOMAL ENTRY; FACTOR 4G EIF4G; MESSENGER-RNA; SECONDARY STRUCTURE; MAMMALIAN TRANSLATION; AP-1 TRANSACTIVATION; PROTEIN-SYNTHESIS; FACTOR EIF-4A; KAPPA-B AB An alpha-helical MA-3 domain appears in several translation initiation factors, including human eukaryotic translation initiation factor 4G (eIF4G) and DAP-5/NAT1/p97, as well as in the tumor suppressor Pdcd4. The function of the MA-3 domain is, however, unknown. C-terminal eIF4G (eIG4Gc) contains an MA-3 domain that is located within the eIF4A-binding region, suggesting a role for eIF4A binding. Interestingly, C-terminal DAP-5/NAT1/p97 contains an MA-3 domain, but it does not bind to eIF4A. Mutation of amino acid residues conserved between Pdcd4 and eIF4Gc but not in DAP-5/NAT1/p97 to the amino acid residues found in the DAP-5/NAT1/p97 indicates that some of these amino acid residues within the MA-3 domain are critical for eIF4A-binding activity. Six Pdcd4 mutants (Pdcd4(E249K), Pdcd4(D253A), Pdcd4(D414K), Pdcd4(D418A), Pdcd4(E249K,D414K), and Pdcd4(D253A,D418A)) lost >90% eIF4A-binding activity. Mutation of the corresponding amino acid residues in the eIF4Gc also produced similar results, as seen for Pdcd4. These results demonstrate that the MA-3 domain is important for eIF4A binding and explain the ability of Pdcd4 or eIF4Gc but not DAP-5/NAT1/p97 to bind to eIF4A. Competition experiments indicate that Pdcd4 prevents ca. 60 to 70% of eIF4A binding to eIF4Gc at a Pdcd4/eIF4A ratio of 1:1, but mutants Pdcd4(D253A) and Pdcd4(D253A,D418A) do not. Translation of stem-loop structured mRNA is susceptible to inhibition by wild-type Pdcd4 but not by Pdcd4(D253A), Pdcd4(D418A), or Pdcd4(D235A,D418A). Together, these results indicate that not only binding to eIF4A but also prevention of eIF4A binding to the MA-3 domain of eIF4Gc contributes to the mechanism by which Pdcd4 inhibits translation. C1 NCI, Canc Res Ctr, Gene Regulat Sect, Frederick, MD 21702 USA. Seoul Natl Univ, Coll Vet Med & Agr Biotechnol, Toxicol Lab, Seoul 151742, South Korea. George Washington Univ, Genet Program, Washington, DC 20037 USA. McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada. RP Yang, HS (reprint author), NCI, Canc Res Ctr, Gene Regulat Sect, Bldg 567,Rm 180, Frederick, MD 21702 USA. EM hyang@nciferf.gov RI Yang, Hsin-Sheng/A-6419-2008; CHO, Myung-Haing/B-7362-2014 NR 45 TC 123 Z9 128 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 2004 VL 24 IS 9 BP 3894 EP 3906 DI 10.1128/MCB.24.9.3894-3906.2004 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 813HL UT WOS:000220898100029 PM 15082783 ER PT J AU Jones, G Song, YT Chung, SY Masison, DC AF Jones, G Song, YT Chung, SY Masison, DC TI Propagation of Saccharomyces cerevisiae [PSI+] prion is impaired by factors that regulate Hsp70 substrate binding SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST PRIONS; ESSENTIAL PROTEIN; CHAPERONE SYSTEM; IN-VITRO; HSP40; HSP90; HSP104; DOMAIN; PSI(+); CELLS AB The Saccharomyces cerevisiae [PSI+] prion is believed to be a self-propagating cytoplasmic amyloid. Earlier characterization of HSP70 (SSA1) mutations suggested that [PSI+] propagation is impaired by alterations that enhance Ssa1p's substrate binding. This impairment is overcome by second-site mutations in Ssa1p's conserved C-terminal motif (GPTVEEVD), which mediates interactions with tetratricopeptide repeat (TPR) cochaperones. Sti1p, a TPR cochaperone homolog of mammalian Hop1 (Hsp70/90 organizing protein), activates Ssa1p ATPase, which promotes substrate binding by Ssa1p. Here we find that in SSA1-21 cells depletion of Sti1p improved [PSI+] propagation, while excess Sti1p weakened it. In contrast, depletion of Fes1p, a nucleotide exchange factor for Ssa1p that facilitates substrate release, weakened [PSI+] propagation, while overproducing Fes1p improved it. Therefore, alterations of Hsp70 cochaperones that promote or prolong Hsp70 substrate binding impair [PSI+] propagation. We also find that the GPTVEEVD motif is important for physical interaction with Hsp40 (Ydj1p), another Hsp70 cochaperone that promotes substrate binding but is dispensable for viability. We further find that depleting Cpr7p, an Hsp90 TPR cochaperone and CyP-40 cyclophilin homolog, improved [PSI+] propagation in SSA1 mutants. Although Cpr7p and Sti1p are Hsp90 cochaperones, we provide evidence that Hsp90 is not involved in [PSI+] propagation, suggesting that Sti1p and Cpr7p functionally interact with Hsp70 independently of Hsp90. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Masison, DC (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 407, Bethesda, MD 20892 USA. EM masisond@helix.nih.gov NR 66 TC 70 Z9 72 U1 1 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 2004 VL 24 IS 9 BP 3928 EP 3937 DI 10.1128/MCB.24.9.3928-3937.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 813HL UT WOS:000220898100032 PM 15082786 ER PT J AU Tanaka, T Dancheck, BL Trifiletti, LC Birnkrant, RE Taylor, BJ Garfield, SH Thorgeirsson, U De Luca, LM AF Tanaka, T Dancheck, BL Trifiletti, LC Birnkrant, RE Taylor, BJ Garfield, SH Thorgeirsson, U De Luca, LM TI Altered localization of retinoid X receptor alpha coincides with loss of retinoid responsiveness in human breast cancer MDA-MB-231 cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; GROWTH-INHIBITION; PHASE-II; NUCLEAR-ORGANIZATION; RESPONSE PATHWAY; CARCINOMA-CELLS; VITAMIN-A; ACID; CHEMOPREVENTION; TRANSCRIPTION AB To understand the mechanism of retinoid resistance, we studied the subcellular localization and function of retinoid receptors in human breast cancer cell lines. Retinoid X receptor alpha (RXRalpha) localized throughout the nucleoplasm in retinoid-sensitive normal human mammary epithelial cells and in retinoid-responsive breast cancer cell line (MCF-7), whereas it was found in the splicing factor compartment (SFC) of the retinoid-resistant MDA-MB-231 breast cancer cell line and in human breast carcinoma tissue. In MDA-MB-231 cells, RXRalpha was not associated with active transcription site in the presence of ligand. Similarly, ligand-dependent RXR homo- or heterodimer-mediated transactivation on RXR response element or RARE showed minimal response to ligand in MDA-MB-231 cells. Infecting MDA-MB-231 cells with adenoviral RXRalpha induced nucleoplasmic overexpression of RXRalpha and resulted in apoptosis upon treatment with an RXR ligand. This suggests that nucleoplasmic RXRalpha restores retinoid sensitivity. Epitope-tagged RXRalpha and a C-terminus deletion mutant failed to localize to the SFC. Moreover, RXRalpha localization to the SFC was inhibited with RXRalpha C-terminus peptide. This peptide also induced ligand-dependent transactivation on RXRE. Therefore, the RXRalpha C terminus may play a role in the intranuclear localization of RXRalpha. Our results provide evidence that altered localization of RXRalpha to the SFC may be an important factor for the loss of retinoid responsiveness in MDA-MB-231 breast cancer cells. C1 NCI, NIH, Bethesda, MD 20892 USA. RP De Luca, LM (reprint author), NCI, NIH, Bldg 37,Rm 4054C,37 Convent Dr, Bethesda, MD 20892 USA. EM delucal@mail.nih.gov NR 56 TC 23 Z9 25 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2004 VL 24 IS 9 BP 3972 EP 3982 DI 10.1128/MCB.24.9.3972-3982.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 813HL UT WOS:000220898100036 PM 15082790 ER PT J AU Qiu, HF Hu, CH Yoon, SP Natarajan, K Swanson, MJ Hinnebusch, AG AF Qiu, HF Hu, CH Yoon, SP Natarajan, K Swanson, MJ Hinnebusch, AG TI An array of coactivators is required for optimal recruitment of TATA binding protein and RNA polymerase II by promoter-bound Gcn4p SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE ACETYLTRANSFERASE COMPLEX; GENERAL TRANSCRIPTION FACTORS; IN-VIVO; SACCHAROMYCES-CEREVISIAE; ACTIVATOR-BINDING; CCR4-NOT COMPLEX; ELONGATION-FACTORS; MEDIATOR COMPLEX; TBP BINDING; YEAST AB Wild-type transcriptional activation by Gcn4p is dependent on multiple coactivators, including SAGA, SWI/SNF, Srb mediator, CCR4-NOT, and RSC, which are all recruited by Gcn4p to its target promoters in vivo. It was not known whether these coactivators are required for assembly of the preinitiation complex (PIC) or for subsequent steps in the initiation or elongation phase of transcription. We find that mutations in subunits of these coactivators reduce the recruitment of TATA binding protein (TBP) and RNA polymerase II (Pol II) by Gcn4p at ARG1, ARG4, and SNZ1, implicating all five coactivators in PIC assembly at Gcn4p target genes. Recruitment of Pol II at SNZ1 and ARG1 was eliminated by mutations in TBP or by deletion of the TATA box, indicating that TBP binding is a prerequisite for Pol 11 recruitment by Gcn4p. However, several mutations in SAGA subunits and deletion of SRB10 had a greater impact on promoter occupancy of Pol II versus TBP, suggesting that SAGA and Srb mediator can promote Pol II binding independently of their stimulatory effects on TBP recruitment. Our results reveal an unexpected complexity in the cofactor requirements for the enhancement of PIC assembly by a single activator protein. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 68 TC 69 Z9 72 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 2004 VL 24 IS 10 BP 4104 EP 4117 DI 10.1128/MCB.24.10.4104-4117.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900003 PM 15121833 ER PT J AU Catez, F Yang, H Tracey, KJ Reeves, R Misteli, T Bustin, M AF Catez, F Yang, H Tracey, KJ Reeves, R Misteli, T Bustin, M TI Network of dynamic interactions between histone H1 and high-mobility-group proteins in chromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROUP CHROMOSOMAL-PROTEINS; FACTOR HMGI-C; LINKER HISTONES; IN-VIVO; GENE-EXPRESSION; DNA-BINDING; MITOTIC PHOSPHORYLATION; LIVING CELLS; TRANSCRIPTION; COMPETITION AB Histone H1 and the high-mobility group (HMG) proteins are chromatin binding proteins that regulate gene expression by modulating the compactness of the chromatin fiber and affecting the ability of regulatory factors to access their nucleosomal targets. Histone H1 stabilizes the higher-order chromatin structure and decreases nucleosomal access, while the HMG proteins decrease the compactness of the chromatin fiber and enhance the accessibility of chromatin targets to regulatory factors. Here we show that in living cells, each of the three families of HMG proteins weakens the binding of H1 to nucleosomes by dynamically competing for chromatin binding sites. The HMG families weaken H1 binding synergistically and do not compete among each other, suggesting that they affect distinct H1 binding sites. We suggest that a network of dynamic and competitive interactions involving HMG proteins and H1, and perhaps other structural proteins, constantly modulates nucleosome accessibility and the local structure of the chromatin fiber. C1 NCI, NIH, Bethesda, MD 20892 USA. N Shore LIJ Res Inst, Lab Biomed Sci, Manhasset, NY 11030 USA. Washington State Univ, Dept Biochem & Biophys, Sch Mol Biosci, Pullman, WA 99164 USA. RP Bustin, M (reprint author), NCI, NIH, Bldg 37,Room 3122B, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015; OI Tracey, Kevin J/0000-0003-1884-6314 NR 63 TC 168 Z9 172 U1 1 U2 3 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 2004 VL 24 IS 10 BP 4321 EP 4328 DI 10.1128/MCB.24.10.4321-4328.2004 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900021 PM 15121851 ER PT J AU Kurenova, E Xu, LH Yang, XH Baldwin, AS Craven, RJ Hanks, SK Liu, ZG Cance, WG AF Kurenova, E Xu, LH Yang, XH Baldwin, AS Craven, RJ Hanks, SK Liu, ZG Cance, WG TI Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; DETACHMENT-INDUCED APOPTOSIS; SURVIVAL SIGNALS; CELL-DEATH; TYROSINE KINASE; HUMAN BREAST; RIP; STAUROSPORINE; ACTIVATION; NECROSIS AB Tumor cells resist the apoptotic stimuli associated with invasion and metastasis by activating survival signals that suppress apoptosis. Focal adhesion kinase (FAK), a tyrosine kinase that is overexpressed in a variety of human tumors, mediates one of these survival signals. Attenuation of FAK expression in tumor cells results in apoptosis that is mediated by caspase 8- and FADD-dependent pathways, suggesting that death receptor pathways are involved in the process. Here, we report a functional link between FAK and death receptors. We have demonstrated that FAK binds to the death domain kinase receptor-interacting protein (RIP). RIP is a major component of the death receptor complex and has been shown to interact with Fas and tumor necrosis factor receptor 1 through its binding to adapter proteins. We have shown that RIP provides proapoptotic signals that are suppressed by its binding to FAK. We thus propose that FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex. C1 Univ Florida, Hlth Sci Ctr, Dept Surg, Gainesville, FL 32610 USA. Univ Florida, Dept Biochem, Gainesville, FL 32610 USA. Univ Florida, Dept Biol Mol, Gainesville, FL 32610 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Cance, WG (reprint author), Univ Florida, Hlth Sci Ctr, Dept Surg, POB 100286,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM cance@surgery.ufl.edu FU NCI NIH HHS [R01 CA065910, CA65910] NR 44 TC 115 Z9 122 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 2004 VL 24 IS 10 BP 4361 EP 4371 DI 10.1128/MCB.24.10.4361-4371.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900025 PM 15121855 ER PT J AU Park, HS Lee, SH Park, D Lee, JS Ryu, SH Lee, WJ Rhee, SG Bae, YS AF Park, HS Lee, SH Park, D Lee, JS Ryu, SH Lee, WJ Rhee, SG Bae, YS TI Sequential activation of phosphatidylinositol 3-kinase, beta Pix, Rac1, and Nox1 in growth factor-induced production of H2O2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; NEUTROPHIL NADPH OXIDASE; COLON EPITHELIAL-CELLS; HYDROGEN-PEROXIDE; GUANOSINE TRIPHOSPHATASES; SUPEROXIDE-PRODUCTION; TISSUE EXPRESSION; FREE SYSTEM; PX DOMAINS; P47(PHOX) AB The generation of reactive oxygen species (ROS) in cells stimulated with growth factors requires the activation of phosphatidylinositol 3-kinase (PI3K) and the Rac protein. We report here that the COOH-terminal region of Nox1, a protein related to gp91(phox) (Nox2) of phagocytic cells, is constitutively associated with PPix, a guanine nucleotide exchange factor for Rac. Both growth factor-induced ROS production and Rac1 activation were completely blocked in cells depleted of betaPix by RNA interference. Rac1 was also shown to bind to the COOH-terminal region of Nox1 in a growth factor-dependent manner. Moreover, the depletion of Nox1 by RNA interference inhibited growth factor-induced ROS generation. These results suggest that ROS production in growth factor-stimulated cells is mediated by the sequential activation of PI3K, betaPix, and Rac1, which then binds to Nox1 to stimulate its NADPH oxidase activity. C1 Ewha Womans Univ, Div Mol Life Sci, Ctr Cell Signalling Res, Seoul 120750, South Korea. Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD USA. NHLBI, Div Mol & Life Sci Postech, NIH, Bethesda, MD USA. RP Bae, YS (reprint author), Ewha Womans Univ, Div Mol Life Sci, Ctr Cell Signalling Res, 11-1 Daehyun Dong, Seoul 120750, South Korea. EM baeys@ewha.ac.kr NR 45 TC 168 Z9 168 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 2004 VL 24 IS 10 BP 4384 EP 4394 DI 10.1128/MCB.24.10.4384-4394.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900027 PM 15121857 ER PT J AU Cui, KR Tailor, P Liu, H Chen, X Ozato, K Zhao, K AF Cui, KR Tailor, P Liu, H Chen, X Ozato, K Zhao, K TI The chromatin-remodeling BAF complex mediates cellular antiviral activities by promoter priming SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; TRUNCATING MUTATIONS; ORDERED RECRUITMENT; INTERFERON-ALPHA; GENE-EXPRESSION; ESSENTIAL ROLES; HUMAN HOMOLOG; IN-VIVO; SWI/SNF; NUCLEOSOME AB The elicitation of cellular antiviral activities is dependent on the rapid transcriptional activation of interferon (IFN) target genes. It is not clear how the interferon target promoters, which are organized into chromatin structures in cells, rapidly respond to interferon or viral stimulation. In this report, we show that alpha IFN (IFN-alpha) treatment of HeLa cells induced hundreds of genes. The induction of the majority of these genes was inhibited when one critical subunit of the chromatin-remodeling SWI/SNF-like BAF complexes, BAF47, was knocked down via RNA interference. Inhibition of BAF47 blocked the cellular response to viral infection and impaired cellular antiviral activity by inhibiting many IFN- and virus-inducible genes. We show that the BAF complex was required to mediate both the basal-level expression and the rapid induction of the antiviral genes. Further analyses indicated that the BAF complex primed some IFN target promoters by utilizing ATP-derived energy to maintain the chromatin in a constitutively open conformation, allowing faster and more potent induction after IFN-alpha treatment. We propose that constitutive binding of the BAF complex is an important mechanism for the IFN-inducible promoters to respond rapidly to IFN and virus stimulation. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. RP Zhao, K (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov NR 45 TC 62 Z9 63 U1 0 U2 3 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 2004 VL 24 IS 10 BP 4476 EP 4486 DI 10.1128/MCB.24.10.4476-4486.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900035 PM 15121865 ER PT J AU Kurzer, JH Argetsinger, LS Zhou, YJ Kouadio, JL O'Shea, JJ Carter-Su, C AF Kurzer, JH Argetsinger, LS Zhou, YJ Kouadio, JL O'Shea, JJ Carter-Su, C TI Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-HORMONE RECEPTOR; ADAPTER PROTEIN; JANUS KINASE; ERYTHROPOIETIN RECEPTOR; CATALYTIC ACTIVITY; BINDING PROTEIN; PHOSPHATASE 1B; SH2 DOMAIN; BCR-ABL; PHOSPHORYLATION AB The tyrosine kinase Janus kinase 2 (JAK2) binds to the majority of the known members of the cytokine family of receptors. Ligand-receptor binding leads to activation of the associated JAK2 molecules, resulting in rapid autophosphorylation of multiple tyrosines within JAK2. Phosphotyrosines can then serve as docking sites for downstream JAK2 signaling molecules. Despite the importance of these phosphotyrosines in JAK2 function, only a few sites and binding partners have been identified. Using two-dimensional phosphopeptide mapping and a phosphospecific antibody, we identified tyrosine 813 as a site of JAK2 autophosphorylation of overexpressed JAK2 and endogenous JAK2 activated by growth hormone. Tyrosine 813 is contained within a YXXL sequence motif associated with several other identified JAK2 phosphorylation sites. We show that phosphorylation of tyrosine 813 is required for the SH2 domain-containing adapter protein SH2-Bbeta to bind JAK2 and to enhance the activity of JAK2 and STAT5B. The homologous tyrosine in JAK3, tyrosine 785, is autophosphorylated in response to interleukin-2 stimulation and is required for SH2-Bbeta to bind JAK3. Taken together these data strongly suggest that tyrosine 813 is a site of autophosphorylation in JAK2 and is the SH2-Bbeta-binding site within JAK2 that is required for SH2-Bbeta to enhance activation of JAK2. C1 Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Grad Program Cellular & Mol Biol, Ann Arbor, MI 48109 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Carter-Su, C (reprint author), Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. EM cartersu@umich.edu FU NCI NIH HHS [P30 CA046592, P30 CA46592]; NIAMS NIH HHS [P60-AR20557]; NIDDK NIH HHS [R01 DK034171, P60-DK20572, P60 DK020572, R56 DK054222, DK54222, R01 DK054222, R37 DK034171, DK34171]; NIGMS NIH HHS [T32 GM007863, T32-GM08322, T32 GM008322, T32 GM07863] NR 46 TC 80 Z9 85 U1 1 U2 3 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 2004 VL 24 IS 10 BP 4557 EP 4570 DI 10.1128/MCB.24.10.4557-4570.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900042 PM 15121872 ER PT J AU Naslavsky, N Boehm, M Backlund, PS Caplan, S AF Naslavsky, N Boehm, M Backlund, PS Caplan, S TI Rabenosyn-5 and EHD1 interact and sequentially regulate protein recycling to the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CLASS-I MOLECULES; TRANSFERRIN RECEPTOR; EARLY ENDOSOMES; TRAFFICKING PATHWAYS; MASS-SPECTROMETRY; ENDOCYTIC PATHWAY; EFFECTOR PROTEIN; MAMMALIAN-CELLS; RAB4; COMPARTMENT AB EHD1 has been implicated in the recycling of internalized proteins to the plasma membrane. However, the mechanism by which EHD1 mediates recycling and its relationship to Rab-family-controlled events has yet to be established. To investigate further the mode of EHD1 action, we sought to identify novel interacting partners. GST-EHD1 was used as bait to isolate a similar to120-kDa species from bovine and murine brain cytosol, which was identified by mass spectrometry as the divalent Rab4/Rab5 effector Rabenosyn-5. We mapped the sites of interaction to the EH domain of EHD1, and the first two of five NPF motifs of Rabenosyn-5. Immunofluorescence microscopy studies revealed that EHD1 and Rabenosyn-5 partially colocalize to vesicular and tubular structures in vivo. To address the functional roles of EHD1 and Rabenosyn-5, we first demonstrated that RNA interference (RNAi) dramatically reduced the level of expression of each protein, either individually or in combination. Depletion of either EHD1 or Rabenosyn-5 delayed the recycling of transferrin and major histocompatibility complex class I to the plasma membrane. However, whereas depletion of EHD1 caused the accumulation of internalized cargo in a compact juxtanuclear compartment, Rabenosyn-5-RNAi caused its retention within a dispersed peripheral compartment. Simultaneous RNAi depletion of both proteins resulted in a similar phenotype to that observed with Rabenosyn-5-RNAi alone, suggesting that Rabenosyn-5 acts before EHD1 in the regulation of endocytic recycling. Our studies suggest that Rabenosyn-5 and EHD1 act sequentially in the transport of proteins from early endosomes to the endosomal recycling compartment and back to the plasma membrane. C1 Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. NICHHD, Cell Biol & Metab Branch, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Metab Anal & Mass Spect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Caplan, S (reprint author), Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, 600 S 42nd St, Omaha, NE 68198 USA. EM scaplan@unmc.edu NR 54 TC 83 Z9 85 U1 0 U2 3 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 2004 VL 15 IS 5 BP 2410 EP 2422 DI 10.1091/mbc.E03-10-0733 PG 13 WC Cell Biology SC Cell Biology GA 817PL UT WOS:000221189300031 PM 15020713 ER PT J AU Hommura, F Katabami, M Leaner, VD Donninger, H Sumter, TF Resar, LMS Birrer, MJ AF Hommura, F Katabami, M Leaner, VD Donninger, H Sumter, TF Resar, LMS Birrer, MJ TI HMG-I/Y is a c-Jun/activator protein-1 target gene and is necessary for c-Jun-induced anchorage-independent growth in Rat1a cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID IFN-BETA GENE; IN-SITU HYBRIDIZATION; PROSTATE-CANCER; DNA-BINDING; DIFFERENTIAL REGULATION; ARCHITECTURAL PROTEIN; TRANSCRIPTION FACTORS; CHROMOSOMAL-PROTEINS; INCREASED EXPRESSION; MALIGNANT PHENOTYPE AB The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1-responsive target genes, we used a doxycycline-inducible c-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by c-Jun. Following induction of c-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of c-Jun expression, and gel mobility shift assays demonstrate that induced c-Jun binds to an AP-1 consensus site at position -1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of c-Jun-overexpressing Ratla cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Ratla cells (although the colonies are smaller than that observed for the cells overexpressing c-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of c-Jun necessary for c-Jun-induced anchorage-independent growth in Ratla cells. C1 Natl Canc Inst, Cell & Canc Biol Branch, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD USA. RP Birrer, MJ (reprint author), Natl Canc Inst, Cell & Canc Biol Branch, Rockville, MD USA. EM birrerm@bprb.nci.nih.gov RI Kim, Seongman/N-6910-2014 NR 66 TC 26 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2004 VL 2 IS 5 BP 305 EP 314 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 828AK UT WOS:000221944600005 PM 15192124 ER PT J AU Minnnaugh, EG Xu, WP Vos, M Yuan, XT Isaacs, JS Bisht, KS Gius, D Neckers, L AF Minnnaugh, EG Xu, WP Vos, M Yuan, XT Isaacs, JS Bisht, KS Gius, D Neckers, L TI Simultaneous inhibition of hsp 90 and the proteasome promotes protein ubiquitination, causes endoplasmic reticulum-derived cytosolic vacuolization, and enhances antitumor activity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HEAT-SHOCK RESPONSE; MULTIPLE-MYELOMA CELLS; FACTOR-KAPPA-B; HSP90 INHIBITORS; IN-VIVO; MOLECULAR CHAPERONES; PROTEOLYTIC PATHWAY; CANCER-THERAPY; GELDANAMYCIN; DEGRADATION AB The ansamycin antibiotic, geldanamycin, targets the hsp 90 protein chaperone and promotes ubiquitin-dependent proteasomal degradation of its numerous client proteins. Bortezomib is a specific and potent proteasome inhibitor. Both bortezomib and the geldanamycin analogue, 17-N-allylamino-17-demethoxy geldanamycin, are in separate clinical trials as new anticancer drugs. We hypothesized that destabilization of hsp 90 client proteins with geldanamycin, while blocking their degradation with bortezomib, would promote the accumulation of aggregated, ubiquitinated, and potentially cytotoxic proteins. Indeed, geldanamycin plus bortezomib inhibited MCF-7 tumor cell proliferation significantly more than either drug alone. Importantly, while control cells were unaffected, human papillomavirus E6 and E7 transformed fibroblasts were selectively sensitive to geldanamycin plus bortezomib. Geldanamycin alone slightly increased protein ubiquitination, but when geldanamycin was combined with bortezomib, protein ubiquitination was massively increased, beyond the amount stabilized by bortezomib alone. In geldanamycin plus bortezomib-treated cells, ubiquitinated proteins were mostly detergent insoluble, indicating that they were aggregated. Individually, both geldanamycin and bortezomib induced hsp 90, hsp 70, and GRP78 stress proteins, but the drug combination superinduced these chaperones and caused them to become detergent insoluble. Geldanamycin plus bortezomib also induced the formation of abundant, perinuclear vacuoles, which were neither lysosomes nor autophagosomes and did not contain engulfed cytosolic ubiquitin or hsp 70. Fluorescence marker experiments indicated that these vacuoles were endoplasmic reticulum derived and that their formation was prevented by cycloheximide, suggesting a role for protein synthesis in their genesis. These observations support a mechanism whereby the geldanamycin plus bortezomib combination simultaneously disrupts hsp 90 and proteasome function, promotes the accumulation of aggregated, ubiquitinated proteins, and results in enhanced antitumor activity. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Rockville, MD 20850 USA. NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Rockville, MD 20850 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Rockville, MD 20850 USA. RP NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM edmim@mail.nih.gov NR 85 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2004 VL 3 IS 5 BP 551 EP 566 PG 16 WC Oncology SC Oncology GA 820MX UT WOS:000221394800005 ER PT J AU Gouaze, V Yu, JY Bleicher, RJ Han, TY Liu, YY Wang, HT Gottesman, MM Bitterman, A Giuliano, AE Cabot, MC AF Gouaze, V Yu, JY Bleicher, RJ Han, TY Liu, YY Wang, HT Gottesman, MM Bitterman, A Giuliano, AE Cabot, MC TI Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; CERAMIDE GLYCOSYLATION; ADRIAMYCIN RESISTANCE; TOPOISOMERASE-II; ANTICANCER DRUGS; LINES; EXPRESSION; METABOLISM; APOPTOSIS AB Resistance to natural product chemotherapy drugs is a major obstacle to successful cancer treatment. This type of resistance is often acquired in response to drug exposure; however, the mechanisms of this adverse reaction are complex and elusive. Here, we have studied acquired resistance to Adriamycin, Vinca alkaloids, and etoposide in MCF-7 breast cancer cells, KB-3-1 epidermoid carcinoma cells, and other cancer cell lines to determine if there is an association between expression of glucosylceramide synthase, the enzyme catalyzing ceramide glycosylation to glucosylceramide, and the multidrug-resistant (MDR) phenotype. This work shows that glucosylceramide levels increase concomitantly with increased drug resistance in the KB-3-1 vinblastine-resistant sublines KB-V.01, KB-V.1, and KB-V1 (listed in order of increasing MDR). The levels of glucosylceramide synthase mRNA, glucosylceramide synthase protein, and P-glycoprotein (P-gp) also increased in parallel. Increased glucosylceramide levels were also present in Adriamycin-resistant KB-3-1 sublines KB-A.05 and KB-A1. In breast cancer, detailed analysis of MCF-7 wild-type and MCF-7-AdrR cells (Adriamycin-resistant) demonstrated enhanced glucosylceramide synthase message and protein, P-gp message and protein, and high levels of glucosylceramide in resistant cells. Similar results were seen in vincristine-resistant leukemia, etoposide-resistant melanoma, and Adriamycin-resistant colon cancer cell lines. Cell-free glucosylceramide synthase activity was higher in lysates obtained from drug-resistant cells. Lastly, glucosylceramide synthase promoter activity was 15-fold higher in MCF-7-AdrR compared with MCF-7 cells. We conclude that selection pressure for resistance to natural product chemotherapy drugs selects for enhanced ceramide metabolism through glucosylceramide synthase in addition to enhanced P-gp expression. A possible connection between glucosylceramide synthase and P-gp in drug resistance biology is suggested. C1 St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA 90404 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Carmel Hosp, Dept Surg A, Haifa, Israel. Palo Alto Med Fdn, Dept Surg, Palo Alto, CA USA. RP Cabot, MC (reprint author), St Johns Hlth Ctr, John Wayne Canc Inst, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. EM cabot@jwci.org RI Gouaze-Andersson, Valerie/O-9180-2014; OI Gouaze-Andersson, Valerie/0000-0002-1797-515X; Liu, Yong-Yu/0000-0002-7968-0162 FU NCI NIH HHS [CA95339] NR 45 TC 87 Z9 100 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2004 VL 3 IS 5 BP 633 EP 639 PG 7 WC Oncology SC Oncology GA 820MX UT WOS:000221394800013 PM 15141021 ER PT J AU Cheng, RYS Hockman, T Crawford, E Anderson, LM Shiao, YH AF Cheng, RYS Hockman, T Crawford, E Anderson, LM Shiao, YH TI Epigenetic and gene expression changes related to transgenerational carcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE transgenerational; gene methylation; ribosomal RNA; T3 thyroid hormone; microarray ID ACUTE LYMPHOBLASTIC-LEUKEMIA; THYROID-HORMONE REGULATION; PROSTATE-CANCER; SERUM TRIIODOTHYRONINE; TRANSCRIPTION FACTOR; FOOD-INTAKE; CELL-LINES; MALE-MICE; PROTEIN; TUMOR AB Transgenerational carcinogenesis refers to transmission of cancer risk to the untreated progeny of parents exposed to carcinogens before mating. Accumulated evidence suggests that the mechanism of this process is epigenetic, and might involve hormonal and gene expression changes in offspring. To begin to test this hypothesis, we utilized a mouse model (NIH Swiss) in which exposure of fathers to Cr(III) chloride 2 wk before mating can alter incidence of neoplastic and nonneoplastic changes in offspring tissues. Utilizing a MS-RDA approach, we found that the sperm of these fathers had a significantly higher percentage of undermethylated copies of the 45S ribosomal RNA gene (rRNA); this finding was confirmed by bisulfite sequencing. Because gene methylation is a known mechanism of expression control in germ cells, and ribosomal RNA levels have been linked to cancer, these findings are consistent with the hypothesis. Secondly, we observed that offspring of Cr(III)-treated fathers were significantly heavier than controls, and had higher levels of serum T3. Possible effects of T3 levels on gene expression in the offspring were examined by microarray analysis of cDNAs from liver. A total of 58 genes, including 25 named genes, had expression ratios that correlated significantly with serum T3 ratios at P less than or equal to 0.001. Some of these genes have potential roles in growth and/or tumor suppression. These results also support the hypothesis of an epigenetic and/or gene expression-based mechanism for transgenerational carcinogenesis. Published 2004 Wiley-Liss, Inc. C1 NCI Frederick, Lab Comparat Carcinogenesis, Ft Detrick, MD 21702 USA. RP Anderson, LM (reprint author), NCI Frederick, Lab Comparat Carcinogenesis, Bldg 538, Ft Detrick, MD 21702 USA. OI Cheng, Robert/0000-0003-0287-6439 NR 68 TC 68 Z9 72 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 2004 VL 40 IS 1 BP 1 EP 11 DI 10.1002/mc.20022 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 818NK UT WOS:000221251600001 PM 15108325 ER PT J AU Appelbaum, L Toyama, R Dawid, IB Klein, DC Baler, R Gothilf, Y AF Appelbaum, L Toyama, R Dawid, IB Klein, DC Baler, R Gothilf, Y TI Zebrafish serotonin-N-acetyltransferase-2 gene regulation: Pineal-restrictive downstream module contains a functional E-box and three photoreceptor conserved elements SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SEROTONIN-N-ACETYLTRANSFERASE; MELATONIN SYNTHESIS; PROTEASOMAL PROTEOLYSIS; CIRCADIAN CLOCK; EXPRESSION; GLAND; PROMOTER; CRX; TRANSCRIPTION; RETINA AB Pineal function is defined by a set of very narrowly expressed genes that encode proteins required for photoperiodic transduction and rhythmic melatonin secretion. One of these proteins is serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT), which controls the daily rhythm in melatonin production. Here, pineal-specific expression of the zebrafish aanat-2 (zfaanat-2) was studied using in vivo transient expression analyses of promoter-reporter constructs; this revealed that specificity is determined by two regions located 12 kb away from each other. One is the 5'-flanking region, and the other is a 257-bp sequence, located 6 kb downstream of the transcribed region. This 3'-sequence, designated pineal-restrictive downstream module (PRDM), has a dual function: enhancement of pineal expression and inhibition of extrapineal expression. The former is an autonomic property of PRDM whereas the later function requires interaction with the upstream regulatory region of zfaanat-2. Functional analyses of the PRDM sequence revealed that three photoreceptor conserved elements (TAATC) and a single perfect E-box (CACGTG) are crucial for the dual function of PRDM. These results indicate that pineal specificity of zfaanat-2 is determined by the dual functionality of the PRDM and the interaction between upstream regulatory region and downstream photoreceptor conserved elements and E-box element. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Gothilf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-61390 Tel Aviv, Israel. EM yoavg@tauex.tau.ac.il NR 41 TC 36 Z9 36 U1 2 U2 3 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 1 PY 2004 VL 18 IS 5 BP 1210 EP 1221 DI 10.1210/me.2003-0439 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 815PO UT WOS:000221054400013 PM 14988431 ER PT J AU Kleta, R Stuart, C Gill, FA Gahl, WA AF Kleta, R Stuart, C Gill, FA Gahl, WA TI Renal glucosuria due to SGLT2 mutations SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE D-glucose; SGLT1; SGLT2; SGLT3; GLUT1; GLUT2; renal Fanconi syndrome; glucosuria AB Isolated renal glucosuria results from mutations in SGLT2, which codes for an active transporter specific for D-glucose and expressed in the luminal membrane of the renal proximal tubule. In affected individuals, glucosuria leads to pursuit of hyperglycemia to exclude defects in glucose metabolism, and to investigation of renal proximal tubular function to exclude renal Fanconi syndrome. Here we present clinical and molecular data regarding a 19-year-old woman with isolated glucosuria. She was compound heterozygous for two SGLT2 mutations, i.e., a new missense mutation, T200K, and a known missense mutation, N654S. Published by Elsevier Inc. C1 NHGRI, Sect Human Biochem Genet, Med Gent Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Rare Dis, Intramural Program, Off Director, Bethesda, MD USA. NIH, Internal Med Consult Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Kleta, R (reprint author), NHGRI, Sect Human Biochem Genet, Med Gent Branch, NIH, Bldg 10,Room 10C-107,MSC 1851,10 Ctr Dr, Bethesda, MD 20892 USA. EM kletar@mail.nih.gov NR 8 TC 28 Z9 31 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2004 VL 82 IS 1 BP 56 EP 58 DI 10.1016/j.ymgme.2004.01.018 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 821DJ UT WOS:000221439900008 PM 15110322 ER PT J AU Kim, DK Kabat, J Borrego, F Sanni, TB You, CH Coligan, JE AF Kim, DK Kabat, J Borrego, F Sanni, TB You, CH Coligan, JE TI Human NKG2F is expressed and can associate with DAP12 SO MOLECULAR IMMUNOLOGY LA English DT Article DE NKG2 family; NKG2F; NK cells; DAP12; ITIM; CD94 ID NATURAL-KILLER-CELL; PROTEIN-TYROSINE PHOSPHATASES; CLASS-I MOLECULES; INHIBITORY RECEPTOR; CUTTING EDGE; NK CELLS; HLA-E; ACTIVATING RECEPTORS; CD94/NKG2 RECEPTORS; KIR2DL4 CD158D AB The NKG2 family of C-lectin type molecules is important for regulating the function of natural killer and subpopulations of T cells. NKG2A/B contains an immunoreceptor tyrosine-based inhibitory motif (ITIM) and accordingly functions as an inhibitory receptor, whereas NKG2C and -E/H associate with DAP12 via a positively charged residue in their transmembrane domains and function as activation receptors. Each of these molecules is paired with CD94 for expression and recognizes HLA-E as a ligand. NKG2F is an orphan gene within the NKG2 family whose translated product would contain both a positively charged residue in its transmembrane region, an intracellular ITIM-like sequence and an extracellular domain (62 residues) that is truncated relative to other NKG2 molecules. We show that NKG2F is expressed as a protein in NK cells. Expression appears to be confined to intracellular compartments probably due to its inability to associate with CD94. It can however associate with DAP12 thereby providing activation signaling potential. We were unable to demonstrate phosphorylation of the Tyr residue in the ITIM-like motif suggesting that it is a mock ITIM. NKG2F could be a receptor component with an as yet unidentified partner(s), could function to regulate cell activation through competition for DAP12 with other receptors. such as NKG2C and -E/H, or it could simply be a vestigial gene product. Published by Elsevier Ltd. C1 NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Lab Allerg Dis, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov NR 44 TC 25 Z9 25 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 2004 VL 41 IS 1 BP 53 EP 62 DI 10.1016/j.molimm.2004.01.004 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 826EO UT WOS:000221812300006 PM 15140575 ER PT J AU Outten, FW Djaman, O Storz, G AF Outten, FW Djaman, O Storz, G TI A suf operon requirement for Fe-S cluster assembly during iron starvation in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; CYSTEINE DESULFURASE ACTIVITY; AZOTOBACTER-VINELANDII; SULFUR CLUSTERS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; GENETIC-ANALYSIS; TRANSFER-RNA; PROTEIN; ISCS AB The suf and isc operons of Escherichia coli have been implicated in Fe-S cluster assembly. However, it has been unclear why E. coli has two systems for Fe-S cluster biosynthesis. We have examined the regulatory characteristics and mutant phenotypes of both operons to discern if the two operons have redundant functions or if their cellular roles are divergent. Both operons are similarly induced by hydrogen peroxide and the iron chelator 2,2'-dipyridyl, although by different mechanisms. Regulation of the isc operon is mediated by IscR, whereas the suf operon requires OxyR and IHF for the response to oxidative stress and Fur for induction by iron starvation. Simultaneous deletion of iscS and most suf genes is synthetically lethal. However, although the suf and isc operons have overlapping functions, they act as distinct complexes because the SufS desulphurase alone cannot substitute for the IscS enzyme. In addition, suf deletion mutants are more sensitive to iron starvation than isc mutants, and the activity of the Fe-S enzyme gluconate dehydratase is diminished in the suf mutant during iron starvation. These findings are consistent with the model that the isc operon encodes the housekeeping Fe-S cluster assembly system in E. coli, whereas the suf operon is specifically adapted to synthesize Fe-S clusters when iron or sulphur metabolism is disrupted by iron starvation or oxidative stress. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM storz@helix.nih.gov OI Outten, Franklin/0000-0002-9095-0194; Storz, Gisela/0000-0001-6698-1241 NR 50 TC 237 Z9 240 U1 3 U2 18 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2004 VL 52 IS 3 BP 861 EP 872 DI 10.1111/j.1365-2958.2004.04025.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 813YC UT WOS:000220941400022 PM 15101990 ER PT J AU Ferdig, MT Cooper, RA Mu, JB Deng, BB Joy, DA Su, XZ Wellems, TE AF Ferdig, MT Cooper, RA Mu, JB Deng, BB Joy, DA Su, XZ Wellems, TE TI Dissecting the loci of low-level quinine resistance in malaria parasites SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRANSMEMBRANE PROTEIN PFCRT; PLASMODIUM-FALCIPARUM; CHLOROQUINE RESISTANCE; MEFLOQUINE RESISTANCE; MULTIDRUG-RESISTANCE; QUANTITATIVE TRAITS; NA+/H+ EXCHANGERS; MUTATIONS; INVITRO; ANTIMALARIALS AB Quinine (QN) remains effective against Plasmodium falciparum, but its decreasing efficacy is documented from different continents. Multiple genes are likely to contribute to the evolution of QN resistance. To locate genes contributing to QN response variation, we have searched a P. falciparum genetic cross for quantitative trait loci (QTL). Results identify additive QTL in segments of chromosomes (Chrs) 13, 7 and 5, and pairwise effects from two additional loci of Chrs 9 and 6 that interact, respectively, with the QTL of Chrs 13 and 7. The mapped segments of Chrs 7 and 5 contain pfcrt, the determinant of chloroquine resistance (CQR), and pfmdr1, a gene known to affect QN responses. Association of pfcrt with a QTL of QN resistance supports anecdotal evidence for an evolutionary relationship between CQR and reduced QN sensitivity. The Chr 13 segment contains several candidate genes, one of which (pfnhe-1) encodes a putative Na+/H+ exchanger. A repeat polymorphism in pfnhe-1 shows significant association with low QN response in a collection of P. falciparum strains from Asia, Africa and Central and South America. Dissection of the genes and modifiers involved in QN response will require experimental strategies that can evaluate multiple genes from different chromosomes in combination. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bldg 4,Room 126,NIH Campus, Bethesda, MD 20892 USA. EM tew@helix.nih.gov RI Ferdig, Michael/C-6627-2016; OI Su, Xinzhuan/0000-0003-3246-3248 FU NIAID NIH HHS [AI055025] NR 51 TC 173 Z9 175 U1 0 U2 10 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2004 VL 52 IS 4 BP 985 EP 997 DI 10.1111/j.1365-2958.2004.04035.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 818FQ UT WOS:000221231400006 PM 15130119 ER PT J AU Rodionov, O Yarmolinsky, M AF Rodionov, O Yarmolinsky, M TI Plasmid partitioning and the spreading of P1 partition protein ParB SO MOLECULAR MICROBIOLOGY LA English DT Article ID INTEGRATION HOST FACTOR; GLOBAL REGULATOR KORB; COLI F-PLASMID; ESCHERICHIA-COLI; CHROMOSOME SEGREGATION; BACTERIOPHAGE-P1 GENE-10; MOLECULAR DISSECTION; MUTATIONAL ANALYSIS; BACILLUS-SUBTILIS; ACTIVE PARTITION AB Bacterial plasmids of low copy number, P1 prophage among them, are actively partitioned to nascent daughter cells. The process is typically mediated by a pair of plasmid-encoded proteins and a cis-acting DNA site or cluster of sites, referred to as the plasmid centromere. P1 ParB protein, which binds to the P1 centromere (parS), can spread for several kilobases along flanking DNA. We argue that studies of mutant ParB that demonstrated a strong correlation between spreading capacity and the ability to engage in partitioning may be misleading, and describe here a critical test of the dependence of partitioning on the spreading of the wild-type protein. Physical constraints imposed on the spreading of P1 ParB were found to have only a minor, but reproducible, effect on partitioning. We conclude that, whereas extensive ParB spreading is not required for partitioning, spreading may have an auxiliary role in the process. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, M (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6044C,37 Convent Dr, Bethesda, MD 20892 USA. EM myarmo@helix.nih.gov NR 42 TC 44 Z9 44 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2004 VL 52 IS 4 BP 1215 EP 1223 DI 10.1111/j.1365-2958.2004.04055.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 818FQ UT WOS:000221231400023 PM 15130136 ER PT J AU Findlay, VJ Townsend, DM Saavedra, JE Buzard, GS Citro, ML Keefer, LK Ji, XH Tew, KD AF Findlay, VJ Townsend, DM Saavedra, JE Buzard, GS Citro, ML Keefer, LK Ji, XH Tew, KD TI Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug SO MOLECULAR PHARMACOLOGY LA English DT Article ID N-TERMINAL KINASE; PROTEIN-KINASE; INDUCED APOPTOSIS; GENE; INHIBITOR; ANALOG; OVEREXPRESSION; RESISTANCE; ENZYMES; COMPLEX AB We have used structure-based design techniques to introduce the drug O-2-[2,4-dinitro-5-(N-methyl-N-4-carboxyphenylamino) phenyl] 1-N,N-dimethylamino) diazen-1-ium-1,2-diolate (PABA/NO), which is efficiently metabolized to potentially cytolytic nitric oxide by the pi isoform of glutathione S-transferase, an enzyme expressed at high levels in many tumors. We have used mouse embryo fibroblasts (MEFs) null for GSTpi (GSTpi(-/-)) to show that the absence of GST pi results in a decreased sensitivity to PABA/NO. Cytotoxicity of PABA/NO was also examined in a mouse skin fibroblast (NIH3T3) cell line that was stably transfected with GSTpi and/or various combinations of gamma-glutamyl cysteine synthetase and the ATP-binding cassette transporter MRP1. Overexpression of MRP1 conferred the most significant degree of resistance, and in vitro transport studies confirmed that a GSTpi-activated metabolite of PABA/NO was effluxed by MRP1 in a GSH-dependent manner. Additional studies showed that in the absence of MRP1, PABA/NO activated the extracellular-regulated and stress-activated protein kinases ERK, c-Jun NH2-terminal kinase (JNK), and p38. Selective inhibition studies showed that the activation of JNK and p38 were critical to the cytotoxic effects of PABA/NO. Finally, PABA/NO produced antitumor effects in a human ovarian cancer model grown in SCID mice. C1 Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Tew, KD (reprint author), Fox Chase Canc Ctr, Dept Pharmacol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM kd_tew@fccc.edu RI Ji, Xinhua/C-9664-2012; Keefer, Larry/N-3247-2014 OI Ji, Xinhua/0000-0001-6942-1514; Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [CA53893, N01-CO12400] NR 44 TC 64 Z9 69 U1 1 U2 14 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 1 PY 2004 VL 65 IS 5 BP 1070 EP 1079 DI 10.1124/mol.65.5.1070 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814CA UT WOS:000220951600004 PM 15102935 ER PT J AU Wang, H Zhao, Y Bradbury, JA Graves, JP Foley, J Blaisdell, JA Goldstein, JA Zeldin, DC AF Wang, H Zhao, Y Bradbury, JA Graves, JP Foley, J Blaisdell, JA Goldstein, JA Zeldin, DC TI Cloning, expression, and characterization of three new mouse cytochrome P450 enzymes and partial characterization of their fatty acid oxidation activities SO MOLECULAR PHARMACOLOGY LA English DT Article ID SENSITIVE K+ CHANNELS; ARACHIDONIC-ACID; EPOXYEICOSATRIENOIC ACIDS; MOLECULAR-CLONING; CORONARY-ARTERIES; FUNCTIONAL-SIGNIFICANCE; EXTRAHEPATIC TISSUES; LIVER MICROSOMES; ESCHERICHIA-COLI; LINOLEIC ACIDS AB The mammalian CYP2C subfamily is one of the largest and most complicated in the cytochrome P450 superfamily. In this report, we describe the organization of the mouse Cyp2c locus, which contains 15 genes and four pseudogenes, all of which are located in a 5.5-megabase region on chromosome 19. We cloned three novel mouse CYP2C cDNAs ( designated CYP2C50, CYP2C54, and CYP2C55) from mouse heart, liver, and colon, respectively. All three cDNAs contain open reading frames that encode 490 amino acid polypeptides that are 57 to 95% identical to other CYP2Cs. The recombinant CYP2C proteins were expressed in Escherichia coli after N-terminal modification, partially purified, and shown to be active in the metabolism of both arachidonic acid ( AA) and linoleic acid, albeit with different catalytic efficiencies and profiles. CYP2C50 and CYP2C54 metabolize AA to epoxyeicosatrienoic acids (EETs) primarily, and linoleic acid to epoxyoctadecenoic acids (EOAs) primarily, whereas CYP2C55 metabolizes AA to EETs and hydroxyeicosatetraenoic acids and linoleic acid to EOAs and hydroxyoctadecadienoic acids. Northern blotting and reverse transcription-polymerase chain reaction analysis reveal that CYP2C50 transcripts are abundant in liver and heart; CYP2C54 transcripts are present in liver, kidney, and stomach; and CYP2C55 transcripts are abundant in liver, colon, and kidney. Immunoblotting studies demonstrate that CYP2C50 protein is expressed in liver and heart, CYP2C54 protein is detected primarily in liver, and CYP2C55 protein is present primarily in colon. Immunohistochemistry reveals that CYP2C55 is most abundant in surface columnar epithelium in the cecum. We conclude that these new CYP2C enzymes are probably involved in AA and linoleic acid metabolism in mouse hepatic and extrahepatic tissues. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 111 TW Alexander Dr,Bldg 101,Room A323, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012 NR 54 TC 47 Z9 52 U1 1 U2 5 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 1 PY 2004 VL 65 IS 5 BP 1148 EP 1158 DI 10.1124/mol.65.5.1148 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814CA UT WOS:000220951600012 PM 15102943 ER PT J AU Liang, XJ Shen, DW Gottesman, MM AF Liang, XJ Shen, DW Gottesman, MM TI Down-regulation and altered localization of gamma-catenin in cisplatin-resistant adenocarcinoma cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE; DESMOSOMAL CADHERINS; CROSS-RESISTANCE; DRUG-RESISTANCE; MOLECULAR-BASIS; PLAKOGLOBIN; ADHESION; LINES; PROTEINS; EXPRESSION AB Resistance to cisplatin, one of the most widely used anticancer chemotherapeutic agents, is a major clinical problem. There is no effective way to predict development of cisplatin resistance in cancers. As determined by reverse transcription-polymerase chain reaction and Western blotting, the expression of gamma-catenin, an adherens junction protein, was decreased in KB-CP20 and 7404-CP20 cells compared with parental-sensitive cells. Short-term treatment with cisplatin of the parental cells resulted in proteolysis of gamma-catenin as evaluated in membrane pellet preparations, and the extent of cleavage increased as cisplatin concentration was raised from 1 to 5 mug/ml during 1 h of treatment. Uncleaved cytoplasmic gamma-catenin increased under the same conditions. These biochemical results were supported by confocal microscopy, which showed a loss of gamma-catenin from adherens plaques after cisplatin treatment. Cleavage of gamma-catenin was specific to cisplatin treatment in that cleavage did not occur after treatment with doxorubicin and cytosine arabinoside. Pretreatment of KB and 7404 cells with cisplatin for 1 h resulted in reduced uptake of [C-14]carboplatin, suggesting that the biochemical changes induced by cisplatin treatment, including cleavage of gamma-catenin, could affect the ability of cells to internalize platinum compounds. Cells transfected with the gamma-catenin gene are sensitive to cisplatin compared with cells transfected with a control vector. Our data suggest that proteolysis and altered localization of gamma-catenin are early markers for the response of cells to cisplatin, and reduced levels of gamma-catenin in resistant cells may indicate an important role for gamma-catenin in mediating or modulating the toxicity of cisplatin in cancer cells. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 1A09, Bethesda, MD 20892 USA. EM mgottesman@nih.gov NR 35 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY 1 PY 2004 VL 65 IS 5 BP 1217 EP 1224 DI 10.1124/mol.65.5.1217 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 814CA UT WOS:000220951600019 PM 15102950 ER PT J AU Aguila, A Goldsmith, ME Gollapalli, SJ Alley, MC Waud, WW Bates, S Fojo, T AF Aguila, A Goldsmith, ME Gollapalli, SJ Alley, MC Waud, WW Bates, S Fojo, T TI Coxsackie-adenovirus receptor (CAR) levels can be increased in human xenografts followed by treatment with FK228, a histone deacetylase inhibitor SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Div Canc Treatment & Diag, NIH, Frederick, MD 21701 USA. So Res Inst, Birmingham, AL 35255 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 618 BP S234 EP S234 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600619 ER PT J AU Arya, SK D'Costa, J Sachdeva, G Cho, J Kachapati, K AF Arya, SK D'Costa, J Sachdeva, G Cho, J Kachapati, K TI Chimeric lentiviral vectors derived from HIV-1 and HIV-2 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins, Baltimore, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 71 BP S29 EP S29 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600072 ER PT J AU Bielawski, JC Fowler, DH Medin, JA AF Bielawski, JC Fowler, DH Medin, JA TI FasL-over-expressing T lymphocytes as effector cells in anti-prostate cancer gene therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Ontario Canc Inst, Div Expt Therapeut, Toronto, ON M4X 1K9, Canada. 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 950 BP S364 EP S364 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600951 ER PT J AU Bosticardo, M Fieschi, C Novelli, F Casanova, JL Candotti, F AF Bosticardo, M Fieschi, C Novelli, F Casanova, JL Candotti, F TI T lymphocyte-directed gene therapy for IL-12R beta 1 deficiency SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Paris 05, Lab Genet Humaine Malad Infect, INSERM, U550,Fac Med Necker, Paris, France. San Giovanni Battista Hosp, Ctr Expt Res & Clin Studies, Turin, Italy. 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 907 BP S346 EP S346 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600908 ER PT J AU Choi, U Yamashita, K Caldwell, L Malech, HL AF Choi, U Yamashita, K Caldwell, L Malech, HL TI In vivo selective enhancement of correction of human X-linked chronic granulomatous disease neutrophils in NOD/SCID mice transplanted with CD34+stem cells transduced with a bicistronic gp91phox/benzyl guanine resistant methylguanine methyltransferase vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NIAID, Host Def Lab, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 176 BP S67 EP S67 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600177 ER PT J AU Cotrim, AP Goldsmith, CM Sowers, AL Mitchell, JB Baum, BJ AF Cotrim, AP Goldsmith, CM Sowers, AL Mitchell, JB Baum, BJ TI Microvessel injury in irradiation damage in salivary glands SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. NCI, Radiat Biol Branch, CCR, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 769 BP S292 EP S292 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600770 ER PT J AU Cresawn, KO Raben, N Plotz, PH Pacak, C Glick, A Byrne, BJ AF Cresawn, KO Raben, N Plotz, PH Pacak, C Glick, A Byrne, BJ TI A skin-restricted conditionally expressing mouse model of Pompe disease for assessment of gene and enzyme replacement therapies SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL USA. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. NCI, NIH, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 859 BP S326 EP S327 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600860 ER PT J AU Ferguson, C Adler, R Sellers, S Schmidt, M von Kalle, C Dunbar, C Calmels, B AF Ferguson, C Adler, R Sellers, S Schmidt, M von Kalle, C Dunbar, C Calmels, B TI Retroviral vector integration into the genome of rhesus macaque long-term repopulating cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Freiburg, Germany. Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. RI calmels, boris/R-2538-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 708 BP S270 EP S270 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600709 ER PT J AU Guo, ZS Naik, A Hu, Y DeMarco, R O'Malley, M Alexander, R Moss, B Lotze, M Bartlett, DL AF Guo, ZS Naik, A Hu, Y DeMarco, R O'Malley, M Alexander, R Moss, B Lotze, M Bartlett, DL TI Systemic cancer therapy with an enhanced tumor-selective vaccinia virus lacking anti-apoptosis viral genes Spi-2 and Spi-1 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NR 1 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 65 BP S27 EP S27 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600066 ER PT J AU Hong, BK Calmels, B Hanawa, H Gray, J Donahue, RE Persons, DA Nienhuis, AW Hematti, P Dunbar, CE AF Hong, BK Calmels, B Hanawa, H Gray, J Donahue, RE Persons, DA Nienhuis, AW Hematti, P Dunbar, CE TI Retroviral insertion site analysis in rhesus macaques transplanted with CD34+ hematopoietic stem cells transduced with a Simian Immunodeficiency Virus-based lentiviral vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RI calmels, boris/R-2538-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 707 BP S269 EP S269 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600708 ER PT J AU Kim, EY Hong, YB Lai, ZN Brady, RO Jung, SC AF Kim, EY Hong, YB Lai, ZN Brady, RO Jung, SC TI Expression and secretion of human glucocerebrosidase mediated by recombinant lentivirus vectors in vitro and in vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Natl Inst Hlth, Div Genet Dis, Dept Biomed Sci, Seoul, South Korea. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 863 BP S328 EP S328 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600864 ER PT J AU Larochelle, A Krouse, A Orlic, D Donahue, RE Dunbar, CE Hematti, P AF Larochelle, A Krouse, A Orlic, D Donahue, RE Dunbar, CE Hematti, P TI AMD3100-mobilized CD34+ cells are phenotypically different and better targets for retroviral transduction than G-CSF-mobilized CD34+ cells in rhesus macaques SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NHLBI, NIH, Bethesda, MD 20892 USA. 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 705 BP S268 EP S268 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600706 ER PT J AU Li, AZ Li, HW Liu, AH Jacobson, L Noh, E Saulle, D Hankins, GR Chriorini, JA Helm, GA AF Li, AZ Li, HW Liu, AH Jacobson, L Noh, E Saulle, D Hankins, GR Chriorini, JA Helm, GA TI Comparison of the osteogenic potential of AAVhBMP6 and ADhBMP6 between two rat strains SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Virginia, Charlottesville, VA USA. NIDCR, Gene Therapeut Branch, Charlottesville, VA USA. NR 0 TC 1 Z9 1 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 890 BP S339 EP S339 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600891 ER PT J AU Li, L Yang, L Kotin, RM AF Li, L Yang, L Kotin, RM TI The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NIH, Lab Biochem Genet, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 759 BP S289 EP S289 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600760 ER PT J AU Liu, GM Kotin, RM Chiorini, JA Davidson, BL AF Liu, GM Kotin, RM Chiorini, JA Davidson, BL TI Neural progenitor cell transduction with AAV serotypes 1 and 4 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Iowa, Program Gene Therapy, Iowa City, IA USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 230 BP S89 EP S89 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600231 ER PT J AU Liu, GM Chiorini, JA Davidson, BL AF Liu, GM Chiorini, JA Davidson, BL TI AAV4 mediated gene transfer in mucopolysaccharidosis type VII mice SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Iowa, Program Gene Therapy, Iowa City, IA USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 229 BP S89 EP S89 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600230 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 Phenotypic correction of hemophilic mice using hematopoietic stem cells transduced with an MSCV-based oncoretroviral vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 George Washington Univ, Med Ctr, Genet Program, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD USA. Amer Red Cross, Holland Lab, Flow Cytometry Facil, Rockville, MD USA. NCI, Surg Branch, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 186 BP S71 EP S72 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600187 ER PT J AU Mootien, S Siedel, NE Bodine, DM Gallagher, PG AF Mootien, S Siedel, NE Bodine, DM Gallagher, PG TI A novel in vivo, lentivirus-based model of alpha-spectrin function SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Yale Univ, New Haven, CT USA. 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 902 BP S344 EP S344 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600903 ER PT J AU Morrison, BJ Sakai, Y Janik, JE Morris, JC AF Morrison, BJ Sakai, Y Janik, JE Morris, JC TI A comparison of adenoviral-mediated gene transfer in human and mouse dendritic cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NCI, Metab Branch, Ctr Canc Res, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 456 BP S173 EP S174 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600457 ER PT J AU Nakai, H Wu, XL Fuess, S Storm, T Burgess, S Grompe, M Kay, MA AF Nakai, H Wu, XL Fuess, S Storm, T Burgess, S Grompe, M Kay, MA TI Hot spots for rAAV2 vector integration in mice SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. NHGRI, Dev Genom Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR USA. NR 1 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 13 BP S6 EP S6 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600014 ER PT J AU Otsu, M Ariga, T Maeyama, Y Yoshida, J Nakajima, S Kida, M Toita, N Hatano, N Kawamura, N Okano, M Kobayashi, R Tatsuzawa, O Onodera, M Candotti, F Kobayashi, K Sakiyama, Y AF Otsu, M Ariga, T Maeyama, Y Yoshida, J Nakajima, S Kida, M Toita, N Hatano, N Kawamura, N Okano, M Kobayashi, R Tatsuzawa, O Onodera, M Candotti, F Kobayashi, K Sakiyama, Y TI Clinical trial in japan of retroviral-mediated gene transfer to bone marrow CD34(+) cells as a treatment of adenosine deaminase (ADA)-deficiency SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Hokkaido Univ, Grad Sch Med, Res Grp Human Gene Therapy, Sapporo, Hokkaido 060, Japan. Hokkaido Univ, Grad Sch Med, Dept Pediat, Sapporo, Hokkaido, Japan. Natl Ctr Child Hlth& Dev, Div Infect Dis & Rheumatol, Tokyo, Japan. Univ Tsukuba, Div Hematol, Tsukuba, Ibaraki 305, Japan. NIH, GMBB, Bethesda, MD 20892 USA. RI Ariga, Tadashi/A-4252-2012 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 175 BP S67 EP S67 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600176 ER PT J AU Ryser, MF Brenner, S Whiting-Theobald, N Lehmann, R Choi, U Linton, GF Kang, E Rudikoff, AG Farese, AM MacVittie, TJ Horwitz, ME Malech, HL AF Ryser, MF Brenner, S Whiting-Theobald, N Lehmann, R Choi, U Linton, GF Kang, E Rudikoff, AG Farese, AM MacVittie, TJ Horwitz, ME Malech, HL TI Insertional analyses in rhesus monkey blood cells after non-myeloablative hematopoietic stem cell marking with a therapeutic onco-retroviral vector for X-linked chronic granulomatous disease SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Clin Carl Gustav Carus, Dept Pediat, Dresden, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Duke Univ, Adult Bone Marrow & Stem Cell Transplantat Progra, Durham, NC 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 915 BP S350 EP S350 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600916 ER PT J AU Sakai, Y Morrison, BJ Janik, JE Morris, JC AF Sakai, Y Morrison, BJ Janik, JE Morris, JC TI Dendritic cells modified using an adenovirus expressing murine IL-12 inhibits development of tumors in a mouse colon cancer model SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 NCI, Metab Branch, Canc Gene Therapy 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 575 BP S217 EP S217 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600576 ER PT J AU Shan, Z Li, J Zheng, C Liu, X Zhang, C Goldsmith, CM Wellner, RB Baum, BJ Wang, S AF Shan, Z Li, J Zheng, C Liu, X Zhang, C Goldsmith, CM Wellner, RB Baum, BJ Wang, S TI Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated minipig parotid glands SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Capital Univ, Salivary Gland Dis Ctr, Fac Stomatol, Beijing, Peoples R China. NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 1029 BP S394 EP S395 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316601030 ER PT J AU Urabe, M Nakakura, T Ozawa, K Kotin, RM AF Urabe, M Nakakura, T Ozawa, K Kotin, RM TI Production of recombinant adeno-associated virus type 5 in insect cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Jichi Med Sch, Div Genet Ther, Minami Kawachi, Tochigi 32904, Japan. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 419 BP S160 EP S161 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600420 ER PT J AU van Geer, MA Pastan, I van Beusechem, VW Haisma, HJ Bosma, PJ Gouma, DJ Wesseling, JG AF van Geer, MA Pastan, I van Beusechem, VW Haisma, HJ Bosma, PJ Gouma, DJ Wesseling, JG TI Targeting of adenovirus vectors to mesothelin via a bispecific antibody reveals enhanced gene transfer to human pancreatic cancer cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 AMC Liver Ctr, Amsterdam, Netherlands. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Univ Groningen, Univ Ctr Pharm, Groningen, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Surg, NL-1105 AZ Amsterdam, Netherlands. RI Haisma, Hidde/E-8964-2014 OI Haisma, Hidde/0000-0003-3997-9052 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 130 BP S51 EP S51 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600131 ER PT J AU Xia, HB Mao, QW Eliason, SL Kiewiet, N Critchfield, J Martins, IH Harper, SQ He, XH Kotin, RM Zoghbi, HY Orr, HT Paulson, HL Davidson, BL AF Xia, HB Mao, QW Eliason, SL Kiewiet, N Critchfield, J Martins, IH Harper, SQ He, XH Kotin, RM Zoghbi, HY Orr, HT Paulson, HL Davidson, BL TI RNAi therapy for dominant neurodegenerative diseases SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Iowa, Program Gene Therapy, Iowa City, IA USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Program Dev Biol, Houston, TX 77030 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 717 BP S273 EP S274 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600718 ER PT J AU Yant, SR Wu, XL Huang, Y Daigle, B AF Yant, SR Wu, XL Huang, Y Daigle, B TI Nonrandom insertion site preferences for the SB transposon in vitro and in vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 817 BP S309 EP S310 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600818 ER PT J AU Zhang, L Button, B Skiadopoulos, MH Dang, Y Bukreyev, A Gabriel, SE Collins, PL Pickles, RJ AF Zhang, L Button, B Skiadopoulos, MH Dang, Y Bukreyev, A Gabriel, SE Collins, PL Pickles, RJ TI Parainfluenza virus-mediated delivery of CFTR to ciliated cells corrects the CF bioelectrical chloride secretory defect and restores the regulation of airway surface liquid depth and mucus transport to cystic fibrosis airway epithelium SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 UNC Chapel Hill, CF Ctr, Chapel Hill, NC USA. NIAID, 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 687 BP S260 EP S261 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600688 ER PT J AU Zhou, XY Gao, GP Owens, RA Calcedo, R Wilson, JM AF Zhou, XY Gao, GP Owens, RA Calcedo, R Wilson, JM TI Evaluation of novel gene transfer vectors derived from infectious molecular clones of primate AAVs SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Penn, Gene Therapy Program, Philadelphia, PA 19104 USA. NIDDK, LMCB, NIH, Bethesda, MD USA. RI Wilson, James/F-9220-2011 OI Wilson, James/0000-0002-9630-3131 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 90 BP S36 EP S36 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600091 ER PT J AU Malling, HV AF Malling, HV TI Incorporation of mammalian metabolism into mutagenicity testing SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Article DE metabolic activation; mutagen assays; cytochrome p450; mutagen-carcinogen correlation; host-mediated assay; somatic cell mutagenesis; transgenics ID SOMATIC MUTATIONS; NUCLEOTIDE-SEQUENCE; NEUROSPORA-CRASSA; ESCHERICHIA-COLI; TRANSGENIC MICE; DIMETHYLNITROSAMINE; ACTIVATION; CARCINOGENS; MUTAGENESIS; BACTERIA AB In the 1950's and 1960's it became obvious that many chemicals in daily use were mutagenic or carcinogenic. but there seemed to be little relation between the two activities. As scientists were debating the cause of this discrepancy. it was hypothesized that mammalian metabolism could form highly reactive intermediates from rather innocuous chemicals and that these intermediates could react with DNA and were mutagenic. This commentary presents the historical development of metabolic activation in mutagenicity tests. beginning with Udenfriend's hydroxylation system. which mimics aspects of mammalian metabolism in a purely chemical Mixture, and extending through procedures that moved closer and closer to incorporating actual mammalian metabolism into the test systems. The stages include microsomal activation systems. host-mediated assays, incorporation of human P450 genes into the target cells or organisms, and detecting, mutations in single cells in vivo. A recent development in this progression is the insertion of recoverable vectors containing mutational targets into the mammalian genome. Since the target genes of transgenic assays are ill the genome. they are not only exposed to active metabolites. but they also undergo the same repair processes as endogenous genes of the mammalian genome. (C) 2003 Elsevier B.V. All rights reserved. C1 NIEHS, Mammalian Mutagenesis Grp, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Malling, HV (reprint author), NIEHS, Mammalian Mutagenesis Grp, Toxicol Lab, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM malling@niehs.nih.gov NR 39 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD MAY PY 2004 VL 566 IS 3 BP 183 EP 189 DI 10.1016/j.mrrev.2003.11.003 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 892LM UT WOS:000226652100001 PM 15082236 ER PT J AU Jackson, CL AF Jackson, CL TI N-terminal acetylation targets GTPases to membranes SO NATURE CELL BIOLOGY LA English DT Editorial Material ID ADP-RIBOSYLATION FACTOR-1; GOLGI-APPARATUS; ARF; PROTEINS; DOMAIN; RECRUITMENT; TRANSPORT; ARL1 AB The small GTPases Arl3p and Arl1p function sequentially to recruit diverse effector proteins to the Golgi apparatus. Similarly to ARF proteins, Arl1p is targeted to membranes by myristoylation. Arl3p, however, is not myristoylated. Recent work demonstrates that Arl3p, and its mammalian orthologue ARFRP1, are targeted to membranes by amino-terminal acetylation, which facilitates recognition by the membrane receptor Sys1p/hSys1. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Jackson, CL (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM cathyj@helix.nih.gov RI Jackson, Catherine/A-3421-2013 OI Jackson, Catherine/0000-0002-0843-145X NR 15 TC 11 Z9 11 U1 1 U2 7 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 2004 VL 6 IS 5 BP 379 EP 380 DI 10.1038/ncb0504-379 PG 2 WC Cell Biology SC Cell Biology GA 821AV UT WOS:000221432600002 PM 15122260 ER PT J AU Becker, KG Barnes, KC Bright, TJ Wang, SA AF Becker, KG Barnes, KC Bright, TJ Wang, SA TI The Genetic Association Database SO NATURE GENETICS LA English DT Letter ID DISORDERS; DISEASE C1 NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Becker, KG (reprint author), NIA, Gene Express & Genom Unit, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM beckerk@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 9 TC 476 Z9 485 U1 0 U2 6 PU NATURE PUBLISHING GROUP 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 2004 VL 36 IS 5 BP 431 EP 432 DI 10.1038/ng0504-431 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 817NA UT WOS:000221183000002 PM 15118671 ER PT J AU Grady, C AF Grady, C TI Ethics of vaccine research SO NATURE IMMUNOLOGY LA English DT Editorial Material ID DEVELOPING-COUNTRIES; TRIALS; ISSUES; BENEFITS AB Vaccination has attracted controversy at every stage of its development and use. Ethical debates should consider its basic goal, which is to benefit the community at large rather than the individual. C1 NIH, Dept Clin Bioeth, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Warren Grant Magnuson Clin Ctr, Bldg 10-1C118, Bethesda, MD 20892 USA. EM cgrady@nih.gov NR 17 TC 9 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP 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 2004 VL 5 IS 5 BP 465 EP 468 DI 10.1038/ni0504-465 PG 4 WC Immunology SC Immunology GA 816HN UT WOS:000221101100005 PM 15116109 ER PT J AU Jacobelli, J Chmura, SA Buxton, DB Davis, MM Krummel, MF AF Jacobelli, J Chmura, SA Buxton, DB Davis, MM Krummel, MF TI A single class II myosin modulates T cell motility and stopping, but not synapse formation SO NATURE IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN PHOSPHORYLATION; NONMUSCLE MYOSIN; IMMUNOLOGICAL SYNAPSE; IMMUNE INTERACTIONS; ANTIGEN; ACTIVATION; DICTYOSTELIUM; MIGRATION; GENE; CYTOKINESIS AB Upon encountering an antigen, motile T cells stop crawling, change morphology and ultimately form an 'immunological synapse'. Although myosin motors are thought to mediate various aspects of this process, the molecules involved and their exact roles are not defined. Here we show that nonmuscle myosin heavy chain IIA, or MyH9, is the only class II myosin expressed in T cells and is associated with the uropod during crawling. MyH9 function is required for maintenance of the uropod and for T cell motility but is dispensable for synapse formation. Phosphorylation of MyH9 in its multimerization domain by T cell receptor-generated signals indicates that inactivation of this motor may be a key step in the 'stop' response during antigen recognition. C1 Univ Calif San Francisco, Dept Pathol, San Francisco, CA 93143 USA. NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Krummel, MF (reprint author), Univ Calif San Francisco, Dept Pathol, 513 Parnassus Ave, San Francisco, CA 93143 USA. EM krummel@itsa.ucsf.edu OI Buxton, Denis/0000-0003-3077-6435 FU NIAID NIH HHS [R01 AI052116, R01-AI52116-01] NR 44 TC 136 Z9 142 U1 0 U2 2 PU NATURE PUBLISHING GROUP 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 2004 VL 5 IS 5 BP 531 EP 538 DI 10.1038/ni1065 PG 8 WC Immunology SC Immunology GA 816HN UT WOS:000221101100018 PM 15064761 ER PT J AU Saul, A AF Saul, A TI The mosquito's innate sting SO NATURE MEDICINE LA English DT Editorial Material ID ANOPHELES-GAMBIAE; PLASMODIUM AB A mosquito protein similar to complement, a mammalian immune-fighting substance, enables the insect to fend off the malaria parasite. C1 NIAID, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. RP Saul, A (reprint author), NIAID, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. EM ASAUL@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 8 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP 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 2004 VL 10 IS 5 BP 455 EP 457 DI 10.1038/nm0504-455 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 818JW UT WOS:000221242400017 PM 15122241 ER PT J AU Harman, FS Nicol, CJ Marin, HE Ward, JM Gonzalez, FJ Peters, JM AF Harman, FS Nicol, CJ Marin, HE Ward, JM Gonzalez, FJ Peters, JM TI Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis SO NATURE MEDICINE LA English DT Article ID PPAR-GAMMA; COLORECTAL-CANCER; POLYP FORMATION; PHASE-II; MICE; TROGLITAZONE; SUPPRESSION; DISRUPTION; LIGANDS; GROWTH AB Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemically induced mouse models, colon polyp formation was significantly greater in mice nullizygous for PPAR-delta. In contrast to previous reports suggesting that activation of PPAR-delta potentiates colon polyp formation, here we show that PPAR-delta attenuates colon carcinogenesis. C1 Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21702 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU NCI NIH HHS [CA89607, CA97999] NR 15 TC 161 Z9 166 U1 0 U2 2 PU NATURE PUBLISHING GROUP 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 2004 VL 10 IS 5 BP 481 EP 483 DI 10.1038/nm1026 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 818JW UT WOS:000221242400024 PM 15048110 ER PT J AU Insel, TR Volkow, ND Landis, SC Li, TK Battey, JF Sieving, P AF Insel, TR Volkow, ND Landis, SC Li, TK Battey, JF Sieving, P TI Limits to growth: why neuroscience needs large-scale science SO NATURE NEUROSCIENCE LA English DT Editorial Material C1 NIMH, NIH, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD USA. NEI, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Insel, TR (reprint author), NIMH, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 5 TC 27 Z9 28 U1 0 U2 0 PU NATURE PUBLISHING GROUP 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 2004 VL 7 IS 5 BP 426 EP 427 DI 10.1038/nn0504-426 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 816HP UT WOS:000221101300007 PM 15114352 ER PT J AU Pavlovich, CP Schmidt, LS AF Pavlovich, CP Schmidt, LS TI Searching for the hereditary causes of renal-cell carcinoma SO NATURE REVIEWS CANCER LA English DT Review ID LINDAU TUMOR-SUPPRESSOR; HOGG-DUBE-SYNDROME; ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; FACTOR MESSENGER-RNA; MET TYROSINE KINASE; GERMAN-SHEPHERD DOG; WILD-TYPE ALLELE; NIHON RAT MODEL; GERMLINE MUTATIONS AB Families with hereditary predispositions to cancer continue to provide a unique opportunity for the identification and characterization of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal-cell carcinoma, and already genes associated with five of these syndromes have been identified - VHL, MET, FH, BHD and HRPT2. These very different genes and the biochemical pathways in which they participate raise interesting questions about the development of renal cancers and could lead to new therapeutic approaches in the near future. So, what is known about hereditary renal cancer at present? C1 Johns Hopkins Bayview Med Ctr, Brady Urol Inst, Baltimore, MD 21224 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Pavlovich, CP (reprint author), Johns Hopkins Bayview Med Ctr, Brady Urol Inst, A-345,4940 Eastern Ave, Baltimore, MD 21224 USA. EM cpavlov2@jhmi.edu; schmidt@ncifcrf.gov NR 168 TC 110 Z9 114 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2004 VL 4 IS 5 BP 381 EP 393 DI 10.1038/nrc1364 PG 13 WC Oncology SC Oncology GA 817DO UT WOS:000221158400016 PM 15122209 ER PT J AU Grossman, Z Min, B Meier-Schellersheim, M Paul, WE AF Grossman, Z Min, B Meier-Schellersheim, M Paul, WE TI Opinion - Concomitant regulation of T-cell activation and homeostasis SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID EXCISION CIRCLE CONTENT; IN-VIVO ACTIVATION; DENDRITIC CELLS; THYMIC FUNCTION; CD8-T-CELL MEMORY; CLONAL EXPANSION; CD4-T-CELL HELP; HIV-1 INFECTION; SELF-TOLERANCE; IMMUNE-SYSTEM AB T cells constitute a heterogeneous, hierarchically organized population, comprising several maturation/differentiation states that have different capacities for clonal expansion and self-renewal. Here, we argue that the relative probabilities of proliferation, differentiation and death - the cellular events that determine the population's structure, as well as its size - are not entirely preprogrammed or fixed; instead, these events are regulated dynamically through the recurrent interaction of lymphocytes with exogenous and endogenous antigens, antigen-presenting cells and each other. C1 Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NIAID, NIH, Bethesda, MD 20892 USA. RP Grossman, Z (reprint author), Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. EM lcgros@post.tau.ac.il RI Grossman, Zvi/A-9643-2008 NR 107 TC 68 Z9 72 U1 0 U2 6 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 2004 VL 4 IS 5 BP 387 EP 395 DI 10.1038/nri1355 PG 9 WC Immunology SC Immunology GA 817ND UT WOS:000221183300017 PM 15122204 ER PT J AU Nakazawa, K McHugh, TJ Wilson, MA Tonegawa, S AF Nakazawa, K McHugh, TJ Wilson, MA Tonegawa, S TI NMDA receptors, place cells and hippocampal spatial memory SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID LONG-TERM POTENTIATION; COMPLEMENTARY LEARNING-SYSTEMS; SITE-SPECIFIC RECOMBINATION; INHIBITORY AVOIDANCE TASK; EPISODIC-LIKE MEMORY; SPINAL-CORD NEURONS; FREELY-MOVING RAT; PROTEIN-KINASE-A; SYNAPTIC PLASTICITY; KNOCKOUT MICE AB N-methyl-D-aspartate receptors (NMDARs) in the rodent hippocampus have been shown to be essential for spatial learning and memory, and for the induction of long-term synaptic plasticity at various hippocampal synapses. In this review, we examine the evidence concerning the role of NMDARs in hippocampal memory processes, with an emphasis on the function of NMDARs in area CA1 of the hippocampus in memory acquisition, and the unique role of NMDARs in area CA3 in the rapid acquisition and associative retrieval of spatial information. Finally, we discuss the data that have emerged from in vivo hippocampal recording studies that indicate that the activity of hippocampal place cells during behaviour is an expression of a memory trace. C1 MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Picower Ctr Learning & Memory, RIKEN MIT Neurosci Res Ctr, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Tonegawa, S (reprint author), MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. EM tonegawa@mit.edu RI McHugh, Thomas/A-6693-2010; Nakazawa, Kazutoshi/J-6195-2015 OI McHugh, Thomas/0000-0002-1243-5189; Nakazawa, Kazutoshi/0000-0001-5699-9093 NR 167 TC 311 Z9 328 U1 5 U2 50 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2004 VL 5 IS 5 BP 361 EP 372 DI 10.1038/nrn1385 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 817DQ UT WOS:000221158600012 PM 15100719 ER PT J AU Yu, Q Konig, R Pillai, S Chiles, K Kearney, M Palmer, S Richman, D Coffin, JM Landau, NR AF Yu, Q Konig, R Pillai, S Chiles, K Kearney, M Palmer, S Richman, D Coffin, JM Landau, NR TI Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; B MESSENGER-RNA; VIRAL VIF PROTEIN; EDITING ENZYME; REVERSE TRANSCRIPTION; DNA-SYNTHESIS; HYPERMUTATION; TYPE-1; CYTIDINE; GENE AB HIV-1 deleted for the vif accessory gene encapsidates the cellular cytidine deaminase APOBEC3G. Upon infection, the encapsidated APOBEC3G induces G A mutations in the viral reverse transcripts. The G-->A mutations result either from C-->U deamination of the minus strand or deamination of both strands followed by repair of the plus strand. We report here that minus-strand deamination occurred over the length of the virus genome, preferentially at CCCA sequences, with a graded frequency in the 5'-->3' direction. APOBEC3G induced previously undetected C T mutations in the 5' U3 and the primer-binding site, both of which become transiently single-stranded during reverse transcription. In vitro, APOBEC3G bound and deaminated single-stranded DNA (ssDNA) but not double-stranded DNA (dsDNA) or DNA-RNA hybrids. We propose that the requirement for ssDNA accounts for the minus-strand mutations, the 5'-->3' graded frequency of deamination and the rare C T mutations. C1 Salk Inst Biol Studies, Infect Dis Lab, La Jolla, CA 92037 USA. San Diego Healthcare Syst, Vet Adm, La Jolla, CA 92161 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. RP Landau, NR (reprint author), Salk Inst Biol Studies, Infect Dis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM landau@salk.edu FU NIAID NIH HHS [AI27670, AI29164, AI36214, AI38858, AI43638, AI058864]; NIDA NIH HHS [DA014494] NR 36 TC 387 Z9 401 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2004 VL 11 IS 5 BP 435 EP 442 DI 10.1038/nsmb758 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 815VF UT WOS:000221069100010 PM 15098018 ER PT J AU Tuske, S Sarafianos, SG Clark, AD Ding, JP Naeger, LK White, KL Miller, MD Gibbs, CS Boyer, PL Clark, P Wang, G Gaffney, BL Jones, RA Jerina, DM Hughes, SH Arnold, E AF Tuske, S Sarafianos, SG Clark, AD Ding, JP Naeger, LK White, KL Miller, MD Gibbs, CS Boyer, PL Clark, P Wang, G Gaffney, BL Jones, RA Jerina, DM Hughes, SH Arnold, E TI Structures of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DOUBLE-STRANDED DNA; REVERSE-TRANSCRIPTASE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; SELECTIVE EXCISION; NUCLEOSIDE ANALOG; KINETIC MECHANISM; STERIC HINDRANCE; AZT RESISTANCE AB Tenofovir, also known as PMPA, R-9-(2-(phosphonomethoxypropyl)adenine, is a nucleotide reverse transcriptase (RT) inhibitor. We have determined the crystal structures of two related complexes of HIV-1 RT with template primer and tenofovir: (i) a ternary complex at a resolution of 3.0 Angstrom of RT crosslinked to a dideoxy-terminated DNA with tenofovir-diphosphate bound as the incoming substrate; and (ii) a RT DNA complex at a resolution of 3.1 Angstrom with tenofovir at the 3 primer terminus. The tenofovir nucleotide in the tenofovir-terminated structure seems to adopt multiple conformations. Some nucleoside reverse transcriptase inhibitors, including 3TC and AZT, have elements (handles) that project beyond the corresponding elements on normal dNTPs (the substrate envelope). HIV-1 RT resistance mechanisms to AZT and 3TC take advantage of these handles; tenofovir's structure lacks handles that could protrude through the substrate envelope to cause resistance. C1 Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biol & Cell Biol, Key Lab Proteom, Shanghai 200032, Peoples R China. Gilead Sci Inc, Foster City, CA 94404 USA. NCI, HIV Drug Resistance Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA. EM arnold@cabm.rutgers.edu OI 丁, 建平/0000-0001-7029-7346; Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [R01 AI27690, T32 AI50382]; NIGMS NIH HHS [P01 GM56690] NR 34 TC 111 Z9 118 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2004 VL 11 IS 5 BP 469 EP 474 DI 10.1038/nsmb760 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 815VF UT WOS:000221069100015 PM 15107837 ER PT J AU Wolf, M Mousses, S Hautaniemi, S Karhu, R Huusko, P Allinen, M Elkahloun, A Monni, O Chen, YD Kallioniemi, A Kallioniemi, OP AF Wolf, M Mousses, S Hautaniemi, S Karhu, R Huusko, P Allinen, M Elkahloun, A Monni, O Chen, YD Kallioniemi, A Kallioniemi, OP TI High-resolution analysis of gene copy number alterations in human prostate cancer using CGH on cDNA microarrays: Impact of copy number on gene expression SO NEOPLASIA LA English DT Article DE copy number alteration; prostate cancer; gene expression; cDNA microarray; CGH microarray ID COMPARATIVE GENOMIC HYBRIDIZATION; BREAST-CANCER; DNA AMPLIFICATION; PROGRESSION; ANEUPLOIDY; PATTERNS; REVEALS AB Identification of target genes for genetic rearrangements in prostate cancer and the impact of copy number changes on gene expression are currently not well understood. Here, we applied high-resolution comparative genomic hybridization (CGH) on cDNA microarrays for analysis of prostate cancer cell lines. CGH microarrays identified most of the alterations detected by classical chromosomal CGH, as well as a number of previously unreported alterations. Specific recurrent regions of gain (28) and loss (18) were found, and their boundaries defined with sub-megabasepair accuracy. The most common changes included copy number decreases at 13q, and gains at 1q and 5p. Refined mapping identified several sites, such as at 13q (33-44, 49-51, and 74-76 Mbp from the p-telomere), which matched with minimal regions of loss seen in extensive loss of heterozygosity mapping studies of large numbers of tumors. Previously unreported recurrent changes were found at 2p, 2q, 3p, and 17q (losses), and at 3q, 5p, and 6p (gains). Integration of genomic and transcriptomic data revealed the role of individual candidate target genes for genomic alterations as well as a highly significant (P < .0001) overall association between copy number levels and the percentage of differentially expressed genes. Across the genome, the overall impact of copy number on gene expression levels was, to a large extent, attributable to low-level gains and losses of copy number, I corresponding to common deletions and gains of often large chromosomal regions. C1 VTT Tech Res Ctr Finland, FIN-20520 Turku, Finland. Turku Univ, FIN-20520 Turku, Finland. Translat Genom Res Inst, Gaithersburg, MD 20878 USA. Tampere Univ Technol, Inst Signal Proc, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Canc Genet Lab, FIN-33520 Tampere, Finland. Tampere Univ, Inst Med Technol, FIN-33520 Tampere, Finland. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. Univ Helsinki, Biomedicum Biochip Ctr, FIN-00014 Helsinki, Finland. RP Kallioniemi, OP (reprint author), VTT Tech Res Ctr Finland, Itainen Pitkakatu 4, FIN-20520 Turku, Finland. EM olli.kallioniemi@vtt.fi RI Hautaniemi, Sampsa/A-3122-2009; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Hautaniemi, Sampsa/0000-0002-7749-2694; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 NR 25 TC 98 Z9 102 U1 0 U2 1 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2004 VL 6 IS 3 BP 240 EP 247 DI 10.1593/neo.03439 PG 8 WC Oncology SC Oncology GA 821SH UT WOS:000221482400007 PM 15153336 ER PT J AU Forsyth, NR Morales, CP Damle, S Boman, B Wright, WE Kopelovich, L Shay, JW AF Forsyth, NR Morales, CP Damle, S Boman, B Wright, WE Kopelovich, L Shay, JW TI Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient SO NEOPLASIA LA English DT Article DE adenomatous polyposis coli; familial adenomatous polyposis; spontaneous immortalization; telomerase; telomere ID TELOMERASE ACTIVITY; COLORECTAL-CANCER; EPITHELIAL-CELLS; BETA-CATENIN; GENE; APC; MUTATION; ASSOCIATION; FREQUENCY; GERMLINE AB Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancer-suppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, and E6/E7) can lead to escape from senescence, additional doublings, and entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the spontaneously immortalized derivative (C26Ci) cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, and will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention. C1 Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, El Paso, TX USA. Thomas Jefferson Univ, Div Genet & Prevent Med, Philadelphia, PA USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Shay, JW (reprint author), Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. EM jerry.shay@utsouthwestern.edu RI Shay, Jerry/F-7878-2011 FU NCI NIH HHS [CN-85139, CN-85143] NR 24 TC 20 Z9 20 U1 0 U2 0 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2004 VL 6 IS 3 BP 258 EP 265 DI 10.1593/neo.04103 PG 8 WC Oncology SC Oncology GA 821SH UT WOS:000221482400009 PM 15153338 ER PT J AU Lahiri, DK Greig, NH AF Lahiri, DK Greig, NH TI Lethal weapon: amyloid beta-peptide, role in the oxidative stress and neurodegeneration of Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Editorial Material ID LONG-TERM POTENTIATION; REVERSIBLE MEMORY LOSS; PROTEIN FIBRILLOGENESIS; NEUROTOXIC PROPERTIES; LIPID-PEROXIDATION; IN-VIVO; BRAIN; OLIGOMERS; MOUSE; IMMUNIZATION C1 NIA, Neurosci Lab, Drug Design & Dev Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Neurosci Lab, Drug Design & Dev Sect, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dlahiri@iupui.edu; greign@grc.nia.nih.gov NR 49 TC 17 Z9 17 U1 0 U2 0 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 2004 VL 25 IS 5 BP 581 EP 587 DI 10.1016/j.neurobiolaging.2004.02.002 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 832FZ UT WOS:000222254000004 PM 15172733 ER PT J AU Cleveland, A Westergaard, GC Trenkle, MK Higley, JD AF Cleveland, A Westergaard, GC Trenkle, MK Higley, JD TI Physiological predictors of reproductive outcome and mother-infant behaviors in captive rhesus macaque females (Macaca mulatta) SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE 5-hydroxyindoleactetic acid; Macaca mulatta; cortisol; stress; maternal behavior; serotonin ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; NONHUMAN PRIMATE MODEL; EXCESSIVE ALCOHOL-CONSUMPTION; CEREBROSPINAL-FLUID MONOAMINE; DIMINISHED SOCIAL COMPETENCE; INTERINDIVIDUAL DIFFERENCES; VERVET MONKEYS; CSF 5-HIAA; AGGRESSION; SEPARATION AB Previous research has shown that offspring of females with low cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations are less likely to survive the first year of life than are offspring of females with high CSF 5-HIAA concentrations. In addition, studies of free-ranging rhesus macaque males have suggested that individuals with low CSF 5-HIAA concentrations suffer reduced reproductive success relative to their high serotonin counterparts. We examined CSF concentrations of the monoamine metabolites 5-HIAA and homovanillic acid (HVA), and plasma cortisol concentrations as predictors of first-time adult reproductive potential, maternal behavior, and overall social interactions in two groups of captive female rhesus macaques and their first offspring. Repeated CSF and blood samples were obtained from adult females in two social groups, and focal observations were performed for both new mothers and infants during the first month following parturition. We found that the reproductively aged nulliparous females who failed to give birth to their first offspring showed significantly lower CSF 5-HIAA concentrations than those females who gave birth. Among those females that gave birth to offspring, females with low CSF 5-HIAA concentrations and females with high plasma cortisol concentrations were overly protective and restrictive with their infants. CSF HVA concentration was not associated with reproductive output, social behavior, aggression, or mother-infant interactions in this sample of rhesus macaque females. We conclude that low CNS serotonin activity and high stress, measured by high plasma cortisol, are correlated with reduced reproductive success and patterns of high maternal restrictiveness in young adult female rhesus macaques. C1 LABS Virginia Inc, Div Res & Dev, Yemassee, SC 29945 USA. NIAAA, Clin Studies Lab, Bethesda, MD USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res & Dev, 95 Castle Hall Rd,POB 557, Yemassee, SC 29945 USA. EM GWPRIMATE@netscape.net FU NCRR NIH HHS [5U42RR05083, R24RR09983] NR 56 TC 19 Z9 20 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2004 VL 29 IS 5 BP 901 EP 910 DI 10.1038/sj.npp.1300361 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 813PS UT WOS:000220919600007 PM 14666122 ER PT J AU Geiman, TM Sankpal, UT Robertson, AK Chen, Y Mazumdar, M Heale, JT Schmiesing, JA Kim, W Yokomori, K Zhao, YM Robertson, KD AF Geiman, TM Sankpal, UT Robertson, AK Chen, Y Mazumdar, M Heale, JT Schmiesing, JA Kim, W Yokomori, K Zhao, YM Robertson, KD TI Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOMIC METHYLATION PATTERNS; XENOPUS EGG EXTRACTS; PERICENTRIC HETEROCHROMATIN; IMMUNODEFICIENCY SYNDROME; CHROMATIN MODIFICATION; MAMMALIAN DEVELOPMENT; HISTONE DEACETYLASE; REMODELING COMPLEX; PROTEIN COMPLEXES; TOPOISOMERASE-II AB Proper patterns of genome-wide DNA methylation, mediated by DNA methyltransferases DNMT1, -3A and -3B, are essential for embryonic development and genomic stability in mammalian cells. The de novo DNA methyltransferase DNMT3B is of particular interest because it is frequently overexpressed in tumor cells and is mutated in immunodeficiency, centromere instability and facial anomalies (ICF) syndrome. In order to gain a better understanding of DNMT3B, in terms of the targeting of its methylation activity and its role in genome stability, we biochemically purified endogenous DNMT3B from HeLa cells. DNMT3B co-purifies and interacts, both in vivo and in vitro, with several components of the condensin complex (hCAP-C, hCAP-E and hCAP-G) and KIF4A. Condensin mediates genome-wide chromosome condensation at the onset of mitosis and is critical for proper segregation of sister chromatids. KIF4A is proposed to be a motor protein carrying DNA as cargo. DNMT3B also interacts with histone deacetylase 1 (HDAC1), the co-repressor SIN3A and the ATP-dependent chromatin remodeling enzyme hSNF2H. Further more, DNMT3B co-localizes with condensin and KIF4A on condensed chromosomes throughout mitosis. These studies therefore reveal the first direct link between the machineries regulating DNA methylation and mitotic chromosome condensation in mammalian cells. C1 NCI, Epigenet Gene Regulat & Canc Sect, LRBGE, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol & Gene Express Sect, LRBGE, NIH, Bethesda, MD 20892 USA. UT SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea. RP Robertson, KD (reprint author), Univ Florida, Dept Biochem & Mol Biol, Box 100245, Gainesville, FL 32610 USA. EM keithr@ufl.edu FU NCI NIH HHS [CA85146, U01 CA085146]; NIGMS NIH HHS [GM59150, R01 GM059150] NR 71 TC 81 Z9 89 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2004 VL 32 IS 9 BP 2716 EP 2729 DI 10.1093/nar/gkh589 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 825HM UT WOS:000221746900015 PM 15148359 ER PT J AU Goonesekere, NCW Lee, B AF Goonesekere, NCW Lee, B TI Frequency of gaps observed in a structurally aligned protein pair database suggests a simple gap penalty function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SEQUENCE ALIGNMENT; INSERTIONS; DELETIONS; EVOLUTION; CLASSIFICATION; SUBSTITUTION; RECOGNITION; PSEUDOGENES; FEATURES AB Gap penalty is an important component of the scoring scheme that is needed when searching for homologous proteins and for accurate alignment of protein sequences. Most homology search and sequence alignment algorithms employ a heuristic 'affine gap penalty' scheme q + r x n, in which q is the penalty for opening a gap, r the penalty for extending it and n the gap length. In order to devise a more rational scoring scheme, we examined the pattern of gaps that occur in a database of structurally aligned protein domain pairs. We find that the logarithm of the frequency of gaps varies linearly with the length of the gap, but with a break at a gap of length 3, and is well approximated by two linear regression lines with R-2 values of 1.0 and 0.99. The bilinear behavior is retained when gaps are categorized by secondary structures of the two residues flanking the gap. Similar results were obtained when another, totally independent, structurally aligned protein pair database was used. These results suggest a modification of the affine gap penalty function. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5120,37 Convent Dr MSC 4264, Bethesda, MD 20892 USA. EM bk@nih.gov NR 27 TC 12 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2004 VL 32 IS 9 BP 2838 EP 2843 DI 10.1093/nar/gkh610 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 825HM UT WOS:000221746900027 PM 15155852 ER PT J AU Jones, A Cusack, G Chisholm, L AF Jones, A Cusack, G Chisholm, L TI Patient intensity in an ambulatory oncology research center: A step forward for the field of ambulatory care - Part II SO NURSING ECONOMICS LA English DT Article ID OUTCOMES; SYSTEMS; IMPACT AB In Part II of the series regarding the implementation of the Ambulatory Intensity System (AIS), the authors describe aspects of integrating the tool with the patient scheduling system, improving reliability of data collection from the staff, and emphasizing performance improvement throughout the process. Implementation success was attributed to creating a data collection tool that required fewer than 30 seconds to complete, fostering enthusiasm and focus through ongoing education, and giving routine feedback to staff. With a flexible appointment scheduling system and knowledge of the resource requirements for different types of visits, the patient scheduling system was adapted to integrate a consideration for intensity while prospectively scheduling appointments. Data from the AIS supported a performance auditing process identifying opportunities to further focus chart documentation, delegate tasks to ancillary staff, and improve time management. C1 NIH, Warren G Magnuson Clin Ctr, Crit & Acute Care Serv, Bethesda, MD 20892 USA. RP Jones, A (reprint author), NIH, Warren G Magnuson Clin Ctr, Crit & Acute Care Serv, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 4 Z9 4 U1 0 U2 4 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD MAY-JUN PY 2004 VL 22 IS 3 BP 120 EP 123 PG 4 WC Nursing SC Nursing GA 046GV UT WOS:000237800400003 PM 15211914 ER PT J AU Reimer, RA Leone-Vautravers, P Zbinden, I Harris, CC Pfeifer, AMA Mace, K AF Reimer, RA Leone-Vautravers, P Zbinden, I Harris, CC Pfeifer, AMA Mace, K TI Dysregulation of fatty acid synthase mRNA in immortalized human hepatocyte cell lines in response to high glucose and the absence of GLUT2 SO NUTRITION RESEARCH LA English DT Article DE lipogenesis; fatty acid synthase; GLUT2; hepatocyte cell line; triglyceride ID PYRUVATE-KINASE GENE; ELEMENT-BINDING PROTEIN-1C; ADIPOSE-TISSUE; SKELETAL-MUSCLE; RAT HEPATOCYTES; LIPOGENIC GENES; UP-REGULATION; EXPRESSION; LIVER; INSULIN AB The lipogenic pathway has been extensively studied in rodent hepatocytes but poorly studied in human cells. This study examined the effect of glucose and hormones on fatty acid synthase (FAS) gene expression and intracellular lipid synthesis in a human hepatocyte cell line (T-9A4 cells). In low passage cells expressing glucose transporter type 2 (GLUT2) rnRNA, FAS mRNA expression and triacylglycerol (TAG) synthesis increased in response to glucose and the presence of insulin and triiodothyronine (T-3). With increasing passages, the cells no longer expressed the GLUT2 gene, and levels of FAS mRNA were consistently elevated compared to GLUT2 (+) cells. Triglyceride synthesis was also consistently higher in the GLUT2 (-) cells. Glucose-6-phosphate (G-6-P) was constitutively high in GLUT2 (-) cells but increased in response to glucose in GLUT2 (+) cells. In the absence of GLUT2, glucose may be trapped in cells, continuously fueling the generation of G-6-P or subsequent metabolic intermediates that promote FAS gene transcription. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calgary, Fac Kinesiol & Med, Calgary, AB T2N 1N4, Canada. Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Reimer, RA (reprint author), Univ Calgary, Fac Kinesiol & Med, 2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada. EM reimer@ucalgary.ca NR 47 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 2004 VL 24 IS 5 BP 321 EP 336 DI 10.1016/nutres.2004.01.002 PG 16 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 831BW UT WOS:000222168900001 ER PT J AU Warner, EE Mulshine, JL AF Warner, Elizabeth E. Mulshine, James L. TI Lung cancer screening with spiral CT: Toward a working strategy SO ONCOLOGY-NEW YORK LA English DT Article ID HELICAL COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS; ACTION PROJECT; RETINOIC ACID; CARCINOMA; RESECTION; SURVIVAL; LOBECTOMY; MORTALITY; SMOKERS AB Given that there is no validated test for early lung cancer detection, the current standard approach to lung cancer detection is to wait for, signs or symptoms to develop. In that setting, newly detected lung cancer is generally rapidly fatal resulting in over 157, 000 deaths annually. Sole dependence on tobacco control is an insufficient public health response to lung cancer, since most newly diagnosed individuals are either former smokers or never smokers. Finding a more effective way to diagnose premetastatic lung cancer would be a crucial step toward an improved lung cancer-related mortality rate. Based on studies of breast cancer screening, we know that achieving optimal benefit from early cancer detection also involves defining the most effective, efficient, and safest approach to the clinical management of screen-identified lung cancer. In this review, we consider how to build on the successes of other cancer screening efforts to detect and manage early lung cancer. This involves outlining the specific elements for lung cancer that could make a screening program safe, affordable, and effective. We also explore the current standards of early lung cancer management and target areas where potential pitfalls and opportunities for improvement exist. C1 NCI, Expt Intervent Sect, Cell & Canc Biol Branch, Upper Aerodigest Chemoprevent Fac,Canc Res Ctr, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NCI, Expt Intervent Sect, Cell & Canc Biol Branch, Upper Aerodigest Chemoprevent Fac,Canc Res Ctr, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mulshinej@bprb.nci.nih.gov NR 82 TC 15 Z9 15 U1 1 U2 3 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 2004 VL 18 IS 5 BP 564 EP 575 PG 12 WC Oncology SC Oncology GA 052DJ UT WOS:000238211000005 PM 15209187 ER PT J AU Ivy, PS Schoenfeldt, M AF Ivy, PS Schoenfeldt, M TI Current clinical trials of 17-AAG and 17-DMAG - Referral resource SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Ivy, PS (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 19 Z9 20 U1 1 U2 2 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 2004 VL 18 IS 5 BP 610 EP 610 PG 1 WC Oncology SC Oncology GA 052DJ UT WOS:000238211000010 PM 15209189 ER PT J AU Hagenauer, B Maier-Salamon, A Thalhammer, T Zollner, P Senderowicz, A Jager, W AF Hagenauer, B Maier-Salamon, A Thalhammer, T Zollner, P Senderowicz, A Jager, W TI Metabolism of UCN-01 in isolated perfused rat liver: Role of Mrp2 in the biliary excretion of glucuronides SO ONCOLOGY REPORTS LA English DT Article DE UCN-01; metabolism; glucuronide; isolated perfused rat liver; Mrp2 ID PROTEIN-KINASE INHIBITOR; CELL-CYCLE; ALTERED PHARMACOKINETICS; ANTITUMOR-ACTIVITY; ANTICANCER DRUG; 7-HYDROXYSTAUROSPORINE; STAUROSPORINE; PHASE; GLYCOPROTEIN; POTENTIATION AB UCN-01 is a promising, novel kinase inhibitor currently undergoing clinical development. Though UCN-01 shows pronounced antitumor activity, its metabolism and hepatic transport system is still unknown. To investigate the biotransformation and biliary excretion of UCN-01, livers of Wistar and Mrp2-deficient TR rats were perfused with UCN-01 (0.2 muM) in a single pass system. In bile and perfusate, native UCN-01 and 5 novel metabolites (M1-M5) were quantified by HPLC and identified as glucuronides by enzymatic hydrolysis with B-glucuronidase and mass spectroscopy. Cumulative efflux of UCN-01 and its. metabolites M1-M5 into perfusate of Wistar rats was low (<0.14%) whereas total biliary excretion was up to 53-fold higher, representing 1.74, 0.54, 0.21, 1.17, 0.85 and 0.52% of infused UCN-01, respectively. After 60 min of perfusion, liver cells still contained similar to95% of applied UCN-01. Biliary excretion greatly differs in TR- rats. While cumulative biliary excretion of UCN-01 and its metabolites M1-M5 was significantly reduced to 8.3, 5.3, 31.8, 10.4, 13.2 and 7.8%, efflux into perfusate was increased up to 2.2-fold. This indicates that in control rats, UCN-01 and its glucuronides are almost exclusively eliminated into bile by Mrp2. In summary, UCN-01 is extensively metabilized in the rat liver to 5 novel glucuronides mainly excreted into bile by Mrp2. Metabolism and biliary excretion of UCN-01 must be taken into consideration also during cancer therapy of patients. C1 Univ Vienna, Inst Pharmaceut Chem, A-1090 Vienna, Austria. Univ Vienna, AKH, Dept Pathophysiol, A-1010 Vienna, Austria. Univ Vienna, Inst Analyt Chem, A-1090 Vienna, Austria. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Mol Therapeut Unit, Bethesda, MD 20892 USA. RP Jager, W (reprint author), Univ Vienna, Inst Pharmaceut Chem, Althanstr 14, A-1090 Vienna, Austria. EM walter.jaeger@univie.ac.at RI Jager, Walter/I-6242-2013 OI Jager, Walter/0000-0002-4970-8179 NR 25 TC 6 Z9 6 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 PY 2004 VL 11 IS 5 BP 1069 EP 1075 PG 7 WC Oncology SC Oncology GA 811JP UT WOS:000220768500020 PM 15069549 ER PT J AU Doszkocs, TE Zamora, A AF Doszkocs, TE Zamora, A TI Dictionary services and spelling aids for Web searching SO ONLINE LA English DT Article ID LANGUAGE C1 Natl Lib Med, Specialized Informat Serv Div, Bethesda, MD 20894 USA. RP Doszkocs, TE (reprint author), Natl Lib Med, Specialized Informat Serv Div, Bethesda, MD 20894 USA. EM doszocs@nlm.nh.gov; Zamora@mindspring.com NR 9 TC 0 Z9 0 U1 0 U2 0 PU ONLINE INC PI WILTON PA 213 DANBURY RD, WILTON, CT 06897-4007 USA SN 0146-5422 J9 ONLINE JI Online PD MAY-JUN PY 2004 VL 28 IS 3 BP 16 EP 21 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA 816JP UT WOS:000221106500003 ER PT J AU Srivastava, S Taylor, P Wood, LV Lee, SS Robinson, MR AF Srivastava, S Taylor, P Wood, LV Lee, SS Robinson, MR TI Post-surgical scleritis associated with the ganciclovir implant SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID EXTRUSION AB Although the ganciclovir implant is an effective and well-tolerated treatment for cytomegalovirus retinitis in patients with human immunodeficiency virus infection, complications that may occur include retinal detachment, implant extrusion, and endophthalmitis. A 22-year-old woman with human immunodeficiency virus infection presented with a painful left eye with scleritis overlying previous ganciclovir implant sclerotomy sites. The inflammation progressed 360degrees around the pars Plana with progressive thinning at the implant sites. Post-surgical necrotizing scleritis is another complication that can occur in patients with ganciclovir implants. C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD USA. RP Robinson, MR (reprint author), NEI, NIH, 10-10S229,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1082-3069 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD MAY-JUN PY 2004 VL 35 IS 3 BP 254 EP 255 PG 2 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 819WI UT WOS:000221346400014 PM 15185797 ER PT J AU Gopal, V Harrington, JA Goren, A Gannot, I AF Gopal, V Harrington, JA Goren, A Gannot, I TI Coherent hollow-core waveguide bundles for infrared imaging SO OPTICAL ENGINEERING LA English DT Article DE hollow waveguides; IR fiber optics; IR imaging; coherent fiber bundles ID ORDERED BUNDLES; GLASS; FIBERS; SILVER; ATTENUATION AB Coherent IR fiber optic bundles for use in IR imaging from 2 to 12 mum are fabricated from rigid hollow-glass waveguide arrays. The bore of each hollow glass tube in the bundle is coated with thin films of metallic Ag followed by Agl for enhanced reflectivity. The coating of the rigid bundle is done using liquid phase chemistry techniques applied to all tubes simultaneously. The hollow-glass arrays are composed of up to 900 individual tubes with bore sizes as small as 50 mum. Several rigid hollow-core arrays are used to transmit an IR image of a small loop of hot wire and a sample of tissue heated by a CO2 laser. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Rutgers State Univ, Dept Ceram & Mat Engn, Piscataway, NJ 08854 USA. Tel Aviv Univ, Dept Biomed Engn, Fac Engn, IL-69978 Tel Aviv, Israel. NIH, Bethesda, MD 20892 USA. RP Gopal, V (reprint author), Rutgers State Univ, Dept Ceram & Mat Engn, 607 Taylor Rd, Piscataway, NJ 08854 USA. EM jaharrin@rci.rutgers.edu NR 17 TC 17 Z9 18 U1 2 U2 9 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 0091-3286 J9 OPT ENG JI Opt. Eng. PD MAY PY 2004 VL 43 IS 5 BP 1195 EP 1199 DI 10.1117/1.1687729 PG 5 WC Optics SC Optics GA 821JS UT WOS:000221456900029 ER PT J AU Freitas, VM Scheremeta, B Hoffman, MP Jaeger, RG AF Freitas, VM Scheremeta, B Hoffman, MP Jaeger, RG TI Laminin-1 and SIKVAV a laminin-1-derived peptide, regulate the morphology and protease activity of a human salivary gland adenoid cystic carcinoma cell line SO ORAL ONCOLOGY LA English DT Article DE salivary gland neoplasms; adenoid cystic carcinoma; extracellular matrix; laminin; matrix metalloproteinases ID MANDIBULAR EPITHELIAL-CELLS; BASEMENT-MEMBRANE PROTEINS; MATRIX METALLOPROTEINASES; IN-VITRO; PLEOMORPHIC ADENOMA; PRIMARY CULTURE; N-CAM; COLLAGEN; GROWTH; INVASION AB In a previous paper, we demonstrated that laminin-1 and its derived peptide SIKVAV modulates the morphology of an adenoid cystic carcinoma cell line (CAC2 cells). Light microscopy of CAC2 cells grown in three-dimensional preparations of SIKVAV-enriched laminin-1 showed the presence of pseudocystic spaces. Pseudocysts are hallmarks of adenoid cystic carcinoma in vivo. We hypothesized that these pseudocystic spaces could be due to the protease-inducing/ activating rote of SIKVAV. Thus, we studied the presence of matrix metalloproteinases (MMPs) in CAC2 cells treated either by laminin-1 or by SIKVAV-enriched laminin-1. Immunohistochemistry and zymography suggested that SIKVAV enhanced the secretion of MMP-2 and MMP-9 in CAC2 cells. We propose that SIKVAV induces pseudocystic formation probably through the secretion of MMPs 2 and 9. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Sao Paulo, Inst Biomed Sci, Dept Histol & Embryol, BR-05508900 Sao Paulo, Brazil. Penn State Univ, University Pk, PA 16802 USA. NIDCR, CDBRB, NIH, Bethesda, MD USA. RP Jaeger, RG (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Histol & Embryol, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, Brazil. EM rgjaeger@icb.usp.br RI Freitas, Vanessa/D-7897-2012; Jaeger, Ruy/G-8230-2011 OI Freitas, Vanessa/0000-0001-9613-8626; NR 28 TC 16 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 2004 VL 40 IS 5 BP 483 EP 489 DI 10.1016/j.oraloncology.2003.10.002 PG 7 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 813NM UT WOS:000220913800004 PM 15006619 ER PT J AU Max, MB AF Max, MB TI Assessing pain candidate gene studies - Editorial SO PAIN LA English DT Editorial Material ID ASSOCIATION C1 Natl Inst Dental & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Max, MB (reprint author), Natl Inst Dental & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. EM mitchell_max@nih.gov FU NIDCR NIH HHS [DE00366] NR 10 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2004 VL 109 IS 1-2 BP 1 EP 3 DI 10.1016/j.pain.2003.12.036 PG 3 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 816XF UT WOS:000221141900001 PM 15082119 ER PT J AU Bonelli, L De Micheli, A Pugliese, V AF Bonelli, L De Micheli, A Pugliese, V TI Diabetes and pancreatic cancer - Reply SO PANCREAS LA English DT Letter ID ENDOMETRIAL CANCER; COLORECTAL-CANCER; BINDING PROTEIN-3; RISK; MELLITUS; MORTALITY; TYPE-2; COHORT; WOMEN; MEN C1 Natl Canc Inst Genova, Clin Epidemiol Unit, Genoa, Italy. Univ Genoa, San Martino Hosp, Dept Transplantat, Unit Diabetol, Genoa, Italy. Natl Canc Inst, Unit Gastrointestinal Endoscopy & Gastroenterol, Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Ctr Digest Endoscopy, Genoa, Italy. RP Bonelli, L (reprint author), Natl Canc Inst Genova, Clin Epidemiol Unit, Genoa, Italy. NR 15 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2004 VL 28 IS 4 BP 451 EP 452 DI 10.1097/00006676-200405000-00019 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 861ZL UT WOS:000224457500019 ER PT J AU Dutta, S Zhang, YM Conway, JM Sallee, FR Biton, V Reed, MD Kearns, GL AF Dutta, S Zhang, YM Conway, JM Sallee, FR Biton, V Reed, MD Kearns, GL TI Divalproex-ER pharmacokinetics in older children and adolescents SO PEDIATRIC NEUROLOGY LA English DT Article ID EXTENDED-RELEASE FORMULATION; VALPROIC ACID; ANTIEPILEPTIC DRUGS; BIOAVAILABILITY; BINDING; EPILEPSY; AGE AB Valproic acid pharmacokinetic profile and tolerability after administration of divalproex sodium extended-release tablets was characterized in older children and adolescents. In this multiple-dose, open-label, pharmacokinetic study, the patients were divided into two age groups, 8-11 years (older children; n = 15) and 12-17 years (adolescents; In = 14). Once-daily administration of divalproex sodium extended-release tablets (doses ranged from 250 to 1750 mg) in older children and adolescents produced relatively flat plasma valproic acid concentration-time profiles over the entire 24-hour dosing interval, similar to the pharmacokinetic performance of this formulation in adults. The mean (standard deviation) oral clearance values for unbound valproic acid were 94.3 (51.8) and 82.3 (28.2) mL/h/kg and for total valproic acid were 11.2 (3.77) and 9.06 (2.03) mL/h/kg in older children and adolescents, respectively. Two patients discontinued for administrative reasons, whereas one discontinued for an adverse event (flulike syndrome). Adverse events reported by three or more patients were flu syndrome (5 patients, 17.2%) and headache (3 patients, 10.3%). Reported adverse events were generally mild to moderate in severity and similar to those reported in previous divalproex studies. This study demonstrates that in older children and adolescents, once-daily administration of divalproex sodium extended-release tablets may potentially be used to sustain plasma valproic acid concentrations within the usually accepted therapeutic ranges for various indications. (C) 2004 by Elsevier Inc. All rights reserved. C1 Abbott Labs, Abbott Pk, IL 60064 USA. Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Epilepsy Program, Little Rock, AR USA. Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA. Univ Missouri, Dept Pediat, Kansas City, KS USA. Univ Missouri, Dept Pharmacol, Kansas City, KS USA. Childrens Mercy Hosp & Clin, Div Pediat Pharmacol & Med Toxicol, Kansas City, MO USA. NICHHD, Pediat Pharmacol Res Unit Network, Bethesda, MD 20892 USA. RP Dutta, S (reprint author), Dept RUPK,Bldg AP13A,100 Abbott Pk Rd, Abbott Pk, IL 60064 USA. NR 15 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD MAY PY 2004 VL 30 IS 5 BP 330 EP 337 DI 10.1016/j.pediatrneurol.2003.12.006 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 827HP UT WOS:000221890600006 PM 15165635 ER PT J AU Stoll, BJ Hansen, N Fanaroff, AA Wright, LL Carlo, WA Ehrenkranz, RA Lemons, JA Donovan, EF Stark, AR Tyson, JE Oh, W Bauer, CR Korones, SB Shankaran, S Laptook, AR Stevenson, DK Papile, LA Poole, WK AF Stoll, BJ Hansen, N Fanaroff, AA Wright, LL Carlo, WA Ehrenkranz, RA Lemons, JA Donovan, EF Stark, AR Tyson, JE Oh, W Bauer, CR Korones, SB Shankaran, S Laptook, AR Stevenson, DK Papile, LA Poole, WK TI To tap or not to tap: High likelihood of meningitis without sepsis among very low birth weight infants SO PEDIATRICS LA English DT Article DE meningitis; sepsis; lumbar puncture; very low birth weight infants ID BACTERIAL-MENINGITIS; NEONATAL MENINGITIS; LUMBAR PUNCTURE; NEWBORN; OUTCOMES; NETWORK AB Context. Neonatal meningitis is associated with significant morbidity and mortality. We speculated that meningitis may be underdiagnosed among very low birth weight (VLBW) infants because of the failure to perform lumbar punctures (LPs) in infants with suspected sepsis. Objective. This study was undertaken to review the epidemiology of late-onset meningitis in VLBW (401 1500 g) infants and to evaluate the concordance of cerebrospinal fluid (CSF) and blood culture ( BC) results. Methods. VLBW infants (excluding those with intraventricular shunts) born at centers of the National Institute of Child Health and Human Development Neonatal Research Network from September 1, 1998, through December 31, 2001, were studied. Late-onset meningitis was defined by culture-based criteria and classified as meningitis with or without associated sepsis. Unadjusted comparisons were made using chi(2) tests and adjusted comparisons using regression models. Results. Of 9641 VLBW infants who survived >3 days, 2877 (30%) had greater than or equal to1 LPs, and 6056 (63%) had greater than or equal to1 BC performed after day 3. One hundred thirty-four infants had late-onset meningitis (1.4% of all patients; 5% of those with an LP). Pathogens associated with meningitis were similar to those associated with sepsis. One third (45 of 134) of the infants with meningitis had negative BCs. Lower gestational age and prior sepsis increased risk for meningitis. Compared with uninfected infants, those with meningitis had a longer time on mechanical ventilation (28 vs 18 days), had longer hospitalizations (91 vs 79 days), were more likely to have seizures (25% vs 2%), and were more likely to die (23% vs 2%). Conclusions. Meningitis is a serious complication among VLBW infants, associated with increased severity of illness and risk of death. Of note, one third of the infants with meningitis had meningitis in the absence of sepsis. Because CSF cultures were performed only half as often as BCs, this discordance in blood and CSF culture results suggests that meningitis may be underdiagnosed among VLBW infants. C1 Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. NICHHD, Bethesda, MD 20892 USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. Harvard Univ, Childrens Hosp, Joint Program Neonatol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Sch Med, Ctr Clin Res & Evidence Based Med, Houston, TX USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. Univ Miami, Dept Pediat, Miami, FL 33152 USA. Univ Tennessee, Newborn Ctr, Memphis, TN USA. Wayne State Univ, Div Neonatal & Perinatal Med, Detroit, MI USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. Stanford Univ, Med Ctr, Div Neonatol, Palo Alto, CA 94304 USA. Univ New Mexico, Sch Med, Dept Pediat, Albuquerque, NM 87131 USA. RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Dept Pediat, 2040 Ridgewood Dr NE, Atlanta, GA 30322 USA. FU NCRR NIH HHS [M01 RR 00070, M01 RR 00750, M01 RR 00997, M01 RR 01032, M01 RR 02172, M01 RR 02635, M01 RR 06022, M01 RR 08084]; NICHD NIH HHS [U10 HD27871, U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216, U10 HD40689] NR 15 TC 66 Z9 72 U1 2 U2 3 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 2004 VL 113 IS 5 BP 1181 EP 1186 DI 10.1542/peds.113.5.1181 PG 6 WC Pediatrics SC Pediatrics GA 817HS UT WOS:000221169200002 PM 15121927 ER PT J AU Poindexter, BB Ehrenkranz, RA Stoll, BJ Wright, LL Poole, WK Oh, W Bauer, CR Papile, LA Tyson, JE Carlo, WA Laptook, AR Narendran, V Stevenson, DK Fanaroff, AA Korones, SB Shankaran, S Finer, NN Lemons, JA AF Poindexter, BB Ehrenkranz, RA Stoll, BJ Wright, LL Poole, WK Oh, W Bauer, CR Papile, LA Tyson, JE Carlo, WA Laptook, AR Narendran, V Stevenson, DK Fanaroff, AA Korones, SB Shankaran, S Finer, NN Lemons, JA CA Natl Inst Child Hlth Human Dev Neo TI Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 04-07, 2002 CL BALTIMORE, MD SP Pediat Acad Soc DE glutamine; parenteral nutrition; extremely low birth weight infants; randomized clinical trial ID BONE-MARROW TRANSPLANTATION; AMINO-ACID MIXTURE; PROTEIN-METABOLISM; CLINICAL-TRIALS; PRETERM INFANTS; DOUBLE-BLIND; NUTRITION; MORBIDITY AB Background. Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known. Methods. We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis. Results. Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation. Conclusions. Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population. C1 Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. NICHHD, Bethesda, MD 20892 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. Univ Miami, Dept Pediat, Miami, FL 33152 USA. Univ New Mexico, Sch Med, Dept Pediat, Albuquerque, NM 87131 USA. Univ Texas, Hlth Sci Ctr, Sch Med, Ctr Clin Res & Evidence Based Med, Houston, TX USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. Stanford Univ, Med Ctr, Div Neonatol, Palo Alto, CA 94304 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Univ Tennessee, Newborn Ctr, Memphis, TN USA. Wayne State Univ, Div Neonatol & Perinatal Med, Detroit, MI USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. RP Poindexter, BB (reprint author), James Whitcomb Riley Hosp Children, 699 West Dr,RR 208, Indianapolis, IN 46202 USA. EM bpoindex@iupui.edu FU NCRR NIH HHS [M01 RR08084, M01 RR 00997, M01 RR 06022, M01 RR00070, M01 RR00750]; NICHD NIH HHS [U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40689] NR 27 TC 95 Z9 103 U1 0 U2 3 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 2004 VL 113 IS 5 BP 1209 EP 1215 DI 10.1542/peds.113.5.1209 PG 7 WC Pediatrics SC Pediatrics GA 817HS UT WOS:000221169200006 PM 15121931 ER PT J AU Neu, N Leighty, R Adeniyi-Jones, S Diaz, C Handelsman, E Kaufman, G Paul, ME Rich, K Mofenson, L Pitt, J AF Neu, N Leighty, R Adeniyi-Jones, S Diaz, C Handelsman, E Kaufman, G Paul, ME Rich, K Mofenson, L Pitt, J CA Women Infants Transmission Study TI Immune parameters and morbidity in hard drug and human immunodeficiency virus-exposed but uninfected infants SO PEDIATRICS LA English DT Article DE HIV exposed infants; drug use; infant lymphocyte markers ID CHEMOKINE-INDUCED CHEMOTAXIS; T-LYMPHOCYTES; CELL-FUNCTION; MORPHINE; METHADONE; CHILDREN; HIV; MOTHERS; ABNORMALITIES; SUPPRESSION AB Objective. To examine the association of maternal hard drug use (injection drugs, cocaine, and opiates) on lymphocyte subsets and clinical morbidity in uninfected infants who are born to human immunodeficiency virus-infected mothers who were enrolled in the Women and Infants Transmission Study (1990-2000). Methods. Maternal hard drug use was identified by self-report and/or urine toxicology. Infant evaluations occurred at birth and at 1, 2, 4, 6, 9, 12, 18, and 24 months of age. Results. A total of 401 (28%) of the 1436 uninfected infants were born to drug-using mothers. Maternal CD4 lymphocyte percentage and RNA at delivery were not significantly different between drug users and nonusers. Infants who were born to drug-using mothers had lower mean gestational age (37.8 vs 38.5 weeks) and birth weight (2.9 vs 3.1 kg). Infants with intrauterine drug exposure had lower CD4 lymphocyte percentage over the first 4 months of life after adjusting for covariates and higher natural killer lymphocyte percentage. When the analysis was stratified by time period of entry, the incidence of clinical events was not different between infants who were born to drug users versus nonusers. Conclusion. Maternal hard drug use is associated with immunologic changes in infants early in life, although these changes did not seem to be associated with increased risk of infections. C1 Columbia Univ, New York, NY 10032 USA. C TASC, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Univ Puerto Rico, San Juan, PR 00936 USA. SUNY Downstate, New York, NY USA. Boston Med Ctr, Boston, MA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Illinois, Chicago, IL USA. NICHHD, Bethesda, MD 20892 USA. RP Neu, N (reprint author), Columbia Univ, 622 W 168th St,PH4-468, New York, NY 10032 USA. EM nn45@columbia.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [RR00645, RR00188]; NIAID NIH HHS [1 U01 AI 50274-01, N01 AI 85339, U01 AI 34841, U01 AI 34858]; NICHD NIH HHS [U01 HD 36117, U01 HD 41983]; NIDA NIH HHS [9U01 DA 15054, U01 DA 15053] NR 31 TC 7 Z9 7 U1 0 U2 3 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 2004 VL 113 IS 5 BP 1260 EP 1266 DI 10.1542/peds.113.5.1260 PG 7 WC Pediatrics SC Pediatrics GA 817HS UT WOS:000221169200014 PM 15121939 ER PT J AU Chen, AM Rogan, WJ AF Chen, AM Rogan, WJ TI Breastfeeding and the risk of postneonatal death in the United States SO PEDIATRICS LA English DT Article DE breastfeeding; infant mortality; cause of death; risk; logistic models ID INFANT-MORTALITY; INFECTIOUS-DISEASES; VITAL-STATISTICS; MILK; DIARRHEAL; CHILDREN; AGE AB Objective. Breastfed infants in the United States have lower rates of morbidity, especially from infectious disease, but there are few contemporary studies in the developed world of the effect of breastfeeding on postneonatal mortality. We evaluated the effect of breastfeeding on postneonatal mortality in United States using 1988 National Maternal and Infant Health Survey (NMIHS) data. Methods. Nationally representative samples of 1204 infants who died between 28 days and 1 year from causes other than congenital anomaly or malignant tumor ( cases of postneonatal death) and 7740 children who were still alive at 1 year ( controls) were included. We calculated overall and cause-specific odds ratios for ever/never breastfeeding among all children, conducted race and birth weight - specific analyses, and looked for duration response effects. Results. Overall, children who were ever breastfed had 0.79 (95% confidence interval [CI]: 0.67 - 0.93) times the risk of never breastfed children for dying in the postneonatal period. Longer breastfeeding was associated with lower risk. Odds ratios by cause of death varied from 0.59 ( 95% CI: 0.38 - 0.94) for injuries to 0.84 ( 95% CI: 0.67 - 1.05) for sudden infant death syndrome. Conclusions. Breastfeeding is associated with a reduction in risk for postneonatal death. This large data set allowed robust estimates and control of confounding, but the effects of breast milk and breastfeeding cannot be separated completely from other characteristics of the mother and child. Assuming causality, however, promoting breastfeeding has the potential to save or delay similar to 720 postneonatal deaths in the United States each year. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-02, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 27 TC 112 Z9 116 U1 5 U2 11 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 2004 VL 113 IS 5 BP E435 EP E439 DI 10.1542/peds.113.5.e435 PG 5 WC Pediatrics SC Pediatrics GA 817HS UT WOS:000221169200062 PM 15121986 ER PT J AU Vallon, V Richter, K Huang, DY Rieg, T Schnermann, J AF Vallon, V Richter, K Huang, DY Rieg, T Schnermann, J TI Functional consequences at the single-nephron level of the lack of adenosine A1 receptors and tubuloglomerular feedback in mice SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE micropuncture; single nephron filtration rate; pressure oscillations; sodium reabsorption; tubular pressure; tubuloglomerular feedback ID A(1) RECEPTOR ANTAGONIST; GLOMERULAR-FILTRATION-RATE; THICK ASCENDING LIMB; POTENTIAL ROLE; NITRIC-OXIDE; ADENOSINE; TRANSPORT; RAT; PRESSURE; KW-3902 AB Mice deficient for adenosine A1 receptors (A1AR) lack tubuloglomerular feedback (TGF). In vivo micropuncture experiments were performed under anesthesia in A1AR-deficient and wild-type littermate mice to study the effects of chronic absence of A1AR on fluid and Na+ reabsorption along the nephron, as well as the functional consequences at the single-nephron level of the lack TGF. Evidence is provided for an A1AR-mediated tonic inhibition of Na+ reabsorption in a water-impermeable segment of the loop of Henle, possibly the thick ascending limb. In contrast, proximal tubular reabsorption of fluid, Na+ and K+ was unaffected by the chronic absence of A1AR. Experiments in which artificial tubular fluid was added to free-flowing late-proximal tubules demonstrated an essential role of A1AR/TGF in the stabilization of fluid and Na+ delivery to the distal nephron. Further, the occurrence of spontaneous oscillations of hydrostatic pressure in proximal tubule (P-PT) at a frequency of about 32 mHz depended on intact A1AR/TGF. In comparison, the normal, stabilizing reduction in P-PT following the initial rise in P-PT during sustained small increases in proximal tubular flow rate does not require A1AR/TGF; TGF-independent mechanisms appear to compensate in this regard for a lack of TGF under physiological conditions and the lack of TGF is unmasked only when supraphysiological flow rates overwhelm TGF-independent compensation. C1 Univ Tubingen, Inst Pharmacol & Toxicol, D-72074 Tubingen, Germany. NIDDK, NIH, Bethesda, MD USA. RP Vallon, V (reprint author), Univ Calif San Diego, Div Nephrol Hypertens, 3350 La Jolla Village Dr 9151, San Diego, CA 92161 USA. EM vvallon@ucsd.edu NR 38 TC 40 Z9 40 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAY PY 2004 VL 448 IS 2 BP 214 EP 221 DI 10.1007/s00424-004-1239-8 PG 8 WC Physiology SC Physiology GA 813XJ UT WOS:000220939500011 PM 14767772 ER PT J AU Gilpin, NW Stewart, RB Elder, RL Kho, Y Murphy, JM Li, TK Badia-Elder, NE AF Gilpin, NW Stewart, RB Elder, RL Kho, Y Murphy, JM Li, TK Badia-Elder, NE TI Sedative and motor-impairing effects of neuropeptide Y and ethanol in selectively bred P and NP rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE neuropeptide Y; ethanol sedation; spontaneous motor activity; alcohol-preferring and -nonpreferring rats ID ALCOHOL-PREFERRING P; INDUCED SLEEP; RELEASE; SUCROSE; SENSITIZATION; CONSUMPTION; INCREASES; BEHAVIOR AB Past findings suggest a positive association between endogenous neuropeptide Y (NPY) activity and ethanol-induced sedation, and there is evidence for additive effects of administered NPY with sedative-hypnotics. The present investigation examined the effects of intracerebroventricular NPY injection on ethanol-induced sedation and motor impairment in selectively bred alcohol-preferring (P) and -nonpreferring (NP) rats. In Experiment 1, P and NP rats were assessed for loss and recovery of righting reflex (RR) following infusion with either NPY (10.0 mug) or aCSF followed by ethanol injection (2.5 g/kg ip). NPY reduced time to lose RR and increased time to regain RR similarly in P and NP rats. Blood-ethanol levels (BELs) were lower at time of recovery in NPY-treated rats relative to aCSF controls. Thus, NPY enhanced ethanol-induced sedation. In Experiment 2, P and NP rats pretreated with either saline or ethanol (1.0 g/kg ip) were assessed for motor activity following infusion with either NPY (2.5, 5.0, or 10.0 mug) or aCSF. Ethanol alone and NPY alone suppressed motor activity, but there were no additive effects between the two. Taken together, these results provide partial support for past observations of additivity between NPY and drug-induced sedation, and suggest a role for NPY in the neurobehavioral effects of acute ethanol exposure. (C) 2004 Elsevier Inc. All rights reserved. C1 Purdue Sch Sci, Dept Psychol, IUPUI, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Psychiat, Bloomington, IN 47405 USA. Indiana Univ, Sch Med, Dept Med, Bloomington, IN 47405 USA. Indiana Univ, Sch Med, Dept Biochem, Bloomington, IN 47405 USA. NIAAA, NIH, Bethesda, MD USA. RP Badia-Elder, NE (reprint author), Purdue Sch Sci, Dept Psychol, IUPUI, LD 124,402 N Blackford St, Indianapolis, IN 46202 USA. EM nbadiael@iupui.edu RI Gilpin, Nicholas/K-9528-2014 OI Gilpin, Nicholas/0000-0001-8901-8917 FU NIAAA NIH HHS [AA10717, AA12857, AA10722, AA07611] NR 29 TC 10 Z9 10 U1 0 U2 0 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 2004 VL 78 IS 1 BP 65 EP 73 DI 10.1016/j.pbb.2004.02.012 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 827ZH UT WOS:000221941700008 PM 15159135 ER PT J AU Coates, PM Chausmer, A AF Coates, PM Chausmer, A TI Psychoactive plants - Introduction SO PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID NONVITAMIN; PREVALENCE; STUDENTS C1 NIDA, Translat Res Branch, Div Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Chausmer, A (reprint author), NIDA, Translat Res Branch, Div Neurosci & Behav Res, NIH, Room 4282,MSC 9555,6001 Execut Blvd, Bethesda, MD 20892 USA. EM coatesp@od.nih.gov; achausme@nida.nih.gov NR 5 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY PY 2004 VL 102 IS 2 BP 97 EP 98 DI 10.1016/j.pharmathera.2004.03.001 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 828OU UT WOS:000221983400001 ER PT J AU Roth, BL Lopez, E Beischel, S Westkaemper, RB Evans, JM AF Roth, BL Lopez, E Beischel, S Westkaemper, RB Evans, JM TI Screening the receptorome to discover the molecular targets for plant-derived psychoactive compounds: a novel approach for CNS drug discovery SO PHARMACOLOGY & THERAPEUTICS LA English DT Article DE receptorome; molecular targets; psychoactive compounds ID ST-JOHNS-WORT; PROTEIN-COUPLED RECEPTOR; RANDOMIZED CONTROLLED TRIAL; KAPPA-OPIOID-RECEPTOR; SAGE SALVIA-DIVINORUM; FORCED SWIMMING TEST; HYPERICUM-PERFORATUM; SALVINORIN-A; IN-VITRO; ANTIDEPRESSANT ACTIVITY AB Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated targets for CNS drug discovery. This review article focuses on an unbiased, discovery-based approach aimed at uncovering the molecular targets responsible for psychoactive drug actions wherein the main active ingredients of psychoactive plants are screened at the "receptorome" (that portion of the proteome encoding receptors). An overview of the receptorome is given and various in silico, public-domain resources are described. Newly developed tools for the in silico mining of data derived from the National Institute of Mental Health Psychoactive Drug Screening Program's (NIMH-PDSP) K(i) Database (K(i) DB) are described in detail. Additionally, three case studies aimed at discovering the molecular targets responsible for Hypericum perforatum, Salvia divinorum, and Ephedra sinica actions are presented. Finally, recommendations are made for future studies. (C) 2004 Elsevier Inc. All rights reserved. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Med Chem, Richmond, VA 23284 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, 2109 Adelbert Rd, Cleveland, OH 44106 USA. EM bryan.roth@case.edu RI Roth, Bryan/F-3928-2010 NR 65 TC 72 Z9 72 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD MAY PY 2004 VL 102 IS 2 BP 99 EP 110 DI 10.1016/j.pharmthera.2004.03.004 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 828OU UT WOS:000221983400002 PM 15163592 ER PT J AU Xie, RH Bryant, GW Sun, GY Kar, T Chen, ZF Smith, VH Araki, Y Tagmatarchis, N Shinohara, H Ito, O AF Xie, RH Bryant, GW Sun, GY Kar, T Chen, ZF Smith, VH Araki, Y Tagmatarchis, N Shinohara, H Ito, O TI Tuning spectral properties of fullerenes by substitutional doping SO PHYSICAL REVIEW B LA English DT Article ID DENSITY-FUNCTIONAL THEORY; HYDROAZAFULLERENE C59HN; BN-SUBSTITUTION; C-60; HETEROFULLERENES; DERIVATIVES; CHEMISTRY; (C59N)(2); NITROGEN; STATE AB We propose a substitutional doping approach to achieve tunable optical properties from fullerenes. Taking C-60 as an example and using time-dependent density functional theory, we compute the absorption spectra of heterofullerenes C60-n-mNnBm, and demonstrate that their optical gaps and first triplet energies can be tuned from the near-infrared up to the ultraviolet by tailoring the dopant numbers n and m. This is supported by experiment and suggests heterofullerenes as single-molecule fluorescent probes and as building blocks for the bottom-up assembly of tunable luminescent devices. For the example of C59HN, we discuss the effect of organic functionalization, which is needed for device fabrication, on optical properties. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Utah State Univ, Dept Chem & Biochem, Logan, UT 84322 USA. Univ Georgia, Computat Chem Annex, Athens, GA 30602 USA. Univ Erlangen Nurnberg, Inst Organ Chem, D-91054 Erlangen, Germany. Queens Univ, Dept Chem, Kingston, ON K7L 3N6, Canada. Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan. Univ Trieste, Dept Pharmaceut Sci, I-34127 Trieste, Italy. Nagoya Univ, Dept Chem, Nagoya, Aichi 4648602, Japan. RP Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RI Chen, Zhongfang/A-3397-2008; Araki, Yasuyuki/N-5281-2016 NR 45 TC 39 Z9 39 U1 1 U2 5 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1098-0121 EI 1550-235X J9 PHYS REV B JI Phys. Rev. B PD MAY PY 2004 VL 69 IS 20 AR 201403 DI 10.1103/PhysRevB.69.201403 PG 4 WC Physics, Condensed Matter SC Physics GA 830BD UT WOS:000222095700017 ER PT J AU Dawid, IB AF Dawid, IB TI Organizing the vertebrate embryo - A balance of induction and competence SO PLOS BIOLOGY LA English DT Editorial Material ID FIBROBLAST-GROWTH-FACTOR; NEURAL INDUCTION; BETA-CATENIN; MESODERM INDUCTION; XENOPUS EMBRYOS; FGF; DIFFERENTIATION; GASTRULATION; SIGNALS; PATTERN C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov NR 26 TC 1 Z9 1 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAY PY 2004 VL 2 IS 5 BP 579 EP 582 AR e127 DI 10.1371/journal.pbio.0020127 PG 4 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 823GZ UT WOS:000221599500007 PM 15138497 ER PT J AU Kouprina, N Pavlicek, A Mochida, GH Solomon, G Gersch, W Yoon, YH Collura, R Ruvolo, M Barrett, JC Woods, CG Walsh, CA Jurka, J Larionov, V AF Kouprina, N Pavlicek, A Mochida, GH Solomon, G Gersch, W Yoon, YH Collura, R Ruvolo, M Barrett, JC Woods, CG Walsh, CA Jurka, J Larionov, V TI Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion SO PLOS BIOLOGY LA English DT Article ID CEREBRAL CORTICAL SIZE; HUMAN INHERITED DISEASE; MAJOR DETERMINANT; SEQUENCE ALIGNMENT; POSITIVE SELECTION; ALU-SEQUENCES; DNA-SEQUENCES; CODON USAGE; TRANSLOCATION; SUBSTITUTION AB Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size. C1 NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Genet Informat Res Inst, Mountain View, CA USA. Howard Hughes Med Inst, Dept Neurol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Harvard Univ, Cambridge, MA 02138 USA. St James Univ Hosp, Leeds, W Yorkshire, England. RP Jurka, J (reprint author), NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. EM jurka@girinst.org; larionov@mail.nih.gov RI woods, christopher/A-1361-2010 NR 43 TC 108 Z9 119 U1 3 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAY PY 2004 VL 2 IS 5 BP 653 EP 663 AR e126 DI 10.1371/journal.pbio.0020126 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 823GZ UT WOS:000221599500015 PM 15045028 ER PT J AU Cullen, KW Klesges, LM Sherwood, NE Baranowski, T Beech, B Pratt, C Zhou, A Rochon, J AF Cullen, KW Klesges, LM Sherwood, NE Baranowski, T Beech, B Pratt, C Zhou, A Rochon, J TI Measurement characteristics of diet-related psychosocial questionnaires among African-American parents and their 8- to 10-year-old daughters: results from the Girls' health Enrichment Multi-site Studies SO PREVENTIVE MEDICINE LA English DT Article DE parents; daughters; FJV ID VEGETABLE CONSUMPTION; NUTRITION EDUCATION; COGNITIVE MODEL; FOOD-INTAKE; FAT; CHILDREN; FRUIT; INTERVENTION; RELIABILITY; PREDICTORS AB Objective. This paper presents the reliability and validity of several diet-related psychosocial questionnaires. Methods. At baseline and 12 weeks follow-up, parents/caregivers of one hundred fifty 8- to 10-year-old African-American completed questionnaires on food preparation habits for their daughter, perceived home barriers to healthy eating, and fruit, juice, vegetable (FJV), low-fat and high-fat food availability. Girls completed a sweetened beverage preferences questionnaire and two 24-h dietary recalls assess intake. Principal components analyses were conducted for two newly designed measures. Internal consistency was calculated and construct validity was assessed between the psychosocial scales and obesity-related dietary variables. Results. Low-fat and high-fat food preparation for daughters, and perceived home barriers to eating low-fat food and FJV subscales were derived from the new questionnaires. Internal consistency reliabilities were moderate (0.58) to substantial (0.80) across all new and existing scales. Test-retest reliabilities were moderate (0.44) to substantial (0.79). Girls' intake of fat as a percentage of energy was positively related to parental high-fat food preparation for daughters (P < 0.01) and negatively related to parental low-fat food preparation practices for daughters (P < 0.05). Conclusions. Measures of family influences on FJV, fat, and sweetened beverage consumption were internally consistent with moderate to substantial stability. Scales for low-fat and high-fat food preparation practices for daughters achieved construct validity with fat consumption in the hypothesized direction. Family food preparation habits appear to be important targets for future interventions. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Univ Memphis, Memphis, TN 38152 USA. HealthPartners Res Fdn, Minneapolis, MN 55454 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Duke Clin Res Inst, Durham, NC 27715 USA. RP Cullen, KW (reprint author), Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, 1100 Bates St, Houston, TX 77030 USA. EM kcullen@bcm.tmc.edu OI Baranowski, Tom/0000-0002-0653-2222 FU NHLBI NIH HHS [U01 HL62662, U01 HL62663, U01 HL62668, U01 HL65160, U01 HL62732] NR 33 TC 32 Z9 32 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S34 EP S42 DI 10.1016/j.ypmed.2003.05.002 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700004 PM 15072857 ER PT J AU Cullen, KW Himes, JH Baranowski, T Pettit, J Stevens, M Slawson, DL Obarzanek, E Murtaugh, M Matheson, D Sun, W Rochon, J AF Cullen, KW Himes, JH Baranowski, T Pettit, J Stevens, M Slawson, DL Obarzanek, E Murtaugh, M Matheson, D Sun, W Rochon, J TI Validity and reliability of a behavior-based food coding system for measuring fruit, 100% fruit juice, vegetable, and sweetened beverage consumption: results from the Girls Health Enrichment Multisite Studies SO PREVENTIVE MEDICINE LA English DT Article DE obesity; prevention; female; African American; children; diet; fruit; vegetables; juice; sweetened beverages; water; validity; reliability ID OBESITY; CHILDHOOD; CHILDREN; RECALLS; DRINKS AB Background. This paper presents the rationale, reliability, and validity of a behavior-based food coding system for measuring fruit (F), juice (J), vegetable (V), sweetened beverage, and water consumption in children. Methods. Coding algorithms for FJV, sweetened beverages, and water were developed for use with the Nutrition Data System for Research (NDS-R). Two hundred and ten 8- to 10-year-old African American girls at four field centers completed two 24-h dietary recalls at baseline and at 12 weeks follow-up after a weight gain prevention intervention. Differences in mean baseline consumption of selected food variables and other selected nutrients across the four field centers were analyzed. Intraclass correlation coefficients (ICCs) for reliability across 2 days of food recalls and 12-week test-retest reliability correlations were calculated. For the purposes of this paper, nutrient intake estimates were considered construct validators of food intake, and validity was assessed by con-elating the coded food variable servings with nutrient intake. Results. ICCs varied from zero (0.001 for beta carotene equivalents) to moderate (0.44 for sucrose), indicating substantial instability in consumption or reporting. Twelve-week test-retest correlations were slight to moderate (0.09 for lycopene to 0.49 for folate). FJV consumption was negatively related to percent energy from fat (r = - 0.28; P = 0.001) and positively related to other nutrients. Sweetened beverage consumption was positively related to energy, sucrose, fructose, and vitamin C consumption. Conclusions. This behavior-based food coding system demonstrated construct validity among 8- to 10-year-old African American girls and can measure the desired food groups. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Childrens Nutr Res Ctr, Div Pediat, Houston, TX 77030 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Univ Memphis, Memphis, TN 38152 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Stanford Univ, Ctr Res Dis Prevent, Stanford, CA 94305 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Duke Clin Res Inst, Durham, NC 27715 USA. RP Cullen, KW (reprint author), Baylor Coll Med, Childrens Nutr Res Ctr, Div Pediat, Houston, TX 77030 USA. EM kcullen@bcm.tmc.cdu OI Murtaugh, Maureen/0000-0001-5281-0302; Baranowski, Tom/0000-0002-0653-2222 FU NHLBI NIH HHS [U01 HL65160, U01 HL62732, U01 HL62663, U01 HL62668, U01 HL62662] NR 21 TC 23 Z9 23 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 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S24 EP S33 DI 10.1016/j.ypmed.2003.05.001 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700003 PM 15072856 ER PT J AU Cullen, KW Watson, K Himes, JH Baranowski, T Rochon, J Waclawiw, M Sun, W Stevens, M Slawson, DL Matheson, D Robinson, TN AF Cullen, KW Watson, K Himes, JH Baranowski, T Rochon, J Waclawiw, M Sun, W Stevens, M Slawson, DL Matheson, D Robinson, TN TI Evaluation of quality control procedures for 24-h dietary recalls: results from the Girls health Enrichment Multisite Studies SO PREVENTIVE MEDICINE LA English DT Article DE female African-American; girls; diet; fruit; vegetables; juice; sweetened beverages; water; quality control; diet assessment; generalizability theory ID TOTAL-ENERGY EXPENDITURE; DOUBLY LABELED WATER; CHILDREN; AGREEMENT; ACCURACY; VALIDITY AB Background. Quality control methods are key components of dietary assessment, but have rarely been evaluated. Methods. One hundred forty-four 8-10-year-old African-American girls at three field centers completed two 24-h dietary recalls at baseline before a pilot weight gain prevention intervention (one recall collected in-person and one by telephone). The dietary recall data were initially reviewed by the dietary interviewer (Phase 1), then by a local lead nutritionist at the field center (Phase 2), and then by the Nutrition Coordinating Center (NCC) (Phase 3); any differences identified by NCC were reconciled (Phase 4). Bland-Altman and generalizability theory methods were used to assess agreement of consumption for selected food variables and nutrients between phases. Results. Only small differences occurred. Quality control procedures primarily reduced the variances of nutrients rather than caused the means to shift. Most of the variability among phases was due to individual level variability in dietary intake. Conclusions. Decisions to review dietary recall data beyond local review should be based on the level of precision and accuracy required for the study outcomes and the availability of financial resources. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Duke Clin Res Inst, Durham, NC 27715 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Univ Memphis, Memphis, TN 38152 USA. Stanford Univ, Ctr Res Dis Prevent, Palo Alto, CA 94025 USA. RP Cullen, KW (reprint author), Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, 1100 Bates St, Houston, TX 77030 USA. EM kcullen@bcm.tmc.edu OI Baranowski, Tom/0000-0002-0653-2222 FU NHLBI NIH HHS [U01 HL62663, U01 HL62662, U01 HL62668, U01 HL62732, U01 HL65160] NR 24 TC 14 Z9 14 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S14 EP S23 DI 10.1016/j.ypmed.2003.10.014 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700002 PM 15072855 ER PT J AU Klesges, LM Baranowski, T Beech, B Cullen, K Murray, DM Rochon, J Pratt, C AF Klesges, LM Baranowski, T Beech, B Cullen, K Murray, DM Rochon, J Pratt, C TI Social desirability bias in self-reported dietary, physical activity and weight concerns measures in 8- to 10-year-old African-American girls: results from the Girls health Enrichment Multisite Studies (GEMS) SO PREVENTIVE MEDICINE LA English DT Article DE bias; social desirability; physical activity assessment; diet assessment; health behavior; children; African-American; self-report; confounding ID IDEAL BODY-SIZE; ENERGY-INTAKE; ADOLESCENT GIRLS; CHILDREN; FOOD; VALIDATION; VALIDITY; PREADOLESCENT; INTERVENTION; ANXIETY AB Background. Social desirability (SocD) may bias children's self-reported health behaviors and attitudes and confound relationships with health outcome measures. Methods. Ninety-five, 8- to 10-year-old African-American girls completed dietary recalls, a physical activity checklist, psychosocial questionnaires related to diet, and physical activity; and 3 days of physical activity monitoring. Potential SocD construct bias was investigated by comparing designated criterion measures of physical activity, beverage intake, and body mass index (BMI) with respective self-reported measures related to activity, beverage preferences, and body image and weight concerns in cross-sectional regression models. Potential confounding by SocD of associations between self-reported behaviors with BMI was assessed using change-in-coefficient regression analyses. Results. Controlling for age and BMI, overestimates of self-reported activity (P = 0.02), underestimates of sweetened beverage preferences (P= 0.02), and lower ratings of weight concems and dieting behaviors (P's < 0.05) were related to SocD. Confounding by SocD of associations between self-reported physical activity and energy intake with BMI was found. Conclusions. In 8- to 10-year-old African-American girls, SocD was found to bias self-reports of diet and physical activity and confound associations between BMI and self-reported physical activity and energy intake. Methods to measure and control SocD bias are needed to reduce potential distortion of relationships between diet and physical activity and health outcomes. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Klesges, LM (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, 66 N Pauline,Suite 633, Memphis, TN 38163 USA. EM lklesges@utmem.edu RI Schmoelz, Camilie/D-1707-2012; OI Schmoelz, Camilie/0000-0003-2221-9954; Baranowski, Tom/0000-0002-0653-2222 FU NHLBI NIH HHS [U01 HL62668, U01 HL62663, U01 HL62732, U01 HL65160]; PHS HHS [U01 H162662] NR 51 TC 98 Z9 100 U1 3 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S78 EP S87 DI 10.1016/j.ypmed.2003.07.003 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700009 PM 15072862 ER PT J AU Sherwood, NE Beech, BM Klesges, LM Story, M Killen, J McDonald, T Robinson, TN Pratt, C Zhou, AN Cullen, K Baranowski, J AF Sherwood, NE Beech, BM Klesges, LM Story, M Killen, J McDonald, T Robinson, TN Pratt, C Zhou, AN Cullen, K Baranowski, J TI Measurement characteristics of weight concern and dieting measures in 8-10-year-old African-American girls from GEMS pilot studies SO PREVENTIVE MEDICINE LA English DT Article DE body image; weight concern; dieting; measurernent; youth; psychosocial factors; African-Americans ID CHILDRENS PHYSICAL-ACTIVITY; WHITE PREADOLESCENT GIRLS; BODY-IMAGE; SELF-ESTEEM; US ADULTS; ADOLESCENT FEMALES; 3RD-GRADE CHILDREN; NATIONAL-HEALTH; POTENTIAL RISK; UNITED-STATES AB Background. Reliability and validity were established for weight concern measures completed by 8- 10-year-old African-American girls participating in a pilot obesity prevention program. Methods. Two hundred ten girls and parents participated in the program. Girls completed subscales of the McKnight Risk Fact Survey (MRFS) and body silhouette ratings, had height, weight, and body fat measured, wore accelerometers for 3 days, and completed two dietary recalls. Principal components analysis, internal consistency, and test-retest reliability were computed for weight concerns and body image measures along with convergent validity with body mass index (BMI), percent body fat (PBF), physical activity, and dietary intake. Results. A Moderate Weight Control Behaviors (MWCB) subscale was derived from the MRFS. Overconcern with Weight and Shape (OWS) was a stand-alone scale. Internal consistency estimates for the scales were substantial ranging from 0.71 to 0.84. Test-retest reliabilities were moderate (0.45-0.58). OWS, MWCB, body silhouette rating, and body size discrepancy were positively associated with BMI and PBF. The "like to look" silhouette rating was negatively associated with PBF. Conclusions. Weight concern measures had reasonable levels of internal consistency and promising validity, but only moderate test-retest reliability among preadolescent African-American girls. Refinement and further validation of weight concern measures in this population are warranted. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 HealthPartners Res Fdn, Minneapolis, MN 55440 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Univ Memphis, Ctr Community Hlth, Memphis, TN 38157 USA. Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38105 USA. Stanford Univ, Div Gen Pediat, Palo Alto, CA 94304 USA. Stanford Univ, Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Rockville, MD 20852 USA. Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. RP Sherwood, NE (reprint author), HealthPartners Res Fdn, Mail Stop 21111R,POB 1524, Minneapolis, MN 55440 USA. EM Nancy.E.Sherwood@HealthPartners.com RI Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 NR 49 TC 15 Z9 15 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S50 EP S59 DI 10.1016/j.ypmed.2003.12.031 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700006 PM 15072859 ER PT J AU Sherwood, NE Taylor, WC Treuth, M Klesges, LM Baranowski, T Zhou, AN Pratt, C McClanahan, B Robinson, TN Pruitt, L Miller, W AF Sherwood, NE Taylor, WC Treuth, M Klesges, LM Baranowski, T Zhou, AN Pratt, C McClanahan, B Robinson, TN Pruitt, L Miller, W TI Measurement characteristics of activity-related psychosocial measures in 8- to 10-year-old African-American girls in the Girls health Enrichment Multisite Study (GEMS) SO PREVENTIVE MEDICINE LA English DT Article DE physical activity; measurernent; youth; psychosocial variables; African-Americans; self-efficacy; self-concept; activity preference ID CHILDRENS PHYSICAL-ACTIVITY; DETERMINANTS; WHITE; ADOLESCENTS; VALIDATION; VALIDITY; YOUTH AB Background. This paper presents reliability and validity analyses of physical activity-related psychosocial questionnaires completed by 8-to 10-year-old African-American girls at baseline and follow-up assessments of pilot intervention studies in the Girls health Enrichment Multi-site Study (GEMS). Methods. Two hundred ten girls participated in the GEMS 12-week pilot studies and had their height and weight measured, wore an accelerometer for 3 days and completed a measure of their usual physical activity (PA) at baseline and after the 12-week intervention. Subgroups of girls also completed physical activity-related psychosocial measures at these two time points including: (a) self-concept; (b) self-efficacy; (c) outcome expectancies; and d) preferences. Principal components analysis was conducted on the psychosocial measures obtained at baseline. Cronbach's alpha and test-retest reliability were computed. Convergent validity was assessed by correlating the baseline psychosocial measures with baseline physical activity measures and body mass index (BMI). Results. The following sub-scales were derived: Activity Preference, Positive Expectancies and Negative Expectancies for physical activity. Physical Performance Self-Concept and Self-Efficacy for physical activity were kept as single dimensional scales. Sub-scales, derived from principal components analyses, were Activity Preference, Positive Expectancies, and Negative Expectancies for physical activity. Internal consistency estimates for the various scales were substantial to excellent (0.67-0.85), while test-retest reliability estimates were fair to moderate (0.22-0.56). Correlations between the PA psychosocial sub-scales and measured levels of activity measures showed evidence of convergent validity for the Activity Preference sub-scale, although social desirability may have influenced the significant associations observed. Conclusions. The Activity Preference was a fairly reliable and valid measure. Further studies are needed to examine the utility of activity related psychosocial measures in interventions to increase physical activity among preadolescent African-American girls. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Hlth Partners Res Fdn, Minneapolis, MN 55440 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. Baylor Coll Med, Houston, TX 77030 USA. George Washington Univ, Washington, DC 20052 USA. NHLBI, Bethesda, MD 20892 USA. Univ Memphis, Memphis, TN 38152 USA. Stanford Univ, Div Gen Pediat, Stanford, CA 94305 USA. Stanford Univ, Ctr Res Dis Prevent, Stanford, CA 94305 USA. RP Sherwood, NE (reprint author), Hlth Partners Res Fdn, Mail Stop 23303G,POB 1524, Minneapolis, MN 55440 USA. EM Nancy.E.Sherwood@HealthPartners.com RI Schmoelz, Camilie/D-1707-2012; OI Schmoelz, Camilie/0000-0003-2221-9954; Baranowski, Tom/0000-0002-0653-2222 NR 34 TC 26 Z9 26 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S60 EP S68 DI 10.1016/j.ypmed.2003.12.030 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700007 PM 15072860 ER PT J AU Taylor, WC Baranowski, T Klesges, LM Sydney, E Pratt, C Rochon, J Zhou, A AF Taylor, WC Baranowski, T Klesges, LM Sydney, E Pratt, C Rochon, J Zhou, A TI Psychometric properties of optimism and pessimism: results from the girls' health enrichment multisite studies SO PREVENTIVE MEDICINE LA English DT Article DE optimism; pessimism; GEMS ID CHILDRENS PHYSICAL-ACTIVITY; SEDENTARY BEHAVIOR; OBESE CHILDREN; ADOLESCENTS; SELF; OVERWEIGHT; VALIDATION; CHILDHOOD; STUDENTS AB Background. This study investigated the relationships among optimism, pessimism, physical activity, and dietary behaviors among 8- to 10-year-old African-American girls in the Girls' Health Enrichment Multisite Studies (GEMS). Methods. Ninety-two girls were randomly assigned to a 12-week physical activity and diet intervention or comparison group and completed psychosocial assessments including the Youth Life Orientation Test (YLOT) of optimism and pessimism, physical performance self-concept, physical activity self-efficacy, physical activity outcome expectancies, and physical activity and sedentary preferences. Also, preferences for bottled water and sweetened beverages were assessed. Physical activity and dietary intake were assessed by self-report and parent-report at baseline and follow-up. Also, physical activity was objectively assessed by wearing an accelerometer for 3 days. The psychometric properties of the optimism-pessimism subscales were analyzed. Results. The measures of optimism and pessimism in children were reliable (r = 0.75-0.82). In the multiple regression analyses without the intervention interaction terms, pessimism was positively and significantly related to increases in MET-adjusted usual activity (P = 0.008) and sedentary behaviors (P = 0.0004). Additionally, a negative (P = 0.026) pessimism by intervention interaction term for MET-adjusted usual activity was found such that the intervention group had a lower change in physical activity per unit increase in pessimism compared to the control group. Conclusions: Among 8- to 10-year-old African-American girls, pessimism was related to increased sedentary behaviors and usual activity. Previous studies have reported relationships between optimism and health-compromising behaviors. This study found that pessimism may positively or negatively influence efforts to increase health-promoting behaviors. Future research should confirm and clarify the meaning of these findings. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, CHPPR, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Tennessee, Memphis, TN 38152 USA. NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Rockville, MD 20852 USA. Pacific Univ, Portland, OR 97205 USA. Duke Univ, Durham, NC 27715 USA. RP Taylor, WC (reprint author), Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, CHPPR, 7000 Fannin St,Suite 2670, Houston, TX 77030 USA. EM wtaylor@sph.uth.tmc.edu RI Schmoelz, Camilie/D-1707-2012; OI Schmoelz, Camilie/0000-0003-2221-9954; Baranowski, Tom/0000-0002-0653-2222 FU NHLBI NIH HHS [U01 HL62662, U01 HL62663, U01 HL62668, U01 HL62732, U01 HL65160] NR 31 TC 15 Z9 15 U1 4 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S69 EP S77 DI 10.1016/j.ypmed.2003.10.015 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700008 PM 15072861 ER PT J AU Treuth, MS Sherwood, NE Baranowski, T Butte, NF Jacobs, DR McClanahan, B Gao, S Rochon, J Zhou, A Robinson, TN Pruitt, L Haskell, W Obarzanek, E AF Treuth, MS Sherwood, NE Baranowski, T Butte, NF Jacobs, DR McClanahan, B Gao, S Rochon, J Zhou, A Robinson, TN Pruitt, L Haskell, W Obarzanek, E TI Physical activity self-report and accelerometry measures from the Girls health Enrichment Multi-site Studies SO PREVENTIVE MEDICINE LA English DT Article DE accelerometer; physical activity assessment; reliability; validity ID VALIDATION; VALIDITY; RELIABILITY; CHILDREN; YOUTH AB Background. Valid and reliable physical activity checklists are needed to assess effectiveness of interventions. This study tested the validity and reliability of the Girls health Enrichment Multi-site Studies (GEMS) Activity Questionnaire. Methods. Two-hundred and ten African-American girls completed the GEMS Activity Questionnaire (GAQ), a checklist of 28 physical and 7 sedentary activities, including TV viewing, inquiring whether performed on the previous day ("yesterday"), and whether usually performed ("usual"). The girls wore an accelerometer (used as the criterion for validity) for three consecutive days at baseline and after a 12-week pilot intervention. Data from 172 girls at baseline and follow-up were usable for this report. Results. Girls were (mean +/- SD) 8.8 +/- 0.8 years old with a BMI of 22.3 +/- 5.9 kg/m(2). The intraclass correlation (ICC) examining reliability for the accelerometer across 3 days at baseline for the combined group was fair (ICC = 0.33, P < 0.21). The test-retest reliability coefficient for the 18-item MET-weighted GAQ yesterday scores for the comparison group of girls was 0.57 (P < 0.001). At baseline and follow-up, nonsignificant correlations were observed between 3-day accelerometer counts/minute and GAQ 18-item usual score for both comparison and intervention groups. A significant correlation was found between change in accelerometer minutes of moderate-to-vigorous activity (MVPA) between 12 noon and 6 PM and change in GAQ physical activities in the comparison girls (R = 0.35, P < 0.01). The TV-usual score was correlated with 3-day accelerometer counts/minute (R = -0.19, P = 0.02) at baseline for the total sample. Conclusions. Correlations between the GAQ and accelerometer were low, indicating low validity. Although the GAQ may be helpful in describing types of physical activities performed, it needs further development to improve its psychometric properties. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD 21205 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. USDA ARS, Childrens Nutr Res Ctr, Baylor Coll Med, Houston, TX 77030 USA. Univ Oslo, Inst Nutr Res, Oslo, Norway. Univ Memphis, Ctr Community Hlth, Memphis, TN 38152 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Stanford Univ, Div Gen Pediat, Stanford, CA 94305 USA. Stanford Univ, Ctr Res Dis Prevent, Stanford, CA 94305 USA. Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Treuth, MS (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, 615 N Wolfe St, Baltimore, MD 21205 USA. EM mtreuth@jhsph.edu RI Schmoelz, Camilie/D-1707-2012; OI Schmoelz, Camilie/0000-0003-2221-9954; Baranowski, Tom/0000-0002-0653-2222 FU NHLBI NIH HHS [U01 HL62732, U01 HL62662, U01 HL62663, U01 HL62668, U01 HL65160] NR 16 TC 47 Z9 50 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 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2004 VL 38 SU S BP S43 EP S49 DI 10.1016/j.ypmed.2003.01.001 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 816QZ UT WOS:000221125700005 PM 15072858 ER PT J AU Feher, A Boross, P Sperka, T Oroszlan, S Tozser, J AF Feher, A Boross, P Sperka, T Oroszlan, S Tozser, J TI Expression of the murine leukemia virus protease in fusion with maltose-binding protein in Escherichia coli SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE retroviral protease; purification; MLV ID HIGH-LEVEL EXPRESSION; IMMUNODEFICIENCY-VIRUS; HIV-1; GENE; POLYPEPTIDES; PURIFICATION; SPECIFICITY; SUPPRESSION; INHIBITORS; RESISTANCE AB The protease of murine leukemia virus (MLV) was cloned into pMal-c2 vector, expressed in fusion with maltose-binding protein (MBP), and purified to homogeneity after Factor Xa cleavage of the chimeric protein. Substantial degradation of the fusion protein was observed during expression, which severely diminished the yield. The degree of degradation of the fusion protein was even more pronounced when a single-chain form of the MLV protease was cloned after the gene coding for MBP. To increase the yield, a hexahistidine tag with an additional Factor Xa cleavage site was cloned after the protease and nickel chelate affinity chromatography was used as the first purification step. The modified procedure resulted in substantially higher yield as compared to the original procedure. The degradation of hexahistidine-tagged active site mutant MLV protease was very low and comparable to that obtained with hexahistidine-tagged MBP, but purified MLV protease alone was not able to degrade purified MBP, suggesting that during expression the active MLV protease may activate bacterial proteases which appear to be responsible for the degradation of the fusion proteins. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, Debrecen, Hungary. NCI, HIV Drug Resistance Program, Frederick, MD USA. RP Tozser, J (reprint author), Univ Debrecen, Dept Biochem & Mol Biol, Res Ctr Mol Med, Med & Hlth Sci Ctr, Debrecen, Hungary. EM tozser@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 31 TC 10 Z9 11 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 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAY PY 2004 VL 35 IS 1 BP 62 EP 68 DI 10.1016/j.pep.2004.01.008 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 809DO UT WOS:000220617600009 PM 15039067 ER PT J AU Bai, YW Zhou, HY Zhou, YQ AF Bai, YW Zhou, HY Zhou, YQ TI Critical nucleation size in the folding of small apparently two-state proteins SO PROTEIN SCIENCE LA English DT Article DE topology; total contact distance; folding rate; nucleation size ID SINGLE-DOMAIN PROTEINS; STATE HYDROGEN-EXCHANGE; BETA-HAIRPIN FORMATION; TRANSITION-STATE; CONTACT ORDER; SECONDARY STRUCTURE; RATE PREDICTION; SIMPLE-MODEL; KINETICS; RATES AB For apparently two-state proteins, we found that the size (number of folded residues) of a transition state is mostly encoded by the topology, defined by total contact distance (TCD) of the native state, and correlates with its folding rate. This is demonstrated by using a simple procedure to reduce the native structures of the 41 two-state proteins with native TCD as a constraint, and is further supported by analyzing the results of eight proteins from protein engineering studies. These results support the hypothesis that the major rate-limiting process in the folding of small apparently two-state proteins is the search for a critical number of residues with the topology close to that of the native state. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Howard Hughes Med Inst, Ctr Single Mol Biophys, Dept Physiol & Biophys, Buffalo, NY 14214 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov; yqzhou@buffalo.edu RI Zhou, Yaoqi/B-3284-2009 OI Zhou, Yaoqi/0000-0002-9958-5699 FU NIGMS NIH HHS [R01 GM 068530, R01 GM 966049, R01 GM068530] NR 53 TC 27 Z9 27 U1 2 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2004 VL 13 IS 5 BP 1173 EP 1181 DI 10.1110/ps.03587604 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KW UT WOS:000221042200001 PM 15075405 ER PT J AU Fantegrossi, WE Kiessel, CL Leach, PT Van Martin, C Karabenick, RL Chen, X Ohizumi, Y Ullrich, T Rice, KC Woods, JH AF Fantegrossi, WE Kiessel, CL Leach, PT Van Martin, C Karabenick, RL Chen, X Ohizumi, Y Ullrich, T Rice, KC Woods, JH TI Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE MDMA; nantenine; toxicity; hyperthermia ID HEAD-TWITCH RESPONSE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; (+/-)-NANTENINE DERIVATIVES; RECEPTOR ANTAGONIST; RAT; SEROTONIN; RELEASE; SYSTEM; BRAIN; NEUROTRANSMITTERS AB Rationale. No selective antagonists for the effects of MDMA have yet been identified. The structurally-similar, naturally-occurring plant alkaloid nantenine (9,10-methylenedioxy-1,2 dimethoxyaporphine) may represent such a compound. Objectives. To investigate the capacity of nantenine to block and/or reverse MDMA-induced hyperthermia, lethality, locomotor stimulation, and head twitches in mice, and to compare these actions with those of the selective alpha(1) antagonist prazosin and the selective 5-HT2A antagonist M100907. Methods. Pretreatments of either 10 mg/kg nantenine or 1 mg/kg prazosin were administered 15 min before 32 mg/kg MDMA; core temperature and locomotor stimulation were then monitored via radiotelemetry for at least 3 h. In further hyperthermia studies, 32 mg/kg MDMA was administered first and temperature was allowed to rise for 30 min; 10 mg/kg nantenine, 1 mg/kg prazosin, or 1 mg/kg M100907 was then administered in an attempt to reverse MDMA-induced hyperthermia. In lethality assays, percent lethality was quantified 2 h after MDMA injection in two distinct housing conditions, one or 12 mice per cage, with or without 15 min pretreatments of 10 mg/kg nantenine or 1 mg/kg prazosin. Drug elicited head twitches were quantified for 10 min following administration of either MDMA enantiomer, with and without pretreatments of 1 mg/kg nantenine, 0.1 mg/kg prazosin, or 0.001 mg/kg M100907. Results. Nantenine blocked and rapidly reversed MDMA-induced hyperthermia, attenuated lethality in both housing conditions, and reduced MDMA-induced locomotor stimulation and head twitches in mice. Prazosin blocked, but did not reverse, MDMA-induced hyperthermia, attenuated lethality (more effectively in singly-housed animals), and reduced MDMA-induced locomotor stimulation and head twitches. M100907 did not reverse MDMA-induced hyperthermia, but effectively blocked drug-elicited head twitches. Conclusions. Nantenine functions as an effective antagonist against a wide range of MDMA-induced effects in mice. The antagonist actions of this compound at serotonin and adrenergic receptors may be differentially implicated across endpoints. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmaceut Mol Biol, Aoba Ku, Sendai, Miyagi 9808578, Japan. RP Fantegrossi, WE (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. EM billfan@umich.edu FU NIDA NIH HHS [DA09161, DA05923] NR 32 TC 40 Z9 40 U1 0 U2 1 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 2004 VL 173 IS 3-4 BP 270 EP 277 DI 10.1007/s00213-003-1741-2 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 818ZZ UT WOS:000221284300006 PM 14740148 ER PT J AU Pao, M Wiggs, EA Anastacio, MM Hyun, J DeCarlo, ES Miller, JT Anderson, VL Malech, HL Gallin, JI Holland, SM AF Pao, M Wiggs, EA Anastacio, MM Hyun, J DeCarlo, ES Miller, JT Anderson, VL Malech, HL Gallin, JI Holland, SM TI Cognitive function in patients with chronic granulomatous disease: A preliminary report SO PSYCHOSOMATICS LA English DT Article ID MENTAL-RETARDATION; CYSTIC-FIBROSIS; NADPH OXIDASE; MICE; INVOLVEMENT AB Chronic granulomatous disease is an inherited immunodeficiency in which phagocytes fail to generate superoxide and its metabolites, resulting in severe recurrent infections and frequent hospitalizations. Chronic illness and frequent hospitalizations can affect growth and development as well as social and educational opportunities. Since no data have been reported on cognitive functioning in patients with this illness, the authors sought to examine cognitive function in a group of patients with chronic granulomatous disease. A retrospective chart review of 26 patients seen and followed at the National Institutes of Health who had received cognitive testing at the request of parent or staff was performed. Demographic information including medical, psychiatric, and developmental histories was gathered. Six patients (23%) were found to have an IQ of 70 or below, indicative of cognitive deficits, and all of those patients had defects in the membrane-linked cytochrome b558. The prevalence of cognitive deficits in this selected population of chronic granulomatous disease patients was high. The determination of the true distribution of cognitive functioning in the general chronic granulomatous disease population is important, since cognitive deficits have implications for educational planning and potential therapies such as transplantation and gene therapy in children. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov NR 23 TC 40 Z9 42 U1 2 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2004 VL 45 IS 3 BP 230 EP 234 DI 10.1176/appi.psy.45.3.230 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 816JZ UT WOS:000221107500008 PM 15123849 ER PT J AU Li, WB Friedland, W Jacob, P Panyutin, IG Paretzke, HG AF Li, WB Friedland, W Jacob, P Panyutin, IG Paretzke, HG TI Simulation of I-125 decay in a synthetic oligodeoxynucleotide with normal and distorted geometry and the role of radiation and non-radiation actions SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Article ID MONTE-CARLO-SIMULATION; DNA STRAND BREAKAGE; AQUEOUS-SOLUTION; ENERGY-TRANSFER; LIQUID WATER; I125 DECAY; ELECTRONS; COMPLEX; DISTRIBUTIONS; IRRADIATION AB Within the track structure code PARTRAC, DNA strand break induction by direct and indirect radiation action was calculated for the E. coli catabolite gene activator protein (CAP) DNA complex with I-125 located at the position of the H-5 atom of the cytosine near the center. The shape of the resulting DNA fragment size distributions was found to be in reasonable agreement with corresponding experimental results. However, the calculated yield was considerably lower than the measured one. To study possible reasons for this, recently published experimental data on DNA strand breaks in a 41-mer synthetic oligodeoxynucleotide (oligoDNA) with incorporated I-125 were analyzed aiming at an evaluation of the non-radiation-related component due to the neutralization of the initially highly charged Te-125m daughter ion. This was done by assuming that the differences between simulated radiation-induced distribution and the measured total fragment size distributions were due to the neutralization process. The neutralization effect defined in this way was found to dominate the strand breakage frequency within a range of 5-7 base pairs around the I-125 decay site on both strands. After implementing this neutralization effect derived from the oligoDNA analysis into the PARTRAC simulation for the CAP-DNA complex, the agreement of the calculated DNA fragment distributions with the corresponding experimental data was considerably improved. The results indicate that DNA conformation may be explored by incorporation of I-125 into the DNA, measurement of fragment size distributions, and comparison with simulation calculation for various hypothetical DNA models. C1 GSF, Natl Res Ctr Environm & Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany. NIH, Dept Nucl Med, Bethesda, MD 20854 USA. RP Li, WB (reprint author), GSF, Natl Res Ctr Environm & Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany. EM wli@gsf.de RI Li, Weibo/M-7475-2013 FU PHS HHS [263-MM91831] NR 40 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD MAY PY 2004 VL 43 IS 1 BP 23 EP 33 DI 10.1007/s00411-004-0231-1 PG 11 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA 817QQ UT WOS:000221192400004 PM 15042380 ER PT J AU Chang, I Mikityansky, I Wray-Cahen, D Pritchard, W Karanian, JW Wood, BJ AF Chang, I Mikityansky, I Wray-Cahen, D Pritchard, W Karanian, JW Wood, BJ TI Effects of perfusion on radiofrequency ablation in Swine kidneys SO RADIOLOGY LA English DT Article DE animals; experimental study; kidney, interventional procedures; kidney, perfusion; radiofrequency (RF) ablation ID RENAL-CELL CARCINOMA; NEPHRON SPARING SURGERY; PORCINE MODEL; IN-VIVO; VASCULAR OCCLUSION; THERMAL ABLATION; LESION SIZE; BLOOD-FLOW; FOLLOW-UP; EXPERIENCE AB PURPOSE: To evaluate the effect of vascular occlusion on the size of radiofrequency (RF) ablation lesions and to evaluate embolization as an occlusion method. MATERIALS AND METHODS: The kidneys of six swine were surgically exposed. Fifteen RF ablation lesions were created in nine kidneys by using a 2-cm-tip single-needle ablation probe in varying conditions: Seven lesions were created with normal blood flow and eight were created with blood flow obstructed by means of vascular clamping (n = 5) or renal artery embolization (n = 3). The temperature, applied voltage, current, and impedance were recorded during RF ablation. Tissue-cooling curves acquired for 2 minutes immediately after the ablation were compared by using regression analysis. Lesions were bisected, and their maximum diameters were measured and compared by using analysis of variance. RESULTS: The mean diameter of ablation lesions created when blood flow was obstructed was 60% greater than that of lesions created when blood flow was normal (1.38 cm +/- 0.05 [standard error of mean] vs 0.86 cm +/- 0.07, P < .001). The two methods of flow obstruction yielded lesions of similar mean sizes: 1.40 cm 0.06 with vascular clamping and 1.33 cm +/- 0.07 with embolization. The temperature at the probe tip when lesions were ablated with normal blood flow decreased more rapidly than did the temperature when lesions were ablated after flow obstruction (P <.001). but no significant differences in tissue-cooling curves between the two flow obstruction methods were observed. CONCLUSION: Obstruction of renal blood flow before and during RF ablation resulted in larger thermal lesions with potentially less variation in size compared with the lesions created with normal nonobstructed blood flow. Selective arterial embolization of the kidney vessels may be a useful adjunct to RF ablation of kidney tumors. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20852 USA. NIH, Dept Diagnost Radiol, Special Procedures Div, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Chang, I (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, 12725 Twinbrook Pkwy,HFZ-133, Rockville, MD 20852 USA. EM iac@cdrh.fda.gov FU Intramural NIH HHS [Z99 CL999999] NR 34 TC 50 Z9 54 U1 0 U2 1 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 2004 VL 231 IS 2 BP 500 EP 505 DI 10.1148/radiol.2312021248 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 817CH UT WOS:000221155100029 PM 15128994 ER PT J AU Citrin, D Susil, R Gustafson, G Ning, H Miller, R Lessard, E Pouliot, J Coleman, C Camphausen, K Menard, C AF Citrin, D Susil, R Gustafson, G Ning, H Miller, R Lessard, E Pouliot, J Coleman, C Camphausen, K Menard, C TI MRI-Guided HDR prostate brachytherapy in a Standard 1.5T scanner SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT GEC/ESTRO/GLAC/ABS Joint Brachytherapy Meeting CY MAY 13-15, 2004 CL Barcelona, SPAIN SP GEC, ESTRO, GLAC, ABS C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2004 VL 71 SU 2 MA 219 BP S98 EP S98 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 835GB UT WOS:000222468200220 ER PT J AU Lessard, E Hsu, IC Speight, J Vigneault, E Lachance, B Beaulieu, L Menard, C Ning, H Pouliot, J AF Lessard, E Hsu, IC Speight, J Vigneault, E Lachance, B Beaulieu, L Menard, C Ning, H Pouliot, J TI Clinical benefits of a class solution for inversely planned HDR prostate brachytherapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT GEC/ESTRO/GLAC/ABS Joint Brachytherapy Meeting CY MAY 13-15, 2004 CL Barcelona, SPAIN SP GEC, ESTRO, GLAC, ABS C1 UCSF, San Francisco, CA USA. CHUQ, Quebec City, PQ, Canada. NIH, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2004 VL 71 SU 2 MA 267 BP S116 EP S116 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 835GB UT WOS:000222468200267 ER PT J AU Newbold, RR Jefferson, WN Padilla-Banks, E Haseman, J AF Newbold, RR Jefferson, WN Padilla-Banks, E Haseman, J TI Developmental exposure to diethylstilbestrol (DES) alters uterine response to estrogens in prepubescent mice: low versus high dose effects SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE environmental estrogens; endocrine disruptors; developmental programming; estrogen receptor alpha; ER alpha; uterine lactoferrin; dose-response; low dose effects ID FETAL EXPOSURE; NEONATAL EXPOSURE; IMMATURE MOUSE; FEMALE MICE; EXPRESSION; ESTRADIOL; RECEPTOR; METHOXYCHLOR; SENSITIVITY; CHEMICALS AB Outbred CD-1 mice received subcutaneous injections on neonatal days 1-5 with DES (0.0001-1000 mug/kg per day), a model xenoestrogen. At 17 days of age, uterine wet weight increase in response to estrogen was altered in neonatally DES-treated mice compared to controls. The response varied depending on the neonatal DES dose; a low dose (0.01 mug/kg) caused an enhanced uterine response but higher neonatal doses dampened the response. Western blots and immunolocalization of estrogen receptor alpha (ERalpha) showed high ER levels at DES 0.01 mug/kg, but decreased levels at higher doses compared to controls. Genes responding through ER-mediated pathways (c-fos, proliferating cell nuclear antigen (PCNA), and lactoferrin (LF)) mirrored altered wet weight responses, i.e., enhancement at low doses and dampening at higher doses. A similar dose-response curve was seen in 4 months old ovariectomized DES-treated mice suggesting the altered response was long-term. These data suggest xenoestrogen exposure during critical developmental windows alters hormone programming so that the uterus responds abnormally to estrogen later in life, and that the response differs following high versus low doses of neonatal exposure. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, POB 12233,Mail Drop E4-02, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov NR 29 TC 64 Z9 72 U1 1 U2 3 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 PY 2004 VL 18 IS 3 BP 399 EP 406 DI 10.1016/j.reprotox.2004.01.007 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 817BS UT WOS:000221153600003 PM 15082075 ER PT J AU Stumvoll, M Tataranni, PA Bogardus, C AF Stumvoll, M Tataranni, PA Bogardus, C TI The role of glucose allostasis in type 2 diabetes SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE glucose homeostasis; insulin resistance; insulin secretion; glucotoxicity ID BETA-CELL FUNCTION; INSULIN SENSITIVITY; TOLERANCE; RISK C1 Univ Tubingen, Med Klin, D-72076 Tubingen, Germany. NIDDKD, Clin Diabet & Nutr Sect, NIH, Dept Hlth & Human Serv, Phoenix, AZ 85016 USA. RP Stumvoll, M (reprint author), Univ Tubingen, Med Klin, Otfried Muller Str 10, D-72076 Tubingen, Germany. EM michael.stumvoll@med.uni-tuebingen.de NR 17 TC 9 Z9 9 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAY PY 2004 VL 5 IS 2 BP 99 EP 103 DI 10.1023/B:REMD.0000021430.56457.2c PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819WD UT WOS:000221345800002 PM 15041784 ER PT J AU Leon-Sarmiento, FE Bayona-Prieto, J Leon-S, ME AF Leon-Sarmiento, FE Bayona-Prieto, J Leon-S, ME TI Blink reflex (R3) and facial palsy SO REVISTA DE NEUROLOGIA LA Spanish DT Editorial Material ID BLEPHAROSPASM C1 Santander Univ, UIS, Sch Med, Santander, Spain. Neuronet Inst Colombiano Neurociencias Aplicadas, Bucaramanga, Colombia. Univ Pamplona, Norte Santander, Colombia. RP Leon-Sarmiento, FE (reprint author), NINDS, Med Neurol Branch, NIH, 10 Ctr Dr,Bldg 10 5N 226, Bethesda, MD 20892 USA. EM leonf@ninds.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU REVISTA DE NEUROLOGIA PI BARCELONA PA C/O CESAR VIGUERA, EDITOR, APDO 94121, 08080 BARCELONA, SPAIN SN 0210-0010 J9 REV NEUROLOGIA JI Rev. Neurologia PD MAY 1 PY 2004 VL 38 IS 9 BP 899 EP 900 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 860XC UT WOS:000224376300021 PM 15152365 ER PT J AU Catherino, W Salama, A Potlog-Nahari, C Leppert, P Tsibris, J Segars, J AF Catherino, W Salama, A Potlog-Nahari, C Leppert, P Tsibris, J Segars, J TI Gene expression studies in leiomyomata: New directions for research SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE leiomyomata; microarray; extracellular matrix; molecular genetics; fibroids ID TRANSFORMING GROWTH FACTOR-BETA-3; SIGNAL-TRANSDUCTION PATHWAY; ACTIVATED RECEPTOR-GAMMA; SMOOTH-MUSCLE-CELLS; UTERINE LEIOMYOMATA; TGF-BETA; EXTRACELLULAR-MATRIX; HORMONE ANALOG; MYOMETRIUM; PROTEOGLYCANS AB Uterine leiomyomata (fibroids) are a leading women's health problem, resulting in significant morbidity and surgical intervention. As benign clonal tumors, leiomyomata also represent a target well suited to molecular analysis. Familial studies and genetic syndromes featuring leiomyomata provide compelling evidence that genetic alterations may cause fibroid development, but the specific genes involved in leiomyoma development have not been identified. Microarrays permit simultaneous comparison of the relative expression of thousands of genes, thereby highlighting specific genes that may play a role in the development of leiomyomata. Microarray studies conducted by several laboratories have identified candidate genes. However, few gene products have been confirmed with alternative experimental approaches. The objective of this article is to focus on the insights provided by microarray studies investigating leiomyoma development. Such studies suggest that although hormonal control of leiomyoma growth is observed, there are other critical pathways involved in development of the leiomyoma cell phenotype that warrant investigation. In particular, expression of extracellular matrix genes in leiomyomata is deranged and such genes represent potential novel targets for therapy. C1 NICHD, PREB, NIH, Bethesda, MD 20862 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Univ S Florida, Dept Obstet & Gynecol, Tampa, FL 33620 USA. RP Catherino, W (reprint author), NICHD, PREB, NIH, Bldg 10,Room 9D-42,9000 Rockville Pike, Bethesda, MD 20862 USA. NR 54 TC 19 Z9 22 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD MAY PY 2004 VL 22 IS 2 BP 83 EP 90 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 824YC UT WOS:000221722100002 PM 15164303 ER PT J AU Yao, L Stanczak, J Boutin, RD AF Yao, L Stanczak, J Boutin, RD TI Presumptive subarticular stress reactions of the knee: MRI detection and association with meniscal tear patterns SO SKELETAL RADIOLOGY LA English DT Article DE MRI; knee injury; stress fracture; avascular necrosis; meniscus; meniscal tear ID SUBCHONDRAL INSUFFICIENCY FRACTURE; MEDIAL FEMORAL CONDYLE; SPONTANEOUS OSTEONECROSIS; HEAD; BONE AB Objective. MRI detects subchondral marrow findings in painful knees which bear resemblance to spontaneous osteonecrosis of the knee (SONK). Gathering evidence suggests that the primary or predominant pathogenesis of these lesions is physical stress. This study analyzes the patient characteristics and meniscal pathology associated with these lesions-herein referred to as "presumptive subarticular stress related" (PSSR) lesions. Design and patients. All patients were scanned using a standardized imaging protocol. The criterion for a PSSR lesion was a subchondral marrow edema pattern encompassing a more focal, low-signal zone adjacent to or contiguous with the subchondral cortex. Patients were identified using an electronic database search of cases reported by one experienced musculoskeletal radiologist. Results. Twenty-five PSSR lesions were identified among 1,948 MRI evaluations of the knee. Twenty-one PSSR lesions occurred in the medial compartment, and four occurred in the lateral compartment. There was no sex predilection. Patients with PSSR lesions were older than other patients undergoing MRI evaluation (mean 66 years versus 52 years, P<0.001). Meniscal tears occurred more commonly in cases with PSSR lesions than in the group as a whole (76% versus 45%, P<0.001). Radial and posterior root tears were more common in knees with PSSR lesions than in other knees with meniscal tears (53% versus 26%, P<0.01). Conclusions. PSSR lesions are associated with meniscal tears and, more specifically, with meniscal tear patterns that dramatically increase contact forces across the knee joint. This observation supports the hypothesis that mechanical stress is important in the pathogenesis of these subarticular lesions that are detected by MRI. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Fairfax Radiol Consultants PC, Fairfax, VA 22031 USA. MedTel Int, Mclean, VA 22102 USA. RP Yao, L (reprint author), NIH, Dept Diagnost Radiol, Bldg 10,Room 1C640,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. EM lyao@cc.nih.gov NR 17 TC 26 Z9 26 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 2004 VL 33 IS 5 BP 260 EP 264 DI 10.1007/s00256-004-0751-4 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 812SZ UT WOS:000220860500002 PM 14999432 ER PT J AU Ding, JZ Nieto, FJ Beauchamp, NJ Harris, TB Robbins, JA Hetmanski, JB Fried, LP Redline, S AF Ding, JZ Nieto, FJ Beauchamp, NJ Harris, TB Robbins, JA Hetmanski, JB Fried, LP Redline, S TI Sleep-disordered breathing and white matter disease in the brainstem in older adults SO SLEEP LA English DT Article DE arousal; cerebrovascular disorders; polysomnography; magnetic resonance imaging ID INFANT AROUSAL RESPONSE; CARDIOVASCULAR HEALTH; HEART HEALTH; LESIONS; APNEA; ASSOCIATION; INFARCTION; MR; HYPERINTENSITIES; ABNORMALITIES AB Study Objectives: To examine whether sleep-disordered breathing is associated with white matter disease in the brainstem. Design: A population-based longitudinal study. Setting: Allegheny County, PA; Sacramento County, CA; and Washington County, MD. Patients or Participants: A total of 789 individuals, aged 68 years or older, drawn from the Sleep Heart Health Study. Interventions: N/A. Measurements and Results: The participants underwent home polysomnography in 1995-1998 and cerebral magnetic resonance imaging in both 1992-1993 and 1997-1998. The apnea-hypopnea index was not associated with white matter disease in the brainstem, with or without adjusting for age, sex, race, community, body mass index, smoking status, alcohol use, systolic blood pressure, and the use of antihypertensive medication. In contrast, the arousal index (number of arousals per hour of sleep) was inversely associated with brainstem white matter disease (odds ratio = 0.75 for a SD increase in the arousal index, 95% confidence interval: 0.62, 0.92). Conclusions: The frequency of apneas and hypopneas was not associated with brainstem white matter disease in these older adults. A unique relationship with arousal frequency suggests that ischemic changes in the brainstem may be associated with arousals during sleep. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Wisconsin, Sch Med, Dept Populat Hlth Sci, Madison, WI USA. Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Div Clin Epidemiol, Cleveland, OH 44106 USA. RP Ding, JZ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM jding@jhsph.edu FU NHLBI NIH HHS [N01-HC-85081, U01HL53934, N01-HC-85085, U01HL53931, N01-HC-85079, U01HL53941, N01-HC-85086, N01-HC-85082, U01HL53940, U01HL53938, N01-HC-85083, U01HL53916, N01-HC-85084, N01-HC-85080, U01HL53937] NR 36 TC 25 Z9 25 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2004 VL 27 IS 3 BP 474 EP 479 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OU UT WOS:000223169000018 PM 15164901 ER PT J AU Gau, SSF Soong, WT Merikangas, KR AF Gau, SSF Soong, WT Merikangas, KR TI Correlates of sleep-wake patterns among children and young adolescents in Taiwan SO SLEEP LA English DT Article DE sleep-wake patterns; M/E scale; evening type; mood symptoms ID PHASE SYNDROME; DAYTIME SLEEPINESS; MORNINGNESS-EVENINGNESS; BODY-TEMPERATURE; PUBERTAL CHANGES; SCHOOL STUDENTS; OBESE CHILDREN; DISORDERS; RHYTHM; MELATONIN AB Study Objective: To determine correlates of morning and evening sleep-wake patterns in a community sample of children. Design: A school-based cross-sectional survey. Participants: Sample included 1572 students, grades 4 to 8 (response rate, 98.4%), using a multistage sampling method. Interventions: N/A. Measurements and Results: Student participants completed a Sleep Habits Questionnaire, which included sleep schedules, a mood scale, substance use, the morningness/eveningness (M/E) scale, pubertal development scale, sleep disturbance scale, and parental monitoring scale. The morning (n = 367) and evening (n = 364) groups were operationally defined as participants who scored in the top or bottom 25% of the M/E scale, respectively. Linear mixed and tree-based classification models were used to explore correlates of sleep-wake patterns. Our results showed the evening type was associated with older school grade level, increased coffee drinking, moodiness, decreased parental monitoring, daytime sleepiness, and several sleep disturbances, including early insomnia, fear of sleeping in darkness, bedwetting, and going to bed later than 3 am. The 2 most potent discriminators between evening and morning subtypes were higher grade level, an index of age, and moodiness. The association of moodiness with the evening type was greater in boys than girls. Conclusions: These findings suggest that further research should address explanations for the association between evening type and mood and anxiety symptoms, including order of the effects, developmental factors, environmental determinants of sleep time such as school start time and parental bedtime monitoring, and circadian maturation. C1 Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 100, Taiwan. Natl Taiwan Univ, Coll Med, Dept Psychiat, Taipei 100, Taiwan. NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Progam, Intramural Res Program,NIH,Dept HHS, Bethesda, MD 20892 USA. RP Gau, SSF (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung Shan S Rd, Taipei 100, Taiwan. EM gaushufe@ntu.edu.tw OI Gau, Susan Shur-Fen/0000-0002-2718-8221 NR 84 TC 46 Z9 48 U1 1 U2 8 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2004 VL 27 IS 3 BP 512 EP 519 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OU UT WOS:000223169000025 PM 15164908 ER PT J AU Kadiiska, MB Ghio, AJ Mason, RP AF Kadiiska, MB Ghio, AJ Mason, RP TI ESR investigation of the oxidative damage in lungs caused by asbestos and air pollution particles SO SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY LA English DT Article; Proceedings Paper CT 8th International Workshop on Electron Magnetic Resonance of Disordered Systems CY JUN 07-16, 2003 CL Sofia, BULGARIA DE ESR; spin trap; asbestos; oil fly ash; free radicals in vivo ID ENHANCED LIPID-PEROXIDATION; EPITHELIAL-CELL APOPTOSIS; FREE-RADICAL FORMATION; IN-VIVO EVIDENCE; OIL FLY-ASH; HYDROGEN-PEROXIDE; SUPEROXIDE-DISMUTASE; SOYBEAN LIPOXYGENASE; CROCIDOLITE ASBESTOS; MOLECULAR-BASIS AB Exposure to asbestos and air pollution particles can be associated with increased human morbidity and mortality. However, the molecular mechanism of lung injuries remains unknown. It has been postulated that the in vivo toxicity results from the catalysis of free radical generation. Using electron spin resonance (ESR) in conjunction with the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) we previously investigated in vivo free radical production by rats treated with intratracheal instillation of asbestos (crocidolite fibers) and an emission source air pollution particle (oil fly ash). In this report we compare the effect of two different exposures on the type of free radicals they induce in in vivo animal model. Twenty-four hours after the exposure, ESR spectroscopy of the chloroform extract from lungs of animals exposed to either asbestos or oil fly ash gave a spectrum consistent with a carbon-centered radical adduct (a(N) = 15.01 G and a(H) = 2.46 G). To test whether free radical formation occurred in vivo and not in vitro, a number of control experiments were performed. Combinations (both individually and together) of asbestos or oil fly ash and 4-POBN were added to lung homogenate of unexposed rats prior to chloroform extraction. No detectable ESR signal resulted. To exclude the possibility of ex vivo free radical generation, asbestos or oil fly ash was added to lung homogenate of an animal treated with 4-POBN. Also, 4-POBN was added to lung homogenate from rats instilled with asbestos or oil fly ash. Neither system produced radical adducts, indicating that the ESR signal detected in the lung extracts of the treated animals must be produced in vivo and not ex vivo or in vitro. In conclusion, ESR analysis of lung tissue demonstrated that both exposures produce lipid-derived radical metabolites despite their different composition and structure. Analogously, both exposures provide evidence of in vivo enhanced lipid peroxidation. Furthermore, it is concluded that without the presence of a spin-trapping agent, no free radical metabolites could be detected directly by ESR in either exposure. (C) 2003 Published by Elsevier B.V. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. US EPA, Res Triangle Pk, NC 27709 USA. RP Kadiiska, MB (reprint author), NIEHS, NIH, MD F0-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM kadiiska@niehs.nih.gov NR 56 TC 19 Z9 19 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1386-1425 J9 SPECTROCHIM ACTA A JI Spectroc. Acta Pt. A-Molec. Biomolec. Spectr. PD MAY PY 2004 VL 60 IS 6 BP 1371 EP 1377 DI 10.1016/j.saa.2003.10.035 PG 7 WC Spectroscopy SC Spectroscopy GA 822ZB UT WOS:000221578400018 PM 15134737 ER PT J AU Bykowski, JL Latour, LL Warach, S AF Bykowski, JL Latour, LL Warach, S TI More accurate identification of reversible ischemic injury in human stroke by cerebrospinal fluid suppressed diffusion-weighted imaging SO STROKE LA English DT Article DE magnetic resonance imaging; cerebral ischemia; cerebrospinal fluid; stroke, acute ID HEMORRHAGIC TRANSFORMATION; CEREBRAL-ISCHEMIA; LESION VOLUMES; TIME-COURSE; COEFFICIENT; PERFUSION; TISSUE; BRAIN; MRI; EVOLUTION AB Background and Purpose - The apparent diffusion coefficient ( ADC) derived from diffusion-weighted (DWI) MRI has been used to differentiate reversible from irreversible ischemic injury. However, the ADC can be falsely elevated by partial volume averaging of cerebrospinal fluid (CSF) with parenchyma, limiting the accuracy of this approach. This study tested the hypothesis that the accuracy of differentiating reversible from irreversible ischemic injury could be improved by CSF suppression at image acquisition. Methods - Sixteen patients presenting within 6 hours from symptoms, and having partial reversal of the acute lesion on DWI were studied using conventional CSF-suppressed DWI. Lesions were segmented from coregistered acute DWI and follow-up fluid-attenuated inversion recovery ( FLAIR) series. The segmented volumes were applied to conventional ( ADCC) and CSF-suppressed ADC (wADC(FLIPD)) maps to classify each voxel as progressed to infarct or reversed. Individual voxel ADC values were pooled across all patients. Sensitivity to predict reversal, specificity, and accuracy were calculated for both methods. Results - A total of 25 313 voxels were classified as progressed and 31 952 voxels reversed. Across all lesion voxels, ADC(FLIPD) values more accurately depicted tissue fate compared with ADCC values (P < 0.0001). The largest difference in the two methods was in voxels with <75% parenchyma, where the accuracy of ADCC was only 50% compared with 62% for ADC(FLIPD). Conclusion - CSF-suppressed ADC measurements gave a more accurate identification of reversible ischemic injury in this sample. We predict that multimodal MRI models of tissue viability in ischemic stroke will be more accurate if CSF-suppressed ADC measurements are used. C1 NINDS, NIH, Sect Stroke & Therapeut, Bethesda, MD USA. RP Warach, S (reprint author), 10 Ctr Dr,B1-D733,Mail Stop Code 1063, Bethesda, MD 20892 USA. EM warachs@ninds.nih.gov NR 33 TC 15 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD MAY PY 2004 VL 35 IS 5 BP 1100 EP 1106 DI 10.1161/01.STR.0000125867.86298.6a PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 814PY UT WOS:000220987800014 PM 15060314 ER PT J AU Prutzman, KC Gao, GH King, ML Iyer, VV Mueller, GA Schaller, MD Campbell, SL AF Prutzman, KC Gao, GH King, ML Iyer, VV Mueller, GA Schaller, MD Campbell, SL TI The focal adhesion targeting domain of focal adhesion kinase contains a hinge region that modulates tyrosine 926 phosphorylation SO STRUCTURE LA English DT Article ID SIDE-CHAIN RESONANCES; DIPOLAR COUPLINGS; TERMINAL DOMAIN; PROTEIN STRUCTURES; STRUCTURAL BASIS; LARGER PROTEINS; BACKBONE AMIDE; NMR STRUCTURES; PAXILLIN; BINDING AB The focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK) is critical for recruitment of FAK to focal adhesions and contains tyrosine 926, which, when phosphorylated, binds the SH2 domain of Grb2. Structural studies have shown that the FAT domain is a four-helix bundle that exists as a monomer and a dimer due to domain swapping of helix 1. Here, we report the NMR solution structure of the avian FAT domain, which is similar in overall structure to the X-ray crystal structures of monomeric forms of the FAT domain, except that loop 1 is longer and less structured in solution. Residues in this region undergo temperature-dependent exchange broadening and sample aberrant phi and psi angles, which suggests that this region samples multiple conformations. We have also identified a mutant that dimerizes similar to8 fold more than WT FAT domain and exhibits increased phosphorylation of tyrosine 926 both in vitro and in vivo. C1 Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Cardiovasc Biol Ctr, Chapel Hill, NC 27599 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Schaller, MD (reprint author), Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. EM crispy4@med.unc.edu; campbesl@med.unc.edu OI Iyer, Vidhya/0000-0002-5927-1927 FU NHLBI NIH HHS [HL 45100]; NIDCR NIH HHS [DE 13079]; NIGMS NIH HHS [GM 57943] NR 58 TC 30 Z9 31 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2004 VL 12 IS 5 BP 881 EP 891 DI 10.1016/S0969-2126(04)00097-8 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 821VD UT WOS:000221490200018 PM 15130480 ER PT J AU Moore, RJ Chamberlain, RM Khuri, FR AF Moore, RJ Chamberlain, RM Khuri, FR TI A qualitative study of head and neck cancer SO SUPPORTIVE CARE IN CANCER LA English DT Article DE SCCHN; primary disease; qualitative; suffering; communication; QOL ID SQUAMOUS-CELL CARCINOMA; OF-LIFE; ORAL-CAVITY; PHARYNGEAL CANCER; PAIN; MANAGEMENT; LARYNGECTOMY; DISSECTION; DEPRESSION; ANXIETY AB The findings presented contribute to quality of life (QOL) research by highlighting the significance of factors affecting the communication by patients with primary-stage squamous cell carcinoma of the head and neck cancer (SCCHN) of their experiences of suffering after treatment to their clinicians. Qualitative research methodology based on open-ended interviews with 18 survivors of American Joint Committee on Cancer primary stage I and II SCCHN were used. The interviews were transcribed verbatim and thematically analyzed. Three important themes emerged: (1) a diminished self (2) fears of addiction, and (3) hopelessness and the loss of meaning in life after SCCHN. The findings indicate that SCCHN patients under-report their experiences mainly due to fear. As a consequence, and perhaps due to a failure on the part of clinicians and patients to adequately address such fears, SCCHN patients may experience greater psychological morbidity, becoming increasingly fatalistic about biomedicine's ability to restore them to health after cancer despite being "cured", or to relieve related symptoms. This qualitative study provides a perspective as to why such under-reporting occurs, thereby potentially enhancing clinician-patient communication and the QOL of SCCHN patients who present with curable disease. C1 NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Emory Univ, Dept Clin & Translat Res Hematol & Oncol, Atlanta, GA 30322 USA. RP Moore, RJ (reprint author), NINDS, Lab Funct & Mol Imaging, Bldg 10,Room B1D106,10 Ctr Dr,MSC 1065, Bethesda, MD 20892 USA. EM moorer2001uk@yahoo.co.uk FU NCI NIH HHS [3R25 CA5770-8S2] NR 50 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 2004 VL 12 IS 5 BP 338 EP 346 DI 10.1007/s00520-003-0532-y PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 814IA UT WOS:000220967200008 PM 15064931 ER PT J AU Oz, M Woods, AS Shippenberg, T Kaminski, RM AF Oz, M Woods, AS Shippenberg, T Kaminski, RM TI Effects of extracellular pH on the dynorphin a inhibition of N-methyl-D-aspartate receptors expressed in Xenopus oocytes SO SYNAPSE LA English DT Article DE N-methyl-D-aspartate receptor; glutamate receptor; dynorphin; proton; Xenopus oocyte ID EXCITATORY AMINO-ACIDS; NMDA-RECEPTOR; DORSAL HORN; MECHANISM; NEURONS; POTENTIATION; SENSITIVITY; INCREASES; RESPONSES; ACIDOSIS AB Dynorphin A (Dyn A) (1-17), the postulated endogenous ligand for the kappa-opioid receptor, inhibits N-methyl-D-aspartate (NMDA) receptor-mediated currents in neuronal preparations and in Xenopus oocytes expressing recombinant NMDA receptors. Although direct interactions of Dyn A with the NMDA receptor have been reported, the mechanisms mediating the inhibitory actions of Dyn A are unknown. Extracellular pH is a crucial factor regulating NMDA receptor function. To date, however, the influence of pH on the inhibitory actions of Dyn A has not been examined. In the present study we used voltage-clamp recording techniques in Xenopus oocytes expressing recombinant NR1A/2A receptors to address this issue. We report that decreasing the pH of the external solution from 7.5 to 6.7 significantly enhances Dyn A inhibition of NMDA receptor-mediated currents. On the contrary, increasing the pH of the external solution to 9.2 prevents the inhibitory action of Dyn A. The influence of external pH was independent of membrane potential and the potentiation of inhibition with decreasing pH was not associated with alterations in the charge of the Dyn A molecule. These findings demonstrate that Dyn A inhibition of the NMDA receptor current is pH-dependent. They further suggest that the efficacy of neuronally released Dyn A in inhibiting NMDA receptor function may be increased in response to nerve injury and other conditions associated with decreased extracellular pH. Published 2004 Wiley-Liss, Inc.dagger C1 NIDA, IRP, Integrat Neurosci Sect, DHHS,NIH, Baltimore, MD 21224 USA. NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA. NIDA, Intramural Res Program, Chem & Drug Metab Branch, NIH,DHHS, Baltimore, MD USA. RP Shippenberg, T (reprint author), NIDA, IRP, Integrat Neurosci Sect, DHHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM tshippen@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 28 TC 4 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2004 VL 52 IS 2 BP 84 EP 88 DI 10.1002/syn.20009 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 808NI UT WOS:000220575400002 PM 15034914 ER PT J AU Spivak, CE Beglan, CL AF Spivak, CE Beglan, CL TI Kinetics of beta-funaltrexamine binding to wild-type and mutant mu-opioid receptors expressed in Chinese hamster ovary cells SO SYNAPSE LA English DT Article DE radioligand binding; rate constant; ligand saturation curve; naloxone ID SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; 6TH TRANSMEMBRANE DOMAIN; LIGAND-BINDING; ADENOSINE RECEPTOR; 3-DIMENSIONAL MODELS; SIGNAL-TRANSDUCTION; ANTAGONIST-BINDING; ACTIVATION; RESIDUES AB The two-stage reaction whereby the antagonist beta-funaltrexamine (beta-FNA) binds covalently to mu opioid receptors makes it a highly discriminating probe into the tertiary structure of the receptor's recognition pocket. To obtain a quantitative measure of how well this pocket is preserved in a mutated form of the receptor, in which His-297 is substituted with glutamine, we employed [H-3]-beta-FNA to evaluate the kinetic rate constants for both the reversible as well as the irreversible stages of its binding to wild-type and mutant H297Q mu receptors stably expressed in Chinese hamster ovary cells. The expression levels of the wild-type and mutant H297Q receptors were matched by exploiting the variation in receptor density as a function of plating day and by raising the expression level by pretreatment with naloxone. We found that all of the kinetic rate constants for [H-3]-beta-FNA were diminished by about one-half at the mutant H297Q mu receptors with respect to wild-type receptors. By comparison, the association rate constant of [H-3]-naloxone likewise decreased by one-half, however, the dissociation rate constant increased 5-fold at the mutant H297Q receptor. We conclude that the mutation has had only minor influence on the recognition site and that the function of position 297 is more likely as a link in the transduction chain. Published 2004 Wiley-Liss, Inc.dagger C1 NIDA, Intramural Res Program, Cellular Neurobiol Branch, NIH,DHHS, Baltimore, MD 21224 USA. RP Spivak, CE (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Branch, NIH,DHHS, 333 Cassell Dr,Triad Bldg,Room 3307, Baltimore, MD 21224 USA. EM espivak@intra.nida.nih.gov NR 63 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2004 VL 52 IS 2 BP 123 EP 135 DI 10.1002/syn.20014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 808NI UT WOS:000220575400006 PM 15034918 ER PT J AU Zaragoza, C Barrera, R Centeno, F Tapia, JA Mane, MC AF Zaragoza, C Barrera, R Centeno, F Tapia, JA Mane, MC TI Canine pyometra: a study of the urinary proteins by SDS-PAGE and Western blot SO THERIOGENOLOGY LA English DT Article DE pyometra; dog; proteinuria; SDS-PAGE; western blot ID RENAL-DISEASE; GEL-ELECTROPHORESIS; TUBULAR PROTEINURIA; DOGS; DYSFUNCTION AB Canine pyometra often causes glomerulonephritis by immune complex deposition in the glomeruli. Proteinuria, ranging from moderate to severe, may be present secondary to renal damage. To determine urinary protein excretion due to pyometra, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was conducted on urine from 15 bitches with pyometra and 10 healthy bitches. To characterize urinary immunoglobin excretion, Western blot analysis of the urine samples using antibodies to canine IgG and IgA was also performed. Nine bands were detected by electrophoresis in bitches with pyometra, while only four were detected in the healthy animals. The urinary proteins from bitches with pyometra were primarily of glomerular origin; 58% were of medium-high molecular weight (MW), and the remainder were low MW. None of the healthy dogs had IgG or IgA in their urine, whereas three bitches with pyometra had IgG in their urine and another bitch with pyometra had both IgG and IgA. The low proportion of bitches with urinary immunoglobins was probably be due to early diagnosis of the disease. Although only a limited number of dogs was used, this study is apparently the first to characterize the electrophoretic pattern of urinary proteins and to quantify urinary excretion of IgG and IgA in bitches with pyometra. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Extremadura, Fac Vet Sci, Dept Med & Anim Hlth, Caceres 10071, Spain. Univ Extremadura, Dept Biochem Mol Biol & Genet, Caceres 10071, Spain. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Zaragoza, C (reprint author), Univ Extremadura, Fac Vet Sci, Dept Med & Anim Hlth, Avda Univ S-N, Caceres 10071, Spain. EM zaragoza@unex.es RI Centeno, Francisco/F-7287-2016; Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 NR 42 TC 13 Z9 14 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD MAY PY 2004 VL 61 IS 7-8 BP 1259 EP 1272 DI 10.1016/j.theriogenology.2003.07.019 PG 14 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 806FU UT WOS:000220420600006 PM 15036960 ER PT J AU He, SY Jenkins-Keeran, K Woods, LC AF He, SY Jenkins-Keeran, K Woods, LC TI Activation of sperm motility in striped bass via a cAMP-independent pathway SO THERIOGENOLOGY LA English DT Article DE sperm motility; cAMP; signal transduction; striped bass ID PROTEIN-TYROSINE PHOSPHORYLATION; INTRACELLULAR CA2+; RAINBOW-TROUT; SPERMATOZOA; INITIATION; OSMOLALITY; POTASSIUM; CAPACITATION; TELEOSTS; CALCIUM AB The objective of the present study was to identify the effect of osmolality, ions (K+, H+, Ca2+, Mg2+) and cAMP on the initiation of sperm motility in striped bass (Morone saxatilis). Striped bass spermatozoa remained motile in solutions isotonic to seminal plasma (350 mOsm/kg) until osmolality reached 600 mOsm/kg. K+ (0-100 mM) had no effect (P > 0.05) on sperm motility, and sperm displayed a high percentage of motility over a wide range of pH (6.0-8.5). Sperm motility could be initiated in Ca2+-free solutions. In contrast, sperm motility was inhibited (P < 0.01) by solutions containing greater than or equal to10 mM Ca2+, and sperm could not be reactivated by a Ca2+-free solution. This Ca2+ inhibition was not affected by verapamil, a Ca2+ channel blocker. However, if sperm motility was first initiated in a Ca2+-free solution, the addition of Ca2+ solutions, up to 80 mM, failed to inhibit sperm motility, suggesting that Ca2+ inhibited the initiation of motility, but had no control of motile spermatozoa. Mg2+ solutions had similar inhibitory effects on sperm motility as Ca2+ solutions. Therefore, initiation of motility in striped bass sperm may be related to voltage-gated channels across the cell's plasma membrane. Membrane permeable cAMP did not initiate motility of quiescent, intact striped bass spermatozoa, and motility of demembranated sperm could be activated in the absence of cAMP (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. RP Woods, LC (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM curry@umd.edu NR 33 TC 16 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 0093-691X J9 THERIOGENOLOGY JI Theriogenology PD MAY PY 2004 VL 61 IS 7-8 BP 1487 EP 1498 DI 10.1016/j.theriogenology.2003.08.015 PG 12 WC Reproductive Biology; Veterinary Sciences SC Reproductive Biology; Veterinary Sciences GA 806FU UT WOS:000220420600025 PM 15036979 ER PT J AU Francischetti, NMB Mather, TN Ribeiro, JMC AF Francischetti, NMB Mather, TN Ribeiro, JMC TI Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE tissue factor pathway inhibitor; ixodes scapularis; tick saliva; anticoagulant; Kunitz ID ANTICOAGULANT PEPTIDE TAP; COAGULATION-FACTOR VIIA; FACTOR-XA; BLOOD-COAGULATION; FACTOR COMPLEX; STRUCTURAL REQUIREMENTS; CELL-SURFACES; FACTOR-IX; PROTEIN; IDENTIFICATION AB Tick saliva is a rich source of molecules with anti inflammatory, antihemostatic and immunosupressive properties. In this paper, a novel tick salivary gland cDNA with sequence homology to tissue factor pathway inhibitor (TFPI) and coding for a protein called Penthalaris has been characterized from the Lyme disease vector, Ixodes scapularis. Penthalaris is structurally unique and distinct from TFPI or TFPI-like molecules described so far, including Ixolaris, NAPc2, TFPI-1 and TFPI-2. Penthalaris is a 308-amino-acid protein (35 kDa, p1 8.58) with 12 cysteine bridges and 5 tandem Kunitz domains. Recombinant Penthalaris was expressed in insect cells and shown to inhibit factor VIIa (FVIIa)/tissue factor(TF)-induced factor X (FX) activation with an IC50 of similar to100 pM. Penthalaris tightly binds both zymogen FX and enzyme FXa (exosite), but not FVIIa, as demonstrated by column gel-filtration chromatography. At high concentrations, Penthalaris attenuates FVIIa/TF-induced chromogenic substrate (S2288) hydrolysis and FIX activation. In the presence of DEGR-FX or DEGR-FXa, but not des-Gla-DEGR-FXa as scaffolds, tight and stoichiometric inhibition of FVIIa/TF was achieved. In addition, Penthalaris blocks cell surface-mediated FXa generation by monomer (de-encrypted), but not dinner (encrypted) TF in HL-60 cells. Penthalaris may act in concert with Ixolaris and other salivary anti-hemostatics in order to help ticks to successfully feed on blood. Penthalaris is a novel anticoagulant and a tool to study FVIIa/TF-initiated biologic processes. C1 NIAID, Med Entomol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA. RP Francischetti, NMB (reprint author), NIAID, Med Entomol Sect, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Bldg Twinbrook III,Room 2E-2, Rockville, MD 20852 USA. EM ifrancischetti@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 NR 79 TC 45 Z9 46 U1 1 U2 4 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 2004 VL 91 IS 5 BP 886 EP 898 DI 10.1160/TH03-11-0715 PG 13 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 821OR UT WOS:000221471700006 ER PT J AU Aframian, DJ David, R Ben-Bassat, H Shai, E Deutsch, D Baum, BJ Palmon, A AF Aframian, DJ David, R Ben-Bassat, H Shai, E Deutsch, D Baum, BJ Palmon, A TI Characterization of murine autologous salivary gland graft cells: A model for use with an artificial salivary gland SO TISSUE ENGINEERING LA English DT Article ID EPITHELIAL-CELLS; PRIMARY CULTURE; DUCT; LINE; PROLIFERATION; GROWTH; SKIN AB The purpose of this study was to examine the growth and key functional abilities of primary cultures of salivary epithelial cells toward developing an artificial salivary gland. Cultures of epithelial cells originating from submandibular glands of BALB/c mice were established. Parenchymal cells were isolated by a Percoll gradient technique and thereafter seeded on irradiated NIH 3T3 fibroblasts serving as a feeder layer. The isolated cells were termed autologous salivary gland epithelial (ASGE) cells and could be cultivated for at least five passages ( time limit of experiments). ASGE cells presented the typical organizational behavior of epithelial cells and electron microscopy, as well as immunostaining for cytokeratins, confirmed their epithelial origin. Furthermore, measurements of transepithelial resistance and water permeability indicated the ability of the ASGE cells to form a functional epithelial barrier. This study suggests that primary salivary epithelial cells can be obtained that exhibit critical characteristics needed for use with an artificial secretory device. C1 Hebrew Univ Jerusalem, Fac Med Dent, Inst Dent Sci, Jerusalem, Israel. Expt Surg Lab, Jerusalem, Israel. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. RP Palmon, A (reprint author), Hebrew Univ Jerusalem, Fac Med Dent, Inst Dent Sci, Jerusalem, Israel. EM apalmon@cc.huji.ac.il NR 28 TC 13 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD MAY PY 2004 VL 10 IS 5-6 BP 914 EP 920 DI 10.1089/1076327041348518 PG 7 WC Cell & Tissue Engineering SC Cell Biology GA 836DC UT WOS:000222534500027 PM 15265309 ER PT J AU Ward, JM AF Ward, JM TI Controls for immunohistochemistry: Is "brown" good enough? SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 NIAID, Comparat Med Branch, NIH, Rockville, MD 20852 USA. RP Ward, JM (reprint author), NIAID, Comparat Med Branch, NIH, Rockville, MD 20852 USA. EM Jw116y@nih.gov NR 6 TC 9 Z9 9 U1 0 U2 0 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-JUN PY 2004 VL 32 IS 3 BP 273 EP 274 DI 10.1080/01926230490457585 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 818BA UT WOS:000221219400001 PM 15204969 ER PT J AU Dunnick, JK Lieuallen, W Moyer, C Orzech, D Nyska, A AF Dunnick, JK Lieuallen, W Moyer, C Orzech, D Nyska, A TI Cardiac damage in rodents after exposure to bis(2-chloroethoxy)methane SO TOXICOLOGIC PATHOLOGY LA English DT Article DE bis(2-chloroethoxy) methane; cardiotoxictiy; myocyte vacuolization; mitochondrial dysfunction; troponin T; rat; mouse ID ACUTE MYOCARDIAL-INFARCTION; TROPONIN-T MEASUREMENTS; DIAGNOSTIC EFFICIENCY; HYPERTENSIVE-RATS; DOXORUBICIN; CARDIOTOXICITY; CARDIOMYOPATHY; THROMBOSIS; METABOLISM; APOPTOSIS AB We report that an environmental agent, bis(2-chloroethoxy) methane (CEM), caused cardiac toxicity in male and female F344 rats and B6C3F1 mice exposed to the chemical by dermal administration at doses of 0, 50, 100, 200, 400 or 600 mg/kg 5 days a week for up to 14 weeks. Treatment-related deaths occurred in 10/10 male and 10/10 female rats at 600 mg/kg, in 2/10 female rats at 400 mg/kg, and in 3/10 female mice at 600 mg/kg. The heart lesions were more severe in rats than mice, and more severe in females than males. In rats, the no-observed-adverse-effect level ( NOAEL) for the heart lesions was 200 mg/kg for males and 100 mg/kg for females; in mice, it was more than 600 mg/kg for males and 200 mg/kg for females. Multifocal, widespread vacuolization of the myocytes comprised the main morphological feature of the lesions, and only in rats was it accompanied by mononuclear cell infiltration, myocytic necrosis and atrial thrombosis. Hearts from male rats were immunohistochemically stained for troponin T (cTnT) protein. Loss of cytoplasmic cTnT correlated with histopathological damage only in the 600 mg/kg animals. CEM is metabolized to thiodiglycolic acid, a chemical that causes mitochondrial dysfunction. It is hypothesized that mitochondrial damage leads to the heart toxicity from bis( 2-chloroethoxy) methane. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Charles River Labs, Pathol Associates PAI Div, Durham, NC USA. RP Dunnick, JK (reprint author), EC-35,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov FU NIEHS NIH HHS [N01-ES-15460] NR 45 TC 14 Z9 15 U1 0 U2 1 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-JUN PY 2004 VL 32 IS 3 BP 309 EP 317 DI 10.1080/01926230490431501 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 818BA UT WOS:000221219400004 PM 15204972 ER PT J AU Brix, AE Jokinen, MP Walker, NJ Sells, DM Nyska, A AF Brix, AE Jokinen, MP Walker, NJ Sells, DM Nyska, A TI Characterization of bronchiolar metaplasia of the alveolar epithelium in female Sprague-Dawley rats exposed to 3,3 ',4,4 ',5-pentachlorobiphenyl (PCB126) SO TOXICOLOGIC PATHOLOGY LA English DT Article DE PCB126; bronchiolar metaplasia; alveolar epithelium; Toxic Equivalency Factor ID TOXIC EQUIVALENCY FACTORS; FACTORS TEFS; INDUCTION; DIOXINS; PCDDS; PCDFS; PCBS AB To test the dioxin toxic equivalency factor methodology, the National Toxicology Program conducted a series of 2-year rat bioassays of dioxin-like compounds. Following gavage exposure of female Harlan Sprague - Dawley rats to 2,3', 4,4', 5-pentachlorobiphenyl (PCB126), pulmonary alveolar epithelium at the junction of terminal bronchioles and along alveolar ducts was replaced by cuboidal to columnar ciliated cells. Scattered among these were cells exhibiting characteristics consistent with those of Clara cells; they lacked cilia and had a smooth apical surface that protruded into the alveolar space. This lesion was not typical of alveolar epithelial hyperplasia seen in rodent lungs; therefore, studies were done to characterize the lesion. Results of periodic acid-Schiff (PAS) staining, alcian blue (AB) staining, and GSTPi immunohistochemical staining of the lesions seen in treated rats were more similar to normal bronchiolar epithelium than normal alveolar epithelium or alveolar epithelial hyperplasia. These findings, along with the morphology of the cells, provide evidence that this lesion is closer in character to bronchiolar epithelium than alveolar type I or alveolar type II epithelium, and as a result, was called bronchiolar metaplasia. C1 Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. Charles River Co, Pathol Associates Inc, Durham, NC 27713 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Battelle Columbus, Columbus, OH 43201 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, NIH, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 12 TC 12 Z9 12 U1 0 U2 0 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-JUN PY 2004 VL 32 IS 3 BP 333 EP 337 DI 10.1080/01926230490431817 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 818BA UT WOS:000221219400007 PM 15204975 ER PT J AU Nyska, A Cummings, CA Vainshtein, A Nadler, J Ezov, N Grunfeld, Y Gileadi, O Behar, V AF Nyska, A Cummings, CA Vainshtein, A Nadler, J Ezov, N Grunfeld, Y Gileadi, O Behar, V TI Electron Microscopy of wet tissues: A case study in renal pathology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE scanning electron microscopy; imaging; wet samples; kidney ID DIAGNOSIS; PROTEINURIA AB In this report we introduce wet-tissue scanning electron microscopy, a novel technique for direct imaging of wet tissue samples using backscattered electrons. Samples placed in sealed capsules are imaged through a resilient, electron-transparent membrane. The contrast of the imaged samples may be enhanced by chemical staining. The samples several millimeters thick and imaged without sectioning, makes this technique suitable for rapid analysis of tissue specimens. We applied this technique to D-limonene-induced nephropathy where accumulation of hyaline protein droplets is induced in proximal and distal convoluted tubules of the kidney. Images obtained by scanning electron microscopy of hydrated kidney specimens exhibited superior resolution, contrast, and magnification compared with those obtained by conventional light microscopy of paraffin sections. The electron micrographs can be obtained within an hour of tissue removal, whereas preparation for light microscopy requires at least 1 day. These advantages of the wet scanning electron microscopy technique indicate its potential utility in a wide range of applications in histopathology and toxicology. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Charles River Labs Inc, Pathol Associates PAI Div, Durham, NC 27713 USA. QuantomiX Ltd, IL-70400 Ness Ziona, Israel. Harlan Biotech Israel Ltd, IL-76326 Rehovot, Israel. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Gileadi, Opher/F-1105-2013; OI Gileadi, Opher/0000-0001-6886-898X; Ejov, Vladimir/0000-0002-5582-2859 NR 12 TC 14 Z9 14 U1 0 U2 0 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-JUN PY 2004 VL 32 IS 3 BP 357 EP 363 DI 10.1080/01926230490431772 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 818BA UT WOS:000221219400011 PM 15204979 ER PT J AU Moser, VC Phillips, PM Levine, AB McDaniel, KL Sills, RC Jortner, BS Butt, MT AF Moser, VC Phillips, PM Levine, AB McDaniel, KL Sills, RC Jortner, BS Butt, MT TI Neurotoxicity produced by dibromoacetic acid in drinking water of rats SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Society-of-Toxicology CY MAR 17-21, 2002 CL NASHVILLE, TN SP Soc Toxicol DE dibromoacetic acid; disinfection by-products; neurotoxicity; behavior; neuropathology; rats ID DISINFECTION BY-PRODUCTS; GLUTATHIONE TRANSFERASE-ZETA; 90 DAY TOXICITY; DICHLOROACETIC ACID; B6C3F1 MICE; SODIUM DICHLOROACETATE; METABOLISM; SPERMATOTOXICITY; PHARMACOKINETICS; CHLORINATION AB An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids. C1 US EPA, Div Neurotoxicol, NHEERL ORD, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. NIEHS, NTP, Res Triangle Pk, NC 27709 USA. Virginia Tech, Virginia Maryland Reg Coll Vet Med, Blacksburg, VA 24061 USA. Pathol Associates Div Charles River Labs, Frederick, MD 21701 USA. RP Moser, VC (reprint author), US EPA, Div Neurotoxicol, NHEERL ORD, MD B105-04, Res Triangle Pk, NC 27711 USA. EM moser.ginger@epa.gov NR 40 TC 20 Z9 21 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2004 VL 79 IS 1 BP 112 EP 122 DI 10.1093/toxsci/kfh081 PG 11 WC Toxicology SC Toxicology GA 816YT UT WOS:000221145900016 PM 14976349 ER PT J AU Blank, U Rivera, J AF Blank, U Rivera, J TI The ins and outs of IgE-dependent mast-cell exocytosis SO TRENDS IN IMMUNOLOGY LA English DT Review ID PROTEIN-KINASE-C; FC-EPSILON-RI; SYNAPTOSOME-ASSOCIATED PROTEIN; PHOSPHOLIPASE-D; MEMBRANE-FUSION; HIGH-AFFINITY; TYROSINE PHOSPHORYLATION; SECRETORY VESICLES; ALLERGIC RESPONSE; RBL-2H3 CELLS AB Mast cells (MCs) are able to secrete the contents of preformed cytoplasmic secretory granules (SGs) on encountering certain stimulants. For MCs, this process is fundamental to their role in innate and acquired immunity. Immunological adaptation through the production of IgE antibodies, to normally innocuous substances, has kidnapped the MC exocytotic response to cause allergic disease. Thus' understanding the molecular events in IgE-dependent MC exocytosis holds promise for therapeutic intervention. Recent advances, in deciphering the coupling of the high affinity IgE receptor (FcepsilonRI) to the secretory machinery, promote a new paradigm of the molecular coordination of MC exocytosis. A clearer picture of the link between FcepsilonRI stimulation and SG exocytosis is emerging. C1 NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, Bldg 10,Room 9N228, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 74 TC 223 Z9 229 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAY PY 2004 VL 25 IS 5 BP 266 EP 273 DI 10.1016/j.it.2004.03.005 PG 8 WC Immunology SC Immunology GA 821CA UT WOS:000221436000008 PM 15099567 ER PT J AU McClelland, CM Chang, YC Varma, A Kwon-Chung, KJ AF McClelland, CM Chang, YC Varma, A Kwon-Chung, KJ TI Uniqueness of the mating system in Cryptococcus neoformans SO TRENDS IN MICROBIOLOGY LA English DT Editorial Material ID PHEROMONE RECEPTOR GENE; MAP KINASE CASCADE; SACCHAROMYCES-CEREVISIAE; PERFECT STATE; CELL-TYPE; ALPHA; VIRULENCE; PROTEIN; HOMOLOG; LOCUS AB Although the mating system of Cryptococcus neoformans shares many physiological and genetic characteristics with other fungi, there are an increasing number of features that make it unique. The sexual state of C. neoformans is distinct from other basidiomycetes. The mating-type loci contain several mating-type-specific pheromone response pathway genes, including some that function differently in the two mating types. There are also observations of uniparental mitochondrial inheritance from the MATalpha mating type and unidirectional nuclear migration from MATalpha to MATalpha cells. These factors lead us to postulate that MATalpha and MATalpha cells play disparate roles during mating. Furthermore, we surmise that the inherent genetic differences between the two mating types render MATalpha mating-type strains more fit for survival. This might explain the predominance of MATalpha mating types both in nature and in clinical isolates. C1 NIAAA, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAAA, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. EM June_Kwon-Chung@nih.gov NR 43 TC 56 Z9 59 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 2004 VL 12 IS 5 BP 208 EP 212 DI 10.1016/j.tim.2004.03.003 PG 5 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 822OZ UT WOS:000221550800003 PM 15120139 ER PT J AU Hunter, KW AF Hunter, KW TI Ezrin, a key component in tumor metastasis SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID ERM PROTEINS; SUPPRESSOR GENE; C-MET; CANCER; INVASION; PATHWAY; CELLS; CD44; MORPHOGENESIS; CYTOSKELETON AB Identification of the key regulatory molecules in metastasis is crucial for understanding tumor dissemination and for the development of novel interventions. The recent identification of ezrin as a necessary component in the metastasis of osteosarcoma and rhabdomyosarcoma is, therefore, an important advance. Ezrin has been implicated in many roles, for example, as a conduit for signals between metastasis-associated cell-surface molecules and signal transduction components. This suggests that ezrin and, potentially, other members of the ERM (ezrin-radixin-moesin) family have key roles in the coordination of signals and cellular complexes that are required for the successful metastasis of these and other malignancies. C1 CCR, NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), CCR, NCI, Lab Populat Genet, NIH, Bldg 41 Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov NR 36 TC 163 Z9 209 U1 0 U2 5 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 2004 VL 10 IS 5 BP 201 EP 204 DI 10.1016/j.molmed.2004.03.001 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 825DL UT WOS:000221736100001 PM 15121044 ER PT J AU Holmes, A Griebel, G Heilig, M Steckler, T AF Holmes, A Griebel, G Heilig, M Steckler, T TI Response to Roesler et al.: Neuropeptides and stress-related disorders - multiple targets and converging concepts SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Letter ID ANXIETY DISORDERS C1 NIAAA, Sch Behav Sci & Genet, Bethesda, MD 20892 USA. Sanofi Synthelabo, Dept Psychopharmacol, Bagneux, France. Karolinska Inst, NEURTEC Dept, Div Psychiat, Stockholm, Sweden. Janssen Pharmaceut, Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium. RP Holmes, A (reprint author), NIAAA, Sch Behav Sci & Genet, Bethesda, MD 20892 USA. EM holmesan@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2004 VL 25 IS 5 BP 242 EP 243 DI 10.1016/j.tips.2004.03.006 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 822JG UT WOS:000221534700004 ER PT J AU Weeks, DC Walther, MM Stratakis, CA Hwang, JJ Linehan, WM Phillips, JL AF Weeks, DC Walther, MM Stratakis, CA Hwang, JJ Linehan, WM Phillips, JL TI Bilateral testicular adrenal rests after bilateral adrenalectomies in a cushingoid patient with von Hippel-Lindau disease SO UROLOGY LA English DT Article AB We report a case of bilateral testicular masses in a 25-year-old man with von Hippel-Lindau disease presenting with cushingoid symptoms. His medical history was significant for bilateral adrenalectomies secondary to pheochromocytomas, and he began steroid therapy at that time. After exhaustive endocrinologic, radiographic, and physical examinations, the testicular masses were postulated to be active adrenal rest tissue. Bilateral testicular venous sampling found elevated glucocorticoids that were responsive to dexamethasone suppression, which confirmed the testicular masses as testicular adrenal rests without the need for surgical intervention. Successful conservative management consisted of appropriate steroid manipulation and radiographic evaluation and resulted in the resolution of presenting symptoms, a decrease in size of the bilateral testicular masses, and testicular conservation in this young man. (C) 2004 Elsevier Inc. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Unit Genet & Endocrinol, NIH, Bethesda, MD 20892 USA. RP Weeks, DC (reprint author), 3212 Landover St, Alexandria, VA 22305 USA. NR 3 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2004 VL 63 IS 5 DI 10.1016/j.urology.2004.01.023 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 824ET UT WOS:000221669400050 ER PT J AU Lipscomb, J Gotay, C Snyder, C AF Lipscomb, J Gotay, C Snyder, C TI The state of the science of HRQOL assessment in cancer: Findings from the Cancer Outcomes Measurement Working Group SO VALUE IN HEALTH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 220 EP 220 DI 10.1016/S1098-3015(10)62067-0 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600006 ER PT J AU Broder, M Aledort, LM Busch, MP Custer, B Fergusson, DA Goodnough, LT Hendler, RS Hofmann, A Klein, HG Louie, JE Page, PL Sazama, K Shander, A Shulman, IA Spence, RK Sullivan, MT Thurer, RL AF Broder, M Aledort, LM Busch, MP Custer, B Fergusson, DA Goodnough, LT Hendler, RS Hofmann, A Klein, HG Louie, JE Page, PL Sazama, K Shander, A Shulman, IA Spence, RK Sullivan, MT Thurer, RL CA COBCON Working Grp TI Report from the first multidisciplinary cost of blood consensus (COBCON) working group to establish standard methodology SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Cerner Co, Zynx Hlth, Beverly Hills, CA USA. Soc Advancement Blood Management, Englewood, NJ USA. Mt Sinai Sch Med, New York, NY USA. Pacific Blood Syst Inc, San Francisco, CA USA. Univ Ottawa, Ctr Transfus Res, Ottawa, ON K1N 6N5, Canada. Washington Univ, Sch Med, St Louis, MO 63130 USA. Tenet Hlth Syst, Dallas, TX USA. SABM Austria, Vienna, Austria. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. New York Blood Ctr, New York, NY 10021 USA. Amer Red Cross, Washington, DC 20006 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mt Sinai Sch Med, Englewood, NJ USA. Englewood Hosp & Med Ctr, Englewood, NJ USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. St Agnes Hlth Care, Baltimore, MD USA. Natl Blood Data Resource Ctr, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 317 EP 317 DI 10.1016/S1098-3015(10)62366-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600305 ER PT J AU Kleiter, M Malarkey, DE Ruslander, DE Thrall, DE AF Kleiter, M Malarkey, DE Ruslander, DE Thrall, DE TI Expression of cyclooxygenase-2 in canine epithelial nasal tumors SO VETERINARY RADIOLOGY & ULTRASOUND LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Veterinary-Radiology CY DEC, 2002 CL CHICAGO, IL SP Amer Coll Vet Radiol DE canine; cyclooxygenase-2; nasal tumors; radiation therapy ID SQUAMOUS-CELL CARCINOMA; IN-VITRO; RADIATION-THERAPY; COX-2 EXPRESSION; MAMMARY-TUMORS; DOGS; SURVIVAL; RADIOTHERAPY; INHIBITOR; ENHANCEMENT AB Cyclooxygenase-2 (COX-2) is an enzyme upregulated in some human and animal tumors. Enzymatic products are associated with tumorigenic activities. Given the poor response of canine nasal tumors to radiation, we considered the possibility that some of this resistance may be associated with COX-2 expression. To test this, 21 formalin-fixed, paraffin-embedded, and archived biopsy samples from canine epithelial nasal tumors were analyzed for COX-2 expression using immunohistochemistry. The biopsies were collected from dogs prior to radiation therapy. COX-2 expression was present in 17 of 21 (81%) tumors. The expression was observed in several different tumor types, including nasal carcinomas, adenocarcinomas, and squamous cell carcinomas. Samples from five control dogs without nasal neoplasia were also analyzed for COX-2 staining. These specimens were characterized by varying degrees of lymphoplasmacytic rhinitis with scattered regions of COX-2 positive respiratory epithelial and stromal cells. Whether the intensity and distribution of COX-2 expression in nasal tumors can be used as a prognostic marker requires further investigation. A combination therapy of irradiation and a selective COX-2 inhibitor appears worthy of clinical investigation in the treatment of canine epithelial nasal tumors. C1 N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27606 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Kleiter, M (reprint author), N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM Miriam_Kleiter@ncsu.edu NR 47 TC 26 Z9 27 U1 0 U2 3 PU AMER COLL VETERINARY RADIOLOGY PI RALEIGH PA 2520 BEECHRIDGE RD, RALEIGH, NC 27608 USA SN 1058-8183 J9 VET RADIOL ULTRASOUN JI Vet. Radiol. Ultrasound PD MAY-JUN PY 2004 VL 45 IS 3 BP 255 EP 260 DI 10.1111/j.1740-8261.2004.04046.x PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 826QS UT WOS:000221844200013 PM 15200266 ER PT J AU Falanga, V Schrayer, D Cha, JS Butmarc, J Carson, P Roberts, AB Kim, SJ AF Falanga, V Schrayer, D Cha, JS Butmarc, J Carson, P Roberts, AB Kim, SJ TI Full-thickness wounding of the mouse tail as a model for delayed wound healing: accelerated wound closure in Smad3 knock-out mice SO WOUND REPAIR AND REGENERATION LA English DT Article ID SPECIFICITY; EXPRESSION; KINASE; SKIN AB Experimentally induced wounds in animal models are useful in gaining a better understanding of the cellular and molecular processes of wound healing, and in the initial evaluation of the safety and effectiveness of potential therapeutic agents. However, studying delayed healing has proved difficult in animals, whose wounds heal within a few days. In this report, we describe a novel method for establishing mouse wounds that require up to 3 weeks or more for complete closure, and we show the validity of this model in Smad3 null mice, which are known to display accelerated healing. Full-thickness wounds, measuring 0.3 by 1.0 cm, were made down to fascia on the dorsal aspect of the mouse tail in Smad3 knock-out mice and control littermates, approximately I cm distal to the body of the animal. The wounds were left to heal by secondary intention and were assessed histologically by computerized planimetry for wound closure at various times after wounding. The wounds in wild-type mice displayed delayed healing, with full closure occurring between 14 and 25 days after wounding. Complete closure of similar wounds in Smad3 null mice healed 30 percent faster (p < 0.01). By immunostaining for ki67, a marker for proliferation, Smad3 null animals also showed increased proliferation of dermal wound cells by day 4 after wounding. Cultured dermal fibroblasts from Smad3 null mice had increased baseline DNA synthesis and, interestingly, an enhanced response to transforming growth factor-beta1. By Western blot analysis, Smad3 null mice fibroblasts showed a compensatory increase in mitogen-activated protein kinase phosphorylation in response to transforming growth factor-beta1, suggesting that mitogen-activated protein kinase overcompensation together with loss of Smad3 may be involved in the modulation of faster healing. We conclude that this novel tail-wounding model may be useful for studying delayed wound closure. C1 Roger Williams Canc Med Ctr, Dept Dermatol, Providence, RI 02908 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Falanga, V (reprint author), Roger Williams Canc Med Ctr, Dept Dermatol & Skin Surg, Elmhurst Bldg,50 Maude St, Providence, RI 02908 USA. EM vfolongo@bu.edu FU NIAMS NIH HHS [AR 42936, AR 46557]; NIDDK NIH HHS [DK 067836] NR 18 TC 32 Z9 37 U1 1 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY-JUN PY 2004 VL 12 IS 3 BP 320 EP 326 DI 10.1111/j.1067-1927.2004.012316.x PG 7 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 834WN UT WOS:000222441700008 PM 15225210 ER PT J AU Karlsson, AC Younger, SR Martin, JN Grossman, Z Sinclair, E Hunt, PW Hagos, E Nixon, DF Deeks, SG AF Karlsson, AC Younger, SR Martin, JN Grossman, Z Sinclair, E Hunt, PW Hagos, E Nixon, DF Deeks, SG TI Immunologic and virologic evolution during periods of intermittent and persistent low-level viremia SO AIDS LA English DT Article DE immune activation; antiretroviral therapy; HIV-specific cellular immunity; HIV drug resistance/resistance mutations ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL-ACTIVATION; PHENOTYPIC DRUG SUSCEPTIBILITY; RESIDUAL VIRAL REPLICATION; HIV-INFECTED ADULTS; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; IMMUNE-RESPONSES; WHITE PULPS; SUPPRESSION AB Background: HIV replication, HIV-specific T-cell responses and T-cell activation each contributes to disease outcome during untreated HIV infection. The interaction of these factors is not well understood, particularly in the setting of antiretroviral therapy. Methods: This is a longitudinal study of antiretroviral-treated patients with plasma HIV RNA levels < 1000 copies/ml. Patients were divided into three groups: suppressed viremia, intermittent viremia ('blips') and persistent low-level viremia. HIV-specific immunity was measured using interferon-γ ELISPOT. T-cell activation was defined by CD38 and HLA-DR co-expression. Drug resistance was quantified using a phenotypic susceptibility assay. Results: The breadth and the magnitude of the HIV-specific CD8 T-cell response was greater in patients with either intermittent or persistent viremia compared to patients with suppressed viremia. In contrast, T-cell activation was significantly elevated only in those patients with persistent viremia. Patients with persistent low-level viremia had moderate levels of phenotypic antiretroviral drug resistance that increased over time. Virologic failure (confirmed increase in viral load > 1000 HIV RNA copies/ml) was primarily observed in the persistently viremic group. Conclusions: Antiretroviral-treated individuals with intermittent viremia appear to mount an effective HIV-specific T-cell response while not experiencing increases in the level of immune activation. This may limit viral evolution and emergence of drug resistance. In contrast, antiretroviral-treated individuals with persistent low-level viremia exhibit significant increases in overall immune activation and a substantial risk of subsequent treatment failure. It is likely that higher viremia and stronger immune activation act synergistically to accelerate the development of systemic drug resistance. (C) 2004 Lippincott Williams Wilkins. C1 San Francisco Gen Hosp, San Francisco, CA 94110 USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NIH, Bethesda, MD 20892 USA. RP Deeks, SG (reprint author), San Francisco Gen Hosp, 995 Potrero Ave, San Francisco, CA 94110 USA. RI Karlsson, Annika/R-2255-2016; OI Karlsson, Annika/0000-0002-2028-8393; Nixon, Douglas/0000-0002-2801-1786 FU NCRR NIH HHS [5-M01-RR00083-37]; NIAID NIH HHS [AI052745, AI055273, P30 AI27763]; NIMH NIH HHS [P30 MH59037, P30 MH62246] NR 37 TC 69 Z9 70 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 30 PY 2004 VL 18 IS 7 BP 981 EP 989 DI 10.1097/01.aids.0000125906.75228.f5 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 821OG UT WOS:000221470100006 PM 15096800 ER PT J AU Verthelyi, D Wang, VW Lifson, JD Klinman, DM AF Verthelyi, D Wang, VW Lifson, JD Klinman, DM TI CpG oligodeoxynucleotides improve the response to hepatitis B immunization in healthy and SIV-infected rhesus macaques SO AIDS LA English DT Article DE CpG oligodeoxynucleotides; hepatitis B vaccine; rhesus macaques; SIV ID PLASMACYTOID DENDRITIC CELLS; VIRUS-INFECTION; HIV-1 INFECTION; BACTERIAL-DNA; VACCINE; MOTIFS; INDIVIDUALS; ACTIVATION; MONOCYTES; ADJUVANTS AB Objective: The development of an immunogenic vaccine against hepatitis B virus (HBV) is particularly important for HIV-infected patients since shared epidemiological risks result in HIV-infected subjects having a high incidence of HBV, and coinfection with HBV increases the occurrence of hepatotoxicity with aritiretroviral therapy. Although HBV vaccination is recommended to all HIV-positive patients, its efficacy in these patients is reduced. Methods: Healthy (n = 15) and SIV-infected (n = 17) rhesus macaques were immunized with Engerix B alone or combined with type D or type K CpG ODN. SIV plasma RNA levels were determined by a real time reverse transcriptase polymerase chain reaction and antibody titers to HBV surface antigen (HbsAg) were measured by enzyme-linked immunosorbent assay every 2 weeks. Results: In healthy macaques, adding D or K ODN to Engerix B accelerated and boosted the titer of the anti-HbsAg response. In SIV-infected macaques, Engerix B alone elicited no detectable antibody response but a significant response was seen when it was combined with K or D ODN. The antibody titer induced by vaccinating HIV-infected macaques was inversely correlated with their initial viral load, with animals having > 10(7) copies/ml being unable to mount a significant response. No adverse events or changes in SIV viral load were evident during the study. Conclusions: These findings support the development of clinical studies to assess the use of CpG ODN as an adjuvant for HBV vaccination in healthy and immunocompromised HIV-infected subjects. (C) 2004 Lippinecott Williams Wilkins. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. RP Verthelyi, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bldg 29A Rm 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-12400] NR 33 TC 35 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 30 PY 2004 VL 18 IS 7 BP 1003 EP 1008 DI 10.1097/01.aids.0000111474.61782.d1 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 821OG UT WOS:000221470100008 PM 15096802 ER PT J AU Divi, RL Walker, VE Wade, NA Nagashima, K Seilkopf, SK Adams, ME Nesel, CJ O'Neill, JP Abrams, EJ Poirier, MC AF Divi, RL Walker, VE Wade, NA Nagashima, K Seilkopf, SK Adams, ME Nesel, CJ O'Neill, JP Abrams, EJ Poirier, MC TI Mitochondrial damage and DNA depletion in cord blood and umbilical cord from infants exposed in utero to Combivir SO AIDS LA English DT Article DE leukocytes; zidovudine; lamivudine; electron microscopy; PCR-chemiluminescence immunoasssay detection ID HIV-INFECTED WOMEN; REVERSE-TRANSCRIPTASE INHIBITORS; IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL THERAPY; UNINFECTED INFANTS; PATAS MONKEYS; ZIDOVUDINE TREATMENT; NUCLEOSIDE ANALOGS; PREGNANT-WOMEN; UNITED-STATES AB Objective: Although most uninfected infants born to women infected with HIV-1 show no clinical evidence of mitochondrial compromise, mitochondrial dysfunction has been reported in children born to women receiving zidovudine and/or lamivudine during pregnancy. In this pilot study we examined mitochondrial integrity in HIV-1-uninfected infants born to HIV-1-infected women receiving Combivir during pregnancy. Design: Samples of umbilical cord and cord blood were obtained from HIV-1-uninfected infants born to either HIV-1-infected women receiving Combivir therapy during pregnancy (n = 10) or HIV-1-uninfected women (n = 9). Methods: Mitochondrial morphological integrity was examined in umbilical cords (n = 16) by electron microscopy and mtDNA quantity was determined in DNA from cord blood (n = 18) and umbilical cord (n = 18) by PCR-chemiluminescence immunoassay detection. Results: In umbilical cords from six of nine infants born to HIV-1-infected mothers taking Combivir moderate to severe mitochondrial morphological damage was observed (P = 0.011), while none of seven unexposed infants showed similar damage. Compared to unexposed infants, statistically significant mtDNA depletion was observed in umbilical cord (P = 0.006) and cord blood (P = 0.003) from drug-exposed infants. Conclusions: A cohort of HIV-1-uninfected Combivir-exposed infants with no clinical symptoms showed morphological and molecular evidence of mitochondrial damage. (C) 2004 Lippincott Williams Wilkins. C1 NCI, CDI Sect, NIH, Bethesda, MD 20892 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Albany Med Ctr, Childrens Hosp, Dept Pediat, Albany, NY USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. NCI, SAIC, Frederick, MD 21701 USA. SKS Consulting Serv, Siler City, NC USA. Westat Corp, Rockville, MD USA. Univ Vermont, Genet Lab, Burlington, VT USA. Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY USA. Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. RP Poirier, MC (reprint author), NCI, CDI Sect, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [R01-HL72727]; NICHD NIH HHS [R01-HD33648] NR 44 TC 53 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 30 PY 2004 VL 18 IS 7 BP 1013 EP 1021 DI 10.1097/01.aids.0000125905.67605.2c PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 821OG UT WOS:000221470100010 PM 15096804 ER PT J AU You, J Croyle, JL Nishimura, A Ozato, K Howley, PM AF You, J Croyle, JL Nishimura, A Ozato, K Howley, PM TI Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes SO CELL LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; NUCLEAR ANTIGEN; BROMODOMAIN PROTEIN; EPISOMAL MAINTENANCE; VIRUS PLASMIDS; S-PHASE; CELLS; REPLICATION; CHROMATIN; TRANSACTIVATION AB The papillomavirus E2 protein tethers viral genomes to host mitotic chromosomes to ensure genome maintenance. We have identified the bromodomain protein Brd4 as a major cellular interacting partner of the bovine papillomavirus E2. Brd4 associates with mitotic chromosomes and colocalizes with E2 on mitotic chromosomes. The site of E2 binding maps to the C-terminal domain of Brd4. Expression of this C-terminal Brd4 domain functions in a dominant-negative manner to abrogate the colocalization of E2 with Brd4 on mitotic chromosomes, to block association of the viral episomes with Brd4, and to inhibit BPV-1 DNA-mediated cellular transformation. Brd4 also associates with HPV16 E2, indicating that Brd4 binding may be a shared property of all papillomavirus E2 proteins. The interaction of E2 with Brd4 is required to ensure the tethering of viral genomes to the host mitotic chromosomes for persistence of viral episomes in PV-infected cells. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Howley, PM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM peter_howley@hms.harvard.edu FU NCI NIH HHS [P01 CA50661, R01 CA77385] NR 36 TC 239 Z9 245 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 30 PY 2004 VL 117 IS 3 BP 349 EP 360 DI 10.1016/S0092-8674(04)00402-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 817KM UT WOS:000221176400009 PM 15109495 ER PT J AU Wang, SQ Wei, CL Zhao, GL Brochet, DXP Shen, JX Song, LS Wang, W Yang, DM Cheng, HP AF Wang, SQ Wei, CL Zhao, GL Brochet, DXP Shen, JX Song, LS Wang, W Yang, DM Cheng, HP TI Imaging microdomain Ca2+ in muscle cells SO CIRCULATION RESEARCH LA English DT Review DE Ca2+ signaling; Ca2+ sparks; Ca2+ channels; excitation-contraction coupling; sarcoplasmic reticulum ID RAT-HEART CELLS; CHANNELS RYANODINE RECEPTORS; GREEN FLUORESCENT PROTEINS; MAMMALIAN SKELETAL-MUSCLE; CALCIUM-RELEASE CHANNELS; PIG CARDIAC MYOCYTES; SARCOPLASMIC-RETICULUM; VENTRICULAR MYOCYTES; INOSITOL TRISPHOSPHATE; ELEMENTARY EVENTS AB Ca2+ ions passing through a single or a cluster of Ca2+-permeable channels create microscopic, short-lived Ca2+ gradients that constitute the building blocks of cellular Ca2+ signaling. Over the last decade, imaging microdomain Ca2+ in muscle cells has unveiled the exquisite spatial and temporal architecture of intracellular Ca2+ dynamics and has reshaped our understanding of Ca2+ signaling mechanisms. Major advances include the visualization of "Ca2+ sparks" as the elementary events of Ca2+ release from the sarcoplasmic reticulum (SR), "Ca2+ sparklets" produced by openings of single Ca2+-permeable channels, miniature Ca2+ transients in single mitochondria ("marks"), and SR luminal Ca2+ depletion transients ("scraps"). As a model system, a cardiac myocyte contains a 3-dimensional grid of 104 spark ignition sites, stochastic activation of which summates into global Ca2+ transients. Tracking intermolecular coupling between single L-type Ca2+ channels and Ca2+ sparks has provided direct evidence validating the local control theory of Ca2+-induced Ca2+ release in the heart. In vascular smooth muscle myocytes, Ca2+ can paradoxically signal both vessel constriction (by global Ca2+ transients) and relaxation (by subsurface Ca2+ sparks). These findings shed new light on the origin of Ca2+ signaling efficiency, specificity, and versatility. In addition, microdomain Ca2+ imaging offers a novel modality that complements electrophysiological approaches in characterizing Ca2+ channels in intact cells. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Peking Univ, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. First Mil Med Univ, Dept Physiol, Guangzhou, Peoples R China. RP Cheng, HP (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Schock Dr, Baltimore, MD 21224 USA. EM chengp@grc.nia.nih.gov RI Zhao, Guiling/D-3654-2009; Song, Long-Sheng/D-5899-2012; Wei, Chaoliang/A-9008-2013; OI Wang, Wang/0000-0001-9093-412X NR 122 TC 51 Z9 54 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 30 PY 2004 VL 94 IS 8 BP 1011 EP 1022 DI 10.1161/01.RES.0000125883.68447.A1 PG 12 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 816MJ UT WOS:000221113700004 PM 15117829 ER PT J AU Tong, HY Rockman, HA Koch, WJ Steenbergen, C Murphy, E AF Tong, HY Rockman, HA Koch, WJ Steenbergen, C Murphy, E TI G protein-coupled receptor internalization signaling is required for cardioprotection in ischemic preconditioning SO CIRCULATION RESEARCH LA English DT Article DE G beta gamma; phosphatidylinositol 3-kinase; transgenic mice; isolated heart; ischemic preconditioning ID BETA-GAMMA-SUBUNITS; KINASE C-EPSILON; PHOSPHOINOSITIDE 3-KINASE; DEPENDENT ACTIVATION; ADENOSINE RECEPTORS; CONSCIOUS RABBITS; TYROSINE KINASES; ARRESTINS; MEMBRANE; HEART AB The present study is designed to explore the role of G protein-coupled receptors (GPCRs) in the protection afforded by ischemic preconditioning ( PC). We used TG mice with cardiac-specific overexpression of a Gbetagamma-sequestering peptide, betaARKct (TG betaARKct mice), to test whether the protection of PC is Gbetagamma-dependent. To test the role of G(i) protein, we used wild-type mice pretreated with the G(i) inhibitor pertussis toxin. Recovery of left ventricular developed pressure and infarct size were measured as indices of protection. PC induced protection in wild-type mice, but this protection was blocked by pertussis toxin treatment and was also blocked in TG betaARKct mice. To determine the mechanism of Gbetagamma-induced protection in PC, we investigated one of the downstream targets of Gbetagamma, the PI3K/p70S6K pathway. PC-induced phosphorylation of p70S6K was not blocked in TG betaARKct hearts; therefore, we investigated other targets of Gbetagamma. Recent studies suggest a role for Gbetagamma in GPCR internalization. We found that betaARKct, a specific PI3K inhibitor wortmannin, and bafilomycin A(1), which all block receptor recycling, all blocked the protective effect of PC. To additionally test whether PI3K is involved in PC-activated receptor internalization and endosomal signaling, we used TG mice with cardiac-specific overexpression of a catalytically inactive mutant PI3Kgamma, which disrupts the recruitment of functional PI3K to agonist-activated GPCRs in vivo. We found that the catalytically inactive mutant of PI3Kgamma blocks the protection of PC. In summary, these data suggest the novel finding that the cardioprotective effect of PC requires receptor internalization. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol & Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov FU NHLBI NIH HHS [HL-39752, R01 HL039752, HL-56687, HL-61690] NR 35 TC 41 Z9 45 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 30 PY 2004 VL 94 IS 8 BP 1133 EP 1141 DI 10.1161/01.RES.0000126048.32383.6B PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 816MJ UT WOS:000221113700018 PM 15031261 ER PT J AU Seki, T Hong, KH Yun, JY Kim, SJ Oh, SP AF Seki, T Hong, KH Yun, JY Kim, SJ Oh, SP TI Isolation of a regulatory region of activin receptor-like kinase 1 gene sufficient for arterial endothelium-specific expression SO CIRCULATION RESEARCH LA English DT Article DE activin receptor-like kinase 1; artery-specific gene expression; angiogenesis; hereditary hemorrhagic telangiectasia; transforming growth factor-beta ID ADHESION MOLECULE-1 PROMOTER; HUMAN ICAM-2 PROMOTER; FACTOR-BINDING SITES; VASCULAR DEVELOPMENT; TYROSINE KINASE; TRANSGENIC MICE; IN-VIVO; TRANSCRIPTION; CELLS; GATA AB Activin receptor-like kinase 1 (Acvrl1; Alk1) is a type I receptor for transforming growth factor-beta (TGF-beta). ALK1 plays a pivotal role in vascular development and is involved in the development of hereditary hemorrhagic telangiectasia 2 (HHT2), a dominantly inherited vascular disorder, and pulmonary hypertension. We have previously shown that Alk1 is expressed predominantly in arterial endothelial cells (ECs). Despite recent discoveries of a number of artery-specific genes, the regulatory elements of these genes have not been characterized. To investigate the cis-acting elements essential for the artery-specific Alk1 expression, we have generated a series of transgenic constructs with various lengths and regions of Alk1 genomic fragments connected to a LacZ reporter gene, and analyzed the reporter gene expression in transgenic mice. We found that a 9.2-kb genomic fragment, which includes 2.7-kb promoter region and the entire intron 2, is sufficient to drive arterial endothelium-specific expression. The defined regulatory region, as well as the transgenic mouse lines, would be invaluable resources in studying the mechanisms underlying angiogenesis, arteriogenesis, and vascular disorders, such as HHT and pulmonary hypertension. The full text of this article is available online at http://circres.ahajournals.org. C1 Univ Florida, Dept Physiol & Funct Genom, Coll Med, Gainesville, FL 32610 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Oh, SP (reprint author), Univ Florida, Dept Physiol & Funct Genom, Coll Med, 1600 SW Archer Rd,D5-36, Gainesville, FL 32610 USA. EM ohp@phys.med.ufl.edu FU NHLBI NIH HHS [HL64024] NR 38 TC 26 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 30 PY 2004 VL 94 IS 8 BP E72 EP E82 DI 10.1161/01.RES.0000127048.81744.31 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 816MJ UT WOS:000221113700021 PM 15059937 ER PT J AU White, JF Trinh, LB Shiloach, J Grisshammer, R AF White, JF Trinh, LB Shiloach, J Grisshammer, R TI Automated large-scale purification of a G protein-coupled receptor for neurotensin SO FEBS LETTERS LA English DT Article; Proceedings Paper CT 2nd International Conference on Structure, Dynamics and Function of Proteins in Biological Membranes CY OCT 05-10, 2003 CL Monte Verita, Ascona, SWITZERLAND HO Monte Verita DE large-scale purification; G protein-coupled receptor; automation; detergent; neurotensin receptor ID MAMMALIAN-CELL LINES; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI; EXPRESSION; RHODOPSIN; MUTANTS; CONFORMATION; MECHANISM; PEPTIDE; CLONING AB Structure determination of integral membrane proteins requires milligram amounts of purified, functional protein on a regular basis. Here, we describe a protocol for the purification of a G protein-coupled neurotensin receptor fusion protein at the 3-mg or 10-mg level using immobilized metal affinity chromatography and a neurotensin column in a fully automated mode. Fermentation at a 200-1 scale of Escherichia coli expressing functional receptors provides the material needed to feed into the purification routine. Constructs with tobacco etch virus protease recognition sites at either end of the receptor allow the isolation of neurotensin receptor devoid of its fusion partners. The presented expression and purification procedures are simple and robust, and provide the basis for crystallization experiments of receptors on a routine basis. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIDDKD, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Biotechnol Unit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grisshammer, R (reprint author), NIDDKD, Mol Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM rkgriss@helix.nih.gov RI Grisshammer, Reinhard/C-3089-2015 NR 30 TC 60 Z9 62 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 30 PY 2004 VL 564 IS 3 BP 289 EP 293 DI 10.1016/S0014-5793(04)00195-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 817IG UT WOS:000221170600015 PM 15111111 ER PT J AU Oke, M Sarra, R Ghirlando, R Farnaud, S Gorringe, AR Evans, RW Buchanan, SK AF Oke, M Sarra, R Ghirlando, R Farnaud, S Gorringe, AR Evans, RW Buchanan, SK TI The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane beta-barrel SO FEBS LETTERS LA English DT Article; Proceedings Paper CT 2nd International Conference on Structure, Dynamics and Function of Proteins in Biological Membranes CY OCT 05-10, 2003 CL Monte Verita, Ascona, SWITZERLAND HO Monte Verita DE transferrin binding protein A; iron transport; human transferrin; TonB; Neisseria meningitidis ID BINDING PROTEIN-A; GONOCOCCAL TRANSFERRIN RECEPTOR; OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI; CIRCULAR-DICHROISM; IRON ACQUISITION; LIGAND-BINDING; CYTOPLASMIC MEMBRANE; ENERGY TRANSDUCTION; CRYSTAL-STRUCTURE AB Transferrin binding protein A (TbpA) is a TonB-dependent outer membrane protein expressed by pathogenic bacteria for iron acquisition from human transferrin. The N-termi-nal 160 residues (plug domain) of TbpA were overexpressed in both the periplasm and cytoplasm of Escherichia coli. We found this domain to be soluble and monodisperse in solution, exhibiting secondary structure elements found in plug domains of structurally characterized TonB-dependent transporters. Although the TbpA plug domain is apparently correctly folded, we were not able to observe an interaction with human transferrin by isothermal titration calorimetry or nitrocellulose binding assays. These experiments suggest that the plug domain may fold independently of the P-barrel, but extracellular loops of the beta-barrel are required for ligand binding. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIDDKD, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ London Birkbeck Coll, Dept Crystallog, London WC1E 7HX, England. Kings Coll London, Randall Ctr Mol Mechanisms Cell Funct, Div Biomol Sci, Metalloprot Res Grp, London SE1 1UL, England. Hlth Protect Agcy, Salisbury SP4 0JG, Wilts, England. RP Buchanan, SK (reprint author), NIDDKD, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov RI Ghirlando, Rodolfo/A-8880-2009 NR 65 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 30 PY 2004 VL 564 IS 3 BP 294 EP 300 DI 10.1016/S0014-5793(04)00196-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 817IG UT WOS:000221170600016 PM 15111112 ER PT J AU Opresko, PL Cheng, WH Bohr, VA AF Opresko, PL Cheng, WH Bohr, VA TI Junction of RecQ helicase biochemistry and human disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID WERNER-SYNDROME PROTEIN; BLOOMS-SYNDROME HELICASE; STALLED REPLICATION FORKS; HOMOLOGOUS RECOMBINATION; SUBSTRATE-SPECIFICITY; ESCHERICHIA-COLI; DNA-REPLICATION; SACCHAROMYCES-CEREVISIAE; EXONUCLEASE ACTIVITY; FLAP ENDONUCLEASE-1 C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Opresko, Patricia/0000-0002-6470-2189 NR 67 TC 73 Z9 78 U1 1 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 30 PY 2004 VL 279 IS 18 BP 18099 EP 18102 DI 10.1074/jbc.R300034200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500001 PM 15023996 ER PT J AU Tartaix, PH Doulaverakis, M George, A Fisher, LW Butler, WT Qin, CL Salih, E Tan, ML Fujimoto, Y Spevak, L Boskey, AL AF Tartaix, PH Doulaverakis, M George, A Fisher, LW Butler, WT Qin, CL Salih, E Tan, ML Fujimoto, Y Spevak, L Boskey, AL TI In vitro effects of dentin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACIDIC PHOSPHOPROTEIN; OSTEOPONTIN; GENE; SIALOPROTEIN; BIOMINERALIZATION; IDENTIFICATION; INHIBITION; EXPRESSION; GROWTH; CALCIFICATION AB Dentin matrix protein-1 (DMP1) is a mineralized tissue matrix protein synthesized by osteoblasts, hypertrophic chondrocytes, and ameloblasts as well as odontoblasts. DMP1 is believed to have multiple in vivo functions, acting both as a signaling molecule and a regulator of biomineralization. Using a cell-free system in vitro, we evaluated the action of DMP1 in the regulation of hydroxylapatite ( HA) formation and crystal growth. The non-phosphorylated recombinant protein acted as an HA nucleator, increasing the amount of mineral formed in a gelatin gel HA growth system relative to protein-free controls. The recombinant protein phosphorylated in vitro had no detectable effect on HA formation and growth. In contrast, phosphorylated bovine DMP1 expressed in marrow stromal cells with an adenovirus vector containing 29.7 phosphates/mol was an effective inhibitor of HA formation and growth. The native full-length protein appeared to be absent or present in only small amounts in the extracellular matrix of bones and teeth. However, two highly phosphorylated fragments representing the N- and C-terminal portions of DMP1 have been identified, apparently arising from proteolytic cleavage of four X - Asp bonds. The highly phosphorylated C-terminal 57-kDa fragment ( containing 42 phosphates/mol), like the non-phosphorylated DMP1, was an HA nucleator. These data suggest that, in its native form, DMP1 inhibits mineralization, but when cleaved or dephosphorylated, it initiates mineralization. These in vitro data are consistent with the findings in the DMP1 knockout mouse. C1 Hosp Special Surg, Div Res, Mineralized Tissues Lab, Musculoskeletal Integr Program, New York, NY 10021 USA. Columbia Univ, Sch Dent & Oral Surg, New York, NY 10032 USA. Univ Illinois, Dept Oral Biol, Chicago, IL 60612 USA. NIDCR, Matrix Biochem Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Basic Sci, Houston, TX 77030 USA. Harvard Univ, Sch Med, Lab Study Skeletal Dis & Rehabil, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. RP Boskey, AL (reprint author), Hosp Special Surg, Div Res, Mineralized Tissues Lab, Musculoskeletal Integr Program, 535 E 70th St, New York, NY 10021 USA. EM boskeya@hss.edu OI Salih, Erdjan/0000-0003-3322-2323; GEORGE, ANNE/0000-0002-9008-7642; Boskey, Adele/0000-0002-6181-2219 FU NIA NIH HHS [AG17969]; NIDCR NIH HHS [DE04141, DE05092, DE11657] NR 38 TC 116 Z9 120 U1 2 U2 14 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 30 PY 2004 VL 279 IS 18 BP 18115 EP 18120 DI 10.1074/jbc.M314114200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500005 PM 14769788 ER PT J AU Luo, Q Ma, XJ Wahl, SM Bieker, JJ Crossley, M Montaner, LJ AF Luo, Q Ma, XJ Wahl, SM Bieker, JJ Crossley, M Montaner, LJ TI Activation and repression of interleukin-12 p40 transcription by erythroid Kruppel-like factor in macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; BETA-GLOBIN PROMOTER; BOX-BINDING-PROTEIN; FACTOR EKLF; CACCC-BOX; GENE PROMOTER; FACTOR PU.1; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; IL-12 PRODUCTION AB Transcription of interleukin (IL)-12 p40 in myeloid cells is attributed to the recruitment of multiple activated transcription factors such as nuclear factor kappaB (NFkappaB), CCAAT enhancer-binding protein beta, ets-2, PU.1, and so forth. We now provide the first description of the human erythroid Kruppel-like factor ( EKLF) in human primary macrophages and identify the role of EKLF in IL-12 p40 expression. EKLF-specific binding to the CACCC element (-224 to -220) on the human IL-12 p40 promoter was observed in resting human primary macrophages. Functional analysis of the CACCC element revealed a dependent role for EKLF binding in activating IL-12 p40 transcription in resting RAW264.7 cells, whereas EKLF overexpression in the presence or absence of this element repressed IL-12 p40 transcription in interferon gamma/lipopolysaccharide-stimulated RAW264.7 cells. Murine endogenous IL-12 p40 mRNA was consistently induced by overexpressed EKLF in resting RAW264.7 cells, whereas EKLF suppressed IL-12 p40 expression in activated RAW264.7 cells. Modulation of nuclear binding activities at the IL-12 p40 NFkappaB half-site was induced by EKLF for down-regulation of IL-12 p40 transcription in activated RAW264.7 cells, but no effect of EKLF on NFkappaB activity was observed in resting RAW264.7 cells. Taken together, we identify EKLF as a transcription factor in macrophages able to regulate IL-12 p40 transcription depending on the cellular activation status. The bifunctional control of IL-12 p40 by EKLF and its modulation of NFkappaB support a potential function for this factor in orchestrating IL-12 p40 production in macrophages. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10012 USA. NIH, Cellular Immunol Sect, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Univ Sydney, Dept Biochem, Sydney, NSW 2006, Australia. RP Montaner, LJ (reprint author), Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. EM montaner@wistar.upenn.edu RI Crossley, Merlin/D-7888-2011 OI Crossley, Merlin/0000-0003-2057-3642 FU NCI NIH HHS [R01 CA100223, R01 CA100223-01A1]; NIAID NIH HHS [AI51225, AI54891, R01 AI034412, AI34412, R01 AI051225, R01 AI047760, AI47760] NR 55 TC 28 Z9 30 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 30 PY 2004 VL 279 IS 18 BP 18451 EP 18456 DI 10.1074/jbc.M400320200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500044 PM 14976188 ER PT J AU Shnaper, S Sackett, K Gallo, SA Blumenthal, R Shai, Y AF Shnaper, S Sackett, K Gallo, SA Blumenthal, R Shai, Y TI The C- and the N-terminal regions of glycoprotein 41 ectodomain fuse membranes enriched and not enriched with cholesterol, respectively SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 TRANSMEMBRANE GLYCOPROTEIN; TYPE-1 ENVELOPE PROTEIN; SYNTHETIC PEPTIDE; VIRAL FUSION; SECONDARY STRUCTURE; ATOMIC-STRUCTURE; PLASMA-MEMBRANE; MEDIATED FUSION; ENERGY-TRANSFER; GP41 AB To infect target cells, HIV-1 employs a virally encoded transmembrane protein (gp41) to fuse its viral envelope with the target cell plasma membrane. We describe the gp41 ectodomain as comprised of N- and C-terminal subdomains, each containing a heptad repeat as well as a fusogenic region, whose organization is mirrored by the intervening loop region. Recent evidence indicates that the gp41 directed fusion reaction proceeds to initial pore formation prior to gp41 folding into its low energy hairpin conformation. This implies that exposed regions of the gp41 ectodomain are responsible for the bulk of the fusion work, probably through direct protein-membrane interactions. Prevalent fusion models contend that the gp41 ectodomain initially interacts with the target cell surface through its highly hydrophobic N terminus, which is believed to insert into the target membrane, thereby linking the virus to the target cell. This arrangement allows the N- terminal subdomain to interact with the target cell surface, whereas the C-terminal subdomain remains proximal to the virion, allowing interaction with the viral envelope. The composition of the viral envelope and the target cell surface differ due to the virus budding from raft microdomains. We show here that constructs corresponding to the C-terminal subdomain specifically destabilize ordered and cholesterol rich membranes ( 33 molar %), whereas the N- terminal subdomain is more effective in fusing both unordered cholesterol-free membranes and those containing lower amounts of cholesterol ( 10 molar %). Moreover we show that, in the context of the C-terminal subdomain, the heptad repeat contributes helical structure, which may describe the enhanced inhibitory effect of the C-terminal subdomain relative to the C-terminal heptad repeat (C34) alone. Our results are discussed in light of recent findings that showcase the role of exposed gp41 regions in effecting membrane fusion. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM Yechiel.Shai@weizmann.ac.il OI Gallo, Stephen/0000-0001-6043-2153 NR 54 TC 55 Z9 56 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 30 PY 2004 VL 279 IS 18 BP 18526 EP 18534 DI 10.1074/jbc.M304950200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500054 PM 14981088 ER PT J AU Liu, YM Borchert, GL Phang, JM AF Liu, YM Borchert, GL Phang, JM TI Polyoma enhancer activator 3, an Ets transcription factor, mediates the induction of cyclooxygenase-2 by nitric oxide in colorectal cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER; COLON CARCINOGENESIS; EPITHELIAL-CELLS; PEA3 SUBFAMILY; EWING SARCOMA; BETA-CATENIN; EXPRESSION; PROTEIN; BINDING; AP-1 AB Abundant evidence supports the role of cyclooxygenase-2 (COX-2) in colorectal cancer. Nitric oxide ( NO), a pro-inflammatory signaling factor, may regulate COX-2 expression and activity thereby linking hyper-inflammatory states to cancer susceptibility. Previously we showed that NO induced COX-2 expression. Although NO also activated the beta-catenin . T-cell factor/lymphocyte enhancing factor transcriptional pathway, a direct causal link between this pathway and COX-2 expression was not demonstrated. In this current study, we focused on NO-induced transcriptional activity and elucidated its role in COX-2 expression. NO donors stimulated the expression of peroxisome proliferator-activated receptor-delta and c-myc, both downstream genes of beta-catenin. They also induced the expression of polyoma enhancer activator 3 (PEA3) and increased its DNA-binding activity. To establish a role for PEA3 to beta-catenin-induced COX-2, we transfected RKO cells with beta-catenin and found that beta-catenin increased PEA3 expression. Also, there was higher PEA3 in immortal mouse colon epithelium cells (Apc(Min/+)) compared with young adult mouse colon cells (Apc(+/+)). Luciferase reporter assays revealed that, although several transcription factors/coactivator, acting alone or in synergistic combination, induced COX-2 promoter activity, PEA3 was one of the most potent. Interestingly, NO from NO donors or generated endogenously from transfected inducible nitric-oxide synthase, increased PEA3/p300-induced COX-2 promoter activity. We also found that an ETS site (-75/ - 72) and the NF-IL6 site were responsible for COX-2 activity induced by PEA3, PEA3/p300, and NO. Taken together, our results demonstrated that NO through beta-catenin signaling stimulated PEA3 to increase COX-2 activity. In addition, NO augmented the synergistic interaction between PEA3 and CBP/p300. C1 NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,NIH, Bldg 538,Rm 144, Frederick, MD 21702 USA. EM phang@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 43 TC 41 Z9 44 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 2004 VL 279 IS 18 BP 18694 EP 18700 DI 10.1074/jbc.M308136200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500075 PM 14976201 ER PT J AU Boczan, J Leenders, AGM Sheng, ZH AF Boczan, J Leenders, AGM Sheng, ZH TI Phosphorylation of syntaphilin by cAMP-dependent protein kinase modulates its interaction with syntaxin-1 and annuls its inhibitory effect on vesicle exocytosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYSTEINE STRING PROTEIN; LONG-TERM POTENTIATION; CYCLIC-AMP; SYNAPTIC VESICLES; DIFFERENTIAL PHOSPHORYLATION; SECRETORY MACHINERY; ADENYLATE-CYCLASE; NERVE-TERMINALS; SNARE COMPLEX; PC12 CELLS AB cAMP-dependent protein kinase (PKA) can modulate synaptic transmission by acting directly on the neurotransmitter secretory machinery. Here, we identify one possible target: syntaphilin, which was identified as a molecular clamp that controls free syntaxin-1 and dynamin-1 availability and thereby regulates synaptic vesicle exocytosis and endocytosis. Deletion mutation and site-directed mutagenesis experiments pinpoint dominant PKA phosphorylation sites to serines 43 and 56. PKA phosphorylation of syntaphilin significantly decreases its binding to syntaxin-1A in vitro. A syntaphilin mutation of serine 43 to aspartic acid (S43D) shows similar effects on binding. To characterize in vivo phosphorylation events, we generated antisera against a peptide of syntaphilin containing a phosphorylated serine 43. Treatment of rat brain synaptosomes or syntaphilin-transfected HEK 293 cells with the cAMP analogue BIMPS induces in vivo phosphorylation of syntaphilin and inhibits its interaction with syntaxin-1 in neurons. To determine whether PKA phosphorylation of syntaphilin is involved in the regulation of Ca2+-dependent exocytosis, we investigated the effect of overexpression of syntaphilin and its S43D mutant on the regulated secretion of human growth hormone from PC12 cells. Although expression of wild type syntaphilin in PC12 cells exhibits significant reduction in high K+-induced human growth hormone release, the S43D mutant fails to inhibit exocytosis. Our data predict that syntaphilin could be a highly regulated molecule and that PKA phosphorylation could act as an "off" switch for syntaphilin, thus blocking its inhibitory function via the cAMP-dependent signal transduction pathway. C1 NINDS, Synaptic Funct Unit, NIH, Bethesda, MD 20892 USA. RP Sheng, ZH (reprint author), NINDS, Synaptic Funct Unit, NIH, Bldg 36,Rm 5A23,36 Convent Dr, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov NR 51 TC 17 Z9 23 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 2004 VL 279 IS 18 BP 18911 EP 18919 DI 10.1074/jbc.M400496200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500101 PM 14985338 ER PT J AU Ye, L MacDougall, M Zhang, SB Xie, YX Zhang, JH Li, ZB Lu, YB Mishina, YJ Feng, JQ AF Ye, L MacDougall, M Zhang, SB Xie, YX Zhang, JH Li, ZB Lu, YB Mishina, YJ Feng, JQ TI Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization, and expanded cavities of pulp and root canal during postnatal tooth development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENTINOGENESIS IMPERFECTA; HYDROXYAPATITE FORMATION; BONE SIALOPROTEIN; COLLAGEN FIBRILS; GENE; MUTATION; PHOSPHOPROTEIN; MICE; DSPP; EXPRESSION AB The dentin matrix protein-1 (DMP-1) gene is identified in odontoblasts during both embryonic and postnatal development. In vitro study suggests that this noncollagen acidic phosphoprotein plays a role in mineralization. However, deletion of the Dmp-1 gene has little effect on tooth development during embryogenesis. To address the role of DMP-1 in tooth during postnatal development, we analyzed changes of dentinogenesis in Dmp-1 null mice from 3 days after birth to 1 year. Here we show that Dmp-1 null mice postnatally develop a profound tooth phenotype characterized by a partial failure of maturation of predentin into dentin, enlarged pulp chambers, increased width of predentin zone with reduced dentin wall, and hypomineralization. The tooth phenotype of these mice is strikingly similar to that in dentin sialophosphoprotein (Dspp) null mice and shares some features of the human disease dentinogenesis imperfecta III. We have also demonstrated that DSPP levels are reduced in Dmp-1 null mice, suggesting that DSPP is probably regulated by DMP-1 during dentinogenesis. Finally, we show the absence or delayed development of the third molar in Dmp-1 null mice, which is probably secondary to defects in Dmp-1 null bone. Taken together, these studies suggest that DMP-1 is essential for later dentinogenesis during postnatal development. C1 Univ Missouri, Sch Dent, Dept Oral Biol, Kansas City, MO 64108 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat Dent, San Antonio, TX 78284 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Feng, JQ (reprint author), Univ Missouri, Sch Dent, Dept Oral Biol, 650 E 25th St, Kansas City, MO 64108 USA. EM fengj@umkc.edu FU NIDCR NIH HHS [DE00455, DE09875, DE13221, DE13480] NR 38 TC 166 Z9 174 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 2004 VL 279 IS 18 BP 19141 EP 19148 DI 10.1074/jbc.M400490200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500127 PM 14966118 ER PT J AU Kishida, T Kostetskii, I Zhang, ZB Martinez, F Liu, P Walkley, SU Dwyer, NK Blanchette-Mackie, EJ Radice, GL Strauss, JF AF Kishida, T Kostetskii, I Zhang, ZB Martinez, F Liu, P Walkley, SU Dwyer, NK Blanchette-Mackie, EJ Radice, GL Strauss, JF TI Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE REGULATORY PROTEIN; PHOSPHATIDYLCHOLINE TRANSFER PROTEIN; PICK C1-DEFICIENT NEURONS; CHOLESTEROL HOMEOSTASIS; GENE-EXPRESSION; DISTAL AXONS; C1 PROTEIN; DISEASE; STEROIDOGENESIS; TRAFFICKING AB The StAR-related lipid transfer (START) domain, first identified in the steroidogenic acute regulatory protein (StAR), is involved in the intracellular trafficking of lipids. Sixteen mammalian START domain-containing proteins have been identified to date. StAR, a protein targeted to mitochondria, stimulates the movement of cholesterol from the outer to the inner mitochondrial membranes, where it is metabolized into pregnenolone in steroidogenic cells. MLN64, the START domain protein most closely related to StAR, is localized to late endosomes along with other proteins involved in sterol trafficking, including NPC1 and NPC2, where it has been postulated to participate in sterol distribution to intracellular membranes. To investigate the role of MLN64 in sterol metabolism, we created mice with a targeted mutation in the Mln64 START domain, expecting to find a phenotype similar to that in humans and mice lacking NPC1 or NPC2 (progressive neurodegenerative symptoms, free cholesterol accumulation in lysosomes). Unexpectedly, mice homozygous for the Mln64 mutant allele were viable, neurologically intact, and fertile. No significant alterations in plasma lipid levels, liver lipid content and distribution, and expression of genes involved in sterol metabolism were observed, except for an increase in sterol ester storage in mutant mice fed a high fat diet. Embryonic fibroblast cells transfected with the cholesterol side-chain cleavage system and primary cultures of granulosa cells from Mln64 mutant mice showed defects in sterol trafficking as reflected in reduced conversion of endogenous cholesterol to steroid hormones. These observations suggest that the Mln64 START domain is largely dispensable for sterol metabolism in mice. C1 Univ Penn, Sch Med, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. NIDDK, Lipid Cell Biol Sect, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Strauss, JF (reprint author), Univ Penn, Sch Med, Ctr Res Reprod & Womens Hlth, 1354 BRB,421 Curie Blvd, Philadelphia, PA 19104 USA. EM jfs3@mail.med.upenn.edu FU FIC NIH HHS [D43 TW00671]; NICHD NIH HHS [HD06274]; NIDDK NIH HHS [P30 DK 19525] NR 37 TC 53 Z9 54 U1 1 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 30 PY 2004 VL 279 IS 18 BP 19276 EP 19285 DI 10.1074/jbc.M400717200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500141 PM 14963026 ER PT J AU Luo, WQ Williams, J Smallwood, PM Touchman, JW Roman, LM Nathans, J AF Luo, WQ Williams, J Smallwood, PM Touchman, JW Roman, LM Nathans, J TI Proximal and distal sequences control UV cone pigment gene expression in transgenic zebrafish SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GREEN FLUORESCENT PROTEIN; VISUAL PIGMENTS; EMBRYONIC ZEBRAFISH; RHODOPSIN PROMOTER; BRACHYDANIO-RERIO; MOUSE RETINAS; HOMEOBOX GENE; ROD; CRX; PHOTORECEPTORS AB The molecular basis of cone photoreceptor-specific gene expression is largely unknown. In this study, we define cis-acting DNA sequences that control the cell type-specific expression of the zebrafish UV cone pigment gene by transient expression of green fluorescent protein transgenes following their injection into zebrafish embryos. These experiments show that 4.8 kb of 5'-flanking sequences from the zebrafish UV pigment gene direct expression specifically to UV cones and that this activity requires both distal and proximal sequences. In addition, we demonstrate that a proximal region located between -215 and -110 bp (with respect to the initiator methionine codon) can function in the context of a zebrafish rhodopsin promotor to convert its specificity from rod-only expression to rod and UV cone expression. These experiments demonstrate the power of transient transgenesis in zebrafish to efficiently define cis-acting regulatory sequences in an intact vertebrate. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Nathans, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 805 PCTB,725 N Wolfe St, Baltimore, MD 21205 USA. EM jnathans@jhmi.edu NR 33 TC 24 Z9 24 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 30 PY 2004 VL 279 IS 18 BP 19286 EP 19293 DI 10.1074/jbc.M400161200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500142 PM 14966125 ER PT J AU Sun, JY Wu, XS Wu, W Jin, SX Dondzillo, A Wu, LG AF Sun, JY Wu, XS Wu, W Jin, SX Dondzillo, A Wu, LG TI Capacitance measurements at the calyx of Held in the medial nucleus of the trapezoid body SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE exocytosis; endocytosis; capacitance measurements; calyx of held; rat; presynaptic ID ADRENAL CHROMAFFIN CELLS; TRANSMITTER RELEASE; CALCIUM-DEPENDENCE; CENTRAL SYNAPSE; VESICLE FUSION; PATCH-CLAMP; EXOCYTOSIS; ENDOCYTOSIS; SINGLE; CA2+ AB We have recently applied Lindau-Neher's capacitance measurement technique to study vesicle trafficking at the calyx-type synapse in the rat medial nucleus of the trapezoid body (MNTB) in slice conditions. This application made the MNTB synapse an excellent model for the study of exocytosis and endocytosis at conventional active zones. However, the application was only made at calyces that are presumably equivalent to a single-compartment circuit because their passive current transients decayed mono-exponentially. Here, we determined whether the application could be extended to majority of calyces whose passive current transients decayed bi-exponentially. By comparison of calyces with mono- or bi-exponential decay in their passive current transients, we found similar properties in respect to: (1) the capacitance jump induced by trains of action-potential equivalent stimuli, which reflects exocytosis; (2) the size of a releasable vesicle pool; (3) the time course of the decay after the capacitance jump, which reflects endocytosis; and (4) the transient capacitance artifact observed in the presence of Cd2+ that blocks exocytosis. These similar properties were also obtained from modeling calyces as a single- or two-Compartment circuit. Thus, capacitance measurements may be extended to the majority of calyces, which may facilitate the study of rapid vesicle trafficking at conventional active zones. (C) 2003 Published by Elsevier B.V. C1 NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, Room 1C12,Bldg 36,36 Convent Dr, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov NR 27 TC 23 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2004 VL 134 IS 2 BP 121 EP 131 DI 10.1016/j.jneumeth.2003.11.018 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 803MA UT WOS:000220234000002 PM 15003378 ER PT J AU Milanowski, DJ Gustafson, KR Rashid, MA Pannell, LK McMahon, JB Boyd, MR AF Milanowski, DJ Gustafson, KR Rashid, MA Pannell, LK McMahon, JB Boyd, MR TI Gymnangiamide, a cytotoxic pentapeptide from the marine hydroid Gymnangium regae SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CYANOBACTERIUM SYMPLOCA-HYDNOIDES; GARVEIA-ANNULATA; ANTINEOPLASTIC AGENTS; DOLASTATIN 10; EUDENDRIUM-GLOMERATUM; SOLANDERIA-SECUNDA; MASS SPECTROMETRY; NATURAL-PRODUCTS; ISODOLASTATIN-H; AMINO-ACIDS AB A cytotoxic aqueous extract from the marine hydroid Gymnangium regae provided a novel linear pentapeptide, designated gymnangiamide (1). The planar structure of 1 was elucidated by interpretation of spectral data as well as chemical degradation and derivatization studies. In addition to the amino acids isoleucine and phenylserine, this peptide contained N-desmethyldolaisoleuine, O-desmethyldolaproine, and alpha-guanidino serine, three residues that have not previously been reported in a natural product. The absolute configurations of the constituent amino/guanidino acids were determined by chemical degradation and derivatization, followed by HPLC and LC-MS comparison with authentic standards. Gymnangiamide (1) was moderately cytotoxic against a number of human tumor cell lines in vitro. C1 NCI, Mol Targets Dev Program, Canc Res Ctr, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Univ S Alabama, Coll Med, USA, Canc Res Inst, Mobile, AL 36688 USA. RP Gustafson, KR (reprint author), NCI, Mol Targets Dev Program, Canc Res Ctr, Bldg 1052,Room 121, Frederick, MD 21702 USA. EM manuscripts@mail.ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 39 TC 17 Z9 18 U1 3 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 30 PY 2004 VL 69 IS 9 BP 3036 EP 3042 DI 10.1021/jo0303113 PG 7 WC Chemistry, Organic SC Chemistry GA 818TU UT WOS:000221268200016 PM 15104441 ER PT J AU Nguyen, HT Kitner-Triolo, M Evans, MK Zonderman, AB AF Nguyen, HT Kitner-Triolo, M Evans, MK Zonderman, AB TI Factorial invariance of the CES-D in low socioeconomic status African Americans compared with a nationally representative sample SO PSYCHIATRY RESEARCH LA English DT Article DE blacks; ethnicity; depression; factor structure; measurement equivalency ID CONFIRMATORY FACTOR-ANALYSIS; STUDIES DEPRESSION SCALE; OLDER ADULTS; SYMPTOMS; HEALTH; WHITES; GENDER AB This study examined the factor structure of the Center for Epidemiologic Studies Depression Scale (CES-D) in low socioeconomic status African Americans (n = 426). Confirmatory factor analysis indicated that the four factors(1) depressed affect, (2) positive affect, (3) somatic complaints, and (4) interpersonal problems-of the CES-D scale previously found in the general population were supported in this sample. These results were cross-validated in other nationally representative samples of African-American participants (n = 988) and Caucasians (n = 666), and the four-factor structure of the CES-D scale replicated in all three groups in this study. An alternative model was also tested with the factors depressed affect and somatic complaints combined as a single factor, a finding often reported in minority groups. Results indicated a significantly poorer fit for the three-factor model compared with the four-factor model for all three groups. In addition, higher loading differences were significantly evident between African-American and Caucasian groups, while higher loading similarities were found between the two African-American groups. These findings provide further evidence of measurement equivalency of the CES-D scale in samples with differential characteristics including race and socioeconomic status. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Cognit Sect, Lab Personal & Cognit, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. NIA, Hlth Dispar Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Nguyen, HT (reprint author), NIA, Cognit Sect, Lab Personal & Cognit, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM nguyenha@grc.nia.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 NR 36 TC 107 Z9 110 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 30 PY 2004 VL 126 IS 2 BP 177 EP 187 DI 10.1016/j.psychres.2004.02.004 PG 11 WC Psychiatry SC Psychiatry GA 823QV UT WOS:000221629000010 PM 15123397 ER PT J AU Eyler, LT Olsen, RK Jeste, DV Brown, GG AF Eyler, LT Olsen, RK Jeste, DV Brown, GG TI Abnormal brain response of chronic schizophrenia patients despite normal performance during a visual vigilance task SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE continuous performance test; functional magnetic resonance imaging; attention; prefrontal cortex ID POSITRON-EMISSION-TOMOGRAPHY; EVENT-RELATED FMRI; SUSTAINED ATTENTION; FUNCTIONAL MRI; ATYPICAL NEUROLEPTICS; DEVELOPMENTAL COURSE; PREFRONTAL CORTEX; TARGET DETECTION; NAIVE PATIENTS; ACTIVATION AB Deficits of attention are common among individuals with schizophrenia (SZ) and are related both to genetic liability to the disorder and to functional outcome among patients. To explore the brain systems underlying these attentional abnormalities, we compared the response of nine patients with chronic SZ or schizoaffective disorder to that of 10 matched healthy individuals performing a simple visual vigilance task during functional magnetic resonance imaging. The two groups performed equivalently on the task. When the blood oxygen level dependent (BOLD) signal during identification of a target letter among similar-looking letters was compared to the response during fixation trials, both groups showed multiple clusters of significant brain response in widespread cortical regions. Compared with healthy participants, SZ patients showed a diminished response in the inferior frontal cortex and an abnormally enhanced response in right postcentral gyrus, right medial temporal lobe and left cerebellum. The results suggest that abnormalities of functional brain response to attentional tasks can be observed among patients with SZ even when behavioral performance is unimpaired, and provide further evidence that brain systems related to attention are likely to be involved in the pathophysiology of the disorder. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Vet Affairs San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, San Diego, CA 92161 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. NIMH, Clin Brain Disorders Branch, Unite Integrat Neuroimaging, Bethesda, MD 20892 USA. Vet Affairs San Diego Healthcare Syst, Div geriatr Psychiat, La Jolla, CA 92161 USA. RP Brown, GG (reprint author), Vet Affairs San Diego Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Mail Code 151B,3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM gbrown@ucsd.edu OI Olsen, Rosanna/0000-0002-2918-4152 FU NIMH NIH HHS [5 P30 MH49671-09, 5 T32 MH19934-07] NR 56 TC 17 Z9 18 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 30 PY 2004 VL 130 IS 3 BP 245 EP 257 DI 10.1016/j.psychresns.2004.01.003 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 824GB UT WOS:000221673200003 PM 15135158 ER PT J AU Coleman, CN Stone, HB Moulder, JE Pellmar, TC AF Coleman, CN Stone, HB Moulder, JE Pellmar, TC TI Modulation of radiation injury SO SCIENCE LA English DT Editorial Material ID PULMONARY FIBROSIS; NORMAL TISSUE C1 NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Uniformed Serv Univ Hlth Sci, Armed Forces Radiobiol Res Inst, Bethesda, MD 20889 USA. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM pellmar@afrri.usuhs.mil RI Moulder, John/E-6799-2012 NR 14 TC 80 Z9 85 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 30 PY 2004 VL 304 IS 5671 BP 693 EP 694 DI 10.1126/science.1095956 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816JD UT WOS:000221105300032 PM 15118152 ER PT J AU Matveeva, OV Foley, BT Nemtsov, VA Gesteland, RF Matsufuji, S Atkins, JF Ogurtsov, AY Shabalina, SA AF Matveeva, OV Foley, BT Nemtsov, VA Gesteland, RF Matsufuji, S Atkins, JF Ogurtsov, AY Shabalina, SA TI Identification of regions in multiple sequence alignments thermodynamically suitable for targeting by consensus oligonucleotides: application to HIV genome SO BMC BIOINFORMATICS LA English DT Article ID DNA SIGNAL AMPLIFICATION; GENE FAMILY; DESIGN; PROBES; PRIMERS; RNA; HYBRIDIZATION; MICROCOMPUTER; PACKAGE; PROGRAM AB Background: Computer programs for the generation of multiple sequence alignments such as "Clustal W" allow detection of regions that are most conserved among many sequence variants. However, even for regions that are equally conserved, their potential utility as hybridization targets varies. Mismatches in sequence variants are more disruptive in some duplexes than in others. Additionally, the propensity for self-interactions amongst oligonucleotides targeting conserved regions differs and the structure of target regions themselves can also influence hybridization efficiency. There is a need to develop software that will employ thermodynamic selection criteria for finding optimal hybridization targets in related sequences. Results: A new scheme and new software for optimal detection of oligonucleotide hybridization targets common to families of aligned sequences is suggested and applied to aligned sequence variants of the complete HIV-1 genome. The scheme employs sequential filtering procedures with experimentally determined thermodynamic cut off points: 1) creation of a consensus sequence of RNA or DNA from aligned sequence variants with specification of the lengths of fragments to be used as oligonucleotide targets in the analyses; 2) selection of DNA oligonucleotides that have pairing potential, greater than a defined threshold, with all variants of aligned RNA sequences; 3) elimination of DNA oligonucleotides that have self-pairing potentials for intra- and inter-molecular interactions greater than defined thresholds. This scheme has been applied to the HIV-1 genome with experimentally determined thermodynamic cut off points. Theoretically optimal RNA target regions for consensus oligonucleotides were found. They can be further used for improvement of oligo-probe based HIV detection techniques. Conclusions: A selection scheme with thermodynamic thresholds and software is presented in this study. The package can be used for any purpose where there is a need to design optimal consensus oligonucleotides capable of interacting efficiently with hybridization targets common to families of aligned RNA or DNA sequences. Our thermodynamic approach can be helpful in designing consensus oligonucleotides with consistently high affinity to target variants in evolutionary related genes or genomes. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. MGGT, Moscow 125502, Russia. Jikei Univ, Sch Med, Dept Biochem 2, Minato Ku, Tokyo 1058461, Japan. Natl Univ Ireland Univ Coll Cork, Biosci Inst, Cork, Ireland. RP Shabalina, SA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20814 USA. EM olgam@howard.genetics.utah.edu; btf@atlas.lanl.gov; vovanem@online.ru; ray.gesteland@genetics.utah.edu; senya@jikei.ac.jp; john.atkins@genetics.utah.edu; ogurtsov@ncbi.nlm.nih.gov; shabalin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 FU NIGMS NIH HHS [GM48152, R01 GM048152] NR 22 TC 2 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 29 PY 2004 VL 5 AR 44 DI 10.1186/1471-2105-5-44 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 831VX UT WOS:000222225700001 PM 15115544 ER PT J AU Plotkin, JB Dushoff, J Fraser, HB AF Plotkin, JB Dushoff, J Fraser, HB TI Detecting selection using a single genome sequence of M-tuberculosis and P-falciparum SO NATURE LA English DT Article ID NUCLEOTIDE SUBSTITUTION; MOLECULAR EVOLUTION; LIFE-CYCLE; EXPRESSION; LIKELIHOOD; MALARIA; FAMILY; POLYMORPHISM; DROSOPHILA; PROTEINS AB Selective pressures on proteins are usually measured by comparing nucleotide sequences(1). Here we introduce a method to detect selection on the basis of a single genome sequence. We catalogue the relative strength of selection on each gene in the entire genomes of Mycobacterium tuberculosis and Plasmodium falciparum. Our analysis confirms that most antigens are under strong selection for amino-acid substitutions, particularly the PE/PPE family(2) of putative surface proteins in M. tuberculosis and the EMP1 family(3) of cytoadhering surface proteins in P. falciparum. We also identify many uncharacterized proteins that are under strong selection in each pathogen. We provide a genome-wide analysis of natural selection acting on different stages of an organism's life cycle: genes expressed in the ring stage(4) of P. falciparum are under stronger positive selection than those expressed in other stages of the parasite's life cycle. Our method of estimating selective pressures requires far fewer data than comparative sequence analysis, and it measures selection across an entire genome; the method can readily be applied to a large range of sequenced organisms. C1 Harvard Soc Fellows, Cambridge, MA 02138 USA. Bauer Ctr Gen Res, Cambridge, MA 02138 USA. Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Plotkin, JB (reprint author), Harvard Soc Fellows, 7 Divin Ave, Cambridge, MA 02138 USA. EM jplotkin@fas.harvard.edu RI Plotkin, Joshua/E-6947-2013 NR 30 TC 65 Z9 69 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 29 PY 2004 VL 428 IS 6986 BP 942 EP 945 DI 10.1038/nature02458 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816AO UT WOS:000221083000041 PM 15118727 ER PT J AU Gulick, RM Ribaudo, HJ Shikuma, CM Lustgarten, S Squires, KE Meyer, WA Acosta, EP Schackman, BR Pilcher, CD Murphy, RL Maher, WE Witt, MD Reichman, RC Snyder, S Klingman, KL Kuritzkes, DR AF Gulick, RM Ribaudo, HJ Shikuma, CM Lustgarten, S Squires, KE Meyer, WA Acosta, EP Schackman, BR Pilcher, CD Murphy, RL Maher, WE Witt, MD Reichman, RC Snyder, S Klingman, KL Kuritzkes, DR CA AIDS Clin Trials Grp Study A5095 TI Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; CLINICAL-TRIALS; LAMIVUDINE-ZIDOVUDINE; COMBINATION THERAPY; INSULIN-RESISTANCE; DRUG-RESISTANCE; HIV-1-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE AB BACKGROUND Regimes containing three nucleoside reverse-transcriptase inhibitors offer an alternative to regimes containing nonnucleoside reverse-transcriptase inhibitors or protease inhibitors for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection, but data from direct comparisons are limited. METHODS This randomized, double-blind study involved three antiretroviral regimens for the initial treatment of subjects infected with HIV-1: zidovudine - lamivudine - abacavir, zidovudine - lamivudine plus efavirenz, and zidovudine - lamivudine - abacavir plus efavirenz. RESULTS We enrolled a total of 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log(10) (71,434) copies per milliliter and a mean CD4 cell count of 238 per cubic millimeter were enrolled. A scheduled review by the data and safety monitoring board with the use of prespecified stopping boundaries led to a recommendation to stop the triple-nucleoside group and to present the results in the triple-nucleoside group in comparison with pooled data from the efavirenz groups. After a median follow-up of 32 weeks, 82 of 382 subjects in the triple-nucleoside group (21 percent) and 85 of 765 of those in the combined efavirenz groups (11 percent) had virologic failure; the time to virologic failure was significantly shorter in the triple-nucleoside group (P < 0.001). This difference was observed regardless of the pretreatment HIV-1 RNA stratum (at least 100,000 copies per milliliter or below this level; P &LE; 0.001 for both comparisons). Changes in the CD4 cell count and the incidence of grade 3 or grade 4 adverse events did not differ significantly between the groups. CONCLUSIONS In this trial of the initial treatment of HIV-1 infection, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine was virologically inferior to a regimen containing efavirenz and two or three nucleosides. C1 Cornell Univ, Weill Med Coll, New York, NY USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Quest Diagnost, Baltimore, MD USA. Univ Alabama, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Ohio State Univ, Columbus, OH 43210 USA. Harbor UCLA Med Ctr, Los Angeles, CA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Social & Sci Syst, Silver Spring, MD USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gulick, RM (reprint author), Cornell Clin Trials Unit, Box 566,525 E 68th St, New York, NY 10021 USA. EM rgulick@med.cornell.edu OI Murphy, Robert/0000-0003-3936-2052 FU NCRR NIH HHS [RR00096, RR00865, RR00052, RR 02635, RR00044, RR00047, RR00046]; NIAID NIH HHS [AI 27659, AI 27673, AI 46370, AI 46381, AI 25879, AI 46339, AI 25924, AI 25897, AI 25868, AI 46386, AI 51966, AI 42851, AI 27658, AI 39156, AI 32782, AI 25915, AI 27670, AI 27767, AI 27668, AI 25859, AI 25903, AI 42848, AI 38858, AI 50410, AI 38855, AI 34832, AI 32775, AI 27675, AI 27664, AI 28697, AI 27661, AI 46376, AI 01781, AI 27660] NR 37 TC 361 Z9 372 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 2004 VL 350 IS 18 BP 1850 EP 1861 DI 10.1056/NEJMoa031772 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 815ZN UT WOS:000221080300008 PM 15115831 ER PT J AU Stebbing, J Gazzard, B Douek, DC AF Stebbing, J Gazzard, B Douek, DC TI Mechanisms of disease - Where does HIV live? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; T-CELL DEPLETION; FOLLICULAR DENDRITIC CELLS; CEREBROSPINAL-FLUID; TYPE-1 INFECTION; LYMPHOID-TISSUE; DC-SIGN; IN-VIVO; THYMOCYTE DEPLETION C1 NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Fac Med,Dept Immunol, Div Invest Sci, London, England. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM ddouek@nih.gov NR 103 TC 105 Z9 112 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 2004 VL 350 IS 18 BP 1872 EP 1880 DI 10.1056/NEJMra032395 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 815ZN UT WOS:000221080300010 PM 15115833 ER PT J AU Musio, A Mariani, T Montagna, C Zambroni, D Ascoli, C Ried, T Vezzoni, P AF Musio, A Mariani, T Montagna, C Zambroni, D Ascoli, C Ried, T Vezzoni, P TI Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes SO GENE LA English DT Article DE Roberts syndrome; centromere separation; INCENP; ZWINT-1; ZW10; cell cycle ID PHOCOMELIA SYNDROME; HUMAN-CHROMOSOMES; HISTONE H3; LYSINE 9; ABNORMALITIES; FIBROBLASTS; PROTEINS; MITOSIS; CELLS; SITE AB Roberts syndrome is an autosomal recessive disorder characterised primarily by symmetric reduction of all limbs and growth retardation. Patients have been reported to have premature separation of heterochromatin regions of many chromosomes and abnormalities in cell cycle. Given the rarity of the syndrome, the linkage analysis approach is not suitable to identify the responsible gene. In this work, a cell line derived from a patient affected by Roberts syndrome was characterized by cell biology and molecular cytogenetics, including comparative genomic hybridization and spectral karyotype. No recurrent chromosomal rearrangements were identified. Thereafter, based on the fact that premature chromatide separation is a reliable marker of the disease, we used antisense oligonucleotide technologies to inhibit six genes involved in various steps of the correct chromosome segregation, such as chromosome cohesion, kinetochore assembling, spindle checkpoint and spindle formation. We found that the inhibition of INCENP, ZWINT-1, ZW10 genes results in the appearance of mitotic cells characterised by centromere separation, chromosome aneuploidy and micronuclei formation. In addition, INCENP, ZWINT-1, ZW10 anti sense-treated chromosome morphology was very similar to that of Roberts chromosome when analysed by atomic force microscopy. We concluded that INCENP, ZWINT-1, ZW10 gene inhibition results in cellular phenocopies of Roberts syndrome. Taken together, these findings support a possible role of these genes in the pathogenesis of Roberts syndrome. (C) 2004 Elsevier B.V. All rights reserved. C1 CNR, Dipartimento Genoma Umano, Ist Tecnol Biomed, I-20090 Segrate, MI, Italy. CNR, Ist Proc Chim Fis, I-56124 Pisa, Italy. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Musio, A (reprint author), CNR, Dipartimento Genoma Umano, Ist Tecnol Biomed, Via Fratelli Cervi 93, I-20090 Segrate, MI, Italy. EM antonio.musio@itb.cnr.it NR 20 TC 13 Z9 18 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 28 PY 2004 VL 331 BP 33 EP 40 DI 10.1016/j.gene.2004.01.028 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 821XA UT WOS:000221495400004 PM 15094189 ER PT J AU Pan, QP Li, CG Jing, X Kimura, S Rubenstein, J Puelles, L Minoo, P AF Pan, QP Li, CG Jing, X Kimura, S Rubenstein, J Puelles, L Minoo, P TI In vivo characterization of the Nkx2.1 promoter/enhancer elements in transgenic mice SO GENE LA English DT Article DE Nkx2.1; TTF-1; Transgenic mice; promoter; enhancer; morphogenesis; development; tissue-specific gene regulation; lung; brain; thyroid; hypothalamus; trachea ID ENHANCER-BINDING PROTEIN; TRANSCRIPTION FACTOR-I; LUNG MORPHOGENESIS; MOUSE EMBRYOS; ACTIVATES TRANSCRIPTION; BASAL TELENCEPHALON; EPITHELIAL-CELLS; GENE; FOREBRAIN; FETAL AB Nkx2.1 encodes a homeodomain transcription factor whose expression is restricted to the thyroid, lung and specific regions of the forebrain. NKX2.1 plays a key role in the development of the latter organs. In lung epithelial cells, two regions of promoter activity, designated as proximal and distal promoters, map to DNA elements located upstream of exons I and 2 (within intron 1). That both promoters are active in vivo has been demonstrated by the presence of multiple Nkx2.1 mRNA species with distinct and appropriate exonic composition. The mechanisms of Nkx2.1 tissue selective gene expression remain entirely unknown. We have examined the potential of three overlapping DNA fragments, representing a total of approximately 4 kb of potential regulatory DNA from the baboon Nkx2.1 5' flanking region to direct expression of LacZ in transgenic mice during embryonic development. The three constructs include sequences in proximal, distal and both promoters separately. All three fragments directed LacZ expression to the brain of transgenic E 15 and E 18 mouse embryos. In addition to a number of other sites, all three constructs were active in subgroups of cells localized in the hypothalamus, a well-established site of endogenous Nkx2.1 gene expression. Two of the fragments conferred tracheal epithelial-specific LacZ gene expression, but parenchymal lung expression was not observed. None of the three fragments had activity in the thyroid. These data demonstrate the complexity of the Nkx2.1 tissue specific gene regulation and suggest that cis-active elements required for tracheal versus lung morphogenesis may be distinct. The same applies to the brain, which provides the most permissive environment for recognition of Nkx2.1 tissue specific cis-active elements. (C) 2004 Elsevier B.V. All rights reserved. C1 USC, Womens & Childrens Hosp, Sch Med, LAC & USC Med Ctr,Dept Pediat, Los Angeles, CA USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Psychiat, Program Neurobiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, Program Dev Biol, San Francisco, CA 94143 USA. Univ Murcia, Fac Med, Dept Human Anat & Psychobiol, E-30100 Murcia, Spain. RP Minoo, P (reprint author), USC, Womens & Childrens Hosp, Sch Med, LAC & USC Med Ctr,Dept Pediat, 1801 E Marengo St,Room 1G1, Los Angeles, CA USA. EM minoo@hse.usc.edu FU NHLBI NIH HHS [HL56590]; NIDA NIH HHS [R01 DA12462] NR 32 TC 13 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 28 PY 2004 VL 331 BP 73 EP 82 DI 10.1016/j.gene.2004.01.026 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 821XA UT WOS:000221495400008 PM 15094193 ER PT J AU Tsai-Morris, CH Lei, S Jiang, Q Sheng, Y Dufau, ML AF Tsai-Morris, CH Lei, S Jiang, Q Sheng, Y Dufau, ML TI Genomic organization and transcriptional analysis of gonadotropin-regulated testicular RNA helicase - GRTH/DDX25 gene SO GENE LA English DT Article DE dead-box RNA helicase; GRTH/DDX25; genomic organization; transcription; testis ID TRANSLATION INITIATION; E-BOX; SACCHAROMYCES-CEREVISIAE; CELL-LINE; HORMONE; EXPRESSION; FAMILY; ACTIVATION; PROMOTER; PROTEINS AB The gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a new member of the DEAD-box protein family. Phylogenetic analysis revealed that GRTH is distantly related to other members of the family. GRTH is transcriptionally up-regulated by gonadotropin, displays ATPase and RNA helicase activities, and participates in germ cell development. To understand the regulation of GRTH gene expression, we investigated its structural organization and aspects of basal transcriptional regulation at the promoter domain. The 20-kb mouse GRTH gene contains 12 coding exons and all but one of its conserved helicase motifs are contained within single exons. GRTH is a TATA-less gene with multiple transcriptional start sites (TSS), GC-rich sequences and a promoter located within -205/+63 bp of the gene. Sequences -852/-354 and -501/-354 bp caused 40-60% and >80% inhibition of transcription in expressing and non-expressing cells, respectively. Transcriptional activity was recovered only in expressing cells by the addition of upstream sequences (-1085/-852 bp). Sp1/Sp3 supported basal transcriptional activity in all cell types, while E-box was an activator-binding site only in non-expressing cells. These findings indicate that a differential pattern of transcriptional regulation may be involved in the control of GRTH gene expression in a cell-specific manner. Published by Elsevier B.V. C1 NICHD, Sect Mol Endocrinol, ERRB, NIH, Bethesda, MD 20892 USA. RP Tsai-Morris, CH (reprint author), NICHD, Sect Mol Endocrinol, ERRB, NIH, Bldg 49-6A36,49 Convent Dr, Bethesda, MD 20892 USA. EM morrisch@mail.nih.gov NR 30 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 28 PY 2004 VL 331 BP 83 EP 94 DI 10.1016/j.gene.2004.02.004 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 821XA UT WOS:000221495400009 PM 15094194 ER PT J AU Edavettal, SC Carrick, K Shah, RR Pedersen, LC Tropsha, A Pope, RM Liu, J AF Edavettal, SC Carrick, K Shah, RR Pedersen, LC Tropsha, A Pope, RM Liu, J TI A conformational change in heparan sulfate 3-O-sulfotransferase-1 is induced by binding to heparan sulfate SO BIOCHEMISTRY LA English DT Article ID D-GLUCOSAMINYL 3-O-SULFOTRANSFERASE; DIFFERENTIAL CHEMICAL-MODIFICATION; N-DEACETYLASE/N-SULFOTRANSFERASE; HERPES-SIMPLEX-VIRUS; SUBSTRATE SPECIFICITIES; HUMAN CDNAS; IDENTIFICATION; ANTITHROMBIN; EXPRESSION; ISOFORMS AB The 3-O-sulfation of glucosamine by heparan sulfate 3-O-sulfotransferase-1 (3-OST-1) is a key modification step during the biosynthesis of anticoagulant heparan sulfate (HS). In this paper, we present evidence of a conformational change that occurs in 3-OST-1 upon binding to heparan sulfate. The intrinsic fluorescence of 3-OST-1 was increased in the presence of HS, suggesting a conformational change. This apparent conformational change was further investigated using differential chemical modification of 3-OST-1 to measure the solvent accessibility of the lysine residues. 3-OST-1 was treated with acetic anhydride in either the presence or absence of HS using both acetic anhydride and hexadeuterioacetic anhydride under nondenaturing and denaturing conditions, respectively. The relative reactivity of the lysine residues to acetylation and [H-2] acetylation in the presence or absence of HS was analyzed by measuring the ratio of acetylated and deuterioacetylated peptides using matrix-assisted laser desorption ionization mass spectrometry. The solvent accessibilities of the lysine residues were altered differentially depending on their location. In particular, we observed a group of lysine residues in the C-terminus of 3-OST-1 that become more solvent accessible when 3-OST-1 binds to HS. This observation indicates that a conformational change could be occurring during substrate binding. A truncated mutant of 3-OST-1 that lacked this C-terminal region was expressed and found to exhibit a 200-fold reduction in sulfotransferase activity. The results from this study will contribute to our understanding of the interactions between 3-OSTs and HS. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Pharm, Lab Mol Modeling, Chapel Hill, NC 27599 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biochem, Prote Core Facil, Chapel Hill, NC 27599 USA. RP Liu, J (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Room 309,Beard Hall, Chapel Hill, NC 27599 USA. EM jian_liu@unc.edu RI Tropsha, Alexander/G-6245-2014 FU NIAID NIH HHS [AI50050] NR 44 TC 10 Z9 10 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 27 PY 2004 VL 43 IS 16 BP 4680 EP 4688 DI 10.1021/bi0499112 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 814IH UT WOS:000220967900006 PM 15096036 ER PT J AU Schulz, DM Ihling, C Clore, GM Sinz, A AF Schulz, DM Ihling, C Clore, GM Sinz, A TI Mapping the topology and determination of a low-resolution three-dimensional structure of the calmodulin-melittin complex by chemical cross-linking and high-resolution FTICRMS: Direct demonstration of multiple binding modes SO BIOCHEMISTRY LA English DT Article ID RESONANCE MASS-SPECTROMETRY; PHOSPHORYL TRANSFER COMPLEX; TARGET RECOGNITION; PROTEIN COMPLEXES; DIPOLAR COUPLINGS; CRYSTAL-STRUCTURE; PEPTIDE COMPLEX; CENTRAL HELIX; GASTRIC (H+; BEE VENOM AB Calmodulin serves as a calcium-dependent regulator in many metabolic pathways and is known to bind with high affinity to various target proteins and peptides. One such target is the small peptide melittin, the principal component of honeybee venom. The calmodulin-melittin system was used as a model system to gain further insight into target recognition of calmodulin. Using chemical cross-linking in combination with high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS), we have determined the interacting regions within the calcium-dependent calmodulin-melittin complex and thus the orientation of bound melittin. Using ambiguous distance restraints derived from the chemical cross-linking data in combination with recently developed computational methods of conjoined rigid body/torsion angle simulated annealing, we were able to generate low-resolution three-dimensional structure models of the calmodulin-melittin complex, for which no high-resolution structure exists to date. Our data provide evidence for the first time that calmodulin can recognize target peptides in two opposing orientations simultaneously. The general procedure for mapping interacting regions within the complex involves conjugation of calmodulin and melittin with several cross-linking reagents possessing different specificities and spacer lengths, followed by enzymatic proteolysis of the cross-linked complex. The highly complex peptide mixtures were subsequently analyzed by nano-HPLC, which was online coupled to a FTICR mass spectrometer equipped with a nano-electrospray ionization source. The mass spectra obtained in this manner were screened for possible cross-linking products using customized software programs. This integrated approach, exemplified for mapping the topology of the calmodulin-melittin complex. is likely to have wide-ranging implications for structural studies on protein-protein interactions. C1 Univ Leipzig, Fac Chem & Mineral, Biotechnol Biomed Ctr, D-04103 Leipzig, Germany. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Sinz, A (reprint author), Univ Leipzig, Fac Chem & Mineral, Biotechnol Biomed Ctr, Linnestr 3, D-04103 Leipzig, Germany. EM sinz@chemie.uni-leipzig.de RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 67 TC 85 Z9 90 U1 0 U2 18 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 27 PY 2004 VL 43 IS 16 BP 4703 EP 4715 DI 10.1021/bi036149f PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 814IH UT WOS:000220967900009 PM 15096039 ER PT J AU Feigal, EG Sullivan, DC AF Feigal, EG Sullivan, DC TI National cancer institute and imaging - Intersecting scientific opportunity with clinical need SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Letter C1 NCI, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnosis, Canc Imaging Program, Bethesda, MD 20892 USA. RP Feigal, EG (reprint author), NCI, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. EM ef30d@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI SYLVANIA PA PO BOX 1210, SYLVANIA, OH 43560 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PD APR 27 PY 2004 IS 1 BP 3 EP 4 PG 2 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 823HT UT WOS:000221602100002 ER PT J AU French, JA Kanner, AM Bautista, J Abou-Khalil, B Browne, T Harden, CL Theodore, WH Bazil, C Stern, J Schachter, SC Bergen, D Hirtz, D Montouris, GD Nespeca, M Gidal, B Marks, WJ Turk, WR Fischer, JH Bourgeois, B Wilner, A Faught, RE Sachdeo, RC Beydoun, A Glauser, TA AF French, JA Kanner, AM Bautista, J Abou-Khalil, B Browne, T Harden, CL Theodore, WH Bazil, C Stern, J Schachter, SC Bergen, D Hirtz, D Montouris, GD Nespeca, M Gidal, B Marks, WJ Turk, WR Fischer, JH Bourgeois, B Wilner, A Faught, RE Sachdeo, RC Beydoun, A Glauser, TA TI Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new onset epilepsy - Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society SO NEUROLOGY LA English DT Article ID NEWLY-DIAGNOSED EPILEPSY; CONTROLLED CLINICAL-TRIAL; PREVIOUSLY UNTREATED EPILEPSY; DOUBLE-BLIND; LAMOTRIGINE MONOTHERAPY; OXCARBAZEPINE; CARBAMAZEPINE; PHENYTOIN; VALPROATE; SEIZURES AB Objective: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) ( gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide - reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. Results: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary. C1 Univ Penn, Philadelphia, PA 19104 USA. Rush Med Coll, Dept Neurol Sci, Chicago, IL 60612 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Cornell Univ, Weill Med Coll, New York, NY USA. NINDS, NIH, Bethesda, MD 20892 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp San Diego, San Diego, CA USA. Univ Wisconsin Hosp & Clin, Sch Pharm, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, Dept Neurol, Madison, WI 53792 USA. Univ Calif San Francisco, Epilepsy Ctr, San Francisco, CA 94143 USA. Nemours Childrens Clin, Div Neurol, Jacksonville, FL USA. Univ Illinois, Coll Pharm, Dept Pharm Practice & Neurol, Chicago, IL USA. Univ Illinois, Coll Med, Chicago, IL USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Alabama, Sch Med, Dept Neurol, Birmingham, AL USA. Univ Med & Dent New Jersey, Dept Neurol, New Brunswick, NJ 08903 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI USA. Childrens Hosp, Med Ctr, Dept Neurol, Cincinnati, OH 45229 USA. RP French, JA (reprint author), Amer Acad Neurol, TTA Subcomm, 1080 Montreal Ave, St Paul, MN 55116 USA. RI French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU NINDS NIH HHS [U10 NS077311] NR 21 TC 260 Z9 278 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 27 PY 2004 VL 62 IS 8 BP 1252 EP 1260 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 815UM UT WOS:000221067200004 PM 15111659 ER PT J AU French, JA Kanner, AM Bautista, J Abou-Khalil, B Browne, T Harden, CL Theodore, WH Bazil, C Stern, J Schachter, SC Bergen, D Hirtz, D Montouris, GD Nespeca, M Gidal, B Marks, WJ Turk, WR Fischer, JH Bourgeois, B Wilner, A Faught, RE Sachdeo, RC Beydoun, A Glauser, TA AF French, JA Kanner, AM Bautista, J Abou-Khalil, B Browne, T Harden, CL Theodore, WH Bazil, C Stern, J Schachter, SC Bergen, D Hirtz, D Montouris, GD Nespeca, M Gidal, B Marks, WJ Turk, WR Fischer, JH Bourgeois, B Wilner, A Faught, RE Sachdeo, RC Beydoun, A Glauser, TA TI Efficacy and tolerability of the new antiepileptic drugs II: Treatment of refractory epilepsy - Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society SO NEUROLOGY LA English DT Article ID ADD-ON THERAPY; PLACEBO-CONTROLLED TRIAL; LENNOX-GASTAUT-SYNDROME; PARTIAL-ONSET SEIZURES; DOSE-RANGING TRIAL; SECONDARILY GENERALIZED SEIZURES; RESISTANT PARTIAL SEIZURES; COMPLEX PARTIAL SEIZURES; DOUBLE-BLIND; INTRACTABLE EPILEPSY AB Objective: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) ( gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. Methods: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. Results: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. Conclusions: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary. C1 Univ Penn, Philadelphia, PA 19104 USA. Rush Med Coll, Dept Neurol Sci, Chicago, IL 60612 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Cornell Univ, Weill Med Coll, New York, NY USA. NINDS, NIH, Bethesda, MD 20892 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp San Diego, San Diego, CA USA. Univ Wisconsin Hosp & Clin, Dept Neurol, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, Sch Pharm, Madison, WI 53792 USA. Univ Calif San Francisco, Epilepsy Ctr, San Francisco, CA 94143 USA. Nemours Childrens Clin, Div Neurol, Jacksonville, FL USA. Univ Illinois, Coll Pharm, Dept Pharm Practice & Neurol, Chicago, IL 60680 USA. Univ Illinois, Coll Med, Chicago, IL USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Alabama, Sch Med, Dept Neurol, Birmingham, AL USA. Univ Med & Dent New Jersey, Dept Neurol, New Brunswick, NJ 08903 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI USA. Childrens Hosp, Med Ctr, Dept Neurol, Cincinnati, OH 45229 USA. RP French, JA (reprint author), Amer Acad Neurol, TTA Subcomm, 1080 Montreal Ave, St Paul, MN 55116 USA. RI French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU NINDS NIH HHS [U10 NS077311] NR 84 TC 285 Z9 305 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 27 PY 2004 VL 62 IS 8 BP 1261 EP 1273 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 815UM UT WOS:000221067200005 PM 15111660 ER PT J AU Chrousos, GP AF Chrousos, GP TI Is 11 ss-hydroxysteroid dehydrogenase type 1 a good therapeutic target for blockade of glucocorticoid actions? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID CORTICOTROPIN-RELEASING HORMONE; CUSHINGS-SYNDROME; HYPERCORTISOLISM; PSYCHOPATHOLOGY; CORTISOL; STRESS C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHHD, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM chrousog@mail.nih.gov NR 17 TC 36 Z9 37 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6329 EP 6330 DI 10.1073/pnas.0401671101 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900001 PM 15096596 ER PT J AU Tsai-Morris, CH Sheng, Y Lee, E Lei, KJ Dufau, ML AF Tsai-Morris, CH Sheng, Y Lee, E Lei, KJ Dufau, ML TI Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE messenger ribonuclear protein particle; translation; testis; spermiogenesis; sterility ID ANGIOTENSIN-CONVERTING ENZYME; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; MESSENGER-RNA; MOUSE HOMOLOG; BOX PROTEINS; MICE; SPERMIOGENESIS; FAMILY; TESTIS AB Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25), a member of the DEAD-box protein family, is a testis-specific gonadotropin-regulated RNA helicase that is present in Leydig cells and germ cells (meiotic spermatocytes and spermatids). In this study, we observed that GRTH is present in the nucleus, cytoplasm and chromatoid body of germ cells, and is an integral component of messenger ribonuclear protein particles. Male mice with a null mutation in the GRTH gene displayed normal gonadotropin and androgen profiles. However, they were sterile, with azoospermia caused by a complete arrest of spermiogenesis at step 8 of round spermatids and failure to elongate. Round spermatids of the null mice showed marked diminution in the size of chromatoid bodies. The transcription of relevant messages was not altered, but their translation was abrogated in a selective manner. Protein expression of transition proteins 1 and 2 and angiotensin-converting enzyme was completely absent, whereas that of the transcriptional activator cAMP responsive element modulator was intact. These findings indicate that GRTH participates in translational-associated events during germ cell development. Although significant apoptosis was present at the metaphase of meiosis in the GRTH-null mice, spermatogenesis proceeded to step 8 of spermiogenesis when complete arrest occurred. This progression may relate to compensatory gene function(s) and/or the observed up-regulation of DNA repair proteins Rad51 and Dmc1. This study (i) demonstrates that GIRTH is essential for completion of spermatogenesis, (h) provides insights into intrinsic requirements for spermiogenesis, and (fit) establishes a model for studies of male infertility and contraception. C1 NIH, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. NICHHD, NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NIH, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bldg 49-6A-36, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov NR 26 TC 97 Z9 99 U1 1 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 27 PY 2004 VL 101 IS 17 BP 6373 EP 6378 DI 10.1073/pnas.0401855101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900011 PM 15096601 ER PT J AU Silic-Benussi, M Cavallari, L Zorzan, T Rossi, E Hiraragi, H Rosato, A Horie, K Saggioro, D Lairmore, MD Willems, L Chieco-Bianchi, L D'Agostino, DM Ciminale, V AF Silic-Benussi, M Cavallari, L Zorzan, T Rossi, E Hiraragi, H Rosato, A Horie, K Saggioro, D Lairmore, MD Willems, L Chieco-Bianchi, L D'Agostino, DM Ciminale, V TI Suppression of tumor growth and cell proliferation by p13(II), a mitochondrial protein of human T cell leukemia virus type 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; calcium signaling; tumorigenicity; retrovirus ID ACCESSORY PROTEINS; IN-VIVO; PERMEABILITY TRANSITION; NUCLEAR FACTOR; P12(I); G4; ACTIVATION; APOPTOSIS; LOCALIZATION; EXPRESSION AB Human T cell leukemia virus type 1 encodes an "accessory" protein named p13(II) that is targeted to mitochondria and triggers a rapid flux of K+ and Ca2+ across the inner membrane. In this study, we investigated the effects of p13(II) on tumorigenicity in vivo and on cell growth in vitro. Results showed that p13(II) significantly reduced the incidence and growth rate of tumors arising from c-myc and Ha-ras-cotransfected rat embryo fibroblasts. Consistent with these findings, HeLa-derived cell lines stably expressing p13(II) exhibited markedly reduced tumorigenicity, as well as reduced proliferation at high density in vitro. Mixed culture assays revealed that the phenotype of the p13(II) cell lines was dominant over that of control lines and was mediated by a heat-labile soluble factor. The p13II cell lines exhibited an enhanced response to Ca2+-mediated stimuli, as measured by increased sensitivity to C2-ceramide-induced apoptosis and by cAMP-responsive element-binding protein (CREB) phosphorylation in response to histamine. p13(II)-expressing Jurkat T cells also exhibited reduced proliferation, suggesting that the protein might exert similar effects in T cells, the primary target of HTLV-1 infection. These findings provide clues into the function of p13(II) as a negative regulator of cell growth and underscore a link between mitochondria, Ca2+ signaling, and tumorigenicity. C1 Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. NCI, Human Retrovirus Sect, Ft Detrick, MD 21702 USA. Azienda Osped Padova, I-35128 Padua, Italy. Fac Agron, B-5030 Gembloux, Belgium. RP Ciminale, V (reprint author), Univ Padua, Dept Oncol & Surg Sci, Via Gattamelata 64, I-35128 Padua, Italy. EM v.ciminale@unipd.it RI Rosato, Antonio/E-8626-2010; Rossi, Elisabetta/K-4346-2016 OI Rossi, Elisabetta/0000-0002-5242-9568 FU FIC NIH HHS [R03 TW005705, R03TW005705] NR 28 TC 47 Z9 49 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6629 EP 6634 DI 10.1073/pnas.0305502101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900055 PM 15100416 ER PT J AU Bisht, H Roberts, A Vogel, L Bukreyev, A Collins, PL Murphy, BR Subbarao, K Moss, B AF Bisht, H Roberts, A Vogel, L Bukreyev, A Collins, PL Murphy, BR Subbarao, K Moss, B TI Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFECTIOUS PERITONITIS VIRUS; ANTIBODY-DEPENDENT ENHANCEMENT; SARS CORONAVIRUS; REPLICATION; CHALLENGE; MVA; NEUTRALIZATION; PROPAGATION; SEQUENCE; RECEPTOR AB The spike protein (S), a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV) is anticipated to be an important component of candidate vaccines. We constructed recombinant forms of the highly attenuated modified vaccinia virus Ankara (MVA) containing the gene encoding full-length SARS-CoV S with and without a C-terminal epitope tag called MVA/S-HA and MVA/S, respectively. Cells infected with MVA/S or MVA/S-HA synthesized a 200-kDa protein, which was recognized by antibody raised against a synthetic peptide of SARS-CoV S or the epitope tag in Western blot analyses. Further studies indicated that S was N-glycosylated and migrated in SDS polyacrylamide gels with an apparent mass of approximate to160 kDa after treatment with peptide N-glycosiclase F. The acquisition of resistance to endoglycosidase H indicated trafficking of S to the medial Golgi compartment, and confocal microscopy showed that S was transported to the cell surface. Intranasal or intramuscular inoculations of BALB/c mice with MVA/S produced serum antibodies that recognized the SARS S in ELISA and neutralized SARS-CoV in vitro. Moreover, MVA/S administered by either route elicited protective immunity, as shown by reduced titers of SARS-CoV in the upper and lower respiratory tracts of mice after challenge. Passive transfer of serum from mice immunized with MVA/S to naive mice also reduced the replication of SARS-CoV in the respiratory tract after challenge, demonstrating a role for antibody to S in protection. The attenuated nature of MVA and the ability of MVA/S to induce neutralizing antibody that protects mice support further development of this candidate vaccine. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@niaid.nih.gov NR 32 TC 216 Z9 236 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 27 PY 2004 VL 101 IS 17 BP 6641 EP 6646 DI 10.1073/pnas.0401939101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900057 PM 15096611 ER PT J AU Wieland, S Thimme, R Purcell, RH Chisari, FV AF Wieland, S Thimme, R Purcell, RH Chisari, FV TI Genomic analysis of the host response to hepatitis B virus infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-LYMPHOCYTE RESPONSIVENESS; ACUTE VIRAL-HEPATITIS; TRANSGENIC MICE; IFN-GAMMA; INTRACELLULAR INACTIVATION; INTERFERON; CELLS; REPLICATION; FAMILY; RNA AB Previous studies in hepatitis B virus (HBV)-infected humans and chimpanzees suggest that control of HBV infection involves the cells, effector functions, and molecular mediators of the immune response. The objective of the current study was to identify, in the liver of acutely HBV-infected chimpanzees, the spectrum of virus-induced and immune response-related genes that regulate the infection. The results demonstrate that HBV does not induce any genes during entry and expansion, suggesting it is a stealth virus early in the infection. In contrast, a large number of T cell-derived IFN-gamma-regulated genes are induced in the liver during viral clearance, reflecting the impact of an adaptive T cell response that inhibits viral replication and kills infected cells, thereby terminating the infection. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NIH, Hepatitis Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. RP Chisari, FV (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM fchisari@scripps.edu RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU NCI NIH HHS [CA76403, N01-CO-56000, R01 CA076403]; NIAID NIH HHS [AI20001, N01-AI-45180, N01-AI-52705, R01 AI020001, R21 AI052705] NR 43 TC 291 Z9 308 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6669 EP 6674 DI 10.1073/pnas.0401771101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900062 PM 15100412 ER PT J AU Paty, BW Bonner-Weir, S Laughlin, MR McEwan, J Shapiro, AMJ AF Paty, BW Bonner-Weir, S Laughlin, MR McEwan, J Shapiro, AMJ TI Toward development of imaging modalities for islets after transplantation: Insights from the national institutes of health workshop on beta cell imaging SO TRANSPLANTATION LA English DT Review AB Background. Pancreatic islet transplantation can provide insulin independence and near normal glucose control in selected patients with type 1 diabetes mellitus. However, in most cases, achieving insulin independence necessitates the use of at least two do nor pancreases per recipient and the rate of insulin independence may decline after transplantation. To better understand the fate of transplanted islets am the relationship between transplanted islet mass, graft function, and overall glucose homeostasis, an accurate and reproducible method of imaging islets in vivo is needed. Methods. Recent advances in noninvasive imaging techniques such as magnetic resonance imaging positron emission tomography, and other imaging modalities show great promise as potential tools to monitor islet number, mass, and function in the clinical setting. A recent international workshop, "Imaging the Pancreatic Beta Cell," sponsored by the National Institute of Biomedical Imaging and Bioengineering the National Institute of Diabetes and Digestive an Kidney Diseases, and the Juvenile Diabetes Research Foundation International focused on these emerging efforts to develop novel ways of imaging pancreatic beta cells in vivo. Results. Potential clinically applicable techniques in elude the use of directed magnetic resonance contrast agents such as lanthanides (Ln(3+)) and manganese (Mn2+) or magnetic resonance imaging probes such a superparamagnetic iron oxide nanoparticles. Potentia techniques for positron emission tomography imaging include the use of beta cell-specific antibodies, or pharmacologic agents such as glyburide analogs, or D-mannoheptulose. Optical imaging techniques are also being used to evaluate various aspects of beta cell metabolism including intracellular Ca2+ flux, glucokinase activity, and insulin granular exocytosis. Conclusions. The consensus among investigators at the imaging workshop was that an accurate and reproducible in vivo measure of functional islet mass is critically needed to further the strides that have been made in both islet transplantation and diabetes research as a whole. Such measures would potentially allow the assessment of islet engraftment and the early recognition of graft loss, leading to greater improvements in islet graft survival and function. C1 Univ Alberta, Clin Islet Transplant Program, Dept Med, Edmonton, AB, Canada. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. NIDDK, Bethesda, MD USA. Univ Alberta, Dept Oncol, Edmonton, AB, Canada. Univ Alberta, Dept Surg, Edmonton, AB, Canada. RP Paty, BW (reprint author), Univ Alberta, Clin Islet Transplant Program, Dept Med, 2000 Coll Plaza,8215 112th St, Edmonton, AB, Canada. EM bpaty@ualberta.ca NR 25 TC 49 Z9 52 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2004 VL 77 IS 8 BP 1133 EP 1137 DI 10.1097/01.TP.0000113231.90613.0E PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 816SZ UT WOS:000221130900001 PM 15114073 ER PT J AU Doud, MK Schmidt, MW Hines, D Naumann, C Kocourek, A Kashani-Poor, N Zeidler, R Wolf, DA AF Doud, MK Schmidt, MW Hines, D Naumann, C Kocourek, A Kashani-Poor, N Zeidler, R Wolf, DA TI Rapid prefractionation of complex protein lysates with centrifugal membrane adsorber units improves the resolving power of 2D-PAGE-based proteome analysis SO BMC GENOMICS LA English DT Article AB Background: Two-dimensional gel electrophoresis (2D-PAGE) has proven over the years to be a reliable and efficient method for separation of hundreds of proteins based on charge and mass. Nevertheless, the complexity of even the simplest proteomes limits the resolving power of 2D-PAGE. This limitation can be partially alleviated by sample prefractionation using a variety of techniques. Results: Here, we have used Vivapure Ion Exchange centrifugal adsorber units to rapidly prefractionate total fission yeast protein lysate based on protein charge. Three fractions were prepared by stepwise elution with increasing sodium chloride concentrations. Each of the fractions, as well as the total lysate, were analyzed by 2D-PAGE. This simple prefractionation procedure considerably increased the resolving power of 2D-PAGE. Whereas 308 spots could be detected by analysing total protein lysate, 910 spots were observed upon prefractionation. Thorough gel image analysis demonstrated that prefractionation visualizes an additional set of 458 unique fission yeast proteins not detected in whole cell lysate. Conclusions: Prefractionation with Vivapure Q spin columns proved to be a simple, fast, reproducible, and cost-effective means of increasing the resolving power of 2D-PAGE using standard laboratory equipment. C1 Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Proteom Facil, Dept Genet & Complex Dis, Boston, MA 02115 USA. Vivasci Inc, Carlsbad, CA USA. Vivasci AG, Hannover, Germany. RP Wolf, DA (reprint author), Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Proteom Facil, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM mdoud@hsph.harvard.edu; mschmidt@hsph.harvard.edu; David.Hines@vivascience.com; Claudia.Naumann@vivascience.com; Andreas.Kocourek@vivascience.com; Noushin.Kashani-Poor@vivascience.com; Robert.Zeidler@vivascience.com; dwolf@hsph.harvard.edu FU NCRR NIH HHS [S10 RR019028]; NIEHS NIH HHS [ES00002, P30 ES000002]; NIGMS NIH HHS [R01-GM9780, R01 GM059780] NR 4 TC 9 Z9 9 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 26 PY 2004 VL 5 AR 25 DI 10.1186/1471-2164-5-25 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 824OR UT WOS:000221696400001 PM 15109393 ER PT J AU Yamaguchi, Y Itami, S Watabe, H Yasumoto, K Abdel-Malek, ZA Kubo, T Rouzaud, F Tanemura, A Yoshikawa, K Hearing, VJ AF Yamaguchi, Y Itami, S Watabe, H Yasumoto, K Abdel-Malek, ZA Kubo, T Rouzaud, F Tanemura, A Yoshikawa, K Hearing, VJ TI Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation SO JOURNAL OF CELL BIOLOGY LA English DT Article DE pigmentation; regulation; dickkopf; beta-catenin; MITF ID WNT GENE-EXPRESSION; TRANSCRIPTION FACTOR; NEURAL CREST; BETA-CATENIN; WAARDENBURG-SYNDROME; LIMB DEVELOPMENT; HEAD INDUCTION; HUMAN DKK-1; MITF; MICROPHTHALMIA AB We investigated whether or not the topographic regulation of melanocyte differentiation is determined by mesenchymal-epithelial interactions via fibroblast-derived factors. The melanocyte density in palmoplantar human skin (i.e., skin on the palms and the soles) is five times lower than that found in nonpalmoplantar sites. Palmoplantar fibroblasts significantly suppressed the growth and pigmentation of melanocytes compared with nonpalmoplantar fibroblasts. Using cDNA microarray analysis, fibroblasts derived from palmoplantar skin expressed high levels of dickkopf 1 (DKK1; an inhibitor of the canonical Wnt signaling pathway), whereas nonpalmoplantar fibroblasts expressed higher levels of DKK3. Transfection studies revealed that DKK1 decreased melanocyte function, probably through P-catenin-mediated regulation of microphthalmia-associated transcription factor activity, which in turn modulates the growth and differentiation of melanocytes. Thus, our results provide a basis to explain why skin on the palms and the soles is generally hypopigmented compared with other areas of the body, and might explain why melanocytes stop migrating in the palmoplantar area during human embryogenesis. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka 5650871, Japan. Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH 45267 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 NR 65 TC 114 Z9 115 U1 4 U2 8 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 26 PY 2004 VL 165 IS 2 BP 275 EP 285 DI 10.1083/jcb.200311122 PG 11 WC Cell Biology SC Cell Biology GA 816XS UT WOS:000221143200012 PM 15117970 ER PT J AU Longart, M Liu, Y Karavanova, I Buonanno, A AF Longart, M Liu, Y Karavanova, I Buonanno, A TI Neuregulin-2 is developmentally regulated and targeted to dendrites of central neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ErbB receptor; EGF; development; processing ID RECEPTOR-INDUCING ACTIVITY; GAMMA-SECRETASE CLEAVAGE; CEREBELLAR GRANULE CELLS; EPSILON-SUBUNIT GENE; ACETYLCHOLINE-RECEPTOR; ERBB RECEPTORS; GROWTH-FACTOR; NEUROMUSCULAR-JUNCTION; MUSCLE-SPINDLE; NERVOUS-SYSTEM AB Neuregulin-1 (NRG-1) regulates numerous aspects of neural development and synaptic plasticity; the functions of NRG-2 and NRG-3 are presently unknown. As a first step toward understanding how NRGs contribute to distinct aspects of neural development and function, we characterized their regional and subcellular expression patterns in developing brain. The expression of NRG-1-3 mRNAs was compared postnatally (P0, P7, adult) by using in situ hybridization. NRG-1 expression is highest at birth, whereas NRG-2 mRNA levels increase with development; expression of both genes is restricted to distinct brain regions. In contrast, NRG-3 transcripts are abundant in most brain regions throughout development. NRG-2 antibodies were generated to analyze protein processing, expression, and subcellular distribution. As with NRG-1, the transmembrane NRG-2 proprotein is proteolytically processed in transfected HEK 293 cells and in neural tissues, and its ectodomain is exposed and accumulates on the neuron surface. Despite the structural similarities between NRG-1 and NRG-2, we unexpectedly found that NRG-2 colocalizes with MAP2 in proximal primary dendrites of hippocampal neurons in culture and in vivo, although it is not detectable in axons or in axon terminals. These findings were confirmed with NRG-2 ectodomain antisera and epitope-tagged recombinant protein. In cerebellum, NRG-2 colocalizes with calbindin in proximal dendrites and soma of Purkinje cells. In contrast, NRG-1 is highly expressed in axons of dissociated hippocampal neurons, as well as in somas and dendrites. The distinct temporal, regional, and subcellular expression of NRG-2 suggests its unique and nonredundant role in neural function. Published 2004 Wiley-Liss, Inc. C1 NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM buonanno@helix.nih.gov NR 94 TC 38 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 26 PY 2004 VL 472 IS 2 BP 156 EP 172 DI 10.1002/cne.20016 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 809HB UT WOS:000220626700004 PM 15048684 ER PT J AU Julias, JG Boyer, PL McWilliams, MJ Alvord, WG Hughes, SH AF Julias, JG Boyer, PL McWilliams, MJ Alvord, WG Hughes, SH TI Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis SO VIROLOGY LA English DT Article DE HIV-1; 3TC; real-time PCR; 2-LTR circle junction; RNase H activity ID RIBONUCLEASE-H ACTIVITY; RNASE-H; M184V MUTATION; IN-VITRO; RESISTANT VARIANTS; CONFERS RESISTANCE; STERIC HINDRANCE; 3TC RESISTANCE; AMINO-ACIDS; POLYMERASE AB Methionine at position 184 of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) was changed to valine, isoleucine, threonine, or alanine in an HIV-1-based vector. The vectors were analyzed for replication capacity and for resistance to the nucleoside analog 2',3'-dideoxy-3thiacytidine (3TC) using a single-cycle assay. Viruses containing the valine or isoleucine mutations were highly resistant to 3TC and replicated almost as well as the wild-type virus. The virus containing the threonine mutation was resistant to 3TC, but replicated about 30% as well as the wild-type. The alanine mutation conferred partial resistance to 3TC, but replicated poorly. The amounts of viral DNA synthesized decreased in 3TC-treated cells when the cells were infected with wild-type virus and the M184A mutant. The effect of these mutations on the generation of the ends of the linear viral DNA was determined using the sequence of the 2-LTR circle junctions. The M184T mutation increased the proportion of 2-LTR circle junctions containing a tRNA insertion, suggesting that the mutation affected the RNase H activity of RT. