FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Murphy, CB Zhang, Y Troxler, T Ferry, V Martin, JJ Jones, WE AF Murphy, CB Zhang, Y Troxler, T Ferry, V Martin, JJ Jones, WE TI Probing Forster and dexter energy-transfer mechanisms in fluorescent conjugated polymer chemosensors SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID TRANSITION-METAL IONS; SIGNAL AMPLIFICATION; MIGRATION; POLY(ARYLENEETHYNYLENE)S; PHOTOLUMINESCENCE; POLYELECTROLYTES; PHOTOPHYSICS; DEPENDENCE; SENSORS; CORE AB Fluorescence quenching in solutions of a pendant-functionalized conjugated polymer chemosensor (ttp-PPETE) has been evaluated in the presence of a variety of transition metal cations, including Ni2+, Co2+, Cu2+, Fe2+, and Cr6+. Photophysical analysis of the emission quenching revealed a static quenching mechanism that demonstrated strong positive deviations from predicted linear behavior. The enhanced emission quenching mechanism was found to correlate closely with the relative loading of the cationic analytes on the polymer chemosensor. This behavior has been attributed to rapid energy transfer along the polymer backbone. A modified Stern-Volmer static quenching model has been successfully applied that incorporates an energy-transfer term that takes into account different energy-transfer mechanisms. Both Forster and Dexter energy-transfer enhancements were observed for ttp-PPETE quenching depending upon the identity of the quencher analyte involved. Stern-Volmer constants in all cases were on the order of 10(5) M-1 for the transition metals reported. Photophysical characterization for ttp-PPETE includes absorbance, emission, and single-photon counting lifetimes in the absence and presence of varying concentrations of the analytes. C1 SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA. SUNY Binghamton, Inst Mat Res, Binghamton, NY 13902 USA. Univ Penn, NIH, Reg Laser & Biotechnol Lab, Philadelphia, PA 19104 USA. RP Jones, WE (reprint author), SUNY Binghamton, Dept Chem, Vestal Pkwy E, Binghamton, NY 13902 USA. EM wjones@binghamton.edu NR 46 TC 197 Z9 199 U1 6 U2 63 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD FEB 5 PY 2004 VL 108 IS 5 BP 1537 EP 1543 DI 10.1021/jp0301406 PG 7 WC Chemistry, Physical SC Chemistry GA 768UH UT WOS:000188553100006 ER PT J AU Hall, FS Goeb, M Li, XF Sora, L Uhl, GR AF Hall, FS Goeb, M Li, XF Sora, L Uhl, GR TI mu-opioid receptor knockout mice display reduced cocaine conditioned place preference but enhanced sensitization of cocaine-induced locomotion SO MOLECULAR BRAIN RESEARCH LA English DT Article DE transgenic mice; gene knockout; dopamine; opiates; cocaine; conditioned place preference ID VENTRAL TEGMENTAL AREA; G-PROTEIN ACTIVATION; ULTRASTRUCTURAL IMMUNOCYTOCHEMICAL LOCALIZATION; MORPHINE-INDUCED ANALGESIA; MESSENGER-RNA EXPRESSION; CAUDATE-PUTAMEN NUCLEUS; RHESUS-MONKEYS; DEFICIENT MICE; BUPRENORPHINE TREATMENT; LATERAL HYPOTHALAMUS AB The mu-opioid receptor (OPRM1) is expressed in brain regions implicated in reward and locomotor processes. Reduced reward, not only from opiates, but also from several other abused substances has been observed in mice with lifelong deletions of the OPRM1 gene. To further define the roles of mu-opioid receptors in psychostimulant actions, cocaine psychomotor stimulant and rewarding effects were examined in wild-type (WT), heterozygous and homozygous mu-opioid receptor knockout mice. While mu-opioid receptor knockout did not affect basal locomotion, locomotor stimulant effects of cocaine were enhanced in a within-subjects dose-response experiment. However, further study revealed that in mice injected with 20 mg/kg for the first time, there was no difference in the locomotor-stimulating effects of cocaine between knockout and wild-type mice. In a sensitization study (modeled after the conditions in the dose-response experiment) although not observed in WT mice, OPRM1-/- mice did exhibit cocaine sensitization. By stark contrast, and similar to the effects of other rewarding drugs in OPRM1 KO mice, cocaine reward, as assessed by conditioned place preference, was reduced in both homozygous and heterozygous OPRM1 KO mice. The present results confirm a central role of the mu-opioid receptor in drug reward but opposing effects on locomotor sensitization. The reduced cocaine reward identified in heterozygous mu-opioid receptor knockout mice supports the possibility that humans with fewer available mu-opioid receptors might experience less cocaine reward. (C) 2003 Elsevier B.V. All rights reserved. C1 NIDA, Mol Neurobiol Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Hall, FS (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM shall@intra.nida.nih.gov RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 77 TC 43 Z9 43 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB 5 PY 2004 VL 121 IS 1-2 BP 123 EP 130 DI 10.1016/j.molbrainres.2003.10.024 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 779VL UT WOS:000189322200013 ER PT J AU Horning, MS Mayer, ML AF Horning, MS Mayer, ML TI Regulation of AMPA receptor gating by ligand binding core dimers SO NEURON LA English DT Article ID GLUTAMATE-RECEPTOR; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; ION CHANNELS; GLUR2; DESENSITIZATION; ACTIVATION; MECHANISM; SELECTIVITY; MODULATION AB Ionotropic glutamate receptors are tetramers, the isolated ligand binding cores of which assemble as dimers. Previous work on nondesensitizing AMPA receptor mutants, which combined crystallography, ultracentrifugation, and patch-clamp recording, showed that dimer formation by the ligand binding cores is required for activation of ion channel gating by agonists. To define the mechanisms responsible for stabilization of dimer assembly in native AMPA receptors, contacts between the adjacent ligand binding cores were individually targeted by amino acid substitutions, using the GluR2 crystal structure as a guide to design mutants. We show that disruption of a salt bridge, hydrogen bond network, and intermolecular van der Waals contacts between helices D and J in adjacent ligand binding cores greatly accelerates desensitization. Conservation of these contacts in AMPA and kainate receptors indicates that they are important determinants of dimer stability and that the dimer interface is a key structural element in the gating mechanism of these glutamate receptor families. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Horning, MS (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM mlm@helix.nih.gov RI Mayer, Mark/H-5500-2013 NR 24 TC 107 Z9 109 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB 5 PY 2004 VL 41 IS 3 BP 379 EP 388 DI 10.1016/S0896-6273(04)00018-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 821KA UT WOS:000221457900009 PM 14766177 ER PT J AU Young, NS Brown, KE AF Young, NS Brown, KE TI Mechanisms of disease - Parvovirus B19 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID POLYMERASE-CHAIN-REACTION; COLONY FORMATION INVITRO; CHRONIC-FATIGUE-SYNDROME; ERYTHROID LINEAGE CELLS; B19 INFECTION; APLASTIC-ANEMIA; RHEUMATOID-ARTHRITIS; BONE-MARROW; CLINICAL MANIFESTATIONS; FULMINANT-HEPATITIS C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngn@nhlbi.nih.gov NR 126 TC 425 Z9 468 U1 6 U2 26 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 FEB 5 PY 2004 VL 350 IS 6 BP 586 EP 597 DI 10.1056/NEJMra030840 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 770FP UT WOS:000188712800010 PM 14762186 ER PT J AU Bonner, AE Lemon, WJ Devereux, TR Lubet, RA You, M AF Bonner, AE Lemon, WJ Devereux, TR Lubet, RA You, M TI Molecular profiling of mouse lung tumors: association with tumor progression, lung development, and human lung adenocarcinomas SO ONCOGENE LA English DT Article DE lung cancer; expression profiling; mouse model; human; lung development ID OLIGONUCLEOTIDE ARRAYS; EXPRESSION; TUMORIGENESIS AB We have performed oligonucleotide array analysis on various murine lung tissues [normal lungs, lung adenomas, and lung adenocarcinomas (ACs)] using Affymetrix U74Av2 GeneChips to examine the complex genetic changes occurring during lung carcinogenesis. Analysis yielded 20 novel genes differentially expressed in both lung adenomas and ACs versus normal lungs, including the tumor suppressor APC2 and the oncogene Ros 1. In addition, 50 genes were found to be differentially expressed in lung adenomas versus lung ACs, including the differentiation factor Hox C6, the oncogene Ets 2, and the Ras nuclear transport factor, nuclear transport factor 2. To understand the potential relationship between genes expressed in murine lung tumors and its relationship to altered gene expression observed during embryogenesis and postnatal development, tissues from embryonic lungs and from lungs of mice up to 4 weeks following birth were examined using Affymetrix U74Av2 GeneChips. From this analysis, approximately 1300 genes were determined to exhibit differential expression in fetal lung versus postnatal lung. When we compared lung adenomas, lung ACs, and normal lung parenchyma, 24 developmentally regulated genes were found aberrantly expressed in lung tumors; these included the cell cycle control factor CDC5, the cellular differentiation factor TEA domain 4, and the proapoptotic factor BNIP 2. Finally, we compared the murine lung tumor gene expression data to the expression of genes in human lung cancer, in order to assess the relevance of murine lung cancer models in the study of human AC formation. When the 17 human lung ACs and six human lung large cell carcinomas were examined, it was found that 13 of the 17 human lung ACs clustered tightly together in a pattern that was different from the remaining four human lung ACs and six large cell carcinomas, which exhibited a different pattern. Interestingly, the mouse lung adenomas appeared similar to 13 clustered ACs, while mouse lung ACs appeared more similar in pattern to the group consisting of four ACs and six large-cell carcinomas (LCCs). Nevertheless, when compared with the combined human ACs, 39 genes with similar expression changes in murine lung tumors and human ACs/LCCs were identified, such as the oncogene-related BCL7B, the cell cycle regulator CDK4, and the proapoptotic Endophilin B1. Overall, we have determined, for the first time, the expression profiles during murine lung tumor progression and have established, at the molecular level, an association between murine lung tumorigenesis and lung development. We have also attempted to compare the expression profiles found in mouse lung cancers and those in human lung ACs. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [R01CA78797, R01CA58554] NR 16 TC 59 Z9 65 U1 1 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 FEB 5 PY 2004 VL 23 IS 5 BP 1166 EP 1176 DI 10.1038/sj.onc.1207234 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 770UV UT WOS:000188749900015 PM 14647414 ER PT J AU Zhao, FQ Zheng, YC Dong, B Oka, T AF Zhao, FQ Zheng, YC Dong, B Oka, T TI Cloning, genomic organization, expression, and effect on beta-casein promoter activity of a novel isoform of the mouse Oct-1 transcription factor SO GENE LA English DT Article DE beta-casein promoter; differential splicing; gene expression; Oct-1 isoform; protein-DNA binding; transcription regulation ID OCTAMER-BINDING-PROTEINS; POU DOMAIN; GENE-EXPRESSION; ACTIVATION; CONTAINS; CELLS; COACTIVATOR; ELEMENTS; MOTIF; SNRNA AB The ubiquitously expressed transcription factor Oct-1, a member of the POU domain factors, is involved in the regulation of expression of many tissue-specific and house-keeping genes. Multiple alternatively spliced isoforms of Oct-1 have been identified in human and mouse cells. The expression patterns of these isoforms and the analysis of their genomic organization and structure have suggested that the structural variation of Oct-1 isoforms may be important in conferring target and tissue specificity to its transcriptional activity. In this study, we have cloned and sequenced a new mouse Oct-1 isoform, named mOct-1Z. This novel isoform differs markedly at the C-terminus from the previously identified Oct-1 isoforms A, B, and C. It is generated by alternative splicing from the Oct-1 gene and its transcript exhibits a frameshift followed by an early stop codon, thus, its predicted protein has a distinct, much shorter C-terminal tail. However, this truncated isoform could still effectively bind to a consensus Oct-1 motif oligonucleotide and, like Oct-1B, activated the basal promoter activity of the mouse beta-casein gene. Oct-1Z is another ubiquitously expressed Oct-1 isoform, its transcript being detected in all mouse tissues examined, including the mammary gland, liver, lung, kidney, spleen, small intestine mucosa, uterus, and ovary. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Vermont, Dept Anim Sci, Lactat & Mammary Gland Biol Grp, Burlington, VT 05405 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Zhao, FQ (reprint author), Univ Vermont, Dept Anim Sci, Lactat & Mammary Gland Biol Grp, Burlington, VT 05405 USA. EM Feng-Qi.Zhao@uvm.edu NR 34 TC 24 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 4 PY 2004 VL 326 BP 175 EP 187 DI 10.1016/j.gene.2003.10.023 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 772AR UT WOS:000188818600019 PM 14729276 ER PT J AU Miller, FG Emanuel, EJ Rosenstein, DL Straus, SE AF Miller, FG Emanuel, EJ Rosenstein, DL Straus, SE TI Ethical issues concerning research in complementary and alternative medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIALS; LOW-BACK-PAIN; HYPERICUM-PERFORATUM; UNITED-STATES; FOLLOW-UP; DEPRESSION; ACUPUNCTURE; DISORDER; THERAPY AB The use of complementary and alternative medicine (CAM) has grown dramatically in recent years, as has research on the safety and efficacy of CAM treatments. Minimal attention, however, has been devoted to the ethical issues relating to research on CAM. We argue that public health and safety demand rigorous research evaluating CAM therapies, research on CAM should adhere to the same ethical requirements for all clinical research, and randomized, placebo-controlled clinical trials should be used for assessing the efficacy of CAM treatments whenever feasible and ethically justifiable. in addition, we explore the legitimacy of providing CAM and conventional therapies that have been demonstrated to be effective only by virtue of the placebo effect. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 31,Room 2B11, Bethesda, MD 20892 USA. EM sstraus@nih.gov NR 33 TC 68 Z9 69 U1 3 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 4 PY 2004 VL 291 IS 5 BP 599 EP 604 DI 10.1001/jama.291.5.599 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 769LC UT WOS:000188650700025 PM 14762039 ER PT J AU Wallner, P Arthur, D Bartelink, H Connolly, J Edmundson, G Giuliano, A Goldstein, N Hevezi, J Julian, T Kuske, R Lichter, A McCormick, B Orecchia, R Pierce, L Powell, S Solin, L Vicini, F Whelan, T Wong, J Coleman, CN AF Wallner, P Arthur, D Bartelink, H Connolly, J Edmundson, G Giuliano, A Goldstein, N Hevezi, J Julian, T Kuske, R Lichter, A McCormick, B Orecchia, R Pierce, L Powell, S Solin, L Vicini, F Whelan, T Wong, J Coleman, CN TI Workshop on Partial Breast Irradiation: State of the Art and the Science, Bethesda, MD, December 8-10, 2002 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CONFORMAL RADIATION-THERAPY; DETECTED DUCTAL CARCINOMA; CONSERVING SURGERY; CONSERVATIVE SURGERY; LOCAL RECURRENCE; RANDOMIZED TRIAL; TUMOR BED; BRACHYTHERAPY APPLICATOR; SOLE BRACHYTHERAPY; RADICAL-MASTECTOMY AB Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence (partial-breast irradiation [PBI]) and to shorten the duration of treatment (accelerated partial-breast irradiation [APBI]). To consider issues regarding the equivalency of the various radiation therapy approaches and to address future needs for research, quality assurance, and training, the National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, hosted a Workshop on PBI in December 2002. Although 5- to 7-year outcome data on patients treated with PBI and APBI are now becoming available, many issues remain unresolved, including clinical and pathologic selection criteria, radiation dose and fractionation and how they relate to the standard fractionation for whole breast irradiation, appropriate target volume, local control within the untreated ipsilateral breast tissue, and overall survival. This Workshop report defines the issues in relation to PBI and APBI, recommends parameters for consideration in clinical trials and for reporting of results, serves to enhance dialogue among the advocates of the various radiation techniques, and emphasizes the importance of education and training in regard to results of PBI and APBI as they become emerging clinical treatments. C1 NCI, RRP, DCTD, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA. Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. John Wayne Canc Inst, Santa Monica, CA USA. Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA 15212 USA. Arizona Oncol Serv, Scottsdale, AZ USA. Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. European Inst Oncol, Dept Radiotherapy, Milan, Italy. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hamilton Reg Canc Ctr, Support Canc Care Res Unit, Hamilton, ON L8V 1C3, Canada. RP Coleman, CN (reprint author), NCI, RRP, DCTD, NIH, 6130 Execut Blvd,EPN Room 6015A, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov RI Whelan, Timothy/D-3185-2017 NR 50 TC 59 Z9 61 U1 0 U2 1 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 FEB 4 PY 2004 VL 96 IS 3 BP 175 EP 184 DI 10.1093/jnci/djh023 PG 10 WC Oncology SC Oncology GA 778JU UT WOS:000189239100007 PM 14759984 ER PT J AU Zhang, YY Yoneyama, H Wang, Y Ishikawa, S Hashimoto, S Gao, JL Murphy, P Matsushima, K AF Zhang, YY Yoneyama, H Wang, Y Ishikawa, S Hashimoto, S Gao, JL Murphy, P Matsushima, K TI Mobilization of dendritic cell precursors into the circulation by administration of MIP-1 alpha in mice SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; INDUCED FULMINANT-HEPATITIS; CHEMOKINE RECEPTORS CCR1; IN-VITRO; T-CELLS; LIVER; DIFFERENTIATION; POPULATIONS; EXPRESSION AB Background: Dendritic cells (DCs) play a central role in immune responses and may be useful adjuvants for tumor vaccine therapy. We previously reported that F4/80(-)B220(-)CD11c(+) DC precursors expressing the CC chemokine receptors CCR1 and CCR5 are mobilized rapidly into the circulation in mice injected with Propionibacterium acnes and are recruited into inflammatory tissue by macrophage inflammatory protein 1alpha (MIEP-1alpha), which binds to CCR1 and CCR5. Here we investigate the mechanisms of DC precursor mobilization and the antitumor effect of these cells in mice. Methods: Numbers of DC precursors in peripheral blood were determined in P. acnes-treated mice (groups of 10 C57BL/B6 [B6] wild-type mice, CCR1(-/-) mice, CCR5(-/-) mice, and B6 mice treated with antibody to MIP-1alpha or control antibody) and in B6 mice injected with recombinant MIP-1a. MIP-1alpha-mobilized DC precursors matured by treatment,with granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor-alpha and pulsed with B16 melanoma lysates were assayed for their ability to confer protective immunity against tumor challenge in vivo and to induce cytotoxic T lymphocytes against B16 tumor cells in vitro. Results: The recruitment of DC precursors into the circulation by P. acnes administration was higher in B6 mice (12.6%, 95% confidence interval [CI] = 9.1% to 16.1%) than in CCR1(-/-) (9.0%, 95% CI = 7.5% to 10.5%), CCR5(-/-) (6.3%, 95% CI = 5.2% to 7.3%), or anti-MIP-1alpha antibody-treated (6.6%, 95% CI = 5.7% to 7.5%) mice. Injection of MIEP-lot also mobilized DC precursors into the circulation (13.1%, 95% CI = 10.8% to 15.6%). Matured MIP-1alpha-mobilized-DC precursors pulsed with B16 tumor lysates; elicited B16-specific antitumor immunity in vitro and in vivo. Conclusions: MIP-1alpha and its receptors are important in recruiting DC precursors into the circulation. DC precursors mobilized rapidly by MIP-1alpha may provide sufficient useful DC precursors for DC-based vaccination in cancer treatment. C1 Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 1130033, Japan. NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Matsushima, K (reprint author), Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM koujim@m.u-tokyo.ac.jp NR 33 TC 54 Z9 57 U1 0 U2 4 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 FEB 4 PY 2004 VL 96 IS 3 BP 201 EP 209 DI 10.1093/jnci/djh024 PG 9 WC Oncology SC Oncology GA 778JU UT WOS:000189239100010 PM 14759987 ER PT J AU Longo, DL AF Longo, DL TI Re: Radiation therapy in the treatment of Hodgkin's disease - Do you see what I see? Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID CHEMOTHERAPY; CANCER C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, NIH, Gerontol Res Ctr, Box 09,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov NR 6 TC 0 Z9 0 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 FEB 4 PY 2004 VL 96 IS 3 BP 236 EP 237 DI 10.1093/jnci/djh036 PG 2 WC Oncology SC Oncology GA 778JU UT WOS:000189239100017 ER PT J AU Leitzmann, MF Giovannucci, E AF Leitzmann, MF Giovannucci, E TI Re: Zinc supplement use and risk of prostate cancer - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID CELLS; INVASION C1 NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Leitzmann, MF (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Execut Blvd,EPS-MSC 7232, Bethesda, MD 20892 USA. EM leitzmann@mail.nih.gov NR 9 TC 1 Z9 1 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 FEB 4 PY 2004 VL 96 IS 3 BP 240 EP 241 DI 10.1093/jnci/djh046 PG 2 WC Oncology SC Oncology GA 778JU UT WOS:000189239100021 ER PT J AU Levine, C Faden, R Grady, C Hammerschmidt, D Eckenwiler, L Sugarman, J AF Levine, C Faden, R Grady, C Hammerschmidt, D Eckenwiler, L Sugarman, J CA Consortium Examine Clin Res Ethics TI "Special scrutiny": A targeted form of research protocol review SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID SMALLPOX VACCINE; PERINATAL TRANSMISSION; PARKINSONS-DISEASE; CLINICAL RESEARCH; PLACEBO-CONTROLS; TRIALS; SURGERY; ETHICS; DEATH; XENOTRANSPLANTATION AB Research participants require ongoing protection of the kind already established in law and regulation. However, "special scrutiny" for certain types of research is also needed. Three criteria for special scrutiny are 1) research that involves initial experiences of translating new scientific advances into humans, especially when the intervention is novel, irreversible, or both; 2) research with a known or credible risk for significant harm (death or serious disability are the clearest examples) to research participants as a consequence of the experimental intervention and with no potential for offsetting direct medical benefit; or 3) research with a protocol that raises ethical questions about research design or implementation for which there is no consensus. Special scrutiny recognizes that not all research protocols are equally ethically challenging and aims to provide appropriate protection for all research participants. C1 Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Baltimore, MD 21205 USA. United Hosp Fund, New York, NY USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. RP Sugarman, J (reprint author), Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Hampton House 351,624 N Broadway, Baltimore, MD 21205 USA. NR 36 TC 21 Z9 21 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 3 PY 2004 VL 140 IS 3 BP 220 EP 223 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 770BZ UT WOS:000188704500008 PM 14757620 ER PT J AU Lee, CW Kim, S Roh, SH Endoh, H Kodera, Y Maeda, T Kohno, T Wang, JM Swartz, KJ Kim, JI AF Lee, CW Kim, S Roh, SH Endoh, H Kodera, Y Maeda, T Kohno, T Wang, JM Swartz, KJ Kim, JI TI Solution structure and functional characterization of SGTxl, a modifier of Kv2.1 channel gating SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; DEPENDENT K+ CHANNELS; POTATO CARBOXYPEPTIDASE INHIBITOR; 3-DIMENSIONAL SOLUTION STRUCTURE; RELAXATION MATRIX ANALYSIS; DISTANCE GEOMETRY; NMR-SPECTROSCOPY; MOLECULAR DETERMINANTS; COUPLING-CONSTANTS; SECONDARY STRUCTURE AB SGTx1 is a peptide toxin isolated from the venom of the spider Scodra griseipes that has been shown to inhibit outward K+ currents in rat cerebellar granule neurons. Although its amino acid sequence is known to be highly (76%) homologous with that of hanatoxin (HaTx), a well-characterized modifier of Kv2.1 channel gating, the structural and functional characteristics of SGTx1 remain largely unknown. Here we describe the NMR solution structure of SGTx1, the mechanism of its interaction with Kv2.1 channels, and its effect on channel activity once bound. The NMR structure of SGTx1 contains a molecular fold closely resembling the "inhibitor cystine knot" of HaTx, which is composed of an antiparallel beta-sheet and four chain reversals stabilized by three disulfide bonds. Functionally, SGTx1 reversibly inhibited K+ currents in oocytes expressing Kv2.1 channels. Moreover, generation of steady-state activation curves showed that, consistent with other gating modifiers, SGTx1 acted by shifting the activation of the channel to more depolarized voltages. Thus, the surface profile and mechanism of action of SGTx1 are similar to those of HaTx. Still, detailed comparison of SGTx1 with HaTx revealed differences in binding affinity and conformational homogeneity that result from differences in the charge distribution at the binding surface and in the amino acid composition of the respective beta-hairpin structures in the peptides. C1 Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. Kitasato Univ, Sch Sci, Dept Phys, Kanagawa 2288555, Japan. Mitsubishi Kagaku Inst Life Sci, Tokyo 1948511, Japan. NINDS, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Kim, JI (reprint author), Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. EM jikim@kjist.ac.kr FU Intramural NIH HHS [ZIA NS002945-13] NR 57 TC 71 Z9 73 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 3 PY 2004 VL 43 IS 4 BP 890 EP 897 DI 10.1021/bi0353373 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767ZY UT WOS:000188504800007 PM 14744131 ER PT J AU Kim, HY Bigelow, J Kevala, JH AF Kim, HY Bigelow, J Kevala, JH TI Substrate preference in phosphatidylserine biosynthesis for docosahexaenoic acid containing species SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; POLYUNSATURATED FATTY-ACIDS; ELECTROSPRAY-IONIZATION; MASS-SPECTROMETRY; ETHANOL EXPOSURE; ALPHA ACTIVATION; GLIOMA-CELLS; SYNTHASE-II; DECARBOXYLATION; MITOCHONDRIA AB Neuronal membranes contain high levels of phosphatidylserine (PS) and docosahexaenoic acid (22:6n-3, DHA). In this study, substrate preference in PS synthesis was determined to gain insight on the biochemical basis for concentrating PS in neuronal membranes where 22:6n-3 is highly enriched. We first established an in vitro assay method using unilamellar vesicles (LUV) of deuterium-labeled substrates and reversed-phase HPLC/electrospray ionization (ESI) mass spectrometry. The PS production by the incubation of deuterium-labeled substrate and microsomal fractions was monitored. We found that tissue-specific substrate preference exists in PS synthesis. Microsomes from the cerebral cortex synthesized PS from 18:0,22:6-PC most favorably among the PC substrates tested, followed by 18:0,22:5-PC, resulting in the PC substrate preference in the order of 18:0,22:6>18:0,22:5>18:0,20:4=18:0,18:1. Liver microsomes also preferred 18:0,22:6-PC as the substrate in PS synthesis but did not use 18:0,22:5-PC favorably. The 18:0,22:5-PC species was converted to PS at the similar extent as 18:0,20:4- or 18:0,18: 1-PC species in the liver. Both brain and liver microsomes showed a preference for 18:0 over 16:0 as the sn-1 fatty acid. From these data it was deduced that preferential conversion of 18:0,22:6-PC to the corresponding PS species is at least partly responsible for concentrating PS in neuronal tissues where 22:6n-3 is particularly abundant. The distinctive preference for 18:0,22:5-PS observed with brain microsomes may help to maintain PS at a high level in the brain when 22:6n-3 is replaced by 22:5n-3 as in the case of n-3 fatty acid deficiency. C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Kim, HY (reprint author), NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. EM hykim@nih.gov NR 38 TC 48 Z9 52 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 3 PY 2004 VL 43 IS 4 BP 1030 EP 1036 DI 10.1021/bi035197x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767ZY UT WOS:000188504800024 PM 14744148 ER PT J AU Tokumasu, F Hwang, J Dvorak, JA AF Tokumasu, F Hwang, J Dvorak, JA TI Heterogeneous molecular distribution in supported multicomponent lipid bilayers SO LANGMUIR LA English DT Article ID SCANNING OPTICAL MICROSCOPY; ATOMIC-FORCE MICROSCOPY; DOMAIN FORMATION; RAFTS; CHOLESTEROL; MEMBRANES; BIOLOGY AB Membrane domains contribute important structural and functional attributes to biological membranes. We describe the heterogeneous nanoscale distribution of lipid molecules within microscale membrane domains in multicomponent lipid bilayers composed of dipalmitoylphosphatidylcholine (DPPC), dilauroylphosphatidyleholine (DLPC), and cholesterol (chol). The lipids were labeled with the fluorescent lipid analogues Bodipy-PC and DiI-C20:0 to identify the distribution of individual membrane components. We used a near-field scanning optical microscope (NSOM) at room temperature to identify the nanoscale structures in the membrane. Simultaneous multicolor NSOM imaging at the emission maxima of the fluorescent analogues revealed a patchy distribution of Bodipy-PC and DiI-C20:0 indicative of phase separations in the bilayer. In a cholesterol-free system (DPPC/DLPC = 1:1), NSOM images proved that the two phosphatidylcholine molecules can coexist in domains at the micrometer level but form nanoscopic patches within the domains; DPPC occurs at the edge of the domains, whereas DLPC is present throughout the domains. In the presence of cholesterol (DPPC/DLPC = 7:3, chol = 18.9%), the two lipid molecules were more miscible but incomplete phase separations also occurred. The average domain sizes were 140-200 nm, well below the resolution capabilities of diffraction-limited light microscopy techniques; the domains were unresolvable by confocal microscopy. Our high-resolution NSOM studies of membrane domain behavior provide a better understanding of complex membrane phase phenomena in multicomponent biological membranes. C1 NIAID, Biochem & Biophys Parasitol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIST, Opt Technol Div, Phys Lab, Gaithersburg, MD 20899 USA. RP Dvorak, JA (reprint author), NIAID, Biochem & Biophys Parasitol Sect, Lab Malaria & Vector Res, NIH, Bldg 4,Rm B2-11,4 Ctr Dr, Bethesda, MD 20892 USA. EM jdvorak@niaid.nih.gov OI Tokumasu, Fuyuki/0000-0003-2790-1071 FU ORS NIH HHS [Y3-OR-1341-01] NR 17 TC 19 Z9 19 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD FEB 3 PY 2004 VL 20 IS 3 BP 614 EP 618 DI 10.1021/la0355388 PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 769QE UT WOS:000188660600015 PM 15773083 ER PT J AU Preger, E Ziv, I Shabtay, A Sher, I Tsang, M Dawid, IB Altuvia, Y Ron, D AF Preger, E Ziv, I Shabtay, A Sher, I Tsang, M Dawid, IB Altuvia, Y Ron, D TI Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; CELL-PROLIFERATION; MESSENGER-RNAS; EXPRESSION; PATHWAYS; CLONING; BINDING; TRANSLATION; INITIATION AB Receptor tyrosine kinases (RTKs) control a multitude of biological processes and are therefore subjected to multiple levels of regulation. Negative feedback is one of the mechanisms that provide an effective means to control RTK-mediated signaling. Sef has recently been identified as a specific antagonist of fibroblast growth factor (FGF) signaling in zebrafish and subsequently in mouse and human. Sef encodes a putative type I transmembrane protein that antagonizes the Ras/mitogen-activated protein kinase pathway in all three species. Mouse Sef was also shown to inhibit the phosphatidylinositol 3-kinase pathway. We show here that an alternative splicing mechanism generates an isoform of human Sef, hSef-b, which unlike the previously reported Sef (hSef-a) is a cytosolic protein. Contrary to hSef-a, which is ubiquitously expressed, hSef-b transcripts display a restricted pattern of expression in human tissues. hSef-b inhibits FGF-induced cell proliferation and prevents the activation of mitogen-activated protein kinase without affecting the upstream component MAPK kinase. Furthermore, hSef-b does not antagonize FGF induction of the phosphatidylinositol 3-kinase pathway. In addition to the effects on FGF signaling, hSef-b inhibited cellular response. to plate let-derived growth factor but not other RTK ligands. Therefore, alternative splicing of the hSef gene expands the Sef feedback inhibition repertoire of RTK signaling. C1 Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. Natl Inst Child Hlth & Human Dev, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. RP Ron, D (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. EM dinar@techunix.technion.ac.il RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 NR 38 TC 43 Z9 44 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 3 PY 2004 VL 101 IS 5 BP 1229 EP 1234 DI 10.1073/pnas.0307952100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 771QD UT WOS:000188796800025 PM 14742870 ER PT J AU Kurita, K Burgess, SM Sakai, N AF Kurita, K Burgess, SM Sakai, N TI Transgenic zebrafish produced by retroviral infection of in vitro-cultured sperm SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GERM-LINE TRANSMISSION; VIVO GENE-TRANSFER; MOUSE SPERMATOGENIC CELLS; FLUORESCENT PROTEIN; DANIO-RERIO; STEM-CELLS; EXPRESSION; MICE; INJECTION; VECTORS AB Transgenic modification of sperm before fertilization has distinct advantages over conventional transgenic methods. The primary advantage is that the mosaicism inherent in those other techniques is avoided. A culture system using primary cultures of zebrafish male germ cells, in which the differentiation from spermatogonial to functional sperm can occur in vitro, provides the opportunity for genetic modification of sperm in vitro. Here, we report the production of transgenic zebrafish from cultured sperm. The sperm were differentiated from premeiotic germ cells infected with a pseudotyped retrovirus in vitro. The collected sperm were used to perform successful in vitro fertilizations, and transgenic embryos were identified. The transgenic fish transmitted the proviral integration to the next generation in a Mendelian fashion. We report the generation of a transgenic animal by cultured sperm and open the door to many exciting possibilities for the rapid generation of transgenic lines in model organisms such as zebrafish or other animal systems that are otherwise intractable to transgenesis. C1 Fukui Prefectural Univ, Dept Marine Biosci, Obama 9170003, Japan. Fukui Prefectural Univ, Grad Sch Biosci & Biotechnol, Obama 9170003, Japan. NHGRI, Dev Genom Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Sakai, N (reprint author), Natl Inst Genet, Genet Strains Res Ctr, Mishima, Shizuoka 4118540, Japan. EM nosakai@lab.nig.ac.jp OI Burgess, Shawn/0000-0003-1147-0596 NR 41 TC 35 Z9 38 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 FEB 3 PY 2004 VL 101 IS 5 BP 1263 EP 1267 DI 10.1073/pnas.0304265101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 771QD UT WOS:000188796800031 PM 14745028 ER PT J AU Hawari, FI Rouhani, FN Cui, XL Yu, ZX Buckley, C Kaler, M Levine, SJ AF Hawari, FI Rouhani, FN Cui, XL Yu, ZX Buckley, C Kaler, M Levine, SJ TI Release of full-length 55-kDa TNF receptor 1 in exosome-like vesicles: A mechanism for generation of soluble cytokine receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-BINDING-PROTEIN; B-LYMPHOCYTES; CELL-SURFACE; IN-VITRO; ALPHA; MEMBRANE; INHIBITOR; URINE AB Soluble tumor necrosis factor receptors (TNFRs) are important modulators of TNF bioactivity. Proteolytic cleavage of the 28-kDa ectodomain of TNFR1 has been recognized as the mechanism by which soluble TNFR is shed. We now describe the release of exosome-like vesicles as a mechanism for the generation of soluble, full-length 55-kDa TNFR1. We found unexpectedly that the predominant form of soluble TNFR1 in human serum and lung epithelial lining fluid is a full-length 55-kDa protein. Furthermore, supernatants from human vascular endothelial cells contain only full-length 55-kDa TNFR1 that can be sedimented by high-speed centrifugation, floated on sucrose gradients at a density of 1.1 g/ml, and associated with vesicles that range in diameter from 20 nm to 50 nm. We conclude that the release of TNFR1 exosome-like vesicles represents a previously unrecognized mechanism by which constitutive production of soluble cytokine receptors may be regulated, independent of ectodomain cleavage by receptor sheddases. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM levines@nih.gov NR 27 TC 104 Z9 109 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 3 PY 2004 VL 101 IS 5 BP 1297 EP 1302 DI 10.1073/pnas.0307981100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 771QD UT WOS:000188796800037 PM 14745008 ER PT J AU Skapenko, A Leipe, J Niesner, U Devriendt, K Beetz, R Radbruch, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, A Leipe, J Niesner, U Devriendt, K Beetz, R Radbruch, A Kalden, JR Lipsky, PE Schulze-Koops, H TI GATA-3 in human T cell helper type 2 development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Th1/Th2 cells; cellular differentiation; transcription factors; T lymphocytes; siRNA ID TRANSCRIPTION FACTOR GATA-3; AUTOIMMUNE-DISEASE; GENE-EXPRESSION; DIFFERENTIATION; LINEAGE; STIMULATION; ENHANCER; CD28; IL-4 AB The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell-mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3(+/-) individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell-mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3(+/+) controls. Concordant with these data, silencing of GATA-3 in GATA-3(+/+) CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo. C1 Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. Deutsch Rheuma Forschungszentrum, D-10117 Berlin, Germany. Katholieke Univ Leuven, Ctr Human Genet, Dept Clin Genet, B-3300 Louvain, Belgium. Univ Childrens Hosp, D-55101 Mainz, Germany. NIAMSD, Bethesda, MD 20892 USA. RP Schulze-Koops, H (reprint author), Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, Glueckstr 6, D-91054 Erlangen, Germany. EM Schulze-Koops@med3.imed.uni-erlangen.de NR 19 TC 56 Z9 69 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 2 PY 2004 VL 199 IS 3 BP 423 EP 428 DI 10.1084/jem.20031323 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 771HR UT WOS:000188780000013 PM 14757746 ER PT J AU Simons-Morton, B AF Simons-Morton, B TI Prospective association of peer influence, school engagement, drinking expectancies, and parent expectations with drinking initiation among sixth graders SO ADDICTIVE BEHAVIORS LA English DT Article DE adolescents; parenting; social influence; outcome expectations ID ALCOHOL-USE; EARLY ADOLESCENTS; ONSET; PREVENTION; ADJUSTMENT; BEHAVIORS; MEDIATORS; CHILDREN; SMOKING; ABUSE AB Early initiation of drinking increases the lifetime risk for substance abuse and other serious health and social problems. An understanding of the predictors of early initiation is needed if successful preventive interventions are to be developed. Surveys were completed by 1009 sixth grade students at the beginning (Time 1) and end (Time 2) of the school year in four schools in one suburban school district. At Time 1, 55/1009 (5.5%) reported drinking in the past 30 days. From Time 1 to Time 2, the percentage of drinkers increase to 127/1009 (10.9%) of whom 101 were new drinkers. In multiple logistic regression analyses, school engagement was negatively associated and peer influence and drinking expectancies were positively associated with drinking initiation. A significant interaction was found between drinking expectancies and parental expectations. Among sixth graders with high drinking expectancies, those with low parental expectations for their behavior were 2.6 times more likely to start drinking than those with parents with high expectations for their behavior. Positive drinking expectancies were significantly associated with drinking initiation only among teens who believed their parents did not hold strong expectations for them not to drink. This finding held for boys and girls, Blacks and Whites and was particularly strong for Black youth. This finding provides new information about the moderating effect of parental expectations on drinking expectancies among early adolescents. (C) 2003 Elsevier Ltd. All rights reserved. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bldg 6100,Room 7B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Bruce_SimonsMorton@NIH.GOV OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 30 TC 58 Z9 58 U1 3 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD FEB PY 2004 VL 29 IS 2 BP 299 EP 309 DI 10.1016/j.addbeh.2003.08.005 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 768YY UT WOS:000188600000007 PM 14732418 ER PT J AU Barron, JS Duffey, PL Byrd, LJ Campbell, R Ferrucci, L AF Barron, JS Duffey, PL Byrd, LJ Campbell, R Ferrucci, L TI Informed consent for research participation in frail older persons SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material DE clinical trials; ethics; frail elderly; informed consent ID DECISION-MAKING CAPACITY; ALZHEIMERS-DISEASE; CLINICAL-RESEARCH; ELDERLY SUBJECTS; COMPETENCE; ADULTS; INFORMATION; PREDICTORS; IMPACT; ETHICS AB Informed consent has been the most scrutinized and controversial aspect of clinical research ethics. Institutional review boards (IRBs), government regulatory agencies, and the threat of litigation have all contributed to increasingly detailed consent documents that hope to ensure that subjects are not misled or coerced. Unfortunately, the growing regulatory burden on researchers has not succeeded in protecting subjects, but has rather made the consent process less effective and has discouraged research on vulnerable populations. As a matter of fact, investigators and ethicists continue to identify failures of the consenting process, particularly concerning participation in research of older individuals. The challenges involved in ensuring appropriate consent from the elderly include physical frailty, reduced autonomy and privacy, and impaired decision-making capacity due to dementia, delirium, or other neuropsychiatric illnesses. Ageism among investigators also contributes to failure of informed consent. The evaluation and continuing re-evaluation of an individual's decision-making capacity is critical but difficult. In the most extreme cases, the older adult's ability to participate in the consent process is clearly impaired. However, in many instances. the decision-making capacity is only partially impaired but declines during the course of a research project. Implementing methods of effective communication may enable many frail elderly individuals to make informed decisions. Special challenges are posed by research on end-of-life care, which typically involves frail.. older subjects who are uniquely vulnerable, and research is conducted in institutional settings where subtle violations of autonomy are routine. Clearly, the frail elderly represent a vulnerable population that deserves special attention when developing and evaluating an informed consent process. Two important ethical conflicts should be kept in mind. First, although vulnerable older patients must be protected, protection should not prevent research on this important population. Similarly, because informed consent documents are often written to prevent legal jeopardy, these technical documents, expressed in language sometimes difficult to understand, can prevent comprehension of basic issues, defeating the ethical purpose of human protection. (C) 2004, Editrice Kurtis. C1 NIA, Clin Res Branch, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP Ferrucci, L (reprint author), Harbor Hosp, Baltimore Longitudinal Study Aging, Longitudinal Studies Sect, Clin Res Branch,NIA,NIH, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov NR 36 TC 9 Z9 9 U1 1 U2 8 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD FEB PY 2004 VL 16 IS 1 BP 79 EP 85 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 810RN UT WOS:000220721500013 PM 15132296 ER PT J AU Lueders, KK De Rosa, SC Valentin, A Pavlakis, GN Roederer, M Hamer, DH AF Lueders, KK De Rosa, SC Valentin, A Pavlakis, GN Roederer, M Hamer, DH TI A potent anti-HIV immunotoxin blocks spreading infection by primary HIV type 1 isolates in multiple cell types SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXOTOXIN HYBRID PROTEIN; ENVELOPE GLYCOPROTEIN; FLOW-CYTOMETRY; KDEL RECEPTOR; EXPRESSION; ACTIVATION; BINDING; REPLICATION; PROSTRATIN AB Although several immunotoxins that selectively kill HIV-1-infected cells have been described, their clinical utility is limited by low potency against spreading viral infection. We show here that changing the carboxyterminal sequence of an anti-HIV-1 envelope immunotoxin to the consensus endoplasmic reticulum retention sequence KDEL substantially improves its ability to block infection of peripheral blood mononuclear cells by primary HIV-1 isolates without increasing nonspecific toxicity. Polychromatic flow cytometry of peripheral blood mononuclear cells (PBMC) infected with an HIV-1-GFP reporter virus demonstrated that the improved immunotoxin is active against a variety of primary cell types including memory T cells, NK-T cells, and monocyte/macrophages. The subnanomolar potency of this agent suggests that it could be clinically useful either as an adjuvant to highly active antiretroviral therapy (HAART) in drug-resistant patients or to reduce the reservoir of latently infected cells that is implicated in HIV-1 persistence. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NCI, Human Retrovirus Sect, Basic Res Lab, Frederick, MD 21702 USA. RP Hamer, DH (reprint author), NCI, Biochem Lab, NIH, Bld 37,Rm 6002,9000 Rockville Pike, Bethesda, MD 20892 USA. EM deanh@helix.nih.gov RI Roederer, Mario/G-1887-2011 NR 28 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB PY 2004 VL 20 IS 2 BP 145 EP 150 DI 10.1089/088922204773004851 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 778UR UT WOS:000189260200003 PM 15018701 ER PT J AU Malkevitch, N Rohne, D Pinczewski, J Aldrich, K Kalyanaraman, VS Letvin, NL Robert-Guroff, M AF Malkevitch, N Rohne, D Pinczewski, J Aldrich, K Kalyanaraman, VS Letvin, NL Robert-Guroff, M TI Evaluation of combination DNA/replication-competent Ad-SIV recombinant immunization regimens in rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; HOST-RANGE MUTANT; MUCOSAL IMMUNE-RESPONSES; ANKARA BOOST REGIMEN; VACCINIA VIRUS; NEUTRALIZING ANTIBODIES; DNA VACCINES; DISEASE PROGRESSION; VIRAL REPLICATION AB Combination vaccine regimens in which priming with recombinant DNA is followed by boosting with recombinant viral vectors have been shown in previous studies to effectively enhance cellular immunity. However, no information exists concerning possible synergy of the cellular immune response when DNA immunization is followed by administration of a recombinant vector able to replicate. As our approach makes use of replication-competent Ad HIV and SIV recombinants, we performed a pilot experiment in six rhesus macaques in which we compared immunogenicity resulting from priming with one or two DNA recombinants encoding the SIVsmH4 env and rev genes with that elicited by a single replication-competent Ad5hr-SIVenv/rev priming immunization. All macaques were subsequently administered an Ad5hr-SIVenv/rev booster immunization followed by two immunizations with SIV gp120 protein. The choice of the env gene as target immunogen allowed comparison of induced cellular immune responses as well as binding and neutralizing antibodies elicited in serum and mucosal secretions. We report here that all immunized monkeys developed strong cellular immunity to the SIV envelope as shown by secretion of interferon-gamma, lysis of envelope-expressing target cells, and/or proliferation in response to gp120 or inactivated SIV. Similarly, all macaques developed anti-gp120 binding antibodies and neutralizing antibodies in serum and IgG and IgA binding antibodies in mucosal secretions. We did not observe consistently enhanced immune responses in any immunization group. We conclude that two sequential immunizations with the same replication-competent Ad5hr-SIV recombinant is as effective as priming with one or two recombinant DNA vaccines followed by a single Ad5hr-SIV recombinant immunization. C1 NCI, Sect Immune Biol Retroviral Infect, NIH, Basic Res Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. RP Robert-Guroff, M (reprint author), NCI, Sect Immune Biol Retroviral Infect, NIH, Basic Res Lab, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@exchange.nih.gov FU NIAID NIH HHS [N01-AI85343] NR 54 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB PY 2004 VL 20 IS 2 BP 235 EP 244 DI 10.1089/088922204773004969 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 778UR UT WOS:000189260200014 PM 15018712 ER PT J AU Neuhold, LA Guo, QM Alper, J Velazquez, JM AF Neuhold, LA Guo, QM Alper, J Velazquez, JM TI High-throughput troteomics for alcohol research SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID IMAGING MASS-SPECTROMETRY; PROTEIN EXPRESSION; PROTEOMICS AB This report summarizes the proceedings of a satellite symposium of the 2003 Research Society on Alcoholism meeting held on June 21, 2003, in Fort Lauderdale, FL. The goal of this symposium, sponsored by the NIAAA, was to identify new proteomic directions in alcohol research that will (1) enable studies that focus on characterizing protein function, biochemical pathways, and networks to understand alcohol-related illnesses; (2) identify protein-protein interactions, posttranslational modifications, and subcellular localizations; (3) identify molecular targets for medication development; (4) develop biomarkers for susceptibility, dependence, consumption, and relapse, as well as alcohol-induced pathologies; and (5) develop high-throughput drug screens to test the efficacy of therapeutics that control alcohol-induced diseases. The purpose of the symposium was also to promote the application of high-throughput proteomic approaches, including isolation of membrane-bound proteins, in situ proteomics, large-scale two-dimensional separations, protein microarray platforms, mass spectrometry, matrix-assisted laser desorption/ionization, matrix-assisted laser desorption/ionization time-of-flight, liquid chromatography-tandem mass spectrometry, and isotope-coded affinity tags. In addition, the development of protein network maps by using new bioinformatics approaches for database mining was also discussed. C1 NIAAA, Genet & Proteom Res Branch, NIH, Bethesda, MD 20892 USA. RP Neuhold, LA (reprint author), NIAAA, Genet & Proteom Res Branch, NIH, 6000 Execut Blvd,Suite 402, Bethesda, MD 20892 USA. EM lneuhold@willco.niaaa.nih.gov NR 13 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 203 EP 210 DI 10.1097/01.ALC.0000113410.60985.0E PG 8 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400001 PM 15112927 ER PT J AU Morrow, AL Ferrani-Kile, K Davis, MI Shumilla, JA Kumar, S Maldve, R Pandey, SC AF Morrow, AL Ferrani-Kile, K Davis, MI Shumilla, JA Kumar, S Maldve, R Pandey, SC TI Ethanol effects on cell signaling mechanisms SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID PROTEIN-KINASE-C; GAMMA-AMINOBUTYRIC-ACID; CAMP-REGULATED PHOSPHOPROTEIN; NMDA-RECEPTOR; NEUROPEPTIDE-Y; GROWTH-FACTOR; GABA(A) RECEPTORS; FYN-KINASE; IN-VIVO; CEREBRAL-CORTEX C1 Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, Sect Synapt Pharmacol, Rockville, MD USA. Stanford Univ, Sch Med, Dept Anesthesiol, Stanford, CA USA. Univ Illinois, Psychiat Inst, Dept Psychiat, Chicago, IL USA. VA Chicago Hlth Care Syst, Chicago, IL USA. RP Morrow, AL (reprint author), Univ N Carolina, Bowles Ctr Alcohol Studies, 3027 Thurston Bowles Bldg,CB 7178, Chapel Hill, NC 27599 USA. EM morrow@med.unc.edu RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351 FU NIAAA NIH HHS [UO1-AA13CR, AA11863, AA13341, AA05809, AA10005, AA11605]; NINDS NIH HHS [NS13108] NR 80 TC 17 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 217 EP 227 DI 10.1097/01.ALC.0000113439.97498.AC PG 11 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400003 PM 15112929 ER PT J AU Fromme, K de Wit, H Hutchison, KE Ray, L Corbin, WR Cook, TAR Wall, TL Goldman, D AF Fromme, K de Wit, H Hutchison, KE Ray, L Corbin, WR Cook, TAR Wall, TL Goldman, D TI Biological and behavioral markers of alcohol sensitivity SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol sensitivity; serotonin; GABA; ALDH2; ADH2 ID SEROTONIN TRANSPORTER GENE; ALDEHYDE DEHYDROGENASE GENOTYPES; INDIVIDUAL-DIFFERENCES; SUBSTANCE-ABUSE; ETHANOL; RISK; DEPENDENCE; SONS; RESPONSES; POLYMORPHISMS AB This article summarizes a symposium that was organized by Dr. Kim Fromme and presented at the 2003 annual meeting of the Research Society on Alcoholism in Ft. Lauderdale, Florida. The four presentations illustrate the emerging technologies and methods that are now being used to investigate the genetic basis of differential sensitivity to alcohol and their behavioral manifestations. Combining human genotyping with laboratory measures of behavior and subjective reports, these presentations represent state-of-the-art approaches to crossing the bridge from the Decade of the Brain to the Decade of Behavior. Dr. De Wit's paper describes her research on the neurobiological basis for individual differences in sensitivity to the stimulant and sedative effects of alcohol. Evidence suggests that activity of the dopaminergic and GABAergic neurotransmitters underlie these stimulant and sedative effects, respectively. Both Drs. Hutchison's and Corbin's papers describe their research on polymorphisms for the serotonin transporter (SLC6A4) as a determinant of the subjective effects of alcohol challenge. Dr. Hutchinson's and Ms. Ray's findings indicate that individuals with the short form of the SLC6A4 alleles (S) demonstrated a low level of response to alcohol, thus supporting previous research that the S allele may be associated with increased risk for alcohol dependence. In contrast, Dr. Corbin did not find a reliable association between the SLC6A4 genotype and subjective response to alcohol. Mr. Cook's and Dr. Wall's paper adds another dimension to this article by presenting research on both the aldehyde dehydrogenase (ALDH2) and alcohol dehydrogenase (ADH2) genetic variants and their association with the alcohol-related flushing response that is prevalent in Asian populations. Dr. David Goldman provides concluding remarks. C1 Univ Texas, Dept Psychol, Austin, TX 78712 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Univ Calif San Diego, Dept Psychiat, Vet Affairs San Diego Healthcare Syst, Vet Med Res Fdn, La Jolla, CA 92093 USA. Univ Calif San Diego, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA. NIAAA, NIH, Neurogenet Lab, Rockville, MD USA. RP Fromme, K (reprint author), Univ Texas, Dept Psychol, Austin, TX 78712 USA. EM fromme@psy.utexas.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; de Wit, Harriet/0000-0002-7211-8994 FU NCRR NIH HHS [M01RR00827]; NIAAA NIH HHS [R01-AA11683, 5T32-AA07471, K02AA00269, P50AA07611, R01AA11257, T32 AA013525, T32AA13525]; NIDA NIH HHS [DA02812] NR 50 TC 20 Z9 21 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 247 EP 256 DI 10.1097/01.ALC.0000113420.28472.25 PG 10 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400006 PM 15112932 ER PT J AU McBride, WJ Lovinger, DM Machu, T Thielen, RJ Rodd, ZA Murphy, JM Roache, JD Johnson, BA AF McBride, WJ Lovinger, DM Machu, T Thielen, RJ Rodd, ZA Murphy, JM Roache, JD Johnson, BA TI Serotonin-3 receptors in the actions of alcohol, alcohol reinforcement, and alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE serotonin-3 receptor; alcohol reinforcement; mesolimbic dopamine system; Ondansetron; alcoholism treatment ID LATE-ONSET ALCOHOLICS; BIOLOGICALLY PREDISPOSED ALCOHOLICS; VOLUNTARY ETHANOL-CONSUMPTION; NCB-20 NEUROBLASTOMA-CELLS; FREELY MOVING RATS; GATED ION-CHANNEL; 5-HT3 RECEPTOR; DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; PREFERRING P AB This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers and chairs were William J. McBride and David M. Lovinger. The presentations were (1) Mechanisms of alcohol potentiation of 5-HT3 receptor function, by David M. Lovinger and Tina Machu; (2) Chronic alcohol drinking alters 5-HT3 receptors regulating the mesolimbic dopamine system, by Richard J. Thielen; (3) 5-HT3 receptors in the VTA regulate alcohol drinking and the reinforcing effects of alcohol, by Zachary A. Rodd and James M. Murphy; and (4) Ondansetron as a treatment for "biological" alcoholism, by John D. Roache and Bankole A. Johnson. C1 Indiana Univ, Sch Med, Indianapolis, IN USA. NIAAA, Div Clin & Basic Res, Rockville, MD 20852 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. RP McBride, WJ (reprint author), Inst Psychiat Res, 791 Union Dr, Indianapolis, IN 46202 USA. EM wmcbride@iupui.edu RI Rodd, Zachary/L-1580-2015 OI Rodd, Zachary/0000-0002-8105-1920 FU NIAAA NIH HHS [AA07611, AA012964, AA10522, AA10717, AA12262] NR 78 TC 49 Z9 51 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 257 EP 267 DI 10.1097/01.ALC.0000113419.99915.DA PG 11 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400007 PM 15112933 ER PT J AU Thiele, TE Stewart, RB Badia-Elder, NE Geary, N Massi, M Leibowitz, SF Hoebel, BG Egli, M AF Thiele, TE Stewart, RB Badia-Elder, NE Geary, N Massi, M Leibowitz, SF Hoebel, BG Egli, M TI Overlapping peptide control of alcohol self-administration and feeding SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE peptide; melancortin; neuropeptide Y; cholecystokinin; galanin ID MELANOCYTE-STIMULATING HORMONE; NEUROPEPTIDE-Y NPY; CENTRAL-NERVOUS-SYSTEM; ORAL ETHANOL INTAKE; PREFERRING AA RATS; FOOD-INTAKE; ALPHA-MSH; BETA-ENDORPHIN; CONSUMPTION; DRINKING AB This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers and chairpersons were Mark Egli and Todd E. Thiele. The presentations were (1) Voluntary alcohol consumption is modulated by central melanocortin receptors, by Todd E. Thiele; (2) Central infusion of neuropeptide Y reduces alcohol drinking in alcohol-preferring P rats, by Robert B. Stewart and Nancy E. Badia-Elder; (3) The gut peptide cholecystokinin controls alcohol intake in Sardinian alcohol-preferring rats, by Nori Geary and Maurizio Massi; and (4) Hypothalamic galanin: a possible role in excess alcohol drinking, by Sarah F. Leibowitz and Bartley G. Hoebel. C1 Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Perdue Sch Sci, Dept Psychol, Indianapolis, IN USA. New York Presbyterian Hosp, Dept Psychiat, Westchester Div, White Plains, NY USA. Univ Camerino, Dept Pharmacol Sci & Expt Med, I-62032 Camerino, Italy. Rockefeller Univ, Lab Behav Neurosci, New York, NY 10021 USA. Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. NIAAA, DHHS, Div Neurosci & Behav, NIH, Bethesda, MD USA. RP Thiele, TE (reprint author), Univ N Carolina, Dept Psychol, CB 3270, Chapel Hill, NC 27599 USA. EM thiele@unc.edu FU NIAAA NIH HHS [AA12857, AA13573, AA10722, AA12882, AA012880, AA00258] NR 71 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 288 EP 294 DI 10.1097/01.ALC.0000113777.87190.9C PG 7 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400010 PM 15112936 ER PT J AU Le Fauve, CE Litten, RZ Randall, CL Moak, DH Salloum, IM Green, AI AF Le Fauve, CE Litten, RZ Randall, CL Moak, DH Salloum, IM Green, AI TI Pharmacological treatment of alcohol abuse/dependence with psychiatric comorbidity SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE pharmacotherapy; alcoholism treatment; psychiatric comorbidity ID PLACEBO-CONTROLLED TRIAL; COGNITIVE-BEHAVIORAL THERAPY; SOCIAL ANXIETY DISORDER; SUBSTANCE-ABUSE PATIENTS; MAJOR DEPRESSION; DOUBLE-BLIND; MENTAL-DISORDERS; SERTRALINE TREATMENT; GENERAL-POPULATION; COCAINE DEPENDENCE AB This article represents the proceedings of a symposium at the 2003 annual meeting RSA in Fort Lauderdale, FL. It was organized and cochaired by Charlene E. Le Fauve and Carrie L. Randall. The presentations were (1) Introduction, by Charlene E. Le Fauve and Raye Z. Litten; (2) Treatment of co-occurring alcohol use and anxiety disorders, by Carrie L. Randall and Sarah W. Book; (3) Pharmacological treatment of alcohol dependent patients with comorbid depression, by Darlene H. Moak; (4) Efficacy of valproate in bipolar alcoholics: a double blind, placebo-controlled study, by Ihsan M. Salloum, Jack R. Cornelius, Dennis C. Daley, Levent Kirisci, Johnathan Himmelhoch, and Michael E. Thase; (5) Alcoholism and schizophrenia: effects of antipsychotics, by Alan I. Green, Robert E. Drake, Suzannah V. Zimmet, Rael D. Strous, Melinda Salomon, and Mark Brenner; and (6) Conclusions, by Charlene E. Le Fauve; discussant, Raye Z. Litten. Alcohol-dependent individuals have exceptionally high rates of co-occurring psychiatric disorders. Although this population is more likely to seek alcoholism treatment than noncomorbid alcoholics, the prognosis for treatment is often poor, particularly among patients with more severe psychiatric illnesses. Development of effective interventions to treat this population is in the early stages of research. Although the interaction between the psychiatric condition and alcoholism is complex, progress has been made. The NIAAA has supported a number of state-of-the-art pharmacological and behavioral trials in a variety of comorbid psychiatric disorders. Some of these trials have been completed and are presented here. The symposium presented some new research findings from clinical studies with the aim of facilitating the development of treatments that improve alcohol and psychiatric outcomes among individuals with alcohol-use disorders and co-occurring psychiatric disorders. The panel focused on social anxiety disorder, depression, bipolar disorder, and schizophrenia. C1 NIAAA, Treatment Res Branch, Div Clin & Prevent Res, Bethesda, MD USA. Med Univ S Carolina, Ctr Alcohol Programs, Charleston, SC 29425 USA. Univ Pittsburgh, Ctr Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Dartmouth Coll Sch Med, Dept Psychiat, Lebanon, NH USA. RP Le Fauve, CE (reprint author), Div Treatment & Recovery Res, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM clefauve@NIAAA.nih.gov FU NIAAA NIH HHS [AA10476, R29 AA10523] NR 71 TC 36 Z9 37 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 302 EP 312 DI 10.1097/01.ALC.0000113413.37910.D7 PG 11 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400012 PM 15112938 ER PT J AU Conigliaro, J Madenwald, T Bryant, K Braithwaite, S Gordon, A Fultz, SL Maisto, S Samet, J Kraemer, K Cook, R Day, N Roach, D Richey, S Justice, A AF Conigliaro, J Madenwald, T Bryant, K Braithwaite, S Gordon, A Fultz, SL Maisto, S Samet, J Kraemer, K Cook, R Day, N Roach, D Richey, S Justice, A TI The veterans aging cohort study: Observational studies of alcohol use, abuse, and outcomes among human immunodeficiency virus-infected veterans SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE HIV/AIDS; alcohol; comorbidity; outcomes; homelessness ID HEPATITIS-C; HIV-INFECTION; ANTIRETROVIRAL THERAPY; REPORTED ADHERENCE; PROBLEM DRINKING; SEXUAL-BEHAVIOR; CLINICAL-TRIALS; LIVER-DISEASE; SUBSTANCE USE; RISK AB This article represents the proceedings of a symposium at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The organizers/chairs were Joseph Conigliaro and Amy Justice. The presentations were (1) Introduction, by Joseph Conigliaro and Tamra Madenwald; (2) Alcohol and HIV/AIDS: the importance of integrative and translational research, by Kendall Bryant; (3) Alcohol use and abuse among patients with HIV infection, by Joseph Conigliaro and Stephan Maisto; (4) Severity of comorbid alcohol use/abuse in HIV infection, by Amy Justice and Jeffrey Samet; (5) Estimating the impact of alcohol use on long-term HIV outcomes, by Scott Braithwaite and Amy Justice; (6) Homelessness, drug & alcohol use among HIV+ veterans, by Adam Gordon and Robert Cook; and (7) Hepatitis C & alcohol in the VACS 3 study, by Shawn Fultz and Kevin Kraemer. The symposium concluded with a discussion led and facilitated by Diedra Roach. C1 VA Pittsburg Healthcare Syst, Pittsburgh, PA 15240 USA. CHERP, Pittsburgh, PA USA. MIRECC, Pittsburgh, PA USA. CRHC, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. NIAAA, Bethesda, MD USA. Yale Univ, New Haven, CT USA. Syracuse Univ, Syracuse, NY USA. Boston Univ, Ctr Med, Boston, MA USA. RP Conigliaro, J (reprint author), VA Pittsburg Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA. EM joseph.conigliaro@med.va.gov OI Samet, Jeffrey/0000-0002-0897-3400 FU NIA NIH HHS [K 23 AG00826-03]; NIAAA NIH HHS [AA 13566-02] NR 48 TC 26 Z9 26 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 313 EP 321 DI 10.1097/01.ALC.0000113414.73220.21 PG 9 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400013 PM 15112939 ER PT J AU Faden, VB Day, NL Windle, M Windle, R Grube, JW Molina, BSG Pelham, WE Gnagy, EM Wilson, TK Jackson, KM Sher, KJ AF Faden, VB Day, NL Windle, M Windle, R Grube, JW Molina, BSG Pelham, WE Gnagy, EM Wilson, TK Jackson, KM Sher, KJ TI Collecting longitudinal data through childhood, adolescence, and young adulthood: Methodological challenges SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MATERNAL DEPRESSIVE SYMPTOMS; MIDDLE ADOLESCENTS; SUBSTANCE USE; PROBLEM BEHAVIORS; ADJUSTMENT; CHILDREN; ASSOCIATIONS; PATHWAYS; DISCORD AB This article presents the proceedings of a workshop at the 2003 Research Society on Alcoholism meeting in Fort Lauderdale, Florida. The organizers and chairs were Vivian Faden and Nancy Day. The presentations were (1) Lessons Learned From the Lives Across Time Longitudinal Study, by Michael Windle and Rebecca Windle; (2) Methodological Issues in Longitudinal Surveys With Children and Adolescents, by Joel Grube; (3) The Pittsburgh ADHD Longitudinal Study: Methodological and Conceptual Challenges, by Brooke Molina, William Pelham, Elizabeth Gnagy, and Tracey Wilson; and (4) Lessons learned in Conducting Longitudinal Research on Alcohol Involvement: If Only I Had Known Before Hand! by Kristina Jackson and Kenneth Sher. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Prevent Res Ctr, Berkeley, CA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. SUNY Buffalo, Dept Psychol, Buffalo, NY USA. SUNY Buffalo, Dept Pediat, Buffalo, NY USA. Univ Pittsburgh, Ctr Med, ADD Program, Pittsburgh, PA USA. Univ Missouri, Missouri Alcoholism Res Ctr, Columbia, MO 65211 USA. Univ Missouri, Dept Psychol, Columbia, MO 65211 USA. RP Faden, VB (reprint author), NIAAA, NIH, 5635 Fishers Lane Room 2085 MSC 9304, Bethesda, MD 20892 USA. EM vfaden@mail.nih.gov RI Day, Nancy/H-3171-2016 FU NIAAA NIH HHS [K01 AA013938, K01 AA013938-01, R01 AA007861, R37 AA007861] NR 27 TC 25 Z9 25 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2004 VL 28 IS 2 BP 330 EP 340 DI 10.1097/01.ALC.0000113411.33088.FE PG 11 WC Substance Abuse SC Substance Abuse GA 776YR UT WOS:000189147400015 PM 15112941 ER PT J AU Ziegler, RG AF Ziegler, RG TI Phytoestrogens and breast cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID DIETARY PHYTOESTROGENS; PHYTO-ESTROGENS; RISK; WOMEN; SOY; ENTEROLACTONE; LIGNANS C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ziegler, RG (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Execut Plaza S 8098, Bethesda, MD 20892 USA. EM zieglerr@mail.nih.gov NR 14 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2004 VL 79 IS 2 BP 183 EP 184 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 767KN UT WOS:000188438900002 PM 14749221 ER PT J AU Cesari, M Pahor, M Bartali, B Cherubini, A Penninx, BWJH Williams, GR Atkinson, H Martin, A Guralnik, JM Ferrucci, L AF Cesari, M Pahor, M Bartali, B Cherubini, A Penninx, BWJH Williams, GR Atkinson, H Martin, A Guralnik, JM Ferrucci, L TI Antioxidants and physical performance in elderly persons: the Invecchiare in Chianti (InCHIANTI) study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE antioxidants; dietary intake; physical performance; elderly ID DIETARY-INTAKE MEASUREMENTS; LOWER-EXTREMITY FUNCTION; VITAMIN-E; SUBSEQUENT DISABILITY; LIPID-PEROXIDATION; ECCENTRIC EXERCISE; WOMENS HEALTH; EPIC PROJECT; AGE; SUPPLEMENTATION AB Background: Muscle strength and physical performance in old age might be related to the oxidative damage caused by free radicals. Objective: The objective was to assess the correlation of plasma concentrations and daily dietary intakes of antioxidants with skeletal muscle strength and physical performance in elderly persons. Design: This study is part of the Invecchiare in Chianti (InCHIANTI) study, which was conducted in 986 Italians aged greater than or equal to65 y. Physical performance was assessed on the basis of walking speed, ability to rise from a chair, and standing balance. Knee extension strength was assessed with a hand-held dynamometer. The European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire was used to evaluate the daily dietary intakes of vitamin C, vitamin E, beta-carotene, and retinol. Plasma alpha- and gamma-tocopherol concentrations were measured. Adjusted linear regression analyses were used to calculate regression coefficients per SD increase in plasma concentrations and daily dietary intakes. Results: In adjusted analyses, plasma a-tocopherol was significantly correlated with knee extension (beta = 0.566, P = 0.003) and the summary physical performance score (beta = 0.044, P = 0.008). Plasma gamma-tocopherol was associated only with knee extension strength (beta = 0.327, P = 0.04). Of the daily dietary intake measures, vitamin C and beta-carotene were significantly correlated with knee extension strength, and vitamin C was significantly associated with physical performance (beta = 0.029, P = 0.04). Conclusions: Plasma antioxidant concentrations correlate positively with physical performance and strength. Higher dietary intakes of most antioxidants, especially vitamin C, appear to be associated with higher skeletal muscular strength in elderly persons. C1 Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27157 USA. Italian Natl Res Council Aging, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Univ Perugia, Dept Gerontol & Geriatr, I-06100 Perugia, Italy. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NIA, Epidemiol Demog & Biometr Program, Bethesda, MD 20892 USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Cesari, M (reprint author), Wake Forest Univ, Sticht Ctr Aging, 1 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mcesari@wfubmc.edu RI Cesari, Matteo/A-4649-2008; OI Cesari, Matteo/0000-0002-0348-3664; Cherubini, Antonio/0000-0003-0261-9897 FU NIA NIH HHS [P30-AG-021332-01] NR 34 TC 118 Z9 121 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2004 VL 79 IS 2 BP 289 EP 294 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 767KN UT WOS:000188438900017 PM 14749236 ER PT J AU Lee, JS Weyant, RJ Corby, P Kritchevsky, SB Harris, TB Rooks, R Rubin, SM Newman, AB AF Lee, JS Weyant, RJ Corby, P Kritchevsky, SB Harris, TB Rooks, R Rubin, SM Newman, AB TI Edentulism and nutritional status in a biracial sample of well-functioning, community-dwelling elderly: the Health, Aging, and Body Composition Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE edentulism; nutritional status; well-functioning community-dwelling elderly; socioeconomic status; racial-ethnic differences; Health ABC Study ID ORAL-HEALTH; OLDER-ADULTS; TOOTH LOSS; COMPLETE DENTURES; DIETARY-INTAKE; MASTICATORY PERFORMANCE; RISK INDICATORS; NUTRIENT INTAKE; UNITED-STATES; WEIGHT-LOSS AB Background: Edentulism may affect dietary intake in older adults, but the relation between edentulism and nutritional status is not completely understood. Objective: The present study examined whether edentulism is associated with nutritional status and whether there is an interaction between race and edentulism on nutritional status among well-functioning, community-dwelling elderly. Design: The study cohort included 3075 elderly aged 70-79 y (52% women, 42% black) in the Health, Aging, and Body Composition Study. Dietary intake, anthropometric variables, weight change, and serum albumin and lipid concentrations were compared between edentate and dentate participants by the use of multiple linear and logistic regressions. Results: Edentulism was not associated with total energy or food intake but was associated with the food groups consumed, particularly fat, micronutrients, and hard-to-chew foods. Edentulism was more strongly linked to dietary intake in whites than in blacks. Unlike black edentate elderly, white edentate elderly consumed significantly lower energy-adjusted amounts of vitamin A and beta-carotene, higher amounts of energy-adjusted total and saturated fat and cholesterol, and higher percentages of energy from fat than did white dentate elderly. Anthropometry and biochemical indexes were not significantly different by edentulism status in both races. Edentulism was associated with weight gains of >5% in I y in both races. Conclusions: Edentulism was associated with differences in the nutritional status of well-functioning, community-dwelling elderly, more so in whites than blacks. Edentate elders may benefit from dental, medical, and nutrition interventions targeted to addressing these findings. C1 Univ Pittsburgh, Dept Med, Div Geriatr, Pittsburgh, PA 15213 USA. Wake Forest Univ, J Paul Sticht Ctr Aging, Winston Salem, NC USA. NIA, Bethesda, MD 20892 USA. Kent State Univ, Dept Sociol, Kent, OH USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. RP Lee, JS (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr, 130 N Bellefield ave,Room 511, Pittsburgh, PA 15213 USA. EM leej@edc.pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2101, N01-AG-6-2106] NR 65 TC 58 Z9 63 U1 6 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2004 VL 79 IS 2 BP 295 EP 302 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 767KN UT WOS:000188438900018 PM 14749237 ER PT J AU Blanc, S Schoeller, DA Bauer, D Danielson, ME Tylavsky, F Simonsick, EM Harris, TB Kritchevsky, SB Everhart, JE AF Blanc, S Schoeller, DA Bauer, D Danielson, ME Tylavsky, F Simonsick, EM Harris, TB Kritchevsky, SB Everhart, JE TI Energy requirements in the eighth decade of life SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE aging; obesity; malnutrition; African Americans; sex; energy expenditure ID DOUBLY-LABELED WATER; RESTING METABOLIC-RATE; AFRICAN-AMERICANS; PHYSICAL-ACTIVITY; NATIONAL-HEALTH; EXPENDITURE; WOMEN; MEN; AGE; CAUCASIANS AB Background: Knowledge of energy requirements among relatively healthy elderly is limited. Objectives: The objectives of the study were to measure total energy expenditure (TEE)-derived energy requirements in a biracial population of older adults without limitations to daily life and to test these empirical measures against national and international recommendations. Design: TEE (measured by the doubly labeled water method), resting metabolic rate (RMR), activity-related energy expenditure (AEE), and body composition were measured in 288 persons aged 70-79 y selected from the Health, Aging, and Body Composition Study. Results: TEE was lower in women (approximate to530 kcal/d; P < 0.0001) than in men because of the women's lower RMR and AEE. Fat-free mass explained the sex difference in RMR, but body weight failed to account for the women's lower AEE (approximate to1 kcal kg(-1) (.) d(-1); P = 0.007). Blacks had lower TEE than did whites (approximate to100 kcal/d, P = 0.03), and that was explained by blacks' lower RMR. Physical activity level (TEE/RMR) did not differ significantly between sexes and races (1.70 +/- 0.23). The World Health Organization (WHO) recommendations overestimated TEE by 10 +/- 15% (P < 0.0001) in women but not in men, and the dietary reference intakes (DRIs) were accurate to 0 +/- 14% (P = 0.1). Both WHO and DRI recommendations are based on an underestimated physical activity level, and WHO recommendations are based on overestimated RMR. Conclusions: This study of well-functioning older adults confirms the racial difference in energy metabolism and supports the use of the 2002 DRIs. Because the DRIs and WHO recommendations underestimated PAL, new predictive equations of energy requirements are proposed. C1 Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NIDDKD, Bethesda, MD 20892 USA. RP Schoeller, DA (reprint author), Univ Wisconsin, Dept Nutr Sci, 1415 Linden Dr, Madison, WI 53706 USA. EM dschoell@nutrisci.wisc.edu FU NIA NIH HHS [N01-AG-6-2106, N01-AG-6-2102, N01-AG-6-2103] NR 43 TC 41 Z9 41 U1 0 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2004 VL 79 IS 2 BP 303 EP 310 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 767KN UT WOS:000188438900019 PM 14749238 ER PT J AU Sun, SS Chumlea, WC Heymsfield, SB Lukaski, HC Schoeller, D Friedl, K Kuczmarski, RJ Hubbard, VS Flegal, KM Johnson, CL AF Sun, SS Chumlea, WC Heymsfield, SB Lukaski, HC Schoeller, D Friedl, K Kuczmarski, RJ Hubbard, VS Flegal, KM Johnson, CL TI Bioelectrical impedance analysis for predicting body composition: what about the external validity of new regression equations? Reply to U Trippo et al SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID VALIDATION; CHILDREN C1 Lifespan Hlth Res Ctr, Dept Community Hlth, Dayton, OH 45420 USA. St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY USA. USDA ARS, Grand Forks, ND USA. Univ Wisconsin, Madison, WI USA. Mil Operat Med Program, Frederick, MD USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Hyattsville, MD USA. RP Friedl, K (reprint author), Lifespan Hlth Res Ctr, Dept Community Hlth, 3171 Res Blvd, Dayton, OH 45420 USA. EM shumei.sun@wright.ed RI Flegal, Katherine/A-4608-2013 NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 2004 VL 79 IS 2 BP 336 EP 337 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 767KN UT WOS:000188438900026 ER PT J AU Berman, JJ AF Berman, JJ TI Racing to share pathology data SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID PATENTS C1 NCI, Canc Diagnos Program, NIH, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Canc Diagnos Program, NIH, Bethesda, MD 20892 USA. NR 15 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD FEB PY 2004 VL 121 IS 2 BP 169 EP 171 DI 10.1309/F7B40JMQ4F8VPDG6 PG 3 WC Pathology SC Pathology GA 768NX UT WOS:000188550000001 PM 14983928 ER PT J AU Silverberg, MJ Smith, MW Chmiel, JS Detels, R Margolick, JB Rinaldo, CR O'Brien, SJ Munoz, A AF Silverberg, MJ Smith, MW Chmiel, JS Detels, R Margolick, JB Rinaldo, CR O'Brien, SJ Munoz, A TI Fraction of cases of acquired immunodeficiency syndrome prevented by the interactions of identified restriction gene variants SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; chemokines; cytokines; epidemiologic methods; HIV-1; HLA antigens; receptors, chemokine ID MULTICENTER AIDS COHORT; HIV-1 DISEASE PROGRESSION; VIRUS TYPE-1; INFECTION; RESISTANCE; ALLELES; CCR5; PATHOGENESIS; INDIVIDUALS; REGRESSION AB Previous research has demonstrated isolated effects of host genetic factors on the progression of human immunodeficiency virus type 1 (HIV-1) infection. In this paper, the authors present a novel use of multivariable methods for estimating the prevented fraction of acquired immunodeficiency syndrome (AIDS) cases attributable to six restriction genes after accounting for their epidemiologic interactions. The methods presented will never yield a prevented fraction above 1. The study population consisted of a well-characterized cohort of 525 US men with HIV-1 seroconversion documented during follow-up (1984-1996). On the basis of a regression tree approach using a Cox proportional hazards model for times to clinical AIDS, the combinations of genes associated with the greatest protection, relative to the lack of a protective genotype, consisted of: 1) C-C chemokine receptor 5 (CCR5)-Delta32 and C-C chemokine receptor 2 (CCR2)-64I (relative hazard = 0.44); 2) interleukin 10 (IL10)-+/+ in combination with CCR5-Delta32 or CCR2-64I (relative hazard = 0.45); and 3) IL10-+/+ in combination with stromal-derived factor (SDF1)-3 'A and CCR5 promoter P1/similar toP1 (relative hazard = 0.37). Overall, 30% of potential AIDS cases were prevented by the observed combinations of restriction genes (95% confidence interval: 7, 47). However, the combined effect was confined to the first 4 years following HIV-1 seroconversion. Additional research is needed to identify AIDS restriction genes with stronger and long-lasting protection to better characterize the genetic epidemiology of HIV-1. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Sci Applicat Int Corp, Basic Res Program, Frederick, MD USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Silverberg, MJ (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E-7137, Baltimore, MD 21205 USA. EM msilverb@jhsph.edu RI Smith, Michael/B-5341-2012 FU NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [5-M01-RR-00722]; NIAID NIH HHS [U01-AI-35041, U01-AI-35039, U01-AI-35040, U01-AI-35042, U01-AI-37613, U01-AI-37984, U01-AI-35043] NR 32 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2004 VL 159 IS 3 BP 232 EP 241 DI 10.1093/aje/kwh036 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 769FC UT WOS:000188614900005 PM 14742283 ER PT J AU Lissner, L Potischman, N Troiano, R Bengtsson, C AF Lissner, L Potischman, N Troiano, R Bengtsson, C TI Recall of physical activity in the distant past: The 32-year follow-up of the prospective population study of women in Goteborg, Sweden SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias (epidemiology); exercise; mental recall; prospective studies; women ID PARTICIPATION AB It has been of interest to researchers in chronic disease epidemiology to determine whether elderly subjects can accurately recall their physical activity patterns in the distant past. As part of a 32-year follow-up of the Prospective Population Study of Women in Goteborg, Sweden, 433 participants currently aged 70-92 years recalled their leisure-time physical activity at the original examination in 1968, when they had been 38-60 years of age. Using a four-point scale, subjects were originally asked to describe leisure-time activity during the previous 12 months. Identical questions were asked in 2000 describing levels in 1968 and current levels. Subjects were more likely to overestimate their previous activity level than to underestimate it: 43.9% of women classified themselves consistently at both examinations; 48.7% overestimated and 7.4% underestimated their previous activity levels. Using current activity as a proxy for recalled levels did not improve the moderate agreement with activity as originally reported in 1968. The average magnitude of the recall bias (recalled minus original values) amounted to one half of a unit on the four-point scale and was not significantly associated with age or body mass index. In summary, systematic errors were observed in remote physical activity recalls by elderly women, who generally remembered being more active 32 years earlier than they had originally reported. Physical activity recall questionnaires for the distant past should be used with caution, particularly in older populations. C1 Univ Gothenburg, Sahlgrenska Acad, Dept Primary Hlth Care, Inst Community Med Primary Hlth Care, S-40530 Gothenburg, Sweden. Nord Sch Publ Hlth, Gothenburg, Sweden. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP Lissner, L (reprint author), Univ Gothenburg, Sahlgrenska Acad, Dept Primary Hlth Care, Inst Community Med Primary Hlth Care, Box 454, S-40530 Gothenburg, Sweden. EM Lauren.Lissner@medfak.gu.se OI Troiano, Richard/0000-0002-6807-989X NR 8 TC 23 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 2004 VL 159 IS 3 BP 304 EP 307 DI 10.1093/aje/kwh048 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 769FC UT WOS:000188614900013 PM 14742291 ER PT J AU Rick, ME Austin, H Leitman, SF Krizek, DM Aronson, DL AF Rick, ME Austin, H Leitman, SF Krizek, DM Aronson, DL TI Clinical usefulness of a functional assay for the von Willebrand factor cleaving protease (ADAMTS 13) and its inhibitor in a patient with thrombotic thrombocytopenic purpura SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE TTP; ADAMTS 13 assay; von Willebrand factor cleaving protease; plasma exchange ID HEMOLYTIC-UREMIC SYNDROME; PLASMA-EXCHANGE; MICROANGIOPATHIES; METALLOPROTEASE; PURIFICATION; DISEASE; BINDING; FAMILY; MEMBER AB Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed. Am. J. Hematol. 75:96-100, 2004. Published 2004 Wiley-Liss, Inc(dagger). C1 Warren Grant Magnuson Clin Ctr, Dept Lab Med, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. RP Rick, ME (reprint author), Warren Grant Magnuson Clin Ctr, Dept Lab Med, NIH, Bldg 10,Room 2C390,10 Ctr Dr, Bethesda, MD 20892 USA. EM mrick@mail.cc.nih.gov NR 24 TC 13 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD FEB PY 2004 VL 75 IS 2 BP 96 EP 100 DI 10.1002/ajh.10457 PG 5 WC Hematology SC Hematology GA 770CB UT WOS:000188704700007 PM 14755376 ER PT J AU Fox, CS Cupples, LA Chazaro, I Polak, JF Wolf, PA D'Agostino, RB Ordovas, JM O'Donnell, CJ AF Fox, CS Cupples, LA Chazaro, I Polak, JF Wolf, PA D'Agostino, RB Ordovas, JM O'Donnell, CJ TI Genomewide linkage analysis for internal carotid artery intimal medial thickness: Evidence for linkage to chromosome 12 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN RECEPTOR; SCAVENGER RECEPTOR; SR-BI; MYOCARDIAL-INFARCTION; RISK-FACTORS; GENE LOCUS; DEFICIENT MICE; WIDE SCAN; I GENE AB Carotid intimal medial thickness (IMT) is a heritable quantitative measure of atherosclerosis. A genomewide linkage analysis was conducted to localize a quantitative-trait locus (QTL) influencing carotid IMT. Carotid IMT was measured in 596 men and 629 women from 311 extended families (1,242 sib pairs) in the Framingham Heart Study Offspring cohort. B-mode carotid ultrasonography was used to define mean IMT of the carotid artery segments. Multipoint variance-component linkage analysis was performed. Evidence for significant linkage to internal carotid artery (ICA) IMT (two-point log odds [LOD] score 4.1, multipoint LOD score 3.4) was found 161 cM from the tip of the short arm of chromosome 12; these results were confirmed using the GENEHUNTER package ( multipoint LOD score 4.3). No LOD scores >2.0 were observed for common carotid artery (CCA) IMT. Association analysis of a single-nucleotide-polymorphism variant of SCARB1 (minor allele frequency 0.13), a gene in close proximity to the region of peak linkage, revealed a protective association of the missense variant allele in exon 1 of SCARB1, with decreased ICA IMT compared with subjects homozygous for the common allele. Although the exon 1 variant contributed 2% to overall variation in ICA IMT, there was no significant change in the peak LOD score after adjustment in the linkage analyses. These data provide substantial evidence for a QTL on chromosome 12 influencing ICA IMT and for association of a rare variant of SCARB1, or a nearby locus, with ICA IMT. Because this rare SCARB1 variant does not account for our observed linkage, further investigations are warranted to identify additional candidate-gene variants on chromosome 12 predisposing to atherosclerosis phenotypes and clinical vascular disease. C1 NHLBIs Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Dept Neurol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Dept Biostat & Stat, Boston, MA 02215 USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. Tufts Univ, USDA, Human Nutr Res Ctr, Medford, MA 02155 USA. NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM chris@fram.nhlbi.nih.gov OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776, N01-HC-25195, N01HC25195, R01 HL054776]; NINDS NIH HHS [R01 NS017950, R501-NS17950-20] NR 44 TC 60 Z9 61 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD FEB PY 2004 VL 74 IS 2 BP 253 EP 261 DI 10.1086/381559 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 772UM UT WOS:000188860000006 PM 14730480 ER PT J AU Balow, JE Austin, HA AF Balow, JE Austin, HA TI Treatment of proliferative lupus nephritis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID CONTROLLED TRIAL; CYCLOPHOSPHAMIDE; THERAPY; GLOMERULONEPHRITIS; PREDNISONE; AZATHIOPRINE; AMERICANS; DRUGS C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Balow, JE (reprint author), NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NR 21 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD FEB PY 2004 VL 43 IS 2 BP 383 EP 385 DI 10.1053/j.ajkd.2003.12.008 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 773JQ UT WOS:000188921000021 PM 14750105 ER PT J AU Gropman, A Chen, TJ Perng, CL Krasnewich, D Chernoff, E Tifft, C Wong, LJC AF Gropman, A Chen, TJ Perng, CL Krasnewich, D Chernoff, E Tifft, C Wong, LJC TI Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE mtDNA point mutation; mitochondrial disease; G14459A mutation ID HEREDITARY OPTIC NEUROPATHY; DYSTONIA AB Leber hereditary optic neuropathy (LHON)/pediatric onset dystonia is associated with a G to A transition at nucleotide position (np) 14459,within the mitochondrial DNA (mtDNA)encoded ND6 gene. This mutation has been reported in families presenting with LHON alone, LHON plus dystonia, or pediatric dystonia with typical age of onset less than 5 years. The mutation changes a moderately conserved alanine to a valine at amino acid residue 72, which is within the most evolutionarily conserved region of the ND6 protein. Pediatric onset disease is associated with basal ganglia dysfunction, spasticity, and encephalopathy. We report a family with G14459A mtDNA mutation and a broad spectrum of clinical manifestation. The proband was a 3-year-old girl with anarthria, dystonia, spasticity, and mild encephalopathy. MRI of the brain demonstrated bilateral, symmetric basal ganglia lucencies associated with cerebral and systemic lactic acidosis. Her maternal first cousin presented with a new onset limp and mild hemiparesis along with similar MRI findings with a much milder phenotype. Additional investigation of the family members with the mutation has revealed both asymptomatic and symptomatic individuals with variable clinical and laboratory features of mitochondrial disease. This study re-emphasizes the heterogeneous clinical manifestation of homoplasmic G14459A mtDNA mutation even within the same family, and supports the hypothesis that nuclear genes may play a role in modifying the clinical expression of mitochondrial disease. Published 2003 Wiley-Liss, Inc.(dagger). C1 Georgetown Univ, Ctr Med, Inst Mol & Human Genet, Washington, DC 20007 USA. Univ S Alabama, Dept Med Genet, Mobile, AL 36688 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. RP Wong, LJC (reprint author), Georgetown Univ, Ctr Med, Inst Mol & Human Genet, M4000,3800 Reservoir Rd,NW, Washington, DC 20007 USA. EM wonglj@georgetown.edu NR 16 TC 47 Z9 51 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD FEB 1 PY 2004 VL 124A IS 4 BP 377 EP 382 DI 10.1002/ajmg.a.20456 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 769LN UT WOS:000188651700007 PM 14735585 ER PT J AU Klebanoff, MA Hauth, JC MacPherson, CA Carey, JC Heine, RP Wapner, RJ Iams, JD Moawad, A Miodovnik, M Sibai, BM vanDorsten, JP Dombrowski, MP AF Klebanoff, MA Hauth, JC MacPherson, CA Carey, JC Heine, RP Wapner, RJ Iams, JD Moawad, A Miodovnik, M Sibai, BM vanDorsten, JP Dombrowski, MP TI Time course of the regression of asymptomatic bacterial vaginosis in pregnancy with and without treatment SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Society-for-Pediatric-and-Perinatal-Epidemiologic-Research CY JUN 17-18, 2002 CL PALM DESERT, CA SP Soc Pediat & Perinatal Epidemiol Res DE bacterial vaginosis; metronidazole; lactobacilli; vaginal pH; gram stain ID ORAL METRONIDAZOLE; PRETERM BIRTH; CLINDAMYCIN; THERAPY; WOMEN; TRIAL AB Objective: The purpose of this study was to determine the effectiveness of treatment over time, for bacterial vaginosis in pregnancy and the probability of spontaneous resolution with placebo. Study design: Women with asymptomatic bacterial vaginosis on Gram stain were assigned randomly at 16 to 23 weeks of gestation to receive two 2-g doses of metronidazole or placebo 48 hours apart and were re-evaluated for changes in Gram stain score on one occasion >2 weeks later. Results: Of 658 women who underwent metronidazole therapy, treatment was successful (score, <7) in 78% of those women who were seen at 2 to 3.9 weeks of gestation, which was similar to women seen greater than or equal to 10 weeks after treatment. In 683 women who underwent placebo therapy,spontaneous resolution increased significantly from 13% at 2 to 3.9 weeks of gestation to 36% at greater than or equal to 10 weeks of gestation. Spontaneous resolution was more common with lower vaginal pH or lactobacilli on Gram stain at the time of random assignment. Conclusion: The effectiveness of metronidazole therapy of bacterial vaginosis persists for greater than or equal to 10 weeks. Women who underwent placebo therapy had significant remission of bacterial vaginosis over greater than or equal to 10 weeks. Remission was more common when the initial vaginal microbiologic disturbances were less severe. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHHD, US Dept HHS, NIH, Bethesda, MD 20892 USA. NICHHD, US Dept HHS, NIH, Rockville, MD USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Ohio State Univ, Dept Obstet & Gynecol, Cincinnati, OH USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH 45221 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. RP Klebanoff, MA (reprint author), NICHD, DESPR, NIH, Bldg 6100,Room 7B05, Bethesda, MD 20892 USA. EM mk90h@nih.gov FU NIAID NIH HHS [AI 38514]; NICHD NIH HHS [U10 HD27917, U10 HD21410, U10 HD21414, U10 HD27860, U10 HD27861, U10 HD27869, U10 HD27883, U10 HD27889, U10 HD27905, U10 HD27915, U10 HD34116, U10 HD34122, U10 HD34136, U10 HD34208, U10 HD34210, U10 HD36801] NR 19 TC 31 Z9 35 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2004 VL 190 IS 2 BP 363 EP 370 DI 10.1016/j.ajog.2003.08.020 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 778PT UT WOS:000189250500012 PM 14981375 ER PT J AU Gilles, JM Creinin, MD Barnhart, K Westhoff, C Frederick, MM Zhang, J AF Gilles, JM Creinin, MD Barnhart, K Westhoff, C Frederick, MM Zhang, J TI A randomized trial of saline solution-moistened misoprostol versus dry misoprostol for first-trimester pregnancy failure SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE missed abortion; misoprostol; anembryonic pregnancy; fetal death; spontaneous abortion ID EXPECTANT MANAGEMENT; MEDICAL-MANAGEMENT; MISSED ABORTION; VAGINAL MISOPROSTOL; SURGICAL-TREATMENT; CLINICAL-TRIAL; MISCARRIAGE; EVACUATION AB Objective: The purpose of this study was to estimate whether the efficacy of treatment with intravaginal misoprostol for first-trimester pregnancy failure is enhanced by the addition of saline solution. Study design: Eighty women with embryonic/fetal death or anembryonic pregnancy were assigned randomly to receive either 800 mug of misoprostol with saline solution (group I, 41 women) or without (group II, 39 women). Treatment was repeated on day 3 if the gestational sac remained. Curettage was performed if the gestational sac remained on day 8 or as necessary during at least 30 days of follow-up. Data were analyzed with the Student t test and the chi(2) or Fisher exact test. Results: By the first follow-up visit, 73% (group I) and 64% (group II) of women passed the gestational sac (P = .38). By the second follow-up visit, expulsion rates were 83% and 87%, respectively (P = .59). Five subjects in each group underwent curettage. Conclusion: Misoprostol is effective for the treatment of failed first-trimester pregnancy. The expulsion rate is not improved by adding saline solution. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Miami, Miami, FL 33152 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY 10027 USA. Clin Trials & Survey Corp, Baltimore, MD USA. Clin Trials & Survey Corp, Bethesda, MD USA. NICHHD, Baltimore, MD USA. NICHHD, Bethesda, MD 20892 USA. RP Gilles, JM (reprint author), Univ Miami, Miami, FL 33152 USA. FU NCRR NIH HHS [M01 RR000056]; NICHD NIH HHS [N01-HD-1-3321, N01-HD-1-3322, N01-HD-1-3323, N01-HD-1-3324, N01-HD-1-3325] NR 27 TC 24 Z9 27 U1 3 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2004 VL 190 IS 2 BP 389 EP 394 DI 10.1016/j.ajog.2003.08.024 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 778PT UT WOS:000189250500016 PM 14981379 ER PT J AU Watts, DH Balasubramanian, R Maupin, RT Delke, I Dorenbaum, A Fiore, S Newell, ML Delfraissy, JF Gelber, RD Mofenson, LM Culnane, M Cunningham, CK AF Watts, DH Balasubramanian, R Maupin, RT Delke, I Dorenbaum, A Fiore, S Newell, ML Delfraissy, JF Gelber, RD Mofenson, LM Culnane, M Cunningham, CK CA PACTG 316 Study Team TI Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 10th Conference on Retroviruses and Opportunistic Infections CY FEB 10-14, 2003 CL BOSTON, MA DE human immunodeficiency virus infection; pregnancy; antiretroviral therapy ID UNITED-STATES; TRANSMISSION; HOSPITALIZATIONS AB Objective: The purpose of this study was to evaluate rates of maternal toxicity, pregnancy complications, and peripartum morbidity by type and duration of antiretroviral therapy (ART) during pregnancy. Study design: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 316 (PACTG 316) study evaluated the addition of intrapartum/neonatal nevirapine to background ART to reduce perinatal transmission of human immunodeficiency virus-1 (HIV-1). For this secondary analysis, women were categorized into one of six groups on the basis of ART during pregnancy (monotherapy [monoRx], combination without protease inhibitor [PI], combination with PI), and start time (early: before or during first trimester; late: second or third trimester). Results: One thousand four hundred seven women were included: 288 monoRx late, 34 monoRx early, 327 combo, no PI late, 175 combo, no PI early, 320 combo, PI late, and 263 combo, PI early. Symptoms and laboratory abnormalities of moderate grade or more occurred in less than 5% of women. Only gestational diabetes (highest in combo PI early) varied significantly by therapy group. Conclusion: In HIV-infected women receiving prenatal care and ART, adverse events were uncommon. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHHD, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Louisiana State Univ, New Orleans, LA USA. Univ Florida, Jacksonville, FL USA. BioMarin Pharmaceut Inc, Novato, CA USA. Inst Child Hlth, London, England. Biatze Hosp, APHP, Agence Natl Res SIDA, Bangkok, Thailand. Ctr Dis Control, Bangkok, Thailand. SUNY Upstate Med Univ, Syracuse, NY USA. RP Watts, DH (reprint author), NICHD, Adolescent & Maternal AIDS Branch, CRMC, NIH, 6100 Execut Blvd,Room 4B11,MSC 7510, Bethesda, MD 20892 USA. EM hw591@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808; Newell, Marie-Louise/0000-0002-1074-7699 FU NIAID NIH HHS [U01 AI41110] NR 25 TC 60 Z9 63 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2004 VL 190 IS 2 BP 506 EP 516 DI 10.1016/j.ajog.2003.07.018 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 778PT UT WOS:000189250500035 PM 14981398 ER PT J AU Saika, S Kono-Saika, S Ohnishi, Y Sato, M Muragaki, Y Ooshima, A Flanders, KC Yoo, J Anzano, M Liu, CY Kao, WWY Roberts, AB AF Saika, S Kono-Saika, S Ohnishi, Y Sato, M Muragaki, Y Ooshima, A Flanders, KC Yoo, J Anzano, M Liu, CY Kao, WWY Roberts, AB TI Smad3 signaling is required for epithelial-mesenchymal transition of lens epithelium after injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SMOOTH MUSCLE ACTIN; MICE LACKING SMAD3; TGF-BETA; E-CADHERIN; TRANSFORMING GROWTH-FACTOR-BETA-1; SUBCAPSULAR CATARACTS; GENE-EXPRESSION; EYE DEVELOPMENT; PALATAL FUSION AB Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after injury as in cataract extraction, leading to fibrosis of the lens capsule. Fibrosis of the anterior capsule can be modeled in the mouse by capsular injury in the lens, which results in EMT of the lens epithelium and subsequent deposition of extracellular matrix without contamination of other cell types from outside the lens. We have previously shown that signaling via Smad3, a key signal-transducing element downstream of transforming growth factor (TGF)-beta and activin receptors, is activated in lens epithelial cells by 12 hours after injury and that this Smad3 activation is blocked by administration of a TGF-beta2-neutralizing antibody in mice. We now show that EMT of primary lens epithelial cells in vitro depends on TGF-beta expression and that injury-induced EMT in vivo depends, more specifically, on signaling via Smad3. Loss of Smad3 in mice blocks both morphological changes of lens epithelium to a mesenchymal phenotype and expression of the EMT markers snail, a-smooth muscle actin, lumican, and type I collagen in response to injury in vivo or to exposure to exogenous TGF-beta in organ culture. The results suggest that blocking the Smad3 pathway might be beneficial in inhibiting capsular fibrosis after injury and/or surgery. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. Wakayama Med Univ, Dept Pathol, Wakayama 6410012, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33152 USA. Univ Cincinnati, Med Ctr, Dept Ophthalmol, Cincinnati, OH 45221 USA. RP Saika, S (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp NR 57 TC 176 Z9 197 U1 1 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2004 VL 164 IS 2 BP 651 EP 663 DI 10.1016/S0002-9440(10)63153-7 PG 13 WC Pathology SC Pathology GA 768PC UT WOS:000188550500029 PM 14742269 ER PT J AU Doerr, TP Yu, YK AF Doerr, TP Yu, YK TI Electrostatics in the presence of dielectrics: The benefits of treating the induced surface charge density directly SO AMERICAN JOURNAL OF PHYSICS LA English DT Article AB A new method is presented for solving electrostatic boundary value problems with dielectrics or conductors and is applied to systems with spherical geometry. The strategy of the method is to treat the induced surface charge density as the variable of the boundary value problem. Because the potential is expressed directly in terms of the induced surface charge density, the potential is automatically continuous at the boundary. The remaining boundary condition produces an algebraic equation for the surface charge density, which when solved leads to the potential. The surface charge method requires the enforcement of only one boundary condition, and produces the induced surface charge in addition to the potential with no additional labor. The surface charge method also can be applied in nonspherical geometries and provides a starting place for efficient numerical solutions. (C) 2004 American Association of Physics Teachers. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Florida Atlantic Univ, Dept Phys, Boca Raton, FL 33431 USA. RP Doerr, TP (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 12 TC 19 Z9 19 U1 0 U2 3 PU AMER ASSOC PHYSICS TEACHERS AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0002-9505 J9 AM J PHYS JI Am. J. Phys. PD FEB PY 2004 VL 72 IS 2 BP 190 EP 196 DI 10.1119/1.1624115 PG 7 WC Education, Scientific Disciplines; Physics, Multidisciplinary SC Education & Educational Research; Physics GA 764GM UT WOS:000188199100009 ER PT J AU Hees, PS Fleg, JL Dong, SJ Shapiro, EP AF Hees, PS Fleg, JL Dong, SJ Shapiro, EP TI MRI and echocardiographic assessment of the diastolic dysfunction of normal aging: altered LV pressure decline or load? SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE left ventricular deformation; torsion; untwist; noninvasive imaging; left atrial pressure ID LEFT ATRIAL PRESSURE; LEFT-VENTRICULAR RELAXATION; PULMONARY VENOUS FLOW; DOPPLER-ECHOCARDIOGRAPHY; NONINVASIVE ASSESSMENT; MYOCARDIAL-INFARCTION; HYPERTENSIVE PATIENTS; HEART-FAILURE; INDEXES; VELOCITIES AB Changes in diastolic indexes during normal aging, including reduced early filling velocity ( E), lengthened E deceleration time ( DT), augmented late filling ( A), and prolonged isovolumic relaxation time ( IVRT), have been attributed to slower left ventricular ( LV) pressure ( LVP) decay. Indeed, this constellation of findings is often referred to as the " abnormal relaxation" pattern. However, LV filling is determined by the atrioventricular pressure gradient, which depends on both LVP decline and left atrial ( LA) pressure ( LAP). To assess the relative influence of LVP decline and LAP, we studied 122 normal subjects aged 21 - 92 yr by Doppler echocardiography and MRI. LVP decline was assessed by color M- mode ( V-p) and the LV untwisting rate. Early diastolic LAP was evaluated using pulmonary vein flow systolic fraction, pulmonary vein flow diastolic DT, color M- mode ( E/ V-p), and tissue Doppler ( E/ E-m). Linear regression showed the expected reduction of E, increase in A, and prolongation of IVRT and DT with advancing age. There was no relation of age to parameters reflecting the rate of LVP decline. However, older age was associated with reduced E/ V-p ( P = 0.008) and increased pulmonary vein systolic fraction ( P < 0.001), pulmonary vein DT ( P = 0.0026), and E/ E-m ( P < 0.0001), all suggesting reduced early LAP. Therefore, reduced early filling in older adults may be more closely related to a reduced early diastolic LAP than to slower LVP decline. This effect also explains the prolonged IVRT. We postulate that changes in LA active or passive properties may contribute to development of the abnormal relaxation pattern during the aging process. C1 Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Shapiro, EP (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM eshapiro@jhmi.edu FU NHLBI NIH HHS [R01 HL-46223] NR 49 TC 45 Z9 46 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB 1 PY 2004 VL 286 IS 2 BP H782 EP H788 DI 10.1152/ajpheart.01092.2002 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 761ME UT WOS:000187911900037 PM 14551040 ER PT J AU Gray, T Coakley, R Hirsh, A Thornton, D Kirkham, S Koo, JS Burch, L Boucher, R Nettesheim, P AF Gray, T Coakley, R Hirsh, A Thornton, D Kirkham, S Koo, JS Burch, L Boucher, R Nettesheim, P TI Regulation of MUC5AC mucin secretion and airway surface liquid metabolism by IL-1 beta in human bronchial epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE normal human tracheobronchial epithelial; air-liquid interface; cystic fibrosis transmembrane conductance regulator ID CYSTIC-FIBROSIS AIRWAYS; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; ION-TRANSPORT; NEUTROPHIL ELASTASE; PERICILIARY LIQUID; OLIGOMERIC MUCINS; INTERFERON-GAMMA; MESSENGER-RNA; UP-REGULATION AB Mucociliary transport in the airways significantly depends on the liquid and mucin components of the airway surface liquid (ASL). The regulation of ASL water and mucin content during pathological conditions is not well understood. We hypothesized that airway epithelial mucin production and liquid transport are regulated in response to inflammatory stimuli and tested this hypothesis by investigating the effects of the pleiotropic, early-response cytokine, IL-1beta, on cultured primary human bronchial epithelial and second-passage, normal human tracheobronchial epithelial (NHTBE) cell cultures. Fully differentiated NHTBE cultures secreted two major airway mucins, MUC5AC and MUC5B. IL-1beta, in a dose- and time-dependent manner, increased the secretion of MUC5AC, but not MUC5B. MUC5AC mRNA levels were only transiently increased at 1 and 4 h after the start of IL-1beta treatment and returned to control levels thereafter, even though MUC5AC mucin production remained elevated for at least 72 h. Synchronous with elevated MUC5AC secretion, ASL volume increased, its percentage of solid was reduced, and the pH/[HCO3-] of the ASL was elevated. ASL volume changes reflected altered ion transport, including an upregulation of Cl- secretory currents (via CFTR and Ca2+-activated Cl- conductance) and an inhibition of epithelial sodium channel (ENaC)-mediated absorptive Na+ currents. IL-1beta increased CFTR mRNA levels without affecting those for ENaC subunits. The synchronous regulation of ASL mucin and liquid metabolism triggered by IL-1beta may be an important defense mechanism of the airway epithelium to enhance mucociliary clearance during airway inflammation. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. RP Gray, T (reprint author), NIEHS, Pulm Pathobiol Lab, MD C4-09,POB 12233, Res Triangle Pk, NC 27709 USA. NR 55 TC 60 Z9 60 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB 1 PY 2004 VL 286 IS 2 BP L320 EP L330 DI 10.1152/ajplung.00440.2002 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 761ER UT WOS:000187888200012 PM 14527933 ER PT J AU Zhang, Q Kleeberger, SR Reddy, SP AF Zhang, Q Kleeberger, SR Reddy, SP TI DEP-induced fra-1 expression correlates with a distinct activation of AP-1-dependent gene transcription in the lung SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE activator protein-1; mitogen-activated protein kinase; diesel exhaust particles; matrix metalloproteinase-9; fos-related antigen-1 ID BRONCHIAL EPITHELIAL-CELLS; DIESEL EXHAUST PARTICLES; SQUAMOUS DIFFERENTIATION MARKER; ANTIOXIDANT RESPONSE ELEMENT; SMOKE-INDUCED EMPHYSEMA; FOS FAMILY-MEMBERS; IN-VITRO; C-FOS; OXIDATIVE STRESS; TRANSFORMING ACTIVITY AB Recent studies indicate a potential role for Fra-1, a heterodimeric partner of activator protein (AP)-1, in toxicant-induced epithelial injury, repair, and cellular transformation. Here we have investigated the effects of diesel exhaust particles (DEP) on fra-1 expression in C10 cells, a murine lung epithelial cell line. DEP markedly upregulated fra-1, but not fra-2, expression. The increase in fra-1 mRNA expression correlated well with its protein- and DNA-binding activity. DNA-binding assays also revealed a predominant presence of Jun-B and Jun-D in the AP-1 complex. Interestingly, DEP did not alter Jun-B and Jun-D protein levels. Transcriptional analysis revealed that fra-1 induction is regulated in part at the transcriptional level. The - 379 to + 32 bp 5'-flanking region mediated this induction. Furthermore, inhibitors of ERK1/2, JNK1, and p38 mitogen-activated protein kinases (MAPKs) significantly suppressed DEP-stimulated fra-1 transcription, suggesting their involvement in the induction process. Consistent with this finding, DEP stimulated phosphorylation of ERK1/2, JNK1, and p38 MAPKs with a distinct activation pattern. Overexpression of Fra-1 downregulated c-Jun and Nrf2 enhanced AP-1-and ARE-mediated reporter gene expression, respectively. In contrast, Fra-1 had the opposite effect on matrix metalloproteinase (MMP)-9 promoter activity. In particular, it bound to the functional AP-1 site of the MMP-9 promoter after DEP stimulation. Consistent with this result, DEP also markedly upregulated MMP-9 promoter activity. Collectively, these findings suggest that fra-1 induction by DEP may play a role in selectively regulating gene expression involved in alveolar epithelial cell injury and repair. C1 Johns Hopkins Univ, Dept Environm Hlth Sci, Div Physiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Reddy, SP (reprint author), Johns Hopkins Univ, Dept Environm Hlth Sci, Div Physiol, Bloomberg Sch Publ Hlth, Rm W7006,615 N Wolfe St, Baltimore, MD 21205 USA. FU NIEHS NIH HHS [ES-58122, ES-66109, ES-30819, ES-09606, ES-11863] NR 65 TC 29 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD FEB 1 PY 2004 VL 286 IS 2 BP L427 EP L436 DI 10.1152/ajplung.00221.2003 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 761ER UT WOS:000187888200024 PM 14565943 ER PT J AU Lee, HT Xu, H Nasr, SH Schnermann, J Emala, CW AF Lee, HT Xu, H Nasr, SH Schnermann, J Emala, CW TI A(1) adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE acute renal failure; inflammation; ischemic-repefusion injury ID FAILURE; CELLS; RATS; ACTIVATION; ANTAGONIST; KINASE; MODEL; PHASE AB Controversy exists regarding the effect of A(1) adenosine receptor (AR) activation in the kidney during ischemia and reperfusion (I/R) injury. We sought to further characterize the role of A(1) ARs in modulating renal function after I/R renal injury using both pharmacological and gene deletion approaches in mice. A(1) AR knockout mice (A(1)KO) or their wild-type littermate controls (A(1)WT) were subjected to 30 min of renal ischemia. Some A(1)WT mice were subjected to 30 min of renal ischemia with or without pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) or 2-chrolo-cyclopentyladenosine (CCPA), selective A(1) AR antagonist and agonist, respectively. Plasma creatinine and renal histology were compared 24 h after renal injury. A(1)KO mice exhibited significantly higher creatinines and worsened renal histology compared with A(1)WT controls following renal I/R injury. A(1)WT mice pretreated with the A(1) AR antagonist or agonist demonstrated significantly worsened or improved renal function, respectively, after I/R injury. In addition, A(1)WT mice pretreated with DPCPX or CCPA showed significantly increased or reduced markers of renal inflammation, respectively (renal myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF-alpha, and IL-1beta mRNA expression), while demonstrating no differences in indicators of apoptosis. In conclusion, we demonstrate that endogenous or exogenous preischemic activation of A(1) ARs protects against renal I/R injury in vivo via mechanisms leading to decreased necrosis and inflammation. C1 Columbia Univ Coll Phys & Surg, Dept Anesthesiol, Anesthesiol Res Labs, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Lee, HT (reprint author), Columbia Univ Coll Phys & Surg, Dept Anesthesiol, Anesthesiol Res Labs, P&S Box 46 PH-5,630 W 168th St, New York, NY 10032 USA. EM tl128@columbia.edu FU NIDDK NIH HHS [R01 DK-58547] NR 25 TC 85 Z9 88 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB 1 PY 2004 VL 286 IS 2 BP F298 EP F306 DI 10.1152/ajprenal.00185.2003 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 760BT UT WOS:000187791300011 PM 14600029 ER PT J AU Raman, A Schoeller, DA Subar, AF Troiano, RP Schatzkin, A Harris, T Bauer, D Bingham, SA Everhart, JE Newman, AB Tylavsky, FA AF Raman, A Schoeller, DA Subar, AF Troiano, RP Schatzkin, A Harris, T Bauer, D Bingham, SA Everhart, JE Newman, AB Tylavsky, FA TI Water turnover in 458 American adults 40-79 yr of age SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE water intake; twenty-four-hour urine; preformed water; insensible water ID DOUBLY LABELED WATER; X-RAY ABSORPTIOMETRY; HIGH-FIBER DIET; ENERGY-EXPENDITURE; BODY-COMPOSITION; 24-HOUR URINE; CANCER; RISK; COMPLETENESS; CONSUMPTION AB Despite recent interest in water intake, few data are available on water metabolism in adults. To determine the average and range of usual water intake, urine output, and total body water, we administered (2)H oxide to 458 noninstitutionalized 40- to 79-yr-old adults living in temperate climates. Urine was collected in a subset of individuals (n=280) to measure 24-h urine production using p-aminobenzoic acid to ensure complete collection. Preformed water intake was calculated from isotopic turnover and corrected for metabolic water and insensible water absorption from humidity. Preformed water intake, which is water from beverages and food moisture, averaged 3.0 l/day in men (range: 1.4-7.7 l/day) and 2.5 l/day in women (range: 1.2-4.6 l/day). Preformed water intake was lower in 70- to 79 (2.8 l/day)- than in 40- to 49-yr-old men and was lower in 70- to 79 (2.3 l/day)- than in 40- to 49- and 50- to 59-yr-old women. Urine production averaged 2.2 l/day in men (range: 0.6-4.9 l/day) and 2.2 l/day in women (0.9-6.0 l/day). There were no age-related differences in results in women, but 60- to 69-yr-old men had significantly higher urine output than 40- to 49- and 50- to 59-yr-old men. Only the 70- to 79-yr-old group included sufficient blacks for a racial analysis. Blacks in this age group showed significantly lower preformed water intake than did whites. Whites had significantly higher water turnover rates than blacks as well. Multivariate regression indicated that age, weight, height, and body mass index explained <12% of the gender-specific variance in water input or urine output, yet repeat measures indicated that within-individual coefficient of variation was 8% for preformed water intake (n=22) and 9% for 24-h urine production (n=222). These results demonstrate that water turnover is highly variable among individuals and that little of the variance is explained by anthropometric parameters. C1 Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. NIDDKD, Bethesda, MD 20892 USA. MRC, Dunn Human Nutr Unit, Cambridge CB2 2XY, England. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15261 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. RP Schoeller, DA (reprint author), Univ Wisconsin, Dept Nutr Sci, 1415 Linden Dr, Madison, WI 53706 USA. EM dschoell@nutrisci.wisc.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [DK-30031] NR 37 TC 48 Z9 49 U1 0 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB 1 PY 2004 VL 286 IS 2 BP F394 EP F401 DI 10.1152/ajprenal.00295.2003 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 760BT UT WOS:000187791300023 PM 14600032 ER PT J AU van Balkom, BWM Hoffert, JD Chou, CL Knepper, MA AF van Balkom, BWM Hoffert, JD Chou, CL Knepper, MA TI Proteomic analysis of long-term vasopressin action in the inner medullary collecting duct of the Brattleboro rat SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE vasopressin; mass spectrometry; collecting duct ID DIFFERENCE GEL-ELECTROPHORESIS; NITRIC-OXIDE; AQUAPORIN-2 TRAFFICKING; INDUCED ANTIDIURESIS; DIABETES-INSIPIDUS; WATER PERMEABILITY; RENAL MEDULLA; KIDNEY; EXPRESSION; PROTEIN AB Vasopressin regulates water and solute transport in the renal collecting duct. In addition to short-term regulation of aquaporin-2 trafficking, vasopressin also has long-term effects to regulate the abundances of aquaporins-2 and -3 and beta- and gamma-subunits of the epithelial sodium channel in collecting duct principal cells. To investigate further the direct and indirect long-term regulatory actions of vasopressin in the inner medullary collecting duct (IMCD), we used a proteomic approach [ difference gel electrophoresis (DIGE) coupled with MALDI-TOF identification of differentially expressed protein spots]. DDAVP or vehicle was infused subcutaneously in Brattleboro rats for 3 days, and IMCD cells were purified from the inner medullas for proteomic analysis. Forty-three proteins were found to be regulated in response to vasopressin infusion, including 18 that were increased in abundance, 22 that were decreased, and 3 that were shifted in the gel, presumably because of posttranslational modification. Immunocytochemistry confirmed collecting duct expression of several of the proteins that were identified. Immunoblot analysis of nine of the proteins confirmed the changes seen by the DIGE method. Of these nine proteins, six were increased in response to DDAVP infusion: nitric oxide synthase-2 (NOS2), GRP78, heat shock protein-70, annexin II, glutaminase, and cathepsin D. The remaining three were decreased in response to DDAVP: aldehyde reductase I, adenylyl cyclase VI, and carbonic anhydrase II. The findings point to a role for vasopressin in the coordinate regulation of several determinants of nitric oxide levels ( NOS2, arginase II, NADPH oxidase) and of proteins potentially involved in vasopressin escape ( adenylyl cyclase VI and G protein-coupled receptor kinase 4). C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21]; NHLBI NIH HHS [Z01-HL-01282-KE] NR 49 TC 42 Z9 44 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD FEB 1 PY 2004 VL 286 IS 2 BP F216 EP F224 DI 10.1152/ajprenal.00307.2003 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 760BT UT WOS:000187791300003 PM 14532164 ER PT J AU Charney, DS AF Charney, DS TI Psychobiological and vulnerability : Implications for successful adaptation to extreme stress SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; ANXIETY-LIKE BEHAVIOR; ANXIOLYTIC-LIKE ACTION; OVEREXPRESSING TRANSGENIC MICE; PITUITARY-ADRENAL REGULATION; MESSENGER-RNA EXPRESSION; FEAR-POTENTIATED STARTLE; MEDIAL PREFRONTAL CORTEX; SOCIAL-INTERACTION TEST; LONG-TERM POTENTIATION AB Objective: Most research on the effects of severe psychological stress has focused on stress-related psychopathology. Here, the author develops psychobiological models of resilience to extreme stress. Method: An integrative model of resilience and vulnerability that encompasses the neurochemical response patterns to acute stress and the neural mechanisms mediating reward, fear conditioning and extinction, and social behavior is proposed. Results: Eleven possible neurochemical, neuropeptide, and hormonal mediators of the psychobiological response to extreme stress were identified and related to resilience or vulnerability. The neural mechanisms of reward and motivation (hedonia, optimism, and learned helpfulness), fear responsiveness (effective behaviors despite fear), and adaptive social behavior (altruism, bonding, and teamwork) were found to be relevant to the character traits associated with resilience. Conclusions: The opportunity now exists to bring to bear the full power of advances in our understanding of the neurobiological basis of behavior to facilitate the discoveries needed to predict, prevent, and treat stress-related psychopathology. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Charney, DS (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K North Dr,Rm 101, Bethesda, MD 20892 USA. EM charneyd@nih.gov NR 220 TC 589 Z9 621 U1 14 U2 101 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2004 VL 161 IS 2 BP 195 EP 216 DI 10.1176/appi.ajp.161.2.195 PG 22 WC Psychiatry SC Psychiatry GA 818WT UT WOS:000221275900002 PM 14754765 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI Hospital smoking bans and their impact SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID NATIONAL-SURVEY C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.gov NR 8 TC 9 Z9 10 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2004 VL 94 IS 2 BP 185 EP 185 DI 10.2105/AJPH.94.2.185 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 770BP UT WOS:000188703600009 PM 14759925 ER PT J AU Fiore, MC Croyle, RT Curry, SJ Cutler, CM Davis, RM Gordon, C Healton, C Koh, HK Orleans, CT Richling, D Satcher, D Seffrin, J Williams, C Williams, LN Keller, PA Baker, TB AF Fiore, MC Croyle, RT Curry, SJ Cutler, CM Davis, RM Gordon, C Healton, C Koh, HK Orleans, CT Richling, D Satcher, D Seffrin, J Williams, C Williams, LN Keller, PA Baker, TB TI Preventing 3 million premature deaths and helping 5 million smokers quit: A national action plan for tobacco cessation SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SMOKING-CESSATION; COST-EFFECTIVENESS; CIGARETTE CONSUMPTION; CONTROL-PROGRAM; HEALTH-CARE; INTERVENTIONS; CALIFORNIA; CAMPAIGN; EXPENDITURES; TAXES AB In August 2002, the Subcommittee on Cessation of the Interagency Committee on Smoking and Health (ICSH) was charged with developing recommendations to substantially increase rates of tobacco cessation in the United States. The subcommittee's report, A National Action Plan for Tobacco Cessation, outlines 10 recommendations for reducing premature morbidity and mortality by helping millions of Americans stop using tobacco. The plan includes both evidence-based, population-wide strategies designed to promote cessation (e.g., a national quitline network) and a Smokers' Health Fund to finance the programs (through a $2 per pack excise tax increase). The subcommittee report was presented to the ICSH (February 11, 2003), which unanimously endorsed sending it to Secretary Thompson for his consideration. In this article, we summarize the national action plan. C1 Univ Wisconsin, Sch Med, Ctr Tobacco Res & Intervent, Madison, WI 53711 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Illinois, Hlth Res Ctr, Chicago, IL 60680 USA. Univ Illinois, Policy Ctr, Chicago, IL 60680 USA. Amer Assoc Hlth Plans, Washington, DC USA. Henry Ford Hlth Syst, Ctr Hlth Promot & Dis Prevent, Detroit, MI USA. Ctr Med & Medicaid Serv, Baltimore, MD USA. Amer Legacy Fdn, Washington, DC USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Midw Business Grp Hlth, Chicago, IL USA. Morehouse Sch Med, Natl Ctr Primary Care, Atlanta, GA 30310 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Agcy Healthcare Res & Qual, Off Hlth Care Informat, Rockville, MD USA. USN, Dent Corps, Grayslake, IL USA. RP Fiore, MC (reprint author), Univ Wisconsin, Sch Med, Ctr Tobacco Res & Intervent, 1930 Monroe St,Suite 200, Madison, WI 53711 USA. EM mcf@ctri.medicine.wisc.edu FU NIMHD NIH HHS [U54 MD008173] NR 52 TC 162 Z9 163 U1 2 U2 13 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2004 VL 94 IS 2 BP 205 EP 210 DI 10.2105/AJPH.94.2.205 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 770BP UT WOS:000188703600012 PM 14759928 ER PT J AU Fagan, P King, G Lawrence, D Petrucci, SA Robinson, RG Banks, D Marable, S Grana, R AF Fagan, P King, G Lawrence, D Petrucci, SA Robinson, RG Banks, D Marable, S Grana, R TI Eliminating tobacco-related health disparities: Directions for future research SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HARM REDUCTION; AFRICAN-AMERICANS; SMOKING; INTERVENTIONS; STRATEGIES; NICOTINE; USERS AB Certain groups in the United States remain at high risk and suffer disproportionately from tobacco-related illness and death despite progress made in reducing tobacco use. To address gaps in research on tobacco-related disparities and develop a comprehensive agenda aimed at reducing such disparities, representatives from funding agencies, community-based organizations, and academic institutions convened at the National Conference on Tobacco and Health Disparities in 2002. Conference participants reviewed the current research, identified existing gaps, and prioritized scientific recommendations. Panel discussions were organized to address research areas affecting underserved and understudied populations. We report major research recommendations made by the conference participants in several scientific domains. These recommendations will ultimately help guide the field in reducing and eliminating tobacco-related disparities in the United States. C1 NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Behav Hlth, State Coll, PA USA. NCI, Risk Factor Monitoring & Methods Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Ctr Dis Control & Prevent, Off Smoking & Hlth, Natl Ctr Chron Dis Prevent, Atlanta, GA USA. Hlth Evaluat & Learning Profess, Washington, DC USA. State Rhode Isl Dept Hlth, Div Dis Prevent & Control, Providence, RI USA. MasiMax Resources Inc, Rockville, MD USA. RP Fagan, P (reprint author), NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, NIH, Execut Plaza N,Room 4042,6130 Execut Blvd,MSC 7337, Bethesda, MD 20892 USA. EM faganp@mail.nih.gov NR 33 TC 106 Z9 106 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD FEB PY 2004 VL 94 IS 2 BP 211 EP 217 DI 10.2105/AJPH.94.2.211 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 770BP UT WOS:000188703600013 PM 14759929 ER PT J AU Preston, EH Light, JA Kampen, RL Kirk, AD AF Preston, EH Light, JA Kampen, RL Kirk, AD TI Human renal allograft rejection despite the absence of allogeneic passenger leukocytes SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE allorecognition; kidney transplantation; leukocytes; minor histocompatibility antigens ID RAT; TOLERANCE; TRANSPLANTATION; ACCEPTANCE; MIGRATION AB Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sister. Eleven years later he developed renal failure. The sister's marrow was noted to be 100% XY karyotype and free of malignancy. She donated a kidney to her brother. Immunosuppression was tapered following transplantation. After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day. A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he presented with severe rejection that reversed with Thymoglobulin. Renal function returned to baseline and has been stable on conventional immunosuppression. C1 Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. Washington Hosp Ctr, Dept Surg, Washington, DC 20010 USA. NIDDK, Dept Hlth & Human Serv, Transplantat Sect, Transplantat & Autoimmun Branch,NIH, Bethesda, MD USA. RP Preston, EH (reprint author), Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. EM ed.preston@verizon.net RI Kirk, Allan/B-6905-2012 NR 12 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2004 VL 4 IS 2 BP 283 EP 285 DI 10.1046/j.1600-6143.2003.00320.x PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 769HG UT WOS:000188644100021 PM 14974953 ER PT J AU Troendle, JF Korn, EL McShane, LM AF Troendle, JF Korn, EL McShane, LM TI An example of slow convergence of the bootstrap in high dimensions SO AMERICAN STATISTICIAN LA English DT Article DE hypothesis test; microarray data; multivariate data; permutation test; resampling; small sample behavior ID MICROARRAY EXPERIMENTS; CONFIDENCE-INTERVALS; BREAST-TUMORS; TESTS; EXPRESSION AB This article examines the use of bootstrap hypothesis tests for testing the equality of two multivariate distributions. The test statistic used is the maximum of the univariate two-sample t-statistics. Depending upon the type of bootstrap resampling used, the simulation studies show that the test levels are conservative or anti-conservative when the sample sizes are small and the number of variables is large. For small sample sizes, using the bootstrap resampling that preserves the Type I error can lead to a testing procedure that has lower power, sometimes dramatically lower, than a permutation test. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, DHHS, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bldg 10,Room 7B05, Bethesda, MD 20892 USA. EM jt3t@nih.gov NR 19 TC 17 Z9 18 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD FEB PY 2004 VL 58 IS 1 BP 25 EP 29 DI 10.1198/0003130042845 PG 5 WC Statistics & Probability SC Mathematics GA 770WX UT WOS:000188755300008 ER PT J AU Kaminski, RM Zolkowska, D Kozicka, M Kleinrok, Z Czuczwar, SJ AF Kaminski, RM Zolkowska, D Kozicka, M Kleinrok, Z Czuczwar, SJ TI L-histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice SO AMINO ACIDS LA English DT Article DE L-histidine; histamine; antiepileptic drugs; mice; epilepsy ID HISTAMINERGIC NEURON SYSTEM; AMYGDALOID-KINDLED SEIZURES; AMINO-ACIDS; BRAIN; RATS; EPILEPSY; CONVULSIONS; MEMORY AB Endogenous histamine has been reported to be involved in regulation of seizure susceptibility. Enhancement of histamine neurotransmission engendered by L-histidine treatment produces anticonvulsant effects in experimental animals. The present study investigated the influence of L-histidine on the protective effects of carbamazepine and phenytoin against maximal electroshock-induced seizures in mice. L-Histidine, administered at the doses that did not influence the threshold for electroconvulsions (250-500 mg/kg), enhanced by nearly 30% the protective effects of carbamazepine against maximal electroshock-induced seizures. D-Histidine (1000 mg/kg), an inactive isomer of histidine, was without any effect in this regard. L-Histidine (500 mg/kg) also augmented the protective effects of phenytoin. Importantly, the enhancement of the anticonvulsant effects of these antiepileptic drugs produced by L-histidine co-administration was not associated with augmentation of their unwanted effects on memory and motor performance. A pharmacokinetic interaction was also excluded since the free plasma levels of these antiepileptics remained unchanged in the presence of L-histidine. It may be suggested that L-histidine could serve as a beneficial adjuvant for selected antiepileptic drugs. C1 Inst Agr Med, Isotope Lab, Lublin, Poland. Med Univ, Dept Hyg, Lublin, Poland. Med Univ, Dept Pharmacol & Toxicol, Lublin, Poland. Med Univ, Dept Pathophysiol, Lublin, Poland. RP Kaminski, RM (reprint author), NINDS, Epilepsy Res Sect, NIH, 49 Convent Dr,MSC 4457,Bldg 49,Rm 5A75, Bethesda, MD 20892 USA. EM kaminskr@ninds.nih.gov NR 27 TC 1 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD FEB PY 2004 VL 26 IS 1 BP 85 EP 89 DI 10.1007/s00726-003-0005-0 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 769VL UT WOS:000188670400012 PM 14752621 ER PT J AU LeRoith, D AF LeRoith, D TI Non-islet cell hypoglycemia SO ANNALES D ENDOCRINOLOGIE LA French DT Article; Proceedings Paper CT 47th International Endocrinology Clinic Days Meeting CY APR 29-30, 2004 CL Paris, FRANCE DE hypoglycemia; non-islet cell tumor; IGF-2 ID GROWTH-FACTOR-II; INSULIN-RECEPTOR ISOFORM; EXTRAPANCREATIC TUMOR HYPOGLYCEMIA; IGF BINDING-PROTEINS; GENE-EXPRESSION; MESSENGER-RNA; CANCER-CELLS; TUMORIGENESIS; LEIOMYOSARCOMA; CARCINOMA AB NICTH is a fairly uncommon disorder but has been well characterized and the molecular mechanisms involved have given insights into the IGF system, both normal and abnormal. NICTH has brought together the molecular biologists and endocrinologists in a classic cross cultural coordination to study the disorder from all angles and to further understand the disorder. C1 NIDDK, Chief Diabet Branch, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Chief Diabet Branch, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 24 TC 10 Z9 10 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD FEB PY 2004 VL 65 IS 1 BP 99 EP 103 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 820QT UT WOS:000221405100019 PM 15122103 ER PT J AU Gladen, B AF Gladen, B TI Regarding "Persistent organochlorine compounds and birth weight" - Response to letter by Karmaus and Zhu SO ANNALS OF EPIDEMIOLOGY LA English DT Letter ID CHLORINATED PESTICIDES; ASSOCIATION; MILK C1 NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Gladen, B (reprint author), NIEHS, Biostat Branch, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 7 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 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD FEB PY 2004 VL 14 IS 2 BP 152 EP 153 DI 10.1016/j.annepidem.2003.09.007 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 777QF UT WOS:000189188500012 ER PT J AU Farrer, M Kachergus, J Forno, L Lincoln, S Wang, DS Hulihan, M Maraganore, D Gwinn-Hardy, K Wszolek, Z Dickson, D Langston, JW AF Farrer, M Kachergus, J Forno, L Lincoln, S Wang, DS Hulihan, M Maraganore, D Gwinn-Hardy, K Wszolek, Z Dickson, D Langston, JW TI Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications SO ANNALS OF NEUROLOGY LA English DT Article ID LEWY BODY PARKINSONISM; CHROMOSOME 4P; DISEASE; GENE; DEMENTIA; MUTATION; FAMILY; REPEAT; BODIES AB Genomic triplication of the alpha-synuclein gene recently has been associated with familial Parkinson's disease in the Spellman-Muenter kindred. Here, we present an independent family, of Swedish-American descent, with hereditary early-onset parkinsonism with dementia due to alpha-synuclein triplication. Brain tissue available from affected individuals in both kindreds provided the opportunity to compare their clinical, pathological, and biochemical phenotypes. Of note, studies of brain mRNA and soluble protein levels demonstrate a doubling of alpha-synuclein expression, consistent with molecular genetic data. Pathologically, cornu ammonis 2/3 hippocampal neuronal loss appears to be a defining feature of this form of inherited parkinsonism. The profound implications of alpha-synuclein overexpression for idiopathic synucleinopathies are discussed. C1 Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Parkinsons Inst, Sunnyvale, CA USA. RP Farrer, M (reprint author), Mayo Clin Jacksonville, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM farrer.matthew@mayo.edu RI Gwinn, Katrina/C-2508-2009; OI Dickson, Dennis W/0000-0001-7189-7917; Gwinn, Katrina/0000-0002-8277-651X FU NINDS NIH HHS [P01-NS40256] NR 16 TC 383 Z9 394 U1 2 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2004 VL 55 IS 2 BP 174 EP 179 DI 10.1002/ana.10846 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 768YH UT WOS:000188598300006 PM 14755720 ER PT J AU Wait, SD Vortmeyer, AO Lonser, RR Chang, DT Finn, MA Bhowmick, DA Pack, SD Oldfield, EH Zhuang, ZP AF Wait, SD Vortmeyer, AO Lonser, RR Chang, DT Finn, MA Bhowmick, DA Pack, SD Oldfield, EH Zhuang, ZP TI Somatic mutations in VHL germline deletion kindred correlate with mild phenotype SO ANNALS OF NEUROLOGY LA English DT Article ID HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR GENE; FIELD GEL-ELECTROPHORESIS; RENAL-CELL CARCINOMA; SURGICAL-MANAGEMENT; HEREDITARY CANCER; POINT MUTATION; CLEAR-CELL; HEMANGIOBLASTOMAS; HETEROZYGOSITY AB Generally, von Hippel-Lindau (VHL) disease is caused by a germline mutation of the VHL gene (chromosome 3p), and tumorigenesis is initiated from a "second-hit" deletion. A subset of VHL patients have a germline deletion of the VHL gene, and the molecular events leading to tumorigenesis are not fully understood. To determine the molecular pathogenesis of tumor formation in this setting, we analyzed five central nervous system hemangioblastomas from three patients of a single VHL germline deletion kindred, all displaying mild clinical phenotype. Rather than loss of heterozygosity (the "second hit" in VHL germline mutation patients), all tumors from this kindred showed "second-hit" point mutations on the wild-type allele. Moreover, in two patients who each had two hemangioblastomas resected each tumor contained a unique mutation. The specific germline deletion and the overall genetic makeup of the patient did not predict these random "second-hit" point mutations. These results suggest that in patients with germline deletion of a tumor suppressor gene there is a unique genetic mechanism underlying tumorigenesis. This unique genetic mechanism correlates with and may help to understand the mild clinical phenotype seen in these patients. C1 Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov RI Pack, Svetlana/C-2020-2014 NR 32 TC 17 Z9 17 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2004 VL 55 IS 2 BP 236 EP 240 DI 10.1002/ana.10807 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 768YH UT WOS:000188598300013 PM 14755727 ER PT J AU Haughey, NJ Cutler, RG Tamara, A McArthur, JC Vargas, DL Pardo, CA Turchan, J Nath, A Mattson, MP AF Haughey, NJ Cutler, RG Tamara, A McArthur, JC Vargas, DL Pardo, CA Turchan, J Nath, A Mattson, MP TI Perturbation of sphingolipid metabolism and ceramide production in HIV-dementia SO ANNALS OF NEUROLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; AMYOTROPHIC-LATERAL-SCLEROSIS; VIRUS-ASSOCIATED DEMENTIA; INDUCED CELL-DEATH; NEUTRAL SPHINGOMYELINASE; OXIDATIVE STRESS; NEURONAL APOPTOSIS; ACIDIC SPHINGOMYELINASE; CALCIUM DYSREGULATION; ALZHEIMERS-DISEASE AB Infection by the human immunodeficiency virus type 1 (HIV-1) often results in neurological dysfunction including HIV dementia (HIVD). Alterations in cytokine and redox balance are thought to play important roles in the pathogenesis of HIVD, but the specific mechanisms underlying neuronal dysfunction and death are unknown. Activation of cytokine receptors and oxidative stress can induce the production of ceramide from membrane sphingomyelin, and recent findings suggest that ceramide is an important mediator of a form of programmed cell death called apoptosis. We now report that levels of ceramide, sphingomyelin, and hydroxynonenal (HNE) are significantly increased in brain tissues and cerebrospinal fluid of HIVD patients. Exposure of cultured neurons to the neurotoxic HIV proteins gp120 and Tat resulted in increased cellular levels of sphingomyelin, ceramide, and HNE. The ceramide precursor palmitoyl-CoA sensitized neurons to Tat and gp120 toxicity, whereas an inhibitor of ceramide production reduced Tat and gp120-induced increases of ceramide and HNE and protected the neurons from Tat and gp120-induced death. These results suggest that HIV-1 infection may promote a lipid imbalance in neural cells, resulting in an overproduction of ceramide and consequent cellular dysfunction and death. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Haughey, NJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Meyer 6-109,600 N Wolfe St, Baltimore, MD 21287 USA. EM nhaughel@jhmi.edu RI Mattson, Mark/F-6038-2012 FU NIDA NIH HHS [K08 DA016160, K08 DA016160-01A1] NR 53 TC 141 Z9 148 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD FEB PY 2004 VL 55 IS 2 BP 257 EP 267 DI 10.1002/ana.10828 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 768YH UT WOS:000188598300016 PM 14755730 ER PT J AU Alexander, R Mavroukakis, S Libutti, S Pingpank, J Beresneva, T Marden, S Steinberg, S Liewehr, D AF Alexander, R Mavroukakis, S Libutti, S Pingpank, J Beresneva, T Marden, S Steinberg, S Liewehr, D TI Impact of tumor resection (Rxn) and intraperitoneal (IP) chemotherapy (CHRx) on health related quality of life (HRQL) in patients (Pts) with peritoneal surface malignancies (PSM) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 57th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 2004 CL NEW YORK, NEW YORK SP Soc Surg Oncol C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2004 VL 11 IS 2 SU S BP S109 EP S109 DI 10.1007/BF02524154 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 771LD UT WOS:000188786100191 ER PT J AU Alexander, R Libutti, S Pingpank, J Bartlett, D Helsabeck, C Beresneva, T AF Alexander, R Libutti, S Pingpank, J Bartlett, D Helsabeck, C Beresneva, T TI Efficacy of isolated hepatic perfusion (IHP) in patients with progressive unresectable colorectal cancer (CRC) liver metastases (LM) after irinotecan (CPT-11) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 57th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 2004 CL NEW YORK, NEW YORK SP Soc Surg Oncol C1 NCI, Surg Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Div Surg Oncol, Pittsburgh, PA 15260 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2004 VL 11 IS 2 SU S BP S56 EP S56 DI 10.1007/BF02523985 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 771LD UT WOS:000188786100022 ER PT J AU Elaraj, D Weinreich, D Feldman, A Turner, E Libutti, S Alexander, R AF Elaraj, D Weinreich, D Feldman, A Turner, E Libutti, S Alexander, R TI Interferon-inducible protein (IP)-10 inhibition of melanoma xenograft growth in nude mice is associated with alterations in angiogenic gene expression profiles SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 57th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 2004 CL NEW YORK, NEW YORK SP Soc Surg Oncol C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2004 VL 11 IS 2 SU S BP S65 EP S65 DI 10.1007/BF02524015 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 771LD UT WOS:000188786100052 ER PT J AU Finkelstein, SE Klebanoff, CA Antony, PA Hwang, LN Heimann, DM Spiess, PJ Surman, DR Palmer, DC Rosenberg, SA Restifo, NP AF Finkelstein, SE Klebanoff, CA Antony, PA Hwang, LN Heimann, DM Spiess, PJ Surman, DR Palmer, DC Rosenberg, SA Restifo, NP TI IL-7 and IL-15 can trigger cancer regression after adoptive transfer of CD8+T lymphocytes SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 57th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 2004 CL NEW YORK, NEW YORK SP Soc Surg Oncol C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2004 VL 11 IS 2 SU S BP S70 EP S70 DI 10.1007/BF02524031 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 771LD UT WOS:000188786100068 ER PT J AU Gamblin, TC Egorin, MJ Zuhowski, EG Lagattuta, TF Herscher, LL Russo, A Alexander, HR Dedrick, RL Bartlett, DL AF Gamblin, TC Egorin, MJ Zuhowski, EG Lagattuta, TF Herscher, LL Russo, A Alexander, HR Dedrick, RL Bartlett, DL TI Intraperitoneal gemcitabine therapy for advanced adenocarcinoma of the pancreas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 57th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 2004 CL NEW YORK, NEW YORK SP Soc Surg Oncol C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2004 VL 11 IS 2 SU S BP S55 EP S55 DI 10.1007/BF02523982 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 771LD UT WOS:000188786100019 ER PT J AU Rosen, JE Costouros, NG Lorang, D Burns, AL Alexander, HR Skarulis, MC Pingpank, JF Marx, SJ Spiegel, AM Libutti, SK AF Rosen, JE Costouros, NG Lorang, D Burns, AL Alexander, HR Skarulis, MC Pingpank, JF Marx, SJ Spiegel, AM Libutti, SK TI Gland size is associated with changes in gene expression profiles in sporadic parathyroid adenomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 57th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 18-21, 2004 CL NEW YORK, NEW YORK SP Soc Surg Oncol C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2004 VL 11 IS 2 SU S BP S63 EP S63 DI 10.1007/BF02524007 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 771LD UT WOS:000188786100044 ER PT J AU Breedveld, FC Emery, P Keystone, E Patel, K Furst, DE Kalden, JR St Clair, EW Weisman, M Smolen, J Lipsky, PE Maini, RN AF Breedveld, FC Emery, P Keystone, E Patel, K Furst, DE Kalden, JR St Clair, EW Weisman, M Smolen, J Lipsky, PE Maini, RN TI Infliximab in active early rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID RADIOGRAPHIC PROGRESSION; CLINICAL-TRIALS; DMARD THERAPY; DISEASE; METHOTREXATE; DAMAGE; INFLAMMATION; SHARP/VAN; DIAGNOSIS; EFFICACY AB Objective: To examine the impact of the combination of infliximab plus methotrexate (MTX) on the progression of structural damage in patients with early rheumatoid arthritis (RA). Methods: Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy (ATTRACT) study, in which 428 patients with active RA despite MTX therapy received placebo with MTX (MTX-only) or infliximab 3 mg/kg or 10 mg/kg every (q) 4 or 8 weeks with MTX ( infliximab plus MTX) for 102 weeks. Early RA was defined as disease duration of 3 years or less; 82 of the 428 patients (19%) met this definition. Structural damage was assessed with the modified van der Heijde-Sharp score. The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group. Results: The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen. Consistent benefit was seen in the joints of both hands and feet. Conclusions: Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment. Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity. C1 Leiden Univ, Dept Rheumatol, NL-2300 RC Leiden, Netherlands. Univ Leeds, Dept Rheumatol, Acad Unit Musculoskeletal Dis, Leeds, W Yorkshire, England. Univ Toronto, Toronto, ON, Canada. Centocor Inc, Malvern, PA 19355 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Erlangen Nurnberg, Dept Internal Med 3, D-8520 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Clin Immunol, D-8520 Erlangen, Germany. Duke Univ, Med Ctr, Div Rheumatol & Immunol, Durham, NC USA. Univ Vienna, Dept Rheumatol, Vienna, Austria. Lainz Hosp, Dept Med 2, Vienna, Austria. NIAMSD, Intramural Res Program, Bethesda, MD 20892 USA. Kennedy Inst, London, England. Imperial Coll Sch Med, London, England. RP Breedveld, FC (reprint author), Leiden Univ, Dept Rheumatol, Albinusdreef 2,Postbus 9600, NL-2300 RC Leiden, Netherlands. EM f.c.breedveld@lumc.nl NR 39 TC 138 Z9 148 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD FEB 1 PY 2004 VL 63 IS 2 BP 149 EP 155 DI 10.1136/ard.2003.013961 PG 7 WC Rheumatology SC Rheumatology GA 763GT UT WOS:000188067100008 PM 14722203 ER PT J AU Smith, PK Datta, SK Muhlbaier, LH Samsa, G Nadel, A Lipscomb, J AF Smith, PK Datta, SK Muhlbaier, LH Samsa, G Nadel, A Lipscomb, J TI Cost analysis of aprotinin for coronary artery bypass patients: Analysis of the randomized trials SO ANNALS OF THORACIC SURGERY LA English DT Article ID EPSILON-AMINOCAPROIC ACID; CARDIOPULMONARY BYPASS; CARDIAC-SURGERY; DOSE APROTININ; GRAFT PATENCY; DOUBLE-BLIND; MULTICENTER; REVASCULARIZATION; OPERATIONS; REGIMENS AB Background. The full kallikrein-inhibiting dose of aprotinin has been shown to reduce blood loss, transfusion requirements, and the systemic inflammatory response associated with cardiopulmonary bypass graft surgery (CABG). A half-dose regimen, although having a reduced delivery cost, inhibits plasmin and fibrinolysis without substantially effecting kallikrein-mediated inflammation associated with bypass surgery. The differing pharmacologic effects of the two regimens impact the decision-making process. The current study assessed the medical cost offset of full-dose and half-dose aprotinin from short- and long-term perspectives to provide a rational decision-making framework for clinicians. Methods. To estimate CABG admission costs, resource utilization and clinical data from aprotinin clinical trials were combined with unit costs estimated from a Duke University-based cost model. Lifetime medical costs of stroke and acute myocardial infarction were based on previous research. Results. Relative to placebo, the differences in total perioperative cost for primary CABG patients receiving full-dose or half-dose aprotinin were not significant. When lifetime medical costs of complications were considered, total costs in full-dose and half-dose aprotinin-treated patients were not different relative to that of placebo. Total perioperative cost was significantly lower for repeat CABG patients treated with aprotinin, with savings of $2,058 for full-dose and $2,122 for half-dose patients when compared with placebo. Taking lifetime costs of stroke and acute myocardial infarction into consideration, the cost savings estimates were $6,044 for full-dose patients and $4,483 for half-dose patients, due to substantially higher lifetime stroke costs incurred by the placebo patients. Conclusions. Using this cost model, use of full-dose and half-dose aprotinin in primary CABG patients was cost neutral during hospital admission, whereas both dosing regimens were significantly cost saving in reoperative CABG patients. Additional lifetime cost savings were realized relative to placebo due to reduced complication costs, particularly with the full-dose regimen. As the full kallikrein-inhibiting dose of aprotinin has been shown to be safe and effective, the current results support its use in both primary and repeat CABG surgery. No demonstrable economic advantage was observed with the half-dose aprotinin regimen. (C) 2004 by The Society of Thoracic Surgeons. C1 Duke Univ, Med Ctr, Dept Surg, Div Thorac Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Duke Ctr Clin Hlth Policy Res, Durham, NC 27710 USA. Bayer Corp, West Haven, CT USA. NCI, Bethesda, MD 20892 USA. RP Smith, PK (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Thorac Surg, Box 3442, Durham, NC 27710 USA. EM smith058@mc.duke.edu NR 26 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2004 VL 77 IS 2 BP 635 EP 642 DI 10.1016/j.athoracsur.2003.06.008 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 769LQ UT WOS:000188651900057 PM 14759451 ER PT J AU Acosta, EP Bardeguez, A Zorrilla, CD Van Dyke, R Hughes, MD Huang, S Pompeo, L Stek, AM Pitt, J Watts, DH Smith, E Jimenez, E Mofenson, L AF Acosta, EP Bardeguez, A Zorrilla, CD Van Dyke, R Hughes, MD Huang, S Pompeo, L Stek, AM Pitt, J Watts, DH Smith, E Jimenez, E Mofenson, L CA Pediat AIDS Clin Trials Grp 386 Pr TI Pharmacokinetics of saquinavir plus low-dose ritonavir in human immunodeficiency virus-infected pregnant women SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PROTEASE INHIBITORS; FORMULATION AB The physiologic changes that occur during pregnancy make it difficult to predict antiretroviral pharmacokinetics (PKs), but few data exist on the PKs of protease inhibitors in human immunodeficiency virus (HIV)-infected pregnant women. The objective of the present study was to determine the PKs of ritonavir (RTV)-enhanced saquinavir (SQV) in HIV-infected pregnant women by an area under the curve (AUC)-targeted approach. A phase I, formal PK evaluation was conducted with HIV-infected pregnant woman during gestation, during labor and delivery, and at 6 weeks postpartum. The SQV-RTV regimen was 800/100 mg twice a day (b.i.d.), and nucleoside analogs were administered concomitantly. The SQV exposure targeted was an AUC at 24 h of 10,000 ng.h/ml. Participants were evaluated for 12-h steady-state PKs at each time period. Thirteen subjects completed the PK evaluations during gestation, 7 completed the PK evaluations at labor and delivery, and 12 completed the PK evaluations postpartum. The mean baseline weight was 67.4 kg, and the median length of gestation was 23.3 weeks. All subjects achieved SQV exposures in excess of the target AUC. The SQV AUCs at 12 h (AUC(12)s) during gestation (29,373 +/- 17,524 ng.h/ml [mean +/- standard deviation]), during labor and delivery (26,189 +/- 22,138 ng.h/ml), and during the postpartum period (35,376 +/- 26,379 ng.h/ml) were not significantly different. The mean values of the PK parameters for RTV were lower during gestation than during the postpartum period: for AUC(12), 7,811 and 13,127 ng.h/ml, respectively; for trough concentrations, 376 and 632 ng/ml, respectively; and for maximum concentrations, 1,256 and 2,252 ng/ml, respectively (P less than or equal to 0.05 for all comparisons). This is the first formal PK evaluation of a dual protease inhibitor regimen with HIV-infected pregnant women. The level of SQV exposure was sufficient at each time of evaluation. These data demonstrate large variability in SQV and RTV concentrations and suggest that RTV concentrations are altered by pregnancy. These PK results suggest that SQV-RTV at 800/100 mg b.i.d. appears to be a reasonable treatment option for this population. C1 Univ Alabama, Sch Med, Div Clin Pharmacol, Birmingham, AL 35294 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Univ Puerto Rico, San Juan, PR 00936 USA. San Juan City Hosp, San Juan, PR USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ So Calif, Los Angeles, CA USA. Columbia Univ Coll, New York, NY USA. NICHHD, Rockville, MD USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. RP Acosta, EP (reprint author), Univ Alabama, Sch Med, Div Clin Pharmacol, 1530 3rd Ave S,VH 116, Birmingham, AL 35294 USA. EM EAcosta@uab.