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, NCI Frederick, Frederick, MD 21702 USA. NCI Frederick, Data Management Serv, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI Frederick, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 41 TC 19 Z9 21 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 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2004 VL 322 IS 1 BP 13 EP 21 DI 10.1016/j.virol.2004.01.004 PG 9 WC Virology SC Virology GA 812TF UT WOS:000220861100002 PM 15063112 ER PT J AU Dickie, P Roberts, A Uweira, R Witmer, J Sharma, K Kopp, JB AF Dickie, P Roberts, A Uweira, R Witmer, J Sharma, K Kopp, JB TI Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy SO VIROLOGY LA English DT Article DE AIDS; retrovirus; nef; kidney; macrophage ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL PROTEIN-R; MESANGIAL CELLS; EPITHELIAL-CELLS; INFECTED-CELLS; SEGMENTAL GLOMERULOSCLEROSIS; EFFICIENT REPLICATION; GENE-EXPRESSION; TYPE-1 HIV-1; T-CELLS AB Clinical and morphologic features of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), such as proteinuria, sclerosing glomerulopathy, tubular degeneration, and interstitial disease, have been modeled in mice bearing an HIV proviral transgene rendered noninfectious through a deletion in gag/pol. Exploring the genetic basis of HIVAN, HIV transgenic mice bearing mutations in either or both of the accessory genes nef and vpr were created. Proteinuria and focal glomerulosclerosis (FGS) only developed in mice with an intact vpr gene. Transgenic mice bearing a simplified proviral DNA (encoding only Tat and Vpr) developed renal disease characterized by FGS in which Vpr protein was localized to glomerular and tubular epithelia by immunohistochemistry. The dual transgenic progeny of HIV[Tat/Vpr] mice bred to HIV[DeltaVpr] proviral transgenic mice displayed a more severe nephropathy with no apparent increase in Vpr expression, implying that multiple viral genes contribute to HIVAN. However, the unique contribution of macrophage-specific Vpr expression in the development of glomerular disease was underscored by the induction of FGS in multiple murine lines bearing a c-fms/vpr transgene. Crown Copyright (C) 2004 Published by Elsevier Inc. All rights reserved. C1 Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2S2, Canada. Univ Alberta, Hlth Sci Lab Anim Serv, Edmonton, AB T6G 2S2, Canada. NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dickie, P (reprint author), Univ Alberta, Dept Med Microbiol & Immunol, Room 1-40,HMRC Bldg, Edmonton, AB T6G 2S2, Canada. EM peter.dickie@ualberta.ca OI Kopp, Jeffrey/0000-0001-9052-186X NR 62 TC 40 Z9 40 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 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2004 VL 322 IS 1 BP 69 EP 81 DI 10.1016/j.virol.2004.01.026 PG 13 WC Virology SC Virology GA 812TF UT WOS:000220861100008 PM 15063118 ER PT J AU Rollman, E Arnheim, L Collier, B Oberg, D Hall, H Klingstrom, J Dillner, J Pastrana, DV Buck, CB Hinkula, J Wahren, B Schwartz, S AF Rollman, E Arnheim, L Collier, B Oberg, D Hall, H Klingstrom, J Dillner, J Pastrana, DV Buck, CB Hinkula, J Wahren, B Schwartz, S TI HPV-16 L1 genes with inactivated negative RNA elements induce potent immune responses SO VIROLOGY LA English DT Article DE DNA vaccination; HPV-16; tumor immunity; neutralization; T lymphocytes; imiquimod; rGM-CSF ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; CYTOTOXIC T-LYMPHOCYTES; DNA VACCINATION; EPITHELIAL-CELLS; IMMUNIZATION; EXPRESSION; DELIVERY; WOMEN; E6 AB Introduction of point mutations in the 5' end of the human papillomavirus type 16 (HPV-16) L1 gene specifically inactivates negative regulatory RNA processing elements. DNA vaccination of C57B1/6 mice with the mutated L1 gene resulted in improved immunogenicity for both neutralizing antibodies as well as for broad cellular immune responses. Previous reports on the activation of L1 by codon optimization may be explained by inactivation of the regulatory RNA elements. The modified HPV-16 L1 DNA that induced anti-HPV-16 immunity may be seen as a complementary approach to protein subunit immunization against papillomavirus. (C) 2004 Elsevier Inc. All rights reserved. C1 Swedish Inst Infect Dis Control, Dept Virol, S-17182 Solna, Sweden. Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Huddinge Univ Hosp, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Huddinge, Sweden. Western Gen Hosp, MRC, Human Genet Unit, Chromosome Biol Sect, Edinburgh EH4 2XU, Midlothian, Scotland. Uppsala Univ, BMC, Dept Med Biochem & Microbiol, S-75123 Uppsala, Sweden. Lund Univ, Malmo Univ Hosp, Dept Med Microbiol, S-20502 Malmo, Sweden. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Rollman, E (reprint author), Swedish Inst Infect Dis Control, Dept Virol, Tomtebodvagen 34B, S-17182 Solna, Sweden. EM erik.rollman@smi.ki.se RI Arnheim Dahlstrom, Lisen/H-6030-2012; OI Klingstrom, Jonas/0000-0001-9076-1441; Hinkula, Jorma/0000-0003-1908-5609; Buck, Christopher/0000-0003-3165-8094 NR 44 TC 16 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2004 VL 322 IS 1 BP 182 EP 189 DI 10.1016/j.virol.2004.02.002 PG 8 WC Virology SC Virology GA 812TF UT WOS:000220861100017 PM 15063127 ER PT J AU Rosen, JB Breman, JG AF Rosen, JB Breman, JG TI Malaria intermittent preventive treatment in infants, chemoprophylaxis, and childhood vaccinations SO LANCET LA English DT Review ID PLACEBO-CONTROLLED TRIAL; IMMUNE-RESPONSE; MEASLES VACCINATION; ANTIBODY-RESPONSE; CHILDREN; CHLOROQUINE; ANEMIA; AREA AB Context Malaria accounts for 1-3 million deaths yearly worldwide, mostly in children under 5 years of age in sub-Saharan Africa. Laboratory and clinical studies show an association between acute malaria and a decreased response to diphtheria and tetanus toxoids and to meningococcal, salmonella, and Haemophilus influenzae, type b vaccinations. Malaria treatment, chemoprophylaxis, or other forms of parasite suppression might improve the immune response to childhood vaccinations. However, the antimalarial 4-aminoquinolones are immunodepressive, such that antimalarial drugs might depress the vaccine response. Starting point Last year, Julius Massage and colleagues reported a randomised double-blinded placebo-controlled study in 291 infants aged 12-16 weeks in Tanzia (lancet 2003; 361: 1853-60). At enrolment, children received their third dose of combined diphtheria-tetanus-pertussis and poliomyelitis expanded vaccines with the first of three daily doses of amodiaquine intermittent preventive treatment (IPTi) or placebo. After 60 days, children receiving amodiaquine had significantly fewer malaria fevers than controls. Where next The increasing concordance of malaria control and vaccination, movement toward co-administration of IPTi with immunisation, and the increase in travellers to malarious areas who receive concurrent vaccinations and chemoprophylaxis warrant further study. C1 NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Natl Inst Hlth Res Program, Bethesda, MD 20892 USA. RP Rosen, JB (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM jennifer.rosen@uhmc.sunysb.edu NR 13 TC 23 Z9 23 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 24 PY 2004 VL 363 IS 9418 BP 1386 EP 1388 DI 10.1016/S0140-6736(04)16052-2 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 814TF UT WOS:000220996300025 PM 15110499 ER PT J AU Kunkel, TA AF Kunkel, TA TI DNA replication fidelity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID SYN THYMINE DIMER; POLYMERASE-ETA; ERROR-PRONE; LESION-BYPASS; NUCLEOTIDE INCORPORATION; STRUCTURAL INSIGHTS; ESCHERICHIA-COLI; ACTIVE-SITE; INDUCED-FIT; MECHANISM C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 60 TC 335 Z9 340 U1 7 U2 28 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 23 PY 2004 VL 279 IS 17 BP 16895 EP 16898 DI 10.1074/jbc.R400002200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400001 PM 14988392 ER PT J AU Lee, HJ Lim, HM Adhya, S AF Lee, HJ Lim, HM Adhya, S TI An unsubstituted C2 hydrogen of adenine is critical and sufficient at the-11 position of a promoter to signal base pair deformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE HOLOENZYME; OPEN COMPLEX-FORMATION; AROMATIC-AMINO-ACIDS; URACIL-DNA GLYCOSYLASE; AMP RECEPTOR PROTEIN; TRANSCRIPTION INITIATION; CRYSTAL-STRUCTURE; SIGMA-FACTOR; BACILLUS-SUBTILIS; ANGSTROM RESOLUTION AB The conserved A: T base pair at the -11 position of the promoters in Escherichia coli is very sensitive to substitutions. In vitro transcription with the galP1 promoter having a natural or unnatural base in either strand at position -11 showed that only a purine base with no side group at C2 in the nontemplate strand is transcriptionally potent; neither a purine with an amino group at C2 nor a pyrimidine support transcription. The amino group at C6 in the omnipresent adenine at -11 does not play any role in promoting transcription. The nature of the base, complementary or noncomplementary, at -11 in the template strand also does not influence transcription. We propose that the adenine, by becoming extra-helical, interacts with an amino acid(s) of the 2.3-2.4 region of sigma for which an unsubstituted C2 hydrogen is critical. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Chungnam Natl Univ, Coll Nat Sci, Dept Biol, Taejon 305764, South Korea. RP Lim, HM (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM hmlim@cnu.ac.kr; sadhya@helix.nih.gov NR 43 TC 15 Z9 15 U1 0 U2 1 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 23 PY 2004 VL 279 IS 17 BP 16899 EP 16902 DI 10.1074/jbcC400054200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400002 PM 14990576 ER PT J AU Shi, CS Kehrl, JH AF Shi, CS Kehrl, JH TI Pyk2 amplifies epidermal growth factor and c-Src-induced Stat3 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; FOCAL ADHESION KINASE; ACUTE-PHASE RESPONSE; TYROSINE KINASE; ANGIOTENSIN-II; SERINE PHOSPHORYLATION; SIGNALING PATHWAY; JAK/STAT PATHWAY; EPITHELIAL-CELLS; RAC ACTIVATION AB Signal transducers and activators of transcription factors (STATs) mediate many of the cellular responses that occur following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine and serine phosphorylation, which normally occurs as a tightly regulated process. Dysregulated STAT activity may facilitate oncogenesis, as constitutively activated STATs have been found in many human tumors as well as in v-abl- and v-src-transformed cell lines. Pyk2 is a member of the focal adhesion kinase family and can be activated by c-Src, epidermal growth factor receptor ( EGFR), Janus kinase 1, tyrosine kinases, and G-protein-coupled receptor signaling. Although Pyk2 has been implicated in Janus kinase-dependent activation of MAPK and Stat1, no role for Pyk2 in the activation of other STAT proteins has been ascribed. Here, we provide evidence that Pyk2, along with c-Src, facilitates EGFR-mediated Stat3 activation. Pyk2 expression in HeLa cells induces Stat3 reporter gene activation and Stat3 phosphorylation on amino acid residues Tyr-705 and Ser-727. Together Pyk2 and c-Src potently activate Stat3, and Pyk2 enhances Stat3-induced cell proliferation. Moreover, the expression of a dominant negative version of Pyk2 impairs c-Src-induced Stat3 activation and cell proliferation. The treatment of A431 cells with EGF results in the recruitment of c-Src, Pyk2, and Stat3 to the EGFR and the phosphorylation of c-Src, Pyk2, and Stat3. Expression of constructs for dominant negative forms of either Pyk2 or c-Src impair EGF-induced Stat3 phosphorylation. These results indicate that Pyk2 facilitates EGFR- and c-Src-mediated Stat3 activation, thereby implicating Pyk2 activation as a potential co-mediator in triggering Stat3-induced oncogenesis. C1 NIAID, Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bldg 10,Rm 11B08,10 Ctr DR MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@atlas.niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 62 TC 31 Z9 37 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 23 PY 2004 VL 279 IS 17 BP 17224 EP 17231 DI 10.1074/jbc.M311875200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400043 PM 14963038 ER PT J AU Thakurta, AG Gopal, G Yoon, JH Saha, T Dhar, R AF Thakurta, AG Gopal, G Yoon, JH Saha, T Dhar, R TI Conserved nuclear export sequences in Schizosaccharomyces pombe Mex67 and human TAP function in mRNA export by direct nuclear pore interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLEX-FORMATION; PROTEIN EXPORT; BINDING-SITES; FG-REPEAT; YEAST; REQUIRES; DOMAIN; P15; IDENTIFICATION; NUCLEOPORINS AB Mex67, the homolog of human TAP, is not an essential mRNA export factor in Schizosaccharomyces pombe. Here we show that S. pombe encodes a homolog of the TAP cofactor that we have also named p15, whose function in mRNA export is not essential. We have identified and characterized two distinct nuclear export activities, nuclear export signal (NES) I and NES II, within the region of amino acids 434-509 of Mex67. These residues map within the known NTF2-like fold of TAP (amino acids 371-551). We show that the homologs of these two NESs are present and are functionally conserved in TAP. The NES I, NES II, and NES I + II of TAP and Mex67 directly bind with -phenylalanine-glycine(-FG)-containing sequences of S. pombe Nup159 and Nup98 but not with human p62. Mutants of NES I or NES II of Mex67/TAP that do not bind -FG Nup159 and Nup98 in vitro are unable to mediate nuclear export of a heterologous protein in S. pombe and in HeLa cells. Fused with the RNA recognition motifs (RRMs) of Crp79 and green fluorescent protein (GFP) (RRM-NES-GFP), the NES I and NES II of Mex67 or TAP can suppress the mRNA export defect of the Deltap15 rae1-167 synthetic lethal S. pombe strain, suggesting that the NESs can function in the absence of p15. These novel nuclear export sequences may provide additional routes for delivering Mex67/TAP to the nuclear pore complex. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. Sungshin Womens Univ, Dept Biol, Seoul 136742, South Korea. Kangnung Natl Univ, Coll Nat Sci, Div Biol, Kangnung 210702, South Korea. RP NCI, Ctr Canc Res, NIH, Bldg 37,Rm 6138,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dharr@mail.nih.gov NR 33 TC 11 Z9 13 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 23 PY 2004 VL 279 IS 17 BP 17434 EP 17442 DI 10.1074/jbc.M309731200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400069 PM 14963046 ER PT J AU Chen, YR Chen, CL Chen, WG Zweier, JL Augusto, O Radi, R Mason, RP AF Chen, YR Chen, CL Chen, WG Zweier, JL Augusto, O Radi, R Mason, RP TI Formation of protein tyrosine ortho-semiquinone radical and nitrotyrosine from cytochrome c-derived tyrosyl radical SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE; HYDROGEN-PEROXIDE; RIBONUCLEOTIDE REDUCTASE; SPIN-STABILIZATION; INDUCED APOPTOSIS; CATECHOL ESTROGENS; OXIDATIVE STRESS; ANION RADICALS; PHOTOSYSTEM-II; TUMOR-CELLS AB Oxidative alteration of mitochondrial cytochrome c (cyt c) has been linked to disease pathophysiology and is one of the causative factors for pro-apoptotic events. Hydrogen peroxide induces a short-lived cyt c-derived tyrosyl radical as detected by the electron spin resonance (ESR) spin-trapping technique. This investigation was undertaken to characterize the fate and consequences of the cyt c-derived tyrosyl radical. The direct ESR spectrum from the reaction of cyt c with H2O2 revealed a single-line signal with a line width of similar to10 G. The detected ESR signal could be prevented by pretreatment of cyt c with iodination, implying that the tyrosine residue of cyt c was involved. The ESR signal can be enhanced and stabilized by a divalent metal ion such as Zn2+, indicating the formation of the protein tyrosine ortho-semiquinone radical (ToQ(radical anion)). The production of cyt c-derived ToQ(radical anion) is inhibited by the spin trap, 2- methyl-2-nitrosopropane (MNP), suggesting the participation of tyrosyl radical in the formation of the ortho-semiquinone radical. The endothelium relaxant factor nitric oxide is well known to mediate mitochondrial respiration and apoptosis. The consumption of NO by cyt c was enhanced by addition of H2O2 as verified by inhibition electrochemical detection using an NO electrode. The rate of NO consumption in the system containing cyt c/NO/H2O2 was decreased by the spin traps 5,5-dimethyl pyrroline N-oxide and MNP, suggesting NO trapping of the cyt c-derived tyrosyl radical. The above result was further confirmed by NO quenching of the ESR signal of the MNP adduct of cyt c tyrosyl radical. Immunoblotting analysis of cyt c after exposure to NO in the presence of H2O2 revealed the formation of 3-nitrotyrosine. The addition of superoxide dismutase did not change the cyt c nitration, indicating that it is peroxynitrite-independent. The results of this study may provide useful information in understanding the interconnection among cyt c, H2O2, NO, and apoptosis. C1 Ohio State Univ, Coll Med, Dept Internal Med,Div Cardiovasc Med, Davis Heart & Lung Res Inst 607, Columbus, OH 43210 USA. Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05513970 Sao Paulo, Brazil. Univ Republica, Fac Med, Dept Biochem, Montevideo 11800, Uruguay. Univ Republica, Fac Med, Ctr Free Rad & Biomed Res, Montevideo 11800, Uruguay. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chen, YR (reprint author), Ohio State Univ, Coll Med, Dept Internal Med,Div Cardiovasc Med, Davis Heart & Lung Res Inst 607, 473 W 12th Ave, Columbus, OH 43210 USA. EM chen-12@medctr.osu.edu RI Augusto, Ohara/D-3839-2012 OI Augusto, Ohara/0000-0002-7220-4286 FU NHLBI NIH HHS [HL63744, HL65608, R01S-HL38324]; NIEHS NIH HHS [K22 ES011031, K22-ES11031] NR 51 TC 61 Z9 64 U1 0 U2 13 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 23 PY 2004 VL 279 IS 17 BP 18054 EP 18062 DI 10.1074/jbc.M307706200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400141 PM 14761966 ER PT J AU Ma, Y Lang, LX Kiesewetter, DO Vuong, BK Channing, M Ito, Y Eckelman, WC AF Ma, Y Lang, LX Kiesewetter, DO Vuong, BK Channing, M Ito, Y Eckelman, WC TI Purification of the precursor for the automated radiosynthesis of [F-18]FCWAY by counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; preparative chromatography; FCWAY; methoxyphenyl piperazino-pyridinyl fluorocyclohexanecarboxamide ID 5-HT1A ANTAGONISTS AB Radiolabeled FCWAY (N-{2-[4-(2-methoxyphenyl)piperazino]}-N-(2-pyridinyl) trans-4-fluorocyclohexanecarboxamide) was prepared for human positron emission tomography (PET) studies by a simple one-step radiosynthesis. The LC-MS analysis of the products indicated that it contained impurities which may interfere with FCWAY uptake of 5-HT1A receptors and that these impurities were derived from an impurity originally present in the precursor preparation. Since preparative HPLC failed to resolve one of the impurities from the precursor, preparative-scale high-speed counter-current chromatography (HSCCC) was used for purification of this FCWAY precursor. A suitable two-phase solvent system composed of cyclohexane-ethyl acetate-methanol-water at a volume ratio of 1:1:1:1 or 4:5:4:5 was selected based on the partition coefficients of the precursor and impurity as determined by a LC-MS method. Using the second solvent ratio of 4:5:4:5 with the organic phase as a mobile phase, a 2.57 g amount of precursor preparation was successfully purified yielding 2.2 g of the pure precursor by a single run. (C) 2004 Elsevier B.V. All rights reserved. C1 NIH, PET Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ma, Y (reprint author), NIH, PET Dept, Warren Grant Magnuson Clin Ctr, 10 Ctr Dr MSC 1180,Bldg 10,Rm IC401, Bethesda, MD 20892 USA. EM yma@mail.cc.nih.gov NR 9 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 23 PY 2004 VL 1034 IS 1-2 BP 149 EP 153 DI 10.1016/j.chroma.2004.01.059 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 808NS UT WOS:000220576400016 PM 15116924 ER PT J AU Tie, YF Boross, PI Wang, YF Gaddis, L Hussain, AK Leshchenko, S Ghoshl, AK Louis, JM Harrison, RW Weber, IT AF Tie, YF Boross, PI Wang, YF Gaddis, L Hussain, AK Leshchenko, S Ghoshl, AK Louis, JM Harrison, RW Weber, IT TI High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV protease; crystal structure; drug resistance; catalysis ID VIRUS TYPE-1 PROTEASE; STRUCTURE-BASED DESIGN; SUBSTRATE; MUTATIONS; COMPLEX; MUTANTS; ENZYME; P-2-LIGANDS; MECHANISMS; INSIGHTS AB The compound UIC-94017 (TMC-114) is a second-generation HIV protease inhibitor with improved pharmacokinetics that is chemically related to the clinical inhibitor amprenavir. UIC-94017 is a broad-spectrum potent inhibitor active against HIV-1 clinical isolates with minimal cytotoxicity. We have determined the high-resolution crystal structures of UIC-94017 in complexes with wild-type HIV-1 protease (PR) and mutant proteases PRV82A and PRI84V that are common in drug-resistant HIV. The structures were refined at resolutions of 1.10-1.53 Angstrom. The crystal structures of PR and PRI84V with UIC-94017 ternary complexes show that the inhibitor binds to the protease in two overlapping positions, while the PRV82A complex had one ordered inhibitor. In all three structures, UIC-94017 forms hydrogen bonds with the conserved main-chain atoms of Asp29 and Asp30 of the protease. These interactions are proposed to be critical for the potency of this compound against HIV isolates that are resistant to multiple protease inhibitors. Other small differences were observed in the interactions of the mutants with UIC-94017 as compared to PR. PRV82A showed differences in the position of the main-chain atoms of residue 82 compared to PR structure that better accommodated the inhibitor. Finally, the 1.10 Angstrom resolution structure of PRV82A with UIC-94017 showed an unusual distribution of electron density for the catalytic aspartate residues, which is discussed in relation to the reaction mechanism. (C) 2004 Elsevier Ltd. All rights reserved. C1 Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, Debrecen, Hungary. Univ Illinois, Dept Chem, Chicago, IL 60607 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. EM iweber@gsu.edu FU NIGMS NIH HHS [GM53386, GM62920, R01 GM062920] NR 33 TC 136 Z9 144 U1 0 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 23 PY 2004 VL 338 IS 2 BP 341 EP 352 DI 10.1016/j.jmb.2004.02.052 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 813PN UT WOS:000220919100012 PM 15066436 ER PT J AU Pancrazio, JJ Kulagina, NV Shaffer, KM Gray, SA O'Shaughnessy, TJ AF Pancrazio, JJ Kulagina, NV Shaffer, KM Gray, SA O'Shaughnessy, TJ TI Sensitivity of the neuronal network biosensor to environmental threats SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article; Proceedings Paper CT Annual Conference on Toxicology and Risk Assessment CY APR 28-MAY 01, 2003 CL Fairborn, OH ID INDUCED POTASSIUM CURRENT; CELL-BASED BIOSENSORS; STRYCHNINE; RAT; CADMIUM; SYSTEM; SYNCHRONIZATION; RELEASE; SURFACE AB It is widely acknowledged that there is a critical need for broad-spectrum environmental threat detection. While cells/tissue-based biosensors have been discussed for many years as a means of meeting this critical need, these kinds of systems have met with logistic concerns, in particular with regard to stability. our group has been working with cultured neuronal networks, which have the capacity to respond to a wide range of neuroactive compounds and are sufficiently robust to be shipped to end users. The basis of operation involves extracellular recording using thin-film microelectrode arrays where spontaneous bioelectrical activity, that is, spike firing, can be monitored in a noninvasive manner conducive for potentially long-term measurements. This work describes the current status of our efforts for the fabrication of a portable biosensor that incorporates cultured neuronal networks grown over standardized microelectrode arrays. Based on our protocol for aqueous phase sample introduction under constant flow conditions, minimal variation in mean spike rate is observed, consistent with temporal stability, such that changes of >10% are readily distinguished. To demonstrate the capability of this system, changes are reported in mean spike rate and network synchronization resulting from exposure to different model environmental threats, cadmium and strychnine. The sensitivity of this assay approach and implications of the experimental findings for environmental threat detection are discussed. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. RP Pancrazio, JJ (reprint author), NINDS, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM pancrazj@ninds.nih.gov RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 27 TC 15 Z9 15 U1 2 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD APR 23 PY 2004 VL 67 IS 8-10 BP 809 EP 818 DI 10.1080/15287390490428279 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 814CI UT WOS:000220952400015 PM 15192870 ER PT J AU Strebel, K AF Strebel, K TI HIV-1 Vpu: Putting a channel to the TASK SO MOLECULAR CELL LA English DT Editorial Material ID KAPPA-B-ALPHA; BETA-TRCP; PROTEIN; RELEASE AB Vpu is an HIV-encoded protein that enhances virus release. Previously, this activity was correlated with an intrinsic ion channel activity of Vpu. In this issue of Molecular Cell, Hsu et al. (2004) propose an alternative mechanism: they suggest that Vpu functions by inhibiting another ion channel, TASK-1. C1 NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, 4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 6 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 23 PY 2004 VL 14 IS 2 BP 150 EP 152 DI 10.1016/S1097-2765(04)00205-9 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 815OK UT WOS:000221051400003 PM 15099514 ER PT J AU Nagaich, AK Walker, DA Wolford, R Hager, GL AF Nagaich, AK Walker, DA Wolford, R Hager, GL TI Rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling SO MOLECULAR CELL LA English DT Article ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; LASER CROSS-LINKING; MMTV PROMOTER; IN-VIVO; TRANSCRIPTION FACTORS; ESTROGEN-RECEPTOR; PROTEIN DYNAMICS; SWI/SNF COMPLEX; LIVING CELLS AB An ultrafast UV laser crosslinking assay has provided novel insights into the progression of the SWI/SNF-mediated chromatin-remodeling reaction and transcription factor binding in real time. We demonstrate site-specific crosslinking between the glucocorticoid receptor (GR), the hSWI/SNF chromatin-remodeling complex, and the mouse mammary tumor virus (MMTV) promoter assembled in an array of correctly positioned nucleosomes. GR first demonstrates rapid binding to the promoter and then is actively displaced from the template during the remodeling reaction. This displacement reaction requires the hSWI/SNF complex and ATIP, is specific to the nucleoprotein template, and is accompanied by a core histone rearrangement. The hSWI/SNF complex associates with random positions on the chromatin template in the absence of GR but is recruited specifically to the B/C region when GR is included. These results indicate that enhancement of hSWI/SNF-mediated factor accessibility, a hallmark of chromatin remodeling, is in some cases transient, reversible, and periodic. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602,41 Lib Dr, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov NR 49 TC 148 Z9 151 U1 1 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 APR 23 PY 2004 VL 14 IS 2 BP 163 EP 174 DI 10.1016/S1097-2765(04)00178-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 815OK UT WOS:000221051400005 PM 15099516 ER PT J AU Hsu, K Seharaseyon, J Dong, PH Bour, S Marban, E AF Hsu, K Seharaseyon, J Dong, PH Bour, S Marban, E TI Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel SO MOLECULAR CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BACKGROUND K+ CHANNEL; POTASSIUM CHANNEL; TRANSMEMBRANE SEGMENT; ENDOPLASMIC-RETICULUM; PARTICLE RELEASE; ENZYME APOBEC3G; PROTEIN VPU; BETA-TRCP; LONG QT AB Sequence analysis predicted significant structural homology between the HIV-1 accessory protein Vpu and the N-terminal region of TASK-1, a mammalian background K+ channel. If the homology resulted from molecular piracy during HIV-1 evolution, these two proteins may have important functional interactions. Here we demonstrate that TASK and Vpu physically interact in cultured cells and in AIDS lymphoid tissues. The functional consequences were potentially destructive for both components: Vpu abolished TASK-1 current, while overexpressing TASK led to a marked impairment of Vpu's ability to enhance viral particle release. Further, the first 40 amino acids of TASK-1 (part of the homology to Vpu) were capable of enhancing HIV-1 particle release. This virus-host interaction may influence HIV-1/AIDS progression, as well as electrical signaling in infected host tissues. C1 Johns Hopkins Univ, Sch Med, Inst Mol Cardiobiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Program Mol Biophys, Baltimore, MD 21218 USA. NIAID, Bioinformat Core Facil, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Marban, E (reprint author), Johns Hopkins Univ, Sch Med, Inst Mol Cardiobiol, Baltimore, MD 21205 USA. EM marban@jhmi.edu FU NHLBI NIH HHS [R37 HL 36957] NR 48 TC 95 Z9 95 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 23 PY 2004 VL 14 IS 2 BP 259 EP 267 DI 10.1016/S1097-2765(04)00183-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 815OK UT WOS:000221051400013 PM 15099524 ER PT J AU Budanov, AV Sablina, AA Feinstein, E Koonin, EV Chumakov, PM AF Budanov, AV Sablina, AA Feinstein, E Koonin, EV Chumakov, PM TI Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD SO SCIENCE LA English DT Article ID CYSTEINE-SULFINIC ACID; TUBERCULOSIS ALKYLHYDROPEROXIDASE AHPD; ALKYL HYDROPEROXIDE REDUCTASE; OXIDATIVE STRESS; NITROSATIVE STRESS; HYDROGEN-PEROXIDE; DEFENSE; IDENTIFICATION; OVEROXIDATION; INACTIVATION AB Acting as a signal, hydrogen peroxide circumvents antioxidant defense by over-oxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of Prxs containing Cys-SO2H, thus reestablishing the antioxidant firewall. Sestrins contain a predicted redox-active domain homologous to AhpD, the enzyme catalyzing the reduction of a bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine triphosphate-dependent reduction of over-oxidized Prxl in vitro, indicating that unlike AhpD, which is a disulfide reductase, sestrins are cysteine sulfinyl reductases. As modulators of peroxide signaling and antioxidant defense, sestrins constitute potential therapeutic targets. C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. VA Engelhardt Mol Biol Inst, Moscow 119991, Russia. Canc Res Ctr, Moscow 1154785, Russia. Quark Biotech Inc, IL-70400 Ness Ziona, Israel. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Chumakov, PM (reprint author), Cleveland Clin Fdn, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM chumakp@ccf.org NR 30 TC 410 Z9 430 U1 0 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 23 PY 2004 VL 304 IS 5670 BP 596 EP 600 DI 10.1126/science.1095569 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814LB UT WOS:000220975100052 PM 15105503 ER PT J AU Cai, LS Chin, FT Pike, VW Toyama, H Liow, JS Zoghbi, SS Modell, K Briard, E Shetty, HU Sinclair, K Donohue, S Tipre, D Kung, MP Dagostin, C Widdowson, DA Green, M Gao, W Herman, MM Ichise, M Innis, RB AF Cai, LS Chin, FT Pike, VW Toyama, H Liow, JS Zoghbi, SS Modell, K Briard, E Shetty, HU Sinclair, K Donohue, S Tipre, D Kung, MP Dagostin, C Widdowson, DA Green, M Gao, W Herman, MM Ichise, M Innis, RB TI Synthesis and evaluation of two F-18-labeled 6-iodo-2-(4 '-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine derivatives as prospective radioligands for beta-amyloid in Alzheimer's disease SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PLAQUES; BRAIN; BINDING; PET AB This study evaluated F-18-labeled IMPY [6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging beta-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Abeta-aggregates with K-i = 27 +/- 8 and 40 +/- 5 nM, respectively. A "one-pot" method for F-18-2-fluoroethylation and F-18-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26-51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [F-18]FEM-IMPY at 1.2 min, and 5.7% ID/g for [F-18]FPM-IMPY at 0.8 min. These values were similar to those of [I-123/I-123]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [F-18]FEM or [F-18]FPM-IMPY. In contrast to the single-exponential washout of [I-123/I-123]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [F-18] FEM-IMPY and 2.1% ID/g for [F-18]FPM-IMPY. Substantial skull uptake of [F-18]fluoride was also clearly observed. With a view to slow the metabolism of [F-18]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D-4-[F-18]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [F-18]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections of human Alzheimer's disease patients with [F-18]FEM-IMPY showed high displaceable uptake in gray matter and low nonspecific binding in the white matter. This study demonstrates that the IMPY derivatives have favorable in vivo brain pharmacokinetics and a moderate affinity for imaging beta-amyloid plaques; however, further improvements are needed to reduce radioactive metabolites, increase binding affinity, and reduce lipophilicity. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AY, England. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Cai, LS (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cail@intra.nimh.nih.gov FU Intramural NIH HHS [ZIA MH002795-12] NR 23 TC 69 Z9 73 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 22 PY 2004 VL 47 IS 9 BP 2208 EP 2218 DI 10.1021/jm030477w PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 813PH UT WOS:000220918500005 PM 15084119 ER PT J AU Lepper, ER Ng, SSW Gutschow, M Weiss, M Hauschildt, S Hecker, TK Luzzio, FA Eger, K Figg, WD AF Lepper, ER Ng, SSW Gutschow, M Weiss, M Hauschildt, S Hecker, TK Luzzio, FA Eger, K Figg, WD TI Comparative molecular field analysis and comparative molecular similarity indices analysis of thalidomide analogues as angiogenesis inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PARTIAL LEAST-SQUARES; PHASE-II TRIAL; TUMOR-GROWTH; IN-VITRO; CANCER; METABOLITES; COMFA AB Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been shown to require metabolic activation for antiangiogenic activity. A series of 39 compounds, based upon the structure of some of these metabolites, was synthesized and tested for their ability to inhibit microvessel growth in the rat aortic ring assay. The results of this testing have been used as the basis for a three-dimensional quantitative structure-activity relationship (3D-QSAR) study, utilizing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) procedures. The best resulting CoMFA and CoMSIA models have conventional r(2) values of 0.924 and 0.996, respectively. The cross-validated q(2) values are 0.666 and 0.635, respectively. These models offer insight into the structural requirements for activity of thalidomide analogues as angiogenesis inhibitors, since there is only speculative knowledge of the target. Additionally, it appears as though there is more than one active site or mechanism of action. C1 NCI, Mol Pharmacol Sect, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Res Core, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Bonn, Inst Pharmaceut, D-5300 Bonn, Germany. George Washington Univ, Sch Med, Ctr Canc Res, Childrens Res Inst, Washington, DC 20037 USA. George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20037 USA. Univ Leipzig, Inst Pharm Pharmaceut Chem, Leipzig, Germany. Univ Leipzig, Inst Zool, Dept Immunobiol, Leipzig, Germany. Univ Louisville, Dept Chem, Louisville, KY 40292 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Therapeut Branch, NIH, Bldg 10,Rm 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 23 TC 33 Z9 34 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 22 PY 2004 VL 47 IS 9 BP 2219 EP 2227 DI 10.1021/jm0304820 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 813PH UT WOS:000220918500006 PM 15084120 ER PT J AU Shen, M Beguin, C Golbraikh, A Stables, JP Kohn, H Tropsha, A AF Shen, M Beguin, C Golbraikh, A Stables, JP Kohn, H Tropsha, A TI Application of predictive QSAR models to database mining: Identification and experimental validation of novel anticonvulsant compounds SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID K-NEAREST-NEIGHBOR; ANTIEPILEPTIC DRUGS; DERIVATIVES; SELECTION; DESIGN; LIDOCAINE AB We have developed a drug discovery strategy that employs variable selection quantitative structure-activity relationship (QSAR) models for chemical database mining. The approach starts with the development of rigorously validated QSAR models obtained with the variable selection k nearest neighbor (kNN) method (or, in principle, with any other robust model-building technique). Model validation. is based on several statistical criteria, including the randomization of the target property (Y-randomization), independent assessment of the training set model's predictive power using external test sets, and the establishment of the model's applicability domain. All successful models are employed in database mining concurrently; in each case, only variables selected as a result of model building (termed descriptor pharmacophore) are used in chemical similarity searches comparing active compounds of the training set (queries) with those in chemical databases. Specific biological activity (characteristic of the training set compounds) of external database entries found to be within a predefined similarity threshold of the training set molecules is predicted on the basis of the validated QSAR models using the applicability domain criteria. Compounds judged to have high predicted activities by all or the majority of all models are considered as consensus hits. We report on the application of this computational strategy for the first time for the discovery of anticonvulsant agents in the Maybridge and National Cancer Institute (NCI) databases containing ca. 250 000 compounds combined. Forty-eight anticonvulsant agents of the functionalized amino acid (FAA) series were used to build kNN variable selection QSAR models. The 10 best models were applied to mining chemical databases, and 22 compounds were selected as consensus hits. Nine compounds were synthesized and tested at the NIH Epilepsy Branch, Rockville, MD using the same biological test that was employed to assess the anticonvulsant activity of the training set compounds; of these nine, four were exact database hits and five were derived from the hits by minor chemical modifications. Seven of these nine compounds were confirmed to be active, indicating an exceptionally high hit rate. The approach described in this report can be used as a general rational drug discovery tool. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. Univ Houston, Dept Chem, Houston, TX 77204 USA. NINDS, Epilepsy Branch, NIH, Rockville, MD 20852 USA. RP Kohn, H (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, CB 7360, Chapel Hill, NC 27599 USA. EM harold_kohn@unc.edu; alex_tropsha@unc.edu RI Tropsha, Alexander/G-6245-2014 FU NIGMS NIH HHS [GM66940] NR 39 TC 101 Z9 103 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 22 PY 2004 VL 47 IS 9 BP 2356 EP 2364 DI 10.1021/jm030584q PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 813PH UT WOS:000220918500020 PM 15084134 ER PT J AU Morrison, DK AF Morrison, DK TI Cancer - Enzymes play molecular tag SO NATURE LA English DT Editorial Material ID BRAF; MUTATIONS C1 NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. RP Morrison, DK (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. EM dmorrison@ncifcrf.gov NR 11 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 2004 VL 428 IS 6985 BP 813 EP + DI 10.1038/428813a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814CH UT WOS:000220952300026 PM 15103362 ER PT J AU Zhang, C Xiong, W Zheng, H Wang, LC Lu, B Zhou, Z AF Zhang, C Xiong, W Zheng, H Wang, LC Lu, B Zhou, Z TI Calcium- and dynamin-independent endocytosis in dorsal root ganglion neurons SO NEURON LA English DT Article ID ADRENAL CHROMAFFIN CELLS; TEMPERATURE-SENSITIVE MUTANT; SYNAPTIC VESICLE ENDOCYTOSIS; TRANSMITTER RELEASE; RECEPTOR INTERNALIZATION; DROSOPHILA-MELANOGASTER; HIPPOCAMPAL SYNAPSES; REVERSIBLE BLOCKAGE; NEUROTROPHIC FACTOR; MEMBRANE RETRIEVAL AB Synaptic vesicle endocytosis is believed to require calcium and the GTPase dynamin. We now report a form of rapid endocytosis (RE) in dorsal root ganglion (DRG) neurons that, unlike previously described forms of endocytosis, is independent of calcium and dynamin. The RE is tightly coupled to calcium-independent but voltage-dependent secretion (CIVDS). Using FM dye and capacitance measurements, we show that membrane depolarization induces RE in the absence of calcium. Inhibition of dynamin function does not affect RE. The magnitude of RE is proportional to that of preceding CIVDS and stimulation frequency. Inhibitors of protein kinase A (PKA) suppress RE induced by high-frequency depolarization, while PKA activators enhance RE induced by low-frequency depolarization. Biochemical experiments demonstrate that depolarization directly upregulates PKA activity in calcium-free medium. These results reveal a calcium- and dynamin-independent form of endocytosis, which is controlled by neuronal activity and PKA-dependent phosphorylation, in DRG neurons. C1 Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. NICHHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Zhou, Z (reprint author), Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. EM zzhou@ion.ac.cn RI zhou, zhuan/A-8285-2011; Wang, Shirong/G-1698-2011; Xiong, Wei/A-6170-2012; zheng, Hui/I-3573-2013 OI zheng, Hui/0000-0002-2504-9092 NR 51 TC 33 Z9 33 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 22 PY 2004 VL 42 IS 2 BP 225 EP 236 DI 10.1016/S0896-6273(04)00189-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 821KG UT WOS:000221458500008 PM 15091339 ER PT J AU Vourlekis, JS AF Vourlekis, JS TI Interferon gamma-1b for pulmonary fibrosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Vourlekis, JS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM vourlekj@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 22 PY 2004 VL 350 IS 17 BP 1795 EP 1795 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 814AJ UT WOS:000220947300031 ER PT J AU Doan, DN Veal, TM Yan, ZJ Wang, WD Jones, SN Imbalzano, AN AF Doan, DN Veal, TM Yan, ZJ Wang, WD Jones, SN Imbalzano, AN TI Loss of the INI1 tumor suppressor does not impair the expression of multiple BRG1-dependent genes or the assembly of SWI/SNF enzymes SO ONCOGENE LA English DT Article DE INI1; BRG1; SWI/SNF; tumor suppressor; gene regulation ID CHROMATIN-REMODELING COMPLEX; CELL-CYCLE ARREST; TRANSCRIPTIONAL ACTIVATORS; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID-RECEPTOR; MUSCLE DIFFERENTIATION; MULTISUBUNIT COMPLEX; ORDERED RECRUITMENT; INTERFERON-GAMMA; BINDING PROTEIN AB The INI1/hSNF5 tumor suppressor is an integral component of mammalian SWI/SNF chromatin remodeling enzymes that contain SNF2 family ATPases BRM (Brahma) or BRG1 (Brahma Related Gene 1) and that contribute to the regulation of many genes. Genetic studies of yeast SWI/SNF enzyme revealed similar phenotypes when single or multiple components of the enzyme were deleted, indicating a requirement for each subunit. To address the contribution of INI1 in the regulation of SWI/SNF-dependent genes in mammalian cells, we examined the expression of multiple BRG1-dependent, constitutively expressed genes in INI1-deficient cancer cell lines. At least one INI1-deficient line expressed each gene, and reintroduction of INI1 had negligible effects on expression levels. Lack of INI1 also did not prevent interferon gamma (IFNc)-mediated induction of CIITA, which is BRG1 dependent, and GBP-1, which is BRG1 enhanced, and reintroduction of INI1 had minimal effects. Chromatin immunoprecipitation experiments revealed that BRG1 inducibly binds to the CIITA promoter despite the absence of INI1. Unlike yeast deleted for the INI1 homologue, SWI/SNF enzymes in INI1-deficient cells were largely intact. Thus in human cells, SWI/SNF enzyme complex formation and the expression of many BRG1-dependent genes are independent of INI1. C1 Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Imbalzano, AN (reprint author), Univ Massachusetts, Sch Med, Dept Cell Biol, 55 Lake Ave N, Worcester, MA 01655 USA. EM anthony.imbalzano@umassmed.edu NR 73 TC 49 Z9 49 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 22 PY 2004 VL 23 IS 19 BP 3462 EP 3473 DI 10.1038/sj.onc.1207472 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 814LA UT WOS:000220975000021 PM 14990991 ER PT J AU Qian, XL Karpova, T Sheppard, AM McNally, J Lowy, DR AF Qian, XL Karpova, T Sheppard, AM McNally, J Lowy, DR TI E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases SO EMBO JOURNAL LA English DT Article DE cell growth; cell signaling; E-cadherin; MDCK cells; receptor tyrosine kinase ID GROWTH-FACTOR RECEPTOR; CELL-CELL ADHESION; BETA-CATENIN; EPITHELIAL-CELLS; FACTOR-I; PROTEIN; CONTACT; COMPLEX; INSULIN; EXPRESSION AB E-cadherin is an essential adhesion protein as well as a tumor suppressor that is silenced in many cancers. Its adhesion-dependent regulation of signaling has not been elucidated. We report that E-cadherin can negatively regulate, in an adhesion-dependent manner, the ligand-dependent activation of divergent classes of receptor tyrosine kinases (RTKs), by inhibiting their ligand-dependent activation in association with decreases in receptor mobility and in ligand-binding affinity. E-cadherin did not regulate a constitutively active mutant RTK (Neu*) or the ligand-dependent activation of LPA receptors or muscarinic receptors, which are two classes of G protein-coupled receptors. EGFR regulation by E-cadherin was associated with complex formation between EGFR and E-cadherin that depended on the extracellular domain of E-cadherin but was independent of beta-catenin binding or p120-catenin binding. Transfection of E-cadherin conferred negative RTK regulation to human melanoma and breast cancer lines with downregulated endogenous E-cadherin. Abrogation of E-cadherin regulation may contribute to the frequent ligand-dependent activation of RTK in tumors. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 4106, Bethesda, MD 20892 USA. EM drl@helix.nih.gov NR 46 TC 218 Z9 225 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 21 PY 2004 VL 23 IS 8 BP 1739 EP 1748 DI 10.1038/sj.emboj.7600136 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821YO UT WOS:000221499500007 PM 15057284 ER PT J AU Crotti, LB Basrai, MA AF Crotti, LB Basrai, MA TI Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae SO EMBO JOURNAL LA English DT Article DE CSE4; kinetochore; S. cerevisiae; silencing; SPT4 ID MITOTIC CHROMOSOME TRANSMISSION; ASSEMBLY FACTOR-I; CHROMATIN-REMODELING COMPLEX; RNA-POLYMERASE-II; BUDDING YEAST; TRANSCRIPTION ELONGATION; HISTONE VARIANT; GENE; DNA; VIVO AB The kinetochore (centromeric DNA and associated proteins) mediates the attachment of chromosomes to the mitotic spindle apparatus and is required for faithful chromosome transmission. We established that evolutionarily conserved Saccharomyces cerevisiae SPT4, previously identified in genetic screens for defects in chromosome transmission fidelity (ctf), encodes a new structural component of specialized chromatin at kinetochores and heterochromatic loci, with roles in kinetochore function and gene silencing. Using chromatin immunoprecipitation assays (ChIP), we determined that kinetochore proteins Ndc10p, Cac1p, and Hir1p are required for the association of Spt4p to centromeric (CEN) loci. Absence of functional Spt4p leads to altered chromatin structure at the CEN DNA and mislocalization of the mammalian CENP-A homolog Cse4p to noncentromeric loci. Spt4p associates with telomeres (TEL) and HMRa loci in a Sir3p-dependent manner and is required for transcriptional gene silencing. We show that a human homolog of SPT4 (HsSPT4) complements Scspt4-silencing defects and associates with ScCEN DNA in an Ndc10p-dependent manner. Our results highlight the evolutionary conservation of pathways required for genome stability in yeast and humans. C1 Natl Canc Inst, Genet Branch, Bethesda, MD 20889 USA. RP Basrai, MA (reprint author), Natl Canc Inst, Genet Branch, NNMC Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM basraim@nih.gov NR 65 TC 31 Z9 33 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 21 PY 2004 VL 23 IS 8 BP 1804 EP 1814 DI 10.1038/sj.emboj.7600161 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821YO UT WOS:000221499500013 PM 15057281 ER PT J AU Sharpe, S Kessler, N Anglister, JA Yau, WM Tycko, R AF Sharpe, S Kessler, N Anglister, JA Yau, WM Tycko, R TI Solid-state NMR yields structural constraints on the V3 loop from HIV-1 Gp120 bound to the 447-52D antibody Fv fragment SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PRINCIPAL NEUTRALIZING DETERMINANT; IMMUNODEFICIENCY-VIRUS TYPE-1; ANGLE-SPINNING NMR; ROTATING SOLIDS; CHEMICAL-SHIFT; CORRELATION SPECTROSCOPY; ENVELOPE GLYCOPROTEIN; MAGNETIC-RESONANCE; CRYSTAL-STRUCTURE; CONFORMATIONAL PREFERENCES AB Solid-state NMR measurements were performed on the complex of an 18-residue peptide derived from the V3 loop sequence of the gp120 envelope glycoprotein of the HIV-1 MN strain with Fv fragments of the human anti-gp120 monoclonal antibody 447-52D in a frozen glycerol/water solution. The peptide was uniformly N-15- and C-13-labeled in a 7-residue segment containing the conserved GPGR motif in the epitope. N-15 and C-13 NMR chemical shift assignments for the labeled segment were obtained from two-dimensional C-13-C-13 and N-15-C-13 magic-angle spinning NMR spectra. Reductions in C-13 NMR line widths and changes in chemical shifts upon complex formation indicate the adoption of a well-defined, antibody-dependent structure. Intramolecular C-13-C-13 distances in the complex, which constrain the peptide backbone and side chain conformations in the GPGR motif, were determined from an analysis of rotational resonance (RR) data. Structural constraints from chemical shifts and RR measurements are in good agreement with recent solution NMR and crystallographic studies of this system, although differences regarding structural ordering of certain peptide side chains are noted. These experiments explore and help delineate the utility of solid state NMR techniques as structural probes of peptide/protein complexes in general, potentially including membrane-associated hormone/receptor complexes. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM tycko@helix.nih.gov FU NIGMS NIH HHS [GM 53329] NR 80 TC 48 Z9 48 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 21 PY 2004 VL 126 IS 15 BP 4979 EP 4990 DI 10.1021/ja0392162 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 812OX UT WOS:000220849900048 PM 15080704 ER PT J AU Yan, JL Delaglio, F Kaerner, A Kline, AD Mo, HP Shapiro, MJ Smitka, TA Stephenson, GA Zartler, ER AF Yan, JL Delaglio, F Kaerner, A Kline, AD Mo, HP Shapiro, MJ Smitka, TA Stephenson, GA Zartler, ER TI Complete relative stereochemistry of multiple stereocenters using only residual dipolar couplings SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR MAGNETIC RESONANCE; HIGH-RESOLUTION NMR; HIGH-FIELD NMR; MOLECULAR ALIGNMENT; LIQUID-CRYSTALS; ABSOLUTE-CONFIGURATION; PHOSPHOLIPID MICELLES; HUMAN UBIQUITIN; PROTEIN NMR; SPECTROSCOPY AB Residual dipolar couplings (RDCs), in combination with molecular order matrix calculations, were used to unambiguously determine the complete relative stereochemistry of an organic compound with five stereocenters. Three simple one-dimensional experiments were utilized for the measurements of C-13-H-1, C-13-F-19, F-19-H-1, and H-1-H-1 RDCs. The order matrix calculation was performed on each chiral isomer independently. The fits were evaluated by the comparison of the root-mean-square deviation (rmsd) of calculated and measured RDCs. The order tensor simulations based on two different sets of RDC data collected with phage and bicelles are consistent. The resulting stereochemical assignments of the stereocenters obtained from using only RDCs are in perfect agreement with those obtained from the single-crystal X-ray structure. Six RDCs are found to be necessary to run the simulation, and seven are the minimum to get an acceptable result for the investigated compound. It was also shown that 13C-1H and H-1-H-1 RDCs, which are the easiest to measure, are also the most important and information-rich data for the order matrix calculation. The effect of each RDC on the calculation depends on the location of the corresponding vector in the structure. The direct RDC of a stereocenter is important to the configuration determination, but the configuration of stereocenters devoid of protons can also be obtained from analysis of nearby RDCs. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Discovery Chem Res & Technol, Indianapolis, IN 46285 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Lab, Lilly Corp Ctr, Pharmaceut Prod Dev, Indianapolis, IN 46285 USA. RP Shapiro, MJ (reprint author), Triad Therapeut Inc, 9381 Judicial Dr,Suite 200, San Diego, CA 92121 USA. EM shapiro_mike@lilly.com NR 50 TC 49 Z9 49 U1 4 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 21 PY 2004 VL 126 IS 15 BP 5008 EP 5017 DI 10.1021/ja037605q PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 812OX UT WOS:000220849900051 PM 15080707 ER PT J AU Scuteri, A Najjar, SS Muller, DC Andres, R Hougaku, H Metter, EJ Lakatta, EG AF Scuteri, A Najjar, SS Muller, DC Andres, R Hougaku, H Metter, EJ Lakatta, EG TI Metabolic syndrome amplifies the age-associated increases in vascular thickness and stiffness SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID INSULIN-RESISTANCE SYNDROME; INTIMA-MEDIA THICKNESS; DENSITY-LIPOPROTEIN CHOLESTEROL; CROSS-LINK BREAKER; MYOCARDIAL-INFARCTION; PULSE PRESSURE; AORTIC STIFFNESS; RISK-FACTOR; INDEPENDENT PREDICTOR; HYPERTENSIVE PATIENTS AB OBJECTIVES We sought to evaluate whether the clustering of multiple components of the metabolic syndrome (MS) has a greater impact on these vascular parameters than individual components of MS. BACKGROUND Intima-media thickness (IMT) and vascular stiffness have been shown to be independent predictors of adverse cardiovascular events. The MS is defined as the clustering of three or more of the cardiovascular risk factors of dysglycemia, hypertension, dyslipidemia, and obesity. METHODS Carotid IMT and stifness were derived via B-mode ultrasonography in 471 participants from the Baltimore Longitudinal Study on Aging, who were without clinical cardiovascular disease and not receiving antihypertensive therapy. RESULTS The MS conferred a disproportionate increase in carotid IMT (+16%, p < 0.0001) and stiffness (+32%, p < 0.0001), compared with control subjects. Multiple regression models, which included age, gender, smoking, low-density lipoprotein, as well as each individual component of MS as continuous variables, showed that MS was an independent determinant of both IMT (p = 0.002) and stiffness (p = 0.012). The MS was associated with a greater prevalence of subjects whose values were in the highest quartiles of IMT, stiffness, or both. CONCLUSIONS Even after taking into account each individual component of MS, the clustering of at least three of these components is independently associated with increased IMT and stifness. This suggests that the components of MS interact to synergistically impact vascular thickness and stifness. Future studies should examine whether the excess cardiovascular risk associated with MS is partly mediated through the amplified alterations in these vascular properties. (C) 2004 by the American College of Cardiology Foundation C1 NIA, Cardiovasc Sci Lab, Clin Invest Lab, Gerontol Res Ctr,Intramural Res Program,NIH, Baltimore, MD 21224 USA. INRCA, UO Geriatria, Rome, Italy. RP Scuteri, A (reprint author), NIA, Cardiovasc Sci Lab, Clin Invest Lab, Gerontol Res Ctr,Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Scuteria@grc.nia.nih.gov NR 58 TC 239 Z9 252 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 21 PY 2004 VL 43 IS 8 BP 1388 EP 1395 DI 10.1016/j.jacc.2003.10.061 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 813AW UT WOS:000220881000010 PM 15093872 ER PT J AU Domanski, M Proschan, M AF Domanski, M Proschan, M TI The metabolic syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID NUTRITION EXAMINATION SURVEY; PULSE PRESSURE; CARDIOVASCULAR MORBIDITY; NATIONAL-HEALTH; BLOOD-PRESSURE; RISK FACTOR; MORTALITY; DISEASE; ADULTS C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Domanski, M (reprint author), NHLBI, Clin Trials Grp, 6701 Rockledge Dr,Room 8146, Bethesda, MD 20892 USA. EM domanskm@nih.gov NR 20 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 21 PY 2004 VL 43 IS 8 BP 1396 EP 1398 DI 10.1016/j.jacc.2004.01.021 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 813AW UT WOS:000220881000011 PM 15093873 ER PT J AU Jaffe, ES AF Jaffe, ES TI Common threads of mucosa-associated lymphoid tissue lymphoma pathogenesis: From infection to translocation SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GASTRIC MALT LYMPHOMA; B-CELL LYMPHOMA; HELICOBACTER-PYLORI; CHLAMYDIA-TRACHOMATIS; FAS MUTATIONS; BCL10; T(11/18)(Q21,Q21); LYMPHOCYTES; APOPTOSIS; CARCINOMA C1 NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, 10 Ctr Dr,Bldg 10,Rm 2N202 MSC 1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov NR 23 TC 28 Z9 29 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 APR 21 PY 2004 VL 96 IS 8 BP 571 EP 573 DI 10.1093/jnci/djh138 PG 3 WC Oncology SC Oncology GA 813DD UT WOS:000220886900001 PM 15100327 ER PT J AU Kimm, SYS Glynn, NW Obarzanek, E Kriska, AM Daniels, SR Barton, BA Liu, K AF Kimm, SYS Glynn, NW Obarzanek, E Kriska, AM Daniels, SR Barton, BA Liu, K TI Levels of physical activity and changes in body mass index in black and white girls during adolescence SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NHLBI, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Maryland Med Res Inst, Baltimore, MD USA. Northwestern Univ, Sch Med, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 20 PY 2004 VL 109 IS 15 MA LB1 BP E187 EP E187 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 813KO UT WOS:000220906200021 ER PT J AU Kacinko, SL Barnes, AJ Kim, I Moolchan, ET Wilson, L Cooper, GA Reid, C Baldwin, D Hand, CW Huestis, MA AF Kacinko, SL Barnes, AJ Kim, I Moolchan, ET Wilson, L Cooper, GA Reid, C Baldwin, D Hand, CW Huestis, MA TI Performance characteristics of the Cozart (R) RapiScan oral fluid drug testing system for opiates in comparison to ELISA and GUMS following controlled codeine administration SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE opiates; SAMHSA; oral fluid; on-site tests ID GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; SALIVA; PLASMA; PHARMACOKINETICS; METHAMPHETAMINE; ABUSE AB Oral fluid is an interesting alternative matrix for drug testing in many environments, including law enforcement, workplace drug testing, and drug treatment facilities. Performance characteristics of the FDA-cleared, qualitative, Cozart(R) RapiScan Opiate Oral Fluid Drug Testing System (Opiate Cozar(R) RapiScan System or Opiate CRS) were compared to the semiquantitative Cozart(R) Microplate EIA Opiate Oral Fluid Kit (Opiate ELISA) and to gas chromatography/mass spectrometry (GC/MS). The following oral fluid opiate cutoffs were evaluated: the GC/MS limit of quantification (LOQ) of 2.5 mg/l; 15 mug/l currently used for oral fluid testing in the United Kingdom (UK); 30 mug/l (Opiate CRS cutoff); and 40 mug/l, the proposed Substance Abuse and Mental Health Services Administration (SAMHSA) cutoff. Subjects provided informed consent to participate in this IRB-approved research and resided on the closed research ward throughout the study. Three oral codeine doses of 60 mg/70 kg were administered over a 7-day period. After a 3-week break, subjects received three doses of 120 mg/70 kg within 7 days. Oral fluid specimens (N=1273) were analyzed for codeine (COD), norcodeine (NCOD), morphine (MOR) and normorphine (NMOR) by GC/MS with an LOQ of 2.5 mug/l for all analytes. MOR and NMOR were not detected in any sample; 26.5% of the specimens were positive for COD and 13.7% for NCOD. Opiate CRS uses a preset, qualitative cutoff of 10 mug/l; this is equivalent to 30 mug/l in undiluted oral fluid as the oral fluid collection process involves a 1:3 dilution with buffer. Sensitivity, specificity, and efficiency of Opiate CRS compared to Opiate ELISA were 98.6, 98.1, and 98.2% at a 30 mug/l cutoff and 99.0, 96.2, and 96.6% at a 40 mug/l cutoff. Compared to the much lower GC/MS LOQ of 2.5 mug/l, sensitivity, specificity and efficiency were 66.8, 99.3 and 90.7%. Increasing the GC/MS cutoff to the current UK level yielded performance characteristics of 81.5% (sensitivity), 99.3% (specificity), and 95.4% (efficiency). Using a GC/MS cutoff identical to the preset Opiate CRS cutoff yielded sensitivity, specificity, and efficiency of 88.5, 99.2, and 97.5%, respectively. At the proposed SAMSHA confirmation cutoff of 40 mug/l, sensitivity increased with little change in specificity and efficiency (91.3% sensitivity, 98.9% specificity, and 97.5% efficiency). Oral fluid is a suitable matrix for detecting drugs of abuse. Opiate CRS, with a 30 mug/l cutoff, is sufficiently sensitive, specific and efficient for oral fluid opiate analysis, performing similarly to Opiate ELISA at the same cutoff, and having performance characteristics >91% when compared to GC/MS at the proposed SAMHSA cutoff. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Cozart Biosci Ltd, Abingdon OX14 4RU, Oxon, England. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 18 TC 27 Z9 28 U1 0 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD APR 20 PY 2004 VL 141 IS 1 BP 41 EP 48 DI 10.1016/j.forsciint.2003.12.003 PG 8 WC Medicine, Legal SC Legal Medicine GA 814BG UT WOS:000220949600007 PM 15066713 ER PT J AU Qi, XX Li, TG Hao, J Hu, J Wang, J Simmons, H Miura, S Mishina, Y Zhao, GQ AF Qi, XX Li, TG Hao, J Hu, J Wang, J Simmons, H Miura, S Mishina, Y Zhao, GQ TI BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PRIMORDIAL GERM-CELLS; MOUSE EMBRYO; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; MAP KINASE; ES CELLS; DIFFERENTIATION; GASTRULATION; REQUIREMENT; EXPRESSION AB The fate of pluripotent stem cells is tightly controlled during early embryonic development. Both the derivation and the maintenance of embryonic stem cells (ES cells) in vitro depend on feeder cell-derived growth factors that are largely unidentified. To dissect the mechanisms governing pluripotency, we conducted a screen to identify factors that are produced by mouse embryonic fibroblast STO cells and are required to maintain the pluripotency of ES cells. One of the factors is bone morphogenetic protein 4 (BMP4). Unexpectedly, the major effect of BMP4 on the self-renewal of ES cells is accomplished by means of the inhibition of both extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways, and inhibitors of ERK and p38 MAPKs mimic the effect of BMP4 on ES cells. Importantly, inhibition of the p38 MAPK pathway by SB203580 overcomes the block in deriving ES cells from blastocysts lacking a functional Alk3, the BMP type IA receptor. These results uncover a paradigm for BMP signaling in the biology of pluripotent stem cells. C1 Univ Texas, SW Med Ctr, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Zhao, GQ (reprint author), Univ Texas, SW Med Ctr, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA. EM guang.zhao@utsouthwestern.edu FU NICHD NIH HHS [HD36218, R01 HD036218, HD39154, R29 HD036218] NR 45 TC 253 Z9 284 U1 1 U2 27 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 20 PY 2004 VL 101 IS 16 BP 6027 EP 6032 DI 10.1073/pnas.0401367101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814ME UT WOS:000220978000064 PM 15075392 ER PT J AU Gingrich, JR Pelkey, KA Fam, SR Huang, YQ Petralia, RS Wenthold, RJ Salter, MW AF Gingrich, JR Pelkey, KA Fam, SR Huang, YQ Petralia, RS Wenthold, RJ Salter, MW TI Unique domain anchoring of Src to synaptic NMDA receptors via the mitochondrial protein NADH dehydrogenase subunit 2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; BOVINE COMPLEX I; POSTSYNAPTIC DENSITY; TYROSINE PHOSPHORYLATION; HIPPOCAMPAL SYNAPSES; NITRIC-OXIDE; KINASE; MEMBRANE; APOPTOSIS; INDUCTION AB Src is the prototypic protein tyrosine kinase and is critical for controlling diverse cellular functions. Regions in Src define structural and functional domains conserved in many cell signaling proteins. Src also contains a region of low sequence conservation termed the unique domain, the function of which has until now remained enigmatic. Here, we show that the unique domain of Src is a protein-protein interaction region and we identify NADH dehydrogenase subunit 2 (ND2) as a Src unique domain-interacting protein. ND2 is a subunit of complex I in mitochondria, but we find that ND2 interacts with Src outside this organelle at excitatory synapses in the brain. ND2 acts as an adapter protein anchoring Src to the N-methyl-D-aspartate (NMDA) receptor complex, and is crucial for Src regulation of synaptic NMDA receptor activity. By showing an extramitochondrial action for a protein encoded in the mitochondrial genome, we identify a previously unsuspected means by which mitochondria regulate cellular function, suggesting a new paradigm that may be of general relevance for control of Src signaling. C1 Univ Toronto, Hosp Sick Children, Dept Physiol, Brain & Behav Program,Fac Med, Toronto, ON M5G 1X8, Canada. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Salter, MW (reprint author), Univ Toronto, Hosp Sick Children, Dept Physiol, Brain & Behav Program,Fac Med, Toronto, ON M5G 1X8, Canada. EM mike.salter@utoronto.ca NR 48 TC 77 Z9 82 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 20 PY 2004 VL 101 IS 16 BP 6237 EP 6242 DI 10.1073/pnas.0401413101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814ME UT WOS:000220978000100 PM 15069201 ER PT J AU Cai, HX Shoelson, B Chadwick, RS AF Cai, HX Shoelson, B Chadwick, RS TI Evidence of tectorial membrane radial motion in a propagating mode of a complex cochlear model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; INNER-EAR; HAIR CELL; STIFFNESS; REPRESENTATION; HEMICOCHLEA; MECHANICS; VIBRATION; PATTERN AB Knowledge of vibratory patterns in the cochlea is crucial to understanding the stimulation of mechanosensory cells. Experiments to determine the motion of the cochlear partition and surrounding fluid are extremely challenging. As a result, the motion data are incomplete and often contradictory. The bending mechanism of hair bundles, thought to be related to the shear motion and endolymphatic flow between the tectorial membrane (TM) and reticular lamina (RL), is controversial. We, therefore, extend the frequency range of our previous hybrid analytical-finite-element approach to model the basal as well as apical regions of the guinea pig cochlea. We solve the fluid-solid interaction eigenvalue problem for the axial wavenumber, fluid pressure, and vibratory relative motions of the cochlear partition as a function of frequency. A simple monophasic vibratory mode of the basilar membrane is found at both ends of the cochlea. However, this simple movement is associated with a complex frequency-dependent relative deformation between the TM and the RL. We provide evidence of a radial component of TM motion that is out of phase with the RL and that facilitates the bending of outer hair cell stereocilia at appropriate frequencies at both the cochlear base and apex. C1 Natl Inst Deafness & Other Commun Disorders, Sect Audit Mech, NIH, Bethesda, MD 20892 USA. RP Chadwick, RS (reprint author), Bldg 10,Room 5D-49,MSC 1417,10 Ctr Dr, Bethesda, MD 20892 USA. EM chadwick@helix.nih.gov NR 40 TC 35 Z9 36 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 20 PY 2004 VL 101 IS 16 BP 6243 EP 6248 DI 10.1073/pnas.0401395101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814ME UT WOS:000220978000101 PM 15067120 ER PT J AU Hirasawa, M Ohshima, T Takahashi, S Longenecker, G Honjo, Y Veeranna Pant, HC Mikoshiba, K Brady, RO Kulkarni, AB AF Hirasawa, M Ohshima, T Takahashi, S Longenecker, G Honjo, Y Veeranna Pant, HC Mikoshiba, K Brady, RO Kulkarni, AB TI Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; DIRECTED PROTEIN-KINASE; CDC2-LIKE KINASE; P35; PHOSPHORYLATION; MICE; CEREBELLUM; ACTIVATOR; SUBUNIT; GENE AB Cyclin-dependent kinase 5 (Cdk5) is essential for the proper development of the CNS, as is evident from the perinatal lethality of conventional Cdk5 knockout (Cdk5-/-) mice. Cdk5 is also implicated in numerous complex functions of the adult CNS such as synaptic transmission, synaptic plasticity, and neuronal signaling. To elucidate the molecular roles of Cdk5 in the adult CNS, we have abrogated neuronal expression of Cdk5 in perinatal mice by using a cre-loxP system. The Cdk5-loxP flanked mice were crossed with the cre-transgenic mice in which the cre expression is driven by the murine neurofilament-heavy chain promoter, resulting in generation of viable Cdk5 conditional knockout mice with the restricted deletion of the Cdk5 gene in specific neurons beginning around embryonic day 16.5. Twenty-five percent of the Cdk5 conditional knockout mice carrying the heterozygous cre allele had neuronal migration defects confined to brain areas where neuronal migration continues through the perinatal period. These results indicate that abrogation of Cdk5 expression in mature neurons results in a viable mouse model that offers further opportunities to investigate the molecular roles of Cdk5 in the adult CNS. C1 Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. RIKEN, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama 3510198, Japan. Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, 30 Convent Dr,Bldg 30,Room 527, Bethesda, MD 20892 USA. EM ak40m@nih.gov RI Mikoshiba, Katsuhiko/N-7943-2015 NR 26 TC 30 Z9 31 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 20 PY 2004 VL 101 IS 16 BP 6249 EP 6254 DI 10.1073/pnas.0307322101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814ME UT WOS:000220978000102 PM 15067135 ER PT J AU Sparreboom, A Kehrer, DFS Mathijssen, RHJ Xie, R de Jonge, MJA de Bruijn, P Planting, T Eskens, FALM Verheij, C de Heus, G Klaren, A Zhang, S Verhaeghe, T Palmer, PA Verweij, J AF Sparreboom, A Kehrer, DFS Mathijssen, RHJ Xie, R de Jonge, MJA de Bruijn, P Planting, T Eskens, FALM Verheij, C de Heus, G Klaren, A Zhang, S Verhaeghe, T Palmer, PA Verweij, J TI Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor SO BRITISH JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CA SP Amer Soc Clin Oncol DE irinotecan ( CPT-II); R115777 (tipifamib); phase I; farnesyl protein transferase inhibitor; pharmacokinetics ID CLINICAL PHARMACOKINETICS; ADVANCED CANCER; RAS PROTEIN; METABOLISM; THERAPY; FARNESYLTRANSFERASE; DISCOVERY AB The aims of this study were to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of irinotecan given with oral R115777 (tipifarnib), a farnesyl protein transferase inhibitor. Patients were treated with escalating doses of irinotecan with interval-modulated dosing of R115777 (continuously or on days 1-14, and repeated every 21 days). In total, 35 patients were entered onto the trial for a median duration of treatment of 43 days (range, 5-224 days). Neutropenia and thrombocytopenia were the dose-limiting toxicities; other side effects were mostly mild. The MTD was established at R115777 300 mg b.i.d. for 14 consecutive days with irinotecan 350 mg m(-2) given every 3 weeks starting on day 1. Three patients had a partial response and 14 had stable disease. In the continuous schedule, the area under the curves of irinotecan and its active metabolite SN-38 were 20.0% (P = 0.004) and 38.0% (P < 0.001) increased by R115777, respectively. Intermittent dosing of R115777 at a dose of 300 mg b.i.d. for 14 days every 3 weeks is the recommended dose of R115777 in combination with the recommended single-agent irinotecan dose of 350 mg m(-2). C1 Dr Daniel den Hoed Canc Ctr, Erasmus MC, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands. Uppsala Univ, Dept Pharmaceut Biosci, SE-75124 Uppsala, Sweden. Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM SparrebA@mail.mih.gov RI Sparreboom, Alex/B-3247-2008 NR 38 TC 14 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 19 PY 2004 VL 90 IS 8 BP 1508 EP 1515 DI 10.1038/sj.bjc.6601732 PG 8 WC Oncology SC Oncology GA 816SI UT WOS:000221129200008 PM 15083177 ER PT J AU Blancato, J Singh, B Liu, A Liao, DJ Dickson, RB AF Blancato, J Singh, B Liu, A Liao, DJ Dickson, RB TI Correlation of amplification and overexpression of the c-myc oncogene in high-grade breast cancer: FISH, in situ hybridisation and immunohistochemical analyses SO BRITISH JOURNAL OF CANCER LA English DT Article DE c-myc; breast cancer; gene amplification; gene expression ID MAMMARY-GLAND CARCINOGENESIS; CLINICAL-SIGNIFICANCE; GENE AMPLIFICATION; DNA AMPLIFICATION; TESTICULAR CANCER; PROGNOSTIC MARKER; BCL-2 EXPRESSION; UVEAL MELANOMA; CARCINOMA; PRODUCT AB In this study, we analysed gene amplification, RNA expression and protein expression of the c-myc gene on archival tissue specimens of high-grade human breast cancer, using fluorescent in situ hybridisation (FISH), nonradioactive in situ hybridisation and immunohistochemistry. The specific question that we addressed was whether expression of c-Myc mRNA and protein were correlated with its gene copy amplification, as determined by FISH. Although c-Myc is one of the most commonly amplified oncogenes in human breast cancer, few studies have utilised in situ approaches to directly analyse the gene copy amplification, RNA transcription and protein expression on human breast tumour tissue sections. We now report that by using the sensitive FISH technique, a high proportion (70%) of high-grade breast carcinoma were amplified for the c-myc gene, irrespective of status of the oestrogen receptor. However, the level of amplification was low, ranging between one and four copies of gene gains, and the majority (84%) of the cases with this gene amplification gained only one to two copies. Approximately 92% of the cases were positive for c-myc RNA transcription, and essentially all demonstrated c-myc protein expression. In fact, a wide range of expression levels were detected. Statistically significant correlations were identified among the gene amplification indices, the RNA expression scores and protein expression scores. c-myc gene amplification, as detected by FISH, was significantly associated with expression of its mRNA, as measured by the intensity of in situ hybridisation in invasive cells ( P=0.0067), and by the percentage of invasive cells positive for mRNA expression (P=0.0006). c-myc gene amplification was also correlated with the percentage of tumour cells which expressed high levels of its protein, as detected by immunohistochemistry in invasive cells (P=0.0016). Thus, although multiple mechanisms are known to regulate normal and aberrent expression of c-myc, in this study, where in situ methodologies were used to evaluate high-grade human breast cancers, gene amplification of c-myc appears to play a key role in regulating expression of its mRNA and protein. C1 Inst Mol & Human Genet, Washington, DC 20007 USA. Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. Wayne State Univ, Kamanos Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. RP Blancato, J (reprint author), Inst Mol & Human Genet, 3970 Reservoir Rd NW, Washington, DC 20007 USA. EM blancatj@georgetown.edu OI Liu, Aiyi/0000-0002-6618-5082 FU NCI NIH HHS [R01 CA72460, R01 CA072460]; NIA NIH HHS [AG1496] NR 41 TC 66 Z9 68 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 19 PY 2004 VL 90 IS 8 BP 1612 EP 1619 DI 10.1038/sj.bjc.6601703 PG 8 WC Oncology SC Oncology GA 816SI UT WOS:000221129200025 PM 15083194 ER PT J AU Bondy, CA Cheng, CM AF Bondy, CA Cheng, CM TI Signaling by insulin-like growth factor 1 in brain SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE insulin; metabolism; akt; GSK3 beta (glycogen synthase kinase 3 beta); tau; ketogenic diet ID GROWTH-FACTOR-I; TRANSPORTER GENE-EXPRESSION; SYNTHASE KINASE 3-BETA; RAT-BRAIN; FACTOR RECEPTOR; IGF-I; NUTRITIONAL REGULATION; TAU-PHOSPHORYLATION; GLUCOSE-METABOLISM; DENDRITIC GROWTH AB The homologous insulin and insulin-like growth factor (IGF) receptors are both expressed in the brain, in overlapping but distinct neuroanatomical patterns. In contrast to insulin, IGF1 is also highly expressed within the brain and is essential for normal brain development. IGF1 promotes projection neuron growth, dendritic arborization and synaptogenesis. IGF1 acts in ail autocrine and/or paracrine manner to promote glucose utilization, using phosphatidylinositol 3 kinase (PI3K)/Akt, also known as protein kinase B (PKB)/glycogen synthase kinase 3beta (GSK3beta) pathways similar to insulin signaling in peripheral tissues. IGF1 promotes neuronal survival during normal brain development mainly in hippocampal and olfactory systems that depend on postnatal neurogenesis. IGF1's anabolic and neuroprotective roles may be coordinated by inhibition of GSK3beta. The identification of GSK3beta as a major target of brain IGF1 signaling provides a unifying pathway for IGF1's well-established anabolic and anti-apoptotic functions, with IGF1-induced inhibition of GSK3beta triggering multifaceted anabolic and neuroprotective effects. (C) 2004 Elsevier B.V. All rights reserved. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@exchange.nih.gov NR 40 TC 207 Z9 215 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 19 PY 2004 VL 490 IS 1-3 BP 25 EP 31 DI 10.1016/j.ejphar.2004.02.042 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 815YL UT WOS:000221077500004 PM 15094071 ER PT J AU Zhao, WQ Chen, H Quon, MJ Alkon, DL AF Zhao, WQ Chen, H Quon, MJ Alkon, DL TI Insulin and the insulin receptor in experimental models of learning and memory SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Review DE insulin receptor; learning and memory; signal transduction; receptor trafficking; diabetes mellitus; Alzheimer's disease ID CENTRAL-NERVOUS-SYSTEM; LONG-TERM POTENTIATION; BLOOD-BRAIN-BARRIER; HIPPOCAMPAL SYNAPTIC PLASTICITY; DEPENDENT DIABETIC-PATIENTS; VASCULAR ENDOTHELIAL-CELLS; AMYLOID PRECURSOR PROTEIN; GLUCOSE-TRANSPORTER GLUT4; APOLIPOPROTEIN-E GENOTYPE; GROWTH-FACTOR-I AB Insulin is best known for its action on peripheral insulin target tissues such as the adipocyte, muscle and liver to regulate glucose horneostasis. In the central nervous system (CNS), insulin and the insulin receptor are found in specific brain regions where they show evidence of participation in a variety of region-specific functions through mechanisms, that are different from its direct glucose regulation in the periphery. While the insulin/insulin receptor associated with the hypothalamus plays important roles in regulation of the body energy homeostasis, the hippocampus- and cerebral cortex-distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. Emerging evidence has suggested that insulin signaling plays a role in synaptic plasticity by modulating activities of excitatory and inhibitory receptors such as glutamate and GABA receptors, and by triggering signal transduction cascades leading to alteration of gene expression that is required for long-term memory consolidation. Furthermore, deterioration of insulin receptor signaling appears to be associated with aging-related brain degeneration such as the Alzheimer's dementia and cognitive impairment in aged subjects suffering type 2 diabetes mellitus. (C) 2004 Elsevier B.V. All rights reserved. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. NCCAM, LCI, Diabet Unit, NIH, Bethesda, MD 20862 USA. RP Zhao, WQ (reprint author), Blanchette Rockefeller Neurosci Inst, 3rd Floor,Acad & Res Bldg,9601 Med Ctr Dr, Rockville, MD 20850 USA. EM zhaow@brni-jhu.org RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 126 TC 244 Z9 253 U1 4 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 19 PY 2004 VL 490 IS 1-3 BP 71 EP 81 DI 10.1016/j.ejphar.2004.02.045 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 815YL UT WOS:000221077500007 PM 15094074 ER PT J AU Wei, Y Zhang, TY Ito, YC AF Wei, Y Zhang, TY Ito, YC TI Preparative isolation of osthol and xanthotoxol from Common Cnidium Fruit (Chinese traditional herb) using stepwise elution by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; preparative chromatography; pharmaceutical analysis; cnidium monnieri; osthol; xanthotoxol ID SEPARATION; PRODUCTS AB Preparative high-speed counter-current chromatography (HSCCC) was successfully used for isolation and purification of osthol and xanthotoxol from Cnidium monnieri (L.) Cusson (Common Cnidium Fruit) using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1:1:1:1, v/v), and (5:5:6:4, v/v), which had been selected by analytical high-speed counter-current chromatography. Using a preparative unit of the HSCCC centrifuge, about a 308 mg amount of the crude extract was separated, yielding 88.3 mg of osthol and 19.4 mg of xanthotoxol at a high purity of over 98%. (C) 2004 Elsevier B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China. RP Ito, YC (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3334, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov NR 11 TC 63 Z9 71 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 18 PY 2004 VL 1033 IS 2 BP 373 EP 377 DI 10.1016/j.chroma.2004.01.058 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 805XL UT WOS:000220398900023 PM 15088761 ER PT J AU Kaneuchi, M Sasaki, M Tanaka, Y Shiina, H Verma, M Ebina, Y Nomura, E Yamamoto, R Sakuragi, N Dahiya, R AF Kaneuchi, M Sasaki, M Tanaka, Y Shiina, H Verma, M Ebina, Y Nomura, E Yamamoto, R Sakuragi, N Dahiya, R TI Expression and methylation status of 14-3-3 sigma gene can characterize the different histological features of ovarian cancer SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE 14-3-3 sigma; clear cell adenocarcinoma ID BREAST-CANCER; EARLY EVENT; FREQUENT; HYPERMETHYLATION; INACTIVATION; CARCINOMA; SIGMA; CELLS; ADENOCARCINOMA; PROGRESSION AB We hypothesize that 14-3-3 sigma gene expression and its regulation by methylation can characterize histological types of primary human epithelial ovarian cancer. To test this hypothesis, ovarian cancer cell lines and 54 ovarian cancer tissue samples were analyzed for expression and methylation of 14-3-3 sigma gene using methylation specific PCR. The results of our experiments demonstrate that 14-3-3 sigma gene was methylated and inactivated in ES-2 ovarian cell line, which was derived from clear cell adenocarcinoma. Treatment of this cell line with demethylating agent 5-aza-2'-deoxycytidine restored the expression of 14-3-3 sigma gene. In human ovarian cancer tissues, the expression of 14-3-3 sigma protein was inactivated in most of the ovarian clear cell carcinoma tissues. Interestingly, 14-3-3 sigma protein expression was positive in significantly higher percentages of serous (89.5%), endometrioid (90%), and mucinous (81.8%) ovarian adenocarcinoma tissues. The ovarian clear cell carcinoma samples with inactivated 14-3-3 sigma protein were highly methylated, suggesting that inactivation of 14-3-3 sigma gene is through DNA methylation. Using direct DNA sequencing, 14-3-3 sigma gene methylation on all the 17 CpG sites was significantly higher in ovarian clear cell carcinoma as compared to other histological types of ovarian cancer (serous, endometrioid, and mucinous). This is the first report suggesting that 14-3-3 sigma gene expression and methylation status can characterize histological features of different types of ovarian cancer. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Hokkaido Univ, Sch Med, Dept Obstet & Gynecol, Sapporo, Hokkaido 0608638, Japan. NCI, NIH, Rockville, MD USA. RP Dahiya, R (reprint author), Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. EM urologylab@aol.com RI Sakuragi, Noriaki/D-6507-2012 NR 20 TC 40 Z9 45 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 16 PY 2004 VL 316 IS 4 BP 1156 EP 1162 DI 10.1016/j.bbrc.2004.02.171 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 808OV UT WOS:000220579300028 PM 15044106 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, EA Brown, PL TI Brain temperature fluctuations during passive vs. active cocaine administration: clues for understanding the pharmacological determination of drug-taking behavior SO BRAIN RESEARCH LA English DT Article DE brain temperature; neural activation; goal-directed behavior; motivational arousal; addiction; rat ID VENTRAL TEGMENTAL AREA; RESPONSE-INDEPENDENT COCAINE; POSITRON-EMISSION-TOMOGRAPHY; NUCLEUS-ACCUMBENS; BLOOD-FLOW; EXTRACELLULAR DOPAMINE; INTRAVENOUS COCAINE; GLUCOSE-UTILIZATION; SEXUAL INTERACTION; UNRESTRAINED RATS AB While it is generally assumed that cocaine self-administration (SA) is determined and maintained by the pharmacological actions of cocaine in the brain, it is also a drug-motivated and drug-reinforced goal-directed behavior, which is determined by concurrent learning and behavioral performance. To dissociate the contributions of pharmacological and behavioral factors to cocaine SA, it is important to compare cocaine SA with its pharmacological copy, passive intravenous (iv) cocaine administration. This approach was employed in the present study with respect to brain temperatures, a dynamic parameter that reflects metabolic neural activity and shows consistent fluctuations during cocaine SA. Passive cocaine injections performed with the same dose/pattern as SA induced brain temperature fluctuations similar in many ways to those in behaving animals. The initial passive drug administration of a session elevated brain temperature, while subsequent repeated injections were associated with biphasic temperature fluctuations that maintained at a relatively stable plateau. Although the magnitude of these fluctuations was twofold smaller than in behaving animals, passive animals had the same pattern; brain temperatures transiently decreased after cocaine injection, then increased, and were inhibited again by the next cocaine infusion. In contrast to self-administering animals, rats exposed to passive cocaine injections had significantly lower basal temperatures and never showed gradual temperature increases preceding the initial injection. Striking differences in brain temperature dynamics seen in the beginning of a session suggest that during the development of drug-taking behavior the initial cocaine-induced neural activation becomes transformed into behavior-related "anticipatory" neural activation (motivational arousal) that fuels drug seeking and results in the initial drug intake. While this activation is triggered by drug-related cues and enhanced by the initial cocaine intake, subsequent highly cyclical cocaine intakes appear to be primarily pharmacologically determined. Published by Elsevier B.V. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 75 TC 17 Z9 17 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 16 PY 2004 VL 1005 IS 1-2 BP 101 EP 116 DI 10.1016/j.brainres.2004.01.038 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 814IX UT WOS:000220969500013 PM 15044070 ER PT J AU Gladwin, MT Schechter, AN AF Gladwin, MT Schechter, AN TI NO contest - Nitrite versus S-nitroso-hemoglobin SO CIRCULATION RESEARCH LA English DT Editorial Material DE nitric oxide; hemoglobin; S-nitroso-hemoglobin; iron-nitrosyl-hemoglobin; nitrite ID RED-BLOOD-CELLS; HUMAN PLASMA; PHYSIOLOGICAL CONDITIONS; OXIDE BIOAVAILABILITY; HUMAN CIRCULATION; OXYGEN-BINDING; SERUM-ALBUMIN; INHALED NO; IN-VIVO; NITROSOHEMOGLOBIN C1 NIDDK, NIH, Biol Chem Lab, Dept Crit Care Med,CC, Bethesda, MD 20892 USA. NHLBI, NIH, Cardiovasc Branch, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIDDK, NIH, Biol Chem Lab, Dept Crit Care Med,CC, Bldg 10-7D43,10 Ctr Dr, Bethesda, MD 20892 USA. EM mgladwin@cc.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 54 TC 55 Z9 58 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 16 PY 2004 VL 94 IS 7 BP 851 EP 855 DI 10.1161/01.RES.0000126697.64381.37 PG 5 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 816MG UT WOS:000221113400001 PM 15087423 ER PT J AU Shiraishi, I Melendez, J Ahn, Y Skavdahl, M Murphy, E Welch, S Schaefer, E Walsh, K Rosenzweig, A Torella, D Nurzynska, D Kajstura, J Leri, A Anversa, P Sussman, MA AF Shiraishi, I Melendez, J Ahn, Y Skavdahl, M Murphy, E Welch, S Schaefer, E Walsh, K Rosenzweig, A Torella, D Nurzynska, D Kajstura, J Leri, A Anversa, P Sussman, MA TI Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes SO CIRCULATION RESEARCH LA English DT Article DE Akt; apoptosis; nuclear; cardiomyocytes; transgenic ID PROTEIN-TYROSINE-PHOSPHATASE; FORKHEAD TRANSCRIPTION FACTOR; GROWTH-FACTOR-I; NF-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; PROMOTES CELL-SURVIVAL; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSGENIC MICE; FACTOR AFX; CARDIAC MYOCYTES AB Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent studies by our group have found accumulation of activated Akt in the nucleus, suggesting that biologically relevant target(s) of Akt activity may be located there. To test this hypothesis, a targeted Akt construct was created to determine the antiapoptotic action of nuclear Akt accumulation. Nuclear localization of the adenovirally encoded Akt construct was confirmed by confocal microscopy. Cardiomyocytes expressing nuclear-targeted Akt showed no evidence of morphological remodeling such as altered myofibril density or hypertrophy. Nuclear-targeted Akt significantly elevated levels of phospho-Akt and kinase activity and inhibited apoptosis as effectively as myristolated-Akt in hypoxia-induced cell death. Transgenic overexpression of nuclear-targeted Akt did not result in hypertrophic remodeling, altered cardiomyocyte DNA content or nucleation, or enhanced phosphorylation of typical cytoplasmic Akt substrates, yet transgenic hearts were protected from ischemia-reperfusion injury. Gene array analyses demonstrated changes in the transcriptional profile of Akt/nuc hearts compared with nontransgenic controls distinct from prior characterizations of Akt expression in transgenic hearts. Collectively, these experiments show that targeting of Akt to the nucleus mediates inhibition of apoptosis without hypertrophic remodeling, opening new possibilities for therapeutic applications of nuclear-targeted Akt to inhibit cell death associated with heart disease. C1 San Diego State Univ, SDSU Heart Inst, San Diego, CA 92182 USA. San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. New York Med Coll, Cardiovasc Res Inst, Valhalla, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Biosource Int, Hopkinton, MA USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp Res Fdn, Div Mol Cardiovasc Biol, Cincinnati, OH USA. RP Sussman, MA (reprint author), San Diego State Univ, SDSU Heart Inst, 5500 Campanile Dr, San Diego, CA 92182 USA. EM sussman@sciences.sdsu.edu RI Nurzynska, Daria/A-2161-2010; OI TORELLA, Daniele/0000-0002-4915-5084 FU NHLBI NIH HHS [HL66035, HL58224, HL67245] NR 57 TC 148 Z9 155 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 16 PY 2004 VL 94 IS 7 BP 884 EP 891 DI 10.1161/01.RES.0000124394.01180.BE PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 816MG UT WOS:000221113400007 PM 14988230 ER PT J AU Isaacs, JS Jung, YJ Neckers, L AF Isaacs, JS Jung, YJ Neckers, L TI Aryl hydrocarbon nuclear translocator (ARNT) promotes oxygen-independent stabilization of hypoxia-inducible factor-1 alpha by modulating an Hsp90-dependent regulatory pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HELIX-LOOP-HELIX; TUMOR-SUPPRESSOR PROTEIN; TRANSCRIPTION FACTOR; MOLECULAR CHAPERONE; DIOXIN RECEPTOR; HIF-ALPHA; HSP90; COMPLEX; IDENTIFICATION; DEGRADATION AB Hypoxia-inducible factor-1 (HIF-1) is a potent cellular survival factor contributing to tumorigenesis in a broad range of cancers. The functional transcription factor exists as a heterodimeric complex consisting of HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Association of HIF-1 with ARNT is required for its activity; however, no other role has been ascribed to this interaction. We demonstrated previously that pharmacologic inhibition of Hsp90 by geldanamycin (GA) impairs HIF transcription and promotes VHL ((V) under bar on (H) under bar ippel-(L) under bar indau)-independent degradation of the protein, thus implicating Hsp90 as an essential interacting partner for HIF. In this study, we further explore the physiological role for Hsp90 in HIF function. We establish that the PAS ((P) under bar er-(A) under bar RNT-(S) under bar im) domain of HIF is required both to promote association with Hsp90 and confer sensitivity to GA. Coincidentally, this domain also associates with ARNT. Overexpression of ARNT in a VHL-deficient background resulted in substantially increased HIF-1 protein concomitant with increased protein stability. Conversely, down-regulation of endogenous ARNT protein by RNA interference decreased the steady-state HIF protein. ARNT-mediated stabilization of HIF is specific for the Hsp90-dependent pathway, as ARNT was unable to protect HIF from VHL-mediated degradation. We establish that the ability of ARNT to up-regulate HIF and diminish HIF sensitivity to GA is due to its ability to compete for the Hsp90 binding site on HIF. These data elucidate novel functions for ARNT and Hsp90 in regulating HIF function and further illustrate that cofactor association may significantly impact upon the sensitivity of Hsp90 clients to chaperone inhibitors. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Rockville, MD 20850 USA. RP Isaacs, JS (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 9610 Med Ctr Dr,KWC Ste 300, Rockville, MD 20850 USA. EM isaacsj@mail.nih.gov; len@helix.nih.gov NR 33 TC 56 Z9 59 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 16 PY 2004 VL 279 IS 16 BP 16128 EP 16135 DI 10.1074/jbc.M313342200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 811BR UT WOS:000220747900054 PM 14764593 ER PT J AU Karai, LJ Russell, JT Iadarola, MJ Olah, Z AF Karai, LJ Russell, JT Iadarola, MJ Olah, Z TI Vanilloid receptor 1 regulates multiple calcium compartments and contributes to Ca2+-induced Ca2+ release in sensory neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DORSAL-ROOT GANGLION; PROTEIN-KINASE-C; CAPSAICIN-INDUCED DESENSITIZATION; ENDOPLASMIC-RETICULUM; RUTHENIUM RED; DIRECT PHOSPHORYLATION; INTRACELLULAR CALCIUM; SYMPATHETIC NEURONS; CHANNEL ACTIVITY; NERVE-FIBERS AB Vanilloid receptor 1 belongs to the transient receptor potential ion channel family and transduces sensations of noxious heat and inflammatory hyperalgesia in nociceptive neurons. These neurons contain two vanilloid receptor pools, one in the plasma membrane and the other in the endoplasmic reticulum. The present experiments characterize these two pools and their functional significance using calcium imaging and Ca-45 uptake in stably transfected cells or dorsal root ganglion neurons. The plasma membrane localized receptor is directly activated by vanilloids. The endoplasmic reticulum pool was demonstrated to be independently activated with 20 muM capsaicin or 1.6 muM resiniferatoxin using a bathing solution containing 10 muM Ruthenium Red (to selectively block plasma membrane-localized receptors) and 100 muM EGTA. We also demonstrate an overlap between the endoplasmic reticulum-localized vanilloid receptor regulated stores and thapsigargin-sensitive stores. Direct depletion of calcium via activation of endoplasmic reticulum-localized vanilloid receptor 1 triggered store operated calcium entry. Furthermore, we found that, in the presence of low extracellular calcium (10(-5) M), either 2 muM capsaicin or 0.1 nM- 1.6 muM resiniferatoxin caused a pronounced calcium-induced calcium release in either vanilloid receptor-expressing neurons or heterologous expression systems. This phenomenon may allow new insight into how nociceptive neuron function in response to a variety of nociceptive stimuli both acutely and during prolonged nociceptive signaling. C1 NIDCR, Neuronal Gene Express Unit, Pain & Neurosurg Mech Branch, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. RP Olah, Z (reprint author), NIDCR, Neuronal Gene Express Unit, Pain & Neurosurg Mech Branch, NIH, Bldg 49,Rm 1A19,49 Convent Dr,MSC-4410, Bethesda, MD 20892 USA. EM zoltan.olah@nih.gov NR 67 TC 71 Z9 74 U1 1 U2 1 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 16 PY 2004 VL 279 IS 16 BP 16377 EP 16387 DI 10.1074/jbc.M310891200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 811BR UT WOS:000220747900084 PM 14963041 ER PT J AU Greene, EC Mizuuchi, K AF Greene, EC Mizuuchi, K TI Visualizing the assembly and disassembly mechanisms of the MuB transposition targeting complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACTERIOPHAGE-MU; B-PROTEIN; STRAND-TRANSFER; PHAGE-MU; DNA; IMMUNITY; REFLECTS; PATHWAY; FORM; ENDS AB MuB, a protein essential for replicative DNA transposition by the bacteriophage Mu, is an ATPase that assembles into a polymeric complex on DNA. We used total internal reflection fluorescence microscopy to observe the behavior of MuB polymers on single molecules of DNA. We demonstrate that polymer assembly is initiated by a stochastic nucleation event. After nucleation, polymer assembly occurs by a mechanism involving the sequential binding of small units of MuB. MuB that bound to A/T-rich regions of the DNA assembled into large polymeric complexes. In contrast, MuB that bound outside of the A/T-rich regions failed to assemble into large oligomeric complexes. Our data also show that MuB does not catalyze multiple rounds of ATP hydrolysis while remaining bound to DNA. Rather, a single ATP is hydrolyzed, then MuB dissociates from the DNA. Finally, we show that "capping" of the enhanced green fluorescent protein-MuB polymer ends with unlabeled MuB dramatically slows, but does not halt, dissociation. This suggests that MuB dissociation occurs through both an end-dependent mechanism and a slower mechanism wherein subunits dissociate from the polymer interior. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Rm 237,5 Ctr Dr MSC0540, Bethesda, MD 20892 USA. EM kmizu@helix.nih.gov NR 19 TC 15 Z9 15 U1 1 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 16 PY 2004 VL 279 IS 16 BP 16736 EP 16743 DI 10.1074/jbc.M311883200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 811BR UT WOS:000220747900126 PM 14871890 ER PT J AU Abrahamsen, MS Templeton, TJ Enomoto, S Abrahante, JE Zhu, G Lancto, CA Deng, MQ Liu, C Widmer, G Tzipori, S Buck, GA Xu, P Bankier, AT Dear, PH Konfortov, BA Spriggs, HF Iyer, L Anantharaman, V Aravind, L Kapur, V AF Abrahamsen, MS Templeton, TJ Enomoto, S Abrahante, JE Zhu, G Lancto, CA Deng, MQ Liu, C Widmer, G Tzipori, S Buck, GA Xu, P Bankier, AT Dear, PH Konfortov, BA Spriggs, HF Iyer, L Anantharaman, V Aravind, L Kapur, V TI Complete genome sequence of the apicomplexan, Cryptosporidium parvum SO SCIENCE LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; ENTAMOEBA-HISTOLYTICA; ESCHERICHIA-COLI; EIMERIA-TENELLA; PROTEIN; SYNTHASE AB The apicomplexan Cryptosporidium parvum is an intestinal parasite that affects healthy humans and animals, and causes an unrelenting infection in immunocompromised individuals such as AIDS patients. We report the complete genome sequence of C. parvum, type II isolate. Genome analysis identifies extremely streamlined metabolic pathways and a reliance on the host for nutrients. In contrast to Plasmodium and Toxoplasma, the parasite lacks an apicoplast and its genome, and possesses a degenerate mitochondrion that has lost its genome. Several novel classes of cell-surface and secreted proteins with a potential role in host interactions and pathogenesis were also detected. Elucidation of the core metabolism, including enzymes with high similarities to bacterial and plant counterparts, opens new avenues for drug development. C1 Univ Minnesota, Coll Vet Med, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. Univ Minnesota, Biomed Genom Ctr, St Paul, MN 55108 USA. Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. Cornell Univ, Weill Grad Sch Med Sci, Program Immunol, New York, NY 10021 USA. Texas A&M Univ, Coll Vet Med, Dept Vet Pathobiol, College Stn, TX 77843 USA. Tufts Univ, Sch Vet Med, Div Infect Dis, North Grafton, MA 01536 USA. Virginia Commonwealth Univ, Ctr Study Biol Complex, Richmond, VA 23198 USA. Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23198 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. RP Abrahamsen, MS (reprint author), Univ Minnesota, Coll Vet Med, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. EM abe@umn.edu RI ZHU, GUAN/D-8147-2011; Dear, Paul/A-1162-2012; Kapur, Vivek/F-7610-2013; OI Anantharaman, Vivek/0000-0001-8395-0009; Kapur, Vivek/0000-0002-9648-0138 FU NIAID NIH HHS [U01 AI 46397] NR 27 TC 517 Z9 563 U1 7 U2 56 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 16 PY 2004 VL 304 IS 5669 BP 441 EP 445 DI 10.1126/science.1094786 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 812NE UT WOS:000220845400049 PM 15044751 ER PT J AU Waidyanatha, S Rothman, N Li, GL Smith, MT Yin, SN Rappaport, SM AF Waidyanatha, S Rothman, N Li, GL Smith, MT Yin, SN Rappaport, SM TI Rapid determination of six urinary benzene metabolites in occupationally exposed and unexposed subjects SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID S-PHENYLMERCAPTURIC ACID; TRANS-MUCONIC ACID; TRANS,TRANS-MUCONIC ACID; ENVIRONMENTAL EXPOSURE; LIQUID CHROMATOGRAPHY; BIOLOGICAL INDICATOR; MASS-SPECTROMETRY; CIGARETTE SMOKERS; LIVER-MICROSOMES; CHINESE WORKERS AB A gas chromatography-mass spectrometry method for measurement of the main urinary metabolites of benzene, namely, phenol, catechol, hydroquinone, 1,2,4-trihydroxybenzene (trihydroxybenzene), t,t-muconic acid (muconic acid), and S-phenylmercapturic acid (phenylmercapturic acid), is reported. The method is considerably simpler than existing assays. It was applied to urine from benzene-exposed subjects and controls from Shanghai, China. When subjects were divided into controls (n = 44), those exposed to less than or equal to31 ppm benzene (n = 21), and those exposed to >31 ppm benzene (n = 19), Spearman correlations with exposure category were greater than or equal to0.728 (p < 0.0001) for all metabolites except trihydroxybenzene. When exposed subjects were compared on an individual basis, all metabolites, including trihydroxybenzene, were significantly correlated with benzene exposure (Pearson r greater than or equal to 0.472, p less than or equal to 0.002) and with each other (Pearson r greater than or equal to 0.708, p < 0.0001). Ratios of individual metabolite levels to total metabolite levels provided evidence of competitive inhibition of CYP 2E1 enzymes leading to increased production of phenol, catechol, and phenyhmercapturic acid at the expense of hydroquinone, trihydroxybenzene, and muconic acid. Since all metabolites were detected in all control subjects, the method can be applied to persons exposed to environmental levels of benzene. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Prevent Med, Inst Occupat Med, Beijing, Peoples R China. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. EM smr@unc.edu FU NIEHS NIH HHS [P30ES10126, P42ES04705, P42ES05948, P50ES01896, R01ES06721] NR 66 TC 66 Z9 70 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2004 VL 327 IS 2 BP 184 EP 199 DI 10.1016/j.ab.2004.01.008 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 811SI UT WOS:000220791200006 PM 15051535 ER PT J AU Woods, AS Ugarov, M Egan, T Koomen, J Gillig, KJ Fuhrer, K Gonin, M Schultz, JA AF Woods, AS Ugarov, M Egan, T Koomen, J Gillig, KJ Fuhrer, K Gonin, M Schultz, JA TI Lipid/peptide/nucleotide separation with MALDI-ion mobility-TOF MS SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; GAS-PHASE; CHROMATOGRAPHY; PROTEOME; PEPTIDES AB Matrix-assisted laser desorption/ionization when combined with ion mobility-orthogonal time-of-flight mass spectrometry is a viable technique for fast separation and analysis of biomolecules in complex mixtures. Isobaric lipid, peptide, and oligonucleotide ions are preseparated before mass analysis by differences of up to 30% in mobility drift time. Ions of similar chemical type fall along well-defined "trend lines" (with deviations of similar to3%) when plotted in two-dimensional representations of ion mobility as a function of m/z. Discussion of fundamental and technical limitations of the technique point to its potential for being most useful when applied to systems such as bodily fluids and intact tissue, where an alternative chemical or chromatographic preseparation step prior to mass analysis is either impractical or undesirable. C1 NIDA, IRP, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, IRP, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov RI Koomen, John/D-1844-2013 FU NIDA NIH HHS [N44DA-3-7727]; NIGMS NIH HHS [2 R44 GM57736-02] NR 26 TC 83 Z9 84 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 15 PY 2004 VL 76 IS 8 BP 2187 EP 2195 DI 10.1021/ac035376k PG 9 WC Chemistry, Analytical SC Chemistry GA 816FW UT WOS:000221096800005 PM 15080727 ER PT J AU Valizadeh, M Schenk, G Nash, K Oddie, GW Guddat, LW Hume, DA de Jersey, J Burke, TR Hamilton, S AF Valizadeh, M Schenk, G Nash, K Oddie, GW Guddat, LW Hume, DA de Jersey, J Burke, TR Hamilton, S TI Phosphotyrosyl peptides and analogues as substrates and inhibitors of purple acid phosphatases SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE purple acid phosphatase; tartrate resistant acid phosphatase; inhibition and kinetic studies; phosphotyrosyl peptide; osteoporosis ID SOLID-PHASE SYNTHESIS; PIG ALLANTOIC FLUID; BOVINE SPLEEN; SWEET-POTATO; CRYSTAL-STRUCTURE; ACTIVE-SITE; FE-MN; DERIVATIVES; UTEROFERRIN; MECHANISM AB Purple acid phosphatases are metal-containing hydrolases. While their precise biological role(s) is unknown, the mammalian enzyme has been linked in a variety of biological circumstances (e.g., osteoporosis) with increased bone resorption. Inhibition of the human enzyme is a possible strategy for the treatment of bone-resorptive diseases such as osteoporosis. Previously, we determined the crystal structure of pig purple acid phosphatase to 1.55 Angstrom and we showed that it is a good model for the human enzyme. Here, a study of the pH dependence of its kinetic parameters showed that the pig enzyme is most efficient at pH values similar to those encountered in the osteoclast resorptive space. Based on the observation that phosphotyrosine-containing peptides are good substrates for pig purple acid phosphatase, peptides containing a range of phosphotyrosine mimetics were synthesized. Kinetic analysis showed that they act as potent inhibitors of mammalian and plant purple acid phosphatases, with the best inhibitors exhibiting low micromolar inhibition constants at pH 3-5. These compounds are thus the most potent organic inhibitors yet reported for the purple acid phosphatases. (C) 2004 Published by Elsevier Inc. C1 Univ Queensland, Dept Biochem, St Lucia, Qld 4072, Australia. Univ Queensland, Dept Chem, St Lucia, Qld 4072, Australia. Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia. NIH, Div Basic Sci, Med Chem Lab, Bethesda, MD 20892 USA. RP Hamilton, S (reprint author), Univ Queensland, Dept Biochem, St Lucia, Qld 4072, Australia. EM susan.hamilton@mailbox.uq.edu.au RI Nash, Kevin/B-4567-2009; Hume, David/C-7695-2013; Burke, Terrence/N-2601-2014; OI Nash, Kevin/0000-0002-8607-1832; Guddat, Luke/0000-0002-8204-8408; Schenk, Gerhard/0000-0001-8619-0631 NR 46 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 15 PY 2004 VL 424 IS 2 BP 154 EP 162 DI 10.1016/j.abb.2004.01.008 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 810RP UT WOS:000220721700005 PM 15047187 ER PT J AU Langford, CA Talar-Williams, C Sneller, MC AF Langford, CA Talar-Williams, C Sneller, MC TI Mycophenolate mofetil for remission maintenance in the treatment of Wegener's granulomatosis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE Wegener's granulomatosis; mycophenolate mofetil; remission maintenance ID RENAL-TRANSPLANTATION; INDUCED OSTEOPOROSIS; ACUTE REJECTION; THERAPY; METHOTREXATE; VASCULITIS; PREVENTION; EXPERIENCE; PREDNISONE; INDUCTION AB Objective. To examine the safety of mycophenolate mofetil (MMF) for remission maintenance in patients with Wegener's granulomatosis (WG) who had been treated with daily cyclophosphamide (CYC) and glucocorticoids to induce remission. Methods. Fourteen patients were treated for active WG using a standardized regimen of CYC and glucocorticoids for induction of remission and MMF for remission maintenance. Outcome was assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. Results. Remission occurred in all 14 patients (100%) at a median time of 3 months. The median time to discontinuation of glucocorticoids was 8 months. No patients died during protocol treatment and 6 patients (43%) relapsed at a median of 10 months after achieving remission. MMF was well tolerated and no patients had to be withdrawn as a result of medication toxicity. Conclusion. The use of CYC and glucocorticoids for induction of remission and MMF for remission maintenance was well tolerated, but disease relapses were observed. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM clangford@niaid.nih.gov NR 28 TC 108 Z9 120 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2004 VL 51 IS 2 BP 278 EP 283 DI 10.1002/art.20240 PG 6 WC Rheumatology SC Rheumatology GA 811IC UT WOS:000220764600021 PM 15077273 ER PT J AU Charney, DS AF Charney, DS TI Psychobiological mechanisms of resilience and vulnerability to extreme stress: Relevance to prevention and treatment of anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, MADRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 3 BP 1S EP 1S DI 10.1016/j.biopsych.2004.02.016 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300005 ER PT J AU Newhouse, PA Swedo, SE Angold, A Sherwin, B Seidman, S AF Newhouse, PA Swedo, SE Angold, A Sherwin, B Seidman, S TI Hormones and gender across the lifecycle: Influences on psychopathology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Vermont, Clin Neurosci Res Unit, Burlington, VT 05405 USA. NIMH, Pediat & Dev Neuropsychiat Br, Bethesda, MD 20892 USA. Duke Univ, Ctr Dev Epidemiol, Durham, NC 27706 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Columbia Univ, New York, NY 10027 USA. RI Newhouse, Paul/J-4597-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 7 BP 2S EP 3S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300009 ER PT J AU Vawter, MP Segal, E Lempicki, R Mootha, VK AF Vawter, MP Segal, E Lempicki, R Mootha, VK TI Integrating functional genomics for identification of candidate genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Calif Irvine, Irvine, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. NCI, NIH, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21701 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 8 BP 3S EP 3S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300010 ER PT J AU Enoch, MA Robin, RW Ernst, M Goldman, D AF Enoch, MA Robin, RW Ernst, M Goldman, D TI Anxiety: Expressions and origins SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NIMH, Sect Dev & Affect Neurosci, MAP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 12 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300014 ER PT J AU Monk, CS Masten, CL McClure, EB Nelson, EE Zarahn, E Blair, RJR van Mitchell, DG Woldehawariat, G Leibenluft, E Charney, DS Ernst, M Pine, DS AF Monk, CS Masten, CL McClure, EB Nelson, EE Zarahn, E Blair, RJR van Mitchell, DG Woldehawariat, G Leibenluft, E Charney, DS Ernst, M Pine, DS TI Symptom-relevant cognitive measures in development: A foundation for linking neurophysiology to psychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 14 BP 5S EP 5S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300016 ER PT J AU Barr, CS Dvoskin, RL Newman, TK Suomi, SJ Higley, JD AF Barr, CS Dvoskin, RL Newman, TK Suomi, SJ Higley, JD TI CRH gene promoter variation influences LHPA-axis activity in infant rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, Clin Studies Lab, NIH, Poolesville, MD USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 32 BP 10S EP 10S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300034 ER PT J AU Schloesser, RJ Benninghoff, J Zhang, L Gritti, A Vescovi, AL Manji, HK AF Schloesser, RJ Benninghoff, J Zhang, L Gritti, A Vescovi, AL Manji, HK TI Effects of HDAC inhibiton on neural prognitor cells in vitro SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. Hosp San Raffaele, DIBIT, Stem Cell Res Inst, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 42 BP 12S EP 13S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300044 ER PT J AU Casanova, MF Araque, J Giedd, JN Rumsey, JM AF Casanova, MF Araque, J Giedd, JN Rumsey, JM TI Reduced brain size and gyrification in the brains of dyslexic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Louisville, Louisville, KY 40292 USA. Med Coll Georgia, Augusta, GA 30912 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, 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 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 51 BP 15S EP 15S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300053 ER PT J AU Easter, JS Dhanani, M Hodgdon, HB Milham, MP Rakow, A McClure, EB Charney, DS Pine, DS Ernst, M AF Easter, JS Dhanani, M Hodgdon, HB Milham, MP Rakow, A McClure, EB Charney, DS Pine, DS Ernst, M TI Facial expression processing as a functional correlate of amygdala volume in youth with anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 54 BP 16S EP 16S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300056 ER PT J AU Lissek, S Powers, AS Phelps, EA Grillon, C Woldehawariat, G McClure, EB Pine, DS AF Lissek, S Powers, AS Phelps, EA Grillon, C Woldehawariat, G McClure, EB Pine, DS TI Classical fear-conditioning in the anxiety disorders: A meta-analysis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. St Johns Univ, Dept Psychol, Jamaica, NY 11439 USA. NYU, Dept Psychol, New York, NY 10003 USA. RI Lissek, Shmuel/B-6577-2008 NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 57 BP 17S EP 17S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300059 ER PT J AU Hendler, T Mendelsohn, A Bleich, M Pianka, P Cohen, Y Even, R Harari, H Strous, R Assaf, Y AF Hendler, T Mendelsohn, A Bleich, M Pianka, P Cohen, Y Even, R Harari, H Strous, R Assaf, Y TI White matter abnormalities in schizophrenia studied by high b value diffusion MRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Inst Mental Hlth, NIH, Bethesda, MD USA. Tel Aviv Sourasky Med Ctr, Funct Brain Imaging Lab, Tel Aviv, Israel. Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 68 BP 20S EP 20S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300070 ER PT J AU Marenco, S Pierpaoli, C Rohde, GK Honea, RA Barnett, AS Weinberger, DR AF Marenco, S Pierpaoli, C Rohde, GK Honea, RA Barnett, AS Weinberger, DR TI DTI measures are insensitive to the effect of neuroleptics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, CBDB, Bethesda, MD 20892 USA. NICHD, STBB, Bethesda, MD USA. RI Marenco, Stefano/A-2409-2008; Pierpaoli, Carlo/E-1672-2011 OI Marenco, Stefano/0000-0002-2488-2365; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 70 BP 21S EP 21S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300072 ER PT J AU Cardoso, G Schmidt, PJ Daly, RC Haq, NA Hanton, L Ross, JL Nelson, LM Rubinow, DR Bondy, CA AF Cardoso, G Schmidt, PJ Daly, RC Haq, NA Hanton, L Ross, JL Nelson, LM Rubinow, DR Bondy, CA TI Mood disorders, shyness, and social anxiety in women with Turner syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Behav Endocrinol Branch, DHHS, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, DHHS, NIH, Bethesda, MD USA. Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 100 BP 29S EP 29S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300102 ER PT J AU Khine, K Schmidt, PJ Kim, HY Gibson, C Nieman, L Rubinow, DR AF Khine, K Schmidt, PJ Kim, HY Gibson, C Nieman, L Rubinow, DR TI Neurosteroids in PMS during endocrine clamp SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Behav Endocrinol Branch, DHHS, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Mass Spectrometry, LMBB, DHHS,NIH, Rockville, MD 20852 USA. NICHD, Dev Endocrinol Branch, DHHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 99 BP 29S EP 29S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300101 ER PT J AU Zhou, RL Gray, NA Yuan, PX Du, J Zhang, L Williams, PD Chen, G Manji, HK AF Zhou, RL Gray, NA Yuan, PX Du, J Zhang, L Williams, PD Chen, G Manji, HK TI Microarray studies reveal a novel target for the long-term treatment of bipolar disorder: The anti-apoptotic, glucocorticoid receptor chaperone protein, BAG-1 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 106 BP 31S EP 31S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300108 ER PT J AU Jarskog, LF Stroup, TS Alamy, SS Sheitman, BB Hamer, RM Knable, MB Manji, HK Lieberman, JA AF Jarskog, LF Stroup, TS Alamy, SS Sheitman, BB Hamer, RM Knable, MB Manji, HK Lieberman, JA TI Tamoxifen as adjunctive therapy in treatment-refractory schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Duke Univ, Durham, NC 27706 USA. Stanley Med Res Inst, Bethesda, MD USA. NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 143 BP 41S EP 41S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300145 ER PT J AU Singh, J Zarate, CA Quiroz, JA Payne, JL Denicoff, KD Charney, DS Manji, HK AF Singh, J Zarate, CA Quiroz, JA Payne, JL Denicoff, KD Charney, DS Manji, HK TI Pramipexole for bipolar II depression: A placebo-controlled proof of concept study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Expt Therapeut & Pathophysiol Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 144 BP 41S EP 42S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300146 ER PT J AU Bobb, AJ Sporn, AL Greenstein, DK Clasen, LS Stevens, H Gogtay, N Tossell, J Gochman, PA Sharp, WS Lenane, MC Yanovski, JA Rapoport, JL AF Bobb, AJ Sporn, AL Greenstein, DK Clasen, LS Stevens, H Gogtay, N Tossell, J Gochman, PA Sharp, WS Lenane, MC Yanovski, JA Rapoport, JL TI Weight gain related hormones in children treated with clozapine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008; Stevens, Hanna/M-4104-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 145 BP 42S EP 42S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300147 ER PT J AU Insel, TR AF Insel, TR TI Epigenetic mechanisms of behavior: Where nurture meets nature SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 155 BP 45S EP 45S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300157 ER PT J AU Sokolov, BP AF Sokolov, BP TI Methylation and differential expression of the C and T alleles of the serotonin 5-HT2A receptor gene SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIDA, DHHS, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 156 BP 45S EP 45S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300158 ER PT J AU Blier, P Szabo, S Haddjeri, N Richer, M Hen, R Dong, JM AF Blier, P Szabo, S Haddjeri, N Richer, M Hen, R Dong, JM TI Alteration of 5-HT1A-autoreceptor function by antidepressant treatments: Electrophysiological findings SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Florida, Gainesville, FL 32611 USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Lyon 1, F-69365 Lyon, France. Columbia Univ, New York, NY 10027 USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. RI Haddjeri, Nasser/M-6377-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 158 BP 46S EP 46S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300160 ER PT J AU Giedd, JN AF Giedd, JN TI Genetic and nongenetic influence on pre and post pubertal brain development in twins SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Child Psychiat Branch, 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 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 162 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300164 ER PT J AU Gogtay, N AF Gogtay, N TI Brain development in childhood onset psychotic illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 165 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300167 ER PT J AU Rapoport, JL Giedd, JN AF Rapoport, JL Giedd, JN TI Brain imaging in ADHD children SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Child Psychiat Branch, 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 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 164 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300166 ER PT J AU Lopez, V Detera-Wadleigh, S Akula, N Murphy, DL McMahon, FJ AF Lopez, V Detera-Wadleigh, S Akula, N Murphy, DL McMahon, FJ TI Bipolar disorder, suicide, and genetic variation in TPH2 and SERT SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, IRP, Clin Sci Lab, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 218 BP 62S EP 63S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300220 ER PT J AU Bachmann, RF Du, J Chen, J Gray, NA Yuan, PX Manji, HK AF Bachmann, RF Du, J Chen, J Gray, NA Yuan, PX Manji, HK TI Mood stabilizers enhance mitochondrial function through increased Bcl-2 expression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 231 BP 66S EP 66S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300233 ER PT J AU Alim, TN Graves, E Robertson, J Aigbogun, N Hamilton, J Williams, B Brisbane, E Smith, B Lawson, WB Charney, DS AF Alim, TN Graves, E Robertson, J Aigbogun, N Hamilton, J Williams, B Brisbane, E Smith, B Lawson, WB Charney, DS TI Psychopathology in African Americans exposed to trauma SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Howard Univ, Washington, DC 20059 USA. NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RI Alim, Tanya/M-5623-2016 OI Alim, Tanya/0000-0001-6334-8758 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 241 BP 68S EP 69S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300242 ER PT J AU Ernst, M Nelson, EE Monk, CS McClure, EB Pine, DS Charney, DS Blair, RJR Leibenluft, E Jazbec, S Munson, S AF Ernst, M Nelson, EE Monk, CS McClure, EB Pine, DS Charney, DS Blair, RJR Leibenluft, E Jazbec, S Munson, S TI Decision-making and responses to reinforcements from a neurodevelopmental and psychopathology perspective SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, DHHS, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 239 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300240 ER PT J AU Enoch, MA Waheed, JF Harris, CR Goldman, D AF Enoch, MA Waheed, JF Harris, CR Goldman, D TI The influence of COMT Val158Met genotype on alcoholism, smoking and anxiety in an American Indian tribe SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, LNG, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 244 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300245 ER PT J AU Deep-Soboslay, A Weickert, CS Hyde, TM Herman, MM Straub, RE Weinberger, DR Kleinman, JE Lipska, BK AF Deep-Soboslay, A Weickert, CS Hyde, TM Herman, MM Straub, RE Weinberger, DR Kleinman, JE Lipska, BK TI Selection criteria for establishing a brain collection to study gene expression in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 278 BP 79S EP 79S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300278 ER PT J AU Lawson, WB Willis, T Neumeister, A Charney, DS AF Lawson, WB Willis, T Neumeister, A Charney, DS TI Recruitment of African American normal volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Howard Univ, Washington, DC 20059 USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 284 BP 80S EP 81S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300284 ER PT J AU Bonne, O Krausz, Y Lester, H Levin, T Freedman, N Chisin, R Lerer, B AF Bonne, O Krausz, Y Lester, H Levin, T Freedman, N Chisin, R Lerer, B TI Cerebral perfusion in major depression and hypothyroidism before and after treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 302 BP 85S EP 85S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300301 ER PT J AU Moses-Kolko, EL Price, JC Thase, ME Kupfer, DJ Mathis, CA Bogers, WD Berman, SR Drevets, WC AF Moses-Kolko, EL Price, JC Thase, ME Kupfer, DJ Mathis, CA Bogers, WD Berman, SR Drevets, WC TI 5HT(1A) receptor binding potential in depression using PET and [C-11]WAY-100635 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RI Mathis, Chester/A-8607-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 303 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300302 ER PT J AU Bain, EE Neumeister, A Martinez, PE Gold, PW Listwak, S Haim, A Williams, J Gordon, J Charney, DS Drevets, WC AF Bain, EE Neumeister, A Martinez, PE Gold, PW Listwak, S Haim, A Williams, J Gordon, J Charney, DS Drevets, WC TI Cerebrospinal fluid measures of CRH and ACTH in remitted subjects with major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 309 BP 87S EP 87S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300307 ER PT J AU Luff, JA Schmidt, PJ Daly, RC Haq, NA Vanderhoof, VH Nelson, LM Rubinow, DR AF Luff, JA Schmidt, PJ Daly, RC Haq, NA Vanderhoof, VH Nelson, LM Rubinow, DR TI Role of depression in women with premature ovarian failure SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Behav Endocrinol Branch, DHHS, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 312 BP 88S EP 88S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300310 ER PT J AU Insel, TR AF Insel, TR TI The NIMH roadmap for treatment development and interventions research SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 336 BP 94S EP 95S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300332 ER PT J AU Fenton, WS AF Fenton, WS TI Treatment development: From molecules to proof of concept SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Div Mental Disorders Behav Res & AIDS, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 340 BP 95S EP 96S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300336 ER PT J AU Leibenluft, E McClure, EB Dickstein, DP Gorrindo, T Treland, J Pine, DS AF Leibenluft, E McClure, EB Dickstein, DP Gorrindo, T Treland, J Pine, DS TI Response reversal and social cognition deficits in pediatric bipolar disorder: Evidence of amygdala-OFC dysfunction? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, MAP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 349 BP 96S EP 97S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300339 ER PT J AU Blumberg, HP Krystal, JH Kaufman, J Martin, A Charney, DS Peterson, BS AF Blumberg, HP Krystal, JH Kaufman, J Martin, A Charney, DS Peterson, BS TI The sequential expression of subcortical to cortical abnormalities in juvenile bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. Dept Vet Affairs, Depress Res Ctr, West Haven, CT USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 350 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300340 ER PT J AU Dickstein, DP AF Dickstein, DP TI Neuroimaging in phenotypes of pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 351 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300341 ER PT J AU Drevets, WC AF Drevets, WC TI Amygdalo-frontal interactions in major depressive disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 362 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300352 ER PT J AU Neumeister, A Bain, EE Nugent, AC Carson, RE Bonne, O Luckenbaugh, D Eckelman, WC Herscovitch, P Charney, DS Drevets, WC AF Neumeister, A Bain, EE Nugent, AC Carson, RE Bonne, O Luckenbaugh, D Eckelman, WC Herscovitch, P Charney, DS Drevets, WC TI Altered serotonin 1A receptor binding in panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, MAP, Bethesda, MD 20892 USA. NIH, PET Dept, 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 ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 378 BP 104S EP 105S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300368 ER PT J AU Neumeister, A Geraci, M Willis, T Belfer, I Alim, TJ Bonne, O Lawson, WB Goldman, D Charney, DS AF Neumeister, A Geraci, M Willis, T Belfer, I Alim, TJ Bonne, O Lawson, WB Goldman, D Charney, DS TI alpha(2)-adrenoreceptor (AR) polymorphisms and behavioral responses to yohimbine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Howard Univ, Mood & Anxiety Disorders Program, Washington, DC 20059 USA. NIH, NIDCR, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 380 BP 105S EP 105S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300370 ER PT J AU Potenza, MN Brodkin, ES Joe, B Luo, XG Remmers, EF Wilder, RL Nestler, EJ Gelernter, J AF Potenza, MN Brodkin, ES Joe, B Luo, XG Remmers, EF Wilder, RL Nestler, EJ Gelernter, J TI Genomic regions controlling corticosterone levels in rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 384 BP 106S EP 106S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300374 ER PT J AU Agam, G Nadri, C Lipska, BK Weinberger, DR Belmaker, RH AF Agam, G Nadri, C Lipska, BK Weinberger, DR Belmaker, RH TI Are proteins expressed differently in postmortem brain of schizophrenia patients affected in brain of animal models of obstetric complications? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Ben Gurion Univ Negev, Stanley Res Ctr, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Stanley Fdn Res Ctr, IL-84105 Beer Sheva, Israel. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 401 BP 111S EP 112S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300391 ER PT J AU Straub, RE McClintock, BW Halim, ND Lipska, BK Hyde, TM Herman, MM Weinberger, DR Kleinman, JE Weickert, CS AF Straub, RE McClintock, BW Halim, ND Lipska, BK Hyde, TM Herman, MM Weinberger, DR Kleinman, JE Weickert, CS TI Dysbindin protein is decreased in the dorsolateral prefrontal cortex of schizophrenia patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 418 BP 116S EP 116S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300408 ER PT J AU Perlman, WR Webster, MJ Herman, MM Kleinman, JE Weickert, CS AF Perlman, WR Webster, MJ Herman, MM Kleinman, JE Weickert, CS TI Age-related regional expression patterns of estrogen receptor alpha and glucocorticoid receptor mRNA in the human hippocampus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, DHHS, NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 422 BP 117S EP 118S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300412 ER PT J AU Masten, CL Schweder, AE Hodgdon, HB McClure, EB Woldehawariat, G Charney, DS Ernst, M Kaufman, J Pine, DS Monk, CS AF Masten, CL Schweder, AE Hodgdon, HB McClure, EB Woldehawariat, G Charney, DS Ernst, M Kaufman, J Pine, DS Monk, CS TI Effects of maltreatment and psychiatric diagnosis on identification of emotional facial expressions in children SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT 06520 USA. 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RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 479 BP 134S EP 134S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300468 ER PT J AU Bhupali, D Mirza, N Dustin, I Levy, JA Soares, HD Csako, G Putnam, K Cohen, RM Sunderland, T AF Bhupali, D Mirza, N Dustin, I Levy, JA Soares, HD Csako, G Putnam, K Cohen, RM Sunderland, T TI Effects of APOE genotype on beta-amyloid1-42 levels in young adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Pfizer Inc, Pfizer Cent Res, Pharmacogenom & Clin Biochem Measurements Div, Groton, CT 06340 USA. 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Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 498 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300486 ER PT J AU Deak, AH Meftah, S Martinez, PE Eskandari, F Torvik, S Mistry, S Ronsaville, D Reynolds, J Gold, PW Sternberg, E Cizza, G AF Deak, AH Meftah, S Martinez, PE Eskandari, F Torvik, S Mistry, S Ronsaville, D Reynolds, J Gold, PW Sternberg, E Cizza, G TI Circadian endocrine profiles and bonemineral density in premenopausal women with major depression and a comorbid diagnosis of post traumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 503 BP 140S EP 141S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300491 ER PT J AU Spoor, E Levy, JA Cohen, RM Bergeson, J Putnam, K Huey, E Phillips, B Mirza, N Dustin, I Sunderland, T AF Spoor, E Levy, JA Cohen, RM Bergeson, J Putnam, K Huey, E Phillips, B Mirza, N Dustin, I Sunderland, T TI Apolipoprotein E polymorphism: A gender-linked risk factor for depression? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Lab Geriatr Psychiat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 505 BP 141S EP 141S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300493 ER PT J AU Schweder, AE Hodgdon, HB Masten, CL Jazbec, S Charney, DS Kaufman, J Pine, DS Ernst, M AF Schweder, AE Hodgdon, HB Masten, CL Jazbec, S Charney, DS Kaufman, J Pine, DS Ernst, M TI Children's decision-making in the context of risk-taking: The role of maltreatment and psychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 509 BP 142S EP 142S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300497 ER PT J AU Manji, HK AF Manji, HK TI Impairments of cellular plasticity and resilience in severe mood disorders: Therapeutic implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 534 BP 149S EP 149S DI 10.1016/j.biopsych.2004.02.018 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300521 ER PT J AU Hallett, M AF Hallett, M TI The plastic brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 536 BP 150S EP 150S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300523 ER PT J AU Malhotra, AK Goldman, D Sokolov, BP Krystal, JH Stein, E AF Malhotra, AK Goldman, D Sokolov, BP Krystal, JH Stein, E TI Substance abuse: From gene to brain function SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Zucker Hillside Hosp, Glen Oaks, NY USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. NIDA, Mol Psychiat Branch, Baltimore, MD USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NIDA, Neuroimaging Res Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 537 BP 150S EP 150S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300524 ER PT J AU McMahon, FJ Schulze, T Gordon, D Charney, DS AF McMahon, FJ Schulze, T Gordon, D Charney, DS TI Candidate gene studies in mood disorders research SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. RI McMahon, Francis/A-7290-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 543 BP 152S EP 152S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300530 ER PT J AU Newman, TK AF Newman, TK TI MAOA gene promoter polymorphism interacts with infant rearing experience to influence aggression and alcohol consumption in rhesus macaques (Macaca mulatta) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, Lab Neurogenet & Clin Studies, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 551 BP 154S EP 154S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300538 ER PT J AU Xu, K Roy, A Roy, M Finch, T Westly, EA Goldman, D AF Xu, K Roy, A Roy, M Finch, T Westly, EA Goldman, D TI Linkage disequilibrium of GABAA gene cluster on chromosome 4 with heroin addition in an African American population SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, LNG, NIH, Rockville, MD 20852 USA. Vet Affairs Med Ctr, Psychiat Serv, E Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 566 BP 158S EP 159S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300553 ER PT J AU Du, J Chen, J Zhou, RL Chen, JS Manji, HK AF Du, J Chen, J Zhou, RL Chen, JS Manji, HK TI Does the siRNA knockdown of Bcl-2 gene regulate mitochondria oxidative function? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 574 BP 161S EP 161S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300561 ER PT J AU Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Arana, GW George, MS AF Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Arana, GW George, MS TI An fMRI study of healthy fathers hearing infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Clin, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. NICHHD, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 582 BP 163S EP 163S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300569 ER PT J AU McClure, EB Monk, CS Nelson, EE Zarahn, E Leibenluft, E Roberson-Nay, R Schweder, AE Charney, DS Ernst, M Pine, DS AF McClure, EB Monk, CS Nelson, EE Zarahn, E Leibenluft, E Roberson-Nay, R Schweder, AE Charney, DS Ernst, M Pine, DS TI Attention-modulated neural engagement to emotional facial expressions in adolescents with anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, MAP, NIH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. NIMH, PDN, Unit Affect Disorders, NIH, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 586 BP 164S EP 164S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300572 ER PT J AU Low, N Herrell, R Avenevoli, S Merikangas, KR AF Low, N Herrell, R Avenevoli, S Merikangas, KR TI The impact of assortative mating on the familial aggregation of alcohol use and anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, DHHS, NIH, Sect Dev Genet Epidemiol,Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 589 BP 165S EP 165S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300575 ER PT J AU Rakow, A Jazbec, S Hodgdon, HB Nelson, EE Monk, CS McClure, EB Easter, JS Leibenluft, E Pine, DS Ernst, M AF Rakow, A Jazbec, S Hodgdon, HB Nelson, EE Monk, CS McClure, EB Easter, JS Leibenluft, E Pine, DS Ernst, M TI Losing or not losing: Are anxious children different from healthy children SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Affect Disorders Unit, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 591 BP 165S EP 166S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300577 ER PT J AU Steele, SU Marenco, S Barnett, AS van der Veen, JW Egan, MF Weinberger, DR AF Steele, SU Marenco, S Barnett, AS van der Veen, JW Egan, MF Weinberger, DR TI GRM3 genotype is associated with reduced N-acetyl aspartate levels in the frontal cortex: A partial replication SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 597 BP 167S EP 167S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300583 ER PT J AU Sporn, AL Addington, AM Gornick, M Kwon, L Gogtay, N Clasen, LS Greenstein, D Ordonez, AE Bobb, AJ Lenane, MC Gochman, PA Straub, RE Rapoport, JL AF Sporn, AL Addington, AM Gornick, M Kwon, L Gogtay, N Clasen, LS Greenstein, D Ordonez, AE Bobb, AJ Lenane, MC Gochman, PA Straub, RE Rapoport, JL TI ATP10C and UBE3a genes in childhood onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 611 BP 171S EP 171S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300597 ER PT J AU Bain, EE Nugent, AC Carson, RE Luckenbaugh, D Lang, LX Eckelman, WC Neumeister, A Bonne, O Williams, J Gordon, J Charney, DS Drevets, WC AF Bain, EE Nugent, AC Carson, RE Luckenbaugh, D Lang, LX Eckelman, WC Neumeister, A Bonne, O Williams, J Gordon, J Charney, DS Drevets, WC TI Decreased 5-HT1A receptor binding in bipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 636 BP 178S EP 178S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300622 ER PT J AU Mah, L Duan, YF Zarate, CA Singh, J Payne, JL Nugent, AC Charney, DS Drevets, WC AF Mah, L Duan, YF Zarate, CA Singh, J Payne, JL Nugent, AC Charney, DS Drevets, WC TI Glucose metabolism in the amygdala in bipolar II depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Imaging Branch, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 635 BP 178S EP 178S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300621 ER PT J AU Drevets, WC Sills, R Nugent, AC Bain, EE Neumeister, A Price, J Zarate, CA Charney, DS AF Drevets, WC Sills, R Nugent, AC Bain, EE Neumeister, A Price, J Zarate, CA Charney, DS TI Voumetric assessment of the amygdala in mood disorders using high resolution, 3T MRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 650 BP 182S EP 182S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300636 ER PT J AU Smith, MJ Jean-Mary, J Leon-Sarmiento, FE Murphy, DL Wassermann, EM AF Smith, MJ Jean-Mary, J Leon-Sarmiento, FE Murphy, DL Wassermann, EM TI Cortical excitability in Tourette's patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 665 BP 186S EP 186S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300650 ER PT J AU Erickson, K Zarate, CA Bain, EE Cannon, DM Manji, HK Charney, DS Sahakian, BJ Drevets, WC AF Erickson, K Zarate, CA Bain, EE Cannon, DM Manji, HK Charney, DS Sahakian, BJ Drevets, WC TI Neuropsychological performance of medicated bipolar depressed subjects differ from that of unmedicated subjects on a task of emotional processing SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, MAP, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Cambridge CB2 1TN, England. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 671 BP 187S EP 187S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300656 ER PT J AU Quiroz, JA Zarate, CA Singh, J Denicoff, KD Charney, DS Manji, HK AF Quiroz, JA Zarate, CA Singh, J Denicoff, KD Charney, DS Manji, HK TI Riluzole: An investigation of the antidepressant efficacy of an antiglutamatergic agent with neurotrophic properties in bipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA. NIMH, Expt Therapeut & Pathophysiol Branch, Mood & Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 674 BP 188S EP 188S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300659 ER PT J AU Hu, XZ Zhu, GS Lipsky, RH Goldman, D AF Hu, XZ Zhu, GS Lipsky, RH Goldman, D TI HTTLPR allele expression is codominant, correlating with gene effects on fMRI and SPECT imaging intermediate phenotypes, and behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 0 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 684 BP 191S EP 191S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300669 ER PT J AU Siever, LJ New, AS Goodman, M Koenigsberg, HW Buchsbaum, MS Frankle, WG Laruelle, M Gelernter, J Goldman, D AF Siever, LJ New, AS Goodman, M Koenigsberg, HW Buchsbaum, MS Frankle, WG Laruelle, M Gelernter, J Goldman, D TI Behavioral, cognitive, and neuroimaging intermediate phenotypes in impulsive personality disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Mt Sinai Sch Med, Bronx VA Med Ctr, New York, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA. Yale Univ, W Haven VAMC, West Haven, CT USA. NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 687 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300672 ER PT J AU Goldstein, R Volkow, N Chang, L Tomasi, D Caparelli, E Telang, F Squires, N Ernst, T AF Goldstein, R Volkow, N Chang, L Tomasi, D Caparelli, E Telang, F Squires, N Ernst, T TI Human neuroimaging of stress and drug relapse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Brookhaven Natl Lab, Upton, NY 11973 USA. NIDA, Washington, NY USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. RI Tomasi, Dardo/J-2127-2015 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 691 BP 193S EP 193S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300676 ER PT J AU Bertolino, A Caforio, G Latorre, V Petruzzella, V Nappi, G Rubino, V Di Malta, S De Candia, M Torraco, A Blasi, G Scarabino, T Papa, S Callicott, J Weinberger, DR Nardini, M AF Bertolino, A Caforio, G Latorre, V Petruzzella, V Nappi, G Rubino, V Di Malta, S De Candia, M Torraco, A Blasi, G Scarabino, T Papa, S Callicott, J Weinberger, DR Nardini, M TI Dysfunctional prefrontal activation during working memory in schizophrenia controlling for performance and COMT Val(108/158)Met genotype SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Bari, Dept Neurol & Psychiat, I-70121 Bari, Italy. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. IRCCS Casa Sollievo della Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. Univ Bari, Dept Biochem & Med Biol, I-70121 Bari, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 708 BP 198S EP 198S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300693 ER PT J AU Law, AJ Weickert, CS Hyde, TM Kleinman, JE Weinberger, DR Harrison, PJ AF Law, AJ Weickert, CS Hyde, TM Kleinman, JE Weinberger, DR Harrison, PJ TI Expression of Neuregulin-1, a schizophrenia susceptibility gene, in the normal human brain and in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Oxford, Dept Psychiat, Oxford OX1 2JD, England. NIMH, Clin Brain Disorders Branch, NIH, IRP,DHHS, Bethesda, MD 20892 USA. RI Law, Amanda/G-6372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 709 BP 198S EP 199S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300694 ER PT J AU Szeszko, PR Lipsky, RH Mentschel, C Robinson, D Ashtari, M Bilder, RM Kane, JM Malhotra, AK AF Szeszko, PR Lipsky, RH Mentschel, C Robinson, D Ashtari, M Bilder, RM Kane, JM Malhotra, AK TI Brain-derived neurotrophic factor val(66)met polymorphism and hippocampal volume in healthy volunteers and schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Zucker Hillside Hosp, Glen Oaks, NY USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RI Bilder, Robert/A-8894-2008 OI Bilder, Robert/0000-0001-5085-7852 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 713 BP 200S EP 200S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300698 ER PT J AU Du, J Gray, NA Falke, CS Chen, WX Manji, HK AF Du, J Gray, NA Falke, CS Chen, WX Manji, HK TI The role of AMPA receptor trafficking in the pathophysiology and treatment of Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 722 BP 203S EP 203S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300707 ER PT J AU Lorberbaum, JP Kose, S Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Bohning, DE Arana, GW George, MS AF Lorberbaum, JP Kose, S Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Bohning, DE Arana, GW George, MS TI A third fMRI study of healthy mothers hearing infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 728 BP 204S EP 204S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300713 ER PT J AU Lipsky, RH Xu, K Taubman, J Grant, W Jaeger, J Petrides, G Malhotra, AK AF Lipsky, RH Xu, K Taubman, J Grant, W Jaeger, J Petrides, G Malhotra, AK TI Single allele and haplotype based association support a role of the brain derived neurotrophic factor gene in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, NIH, Rockville, MD 20852 USA. Zucker Hillside Hosp, Glen Oaks, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 747 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300730 ER PT J AU Zhu, GS Lipsky, RH Xu, K Ali, S Hyde, TM Kleinman, JE Akhtar, LA Mash, DC Goldman, D AF Zhu, GS Lipsky, RH Xu, K Ali, S Hyde, TM Kleinman, JE Akhtar, LA Mash, DC Goldman, D TI Differential expression of human COMTalleles in brain and lymphoblasts detected by RT-coupled 5 ' nuclease assay SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIAAA, ING, NIH, Rockville, MD 20852 USA. Changhai Hosp, Shanghai, Peoples R China. NIMH, NIH, Bethesda, MD 20892 USA. Univ Miami, Dept Neurol, Miami, FL 33152 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 749 BP 210S EP 210S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300732 ER PT J AU Bachmann, RF Yuan, PX Gray, NA Li, XX Lan, M Chen, G Du, J Manji, HK AF Bachmann, RF Yuan, PX Gray, NA Li, XX Lan, M Chen, G Du, J Manji, HK TI Effects of mood-stabilizers on subcellular ERK signal transduction cascades SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 756 BP 212S EP 212S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300739 ER PT J AU Colantuoni, C Hyde, TM Lehrmann, E Creswell, J Freed, W Becker, KG Wood, WH Kolachana, B Straub, RE Kleinman, JE Weinberger, DR AF Colantuoni, C Hyde, TM Lehrmann, E Creswell, J Freed, W Becker, KG Wood, WH Kolachana, B Straub, RE Kleinman, JE Weinberger, DR TI The normal human cortical gene expression profile as a molecular phenotype impacted by functional genetic polymorphism in the COMT gene SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIDA, Cellular Neurobiol Res Branch, NIH, DHHS, Baltimore, MD USA. NIA, Res Resources Branch, NIH, DHHS, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 765 BP 214S EP 214S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300748 ER PT J AU Yokley, JL Hommer, DW Weinberger, DR Egan, MF AF Yokley, JL Hommer, DW Weinberger, DR Egan, MF TI Antisaccade dysfunction as an intermediate phenotype for schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 793 BP 222S EP 223S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300776 ER PT J AU Cannon, DM Nugent, AC Carson, RE Williams, JM Wood, S Solorio, G Kiesewetter, DO Eckelman, WC Drevets, WC AF Cannon, DM Nugent, AC Carson, RE Williams, JM Wood, S Solorio, G Kiesewetter, DO Eckelman, WC Drevets, WC TI Reduced muscarinic cholinergic2 receptor binding in bipolar disorder using PET and [F-18]FP-TZTP SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Mol Imaging Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Ctr Clin, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009; Carson, Richard/H-3250-2011 OI Cannon, Dara/0000-0001-7378-3411; Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 818 BP 229S EP 230S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300801 ER PT J AU Rich, BA Schmajuk, M Perez-Edgar, K Pine, DS Fox, NA Leibenluft, E AF Rich, BA Schmajuk, M Perez-Edgar, K Pine, DS Fox, NA Leibenluft, E TI Heightened responsivity to reward, punishment, and frustration in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. Univ Maryland, Child Dev Lab, College Pk, MD 20742 USA. RI Perez-Edgar, Koraly/B-8463-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 820 BP 230S EP 230S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300803 ER PT J AU Haim, A Martinez, PE Ronsaville, D Yasuda, M Sullivan, G Cizza, G Cai, J Gabry, K Gold, PW AF Haim, A Martinez, PE Ronsaville, D Yasuda, M Sullivan, G Cizza, G Cai, J Gabry, K Gold, PW TI The association between major depressive disorder and fasting insulin and glucose levels SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Natl Ctr Complimentary & Alternat Med, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 834 BP 234S EP 234S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300817 ER PT J AU Bremner, JD Vythilingam, M Vermetten, E Anderson, G Newcomer, JW Charney, DS AF Bremner, JD Vythilingam, M Vermetten, E Anderson, G Newcomer, JW Charney, DS TI Effects of glucocorticoids on declarative memory function in major depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; cortisol; memory; hippocampus; prefrontal cortex ID CORTICOTROPIN-RELEASING HORMONE; HIPPOCAMPAL VOLUME; GERIATRIC DEPRESSION; CORTISOL HYPERSECRETION; MATERNAL-DEPRIVATION; COGNITIVE-PROCESSES; REPEATED STRESS; MESSENGER-RNA; LONG-TERM; AGED RATS AB Background: Major depression has been associated with hypercortisolemia in a subset oJpatients with depression. Administration of exogenous cortisol and other glucocorticoids to healthy human subjects bas been observed to result in a transient impairment in verbal declarative memory function. The purpose of this study was to assess the effects of the glucocorticoid, dexametbasone, on verbal declarative memory function in patients with untreated unipolar major depressive disorder (MDD). Methods: Fifty two men and women with (n = 28) and without (n = 24) MDD received placebo or daxamethasone (1 mg and 2 mg on 2 successive days) in a double-blind, randomized fashion. Declarative memon, was assessed with paragraph recall at baseline (day 1) and day 3. Results: There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall. In the healthy subjects, memory improved from baseline to day 3 with placebo and was unchanged with dexamethasone, whereas in MDD patients memory function showed a pattern of decreasing with placebo and improving with dexamethasone from baseline to day 3 Conclusions: These findings are consistent with an altered sensitivity of declarativc memory function in MDD to regulation by glucocorticoids. Possible explanations of the findings include alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory, or differential sensitivity to dexamethazone-induced reductions in cortisol, in patients with MDD. C1 Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Dept Psychiat & Behav Sci, Atlanta, GA 30306 USA. Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Dept Sci, Atlanta, GA 30306 USA. Atlanta Vet Affairs Med Ctr, Decatur, GA USA. NIMH, Program Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO USA. RP Bremner, JD (reprint author), Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Dept Psychiat & Behav Sci, 1256 Briarcliff Rd, Atlanta, GA 30306 USA. RI Bremner, James/B-1632-2013; OI Vermetten, Eric/0000-0003-0579-4404 FU NIMH NIH HHS [1P50 MH 58922, 1P50 MH 56120, K02 MH 01510, R01 MH 56120, R01 MH 60395] NR 62 TC 46 Z9 48 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 IS 8 BP 811 EP 815 DI 10.1016/j.biopsych.2003.10.020 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EL UT WOS:000220755100006 PM 15050862 ER PT J AU Gopin, A Rader, C Shabat, D AF Gopin, A Rader, C Shabat, D TI New chemical adaptor unit designed to release a drug from a tumor targeting device by enzymatic triggering SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE prodrug; self-immolative; enzyme; cancer ID CAMPTOTHECIN; ADRIAMYCIN; ACTIVATION; PRODRUGS; CANCER AB A new controlled drug delivery system for selective chemotherapy was developed. It is based on a chemical adaptor unit, that releases a drug by a spontaneous cyclization mechanism after cleavage of an enzymatic substrate. It also provides a generic linkage of a drug with a targeting device in a manner set to be triggered by defined enzymatic activity. The system is generic and allows using a variety of drugs, targeting devices, and enzymes by introducing the corresponding substrate as a trigger for drug release in the chemical adaptor. (C) 2004 Elsevier Ltd. All rights reserved. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Shabat, D (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel. EM chdoron@post.tau.ac.il NR 14 TC 18 Z9 18 U1 1 U2 7 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 APR 15 PY 2004 VL 12 IS 8 BP 1853 EP 1858 DI 10.1016/j.bmc.2004.01.41 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 811EG UT WOS:000220754600004 PM 15051054 ER PT J AU Klion, AD Law, MA Noel, P Kim, YJ Haverty, TP Nutman, TB AF Klion, AD Law, MA Noel, P Kim, YJ Haverty, TP Nutman, TB TI Safety and efficacy of the monoclonal anti-interleukin-5 antibody SCH55700 in the treatment of patients with hypereosinophihc syndrome SO BLOOD LA English DT Article ID INTERLEUKIN-5 AB Four patients with hypereosinophilic syndrome (HIES) refractory to or intolerant of treatment with conventional therapy were treated with a, single 1 mg/kg dose of SCH55700. SCH55700 was extremely well. tolerated. Two of the 4 patients responded with a fall in eosinophil counts to within the normal range within 48 hours of receiving the drug, accompanied by marked improvement in clinical signs and symptoms. Response was not predicted by serum interleukin-5 (IL-5) levels or presence of the FIP1L1/PDGFRA mutation. Eosinophil counts remained suppressed for up to 12 weeks after treatment; however, exacerbation of symptoms and eosinophilia above baseline levels occurred as drug levels waned. Reinstitution of treatment with monthly SCH55700 led to decreased eosinophilia and symptomatic improvement, albeit to a lesser degree than that seen after the initial dose. These data suggest that anti-IL-5 therapy may be useful in the treatment of HIES irrespective of the underlying etiology, although the observed rebound eosinophilia and attenuation of response require further study. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Schering Plough Corp, Inst Res, Kenilworth, NJ 07033 USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM aklion@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 NR 7 TC 91 Z9 94 U1 0 U2 1 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 APR 15 PY 2004 VL 103 IS 8 BP 2939 EP 2941 DI 10.1182/blood-2003-10-3620 PG 3 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500022 PM 15070668 ER PT J AU Bhattacharya, B Miura, T Brandenberger, R Mejido, J Luo, YQ Yang, AX Joshi, BH Ginis, I Thies, RS Amit, M Lyons, I Condie, BG Itskovitz-Eldor, J Rao, MS Puri, RK AF Bhattacharya, B Miura, T Brandenberger, R Mejido, J Luo, YQ Yang, AX Joshi, BH Ginis, I Thies, RS Amit, M Lyons, I Condie, BG Itskovitz-Eldor, J Rao, MS Puri, RK TI Gene expression in human embryonic stem cell lines: unique molecular signature SO BLOOD LA English DT Article ID ZINC-FINGER PROTEIN; IN-VITRO; DIFFERENTIATION; MICROARRAY; PLURIPOTENCY; NEURONS; PRECURSORS; PROGRAMS; CLONING; NANOG AB Human embryonic stem (huES) cells have the ability to differentiate into a variety of cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. However, little is known about the mechanism of differentiation of huES cells and factors regulating cell development. We have used high-quality microarrays containing 16 659 seventy-base pair oligonucleotides to examine gene expression in 6 of the 11 available huES cell lines. Expression was compared against pooled RNA from multiple tissues (universal RNA) and genes enriched in huES cells were identified. All 6 cell lines expressed multiple markers of the undifferentiated state and shared significant homology in gene expression (overall similarity coefficient > 0.85). A common subset of 92 genes was identified that included Nanog, GTCM-1, connexin 43 (GJA1), oct-4, and TDGF1 (cripto). Gene expression was confirmed by a variety of techniques including comparison with databases, reverse transcriptase-polymerase chain reaction, focused cDNA microarrays, and immunocytochemistry. Comparison with published "sternness" genes revealed a limited overlap, suggesting little similarity with other stem cell populations. Several novel ES cell-specific expressed sequence tags were identified and mapped to the human genome. These results represent the first detailed characterization of undifferentiated huES cells and provide a unique set of markers to profile and better understand the biology of huES cells. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Geron Corp, Menlo Pk, CA USA. BresaGen Inc, Athens, GA USA. Univ Georgia, Dept Genet, Athens, GA 30602 USA. Rambam Med Ctr, Dept Obstet & Gynecol, IL-31096 Haifa, Israel. Fac Med, Haifa, Israel. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bldg 29B,Rm 2NN22,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raomah@grc.nia.nih.gov FU NIAMS NIH HHS [PAR-02-023] NR 42 TC 284 Z9 304 U1 1 U2 8 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 APR 15 PY 2004 VL 103 IS 8 BP 2956 EP 2964 DI 10.1182/blood-2003-09-3314 PG 9 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500025 PM 15070671 ER PT J AU Fujiwara, H El Ouriaghli, F Grube, M Price, DA Rezvani, K Gostick, E Sconocchia, G Melenhorst, J Hensel, N Douek, DC Barrett, AJ AF Fujiwara, H El Ouriaghli, F Grube, M Price, DA Rezvani, K Gostick, E Sconocchia, G Melenhorst, J Hensel, N Douek, DC Barrett, AJ TI Identification and in vitro expansion of CD4(+) and CD8(+) T cells specific for human neutrophil elastase SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; WEGENERS-GRANULOMATOSIS WG; CANCER-IMMUNOTHERAPY; ANTIGEN PRESENTATION; DENDRITIC CELLS; PROTEINASE-3; LYMPHOCYTES; DIFFERENTIATION; PEPTIDES AB Human neutrophil elastase (HNE) and proteinase 3 (PRO3) are myeloid tissue-restricted serine proteases, aberrantly expressed by myeloid leukemia cells. PRO3 and HNE share the PR1 peptide sequence that induces HLA-A*0201-restricted cytotoxic T cells (CTLs) with antileukemia reactivity. We studied the entire HNE protein for its ability to induce CTLs. In an 18-hour culture, HNE-loaded monocytes stimulated significant intracellular interferon gamma (IFN-gamma) production by CD4(+) and CD8(+) T cells in 12 of 20 and 8 of 20 healthy individuals, respectively. Lymphocytes from 2 HNE responders were pulsed weekly for 4 weeks to generate HNE-specific CTLs. One of 2 HLA-A*0201-negative individuals inhibited the colony formatioh of HLA-identical chronic myelogenous leukemia progenitor cells (73% inhibition at 50:1 effector-target [E/T] ratio), indicating that peptides other than PR1 can induce leukemia-reactive CTLs. Repetitive stimulations with HNE in 2 of 5 HLA-A*0201(+) individuals increased PR1 tetramer-positive CD8(+) T-cell frequencies from 0.1% to 0.29% and 0.02% to 0.55%, respectively. These CTLs; recognized PR1 peptide or killed HNE-loaded targets. These results indicate that exogenously processed HNE is a source of PR1 peptide as well as other peptide sequences capable of inducing leukemia-specific CD8(+) and CD4(+) T cells. HNE could, therefore, be used in an HLA-unrestricted manner to induce leukemia-reactive CTLs for adoptive immunotherapy. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. RP Barrett, AJ (reprint author), Bldg 10 Rm 7C 103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 45 TC 33 Z9 33 U1 0 U2 0 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 APR 15 PY 2004 VL 103 IS 8 BP 3076 EP 3083 DI 10.1182/blood-2003-07-2424 PG 8 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500042 PM 15070688 ER PT J AU Huang, G Shigesada, K Wee, HJ Liu, PP Osato, M Ito, Y AF Huang, G Shigesada, K Wee, HJ Liu, PP Osato, M Ito, Y TI Molecular basis for a dominant inactivation of RUNX1/AML1 by the leukemogenic inversion 16 chimera SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYOSIN HEAVY-CHAIN; SMOOTH-MUSCLE MYOSIN; CBF-BETA-SMMHC; ACUTE MYELOMONOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; BINDING-FACTOR; TRANSCRIPTION FACTOR; FUSION GENE; DNA-BINDING AB The Runt domain transcription factor, PEBP2/CBF, is a heterodimer composed of 2 subunits. The DNA-binding a subunit, or RUNX protein, interacts with a partner PEBP2beta/CBFbeta through the evolutionarily conserved Runt domain. Each of the genes encoding RUNX1 and PEBP2beta/ CBFbeta is frequently involved in acute myeloid leukemia. The chimeric protein, CBFbeta(PEBP2beta)/SMMHC, is generated as a result of inversion of chromosome 16 in such a way to retain the heterodimerization domain of PEBP2beta at the aminoterminal side fused to the C-terminal coiled-coil region of smooth muscle myosin heavy chain (SMMHC). Here we show that, in the chimeric protein, the second heterodimerization domain is created by the fusion junction, enabling the chimeric protein to interact with RUNX1 at far greater affinity than PEBP2beta and inactivate the RUNX1/AML1 function. To explain why and how heterozygous CBFB/ MYH11 can inactivate homozygous RUNX1 near to completion, we propose a new model for this chimeric protein that consists of a Y-shaped dinner with unpaired N-terminal halves followed by a coiled-coil for the C-terminal region. (C) 2004 by The American Society of Hematology. C1 Natl Univ Singapore, Inst Mol & Cell Biol, Oncol Res Inst, Singapore, Singapore. Kyoto Univ, Inst Virus Res, Kyoto 606, Japan. NHGRI, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), Natl Univ Singapore, Inst Mol & Cell Biol, Oncol Res Inst, 30 Med Dr, Singapore, Singapore. EM itoy@imcb.a-star.edu.sg RI Liu, Paul/A-7976-2012; ASTAR, IMCB/E-2320-2012; Osato, Motomi/N-5056-2014 OI Liu, Paul/0000-0002-6779-025X; Osato, Motomi/0000-0003-3982-9054 NR 43 TC 16 Z9 16 U1 0 U2 0 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 APR 15 PY 2004 VL 103 IS 8 BP 3200 EP 3207 DI 10.1182/blood-2003-07-2188 PG 8 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500057 PM 15070703 ER PT J AU Akin, C Fumo, G Yavuz, AS Lipsky, PE Neckers, L Metcalfe, DD AF Akin, C Fumo, G Yavuz, AS Lipsky, PE Neckers, L Metcalfe, DD TI A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib SO BLOOD LA English DT Article ID KINASE INHIBITOR STI571; MAST-CELL DISEASE; TYROSINE KINASE; WILD-TYPE; SYSTEMIC MASTOCYTOSIS; CLASSIFICATION; RECEPTORS; SURFACE; MECHANISMS; TUMORS AB Mutational analysis of the c-kit gene in a patient with a previously undescribed variant of mast cell disease revealed a germline mutation, Phe522Cys, within the transmembrane portion of the Kit receptor protein. Transfection experiments revealed that the mutation caused ligand-independent autophosphorylation of Kit, which was inhibited by the tyrosine kinase inhibitor imatinib mesylate. The patient's bone marrow biopsy and aspirate displayed unique pathologic features with the presence of excessive numbers of mature-appearing mast cells and absence of aberrant mast cell surface expression of CD2, CD25, and C1335. Therapy with imatinib mesylate resulted in a dramatic improvement in mast cell burden and clinical symptoms. These results highlight the significance of the transmembrane region of Kit in activation of the molecule and its importance in mast cell development and suggest a role for screening for transmembrane c-kit mutations in patients with mastocytosis in association with the decision to use imatinib mesylate. (C) 2004 by The American Society of Hematology. C1 NIAID, Lab Allerg Dis, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Akin, C (reprint author), NIAID, Lab Allerg Dis, Cell & Canc Biol Branch, NIH, 10 Ctr Dr,Rm 11C210, Bethesda, MD 20892 USA. EM cakin@niaid.nih.gov NR 18 TC 204 Z9 206 U1 1 U2 1 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 APR 15 PY 2004 VL 103 IS 8 BP 3222 EP 3225 DI 10.1182/blood-2003-11-3816 PG 4 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500060 PM 15070706 ER PT J AU Gwyn, K Bondy, ML Cohen, DS Lund, MJ Liff, JM Flagg, EW Brinton, LA Eley, JW Coates, RJ AF Gwyn, K Bondy, ML Cohen, DS Lund, MJ Liff, JM Flagg, EW Brinton, LA Eley, JW Coates, RJ TI Racial differences in diagnosis, treatment, and clinical delays in a population-based study of patients with newly diagnosed breast carcinoma SO CANCER LA English DT Article DE breast carcinoma; race; delay; diagnosis; treatment ID ESTROGEN-RECEPTOR STATUS; SOCIOECONOMIC-STATUS; CANCER DIAGNOSIS; WHITE WOMEN; HEALTH-INSURANCE; UNITED-STATES; BLACK-WOMEN; FOLLOW-UP; SURVIVAL; RACE AB BACKGROUND. Few studies have addressed the issue of whether delays in the interval between medical consultation and the diagnosis and treatment of breast carcinoma are greater for African American women than for white women. The authors examined differences with respect to these delays and analyzed the factors that may have contributed to such differences among women ages 20-54 years who had invasive breast carcinoma diagnosed between 1990 and 1992 and who lived in Atlanta, Georgia. METHODS. A total of 251 African American women and 580 white women were interviewed and had their medical records reviewed. The authors estimated racial differences in delay times and used polytomous logistic regression to determine the contributions of various factors (socioeconomic and other) to these differences. RESULTS. Although most women in both groups were treated within 3 months of initial consultation, 22.4% of African American women and 14.3% of white women had clinical delays of > 3 months. Compared with white women, African American women were more likely to experience delays in diagnosis and treatment. Access to care (as represented by method of detection and insurance status) and poverty index partially accounted for these differences in delay time; however, racial differences in terms of delayed treatment and diagnosis remained even after adjustment for contributing factors. CONCLUSIONS. The findings of the current study suggest that among women ages 20-54 years who have breast carcinoma, potentially clinically significant differences in terms of delayed diagnosis and treatment exist between African American women and white women. Improvements in access to care and in socioeconomic circumstances may address these differences to some degree, but additional research is needed to identify other contributing factors. Published 2004 by the American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Unit 424, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. CDCP, Natl Ctr Infect Dis, Div Global Migrat & Quarantine, Surveillance & Epidemiol Branch, Atlanta, GA USA. NCI, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. CDCP, Div Canc Prevent & Control, Atlanta, GA USA. RP Gwyn, K (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Unit 424, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM kgwyn@mdanderson.org RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-95604, N01-PC-35135, R01-CA64292-01A2]; ODCDC CDC HHS [U48 CCU0619515] NR 54 TC 117 Z9 117 U1 4 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2004 VL 100 IS 8 BP 1595 EP 1604 DI 10.1002/cncr.20169 PG 10 WC Oncology SC Oncology GA 810TA UT WOS:000220725400006 PM 15073845 ER PT J AU Chang, SM Prados, MD Yung, WKA Fine, H Junck, L Greenberg, H Robins, HI Mehta, M Fink, KL Jaeckle, KA Kuhn, J Hess, K Schold, C AF Chang, SM Prados, MD Yung, WKA Fine, H Junck, L Greenberg, H Robins, HI Mehta, M Fink, KL Jaeckle, KA Kuhn, J Hess, K Schold, C TI Phase II study of neoadjuvant 1, 3-bis (2-chloroethyl)-1-nitrosourea and temozolomide for newly diagnosed anaplastic glioma - A North American Brain Tumor Consortium Trial SO CANCER LA English DT Article DE anaplastic glioma; 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU); temozolamide; neoadjuvant strategy ID CARMUSTINE PLUS O-6-BENZYLGUANINE; SUPRATENTORIAL MALIGNANT GLIOMA; CLINICAL-TRIALS; CHEMOTHERAPY; RECURRENT; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; ASTROCYTOMA; XENOGRAFTS; DESIGN; ADULTS AB BACKGROUND. Temozolomide (TMZ) and 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) are reported to be active agents in anaplastic glioma (AG). TMZ has also been shown to deplete alkyltransferase, a DNA repair enzyme that contributes to nitrosourea resistance. The objective of the current study was to determine the efficacy and toxicity profile of a combination of these agents before radiotherapy in newly diagnosed AG. METHODS. Eligibility criteria included histologically confirmed newly diagnosed AG with measurable enhancing disease, a Karnofsky performance score (KPS) greater than or equal to 60, normal pulmonary function, and normal laboratory parameters. In addition, informed consent was obtained from all patients. BCNU given at a dose of 150 mg/m(2) intravenously was followed after 2 hours by TMZ given at a dose of 550 mg/m(2) orally on Day 1 of a 42-day cycle to a maximum of 4 cycles, unless there was tumor progression or unacceptable toxicity. RESULTS. Forty-one eligible patients were accrued. Their median age was 40 years. Seventy-six percent of patients had a KPS of 90-100. The histology was 81% anaplastic astrocytoma, 12% anaplastic oligodendroglioma, and 7% mixed tumors. Twenty-two percent of patients did not complete 4 cycles because of toxicity, mainly hematologic. Forty-six percent of patients experienced Grade 3 or 4 (according to National Cancer Institute Common Toxicity Criteria) thrombocytopenia. Twenty percent had Grade 4 granulocytopenia. Two patients died while receiving therapy, I of progressive disease and the other of Pneumocystis carinii pneumonia. The complete and partial response rates were 2% and 27% respectively. An additional 54% of patients had stable disease. Seventeen percent developed progressive disease (10% after the first cycle and 7% after the second cycle). CONCLUSIONS. This neoadjuvant strategy was associated with significant myelo-suppression and a modest response rate in patients with newly diagnosed AG. (C) 2004 American Cancer Society. C1 Univ Calif San Francisco, Neurooncol Serv, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Wisconsin, Dept Radiotherapy, Madison, WI USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75230 USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Univ Texas, Dept Pharmacol, San Antonio, TX 78285 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Univ Pittsburgh, Off Clin Res, Pittsburgh, PA USA. RP Chang, SM (reprint author), Univ Calif San Francisco, Neurooncol Serv, Dept Neurol Surg, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. EM changs@neurosurg.ucsf.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA62399, CA62405, CA62407, CA62412, CA62421, CA62422, CA62426, CA62455]; NCRR NIH HHS [M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR03186] NR 25 TC 34 Z9 35 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2004 VL 100 IS 8 BP 1712 EP 1716 DI 10.1002/cncr.20157 PG 5 WC Oncology SC Oncology GA 810TA UT WOS:000220725400022 PM 15073861 ER PT J AU Poggi, MM AF Poggi, MM TI Eighteen year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy - Author reply SO CANCER LA English DT Letter ID 20-YEAR FOLLOW-UP; CANCER C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Poggi, MM (reprint author), NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2004 VL 100 IS 8 BP 1767 EP 1767 DI 10.1002/cncr.20176 PG 1 WC Oncology SC Oncology GA 810TA UT WOS:000220725400030 ER PT J AU Stein, WD Litman, T Fojo, T Bates, SE AF Stein, WD Litman, T Fojo, T Bates, SE TI Serial Analysis of Gene Expression (SAGE) database analysis of chemosensitivity: Comparing solid tumors with cell lines and comparing solid tumors from different tissue origins SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; ADHESION; CHEMOTHERAPY; RESISTANCE; APOPTOSIS; CONTACT; GROWTH; ADENOCARCINOMA; CARCINOGENESIS; CLASSIFICATION AB Drug sensitivity and resistance has been most extensively studied in cell lines carried in tissue culture. Furthermore, cell lines have been widely used in testing new anticancer agents, despite the widely recognized observation that cell lines are more sensitive to cytotoxic drugs than are their corresponding solid tumors. We used the Serial Analysis of Gene Expression (SAGE) database to identify differences between solid tumors and cell lines, hoping to detect genes that could potentially explain differences in drug sensitivity. SAGE libraries were available for both solid tumors and cell lines from breast, colon, ovarian, pancreatic, and prostate carcinomas and from gliomas and medulloblastomas. Sixty-two genes were identified as overexpressed in tumors. The immune response and complement pathways were the significant common themes, with extracellular matrix (ECM) proteins third. For the 61 genes overexpressed in cell lines, protein synthesis was the dominant theme. We next used the SAGE database to identify genetic differences between tumor types that convey a broad range of survival to the patients that bear them as distant metastases. SAGE gene expression data were correlated with 5-year survivals documented in the SEER (Surveillance, Epidemiology and End-Results) database for patients diagnosed with "distant" or metastatic cancers. These are unlikely to be amenable to surgical resection; therefore, survival here reflects, to some extent, sensitivity to systemic therapy, i.e., chemotherapy. Using survival data as a surrogate of chemotherapy sensitivity, a spectrum can be generated, with testicular cancer at one end and pancreatic cancer at the other. Favorable 5-year survival, despite a distant presentation, correlates with expression of protein synthesis genes. Poor 5-year survival correlates with expression of cell adhesion, cytoskeletal, and ECM genes, a pattern similar to that found to distinguish solid tumors from the more cytotoxin-sensitive cancer cell lines. One interpretation is that resistance to chemotherapy may arise, in part, from the adherent, relatively inert condition (i.e., low in protein synthesis potential) of refractory cancers. Thus, attachment or ECM genes could be targets for anticancer therapy. C1 Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. Univ Copenhagen, Bioinformat Ctr, Copenhagen, Denmark. NCI, NIH, Bethesda, MD 20892 USA. RP Stein, WD (reprint author), Room 208,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdstein@vms.huji.ac.il NR 60 TC 53 Z9 53 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2004 VL 64 IS 8 BP 2805 EP 2816 DI 10.1158/0008-5472.CAN-03-3383 PG 12 WC Oncology SC Oncology GA 811ZS UT WOS:000220810400027 PM 15087397 ER PT J AU Mazzanti, C Zeiger, MA Costourous, N Umbricht, C Westra, WH Smith, D Somervell, H Bevilacqua, G Alexander, HR Libutti, SK AF Mazzanti, C Zeiger, MA Costourous, N Umbricht, C Westra, WH Smith, D Somervell, H Bevilacqua, G Alexander, HR Libutti, SK TI Using gene expression profiling to differentiate benign versus malignant thyroid tumors SO CANCER RESEARCH LA English DT Article ID FINE-NEEDLE ASPIRATION; MESSENGER-RNA AMPLIFICATION; MICROARRAY ANALYSIS; BREAST-CANCER; CLASSIFICATION; BIOPSY; SIGNATURE; PITFALLS; IMPACT AB DNA microarrays allow quick and complete evaluation of a cell's transcriptional activity. Expression genomics is very powerful in that it can generate expression data for a large number of genes simultaneously across multiple samples. In cancer research, an intriguing application of expression arrays includes assessing the molecular components of the neoplastic process and utilizing the data for cancer classification (Miller LD, et al. Cancer Cell 2002;2:353-61). Classification of human cancers into distinct groups based on their molecular profile rather than their histological appearance may prove to be more relevant to specific cancer diagnoses and cancer treatment regimes. Several attempts to formulate a consensus about classification and treatment of thyroid carcinoma based on standard histopathological analysis have resulted in published guidelines for diagnosis and initial disease management (Sherman SI. Lancet 2003;361:501-11). In the past few decades, no improvement has been made in the differential diagnosis of thyroid tumors by fine needle aspiration biopsy, specifically suspicious or indeterminate thyroid lesions, suggesting that a new approach to this should be explored. Therefore, in this study, we developed a gene expression approach to diagnose benign versus malignant thyroid lesions in 73 patients with thyroid tumors. We successfully built a 10 and 6 gene model able to differentiate benign versus malignant thyroid tumors. Our results support the premise that a molecular classification system for thyroid tumors is possible, and this in turn may provide a more accurate diagnostic tool for the clinician managing patients with suspicious thyroid lesions. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Surg, Div Endocrine & Oncol Surg, Baltimore, MD 21205 USA. Weinberg Canc Ctr, Baltimore, MD USA. Univ Pisa, Dept Oncol, Div Surg Mol & Ultrastruct Pathol, Pisa, Italy. Univ Hosp Pisa, Pisa, Italy. RP Libutti, SK (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. EM Steven_Libutti@nih.gov NR 28 TC 111 Z9 112 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2004 VL 64 IS 8 BP 2898 EP 2903 DI 10.1158/0008-5472.CAN-03-3811 PG 6 WC Oncology SC Oncology GA 811ZS UT WOS:000220810400039 PM 15087409 ER PT J AU Zhen, XA Luke, BT Izmirlian, G Umar, A Lynch, PM Phillips, RKS Patterson, S Conrads, TP Veenstra, TD Greenwald, P Hawk, ET Ali, LU AF Zhen, XA Luke, BT Izmirlian, G Umar, A Lynch, PM Phillips, RKS Patterson, S Conrads, TP Veenstra, TD Greenwald, P Hawk, ET Ali, LU TI Serum proteomic profiles suggest celecoxib-modulated targets and response predictors SO CANCER RESEARCH LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; PREVENT COLORECTAL ADENOMAS; CYCLOOXYGENASE-2 INHIBITOR; MASS-SPECTROMETRY; RANDOMIZED-TRIAL; PROSTATE-CANCER; ASPIRIN; CHEMOPREVENTION; ANGIOGENESIS; EXPRESSION AB Cyclooxygenase-2 is a valid target for cancer prevention and treatment. This has been shown in preclinical and clinical cancer prevention studies by using a cyclooxygenase-2 inhibitor, celecoxib. When used in a randomized cancer prevention clinical trial on patients with the inherited autosomal dominant condition, familial adenomatous polyposis, celecoxib proved efficacious. However, a remarkable heterogeneity in patients' responses to the chemopreventive effects of celecoxib was observed. Proteomic profiling of sera from these patients identified several markers, the expression of which was specifically modulated after treatment with celecoxib. A decision tree algorithm identified classifiers for response to celecoxib with relatively high sensitivity but moderate to low specificity. In particular, a spectral feature at m/z 16,961.4 was identified as a strong discriminator between response and nonresponse to celecoxib at the highest dose. C1 NCI, Div Canc Prevent, Bethesda, MD 20893 USA. NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. St Marks Hosp, Imperial Canc Res Fund, London EC1V 2PS, England. RP Ali, LU (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20893 USA. EM alii@mail.nih.gov NR 30 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2004 VL 64 IS 8 BP 2904 EP 2909 PG 6 WC Oncology SC Oncology GA 811ZS UT WOS:000220810400040 ER PT J AU Felix, K Gerstmeier, S Kyriakopoulos, A Howard, OMZ Dong, HF Eckhaus, M Behne, D Bornkamm, GW Janz, S AF Felix, K Gerstmeier, S Kyriakopoulos, A Howard, OMZ Dong, HF Eckhaus, M Behne, D Bornkamm, GW Janz, S TI Selenium deficiency abrogates inflammation-dependent plasma cell tumors in mice SO CANCER RESEARCH LA English DT Article ID ELEVATED MUTANT FREQUENCIES; TRANSGENIC MOUSE MODEL; GLUTATHIONE-PEROXIDASE; BALB/C MICE; POLYMORPHONUCLEAR LEUKOCYTES; INDUCED PLASMACYTOMAGENESIS; THIOREDOXIN REDUCTASE; GENOME REARRANGEMENTS; CANCER PREVENTION; SPERM MATURATION AB The role of the micronutrient, selenium, in human cancers associated with chronic inflammations and persistent infections is poorly understood. Peritoneal plasmacytomas (PCTs) in strain BALB/c (C), the premier experimental model of inflammation-dependent plasma cell transformation in mice, may afford an opportunity to gain additional insights into the significance of selenium in neoplastic development. Here, we report that selenium-depleted C mice (n = 32) maintained on a torula-based low-selenium diet (5-8 mug of selenium/kg) were totally refractory to pristane induction of PCT. In contrast, 11 of 26 (42.3%) control mice maintained on a selenium adequate torula diet (300 mug of selenium/kg) and 15 of 40 (37.5%) control mice fed standard Purina chow (440 mug of selenium/kg) developed PCT by 275 days postpristane. Abrogation of PCT was caused in part by the striking inhibition of the formation of the inflammatory tissue in which PCT develop (pristane granuloma). This was associated with the reduced responsiveness of selenium-deficient inflammatory cells (monocytes and neutrophils) to chemoattractants, such as thioredoxin and chemokines. Selenium-deficient C mice exhibited little evidence of disturbed redox homeostasis and increased mutant frequency of a transgenic lacZ reporter gene in vivo. These findings implicate selenium, via the selenoproteins, in the promotion of inflammation-induced PCT and suggest that small drug inhibitors of selenoproteins might be useful for preventing human cancers linked with chronic inflammations and persistent infections. C1 NCI, Genet Lab, CCR, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. GSF, Inst Clin Mol Biol & Tumor Genet, Munich, Germany. Hahn Meitner Inst Berlin GmbH, D-1000 Berlin, Germany. NCI, Lab Immunoregulat, Frederick, MD 21701 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. RP Janz, S (reprint author), NCI, Genet Lab, CCR, Bldg 37,Room 3140A, Bethesda, MD 20892 USA. EM sj4s@nih.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 87 TC 21 Z9 22 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2004 VL 64 IS 8 BP 2910 EP 2917 DI 10.1158/0008-5472.CAN-03-2672 PG 8 WC Oncology SC Oncology GA 811ZS UT WOS:000220810400041 PM 15087411 ER PT J AU Casar, JC McKechnie, BA Fallon, JR Young, MF Brandan, E AF Casar, JC McKechnie, BA Fallon, JR Young, MF Brandan, E TI Transient up-regulation of biglycan during skeletal muscle regeneration: delayed fiber growth along with decorin increase in biglycan-deficient mice SO DEVELOPMENTAL BIOLOGY LA English DT Article DE biglycan; decorin; embryonic myosin; proteoglycans; skeletal muscle regeneration ID HEPARAN-SULFATE PROTEOGLYCANS; DUCHENNE MUSCULAR-DYSTROPHY; CYCLIN-DEPENDENT KINASES; REPEAT PROTEIN FAMILY; EXTRACELLULAR-MATRIX; FACTOR-BETA; GENE-EXPRESSION; SYNDECAN-1 EXPRESSION; TARGETED DISRUPTION; SATELLITE CELLS AB The onset and progression of skeletal muscle regeneration are controlled by a complex set of interactions between muscle precursor cells and their environment. Decorin is the main proteoglycan present in the extracellular matrix (ECM) of adult muscle while biglycan expression is lower, but both are increased in mdx mice dystrophic muscle. Both of these small leucine-rich proteoglycans (SLRPs) can bind other matrix proteins and to the three TGF-beta isoforms, acting as modulators of their biological activity. We evaluated biglycan and decorin expression in skeletal muscle during barium chloride-induced skeletal muscle regeneration in mice. A transient and dramatic up-regulation of biglycan was associated with newly formed myotubes, whereas decorin presented only minor variations. Studies both in vitro and in intact developing newborn mice showed that biglycan expression is initially high and then decreases during skeletal muscle differentiation and maturation. To further evaluate the role of biglycan during the regenerative process, skeletal muscle regeneration was studied in biglycan-null mice. Skeletal muscle maintains its regenerative capacity in the absence of biglycan, but a delay in regenerated fiber growth and a decreased expression of embryonic myosin were observed despite to normal expression of MyoD and myogenin. Transient up-regulation of decorin during muscle regeneration in these mice may possibly obscure further roles of SLRPs in this process. (C) 2004 Elsevier Inc. All rights reserved. C1 Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular & Mol, Ctr Regulac Celular & Patol,MIFAB, Santiago, Chile. Brown Univ, Dept Neurosci, Providence, RI 02912 USA. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brandan, E (reprint author), Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular & Mol, Ctr Regulac Celular & Patol,MIFAB, Casilla 114-D, Santiago, Chile. EM ebrandan@genes.bio.puc.cl FU NICHD NIH HHS [R01 HD023924-15, HD23924, R01 HD023924]; NINDS NIH HHS [NS23924] NR 60 TC 57 Z9 59 U1 1 U2 2 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 APR 15 PY 2004 VL 268 IS 2 BP 358 EP 371 DI 10.1016/j.ydbio.2003.12.025 PG 14 WC Developmental Biology SC Developmental Biology GA 811YO UT WOS:000220807400009 PM 15063173 ER PT J AU Chae, SS Paik, JH Allende, ML Proia, RL Hla, T AF Chae, SS Paik, JH Allende, ML Proia, RL Hla, T TI Regulation of limb development by the sphingosine 1-phosphate receptor Slp(1)/EDG-1 occurs via the hypoxia/NEGF axis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE angiogenesis; sphingosine 1-phosphate; hypoxia; vascular endothelial growth factor ID PROTEIN-COUPLED RECEPTOR; ENDOTHELIAL-CELLS; VASCULAR MATURATION; SPHINGOSINE-1-PHOSPHATE; ANGIOGENESIS; EDG-1; MORPHOGENESIS; PERICYTES; SYSTEM; VEGF AB Angiogenesis, also known as new blood vessel formation, is regulated coordinately with other tissue differentiation events during limb development. Although vascular endothelial cell growth factor (VEGF) is important in the regulation of angiogenesis, chondrogenesis and osteogenesis during limb development, the role of other angiogenic factors is not well understood. Sphingosine 1-phosphate, a platelet-derived lipid mediator, regulates angiogenesis and vascular maturation via its action on the G-protein-coupled receptor S1P(1) (also known as EDG-1). In addition to vascular defects, abnormal limb development was also observed in S1p-(-/-)(1) mice. Here we show that strong induction of S1P(1) expression is observed in the blood vessels and the interdigital mesenchymal cells during limb development. Deletion of S1P(1) results in aberrant chondrocyte condensation and defective digit morphogenesis. Interestingly, the vasculature in the S1p(1)(-/-) limbs was hyperplastic and morphologically altered. In addition, the hypoxia inducible factor (HIF)-1alpha and its response gene VEGF were induced in S1p(1)(-/-) limbs. However, aberrant regulation of HIF-1alpha. and VEGF were not observed in embryonic fibroblasts derived from S1p(1)(-/-) mice, suggesting a non-cell autonomous effect of S1P, on VEGF expression. Indeed, similar limb defects were observed in endothelium-specific S1P(1) null mice in vivo. These data suggest that the function of S1P(1) in the developing vasculature is essential for proper limb development. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, Farmington, CT 06030 USA. NIDDK, Genet Dis & Dev Branch, NIH, Bethesda, MD 20892 USA. RP Hla, T (reprint author), Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, MC3501,263 Farmington Ave, Farmington, CT 06030 USA. EM hla@nso2.uchc.edu RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 FU NHLBI NIH HHS [HL67330]; PHS HHS [HJL70694] NR 21 TC 36 Z9 36 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2004 VL 268 IS 2 BP 441 EP 447 DI 10.1016/j.ydbio.2004.01.001 PG 7 WC Developmental Biology SC Developmental Biology GA 811YO UT WOS:000220807400015 PM 15063179 ER PT J AU Little, RE Gladen, BC Birmingham, K Shkyryak-Nyzhnyk, ZA Chyslovska, N AF Little, RE Gladen, BC Birmingham, K Shkyryak-Nyzhnyk, ZA Chyslovska, N CA ALSPAC Study Team TI Preterm birth rates in Avon County, England, and urban Ukraine SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE preterm birth; spontaneous preterm birth; eastern Europe; Europe ID PUBLIC-HEALTH; AREAS; MORTALITY; DELIVERY; RISK AB Objective: We compared rates of total and spontaneous preterm birth in Avon County, England and urban Ukraine to explore whether adverse conditions in the former eastern bloc influenced the preterm rate. Study design: Women who had last menstrual period (LMP) in a specified time window were recruited from geographically defined areas. Data were gathered between 1992 and 1995, using maternal questionnaires and medical record abstraction, with comparable methods in both sites insofar as possible. There were 13,731 births in Avon and 3087 in Ukraine. Rates of total and spontaneous preterm births were compared, taking account of maternal characteristics and other relevant variables. Results: The total preterm birth rates were similar (5.9%, Ukraine; 5.5%, Avon) but the spontaneous preterm rate was about 60% higher in Ukraine (5.0% versus 3.1%). Maternal characteristics and measurement differences did not explain the discrepancy. Conclusion: The difference in the spontaneous preterm rates may reflect differences in obstetrical management resulting from shortages of medical supplies and equipment in Ukraine. Published by Elsevier Ireland Ltd. C1 NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Bristol, Dept Child Hlth, Bristol, Avon, England. Inst Pediat Obstet & Gynecol, Kiev, Ukraine. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, NIH, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM gladen@niehs.nih.gov NR 17 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD APR 15 PY 2004 VL 113 IS 2 BP 154 EP 159 DI 10.1016/S0301-2115(03)00372-5 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 813ZN UT WOS:000220945100007 PM 15063952 ER PT J AU Pascale, A Alkon, DL Grimaldi, M AF Pascale, A Alkon, DL Grimaldi, M TI Translocation of protein kinase C-beta II in astrocytes requires organized actin cytoskeleton and is not accompanied by synchronous RACK1 relocation SO GLIA LA English DT Article DE astrocytes; PKC-beta II; phorbol esters; cytoskeleton; RACK1 ID PHORBOL ESTER; INTRACELLULAR RECEPTOR; NUCLEAR-LOCALIZATION; GLIAL-CELLS; ISOZYMES; PROLIFERATION; ALPHA; BRAIN; PHOSPHORYLATION; MICROFILAMENTS AB Protein kinase C (PKC)-betaII is the most abundant PKC isoform in astrocytes. Upon activation, this isoform of PKC translocates from the cytosol to the plasma membrane (PM). In this study, we investigated in astrocytes the modality of PKC-betaII translocation as far as the participation of the receptor for activated C kinase-1 (RACK1) and the requirement for intact cytoskeleton in the process. In astrocytes, Western blots and immunocytochemistry coupled to confocal microscopic quantitative analysis showed that after 5 min of phorbol-12-myiistate-13-acetate (PMA) exposure, native PKC-betaII, but not PKC-betaI, is relocated efficiently from the cytosol to the PM. Translocation of PKC-betaII was not associated with synchronous RACK1 relocation. Furthermore, the quantity of PM-associated PKC-betaII that co-immunoprecipitated with PM-bound RACK1 increased following PMA exposure, indicating a post activation binding of the two proteins in the PM. Because RACK1 and PKC-betaII relocation seemed not to be synchronous, we hypothesized that an intermediate interaction with the cytoskeleton was taking place. In fact, we were able to show that pharmacological disruption of actin-based cytoskeleton greatly deranged PKC-betaII translocation to the PM. The requirement for intact actin cytoskeleton was specific, because depolymerization of tubulin had no effect on the ability of the kinase to translocate to the PM. These results indicate that in astrocytes, RACK1 and PKC-betaII synchronous relocation is not essential for relocation of PKC-betaII to the PM. In addition, we show for the first time that the integrity of the actin cytoskeleton plays a specific role in PKC-betaII movements in these cells. We hypothesize that in glial cells, rapidly occurring changes of actin cytoskeleton arrangement may be involved in the fast reprogramming of PKC targeting to specific PM location to phosphorylate substrates in different cellular locations. Published 2003 Wiley-Liss, Inc.dagger. C1 Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. Univ Pavia, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy. Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. RP Grimaldi, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mgrimaldi@usuhs.mil OI Grimaldi, Maurizio/0000-0002-7331-7055 NR 44 TC 13 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD APR 15 PY 2004 VL 46 IS 2 BP 169 EP 182 DI 10.1002/glia.10354 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 812RO UT WOS:000220856800006 PM 15042584 ER PT J AU Sakamoto, A Liu, J Greene, A Chen, M Weinstein, LS AF Sakamoto, A Liu, J Greene, A Chen, M Weinstein, LS TI Tissue-specific imprinting of the G protein G(s)alpha is associated with tissue-specific differences in histone methylation SO HUMAN MOLECULAR GENETICS LA English DT Article ID PRADER-WILLI-SYNDROME; PSEUDOHYPOPARATHYROIDISM TYPE IB; ALPHA-SUBUNIT G(S)ALPHA; DNA METHYLATION; LYSINE-4 METHYLATION; H3 METHYLTRANSFERASE; CPG METHYLATION; GENE-EXPRESSION; IDENTIFICATION; ACETYLATION AB The G protein G(s)alpha is imprinted in a tissue-specific manner, being primarily expressed from the maternal allele in some tissues, such as renal proximal tubules. The G(s)alpha promoter is unmethylated, but is downstream of a differentially methylated region [the exon 1A differentially methylated region (DMR)] that is methylated on the maternal allele. Maternal G(s)alpha null mutations or loss of maternal-specific exon 1A methylation leads to pseudohypoparathyroidism types 1A or 1B, respectively. We now have examined the chromatin state of each parental allele within the exon 1A-G(s)alpha promoter region by chromatin immunoprecipitation of samples derived from mice with heterozygous deletions within the region using antibodies to covalently modified histones. The exon 1A DMR had allele-specific differences in histone acetylation and methylation, with histone acetylation and H3 lysine 4 (H3K4) methylation of the paternal allele, and H3 lysine 9 (H3K9) methylation of the maternal allele. Both parental alleles had similar levels of histone acetylation and H3K4 methylation within the G(s)alpha promoter and first exon, with no H3K9 methylation. In liver, where G(s)alpha is biallelically expressed, both parental alleles had similar levels of tri- and dimethylated H3K4 within the G(s)alpha first exon. In contrast, in renal proximal tubules there was a greater ratio of tri- to dimethylated H3K4 of G(s)alpha exon 1 in the more transcriptionally active maternal as compared with the paternal allele. These results show that allele-specific differences in G(s)alpha expression correlate in a tissue-specific manner with allele-specific differences in the extent of H3K4 methylation, and are the first demonstration that chronic transcriptional activation in mammals is correlated with trimethylation of H3K4. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov NR 38 TC 33 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2004 VL 13 IS 8 BP 819 EP 828 DI 10.1093/hmg/ddh098 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 807FF UT WOS:000220486700004 PM 14976161 ER PT J AU Corey, L Wald, A Celum, CL Quinn, TC AF Corey, L Wald, A Celum, CL Quinn, TC TI The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: A review of two overlapping epidemics SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Review DE herpes simplex virus infections; HIV acquisition and transmission; genital herpes ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENITAL-ULCER-DISEASE; SEXUALLY-TRANSMITTED-DISEASE; POLYMERASE-CHAIN-REACTION; PLACEBO-CONTROLLED TRIAL; TYPE-2 INFECTION; RISK FACTOR; ACQUIRED IMMUNODEFICIENCY; CLINICAL-DIAGNOSIS; FOSCARNET THERAPY AB Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and herpes simplex virus (HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1 acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda indicate that at all levels of plasma HIV-1 RNA in the source partner, HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo studies suggest that mucosal HIV-1 shedding is more frequent and in greater amounts during mucocutaneous HSV-2 replication, including subclinical mucosal reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most experience frequent subclinical and clinical reactivations of HSV-2. Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons is warranted, especially those who continue to be sexually active, those not on antiretroviral therapy, or those whose disease is not well suppressed by antiretrovirals. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Program Infect Dis, Seattle, WA 98109 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Lab Med, Program Infect Dis, Seattle, WA 98109 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Program Infect Dis, Seattle, WA 98109 USA. Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21218 USA. NIAID, Bethesda, MD 20892 USA. RP Corey, L (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Med, Program Infect Dis, 1100 Fairview Ave N,Room D3-100,POB 19024, Seattle, WA 98109 USA. EM lcorey@u.washington.edu RI Quinn, Thomas/A-2494-2010; Wald, Anna/B-6272-2012 OI Wald, Anna/0000-0003-3486-6438 FU NIAID NIH HHS [AI 30731, AI 47981, AI 52054] NR 92 TC 341 Z9 349 U1 4 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2004 VL 35 IS 5 BP 435 EP 445 DI 10.1097/00126334-200404150-00001 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 809JC UT WOS:000220632000001 PM 15021308 ER PT J AU Dougherty, MK Morrison, DK AF Dougherty, MK Morrison, DK TI Unlocking the code of 14-3-3 SO JOURNAL OF CELL SCIENCE LA English DT Review DE 14-3-3; phosphoserine; signal transduction; cancer; neurodegenerative disorders ID SPINOCEREBELLAR ATAXIA TYPE-1; CREUTZFELDT-JAKOB-DISEASE; PROTEIN PHOSPHATASE 2A; GLYCOGEN-SYNTHASE KINASE-3-BETA; MILLER-DIEKER SYNDROME; COMPLEX GENE-PRODUCTS; ALPHA-SYNUCLEIN; TUBEROUS SCLEROSIS; BREAST-CANCER; IN-VIVO AB One of the most striking 'rags to riches' stories in the protein world is that of 14-3-3, originally identified in 1967 as merely an abundant brain protein. The first clues that 14-3-3 would play an important role in cell biology came almost 25 years later when it was found to interact with various proto-oncogene proteins and signaling proteins. The subsequent identification of 14-3-3 as a phosphoserine/ phosphothreonine-binding protein firmly established its importance in cell signaling. 14-3-3 family members are found in all eukaryotes - from plants to mammals - and more than 100 binding partners have been identified to date. The targets of 14-3-3 are found in all subcellular compartments and their functional diversity is overwhelming - they include transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors. 14-3-3 binding can alter the localization, stability, phosphorylation state, activity and/or molecular interactions of a target protein. Recent studies now indicate that the serine/threonine protein phosphatases PP1 and PP2A are important regulators of 14-3-3 binding interactions, and demonstrate a role for 14-3-3 in controlling the translocation of certain proteins from the cytoplasmic and endoplasmic reticulum to the plasma membrane. New reports also link 14-3-3 to several neoplastic and neurological disorders, where it might contribute to the pathogenesis and progression of these diseases. C1 NCI, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. RP NCI, Lab Prot Dynam & Signaling, Ft Detrick, MD 21702 USA. EM dmorrison@ncifcrf.gov NR 136 TC 284 Z9 296 U1 0 U2 18 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD APR 15 PY 2004 VL 117 IS 10 BP 1875 EP 1884 DI 10.1242/jcs.01171 PG 10 WC Cell Biology SC Cell Biology GA 823JO UT WOS:000221607600004 PM 15090593 ER PT J AU Laham, N Rotem-Yehudar, R Shechter, C Coligan, JE Ehrlich, R AF Laham, N Rotem-Yehudar, R Shechter, C Coligan, JE Ehrlich, R TI Tranferrins receptor association and endosomal localization of soluble HFE are not sufficient for regulation of cellular iron homeostasis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE Hfe; TfR; hemochromatosis; iron metabolism; trafficking ID HEREDITARY HEMOCHROMATOSIS PROTEIN; TRANSFERRIN RECEPTOR; SURFACE EXPRESSION; CRYSTAL-STRUCTURE; HELA-CELLS; WILD-TYPE; HLA-H; BINDING; MACROPHAGES; TRANSPORT AB Iron uptake and storage are tightly regulated to guarantee sufficient iron for essential cellular processes and to prevent the production of damaging free radicals. A non-classical class I MHC molecule, the hemochromatosis factor HFE, has been shown to regulate iron metabolism, potentially via its direct interaction with the transferrin receptor (TfR). In this study, we demonstrate that a soluble beta(2)microglobulin-HFE monochain (sHFE) folds with beta(2)microglobulin (beta(2)m) and associates with the TfR, indicating that the transmembrane and cytoplasmic domains are not necessary for assembly and trafficking through the ER-Golgi network. We also demonstrate human TfR-specific uptake and accumulation of extracellular sHFE by treated cells. The sHFE localized to the endosomal compartment albeit we observed variation in the time taken for endosomal trafficking between different cell types. The sHFE monochain was effective in reducing Tf uptake into cells, however this did not correlate to any changes in TfR or ferritin synthesis, in contrast to the HFE-induced increase and decrease of TfR and ferritin, respectively. These findings of incongruent sHFE activity suggest that either variation in affinity binding of sHFE to TfR prevents efficient modulation of iron-regulated proteins or that HFE has multiple functions some of which may be independent of TfR but dependent on interactions within the endosomal compartment for effective modulation of iron metabolism. (C) 2004 Wiley-Liss, Inc. C1 Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel. NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Laham, N (reprint author), Tel Aviv Univ, Dept Cell Res & Immunol, IL-69978 Ramat Aviv, Israel. EM nlaham@post.tau.ac.il NR 45 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2004 VL 91 IS 6 BP 1130 EP 1145 DI 10.1002/jcb.20015 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810JQ UT WOS:000220701000004 PM 15048869 ER PT J AU Hatakeyama, Y Tuan, RS Shum, L AF Hatakeyama, Y Tuan, RS Shum, L TI Distinct functions of BMP4 and GDF5 in the regulation of chondrogenesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chondrogenesis; condensation; cell fate determination; differentiation; maturation; mesenchymal cells; chondroprogenitors; Sox9; collagen type II; collagen type X ID BONE MORPHOGENETIC PROTEINS; MULTIPOTENTIAL MESENCHYMAL CELLS; DENSITY MICROMASS CULTURES; FACTOR-BETA SUPERFAMILY; LIMB BUD; IN-VITRO; SKELETAL DEVELOPMENT; COLLAGEN GENE; OSTEOBLASTIC DIFFERENTIATION; CHONDROCYTE DIFFERENTIATION AB Bone morphogenetic protein 4 (BMP4) and growth/differentiation factor 5 (GDF5) are closely related protein family members and regulate early cartilage patterning and differentiation. In this study, we compared the functional outcome of their actions systematically at various stages of chondrogenesis in mouse embryonic limb bud mesenchyme grown in micromass cultures. Overall, both growth factors enhanced cartilage growth and differentiation in these cultures. Uniquely, BMP4 not only accelerated the formation and maturation of cartilaginous nodules, but also induced internodular mesenchymal cells to express cartilage differentiation markers. On the other hand, GDF5 increased the number of prechondrogenic mesenchymal cell condensation and cartilaginous nodules, without altering the overall pattern of differentiation. In addition, GDF5 caused a more sustained elevated expression level of Sox9 relative to that associated with BMP4. BMP4 accelerated chondrocyte maturation throughout the cultures and sustained an elevated level of Coll 0 expression, whereas GDF5 caused a transient increase in Col10 expression. Taken together, we conclude that BMP4 is instructive to chondrogenesis and induces mesenchymal cells toward the chondrogenic lineage. Furthermore, BMP4 accelerates the progression of cartilage differentiation to maturation. GDF5 enhances cartilage formation by promoting chondroprogenitor cell aggregation, and amplifying the responses of cartilage differentiation markers. These differences may serve to fine-tune the normal cartilage differentiation program, and can be exploited for the molecular manipulation in biomimetics. J. Cell. Biochem. 91: 1204-1217, 2004. Published 2004 Wiley-Liss, lnc. C1 NIDCR, Pharmacogenet & Injury Program, DBTS, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Shum, L (reprint author), NIDCR, Pharmacogenet & Injury Program, DBTS, NIH,US Dept HHS, Bldg 45,Room 4AN-18B,45 Ctr Dr,MSC 6402, Bethesda, MD 20892 USA. EM ShumL@mail.nih.gov FU NIAMS NIH HHS [Z01AR41114, Z01AR41131] NR 62 TC 78 Z9 88 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2004 VL 91 IS 6 BP 1204 EP 1217 DI 10.1002/jcb.20019 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810JQ UT WOS:000220701000010 PM 15048875 ER PT J AU Lee, H Yi, EC Wen, B Reily, TP Pohl, L Nelson, S Aebersold, R Goodlett, DR AF Lee, H Yi, EC Wen, B Reily, TP Pohl, L Nelson, S Aebersold, R Goodlett, DR TI Optimization of reversed-phase microcapillary liquid chromatography for quantitative proteomics SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE optimization; quantitative proteomics ID CODED AFFINITY TAGS; MASS-SPECTROMETRY; EXPRESSION; PROTEINS; PEPTIDES AB Currently, the field of shotgun proteomics relies primarily on the separation of peptides by reversed-phase microcapillary chromatography (RP-muLC) combined with either electrospray ionization (ESI) or matrix-assisted laser desorption ionization (MALDI) and tandem mass spectrometry (MS/MS) for protein identification as well as quantification. For this purpose we herein describe construction of a RP-muLC-ESI column-emitter along with optimized muLC conditions for using the device to quantify pair-wise changes in protein expression via the isotope coded affinity tag (ICAT (TM)) method that also maximize peak capacity. These optimized RP-muLC parameters required a balance be reached between the disparate needs of quantification which requires good peak shape and identification (i.e. proteome coverage) of proteins via peptide collision induced dissociation (CID) which requires peak capacity be maximized. A complex biological sample from a study of murine acetaminophen toxicity in hepatocyes was chosen for method development because of the high level complexity, but the biological results are not the focus of this manuscript. (C) 2003 Published by Elsevier B.V. C1 Inst Syst Biol, Seattle, WA USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. Bristol Myers Squibb Co, Dept Toxicol, Syracuse, NY USA. NHLBI, Lab Mol Immunol, MOl & Cellular Toxicol Sect, DHHS,NIH, Bethesda, MD 20892 USA. RP Goodlett, DR (reprint author), Inst Syst Biol, Seattle, WA USA. EM goodlett@systemsbiology.org OI Lee, Hookeun/0000-0002-0696-8421 FU NIDA NIH HHS [P30DA015625 P51]; NIEHS NIH HHS [P30ES-07033] NR 17 TC 30 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 15 PY 2004 VL 803 IS 1 BP 101 EP 110 DI 10.1016/j.jchromb.2003.09.005 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 805CD UT WOS:000220343500011 PM 15026003 ER EF