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [U01 AI041089, UO1-AI41089] NR 13 TC 69 Z9 73 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2004 VL 48 IS 2 BP 430 EP 436 DI 10.1128/AAC.48.2.430-436.2004 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 768WC UT WOS:000188592200010 PM 14742191 ER PT J AU Jordan, MK Burstein, AH Rock-Kress, D Alfaro, RM Pau, AK Kovacs, JA Piscitelli, SC AF Jordan, MK Burstein, AH Rock-Kress, D Alfaro, RM Pau, AK Kovacs, JA Piscitelli, SC TI Plasma pharmacokinetics of sulfadiazine administered twice daily versus four times daily are similar in human immunodeficiency virus-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TOXOPLASMIC ENCEPHALITIS; MAINTENANCE THERAPY; HIV-INFECTION; PYRIMETHAMINE; AIDS; METABOLITES AB The pharmacokinetics of 2,000 mg of sulfadiazine administered twice daily (BID) versus those of 1,000 mg administered four times a day were compared in eight human immunodeficiency virus-infected patients. No differences in pharmacokinetic parameters were detected between the regimens. These data provide a pharmacokinetic rationale for BID dosing of sulfadiazine for the treatment and suppression of toxoplasmosis. C1 NIAID, Dept Pharm, NIH, Bethesda, MD 20892 USA. NIAID, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIAID, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov NR 13 TC 5 Z9 6 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2004 VL 48 IS 2 BP 635 EP 637 DI 10.1128/AAC.48.2.635-637.2004 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 768WC UT WOS:000188592200044 PM 14742225 ER PT J AU Chenoweth, MR Somerville, GA Krause, DC O'Reilly, KL Gherardini, FC AF Chenoweth, MR Somerville, GA Krause, DC O'Reilly, KL Gherardini, FC TI Growth characteristics of Bartonella henselae in a novel liquid medium: Primary isolation, growth-phase-dependent phage induction, and metabolic studies SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BACTERIOPHAGE-LIKE PARTICLE; TRENCH FEVER RICKETTSIA; CAT-SCRATCH DISEASE; ROCHALIMAEA-HENSELAE; SP-NOV; BLOOD; DEHYDROGENASE; BACILLIFORMIS; QUINTANA; STRAIN AB Bartonella henselae is a zoonotic pathogen that usually causes a self-limiting infection in immunocompetent individuals but often causes potentially life-threatening infections, such as bacillary angiomatosis, in immunocompromised patients. Both diagnosis of infection and research into the molecular mechanisms of pathogenesis have been hindered by the absence of a suitable liquid growth medium. It has been difficult to isolate B. henselae directly from the blood of infected humans or animals or to grow the bacteria in liquid culture media under laboratory conditions. Therefore, we have developed a liquid growth medium that supports reproducible in vitro growth (3-h doubling time and a growth yield of approximately 5 X 10(8) CFU/ml) and permits the isolation of B. henselae from the blood of infected cats. During the development of this medium, we observed that B. henselae did not derive carbon and energy from the catabolism of glucose, which is consistent with genome nucleotide sequence data suggesting an incomplete glycolytic pathway. Of interest, B. henselae depleted amino acids from the culture medium and accumulated ammonia in the medium, an indicator of amino acid catabolism. Analysis of the culture medium throughout the growth cycle revealed that oxygen was consumed and carbon dioxide was generated, suggesting that amino acids were catabolized in a tricarboxylic acid (TCA) cycle-dependent mechanism. Additionally, phage particles were detected in the culture supernatants of stationary-phase B. henselae, but not in mid-logarithmic-phase culture supernatants. Enzymatic assays of whole-cell lysates revealed that B. henselae has a complete TCA cycle. Taken together, these data suggest B. henselae may catabolize amino acids but not glucose to derive carbon and energy from its host. Furthermore, the newly developed culture medium should improve isolation of B. henselae and basic research into the pathogenesis of the bacterium. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. Louisiana State Univ, Dept Vet Microbiol & Parasitol, Baton Rouge, LA 70803 USA. RP Gherardini, FC (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, 903 S 4th St, Hamilton, MT 59840 USA. EM Fgherardini@niaid.nih.gov RI Somerville, Greg/B-1326-2013 OI Somerville, Greg/0000-0002-0991-8737 NR 27 TC 23 Z9 27 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2004 VL 70 IS 2 BP 656 EP 663 DI 10.1128/AEM.70.2.656-663.2004 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 772RK UT WOS:000188854900002 PM 14766538 ER PT J AU Keel, PK Fichter, M Quadflieg, N Bulik, CM Baxter, MG Thornton, L Halmi, KA Kaplan, AS Strober, M Woodside, DB Crow, SJ Mitchell, JE Rotondo, A Mauri, M Cassano, G Treasure, J Goldman, D Berrettini, WH Kaye, WH AF Keel, PK Fichter, M Quadflieg, N Bulik, CM Baxter, MG Thornton, L Halmi, KA Kaplan, AS Strober, M Woodside, DB Crow, SJ Mitchell, JE Rotondo, A Mauri, M Cassano, G Treasure, J Goldman, D Berrettini, WH Kaye, WH TI Application of a latent class analysis to empirically define eating disorder phenotypes SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OBSESSIVE COMPULSIVE SCALE; LONGITUDINAL DATA-ANALYSIS; BULIMIA-NERVOSA; ANOREXIA-NERVOSA; PSYCHIATRIC-DISORDERS; CONTROLLED FAMILY; VALIDITY; LINKAGE; SAMPLE; WOMEN AB Context: Diagnostic criteria for eating disorders influence how we recognize, research, and treat eating disorders, and empirically valid phenotypes are required for revealing their genetic bases. Objective: To empirically define eating disorder phenotypes. Design: Data regarding eating disorder symptoms and features from 1179 individuals with clinically significant eating disorders were submitted to a latent class analysis. The resulting latent classes were compared on noneating disorder variables in a series of validation analyses. Setting: Multinational, collaborative study with cases ascertained through diverse clinical settings (inpatient, outpatient, and community). Participants: Members of affected relative pairs recruited for participation in genetic studies of eating disorders in which probands met DSM-IV-TR criteria for anorexia nervosa (AN) or bulimia nervosa and had at least 1 biological relative with a clinically significant eating disorder. Main Outcome Measure: Number and clinical characterization of latent classes. Results: A 4-class solution provided the best fit. Latent class 1 (LC1) resembled restricting AN; LC2, AN and bulimia nervosa with the use of multiple methods of purging; LC3, restricting AN without obsessive-compulsive features; and LC4, bulimia nervosa with self-induced vomiting as the sole form of purging. Biological relatives were significantly likely to belong to the same latent class. Across validation analyses, LC2 demonstrated the highest levels of psychological disturbance, and LC3 demonstrated the lowest. Conclusions: The presence of obsessive-compulsive features differentiates among individuals with restricting AN. Similarly, the combination of low weight and multiple methods of purging distinguishes among individuals with binge eating and purging behaviors. These results support some of the distinctions drawn within the DSM-IV-TR among eating disorder subtypes, while introducing new features to define phenotypes. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Univ Munich, Roseneck Hosp Behav Med, Prien Am Chiemsee, Germany. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23284 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Psychiat, White Plains, NY USA. Univ Toronto, Toronto Hosp, Hlth Network, Program Eating Disorders, Toronto, ON, Canada. Univ Toronto, Toronto Hosp, Hlth Network, Dept Psychiat, Toronto, ON, Canada. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnnol, I-56100 Pisa, Italy. Maudsley Hosp & Inst Psychiat, Inst Psychiat, London SE5 8AZ, England. NIH, Bethesda, MD 20892 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Keel, PK (reprint author), Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. EM pamela-keel@uiowa.edu; kayewh@msx.upmc.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Treasure, Janet/0000-0003-0871-4596 FU NIMH NIH HHS [R01-MH61836, R01-MH63758] NR 51 TC 115 Z9 115 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD FEB PY 2004 VL 61 IS 2 BP 192 EP 200 DI 10.1001/archpsyc.61.2.192 PG 9 WC Psychiatry SC Psychiatry GA 769MA UT WOS:000188652800011 PM 14757596 ER PT J AU Smith, JA Vitale, S Reed, GF Grieshaber, SA Goodman, LA Vanderhoof, VH Calis, KA Nelson, LM AF Smith, JA Vitale, S Reed, GF Grieshaber, SA Goodman, LA Vanderhoof, VH Calis, KA Nelson, LM TI Dry eye signs and symptoms in women with premature ovarian failure SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID HUMAN MEIBOMIAN GLAND; VISUAL FUNCTION QUESTIONNAIRE; BLOOD LYMPHOCYTE SUBSETS; ANDROGEN DEFICIENCY; ESTROGEN-RECEPTORS; SJOGRENS-SYNDROME; DIAGNOSTIC-TESTS; TEAR PRODUCTION; OCULAR SURFACE; MESSENGER-RNA AB Objective: To examine whether women with premature ovarian failure (POF) have abnormal findings in ocular surface or tear parameters and whether they report symptoms of ocular discomfort compared with age-matched controls. Methods: Sixty-five patients with POF and 36 age-matched healthy controls were examined for signs and symptoms of dry eye. The Ocular Surface Disease Index questionnaire and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) were administered to the participants. Assessments of ocular surface damage (Oxford and van Bijsterveld scores of vital dye staining) and tear status (Schirmer tests 1 [without anesthesia] and 2 [with anesthesia] and tear breakup time) were performed. Results: Women with POF scored significantly worse than controls on all ocular surface damage parameters: Oxford score (3.2 vs 1.7; P = .001), conjunctival lissamine green (2.1 vs 1.3; P = .02), corneal fluorescein staining (1.2 vs 0.4; P = .005), and van Bijsterveld score (2.1 vs 1.3; P = .02). Further, the proportion of patients with POF meeting the dry eye diagnostic criterion of a van Bijsterveld score greater than or equal to 4 was significantly greater among women with POF than among controls (20% vs 3%; P = .02). The POF group also tended to have worse scores than controls on self-reported symptoms, as measured by the overall Ocular Surface Disease Index (12.5 vs 2.1; P < .001) and the overall NEI-VFQ (94 vs 98; P = .001) after adjustment for age and race. Schirmer test scores and tear breakup time did not differ. Conclusions: Women with POF were more likely to exhibit ocular surface damage and symptoms of dry eye than age-matched controls. They were not, however, more likely to have reduced tear production. To our knowledge, this association between ocular surface disease and POF has not been previously reported. These data provide further evidence of the multifaceted role of sex hormones in the health and disease of the ocular surface. C1 NEI, Div Epidemiol & Clin Res, Ctr Clin, Dev Endocrinol Branch,NICHHD,NIH, Bethesda, MD 20892 USA. RP Smith, JA (reprint author), NEI, Div Epidemiol & Clin Res, Ctr Clin, Dev Endocrinol Branch,NICHHD,NIH, 10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. EM smithj@nei.nih.gov NR 45 TC 56 Z9 59 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2004 VL 122 IS 2 BP 151 EP 156 DI 10.1001/archopht.122.2.151 PG 6 WC Ophthalmology SC Ophthalmology GA 771GH UT WOS:000188776900001 PM 14769589 ER PT J AU Aszalos, A AF Aszalos, A TI P-glycoprotein-based drug-drug interactions: Preclinical methods and relevance to clinical observations SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE drug-drug interactions; P-glycoprotein; polypharmacy; preclinical studies; clinical studies ID BLOOD-BRAIN-BARRIER; CAPILLARY ENDOTHELIAL-CELLS; MULTIDRUG-RESISTANCE; ORAL BIOAVAILABILITY; CELLULAR ACCUMULATION; ANTICANCER DRUG; RAT-LIVER; IN-VIVO; DIGOXIN; EXPRESSION AB Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1 a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Aszalos, A (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 1A09, Bethesda, MD 20892 USA. EM aszalosa@mail.nih.gov NR 39 TC 7 Z9 8 U1 2 U2 3 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD FEB PY 2004 VL 27 IS 2 BP 127 EP 135 DI 10.1007/BF02980095 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 779AA UT WOS:000189272400001 PM 15022711 ER PT J AU Yang, AD Barro, M Gorziglia, MI Patton, JT AF Yang, AD Barro, M Gorziglia, MI Patton, JT TI Translation enhancer in the 3 '-untranslated region of rotavirus gene 6 mRNA promotes expression of the major capsid protein VP6 SO ARCHIVES OF VIROLOGY LA English DT Article ID MINUS-STRAND SYNTHESIS; CONSENSUS SEQUENCE; POLY(A) TAIL; 3' END; EFFICIENT TRANSLATION; GENOME REPLICATION; INITIATION-FACTORS; MOLECULAR-BIOLOGY; BINDING-PROTEIN; INFECTED-CELLS AB The eleven rotavirus mRNAs contain 5'-cap structures and most end with the 3'-consensus sequence 5'-UGACC-3'. The UGACC functions as a common translation enhancer (3'-TE-con) that upregulates viral protein expression through a process mediated by the nonstructural protein NSP3. To address the possibility that gene-specific enhancers are also contained in the untranslated regions (UTRs) of the rotavirus mRNAs, we used rabbit reticulocyte lysates to investigate the translation efficiencies of analog RNAs containing viral-specific 5'-and 3'-UTRs and the open reading frame for chloramphenicol acetyltransferase. These experiments combined with the analysis of full-length viral RNAs and RNAs containing 3'-truncations showed that a highly active enhancer was present near the 5'-end of the 139-nucleotide 3'-UTR of the gene 6 mRNA (3'-TEg6). The 3'-TEg6 represents a functionally independent enhancer, as no other portion of the gene 6 mRNA was required for its activity. The 3'-TEg6 differs significantly from the 3'-TE-con in that the gene 6-specific enhancer does not require viral protein for activity and is formed by a sequence unique to only one of the eleven viral mRNAs. Together, our findings suggest that the 3'-UTR of the gene 6 mRNA contains two TEs, one is gene-specific (3'-TEg6) and the other is common to nearly all rotavirus genes (3'-TE-con). The activity of the 3'-TEg6 is likely important for directing the efficient translation of the gene 6 mRNA at levels sufficient to provide the 780 copies of VP6 necessary for the assembly of each progeny virion. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov NR 36 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD FEB PY 2004 VL 149 IS 2 BP 303 EP 321 DI 10.1007/s00705-003-0211-9 PG 19 WC Virology SC Virology GA 767EW UT WOS:000188428100007 PM 14745597 ER PT J AU Kok, MR Voutetakis, A Yamano, S Wang, J Cotrim, A Katano, H Bossis, I Chiorini, JA Tak, PP Baum, BJ AF Kok, MR Voutetakis, A Yamano, S Wang, J Cotrim, A Katano, H Bossis, I Chiorini, JA Tak, PP Baum, BJ TI Host immune responses to salivary gland administration of recombinant adeno-associated virus serotype 2 vectors SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT 24th European Workshop for Rheumatology Research CY FEB 26-29, 2004 CL Berlin, GERMANY ID GENE-TRANSFER C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PD FEB PY 2004 VL 6 SU 1 MA 78 BP S25 EP S26 DI 10.1186/ar1120 PG 2 WC Rheumatology SC Rheumatology GA 807IJ UT WOS:000220494900078 ER PT J AU Levy, AP Larson, MG Corey, D Lotan, R Vita, JA Benjamin, EJ AF Levy, AP Larson, MG Corey, D Lotan, R Vita, JA Benjamin, EJ TI Haptoglobin phenotype and prevalent coronary heart disease in the Framingham offspring cohort SO ATHEROSCLEROSIS LA English DT Article DE risk factor; diabetes; haptoglobin; coronary artery disease; susceptibility genes; cohort study ID CARDIOVASCULAR-DISEASE; RISK FACTOR; POLYMORPHISM; INDIVIDUALS; MORTALITY; OXIDATION; LDL AB Background: The haptoglobin (Hp) locus is polymorphic with two major alleles denoted 1 and 2. Several recent prospective longitudinal studies have demonstrated conflicting results regarding whether there is an increase or decrease in the relative risk of coronary heart disease (CHD) conferred on individuals homozygous for the haptoglobin 1 allele (Hp 1-1). Methods: We sought to examine the relationship between Hp type and prevalent coronary heart disease in a cross-sectional study from a large community-based cohort, the Framingham Heart Offspring Study (n = 3273). Results: Overall we found no relation between Hp type and CHD prevalence. In secondary analyses we found a different pattern of Hp type and CHD prevalence by diabetes status. In nondiabetics, compared with Hp 1-1, Hp 2-1 (OR 1.71, 95% CI 1.03, 2.83) was associated with excess prevalence of CHD. In contrast in diabetic individuals we observed the opposite pattern; Hp 2-1 (OR 0.49, 95% CI 0.24, 0.99) and Hp 2-2 (OR 0.46, 95% CI 0.22, 0.96) were associated with diminished prevalence of CHD. Conclusions: These data are consistent with an interaction between Hp type and diabetes in the prevalence of CHD. These findings will need to be confirmed in other cohorts and in longitudinal studies. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Technion Israel Inst Technol, Fac Med, Haifa, Israel. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Dept Med,Sect Cardiol & Prevent Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Levy, AP (reprint author), Technion Israel Inst Technol, Fac Med, Haifa, Israel. EM alevy@tx.technion.ac.il OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL64753, N01-HC-25195, R01 HL66195] NR 23 TC 34 Z9 36 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD FEB PY 2004 VL 172 IS 2 BP 361 EP 365 DI 10.1016/j.atherosclerosis.2003.10.014 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 776DJ UT WOS:000189101200019 PM 15019547 ER PT J AU Mischiati, C Finotti, A Sereni, A Boschetti, S Baraldi, PG Romagnoli, R Feriotto, G Jeang, KT Bianchi, N Borgatti, M Gambari, R AF Mischiati, C Finotti, A Sereni, A Boschetti, S Baraldi, PG Romagnoli, R Feriotto, G Jeang, KT Bianchi, N Borgatti, M Gambari, R TI Binding of hybrid molecules containing pyrrolo [2,1-c][1,4]benzodiazepine (PBD) and oligopyrrole carriers to the human immunodeficiency type 1 virus TAR-RNA SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE distamycin; anthramycin; TAR-RNA; transcription; HIV-1; AIDS ID HIV-1 TAT; DNA-BINDING; (PBD)-DISTAMYCIN HYBRID; AROMATIC POLYAMIDINES; BIOLOGICAL-ACTIVITY; SELECTIVE BINDING; DISTAMYCIN-A; TRANSCRIPTION; CYTOTOXICITY; PROTEIN AB The binding properties of a set of four hybrids, prepared combining from one to four polypyrrole minor groove binders and pyrrolo [2,1-c] [1,4]benzodiazepine (PBD), have been studied using as target molecule the HIV-1 TAR-RNA. We found that these hybrids bind to TAR-RNA and inhibit TAR/protein(s) interactions. The anti-proliferative activity of the hybrids has been tested in vitro on HL3T1 cells and compared to the anti-proliferative effects of the natural product distamycin A and PBD. The effects on HIV-1 LTR directed transcription were studied using the chloramphenicol-acetyltransferase gene reporter system, and structure-activity relationships are discussed. The results obtained demonstrate that the hybrids 22-25 exhibit different TAR-RNA binding activity with respect to both distamycin A and PBD. In addition, a direct relationship was found between number of pyrrole rings present in the hybrids 22-25 and anti-proliferative effects. It was found that increased length of the polypyrrole backbone leads to an,increased in vitro anti-proliferative effect, i.e. the hybrid 25, containing the four pyrroles distamycin analogous, is more active than 22, 23 and 24 against cell proliferation. With respect to inhibition of HIV-1 LTR-driven transcription, it was found that the hybrids 23-25 containing two-four pyrroles are active. Therefore, when anti-proliferative effects are considered together with the inhibitory effects of HIV-1 LTR driven transcription, our results suggest that the hybrid 23 is the more interesting, since it exhibits low anti-proliferative activity and inhibits HIV-1 LTR driven transcription both in vitro and in ex vivo experiments. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Gambari, R (reprint author), Univ Ferrara, Dept Biochem & Mol Biol, Via Luigi Borsari 46, I-44100 Ferrara, Italy. EM gam@unife.it RI Jeang, Kuan-Teh/A-2424-2008; Gambari, Roberto/F-9555-2015; Borgatti, Monica/G-2611-2015; Romagnoli, Romeo/G-9887-2015; Bianchi, Nicoletta/H-1902-2015; Finotti, Alessia/C-6268-2012; Baraldi, Pier Giovanni/B-7933-2017 OI Gambari, Roberto/0000-0001-9205-6033; Borgatti, Monica/0000-0001-8470-2496; Bianchi, Nicoletta/0000-0001-9280-6017; Finotti, Alessia/0000-0002-7638-515X; NR 20 TC 11 Z9 11 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD FEB 1 PY 2004 VL 67 IS 3 BP 401 EP 410 DI 10.1016/j.bcp.2003.09.009 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 769DM UT WOS:000188611200002 PM 15037192 ER PT J AU Gilboa, A Shalev, AY Laor, L Lester, H Louzoun, Y Chisin, R Bonne, O AF Gilboa, A Shalev, AY Laor, L Lester, H Louzoun, Y Chisin, R Bonne, O TI Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; functional connectivity; amygdala; prefrontal; cingulate ID POSITRON-EMISSION-TOMOGRAPHY; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW; VIETNAM COMBAT VETERANS; CHILDHOOD SEXUAL-ABUSE; PARTIAL LEAST-SQUARES; SYMPTOM PROVOCATION; PSYCHOPHYSIOLOGICAL ASSESSMENT; BRAIN ACTIVATION; EPISODIC MEMORY AB Background: Persistent, intrusive re-experiencing in posttraumatic stress disorder (PTSD) is commonly construed as a failure of cingulate inhibition (i.e., extinction) over a hyperresponsive amygdala, based primarily on animal research of fear conditioning and the finding of cingulate hypoperfusion in PTSD. Methods: We examined functional connectivity inpatients with PTSD and healthy trauma survivors during repeated symptom provocation using H(2)O(15) positron emission tomography. Results. Memory retrieval networks (right prefrontal cortex, hippocampus, and visual cortex) were common to both groups. Networks supporting autonomic and emotional control and preparatory motor action (amygdala, anterior cingulate, subcallosal gyrus, and premotor cortex) differed between the two groups and became progressively disparate with successive presentations of the traumatic script. Patterns of effective connectivity demonstrated the predominance of direct influences of the amygdala on visual cortex, subcallosal gyrus, and anterior cingulate in PTSD but not in control subjects. There was little evidence for failure of inhibition of cingulate or subcallosal cortex over the amygdala. Conclusions. These patterns might represent excessive influences of the amygdala over regions involved in autonomic, and higher-order visual memory processing in PTSD. The present data suggest that inferenccs of direct correspondence between animal studies and pathophysiology PTSD should be made with caution. C1 Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Nucl Med, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Psychiat, IL-91120 Jerusalem, Israel. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. RP Gilboa, A (reprint author), Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. RI louzoun, yoram/F-5874-2011; Laur, Lucian/J-9351-2014 OI louzoun, yoram/0000-0003-1714-6148; Laur, Lucian/0000-0003-4727-4474 NR 68 TC 117 Z9 126 U1 4 U2 14 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 FEB 1 PY 2004 VL 55 IS 3 BP 263 EP 272 DI 10.1016/j.biopsych.2003.08.004 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 767HK UT WOS:000188434000009 PM 14744467 ER PT J AU Johansson, C Willeit, M Aron, L Smedh, C Ekholm, J Paunio, T Kieseppa, T Lichtermann, D Praschak-Rieder, N Neumeister, A Kasper, S Peltonen, L Adolfsson, R Partonen, T Schalling, M AF Johansson, C Willeit, M Aron, L Smedh, C Ekholm, J Paunio, T Kieseppa, T Lichtermann, D Praschak-Rieder, N Neumeister, A Kasper, S Peltonen, L Adolfsson, R Partonen, T Schalling, M TI Seasonal affective disorder and the G-protein beta-3-subunit C825T polymorphism SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; seasonality; morningness-eveningness; G beta 3; signal transduction; association study ID BETA-3 SUBUNIT GENE; MONONUCLEAR LEUKOCYTES; ASSOCIATION ANALYSIS; MOOD DISORDERS; LIGHT THERAPY; VARIANT; DEPRESSION AB Background: Guanine nucleotide-binding proteins (G-proteins) have been implicated in affective disorders, with reports of altered signal transduction and G-protein levels. Association with seasonal affective disorder (SAD) has been found for the higher activity T-allele of the G-protein beta-3-subunit C825T polymorphism. Methods. European SAD patients (n = 159) and matched controls (n = 159) were genotyped for the C825T. Seasonality and diurnal preference were investigated in subsets of the material (n = 177 and 92, respectively). Results. We found no association between C825T and SAD (chi(2) = .09, p = .96) or seasonality (F = 1.76, p = .18). There was some evidence for an effect on diurnal preference but only in the control group (n = 46, t = - 2.8, Bonferroni corrected p = .045). Conclusions: These results suggest that the G-protein beta-3-subunit 825 T-allele does not play a major role in susceptibility to seasonal affective disorder in the population studied. C1 Karolinska Hosp, Ctr Mol Med L8 00, Dept Mol Med, Karolinska Inst, S-17176 Stockholm, Sweden. Karolinska Inst, Dept Mol Med, Neurogenet Unit, Stockholm, Sweden. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. Natl Publ Hlth Inst, Dept Mol Med, Helsinki, Finland. Umea Univ, Dept Clin Sci, Div Psychiat, Umea, Sweden. Univ Vienna, Dept Gen Psychiat, Vienna, Austria. RP Johansson, C (reprint author), Karolinska Hosp, Ctr Mol Med L8 00, Dept Mol Med, Karolinska Inst, S-17176 Stockholm, Sweden. RI Partonen, Timo/G-1105-2012; Hertzman Johansson, Carolina/D-6570-2013; OI Partonen, Timo/0000-0003-1951-2455; Hertzman Johansson, Carolina/0000-0002-7787-0608; Adolfsson, Rolf/0000-0001-9785-8473 NR 22 TC 13 Z9 15 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 FEB 1 PY 2004 VL 55 IS 3 BP 317 EP 319 DI 10.1016/S0006-3223(03)00640-1 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 767HK UT WOS:000188434000017 PM 14744475 ER PT J AU Confer, DL Leitman, SF Papadopoulos, EB Price, TH Stroncek, DF Robinett, P Braem, B Gandham, S AF Confer, DL Leitman, SF Papadopoulos, EB Price, TH Stroncek, DF Robinett, P Braem, B Gandham, S TI Serious complications following unrelated donor marrow collection: Experiences of the National Marrow Donor Program (R) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 Natl Marrow Donor Program, Minneapolis, MN USA. NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 19 BP 13 EP 14 DI 10.1016/j.bbmt.2003.12.043 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500021 ER PT J AU Kurtzberg, J Wagner, EL Fraser, JK Cairo, MS Jensen, L Cohen, G Carter, SL Kernan, NA AF Kurtzberg, J Wagner, EL Fraser, JK Cairo, MS Jensen, L Cohen, G Carter, SL Kernan, NA TI Results of the cord blood transplantation study (COBLT) unrelated donor banking program SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Emmes Corp, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 40 BP 21 EP 21 DI 10.1016/j.bbmt.2003.12.082 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500042 ER PT J AU Fry, TJ Melchionda, F Mackall, CL AF Fry, TJ Melchionda, F Mackall, CL TI T cell depleted hosts are uniquely susceptible to tolerance induced by non-professional APCS and mediated by IL-10 producing CD8+T cells SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Bologna, S Orsola Hosp, Pediat Oncol Hematol & Cell Therapy Unit, I-40126 Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 46 BP 23 EP 23 DI 10.1016/j.bbmt.2003.12.095 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500048 ER PT J AU Woodliff, J Taylor, C Douek, D Margolis, D Drobyski, W Johnson, B Truitt, R AF Woodliff, J Taylor, C Douek, D Margolis, D Drobyski, W Johnson, B Truitt, R TI Early production of donor-derived CD4+ CD25+ regulatory T cells in patients given hematopoietic stem cell transplants SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 49 BP 25 EP 25 DI 10.1016/j.bbmt.2003.12.102 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500051 ER PT J AU Bociek, GR Pavletic, SZ Foran, J Rubocki, RJ Kuszynski, CA Lynch, JC Bierman, PJ Vose, JM Armitage, JO Joshi, SS Talmadge, JE Enke, CA Wisecarver, JL McGuire, TR AF Bociek, GR Pavletic, SZ Foran, J Rubocki, RJ Kuszynski, CA Lynch, JC Bierman, PJ Vose, JM Armitage, JO Joshi, SS Talmadge, JE Enke, CA Wisecarver, JL McGuire, TR TI Nonmyeloablative allogeneic stem cell transplantation (NST) for lymphoid malignancies using pentostatin/low-dose total body irradiation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. RI Talmadge, James/A-5916-2008 OI Talmadge, James/0000-0002-6328-6056 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 54 BP 27 EP 27 DI 10.1016/j.bbmt.2003.12.109 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500056 ER PT J AU Fry, TJ Wayne, A Fowler, D Hakim, F Love, C Gress, R Bishop, M Mackall, CL AF Fry, TJ Wayne, A Fowler, D Hakim, F Love, C Gress, R Bishop, M Mackall, CL TI Non-myeloablative allogeneic hematopoietic stem cell transplantation with pre-transplant immune depletion results in rapid full donor engraftment in pediatric patients with malignancy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 82 BP 36 EP 37 DI 10.1016/j.bbmt.2003.12.167 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500084 ER PT J AU Foley, J Jung, U Henrikson, R Fowler, D AF Foley, J Jung, U Henrikson, R Fowler, D TI Rapamycin-generated CD4(+), Th2 cells modulate graft-versus-host reaction via an IL-4 dependent mechanism SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 115 BP 47 EP 47 DI 10.1016/j.bbmt.2003.12.227 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500116 ER PT J AU Carson, JM Villalba, H Boyiadzis, M Memon, SA Castro, K Love, C Odom, J Wayne, A Dean, R Fowler, D Bishop, MR Gress, RE Hakim, FT AF Carson, JM Villalba, H Boyiadzis, M Memon, SA Castro, K Love, C Odom, J Wayne, A Dean, R Fowler, D Bishop, MR Gress, RE Hakim, FT TI IL-15 as a potential regulator of peripheral NK and CD8+T cell homeostasis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 153 BP 59 EP 59 DI 10.1016/j.bbmt.2003.12.008 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500153 ER PT J AU Bevans, M Marden, S Leidy, N Soeken, K Rivera, P Cusack, G Mayberry, H Bishop, M Barrett, J AF Bevans, M Marden, S Leidy, N Soeken, K Rivera, P Cusack, G Mayberry, H Bishop, M Barrett, J TI Health-related quality of life and symptom distress in patients undergoing non-myeloablative (NST) versus myeloablative (MT) allogeneic peripheral blood stem cell transplantation (PBSCT) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NIH, Bethesda, MD 20892 USA. MEDTAP Int, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 271 BP 97 EP 97 DI 10.1016/j.bbmt.2003.12.241 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500269 ER PT J AU Haller, SM Bevans, M Curnow, ES Gutierrez, D AF Haller, SM Bevans, M Curnow, ES Gutierrez, D TI Suspected catheter related blood stream infection (CRBSI) in hematology stem cell transplant patients: Tracking rates and outcomes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 282 BP 100 EP 100 DI 10.1016/j.bbmt.2003.12.261 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500280 ER PT J AU Bevans, M Marden, S Mayberry, H Cusack, G Soeken, K Leidy, NK AF Bevans, M Marden, S Mayberry, H Cusack, G Soeken, K Leidy, NK TI Health-related quality of life and symptom distress in patients prior to allogeneic stem cell transplant SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT Tandem BMT 2004 Meeting CY FEB 13-17, 2004 CL ORLANDO, FLORIDA SP Amer Soc Blood & Marrow Transplantat, Int Bone Marrow Transplant Registry, Autologous Blood & Marrow Transplant Registry C1 NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. MEDTAP Int, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD FEB PY 2004 VL 10 IS 2 SU 1 MA 285 BP 101 EP 101 DI 10.1016/j.bbmt.2003.12.267 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 773BH UT WOS:000188877500283 ER PT J AU Berger, VW Zhou, YY Ivanova, A Tremmel, L AF Berger, VW Zhou, YY Ivanova, A Tremmel, L TI Adjusting for ordinal covariates by inducing a partial ordering SO BIOMETRICAL JOURNAL LA English DT Article DE multiple comparisons; non-parametric test; ordinal data; randomized trial; U-statistic ID CLINICAL-TRIALS; CATEGORICAL-DATA; TESTS; SCALE; BIAS AB In the context of randomized clinical trials, multiplicity arises in many forms. One prominent example is when a key endpoint is measured and analyzed both at baseline and after treatment. It is common to analyze each separately, but more efficient to adjust the post-treatment comparisons for the baseline values. Adjustment techniques generally treat the covariate (baseline value, in this case) as either nominal or continuous. Either is problematic when applied to an ordinal covariate, the former because it fails to exploit the natural ordering and the latter because it relies on an artifical notion of linear prediction and differences between values. We propose new methods for adjusting for ordinal covariates without having to treat them as nominal or continuous. Specifically, the information-preserving composite endpoint consists of the pair of values for each patient, one at baseline and one after treatment. Some of these patterns will indicate more improvement than others, yet some pairs of patterns are not comparable. Hence, the ordering is only partial. We develop an approach to testing and deriving estimators of magnitudes of the treatment effect based on comparing each observation in one group to each observation in the other group to which it is comparable. C1 Univ Maryland Baltimore Cty, NCI, Baltimore, MD 21228 USA. Merck, Rahway, NJ 07065 USA. Univ N Carolina, Chapel Hill, NC USA. Cephalon, W Chester, PA 19380 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, NCI, Baltimore, MD 21228 USA. EM vb78c@nih.gov NR 24 TC 11 Z9 11 U1 1 U2 3 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD FEB PY 2004 VL 46 IS 1 BP 48 EP 55 DI 10.1002/bimj.200410012 PG 8 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 801DR UT WOS:000220077100004 ER PT J AU Jung, KY Kim, SK Gao, ZG Gross, AS Melman, N Jacobson, KA Kim, YC AF Jung, KY Kim, SK Gao, ZG Gross, AS Melman, N Jacobson, KA Kim, YC TI Structure-activity relationships of thiazole and thiadiazole derivatives as potent and selective human adenosine A(3) receptor antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE adenosine; A(3) receptor; antagonist; thiazole; thiadiazole ID HIGHLY POTENT; 3,5-DIACYL-2,4-DIALKYLPYRIDINE DERIVATIVES; RAT-BRAIN; INVOLVEMENT; ANALOGS; LIGANDS; BINDING AB 4-(4-Methoxyphenyl)-2-aminothiazole and 3-(4-methoxyphenyl)-5-aminothiadiazole derivatives have been synthesized and evaluated as selective antagonists for human adenosine A(3) receptors. A methoxy group in the 4-position of the phenyl ring and N-acetyl or propionyl substitutions of the aminothiazole and aminothiadiazole templates displayed great increases of binding affinity and selectivity for human adenosine A(3) receptors. The most potent A(3) antagonist of the present series, N-[3-(4-methoxy-phenyl)-[1,2,4]thiadiazol-5-yl]-acetamide (39) exhibiting a K-i value of 0.79 nM at human adenosine A(3) receptors, showed antagonistic property in a functional assay of cAMP biosynthesis involved in one of the signal transduction pathways of adenosine A(3) receptors. Molecular modeling study of conformation search and receptor docking experiments to investigate the dramatic differences of binding affinities between two regioisomers of thiadiazole analogues, (39) and (42), suggested possible binding mechanisms in the binding pockets of adenosine receptors. (C) 2003 Elsevier Ltd. All rights reserved. C1 Kwangju Inst Sci & Technol, Dept Life Sci, Lab Drug Discovery, Gwangju 500712, South Korea. NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kim, YC (reprint author), Kwangju Inst Sci & Technol, Dept Life Sci, Lab Drug Discovery, Gwangju 500712, South Korea. EM yongchul@kjist.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 44 TC 95 Z9 98 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD FEB 1 PY 2004 VL 12 IS 3 BP 613 EP 623 DI 10.1016/j.bmc.2003.10.041 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 769DR UT WOS:000188611600012 PM 14738972 ER PT J AU Malawska, B Kulig, K Spiewak, A Stables, JP AF Malawska, B Kulig, K Spiewak, A Stables, JP TI Investigation into new anticonvulsant derivatives of alpha-substituted N-benzylamides of gamma-hydroxy- and gamma-acetoxybutyric acid. Part 5: Search for new anticonvulsant compounds SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE anticonvulsant activity; N-benzylamides of gamma-hydroxy or gamma-acetoxybutyric acid; molecular modelling; SAR ID PHYSICOCHEMICAL PROPERTIES; RECEPTOR; AMIDES; DRUGS; SEMICARBAZONES; EPILEPSY; RATS AB A series of four N-benzylamides of gamma-hydroxybutyric acid (GHB), that contain N-(4-phenylpiperazine)-, N-(4-benzylpiperazine)rings, N-benzylamino-, or N-(2-phenylethylamine)-groups in the alpha-position of GHB were selected as model compounds, for determining the structural elements responsible for their potential anticonvulsant action. Based on the results of pharmacological, physicochemical, and molecular modelling investigations, the pharmacophore model for anticonvulsant N-substituted amides of GHB was defined. In this model, the presence of the N-benzylamide fragment is essential for activity. In addition, all of the amides. contained another hydrophobic unit (aryl ring) as a distal binding site and H-bond donor. In consideration of these model parameters, a number of N-substituted amides of GHB, containing a hydrophobic moiety such as: N-benzylamino or N-(4-chlorobenzylamino) group in the alpha-position of GHB, and a lipophilic substituent in the amide portion, were prepared. It has been shown that the anticonvulsant activities of the newly synthesized compounds might partially be explained on the basis of their lipophilicity (calculated log P values) and the presence of a hydroxyl group in the molecule. (C) 2003 Elsevier Ltd. All rights reserved. C1 Jagiellonian Univ, Coll Med, Dept Pharmaceut Chem, PL-30688 Krakow, Poland. NINDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Malawska, B (reprint author), Jagiellonian Univ, Coll Med, Dept Pharmaceut Chem, Medyczna 9, PL-30688 Krakow, Poland. EM mfmalaws@cyf-kr.edu.pl NR 20 TC 27 Z9 28 U1 1 U2 6 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 FEB 1 PY 2004 VL 12 IS 3 BP 625 EP 632 DI 10.1016/j.bmc.2003.10.036 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 769DR UT WOS:000188611600013 PM 14738973 ER PT J AU Yeh, IC Hummer, G AF Yeh, IC Hummer, G TI Diffusion and electrophoretic mobility of single-stranded RNA from molecular dynamics simulations SO BIOPHYSICAL JOURNAL LA English DT Article ID PARTICLE MESH EWALD; NUCLEIC-ACIDS; CAPILLARY-ELECTROPHORESIS; DNA-MOLECULES; HYDRODYNAMIC PROPERTIES; FORCE-FIELD; SYSTEMS; PROTEINS; CONSTANT; WATER AB Hydrodynamic properties of small single-stranded RNA homopolymers with three and six nucleotides in free solution are determined from molecular dynamics simulations in explicit solvent. We find that the electrophoretic mobility increases with increasing RNA length, consistent with experiment. Diffusion coefficients of RNA, corrected for finite-size effects and solvent viscosity, agree well with those estimated from experiments and hydrodynamic calculations. The diffusion coefficients and electrophoretic mobilities satisfy a Nernst-Einstein relation in which the effective charge of RNA is reduced by the charge of transiently bound counterions. Fluctuations in the counterion atmosphere are shown to enhance the diffusive spread of RNA molecules drifting along the direction of the external electric field. As a consequence, apparent diffusion coefficients measured by capillary zone electrophoresis can be significantly larger than the actual values at certain experimental conditions. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Rm 132, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 45 TC 59 Z9 62 U1 3 U2 17 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2004 VL 86 IS 2 BP 681 EP 689 PG 9 WC Biophysics SC Biophysics GA 767JV UT WOS:000188437200002 PM 14747307 ER PT J AU Martyn, DA Adhikari, BB Regnier, M Gu, J Xu, SG Yu, LC AF Martyn, DA Adhikari, BB Regnier, M Gu, J Xu, SG Yu, LC TI Response of equatorial X-ray reflections and stiffness to altered sarcomere length and myofilament lattice spacing in relaxed skinned cardiac muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID RABBIT PSOAS MUSCLE; FRANK-STARLING RELATIONSHIP; CROSSBRIDGE CB KINETICS; FROG SKELETAL-MUSCLE; CROSS-BRIDGES; DIFFRACTION PATTERNS; IONIC-STRENGTH; THIN FILAMENT; FORCE DEVELOPMENT; CA2+ SENSITIVITY AB Low angle x-ray diffraction measurements of myofilament lattice spacing (D-1,D-0) and equatorial reflection intensity ratio (I-1,I-1/I-1,I-0) were made in relaxed skinned cardiac trabeculae from rats. We tested the hypothesis that the degree of weak cross-bridge (Xbr) binding, which has been shown to be obligatory for force generation in skeletal muscle, is modulated by changes in lattice spacing in skinned cardiac muscle. Altered weak Xbr binding was detected both by changes in I-1,I-1/I-1,I-0 and by measurements of chord stiffness (chord K). Both measurements showed that, similar to skeletal muscle, the probability of weak Xbr binding at 170-mM ionic strength was significantly enhanced by lowering temperature to 5degreesC. The effects of lattice spacing on weak Xbr binding were therefore determined under these conditions. Changes in D-1,D-0, I-1,I-1/I-1,I-0, and chord K by osmotic compression with dextran T500 were determined at sarcomere lengths (SL) of 2.0 and 2.35 mum. At each SL increasing [ dextran] caused D-1,D-0 to decrease and both I-1,I-1/I-1,I-0 and chord K to increase, indicating increased weak Xbr binding. The results suggest that in intact cardiac muscle increasing SL and decreasing lattice spacing could lead to increased force by increasing the probability of initial weak Xbr binding. C1 Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Martyn, DA (reprint author), Univ Washington, Dept Bioengn, Box 357962, Seattle, WA 98195 USA. EM dmartyn@u.washington.edu FU NHLBI NIH HHS [HL67071, R01 HL067071] NR 51 TC 25 Z9 25 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2004 VL 86 IS 2 BP 1002 EP 1011 PG 10 WC Biophysics SC Biophysics GA 767JV UT WOS:000188437200030 PM 14747335 ER PT J AU Dong, XX Iwasa, KH AF Dong, XX Iwasa, KH TI Tension sensitivity of prestin: Comparison with the membrane motor in outer hair cells SO BIOPHYSICAL JOURNAL LA English DT Article ID VOLTAGE SENSOR; MOTILITY; PROTEIN; ELECTROMOTILITY; CAPACITANCE; STRESS; CHARGE; MODEL AB The membrane motor in outer hair cells undergoes conformational transitions involving charge displacement of similar to0.8 e across the membrane and changes of similar to4 nm(2) in its membrane area. Previous reports have established that the charge transfer in the membrane motor and that in prestin, a membrane protein in the plasma membrane of outer hair cells, are approximately equal. Here, we determine the membrane area changes based on its sensitivity to membrane tension. We found that prestin does undergo area changes and that the magnitude is similar to1 nm(2), smaller than the value 4 nm(2) for outer hair cell motor. This result confirms that prestin is a protein that functions as a membrane motor based on piezoelectricity. The discrepancy in the magnitude could suggest a prestin-containing complex in outer hair cells. C1 Natl Inst Deafness & Other Commun Disorders, Biophys Sect, NIH, Bethesda, MD USA. RP Iwasa, KH (reprint author), NIH, Lab Cellular Biol, 50 South Dr,Rm 4152,MSC-8027, Bethesda, MD 20892 USA. EM iwasa@nih.gov OI Iwasa, Kuni/0000-0002-9397-7704 NR 24 TC 20 Z9 21 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2004 VL 86 IS 2 BP 1201 EP 1208 PG 8 WC Biophysics SC Biophysics GA 767JV UT WOS:000188437200049 PM 14747354 ER PT J AU Tagaya, Y AF Tagaya, Y TI Memory depending in an intimate relationship SO BLOOD LA English DT Editorial Material ID CELLS C1 NCI, Bethesda, MD 20892 USA. RP Tagaya, Y (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2004 VL 103 IS 3 BP 755 EP 756 PG 2 WC Hematology SC Hematology GA 766UK UT WOS:000188393800007 ER PT J AU Kolb, HJ Schmid, C Barrett, AJ Schendel, DJ AF Kolb, HJ Schmid, C Barrett, AJ Schendel, DJ TI Graft-versus-leukemia reactions in allogeneic chimeras SO BLOOD LA English DT Review ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LEUKOCYTE INFUSIONS; CYTOTOXIC T-LYMPHOCYTES; MINOR HISTOCOMPATIBILITY ANTIGENS; KIR LIGAND INCOMPATIBILITY; RELAPSED MULTIPLE-MYELOMA; HOST-DISEASE AB There is a strong graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (SCT) due to elimination of tumor cells by alloimmune effector lymphocytes. When leukemia relapses after allogeneic SCT, donor lymphocyte transfusions (DLTs) can induce sustained remissions in some patients. This, review summarizes the current status on clinical use of DILT, the basis of GVL reactions, problems associated with this therapy, and new strategies to improve DILT. Several multicenter surveys demonstrated that the GVL effect of DILT is most effective in chronic myelogenous leukemia (CIVIL), whereas it is less pronounced in acute leukemia and myeloma. Cytokine stimulation to induce differentiation of myeloid progenitor cells or to up-regulate costimulatory molecules on tumor cells may improve the efficacy of DILT. Infections and graft-versus-host disease (GVHD) are major complications of DLT. Control of GVHD may be improved using suicide gene-modified T cells for DILT, allowing T-cell elimination if severe GVHD develops. Hopefully, in the future, GVL effect can be separated from GVHD through adoptive transfer of selected T cells that recognize leukemia-specific antigens or minor histocompatibility antigens, which are expressed predominantly on hematopoietic cells, thereby precluding attack of normal tissues. In patients with leukemia and lymphomas with fast progression, tumor growth may outpace development of effector T cells. Here it may be preferable to select stem cell transplant donors with HLA-mismatches that allow alloreactive natural killer cells, which appear early after transplantation, to retain their cytolytic function. New approaches for adoptive immune therapy of leukemia, which promise a better prognosis for these patients, are being developed. U 2004 by The American Society of Hematology. C1 Clin Univ Munich Grosshadern, Dept Med 3, D-81377 Munich, Germany. GSF, Natl Res Ctr Environm & Hlth, Clin Cooperat Grp, Munich, Germany. GSF, Natl Res Ctr Environm & Hlth, Inst Mol Immunol, Munich, Germany. NHLBI, NIH, Bethesda, MD 20892 USA. RP Kolb, HJ (reprint author), Clin Univ Munich Grosshadern, Dept Med 3, Marchioninistr 15, D-81377 Munich, Germany. EM hans.kolb@med.uni-muenchen.de NR 124 TC 270 Z9 289 U1 0 U2 6 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 FEB 1 PY 2004 VL 103 IS 3 BP 767 EP 776 DI 10.1182/blood-2003-02-0342 PG 10 WC Hematology SC Hematology GA 766UK UT WOS:000188393800012 PM 12958064 ER PT J AU Persons, DA Allay, JA Bonifacino, A Lu, T Agricola, B Metzger, ME Donahue, RE Dunbar, CE Sorrentino, BP AF Persons, DA Allay, JA Bonifacino, A Lu, T Agricola, B Metzger, ME Donahue, RE Dunbar, CE Sorrentino, BP TI Transient in vivo selection of transduced peripheral blood cells using antifolate drug selection in rhesus macaques that received transplants with hematopoietic stem cells expressing dihydrofolate reductase vectors SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; GREEN FLUORESCENT PROTEIN; SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-CELLS; GENE-THERAPY; NONHUMAN-PRIMATES; REPOPULATING CELLS; EX-VIVO; ONCORETROVIRAL VECTOR; RETROVIRAL VECTORS AB One of the main obstacles for effective human gene therapy for hematopoietic disorders remains the achievement of an adequate number of genetically corrected blood cells. One approach to this goal is to incorporate drug resistance genes into vectors to enable in vivo selection of hematopoletic stem cells (HSCs). Although a number of drug resistance vectors enable HSC selection in murine systems, little is known about these systems in large animal models. To address this issue, we transplanted cells transduced with dihydrofolate resistance vectors into 6 rhesus macaques and studied whether selection of vector-expressing cells occurred following drug treatment with trimetrexate and nitrobenzylmercaptopurineriboside-phosphate. In some of the 10 administered drug treatment courses, substantial increases in the levels of transduced peripheral blood cells were noted; however, numbers returned to baseline levels within 17 days. Attempts to induce stem cell cycling with stem cell factor and granulocyte-colony stimulating factor prior to drug treatment did not lead to sustained enrichment for transduced cells. These data highlight an important species-specific difference between murine and nonhuman primate models for assessing in vivo HSC selection strategies and emphasize the importance of using drugs capable of inducing selective pressure at the level of HSCs. (C) 2004 by The American Society of Hematology. C1 St Jude Childrens Res Hosp, Div Expt Hematol, Dept Hematol Oncol, Memphis, TN 38105 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Sorrentino, BP (reprint author), St Jude Childrens Res Hosp, Div Expt Hematol, Dept Hematol Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM brian.sorrentino@stjude.org FU NCI NIH HHS [P30 CA 21765]; NHLBI NIH HHS [P01 HL 53749] NR 45 TC 33 Z9 36 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 FEB 1 PY 2004 VL 103 IS 3 BP 796 EP 803 DI 10.1182/blood-2003-05-1572 PG 8 WC Hematology SC Hematology GA 766UK UT WOS:000188393800016 PM 12920024 ER PT J AU Bystrom, J Wynn, TA Domachowske, JB Rosenberg, HF AF Bystrom, J Wynn, TA Domachowske, JB Rosenberg, HF TI Gene microarray analysis reveals interleukin-5-dependent transcriptional targets in mouse bone marrow SO BLOOD LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; EOSINOPHIL-DERIVED NEUROTOXIN; IL-5 RECEPTOR EXPRESSION; SIGNAL-TRANSDUCTION; SCHISTOSOMA-MANSONI; EXPERIMENTAL ASTHMA; IN-VIVO; T-CELLS; B-CELLS; MICE AB Interleukin-5 (IL-5) is a hematopoietic differentiation factor that promotes the development of mature eosinophils from progenitors in bone marrow. We present a multifactorial microarray study documenting the transcriptional events in bone marrow of wild-type and IL-5-deficient mice at baseline and in response to infection with Schistosoma mansoni. The microarray data were analyzed by a 4-way subtractive algorithm that eliminated confounding non-IL-5-related sequelae of schistosome infection as well as alterations in gene expression among uninfected mice. Among the most prominent findings, we observed 7- to 40-fold increased expression of transcripts encoding the classic eosinophil granule proteins (eosinophil peroxidase, major basic protein, the ribonucleases) together with arachidonate-15-lipoxygenase and protease inhibitor plasminogen activator inhibitor 2 (PAI-2), in the IL-5-producing, infected wild-type mice only. This was accompanied by increased transcription of genes involved in secretory protein biosynthesis and granule-vesicle formation. Interestingly, we did not detect increased expression of genes encoding eosinophil-related chemokine receptors (CCR1, CCR3) or members of the GATA or CCAAT/enhancer binding protein (C/EBP) transcription factor families. These data suggest that the IL-5-responsive progenitors in the mouse bone marrow are already significantly committed to the eosinophil lineage and that IL-5 promotes differentiation of these committed progenitors into cells with recognizable and characteristic cytoplasmic granules and granule proteins. (C) 2004 by The American Society of Hematology. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. SUNY Syracuse, Upstate Med Univ, Dept Pediat, Syracuse, NY USA. RP Bystrom, J (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 11N104, Bethesda, MD 20892 USA. EM jbystrom@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 65 TC 32 Z9 32 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 FEB 1 PY 2004 VL 103 IS 3 BP 868 EP 877 DI 10.1182/blood-2003-08-2778 PG 10 WC Hematology SC Hematology GA 766UK UT WOS:000188393800025 PM 14525773 ER PT J AU Fumo, G Akin, C Metcalfe, DD Neckers, L AF Fumo, G Akin, C Metcalfe, DD Neckers, L TI 17-allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells SO BLOOD LA English DT Article ID PROTOONCOGENE C-KIT; RECEPTOR TYROSINE KINASE; LEUKEMIA-CELLS; HSP90 INHIBITORS; SIGNAL-TRANSDUCTION; HUMAN MASTOCYTOSIS; DOMAIN MUTATIONS; CATALYTIC DOMAIN; WILD-TYPE; V-KIT AB Mutations in the proto-oncogene c-kit cause constitutive kinase activity of its product, KIT protein, and are associated with human mastocytosis and gastrointestinal stromal tumors (GISTs). Although currently available tyrosine kinase inhibitors are effective in the treatment of GISTs, there has been limited success in the treatment of mastocytosis. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin antibiotic, which binds to heat shock protein 90 (hsp90) causes destabilization of various hsp90- dependent kinases; important in oncogenesis. Treatment with 17-AAG of the mast cell line HMC-1.2, harboring the Asp816Val and VaI560Gly KIT mutations, and the cell line HMC-1.1, harboring a single VaI560GIy mutation, causes both the level and activity of KIT and downstream signaling molecules AKT and STAT3 to be downregulated following drug exposure. These data were validated using Cos-7 cells transfected with wild-type and mutated KIT. 17-AAG promotes cell death of both HMC mast cell lines. In addition, neoplastic mast cells isolated from patients with mastocytosis, incubated with 17-AAG ex vivo, are selectively sensitive to the drug compared to the mononuclear fraction. These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer. C1 NCI, Cell & Canc Biol Branch, Canc Res Ctr, NIH, Rockville, MD 20850 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Cell & Canc Biol Branch, Canc Res Ctr, NIH, 9610 Med Ctr Dr,Ste 300, Rockville, MD 20850 USA. EM len@helix.nih.gov OI Akin, Cem/0000-0001-6301-4520 NR 56 TC 111 Z9 118 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 FEB 1 PY 2004 VL 103 IS 3 BP 1078 EP 1084 DI 10.1182/blood-2003-07-2477 PG 7 WC Hematology SC Hematology GA 766UK UT WOS:000188393800055 PM 14551138 ER PT J AU Bandopadhyay, R Kingsbury, AE Cookson, MR Reid, AR Evans, IM Hope, AD Pittman, AM Lashley, T Canet-Aviles, R Miller, DW McLendon, C Strand, C Leonard, AJ Abou-Sleiman, PM Healy, DG Ariga, H Wood, NW de Silva, R Revesz, T Hardy, JA Lees, AJ AF Bandopadhyay, R Kingsbury, AE Cookson, MR Reid, AR Evans, IM Hope, AD Pittman, AM Lashley, T Canet-Aviles, R Miller, DW McLendon, C Strand, C Leonard, AJ Abou-Sleiman, PM Healy, DG Ariga, H Wood, NW de Silva, R Revesz, T Hardy, JA Lees, AJ TI The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease SO BRAIN LA English DT Article DE DJ-1; Parkinson's disease; immunohistochemistry; 2D gel electrophoresis; paraquat ID RECESSIVE JUVENILE PARKINSONISM; ALPHA-SYNUCLEIN; SUBSTANTIA-NIGRA; LEWY BODIES; GLIAL-CELLS; NEURODEGENERATIVE DISORDERS; DOPAMINE NEURONS; OXIDATIVE STRESS; PROTEIN; PROTEASOME AB Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to cause early-onset, autosomal recessive Parkinson's disease. As no information is available regarding the distribution of DJ-1 protein in the human brain, in this study we used a monoclonal antibody for DJ-1 to map its distribution in frontal cortex and substantia nigra, regions invariably involved in Parkinson's disease. Western blotting of human frontal cortex showed DJ-1 to be an abundant protein in control, idiopathic Parkinson's disease, cases with clinical and pathological phenotypes of Parkinson's disease with R98Q polymorphism for DJ-1, and in progressive supranuclear palsy (PSP) brains. We also showed that DJ-1 immunoreactivity (IR) was particularly prominent in astrocytes and astrocytic processes in both control and Parkinson's disease frontal cortex, whereas neurons showed light or no DJ-1 IR. Only occasional Lewy bodies (LBs), the pathological hallmarks of Parkinson's disease, showed faint DJ-1 IR, localized to the outer halo. In preclinical studies we showed that DJ-1 is expressed in primary hippocampal and astrocyte cultures of mouse brain. By 2D gel analysis we also showed multiple pI isoforms for DJ-1 ranging between 5.5-6.6 in both control and Parkinson's disease brains, whilst exposure of M17 cells to the oxidizing agent paraquat was manifested as a shift in pI of endogenous DJ-1 towards more acidic isoforms. We conclude that DJ-1 is not an essential component of LBs and Lewy neurites, is expressed mainly by astrocytes in human brain tissue and is sensitive to oxidative stress conditions. These results are consistent with the hypothesis that neuronal-glial interactions are important in the pathophysiology of Parkinson's disease. C1 Royal Free & Univ Coll Med Sch, Reta Lila Weston Inst Neurol Studies, London W1T 4JF, England. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. UCL, Dept Mol Endocrinol, London, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Hokkaido Univ, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido, Japan. Japan Sci & Technol Corp, CREST, Kawaguchi, Japan. RP Lees, AJ (reprint author), Royal Free & Univ Coll Med Sch, Reta Lila Weston Inst Neurol Studies, 46 Cleveland St, London W1T 4JF, England. EM a.lees@ion.ucl.ac.uk RI de Silva, Rohan/C-1734-2008; Evans, Ian/C-8533-2009; Lashley, Tammaryn/D-2583-2009; Hardy, John/C-2451-2009; Pittman, Alan/D-6231-2012; Lees, Andrew/A-6605-2009; Ariga, Hiroyoshi/B-5895-2013; Bandopadhyay, Rina /C-7926-2009; Wood, Nicholas/C-2505-2009; Revesz, Tamas/A-8732-2010 OI de Silva, Rohan/0000-0002-5052-5775; Ariga, Hiroyoshi/0000-0001-7384-2143; Wood, Nicholas/0000-0002-9500-3348; Revesz, Tamas/0000-0003-2501-0259 FU Parkinson's UK [G-4029] NR 56 TC 240 Z9 253 U1 4 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD FEB PY 2004 VL 127 BP 420 EP 430 DI 10.1093/brain/awh054 PN 2 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 766RT UT WOS:000188389900018 PM 14662519 ER PT J AU Gomes, JAP Dua, HS Rizzo, LV Nishi, M Joseph, A Donoso, LA AF Gomes, JAP Dua, HS Rizzo, LV Nishi, M Joseph, A Donoso, LA TI Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; HUMAN CONJUNCTIVA; IMMUNE-SYSTEM; T-CELLS; ALPHA(E)BETA(7) INTEGRIN; MONOCLONAL-ANTIBODY; CORNEAL EPITHELIUM; E-CADHERIN; S-ANTIGEN AB Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes. C1 Wills Eye Hosp & Res Inst, Div Res, Philadelphia, PA 19107 USA. Univ Fed Sao Paulo, UNIFESP, Sao Paulo, Brazil. Univ Nottingham, Dept Ophthalmol, Nottingham NG7 2RD, England. NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. Fund EJ Zerbini, Sao Paulo, Brazil. RP Dua, HS (reprint author), Univ Nottingham Hosp, Queens Med Ctr, Eye Ear Nose & Throat Ctr, Div Ophthalmol & Visual Sci, B Floor, Nottingham NG7 2UH, England. EM harminder.dua@nottingham.ac.uk RI Rizzo, Luiz Vicente/B-4458-2009; Dua, Harminder/F-3656-2011 NR 47 TC 8 Z9 9 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD FEB 1 PY 2004 VL 88 IS 2 BP 280 EP 285 DI 10.1136/bjo.2003.017731 PG 6 WC Ophthalmology SC Ophthalmology GA 765UT UT WOS:000188302800032 PM 14736792 ER PT J AU Pautler, SE Walther, MM AF Pautler, SE Walther, MM TI Surgical images: soft tissue Laparoscopic resection of a renal hilar pheochromocytoma SO CANADIAN JOURNAL OF SURGERY LA English DT Article C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, Bldg 10,Rm 2B47,10 Ctr Dr, Bethesda, MD 20892 USA. EM macw@nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0008-428X J9 CAN J SURG JI Can. J. Surg. PD FEB PY 2004 VL 47 IS 1 BP 52 EP 53 PG 2 WC Surgery SC Surgery GA 774JR UT WOS:000188976800011 PM 14997926 ER PT J AU Prout, GR Wesley, MN McCarron, PG Chen, VW Greenberg, RS Mayberry, RM Edwards, BK AF Prout, GR Wesley, MN McCarron, PG Chen, VW Greenberg, RS Mayberry, RM Edwards, BK TI Survival experience of black patients and white patients with bladder carcinoma SO CANCER LA English DT Article DE bladder carcinoma; race; sociodemographic factors; extent of disease; survival; population study ID FOLLOW-UP; CANCER; CHEMOTHERAPY; MANAGEMENT; TRIAL; T3 AB BACKGROUND. Blacks are less likely than whites to develop bladder carcinoma. However, once they are diagnosed, black patients experience poorer survival. The authors investigated which factors were related to survival differences in black patients and white patients with bladder carcinoma stratified by extent of disease. METHODS. A population-based cohort of black patients with bladder carcinoma and a random sample of frequency-matched white patients with bladder carcinoma, stratified by age and gender, were identified through cancer registry systems in Atlanta, New Orleans, and San Francisco/Oakland. Patients had no previous cancer history and were ages 20-79 years at the time they were diagnosed with bladder carcinoma in 1985-1987. Medical records were reviewed at initial diagnosis, and 77% of patients were interviewed. Tumor grade, T classification, and other variables, including age, socioeconomic position, symptom duration, smoking history, and comorbidities, were recorded. Survival of black patients and white patients by extent of disease was modeled using Cox regression analysis. RESULTS. A greater proportion of black patients had histologic types of tumors that were associated with poorer survival. Among those with pure urothelial carcinoma, black patients had greater extent of disease at the time of diagnosis. Within specific extent-of-disease categories, there was some evidence of poorer survival for black patients with T2 tumors and strong evidence of poorer survival among those with T3 tumors compared with white patients. Black patients with muscle-invasive carcinoma who died within 6 months of diagnosis tended to present with life-threatening symptoms. Black patients and white patients did not differ with respect to diagnostic tests performed or therapy given. CONCLUSIONS. Black patients with bladder carcinoma had poorer survival due to greater extent of disease at diagnosis and a higher proportion of more aggressive histologies compared with white patients. Within urothelial carcinomas, by extent of disease (clinical/pathologic stage) these black/white survival differences were limited to patients with muscle invasion (T2 and T3 tumors). C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Louisiana State Univ, Hlth Sci Ctr, Program Epidemiol, Louisiana Tumor Registry, New Orleans, LA USA. Med Univ S Carolina, Charleston, SC 29425 USA. Morehouse Sch Med, Program Healthcare Effectiveness Res, Atlanta, GA 30310 USA. RP Edwards, BK (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd, Bethesda, MD 20892 USA. EM be2w@nih.gov FU NCI NIH HHS [N01-CN-45175, N01-CN-25501, N01-CN-35043, N01-CN-45174, N02-PC-75003, N01-CN-75401, N01-CN-45176] NR 25 TC 32 Z9 32 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2004 VL 100 IS 3 BP 621 EP 630 DI 10.1002/cncr.11942 PG 10 WC Oncology SC Oncology GA 769DP UT WOS:000188611400024 PM 14745881 ER PT J AU Abrams, SI AF Abrams, SI TI Regulation of tumor progression by anti-neoplastic T cell responses SO CANCER BIOLOGY & THERAPY LA English DT Review DE cytotoxic T lymphocytes; immunotherapy; neoplasia; tumor escape; tumor immunity ID RECOMBINANT VACCINIA VIRUS; CTL ADOPTIVE IMMUNOTHERAPY; FLICE-INHIBITORY PROTEIN; TRANSGENIC MOUSE MODEL; HUMAN DENDRITIC CELLS; CARCINOEMBRYONIC ANTIGEN; IMMUNE-RESPONSES; CANCER-PATIENTS; FAS LIGAND; PHASE-I AB A central paradox in tumor immunology is the seeming coexistence of a developing or progressing tumor burden in the absence of a therapeutically effective host anti-neoplastic response. It is now generally thought, however, that the host, whether mouse or human, can mount a T cell response against a developing malignancy without any prior immunization. Ostensibly, the nature or potency of that antitumor response is frequently insufficient to alter the course of neoplastic progression. Consequently, cancer immunotherapy was born from the idea that a preexisting or newly induced immune response may be intensified to achieve clinical regression. At the heart of that matter is the capacity of the host immune system to not only phenotypically distinguish normal from malignant cells, but also to functionally mediate antitumor activity. In both preclinical models and clinical settings, a plethora of tumor-associated or tumor-specific antigens have now been identified that can induce anti-neoplastic CD4(+) or CD8(+) T cell responses. Thus, immunization against neoplastic disease is attainable and, in several cases, overcomes potential mechanisms of immune tolerance and escape. In terms of objective clinical responses, however, the results have been less dramatic, and only a smaller proportion of patients have undergone significant disease regression. These responses have been observed mainly in clinical settings of adoptive T cell therapy, as compared with vaccination approaches. Nonetheless, these studies collectively provide the rationale for the further development and application of active and adoptive immunotherapies, perhaps in combination with each other or with oncological interventions, to promote more meaningful and sustainable anti-neoplastic immune responses and clinical outcomes. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 5B46, Bethesda, MD 20892 USA. EM sa47z@nih.gov NR 84 TC 7 Z9 7 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB PY 2004 VL 3 IS 2 BP 140 EP 146 PG 7 WC Oncology SC Oncology GA 821RC UT WOS:000221479200003 PM 14739786 ER PT J AU Gills, JJ Granville, CA Dennis, PA AF Gills, JJ Granville, CA Dennis, PA TI Targeting aberrant signal transduction pathways in lung cancer SO CANCER BIOLOGY & THERAPY LA English DT Review DE lung cancer; signal transduction; kinase ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; NICOTINIC ACETYLCHOLINE-RECEPTORS; PROMOTES CELLULAR-SURVIVAL; GASTRIN-RELEASING-PEPTIDE; POOR-PROGNOSIS; RAS MUTATIONS; DIFFERENTIAL EXPRESSION; CONSTITUTIVE ACTIVATION; TUMOR ANGIOGENESIS AB Lung cancer is the deadliest form of cancer in the world and is most commonly associated with smoking. Current treatment strategies are largely ineffective due to advanced stage at diagnosis and the inherent therapeutic resistance of lung cancer cells. To improve patient outcomes, many studies have been designed to identify molecular alterations in lung cancer in order to develop new therapeutic strategies. Molecular alterations in lung cancer include genetic changes, epigenetic changes, and changes in the expression or activity of kinases that comprise signaling pathways within cells. Signaling pathways are attractive targets for lung cancer therapy because activation of signaling pathways contributes to tumor growth and therapeutic resistance, and constitutively active signaling commonly occurs in lung cancer. This review will discuss signaling pathways that are relevant to lung cancer. We will discuss specific signaling aberrations found in lung cancers, review the status of signaling inhibitors being developed for lung cancer, identify emerging targets, and provide recommendations for the development of agents designed to inhibit signal transduction. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Navy Med Oncol, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Navy Med Oncol, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 131 TC 3 Z9 3 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB PY 2004 VL 3 IS 2 BP 147 EP 155 PG 9 WC Oncology SC Oncology GA 821RC UT WOS:000221479200004 PM 14764993 ER PT J AU Hodge, DR Xiao, WH Wang, LH Li, DP Farrar, WL AF Hodge, DR Xiao, WH Wang, LH Li, DP Farrar, WL TI Activating mutations in STAT3 and STAT5 differentially affect cellular proliferation and apoptotic resistance in multiple myeloma cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE multiple myeloma; IL-6; IGF-1; activated STAT factors; cytokine mediated resistance to apoptosis ID DEXAMETHASONE-INDUCED APOPTOSIS; PERIPHERAL-BLOOD CELLS; CONSTITUTIVE ACTIVATION; GROWTH-HORMONE; TYROSINE PHOSPHORYLATION; AUTOCRINE INTERLEUKIN-6; TRANSCRIPTION FACTORS; KINASE-ACTIVITY; ACUTE-LEUKEMIA; UP-REGULATION AB Multiple Myeloma (MM) is a progressive malignancy with poor prognosis, commonly treated by the use of the glucocorticoid Dexamethasone. Myeloma cells resist Dexamethasone induced apoptosis when exposed to IL-6 or IGF-1, both of which are known to activate several signaling cascades. For the first time, we show the actual contribution of downstream mediators, i.e., activated STAT factors, independent of the contribution of their upstream signaling pathways, on the proliferation and Dexamethasone rescue effects of IL-6 and IGF-1 in Multiple Myeloma. Retroviral transduction of cytokine dependent myeloma cells with activated STAT transcription factor constructs overcomes the cells dependence on cytokines for growth, allowing proliferation even in very low serum levels. However, the rescue of these previously cytokine dependent cells with activated STATs does not result in an increase in resistance to Dexamethasone induced apoptosis. Despite the presence of activated STAT3 and STAT5a, apoptosis is induced upon exposure to micromolar levels of Dexamethasone, and IL-6 or IGF-1 is still required to rescue the cells. The ability of these factors to block apoptosis is abrogated by the addition of PI-3 Kinase specific inhibitors, but not inhibitors that target the MAP Kinase pathway. However, ectopic expression of activated STAT3 results in partial rescue from apoptosis of cells treated with FAS ligand. Our data suggests that mechanisms of resistance to induced apoptosis and cellular proliferation are separate and distinct in cytokine dependent myeloma cells. C1 NCI, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Ctr Canc Res, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. RP Farrar, WL (reprint author), NCI, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Ctr Canc Res, POB B,Bldg 560,Rm 31-76, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 NR 42 TC 10 Z9 10 U1 1 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB PY 2004 VL 3 IS 2 BP 188 EP 194 PG 7 WC Oncology SC Oncology GA 821RC UT WOS:000221479200013 PM 14726660 ER PT J AU Vallera, DA Elson, M Brechbiel, MW Dusenbery, KE Burns, LJ Jaszcz, WB Ramsay, NK Panoskaltsis-Mortar, A Kuroki, DW Wagner, JE Vitetta, ES Kersey, JH AF Vallera, DA Elson, M Brechbiel, MW Dusenbery, KE Burns, LJ Jaszcz, WB Ramsay, NK Panoskaltsis-Mortar, A Kuroki, DW Wagner, JE Vitetta, ES Kersey, JH TI Radiotherapy of CD19 expressing Daudi tumors in nude mice with yttrium-90-labeled anti-CD19 antibody SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE radiopharmaceutical; radioimmunoconjugate; Y-90; leukemia; bone marrow transplantation; nude mice; tumor; anti-CD19 ID NON-HODGKINS-LYMPHOMA; MAJOR HISTOCOMPATIBILITY BARRIER; SIGNAL-TRANSDUCTION MOLECULE; ANTI-LY1 MONOCLONAL-ANTIBODY; B-CELL DIFFERENTIATION; VERSUS-HOST-DISEASE; PHASE-I; IDEC-Y2B8 RADIOIMMUNOTHERAPY; IBRITUMOMAB TIUXETAN; LYMPHOCYTES-B AB Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope Y-90 to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more Y-90 anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control Y-90-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of Y-90 anti-CD19 antibodies in treating B-cell malignancies. C1 Univ Minnesota, Ctr Canc, Dept Therapeut Radiol Radiat Oncol, Minneapolis, MN 55455 USA. Natl Canc Inst, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD USA. Univ Minnesota, Ctr Canc, Dept Med, Minneapolis, MN USA. Univ Minnesota, Ctr Canc, Dept Lab Med & Pathol, Minneapolis, MN USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX USA. RP Vallera, DA (reprint author), Univ Minnesota, Ctr Canc, Dept Therapeut Radiol Radiat Oncol, Mayo Mail Code 367,Harvard St,E River Rd, Minneapolis, MN 55455 USA. EM valle001@tc.umn.edu NR 42 TC 19 Z9 22 U1 1 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 2004 VL 19 IS 1 BP 11 EP 23 DI 10.1089/108497804773391630 PG 13 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 803KD UT WOS:000220229100002 PM 15068607 ER PT J AU Samanic, C Gridley, G Chow, WH Lubin, J Hoover, RN Fraumeni, JF AF Samanic, C Gridley, G Chow, WH Lubin, J Hoover, RN Fraumeni, JF TI Obesity and cancer risk among white and black United States veterans SO CANCER CAUSES & CONTROL LA English DT Article DE epidemiology; incidence studies; neoplasms; obesity; race; United States ID BODY-MASS INDEX; GROWTH-FACTOR-I; PANCREATIC-CANCER; PHYSICAL-ACTIVITY; PROSTATE-CANCER; COLORECTAL-CANCER; GASTRIC CARDIA; MALIGNANT-MELANOMA; MULTIPLE-MYELOMA; CELL CARCINOMA AB Background: Obesity has been linked to excess risk for many cancers, but the evidence remains tenuous for some types. Although the prevalence of obesity varies by race, few studies of obesity-related cancer risk have included non-white subjects. Methods: In a large cohort of male US veterans (3,668,486 whites; 832,214 blacks) hospitalized with a diagnosis of obesity between 1969 and 1996, we examined risk for all major cancer sites and subsites. Person-years accrued from the date of first obesity diagnosis until the occurrence of a first cancer, death, or the end of the observation period (September 30, 1996). We calculated age- and calendar-year adjusted relative risks (RR) and 95% confidence intervals (CI) for cancer among white and black veterans, comparing obese men to men hospitalized for other reasons, with obesity status as time-dependent. For selected cancers, we performed additional analyses stratified by specific medical conditions related to both obesity and risk of those cancers. To determine whether obesity-related cancer risks differed significantly between white and black men, we evaluated heterogeneity of risk for each cancer site. Results: Among white veterans, risk was significantly elevated for several cancers, including cancers of the lower esophagus, gastric cardia, small intestine, colon, rectum, gallbladder and ampulla of vater, male breast, prostate, bladder, thyroid, and connective tissue, and for malignant melanoma, multiple myeloma, chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Excess risks initially observed for cancers of the liver and pancreas persisted among men without a history of diabetes or alcoholism. Among black veterans, risks were significantly elevated for cancers of the colon, extrahepatic bile ducts, prostate, thyroid, and for malignant melanoma, multiple myeloma, CLL and AML. Conclusions: Obese men are at increased risk for several major cancers as well as a number of uncommon malignancies, a pattern generally similar for white and black men. Due to the increasing prevalence of obesity and overweight worldwide, it is important to clarify the impact of excess body weight on cancer and to elucidate the mechanisms involved. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Samanic, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,Room 8115, Bethesda, MD 20892 USA. EM samanicc@mail.nih.gov NR 65 TC 197 Z9 203 U1 1 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2004 VL 15 IS 1 BP 35 EP 43 DI 10.1023/B:CACO.0000016573.79453.ba PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774YY UT WOS:000189015000005 PM 14970733 ER PT J AU Sturgeon, SR Potischman, N Malone, KE Dorgan, JF Daling, J Schairer, C Brinton, LA AF Sturgeon, SR Potischman, N Malone, KE Dorgan, JF Daling, J Schairer, C Brinton, LA TI Serum levels of sex hormones and breast cancer risk in premenopausal women: a case-control study (USA) SO CANCER CAUSES & CONTROL LA English DT Article DE androgens; endogenous sex; epidemiology; estrogens; hormones; premenopausal breast cancer; progesterone ID MENSTRUAL-CYCLE; DEHYDROEPIANDROSTERONE; PLASMA; EPIDEMIOLOGY; PROGESTERONE; ANDROGENS; SULFATE AB High levels of serum estrogens and androgens have been convincingly linked with an increased risk of breast cancer among postmenopausal women. By contrast, the role of blood levels of these hormones in the etiology of premenopausal breast cancer is not well understood. In a case-control study, we sought to examine associations between levels of serum estradiol, sex-hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), testosterone, androstenedione and progesterone and risk of premenopausal breast cancer. Cases of breast cancer under age 45 were identified using rapid ascertainment systems in Seattle/Puget Sound, Washington and control subjects were identified from the same area through random digit dialing methods. A total of 169 eligible breast cancer cases and 195 control subjects donated blood (either before or six or more weeks after surgery) and were interviewed using a standardized questionnaire. The fully adjusted risk ratios and 95% confidence intervals for the highest versus lowest tertiles of estradiol, according to menstrual cycle phase, were 3.10 (0.8-12.7) for early follicular, 0.54 (0.2-1.7) for late follicular and 0.60 (0.3-1.4) for luteal. Risks for highest versus lowest quartiles of SHBG and androgens were 0.81 (0.4-1.6) for SHBG, 2.42 (1.1-5.2) for DHEA, 1.12 (0.6-2.5) for testosterone, and 1.33 (0.6-2.8) for androstenedione. For luteal progesterone, the RR for the highest versus lowest tertile was 0.55 (0.2-1.4). In summary, we did not find a convincing association between serum SHBG, estradiol, testosterone or androstenedione and premenopausal breast cancer risk. Observed differences between cases and controls subjects in serum levels of DHEA and luteal phase progesterone should be investigated further in large prospective studies. C1 Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. NCI, Appl Res Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Biostat Branch, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Sturgeon, SR (reprint author), Univ Massachusetts, Dept Biostat & Epidemiol, 715 N Pleasant St,Arnold House 407, Amherst, MA 01003 USA. EM sstur-geon@schoolph.umass.edu RI Perez , Claudio Alejandro/F-8310-2010; Brinton, Louise/G-7486-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Brinton, Louise/0000-0003-3853-8562 NR 28 TC 39 Z9 42 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2004 VL 15 IS 1 BP 45 EP 53 DI 10.1023/B:CACO.0000016574.79728.11 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774YY UT WOS:000189015000006 PM 14970734 ER PT J AU Inskip, PD Devesa, SS Fraumeni, JF AF Inskip, PD Devesa, SS Fraumeni, JF TI Processed meat consumption and adult gliomas in a Maryland cohort - Reply SO CANCER CAUSES & CONTROL LA English DT Letter ID UVEAL MELANOMA C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Inskip, PD (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 7052,6120 Execut Blvd, Bethesda, MD 20892 USA. EM inskippe@mail.nih.gov NR 7 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2004 VL 15 IS 1 BP 101 EP 102 DI 10.1023/B:CACO.0000016571.38245.83 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774YY UT WOS:000189015000015 ER PT J AU Gamero, AM Young, HA Wiltrout, RH AF Gamero, AM Young, HA Wiltrout, RH TI Inactivation of Stat3 in tumor cells: Releasing a brake on immune responses against cancer? SO CANCER CELL LA English DT Article ID INNATE AB A model of immune evasion mediated by tumors expressing constitutively activated Stat3 was recently proposed in Nature Medicine by Wang et al., suggesting opportunities for a new therapeutic approach for cancer. C1 NCI, Ctr Canc Res, Lab Expt Immunol, Frederick, MD 21702 USA. RP Gamero, AM (reprint author), NCI, Ctr Canc Res, Lab Expt Immunol, Frederick, MD 21702 USA. EM wiltroutr@mail.ncifcrf.gov NR 9 TC 45 Z9 49 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2004 VL 5 IS 2 BP 111 EP 112 DI 10.1016/S1535-6108(04)00028-5 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 779GG UT WOS:000189286500004 PM 14998485 ER PT J AU D'Angelo, A Garzia, L Andre, A Carotenuto, P Aglio, V Guardiola, O Arrigoni, G Cossu, A Palmieri, G Aravind, L Zollo, M AF D'Angelo, A Garzia, L Andre, A Carotenuto, P Aglio, V Guardiola, O Arrigoni, G Cossu, A Palmieri, G Aravind, L Zollo, M TI Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis SO CANCER CELL LA English DT Article ID HUMAN BREAST-CARCINOMA; INHIBITORY-ACTIVITY; PROTEIN; CELLS; MOTILITY; TRANSFECTION; MUTATION; OVEREXPRESSION; EXPRESSION; 5-FLUOROURACIL AB We identify a new enzymatic activity underlying metastasis in breast cancer and describe its susceptibility to therapeutic inhibition. We show that human prune (h-prune), a phosphoesterase DHH family appertaining protein, has a hitherto unrecognized cyclic nucleotide phosphodiesterase activity effectively suppressed by dipyridamole, a phosphodiesterase inhibitor. H-prune physically interacts with nm23-H1, a metastasis suppressor gene. The h-prune PDE activity, suppressed by dipyridamole and enhanced by the interaction with nm23-H1, stimulates cellular motility and metastasis processes. Out of 59 metastatic breast cancer cases analyzed, 22 (37%) were found to overexpress h-prune, evidence that this novel enzymatic activity is involved in promoting cancer metastasis. C1 Telethon Inst Genet & Med, I-80131 Naples, Italy. Univ Milan, Osped San Raffaele, HSR, Dept Anat & Pathol, I-20127 Milan, Italy. Univ Sassari, Dept Pathol, Azienda ASL 1, I-07100 Sassari, Italy. Consiglio Nazl Ric Tramariglio, Sez Sassari, Ist Chim Biomol, Alghero, Italy. Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. RP Zollo, M (reprint author), Telethon Inst Genet & Med, Via Pietro Castellino 111, I-80131 Naples, Italy. EM zollo@tigem.it OI COSSU, Antonio Giuseppe Maria/0000-0002-2390-2205; Palmieri, Giuseppe/0000-0002-4350-2276 FU Telethon [TGM03Z04, TGM06S01] NR 39 TC 79 Z9 81 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2004 VL 5 IS 2 BP 137 EP 149 DI 10.1016/S1535-6108(04)00021-2 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 779GG UT WOS:000189286500009 PM 14998490 ER PT J AU Hurt, EM Wiestner, A Rosenwald, A Shaffer, AL Campo, E Grogan, T Bergsagel, PL Kuehl, WM Staudt, LM AF Hurt, EM Wiestner, A Rosenwald, A Shaffer, AL Campo, E Grogan, T Bergsagel, PL Kuehl, WM Staudt, LM TI Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PLASMA-CELLS; TRANSCRIPTION FACTOR; DRUG-RESISTANCE; E-CADHERIN; EXPRESSION; INTERLEUKIN-6; DIFFERENTIATION; APOPTOSIS; SECRETION AB The oncogene c-maf is translocated in similar to5%-10% of multiple myelomas. Unexpectedly, we observed c-maf expression in myeloma cell lines lacking c-maf translocations and in 50% of multiple myeloma bone marrow samples. By gene expression profiling, we identified three c-maf target genes: cyclin D2, integrin beta7, and CCR1. c-maf transactivated the cyclin D2 promoter and enhanced myeloma proliferation, whereas dominant inhibition of c-maf blocked tumor formation in immunodeficient mice. c-maf-driven expression of integrin beta7 enhanced myeloma adhesion to bone marrow stroma and increased production of VEGF. We propose that c-maf transforms plasma cells by stimulating cell cycle progression and by altering bone marrow stromal interactions. The frequent overexpression of c-maf in myeloma makes it an attractive target for therapeutic intervention. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Barcelona, E-08036 Barcelona, Spain. Univ Arizona, Sch Med, Tucson, AZ 85724 USA. Weill Sch Med, New York, NY 10021 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov RI Bergsagel, Peter/A-7842-2011; OI Bergsagel, Peter/0000-0003-1523-7388; Campo, elias/0000-0001-9850-9793 NR 35 TC 206 Z9 209 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2004 VL 5 IS 2 BP 191 EP 199 DI 10.1016/S1535-6108(04)00019-4 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 779GG UT WOS:000189286500013 PM 14998494 ER PT J AU Nivens, MC Felder, T Galloway, AH Pena, MMO Pouliot, JJ Spencer, HT AF Nivens, MC Felder, T Galloway, AH Pena, MMO Pouliot, JJ Spencer, HT TI Engineered resistance to camptothecin and antifolates by retroviral coexpression of tyrosyl DNA phosphodiesterase-I and thymidylate synthase SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE camptothecin; antifolates; drug resistance; thymidylate synthase; tyrosyl DNA phosphodiesterase ID TOPOISOMERASE-I; HEMATOPOIETIC-CELLS; COVALENT COMPLEXES; ESCHERICHIA-COLI; DRUG SELECTION; BONE-MARROW; COMET ASSAY; MECHANISM; DAMAGE; GENE AB Purpose. Gene transfer of cDNA sequences that confer drug resistance can be used (1) to protect hematopoietic cells against the toxic effects of chemotherapy, (2) for in vivo enrichment of genetically engineered cells and (3) to protect cytotoxic T lymphocytes in drug-resistant immunotherapy approaches for the treatment of cancer. We have previously developed strategies to confer resistance to agents targeting thymidylate synthase (TS) and have now expanded our drug resistance strategies to include retroviral expression of tyrosyl-DNA phosphodiesterase (TDP-I), an enzyme recently implicated in the repair of topoisomerase-I (Top-I)/DNA lesions induced by camptothecin (CPT). The combination of TS and Top-I inhibition has been shown to be an effective treatment for several types of cancer. Materials and methods. Retroviral vectors were generated that individually encoded TS and TDP-I or that coexpressed both enzymes. Murine fibroblast and Chinese hamster lung transfectants were generated with the vectors and resistance to TS- and Top-I-directed inhibitors was tested. Murine bone marrow progenitor cells were also transduced using recombinant retroviruses encoding TS and TDP-I and the degree of drug resistance conferred to gene-modified cells was tested. Results. Enforced expression of TDP-I increased TDP-I activity in gene-modified cells and conferred up to threefold resistance to CPT. The degree of resistance was dependent on the duration of drug treatment. Simultaneous expression of the TS gene encoding E. coli TS optimized for expression in mammalian cells (optecTS) and TDP-I conferred extremely high-level resistance to concurrent treatment with the TS-inhibitor BW1843U89 and CPT. Furthermore, by direct analysis of DNA fragmentation using the comet assay, substantial protection was conferred (fourfold) against DNA fragmentation associated with combination drug treatments by dual enzyme expression compared to non-modified cells. Hematopoietic progenitor assays of murine bone marrow cells transduced with retroviral vectors encoding TS and TDP-I showed that bone marrow cells could be protected from the cytotoxic effects of TS and Top-I inhibition. Conclusions. Enforced expression of optecTS and TDP-I conferred antifolate and CPT resistance to genetically modified cells. Additionally, this work further illustrated a role for TDP-I in the repair of dead-end Top-I complexes and implied that TDP-I expression analysis may aid in predicting the therapeutic effectiveness of the CPT class of compounds. C1 Emory Univ, Sch Med, Dept Pediat, Div Hematol Oncol & Bone Marrow Transplantat, Atlanta, GA 30322 USA. Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Spencer, HT (reprint author), Emory Univ, Sch Med, Dept Pediat, Div Hematol Oncol & Bone Marrow Transplantat, 2040 Ridgewood Dr NE, Atlanta, GA 30322 USA. NR 31 TC 27 Z9 28 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD FEB PY 2004 VL 53 IS 2 BP 107 EP 115 DI 10.1007/s00280-003-0717-6 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 757EW UT WOS:000187548500003 PM 14605862 ER PT J AU Miller, SM Bowen, DJ Campbell, MK Diefenbach, MA Gritz, ER Jacobsen, PB Stefanek, M Fang, CY Lazovich, D Sherman, KA Wang, C AF Miller, SM Bowen, DJ Campbell, MK Diefenbach, MA Gritz, ER Jacobsen, PB Stefanek, M Fang, CY Lazovich, D Sherman, KA Wang, C TI Current research promises and challenges in behavioral oncology: Report from the American Society of Preventive Oncology Annual Meeting, 2002 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID BREAST-CANCER SUSCEPTIBILITY; TAILORED NUTRITION EDUCATION; HEREDITARY COLON-CANCER; COLORECTAL-CANCER; OVARIAN-CANCER; RISK PERCEPTION; PSYCHOLOGICAL DISTRESS; DECISION-MAKING; HEALTH BEHAVIOR; ADDICTIVE BEHAVIORS AB The Behavioral Oncology Interest Group of the American Society of Preventive Oncology held a Roundtable session on March 10, 2002, at the American Society of Preventive Oncology annual meeting in Bethesda, Maryland, to discuss the current state-of-the-science in behavioral approaches to cancer prevention and control and to delineate priorities for additional research. Four key areas were considered: (a) behavioral approaches to cancer genetic risk assessment and testing; (b) biological mechanisms of psychosocial effects on cancer; (c) the role of risk perceptions in cancer screening adherence; and (d) the impact of tailored and targeted interventions on cancer prevention and control research. The evidence reviewed indicates that behavioral approaches have made significant contributions to cancer prevention and control research. At the same time, there is a need to more closely link future investigations to the underlying base of behavioral science principles and paradigms that guide them. To successfully bridge the gap between the availability of effective new cancer prevention and control technologies and the participants they are meant to serve will require the development of more integrative conceptual models, the incorporation of more rigorous methodological designs, and more precise identification of the individual and group characteristics of the groups under study. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Bowen, DJ (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM SM_Miller@fccc.edu RI Fang, Carolyn/A-2324-2008; OI Fang, Carolyn/0000-0002-0575-3867; Sherman, Kerry/0000-0001-7780-6668 FU NCI NIH HHS [CA06927] NR 118 TC 20 Z9 20 U1 6 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 171 EP 180 DI 10.1158/1055-9965.EPI-463-2 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200001 PM 14973109 ER PT J AU Taplin, SH Ichikawa, L Buist, DSM Seger, D White, E AF Taplin, SH Ichikawa, L Buist, DSM Seger, D White, E TI Evaluating organized breast cancer screening implementation: The prevention of late-stage disease? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COST-EFFECTIVENESS; MORTALITY REDUCTION; MAMMOGRAPHY USE; PROGRAM; SERVICES; AGE; CONTROVERSY; OUTCOMES; DELIVERY; RISK AB The objective of our study was to evaluate organized breast cancer screening implementation by measuring the association between screening program enrollment and late-stage disease. Our setting was a health plan using mailed mammography reminders to women ages greater than or equal to40. We conducted yearly cross-sectional summaries of mammography experience and late-stage (regional or distant Surveillance Epidemiology and End Results Reporting (SEER) stage) breast cancer occurrence for all of the health-plan women ages greater than or equal to40 (1986-1998). We estimated the odds of late-stage breast cancer among health-plan and surrounding community women because it was too early to compare changes in mortality. We also estimated the odds of late-stage disease (1995-1998) associated with program enrollment and mammography screening among health-plan women. We found that mammography-within-two-years increased within the health plan from 25.9% to 51.2% among women ages 40-49 and from 32.9% to 74.7% among women ages greater than or equal to50. Health-plan late-stage rates were lower than those in the surrounding community [ages 40-49: odds ratio (OR), 0.87; 95% confidence interval (CI), 0.77-0.99; ages 50-79: OR, 0.86; 95% CI, 0.80-0.92] and declined parallel to the community. Among health-plan cancer cases, women ages greater than or equal to43 who were enrolled in the screening program and who had at least one program mammogram were less likely to have late-stage disease compared with the women not enrolled in the program (OR, 0.31; 95% CI, 0.16-0.61) but the odds of late-stage was also reduced among program-enrolled women not receiving program mammograms (OR, 0.45; 95% CI, 0.21-0.95). We concluded that enrollment in organized screening is associated with increased likelihood of mammography and reduced odds of late-stage breast cancer. Addressing the concerns of un-enrolled women and those without mammograms offers an opportunity for further late-stage disease reduction. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Taplin, SH (reprint author), NCI, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA63731] NR 40 TC 57 Z9 60 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 225 EP 234 DI 10.1158/1055-9965.EPI-03-0206 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200008 PM 14973097 ER PT J AU Hakim, IA Harris, RB Chow, HHS Dean, M Brown, S Ali, IU AF Hakim, IA Harris, RB Chow, HHS Dean, M Brown, S Ali, IU TI Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers: Role of glutathione S-transferase genotypes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LUNG-CANCER RISK; PERFORMANCE LIQUID-CHROMATOGRAPHY; TRANS-STILBENE OXIDE; GSTM1 NULL GENOTYPE; URINARY 8-HYDROXY-2-DEOXYGUANOSINE; ELECTROCHEMICAL DETECTION; GENETIC SUSCEPTIBILITY; GSTT1 POLYMORPHISMS; BIOLOGICAL-FLUIDS; BLACK TEA AB Glutathione S-transferase (GST), a member of the phase II group of xenobiotic metabolizing enzymes, has been intensively studied at the levels of phenotype and genotype. The GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null-allele variant in which the entire gene is absent. The null genotype for both enzymes has been associated with many different types of tumors. The aim of this study was to determine the possible differences in increased oxidative stress susceptibility to smoking within the GSTM1 and GSTT1 genotypes and the impact of high tea drinking on this. We designed a Phase II randomized, controlled, three-arm tea intervention trial to study the effect of high consumption (4 cups/day) of decaffeinated green or black tea, or water on oxidative DNA damage, as measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a 4-month period and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect modifiers. A total of 133 heavy smokers (100 females and 33 males) completed the intervention. GSTM1 and GSTT1 genotype statuses were determined with a PCR-based approach. Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG, with or without adjustment for potential confounders. Finally, we studied whether the effect of treatment varied by GSTM1 and green tea showed a decrease in urinary 8-OHdG levels after 4 months. Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed significant effect for green tea consumption (P = 0.001). The change from baseline was significant in both GSTM1-positive (t = -2.99; P = 0.006) and GSTT1-positive (P = 0.004) green tea groups, but not in the GSTM1-negative (P = 0.07) or GSTT1-negative (P = 0.909) green tea groups. Decaffeinated black tea consumption had no effect on urinary 8-OHdG levels among heavy smokers. Our data show that consumption of 4 cups of tea/day is a feasible and safe approach and is associated with a significant decrease in urinary 8-OHdG among green tea consumers after 4 months of consumption. This finding also suggests that green tea intervention may be effective in the subgroup of smokers who are GSTM1 and/or GSTT1 positive. C1 Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ 85721 USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Hakim, IA (reprint author), Arizona Canc Ctr, 1515 N Campbell Ave,POB 245024, Tucson, AZ 85724 USA. EM ihakim@azcc.arizona.edu RI Ali, Imran/F-7710-2010; OI Ali, Imran/0000-0001-6511-8374; Dean, Michael/0000-0003-2234-0631 NR 56 TC 32 Z9 33 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 242 EP 249 DI 10.1158/1055-9965.EPI-03-0193 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200010 PM 14973088 ER PT J AU Michaud, DS Mysliwiec, PA Aldoori, W Willett, WC Giovannucci, E AF Michaud, DS Mysliwiec, PA Aldoori, W Willett, WC Giovannucci, E TI Peptic ulcer disease and the risk of bladder cancer in a prospective study of male health professionals SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI INFECTION; CHRONIC ATROPHIC GASTRITIS; RENAL PELVIS; US MEN; PHENACETIN; WOMEN; ACETAMINOPHEN; ANALGESICS; CARCINOGENESIS; PATHOGENESIS AB Helicobacter pylori is a risk factor for gastric and duodenal ulcers, but gastric ulcers generally occur in individuals who have low acid production and diffuse gastritis, whereas duodenal ulcers are more likely to occur with high acid output and antrum-predominant gastritis. Low acid production, gastritis, and ulcer healing each contribute to poor antioxidant absorption, oxidative stress, and elevated nitrite levels in the stomach. N-Nitrosamines are known carcinogens, and nitrate ingestion has been related to bladder cancer risk. Consequently, we hypothesized that the gastric conditions associated with gastric ulcers may contribute to elevated bladder cancer risk. We thus examined the association between self-reported history of peptic ulcer disease and the risk of bladder cancer (414 cases) over 14 years of follow-up in the Health Professional Follow-Up Study. Cox proportional hazards models were performed to adjust for known risk factors of bladder cancer. Men who reported a gastric ulcer before 1986 had a significantly higher risk of bladder cancer compared with those with no history of gastric ulcer (relative risk = 1.55, 95% confidence interval = 1.03-2.33, controlling for smoking and other potential confounders). No association was observed for duodenal ulcers (multivariate relative risk = 0.97, 95% confidence interval = 0.68-1.38). The ulcers in this study were based solely on self-report and not medical records; consequently, misclassification of ulcers may have occurred. Although intriguing, these findings need to be replicated. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Calif Davis, Div Gastroenterol Hepatol, Sacramento, CA 95817 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Michaud, DS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge 920, Boston, MA 02115 USA. EM dmichaud@hsph.harvard.edu RI Michaud, Dominique/I-5231-2014 NR 33 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 250 EP 254 DI 10.1158/1055-9965.EPI-03-0174 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200011 PM 14973090 ER PT J AU Cantwell, M Mittl, B Curtin, J Carroll, R Potischman, N Caporaso, N Sinha, R AF Cantwell, M Mittl, B Curtin, J Carroll, R Potischman, N Caporaso, N Sinha, R TI Relative validity of a food frequency questionnaire with a meat-cooking and heterocyclic amine module SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GRILLED RED MEAT; WELL-DONE; COLORECTAL ADENOMAS; VARYING DEGREES; UNITED-STATES; COLON CANCER; RISK; VALIDATION; MUTAGENS; CHICKEN AB The nutrient and heterocyclic amine (HCA) intake of 165 healthy participants was assessed using a self-administered food frequency questionnaire (FFQ), which included a meat-cooking practices module. A database containing the HCA [2-amino-3,8-dimethylimadazo [4,541 quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimadazo [4,5-b] pyridine (PhIP)] composition of various types of meat, cooked by different methods and to varying degrees, was developed and validated in conjunction with this module. The relative validity of dietary and HCA intake estimated by the FFQ was investigated using multiple food diaries (3 sets of 4 nonconsecutive day diaries completed over a 3-month period) as the reference method. Crude correlation coefficients of HCA intake assessed by the FFQ and food diaries were 0.43 [95% confidence interval (CI) 0.30-0.55] for MeIQx and 0.22 (95% CI 0.07-0.36) for PhIP intake. Deattenuated correlations were 0.60 (95% CI 0.49-0.69) and 0.36 (95% CI 0.22-0.49), respectively. Absolute MeIQx and PhIP intake was, however, underestimated by the FFQ (21.9 and 78.1 ng/day) compared with the food diaries (34.9 and 263.8 ng/day). The FFQ underestimated total red meat intake, the percentage of consumers, and the median intake of roast/baked and microwaved red meat. PhIP intake was severely underestimated by the FFQ and was most likely because of an underestimation of the percentage of people who cooked chicken using PhIP-producing cooking methods such as broiling and pan-frying. Additionally, the FFQ overestimated the percentage of consumers of baked chicken, a cooking method that produces less PUP. In conclusion, although the FFQ and meat module underestimated absolute MeIQx and PhIP intake, its ability to rank individuals according to intake was acceptable. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Westat Corp, Rockville, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Cantwell, M (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 3034,6120 Execut Blvd, Rockville, MD 20852 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 34 TC 47 Z9 48 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 293 EP 298 DI 10.1158/1055-9965.EPI-270-2 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200018 PM 14973110 ER PT J AU Viscidi, RP Schiffman, M Hildesheim, A Herrero, R Castle, PE Bratti, MC Rodriguez, AC Sherman, ME Wang, S Clayman, B Burk, RD AF Viscidi, RP Schiffman, M Hildesheim, A Herrero, R Castle, PE Bratti, MC Rodriguez, AC Sherman, ME Wang, S Clayman, B Burk, RD TI Seroreactivity to human papillomavirus (HPV) types 16, 18, or 31 and risk of subsequent HPV infection: Results from a population-based study in Costa Rica SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VIRUS-LIKE PARTICLES; WOMEN; VACCINE; IMMUNIZATION; ANTIBODIES; TRIAL AB Whether antibodies to human papillomavirus (HPV) capsids, elicited by natural infection, are protective is unknown. This question was addressed in a population-based cohort of 7046 women in Costa Rica by examining the association between baseline seroreactivity to HPV-16 HPV-18, or HPV-31 virus-like particles and the risk of subsequent HPV infection at a follow-up visit 5-7 years after enrollment. Seropositivity to HPV-16, HPV-18, or HPV-31 was not associated with a statistically significant decreased risk of infection with the homologous HPV type [relative risk (RR) and [95% confidence interval (CI)], 0.74 (0.45-1.2), 1.5 (0.83-2.7), and 0.94 (0.48 -1.8), respectively]. Seropositivity to HPV-16 or HPV-31 was not associated with a decreased risk of infection with HPV-16 or its genetically related types [RR (95% CI), 0.82 (0.61-1.1) and 0.93 (0.68-1.2), respectively]. Seropositivity to HPV-18 was not associated with a decreased risk of infection with HPV-18 or its genetically related types (RR 1.3; 95% CI 1.0-1.8). Thus, we did not observe immunity, although a protective effect from natural infection cannot be excluded because of the,limits of available assays and study designs. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. Costa Ricam Fdn Hlth Sci, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Viscidi, RP (reprint author), Johns Hopkins Univ Hosp, Blalock Room 1105,600 N Wolfe St, Baltimore, MD 21287 USA. EM rviscid1@jhem.jhmi.edu FU NCI NIH HHS [CA78527, N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-506535, N02-CP-81024-50] NR 14 TC 112 Z9 117 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2004 VL 13 IS 2 BP 324 EP 327 DI 10.1158/1055-9965.EPI-03-0166 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 774XG UT WOS:000189011200023 PM 14973086 ER PT J AU Terabe, M Park, JM Berzofsky, JA AF Terabe, M Park, JM Berzofsky, JA TI Role of IL-13 in regulation of anti-tumor immunity and tumor growth SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article ID REED-STERNBERG CELLS; RECEPTOR-ALPHA CHAIN; STIMULATORY FACTOR-I; INTERLEUKIN-13 RECEPTOR; T-CELLS; STAT6-DEFICIENT MICE; HODGKIN LYMPHOMA; CUTTING EDGE; B-CELLS; ENDOTHELIAL-CELLS AB Major mediators of anti-tumor immunity are CD4(+) T(H)1 cells and CD8(+) cytotoxic T lymphocytes (CTLs). In tumor-bearing animals, the T(H)1- and CTL-mediated anti-tumor immunity is down-regulated in multiple ways. Better understanding of negative regulatory pathways of tumor immunity is crucial for the development of anti-tumor vaccines and immunotherapies. Since immune deviation toward T(H)2 suppresses T(H)1 development, it has been thought that induction affecting a T(H)2 immune response is one of the mechanisms that down-regulate effective tumor immune responses. Recent studies using T(H)2-deficient signal transducer and activator (Stat6) KO mice demonstrated that this hypothesis was the case. IL-13 is one of the T(H)2 cytokines that has very similar features to IL-4 through sharing some receptor components and Stat6 signal transduction. It has been thought that IL-13 is not as critical for immune deviation as IL-4 since it cannot directly act on T cells. However, recent studies of IL-13 reveal that this cytokine plays a critical role in many aspects of immune regulation. Studies from our lab and others indicate that IL-13 is central to a novel immunoregulatory pathway in which NKT cells suppress tumor immunosurveillance. Here we will describe biological properties and functions of IL-13, its role in the negative regulation of anti-tumor immunity, and effects of IL-13 on tumor cells themselves. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Terabe, M (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Ctr Canc Res,NIH, Bldg 10,Room 6B-12,MSC 1578,10 Ctr Dr, Bethesda, MD 20892 USA. NR 78 TC 98 Z9 108 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 2004 VL 53 IS 2 BP 79 EP 85 DI 10.1007/s00262-003-0445-0 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA 754HE UT WOS:000187309400004 PM 14610620 ER PT J AU Pack, SD Alper, OM Stromberg, K Augustus, M Ozdemirli, M Miermont, AM Klus, G Rusin, M Slack, R Hacker, NF Ried, T Szallasi, Z Alper, O AF Pack, SD Alper, OM Stromberg, K Augustus, M Ozdemirli, M Miermont, AM Klus, G Rusin, M Slack, R Hacker, NF Ried, T Szallasi, Z Alper, O TI Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CANCER CELLS; ZD1839 IRESSA; PROLIFERATION; AMPLIFICATION; APOPTOSIS; DOMAIN; PARP AB Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype. C1 NCI, NIH, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot,NCI,NIH, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Bethesda, MD 20014 USA. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD USA. Georgetown Univ, Sch Med, Inst Mol & Human Genet, Vincent T Lombardi Canc Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Pathol Lab, Vincent T Lombardi Canc Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Dept Oncol, Vincent T Lombardi Canc Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Dept Biostat, Vincent T Lombardi Canc Ctr, Washington, DC USA. Harvard Univ, Sch Med, Childrens Hosp Informat Program, Boston, MA 02115 USA. RP Alper, OM (reprint author), NCI, NIH, Human Carcinogenesis Lab, Bldg 10,Room 5D37,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oa4@georgetown.edu RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [2P30-CA-51008]; NCRR NIH HHS [1S10RR15768-01] NR 19 TC 26 Z9 28 U1 0 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 FEB 1 PY 2004 VL 64 IS 3 BP 789 EP 794 DI 10.1158/0008-5472.CAN-03-1982 PG 6 WC Oncology SC Oncology GA 771VF UT WOS:000188806200002 PM 14871800 ER PT J AU Nanda, A Carson-Walter, EB Seaman, S Barber, TD Stampfl, J Singh, S Vogelstein, B Kinzler, KW St Croix, B AF Nanda, A Carson-Walter, EB Seaman, S Barber, TD Stampfl, J Singh, S Vogelstein, B Kinzler, KW St Croix, B TI TEM8 interacts with the cleaved C5 domain of collagen alpha 3(VI) SO CANCER RESEARCH LA English DT Article ID ANTHRAX LETHAL FACTOR; TUMOR-GROWTH; ANGIOGENESIS; EXPRESSION; INHIBITOR; MATRIX AB Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue. We used the extracellular domain of TEM8 to search for ligands and identified the alpha3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha3(VI) was mapped to its COOH-terminal C5 domain. Remarkably, collagen alpha3(VI) is also preferentially expressed in tumor endothelium in a pattern concordant with that of TEM8. These results suggest that the TEM8/C5 interaction may play an important biological role in tumor angiogenesis. C1 NCI, Mouse Canc Gneet Program, Tumor Angiogenesis Sect, Frederick, MD 21702 USA. Johns Hopkins Sch Med, Program Human Genet & Mol Biol, Baltimore, MD USA. Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Johns Hopkins Sch Med, Howard Hughes Med Inst, Baltimore, MD USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Imgenex Corp, San Diego, CA USA. RP St Croix, B (reprint author), NCI, Mouse Canc Gneet Program, Tumor Angiogenesis Sect, Frederick, MD 21702 USA. EM stcroix@ncifcrf.gov RI Seaman, Steven/A-2755-2013 OI Seaman, Steven/0000-0003-3349-3334 NR 14 TC 107 Z9 110 U1 0 U2 5 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 FEB 1 PY 2004 VL 64 IS 3 BP 817 EP 820 DI 10.1158/0008-5472.CAN-03-2408 PG 4 WC Oncology SC Oncology GA 771VF UT WOS:000188806200007 PM 14871805 ER PT J AU Ng, SSW Figg, WD Sparreboom, A AF Ng, SSW Figg, WD Sparreboom, A TI Taxane-mediated antiangiogenesis in vitro: Influence of formulation vehicles and binding proteins SO CANCER RESEARCH LA English DT Article ID CREMOPHOR EL; DOCETAXEL TAXOTERE; PACLITAXEL; ANGIOGENESIS; VIVO; CHEMOTHERAPY; INHIBITION; THERAPY; CANCER; MICE AB Paclitaxel (Taxol) and docetaxel (Taxotere) have been shown to inhibit angiogenesis at low concentrations that do not affect cancer cell proliferation. Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis. The data show that clinically relevant concentrations of the vehicles and binding proteins nullify the antiangiogenic activity of both taxanes. It is suggested that these agents may need to be used at much higher doses than anticipated for effective antiangiogenic chemotherapy. C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, NIH, Bethesda, MD 20892 USA. Canc Res Ctr, Canc Therapeut Branch, Mol Pharmacol Sect, Bethesda, MD USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, NIH, Bldg 10,Room 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 22 TC 53 Z9 54 U1 0 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 FEB 1 PY 2004 VL 64 IS 3 BP 821 EP 824 DI 10.1158/0008-5472.CAN-03-3391 PG 4 WC Oncology SC Oncology GA 771VF UT WOS:000188806200008 PM 14871806 ER PT J AU Rusyn, I Asakura, S Pachkowski, B Bradford, BU Denissenko, MF Peters, JM Holland, SM Reddy, JK Cunningham, ML Swenberg, JA AF Rusyn, I Asakura, S Pachkowski, B Bradford, BU Denissenko, MF Peters, JM Holland, SM Reddy, JK Cunningham, ML Swenberg, JA TI Expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemical-induced chronic oxidative stress: Identification of the molecular source of radicals responsible for DNA damage by peroxisome proliferators SO CANCER RESEARCH LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; ACYL-COA OXIDASE; MOUSE-LIVER; APURINIC/APYRIMIDINIC SITES; MAMMALIAN-CELLS; BETA-OXIDATION; MICE; CARCINOGENESIS; DEFICIENT; MECHANISM AB Oxidative stress to DNA is recognized as one of the mechanisms for the carcinogenic effects of some environmental agents. Numerous studies have been conducted in an attempt to document the fact that chemical carcinogens that are thought to induce production of oxidants also cause the formation of oxidative DNA lesions. Although many DNA adducts continue to be useful biomarkers of dose/effect, changes in gene expression have been proposed to be a practical novel tool for studying the role of chemically induced oxidative DNA damage. Here, we hypothesized that expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemically induced chronic oxidative stress. To test this hypothesis, mice were treated with a known rodent carcinogen and peroxisome proliferator, WY-14,643 (500 ppm, 1 month). A number of end points that are commonly used to assess oxidative DNA damage were considered. Our data demonstrate that no difference in 8-oxoguanine, the number of abasic sites, or single strand breaks can be detected in genomic DNA from livers of control or WY-treated animals. However, a concordant marked induction of genes specific for the long-patch base excision DNA repair, a predominant pathway that removes oxidized DNA lesions in vivo, was observed in livers of WY-treated mice. Kupffer cell NADPH oxidase, and peroxisomes in parenchymal cells have been proposed as the potential sources of peroxisome proliferator-induced oxidants. The analysis of expression of base excision DNA repair genes was used to assess whether this biomarker of oxidative stress can be used to determine the source of oxidants. The data suggest that DNA-damaging oxidants are generated by enzymes that are induced after activation of peroxisome proliferator activator receptor a, such as those involved in lipid metabolism in peroxisomes, and are not the result of activation of NADPH oxidase in Kupffer cells. We conclude that expression of base excision DNA repair genes is a sensitive in vivo biomarker for chemically induced oxidative stress to DNA that can be successfully used for the identification of the molecular source of radicals responsible for DNA damage in vivo. C1 Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Lab Mol Carcinogenesis & Mutagenesis, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Lab Environm Genome, Chapel Hill, NC 27599 USA. Sequenom Inc, San Diego, CA 92121 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, 357 Rosenau Hall CB 7431, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Peters, Jeffrey/D-8847-2011; Rusyn, Ivan/S-2426-2016 FU NCI NIH HHS [CA16086]; NIEHS NIH HHS [ES05948, ES10126, ES11391, ES11660]; NIGMS NIH HHS [GM23750] NR 47 TC 72 Z9 73 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 FEB 1 PY 2004 VL 64 IS 3 BP 1050 EP 1057 DI 10.1158/0008-5472.CAN-03-3027 PG 8 WC Oncology SC Oncology GA 771VF UT WOS:000188806200039 PM 14871837 ER PT J AU Feril, LB Tsuda, Y Kondo, T Zhao, QL Ogawa, R Cui, ZG Tsukada, K Riesz, P AF Feril, LB Tsuda, Y Kondo, T Zhao, QL Ogawa, R Cui, ZG Tsukada, K Riesz, P TI Ultrasound-induced killing of monocytic U937 cells enhanced by 2,2 '-azobis(2-amidinopropane) dihydrochloride SO CANCER SCIENCE LA English DT Article ID HYPERTHERMIA-INDUCED APOPTOSIS; FREE-RADICAL INITIATOR; ECHO CONTRAST AGENT; IN-VITRO; DISSOLVED-GASES; GENE TRANSFECTION; LEUKEMIC-CELLS; GLIOMA-CELLS; MEMBRANE; HEMATOPORPHYRIN AB To determine the effect of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) on ultrasound (US)-induced cell killing, human monocytic leukemia cells (U937) were incubated at various temperatures (25.0, 37.0 and 40.0degreesC for 1 min in air-saturated phosphate-buffered solution (PBS) containing 50 mM AAPH before exposure to nonthermal 1 MHz US for 1 min at an intensity of 2.0 W/cm(2). Cell viability was determined by means of the Trypan blue dye exclusion test immediately after sonication. Apoptosis was measured after 6-h incubation post-sonication by flow cytometry. Free radicals generated by AAPH, a temperature-dependent free radical generator, or US or both were also investigated using electron paramagnetic resonance (EPR) spin trapping. The results showed that US-induced cell lysis and apoptosis were enhanced in the presence of AAPH regardless of the temperature at the time of sonication. At 40.0degreesC, US alone induced increased cell killing, while AAPH alone is capable of inducing significant but minimal apoptosis at this temperature. Although free radicals were increased in the combined treatment, this increase did not correlate well with cell killing. The mechanism of enhancement points to the increased uptake of the agent during sonication rather than potentiation by AAPH. These findings suggest the clinical potential of temperature-dependent free radical generators in cancer therapy with therapeutic US. C1 Toyama Med & Pharmaceut Univ, Dept Radiol Sci, Toyama 9300194, Japan. Toyama Med & Pharmaceut Univ, Dept Surg 2, Toyama 9300194, Japan. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Kondo, T (reprint author), Toyama Med & Pharmaceut Univ, Dept Radiol Sci, 2630 Sugitani, Toyama 9300194, Japan. EM kondot@ms.toyama-mpu.ac.jp NR 33 TC 33 Z9 36 U1 0 U2 1 PU JAPANESE CANCER ASSOC PI TOKYO PA C/O JAPANESE FOUNDATION CANCER RESEARCH,1-37-1, KAMI-IKEBUKURO, TOSHIMA-KU, TOKYO, 170-0012, JAPAN SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD FEB PY 2004 VL 95 IS 2 BP 181 EP 185 DI 10.1111/j.1349-7006.2004.tb03201.x PG 5 WC Oncology SC Oncology GA 779UE UT WOS:000189319100013 PM 14965370 ER PT J AU Horn, EJ Albor, A Liu, YG El-Hizawi, S Vanderbeek, GE Babcock, M Bowden, GT Hennings, H Lozano, G Weinberg, WC Kulesz-Martin, M AF Horn, EJ Albor, A Liu, YG El-Hizawi, S Vanderbeek, GE Babcock, M Bowden, GT Hennings, H Lozano, G Weinberg, WC Kulesz-Martin, M TI RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties SO CARCINOGENESIS LA English DT Article ID INDUCED TERMINAL DIFFERENTIATION; MOUSE EPIDERMAL-CELLS; B-RADIATION; KERATINOCYTE APOPTOSIS; UBIQUITIN LIGASE; GENE-EXPRESSION; WILD-TYPE; P53; GROWTH; LOCALIZATION AB (Tri) under bar partite (m) under bar otif protein 32, Trim32, mRNA and protein expression was elevated in independently transformed and tumorigenic keratinocytes of a mouse epidermal carcinogenesis model, in ultraviolet B (UVB)-induced squamous cell carcinomas (SCC), and in similar to20-25% of chemically induced mouse papillomas and human head and neck SCCs. This suggests that elevated Trim32 expression occurs frequently in experimental epidermal carcinogenesis and is relevant to human cancer. Transduced Trim32 increased colony number in an epidermal in vitro transformation assay and epidermal thickening in vivo when skin-grafted to athymic nu/nu mice. These effects were not associated with proliferation and were not sufficient for tumorigenesis, even with 12-O-tetradecanoylphorbol-13-acetate treatment or defects in the tumor suppressor p53. However, transduced Trim32 inhibited the synergistic effect of tumor necrosis factor alpha (TNFalpha) on UVB-induced apoptosis of keratinocytes in vitro and the apoptotic response of keratinocyte grafts exposed to UVB-light in vivo. Consistent with its RING domain, Trim32 exhibited characteristics of E3-ubiquitin ligases, including being ubiquitylated itself and interacting with ubiquitylated proteins, with increases in these properties following treatment of cultured keratinocytes with TNFalpha/UVB. Interestingly, missense point mutation of human TRIM32 has been reported in Limb-Girdle Muscular Dystrophy Type 2H, an autosomal recessive disease. We propose a model in which Trim32 activities as an E3-ubiquitin ligase favor initiated cell survival in carcinogenesis by blocking UVB-induced TNFalpha apoptotic signaling. C1 Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. SUNY Buffalo, Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Univ Arizona, Dept Radiat Oncol, Tucson, AZ 85724 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. US FDA, Immunobiol Lab, Rockville, MD 20857 USA. RP Kulesz-Martin, M (reprint author), Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97239 USA. EM kuleszma@ohsu.edu RI Weinberg, Wendy/A-8920-2009 FU NCI NIH HHS [CA16056, R01 CA098577, CA69533, CA31101] NR 43 TC 67 Z9 73 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2004 VL 25 IS 2 BP 157 EP 167 DI 10.1093/carcin/bgh003 PG 11 WC Oncology SC Oncology GA 771NQ UT WOS:000188792800001 PM 14578165 ER PT J AU Estensen, RD Jordan, MM Wiedmann, TS Galbraith, AR Steele, VE Wattenberg, LW AF Estensen, RD Jordan, MM Wiedmann, TS Galbraith, AR Steele, VE Wattenberg, LW TI Effect of chemopreventive agents on separate stages of progression of benzo[alpha]pyrene induced lung tumors in A/J mice SO CARCINOGENESIS LA English DT Article ID PULMONARY CARCINOGENESIS; AEROSOLIZED BUDESONIDE; CANCER PREVENTION; MOUSE LUNG; MYOINOSITOL; BIOMARKERS; INHIBITION; NEOPLASIA; STRAIN AB The effects of aerosol budesonide and dietary myo-inositol on progression of benzo[alpha]pyrene (B[alpha]P) induced carcinogenesis were studied in A/J mouse lung. First, we determined when to intervene in the carcinogenesis process by exposing several animals to B[alpha]P at 100 and 150 mg/kg of body wt. Groups of these animals were necropsied from 1 to 36 weeks post-carcinogen. The presence of different categories of lung tumors was noted over the 36 week time period. Hyperplasia first appeared similar to6 weeks post-carcinogen followed by adenoma at 9 weeks, then by carcinoma at 26 weeks. From this temporal sequence we determined we could test for effects of preventive agents on progression to hyperplasia by intervening at 3 weeks, for effects on progression to adenoma by intervening at 6 weeks and for effects on progression to carcinoma by intervention at 12 weeks. Intervention at 3 weeks post-carcinogen with aerosolized budesonide delayed both hyperplasia and adenoma formation. Once hyperplasia appeared in budesonide treated animals, however, it increased at the same rate as in control animals, indicating a delay in progression. Progression from adenoma to carcinoma was reduced when budesonide was given 12 weeks post-carcinogen. Dietary myo-inositol failed to suppress progression from adenoma to carcinoma when started 12 weeks post-carcinogen. In summary, budesonide is a chemopreventive agent that has inhibitory effects on B[alpha]P induced carcinogenesis of the lung in A/J mice at all stages of progression from hyperplasia formation to cancer. C1 Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Estensen, RD (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. EM esten001@umn.edu FU NCI NIH HHS [N01-CN-85069] NR 20 TC 46 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 2004 VL 25 IS 2 BP 197 EP 201 DI 10.1093/carcin/bgg196 PG 5 WC Oncology SC Oncology GA 771NQ UT WOS:000188792800005 PM 14578161 ER PT J AU Du, CW Pan, YT MacGowan, GA Koretsky, AP AF Du, CW Pan, YT MacGowan, GA Koretsky, AP TI Decreasing motion artifacts in calcium-dependent fluorescence transients from the perfused mouse heart using frequency filtering SO CELL CALCIUM LA English DT Article DE motion artifacts; calcium-dependent fluorescence; perfused heart; mouse; frequency filtering ID ALTERNANS; CA2+ AB A strategy has been developed for the removal of motion artifact and noise in calcium-dependent fluorescence transients from the perfused mouse heart using frequency filtering. An analytical model indicates that the spectral removal of motion artifacts is independent of the phase shift of the motion waveform in the frequency domain, and thus to the time shift (or delay) of motion in the time domain. This is based on the "shift theorem" of Fourier analysis, which avoids erroneous correction of motion artifact when using the motion signal obtained using reflectance from the heart. Several major steps are adopted to implement this model for elimination of motion as well as detection noise from the fluorescence transient signals from the calcium-sensitive probe Rhod-2. These include (1) extracting the fluorescence calcium transient signal from the raw data by using power spectrum density (PSD) in the frequency domain by subtracting the motion recorded using the reflectance of excitation light, (2) digitally filtering out the random noise using multiple bandpass filters centralized at harmonic frequencies of the transients, and (3) extracting high frequency noise with a Gaussian Kernel filter method. The processed signal of transients acquired with excessive motion artifact is comparable to transients acquired with minimal motion obtained by immobilizing the heart against the detection window, demonstrating the usefulness of this technique. Published by Elsevier Ltd. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11794 USA. SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11790 USA. Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA USA. RP Koretsky, AP (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bldg 10,B1D-69B,MSC 1060,9000 Rockville Pick, Bethesda, MD 20892 USA. EM koretskya@ninds.nih.gov RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 24 TC 1 Z9 1 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD FEB PY 2004 VL 35 IS 2 BP 141 EP 153 DI 10.1016/j.ceca.2003.08.005 PG 13 WC Cell Biology SC Cell Biology GA 769JH UT WOS:000188646600006 PM 14706288 ER PT J AU Roberts, BT Wickner, RB AF Roberts, BT Wickner, RB TI A new kind of prion - A modified protein necessary for its own modification SO CELL CYCLE LA English DT Article DE prion; protease B (PrB); Creutzfeldt-Jacob disease; Mad Cow disease; transmissible; spongiform encephalopathies (TSEs); Saccharomyces cerevisiae; Podospora anserina ID YEAST SACCHAROMYCES-CEREVISIAE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; IN-VITRO; SUP35 PROTEIN; HETEROKARYON INCOMPATIBILITY; MOLECULAR-GENETICS; SCRAPIE PRION; INHERITANCE; AGENT; PRP AB We recently described an infectious protein ( prion) unrelated to amyloid formation, that is an enzyme whose precursor can only be activated by the active form of the enzyme. All previously described infectious proteins are self-propagating amyloid forms of chromosomally encoded proteins. The infectious enzyme, vacuolar protease B (PrB), can activate its own precursor in an indefinitely self-propagating process. Transfer from cell to cell of cytoplasm containing active protease B transmits this non-chromosomal gene. The importance of this system is that many protein-modifying enzymes may act on themselves, and if conditions are right, may become prions as well. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 44 TC 4 Z9 4 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB PY 2004 VL 3 IS 2 BP 100 EP 103 PG 4 WC Cell Biology SC Cell Biology GA 833TD UT WOS:000222361200002 PM 14712063 ER PT J AU Melillo, G AF Melillo, G TI HIF-1: A target for cancer, ischemia and inflammation - Too good to be true? SO CELL CYCLE LA English DT Editorial Material DE HIF-1; hypoxia; tumor microenvironment; metastasis; molecular targets; cancer therapeutics ID HYPOXIA-INDUCIBLE FACTOR-1; CHEMOKINE RECEPTOR CXCR4; ANGIOGENESIS; ACTIVATION; THERAPY; TUMORS; GROWTH C1 NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Sci Applicat Int Corp,Frederick Inc, Frederick, MD 21702 USA. RP Melillo, G (reprint author), NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Sci Applicat Int Corp,Frederick Inc, Bldg 432,Room 218, Frederick, MD 21702 USA. EM melillog@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 18 TC 44 Z9 45 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB PY 2004 VL 3 IS 2 BP 154 EP 155 PG 2 WC Cell Biology SC Cell Biology GA 833TD UT WOS:000222361200018 PM 14712079 ER PT J AU Rapisarda, A Shoemaker, RH Melillo, G AF Rapisarda, A Shoemaker, RH Melillo, G TI Targeting topoisomerase I to inhibit hypoxia inducible factor 1 SO CELL CYCLE LA English DT Article DE topoisomerase I; hypoxia; molecular targets; cancer therapeutics; HIF-1 ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; FACTOR 1-ALPHA; TUMOR-GROWTH; PHASE-II; FACTORS HIF-1-ALPHA; GENE-EXPRESSION; NECK-CANCER; TOPOTECAN; ANGIOGENESIS AB HIF-1 is a key factor in cancer progression. Efforts are underway to identify and develop small molecules that inhibit HIF-1 transcriptional activity. The best targets and the best ways to develop HIF-1 inhibitors are open questions. However, several "nonselective" HIF-1 inhibitors have been identified, which are either in the clinic or under development. In this article, we discuss how topoisomerase I poisons, which inhibit HIF-1alpha protein accumulation and transcriptional activity, can be "rationally" used to target HIF-1 for cancer therapy. C1 NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Frederick Inc, Div Dev Therapeut, Tumor Hypoxia Lab, Frederick, MD USA. RP Melillo, G (reprint author), NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Bldg 432,Room 218, Frederick, MD 21702 USA. EM melillog@ncifcrf.gov NR 51 TC 41 Z9 43 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB PY 2004 VL 3 IS 2 BP 172 EP 175 PG 4 WC Cell Biology SC Cell Biology GA 833TD UT WOS:000222361200023 PM 14712084 ER PT J AU Meetei, AR Yan, ZJ Wang, W AF Meetei, AR Yan, ZJ Wang, W TI FANCL replaces BRCA1 as the likely ubiquitin ligase responsible for FANCD2 monoubiquitination SO CELL CYCLE LA English DT Article DE Fanconi anaemia; FANCD2; ubiquitin ligase; PHF9; FANCL; BRCA1 ID ANEMIA PROTEINS; NUCLEAR-COMPLEX; PATHWAY AB Monoubiquitination of FANCD2 is a key step in the DNA damage response pathway involving Fanconi anemia proteins and the breast cancer susceptibility gene products, BRCA1 and BRCA2. One critical unresolved issue is the identity of the ubiquitin ligase responsible for this reaction. Two proteins, BRCA1 and FANCL(PHF9), have been suggested to be this ligase. Here we found that FANCL, but not BRCA1, evolutionarily co-exists with FANCD2 in several species. Moreover, the proportion of FANCD2 in chromatin and nuclear matrix is drastically reduced in a cell line mutated in FANCL but not in that mutated in BRCA1. This defective distribution of FANCD2 in the FANCL-mutant cell line is likely due to its defective monoubiquitination because the monoubiquitinated FANCD2 preferentially associates with chromatin and nuclear matrix, whereas non-ubiquitinated FANCD2 largely resides in the soluble fraction. Our data support the notion that FANCL, but not BRCA1, is the likely ligase for FANCD2 monoubiquitination. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Wang, W (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,TRIAD Ctr Room 3000, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov NR 18 TC 69 Z9 73 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB PY 2004 VL 3 IS 2 BP 179 EP 181 PG 3 WC Cell Biology SC Cell Biology GA 833TD UT WOS:000222361200025 PM 14712086 ER PT J AU Petrus, MJ Wilhelm, DE Murakami, M Kappas, NC Carter, AD Wroble, BN Sible, JC AF Petrus, MJ Wilhelm, DE Murakami, M Kappas, NC Carter, AD Wroble, BN Sible, JC TI Altered expression of Chk1 disrupts cell cycle remodeling at the midblastula transition in Xenopus laevis embryos SO CELL CYCLE LA English DT Article DE cell cycle; checkpoints; Chk1; embryo; midblastula transition; Xenopus; Wee1 ID MAJOR DEVELOPMENTAL TRANSITION; MITOTIC ENTRY; CHECKPOINT; APOPTOSIS; KINASE; TIMER; DEGRADATION; OOCYTES; PHOSPHORYLATION; TRANSCRIPTION AB Studies in several model systems, including Xenopus laevis oocytes and embryos, have indicated that the checkpoint kinase, Chk1, is required for early development, even in the absence of damaged or unreplicated DNA. Chk1 is transiently activated at the midblastula transition (MBT) in Xenopus, a time when the cell cycle remodels from rapid embryonic cleavage cycles to longer, more regulated somatic cell cycles. To better understand the role of Chk1 in cell cycle remodeling, mRNA encoding Chk1 was microinjected into 1-cell stage embryos, and the effects on both the MBT and on the expression of several cell cycle regulators were examined. Zygotic transcription, a hallmark of the MBT that depends upon the nucleocytoplasmic (N/C) ratio, was blocked, as was degradation of maternal cyclin E, an event of the MBT that occurs independent of the N/C ratio. Levels of mitotic cyclins were elevated throughout early development, consistent with cell cycle arrest at G(2)/M. In these embryos, Cdc25A level was low, whereas Cdc25C level was not affected. Furthermore, the level of Wee1 increased at 6 hrs post-fertilization (pf), the time at which the MBT normally occurs, even though these embryos did not demonstrate any known markers of the MBT. These studies suggest that in addition to targeting Cdc25A for degradation, Chk1 may also function in cell cycle remodeling at the MBT by stabilizing Wee1 until it is replaced by the somatic Wee2 protein during gastrulation. C1 Virginia Polytech Inst & State Univ, Dept Biol, Blacksburg, VA 24061 USA. NCI, ABL, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Sible, JC (reprint author), Virginia Polytech Inst & State Univ, Dept Biol, Blacksburg, VA 24061 USA. EM siblej@vt.edu FU NIGMS NIH HHS [GM59688] NR 37 TC 7 Z9 7 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD FEB PY 2004 VL 3 IS 2 BP 212 EP 216 PG 5 WC Cell Biology SC Cell Biology GA 833TD UT WOS:000222361200030 PM 14712091 ER PT J AU Pan, HN Hong, F Radaeva, S Gao, B AF Pan, Hongna Hong, Feng Radaeva, Svetlana Gao, Bin TI Hydrodynamic Gene Delivery of Interleukin-22 Protects the Mouse Liver from Concanavalin A-, Carbon Tetrachloride-, and Fas Ligand-Induced Injury via Activation of STAT3 SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Article DE IL-22; STAT3; hydrodynamic gene therapy; liver injury AB Interleukin-22 (IL-22) is a recently identified T cell-derived cytokine whose biological significance remains obscure. Previously, we have shown that IL-22 plays a protective role in T cell-mediated hepatitis induced by Concanavalin A (Con A), acting as a survival factor for hepatocytes. In the present paper, we demonstrate that hydrodynamic gene delivery of IL-22 cDNA driven either by a liver-specific albumin promoter or a human cytomegalovirus (CMV) promoter results in IL-22 protein expression, STAT3 activation, and expression of several anti-apoptotic proteins, including Bcl-xL, Bcl-2, and Mcl-1 in the liver. Immunohistochemical analysis reveals that IL-22 protein expression is mainly detected in the cytoplasm of hepatocytes. Overexpression of IL-22 by hydrodynamic gene delivery significantly protects against liver injury, necrosis, and apoptosis induced by administration of Con A, carbon tetrachloride (CCl4), or the Fas agonist Jo-2 mAb. Western blot analyses show that overexpression of IL-22 significantly enhances activation of STAT3 and expression of Bcl-xL, Bcl-2, and Mcl-1 proteins in liver injury induced by Con A. In conclusion, hydrodynamic gene delivery of IL-22 protects against liver injury induced by a variety of toxins, suggesting the therapeutic potential of IL-22 in treating human liver disease. C1 [Pan, Hongna; Hong, Feng; Radaeva, Svetlana; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, NIH, Pk Bldg Rm 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 34 TC 107 Z9 115 U1 0 U2 1 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD FEB PY 2004 VL 1 IS 1 BP 43 EP 49 PG 7 WC Immunology SC Immunology GA V31ZS UT WOS:000208922100007 PM 16212920 ER PT J AU Tao, HY Wu, CF Zhou, Y Gong, WH Zhang, X Iribarren, P Zhao, YQ Le, YY Wang, JM AF Tao, Hengyi Wu, Chunfu Zhou, Ye Gong, Wanghua Zhang, Xia Iribarren, Pablo Zhao, Yuqing Le, Yingying Wang, Jiming TI The Grape Component Resveratrol Interferes with the Function of Chemoattractant Receptors on Phagocytic Leukocytes SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Article DE resveratrol; chemoattractants; receptors; signaling; inflammation AB Resveratrol (3, 5, 4'-trihydroxystilbene) (RV) is a constituent of grape seeds with anti-inflammatory and anti-oxidant activities. In this study, we examined the capacity of RV to modulate the function of G protein-coupled chemoattractant receptors, which play important roles in inflammation and immune responses. RV, over a non-cytotoxic concentration range, inhibited chemotactic and calcium mobilization responses of phagocytic cells to selected chemoattractants. At low micromolar concentrations RV potently reduced superoxide anion production by phagocytic leukocytes in response to the bacterial chemotactic peptide fMLF, a high affinity ligand for formylpeptide receptor FPR, and A beta(42), an Alzheimer's disease-associated peptide and a ligand for the FPR variant FPRL1. In addition, RV reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and the activation of nuclear factor NF-.B induced by formylpeptide receptor agonists. These results suggest that the inhibition of the function of chemoattractant receptors may contribute to the anti-inflammatory properties of RV. Thus, RV may be therapeutically promising for diseases in which activation of formylpeptide receptors contributes to the pathogenic processes. C1 [Tao, Hengyi; Zhou, Ye; Iribarren, Pablo; Le, Yingying; Wang, Jiming] NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. [Zhang, Xia] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Gong, Wanghua] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Wu, Chunfu] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. [Zhao, Yuqing] Res Ctr Modernizat Chinese Mat Med Liaoning Prov, Shenyang 110000, Peoples R China. [Tao, Hengyi] Shanghai Changzheng Hosp, Dept Naut Med, Shanghai, Peoples R China. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 FU Joint Key Research Project Funds from Second Military Medical University, Shanghai, People's Republic of China [LH 2003-01]; National Cancer Institute, National Institutes of Health [NO1-CO-12400]; USA Government FX The authors thank Dr. Joost J. Oppenheim for reviewing the manuscript, Ms. Nancy Dunlop for technical support and Ms. Cheryl Fogle and Ms. Cheryl Nolan for secretarial assistance. HT was also supported in part with Joint Key Research Project Funds from Second Military Medical University, Shanghai, People's Republic of China, under contract No. LH 2003-01. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract No. NO1-CO-12400.; The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government. The publisher or recipient acknowledges right of the USA Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article. NR 38 TC 11 Z9 12 U1 0 U2 1 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD FEB PY 2004 VL 1 IS 1 BP 50 EP 56 PG 7 WC Immunology SC Immunology GA V31ZS UT WOS:000208922100008 PM 16212921 ER PT J AU Jiang, Q Benbernou, N Chertov, O Khaled, AR Wooters, J Durum, SK AF Jiang, Q Benbernou, N Chertov, O Khaled, AR Wooters, J Durum, SK TI IL-7 induces tyrosine phosphorylation of clathrin heavy chain SO CELLULAR SIGNALLING LA English DT Article DE IL-7; IL-7 receptor; clathrin; tyrosine phosphorylation; Jak3 ID RECEPTOR-GAMMA-CHAIN; DEFECTIVE LYMPHOID DEVELOPMENT; MICE LACKING JAK3; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; JANUS KINASE; T-CELLS; ACTIVATION; CYTOKINE; BCL-2 AB IL-7 induction of protein tyrosine phosphorylation was examined in an IL-7-dependent thymocyte cell line, D1, which was generated from a P53(-/-) mouse. Anti-phosphotyrosine antibody was used both to immunoprecipitate and Western blot, and showed that IL-7 induced tyrosine phosphorylation of a protein with a molecular weight of approximately 200 kDa. The P200 band was purified by reversed-phase high-performance liquid chromatography. Amino acid sequencing by mass spectrometry revealed three peptides identical to rat clathrin heavy chain (CHC) 1 (192 kDa), and this was confirmed by blotting with an anti-clathrin antibody. Stimulation of normal pro-T cells by IL-7 showed an increased tyrosine phosphorylation of clathrin heavy chain. Tyrosine phosphorylation of clathrin heavy chain was strongly induced by IL-7 and to a lesser extent by IL-4, while no effect could be observed with the cytokines IL-2, IL-9 and IL-15, whose receptors share the gamma(c) chain. Phosphorylation of clathrin heavy chain was found to be sensitive to Jak3 inhibitors but not to Src inhibitors. Clathrin is involved in internalization of many receptors, and its phosphorylation by IL-7 stimulation may affect the internalization of the IL-7 receptor. Published by Elsevier Inc. C1 NCI, Mol Immunoregulat Lab, CCR, NIH, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Intramural Res Support Program, Cambridge, MA 02140 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, CCR, NIH, Room 31-71,Bldg 560, Frederick, MD 21702 USA. NR 31 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD FEB PY 2004 VL 16 IS 2 BP 281 EP 286 DI 10.1016/S0898-6568(03)00138-4 PG 6 WC Cell Biology SC Cell Biology GA 750NJ UT WOS:000187002400015 PM 14636898 ER PT J AU Sipe, HJ Jaszewski, AR Mason, RP AF Sipe, HJ Jaszewski, AR Mason, RP TI Fast-flow EPR spectroscopic observation of isoniazid, iproniazid, and phenylhydrazine hydrazyl radicals SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ELECTRON-PARAMAGNETIC RESONANCE; MYCOBACTERIUM-TUBERCULOSIS KATG; BASIS-SETS; OXIDATION; SPECTRA; METHEMOGLOBIN; PEROXIDASE; ACTIVATION; HEMOGLOBIN; DERIVATIVES AB Hydrazyl radical intermediates have been suggested as important intermediates in the biochemistry of hydrazides and hydrazines. Although spin-trapping studies have intercepted those species previously, there has been no report of the direct observation of the unstable hydrazyl radicals of isoniazid and iproniazid. We have employed the fast-flow technique in electron paramagnetic resonance (EPR) spectroscopy to measure spectra for the short-lived hydrazyl radicals of a family of hydrazides, including the pharmacologically important compounds isoniazid and iproniazid, as well as for a series of phenylhydrazines. Our investigations of the phenylhydrazine radical and the related chloro-substituted analogues have allowed definitive assignments of the hyperfine coupling constants of that toxicologically important free radical. Theoretical values of hyperfine coupling constants, calculated by density functional formalism, provided a guide to assignments for the hydrazyl species and confirmed the experimentally based assignments for phenylhydrazyl radical. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 34 TC 10 Z9 10 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD FEB PY 2004 VL 17 IS 2 BP 226 EP 233 DI 10.1021/tx0341759 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 775YF UT WOS:000189087700012 PM 14967010 ER PT J AU Jantz, D Amann, BT Gatto, GJ Berg, JM AF Jantz, D Amann, BT Gatto, GJ Berg, JM TI The design of functional DNA-binding proteins based on zinc finger domains SO CHEMICAL REVIEWS LA English DT Review ID TRANSCRIPTION FACTOR-IIIA; CRYSTAL-STRUCTURE; GENE-EXPRESSION; RESTRICTION ENZYMES; DEPENDENT STRUCTURE; THIOLATE COMPLEXES; LINKER SEQUENCES; CLEAVAGE DOMAIN; METAL-BINDING; FACTOR TFIIIA C1 Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. RP Berg, JM (reprint author), Natl Inst Gen Med Sci, Bethesda, MD 20892 USA. EM bergj@mail.nih.gov OI Berg, Jeremy/0000-0003-3022-0963 NR 108 TC 86 Z9 86 U1 2 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 J9 CHEM REV JI Chem. Rev. PD FEB PY 2004 VL 104 IS 2 BP 789 EP 799 DI 10.1021/cr020603o PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 773QM UT WOS:000188934400015 PM 14871141 ER PT J AU Hemila, H Virtamo, J Albanes, D Kaprio, J AF Hemila, H Virtamo, J Albanes, D Kaprio, J TI Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers SO CHEST LA English DT Article DE alcohol; alpha-tocopherol; antioxidants; body mass index; clinical trial; coffee; cohort study; community-acquired pneumonia; diet; risk factors ID COMMUNITY-ACQUIRED PNEUMONIA; RANDOMIZED CONTROLLED-TRIAL; HEALTHY ELDERLY SUBJECTS; RISK-FACTORS; CIGARETTE-SMOKING; IMMUNE-RESPONSE; LUNG-FUNCTION; POPULATION; INFECTIONS; DIETARY AB Background: Vitamin E and beta-carotene affect various measures of immune function and accordingly might influence the predisposition of humans to infections. However, only few controlled trials have tested this hypothesis. Study objective: To examine whether vitamin E or beta-carotene supplementation affects the risk of pneumonia in a controlled trial. Design and setting: The Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study, a randomized, double-blind, placebo-controlled trial that examined the effects of vitamin E, 50 mg/d, and beta-carotene, 20 mg/d, on lung cancer using a 2 X 2 factorial design. The trial was conducted in the general community in southwestern Finland in 1985 to 1993; the intervention lasted for 6.1 years (median). The hypothesis being tested in the present study was formulated after the trial was closed. Participants: ATBC study cohort of 29,133 men aged 50 to 69 years, who smoked at least five cigarettes per day, at baseline. Main outcome measure: The first occurrence of hospital-treated pneumonia was retrieved from the national hospital discharge register (898 cases). Results: Vitamin E supplementation had no overall effect on the incidence of pneumonia (relative risk [RR], 1.00; 95% confidence interval [CI], 0.88 to 1.14) nor had beta-carotene supplementation (RR, 0.98; 95% CI, 0.85 to 1.11). Nevertheless, the age of smoking initiation was a highly significant modifying factor. Among subjects who had initiated smoking at a later age (greater than or equal to 21 years; n = 7,469 with 196 pneumonia cases), vitamin E supplementation decreased the risk of pneumonia (BR, 0.65; 95% CI, 0.49 to 0.86), whereas beta-carotene supplementation increased the risk (RR, 1.42; 95% CI, 1.07 to 1.89). Conclusions: Data from this large controlled trial suggest that vitamin E and beta-carotene supplementation have no overall effect on the risk of hospital-treated pneumonia in older male smokers, but our subgroup finding that vitamin E seemed to benefit subjects who initiated smoking at a later age warrants further investigation. C1 Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hemila, H (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41, FIN-00014 Helsinki, Finland. EM harri.hemila@helsinki.fi RI Kaprio, Jaakko/A-1820-2008; Albanes, Demetrius/B-9749-2015; OI Hemila, Harri/0000-0002-4710-307X; Kaprio, Jaakko/0000-0002-3716-2455 FU NCI NIH HHS [N01 CN 45165] NR 47 TC 36 Z9 37 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2004 VL 125 IS 2 BP 557 EP 565 DI 10.1378/chest.125.2.557 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 774KJ UT WOS:000188978400032 PM 14769738 ER PT J AU Stuart, M Weinrich, M AF Stuart, M Weinrich, M TI Integrated health system for chronic disease management - Lessons learned from France SO CHEST LA English DT Article DE chronic care model; home ventilation; Olmstead decision; respiratory insufficiency or failure ID LIFE-SUPPORTED PERSONS; PROLONGED MECHANICAL VENTILATION; LONG-TERM OXYGEN; HOME CARE; OUTCOMES; COST; PREVALENCE; COPD; ASSOCIATION; DISABILITY AB Rated number one in overall health system performance by the World Health Organization, the French spend less than half the amount on annual health care per capita that the United States spends. One contributing factor may be the attention given to chronic care. Since the mid-1900s, the French have developed regional community-based specialty systems for patients with chronic respiratory insufficiency or failure. COPD is the major cause of respiratory failure, the fourth leading cause of death in the United States, and its prevalence is increasing. Despite the clinical success of home mechanical ventilation and the potential for cost savings, providing such services in the United States remains a challenge. Lessons from France can inform the development of cost-effective chronic care models in the United States In this article, we review the French experience in the context of the United States Supreme Court's Olmstead decision, mandating that people in "more restrictive settings" such as nursing homes be offered community-based supports. We suggest that regional demonstration projects for patients with chronic respiratory failure or insufficiency can provide an important step in the development of effective chronic care systems in the United States. C1 Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, Hlth Adm & Policy Program, Baltimore, MD 21250 USA. NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. RP Stuart, M (reprint author), Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, Hlth Adm & Policy Program, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM stuart@umbc.edu NR 59 TC 20 Z9 21 U1 0 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2004 VL 125 IS 2 BP 695 EP 703 DI 10.1378/chest.125.2.695 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 774KJ UT WOS:000188978400048 PM 14769754 ER PT J AU Sternberg, KJ Knutson, JF Lamb, ME Baradaran, LP Nolan, CM Flanzer, S AF Sternberg, KJ Knutson, JF Lamb, ME Baradaran, LP Nolan, CM Flanzer, S TI The Child Maltreatment Log: A computer-based program for describing research samples SO CHILD MALTREATMENT LA English DT Review DE child abuse; child neglect; physical abuse; sexual abuse; systematic definitions; systematic data collection; computerized data collection ID BEHAVIOR PROBLEMS; FAMILY VIOLENCE; PHYSICAL AGGRESSION; SEXUAL-ABUSE; ADJUSTMENT; IMPACT; DISABILITIES; PREDICTORS; DIMENSIONS; FREQUENCY AB The Child Maltreatment Log (CML) is a computer-based program designed to record information about children's maltreatment experiences and associated life events. Addressing concerns posed by scientific panels and grant review panels, the CML was designed to improve upon existing instruments to facilitate collaboration among researchers interested in maltreatment. The CML encourages researchers to collect information from multiple sources and informants concerning children's maltreatment experiences. Rather than classifying types of maltreatment a priori, the CML allows researchers to describe children's experiences using objective descriptors pertaining to potential acts of abuse, potential Perpetrators, frequency, onset, consequential injuries, and treatment. The CML can be downloaded by interested agencies and groups without charge. C1 NICHHD, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. EM Michael_Lamb@nih.gov FU NIMH NIH HHS [MH61731] NR 106 TC 12 Z9 12 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5595 J9 CHILD MALTREATMENT JI Child Maltreatment PD FEB PY 2004 VL 9 IS 1 BP 30 EP 48 DI 10.1177/1077559503261265 PG 19 WC Family Studies; Social Work SC Family Studies; Social Work GA 856FA UT WOS:000224029900003 PM 14870996 ER PT J AU Geho, DH Petricoin, EF Liotta, LA AF Geho, DH Petricoin, EF Liotta, LA TI Blasting into the microworld of tissue proteomics: A new window on cancer - Commentary re S. A. Schwartz et al, protein profiling in brain tumors using mass spectrometry: Feasibility of a new technique for the analysis of protein expression. Clin. Cancer Res., 10 : 981-987, 2004. SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID IMMOBILIZED PH GRADIENTS; PROSTATE-CANCER; 2-DIMENSIONAL ELECTROPHORESIS; PATTERNS; SERUM; MICROARRAYS C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Food & Drug Adm, Ctr Biol Evaluat & Res, Bethesda, MD USA. Clin Proteom Program, Food & Drug Adm, NCI, Bethesda, MD USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, Ctr Canc Res, Room 2A33,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM lance@helix.nih.gov NR 26 TC 15 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 825 EP 827 DI 10.1158/1078-0432.CCR-1223-3 PG 3 WC Oncology SC Oncology GA 774MF UT WOS:000188982700003 PM 14871957 ER PT J AU Asgharian, B Chen, YJ Patronas, NJ Peghini, PL Reynolds, JC Vortmeyer, A Zhuang, ZP Venzon, DJ Gibril, F Jensen, RT AF Asgharian, B Chen, YJ Patronas, NJ Peghini, PL Reynolds, JC Vortmeyer, A Zhuang, ZP Venzon, DJ Gibril, F Jensen, RT TI Meningiomas may be a component tumor of multiple endocrine neoplasia type 1 SO CLINICAL CANCER RESEARCH LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ASYMPTOMATIC MENINGIOMAS; SPORADIC MENINGIOMAS; NATURAL-HISTORY; PITUITARY-ADENOMA; ALLELIC LOSSES; BRAIN-TUMORS; MEN1 GENE; INCIDENTAL MENINGIOMAS AB Purpose: Recently, an increased incidence of some non-endocrine tumors are reported in patients with multiple endocrine neoplasia type I (MEN 1). There are rare reports of meningiomas and other central nervous system tumors in these patients, but it is unknown if they are more frequent or if allelic loss of the MEN] gene is important in their pathogenesis. The aim of this study was to address these two latter questions. Experimental Design: Results from a prospective study of 74 MEN 1 patients with suspected/proven pancreatic endocrine tumors (PETs) were analyzed, as well as molecular studies performed on a resected meningioma. All patients had serial brain imaging studies (computed tomography, magnetic resonance imaging, and octreoscanning since 1994) and yearly studies evaluating MEN 1 involvement with a mean follow-up of 7.2 years. Results were compared with 185 patients with sporadic Zollinger-Ellison syndrome. Results: Six patients (8%) had meningiomas. Meningiomas were single and found late in the MEN 1 course (mean age = 51 years). Magnetic resonance imaging/computed tomography were more sensitive than octreoscanning. Their diagnosis averaged 18 years after the onset of hyperparathyroidism, 10-15 years after pituitary disease or PETs. Meningiomas were 11 times more frequent in patients with PETs with MEN I than without MEN 1 (P = 0.017). No clinical, laboratory, or MEN I feature distinguished patients with meningiomas. Meningiomas were asymptomatic and 60% showed no growth. A resected meningioma showed loss of heterozygosity at 11q13 and 1p, including at p73 and ARHI/NOEY2 locus, but not at the neurofibromatosis 2 gene locus. Conclusions: These results show meningiomas are not an infrequent occurrence in MEN 1, and loss of the function of the MEN1 gene product plays a role in their pathogenesis in these patients. C1 NIDDK, DDB, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Diagnost Radiol Dept, Bethesda, MD USA. NINDS, NIH, Surg Neurol Branch, Mol Pathogenesis Unit, Bethesda, MD USA. NIH, Biostat & Data Management Sect, NCI, Bethesda, MD USA. RP Jensen, RT (reprint author), NIDDK, DDB, NIH, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Venzon, David/B-3078-2008 NR 91 TC 37 Z9 39 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 869 EP 880 DI 10.1158/1078-0432.CCR-0938-3 PG 12 WC Oncology SC Oncology GA 774MF UT WOS:000188982700008 PM 14871962 ER PT J AU Schwartz, SA Weil, RJ Johnson, MD Toms, SA Caprioli, RM AF Schwartz, SA Weil, RJ Johnson, MD Toms, SA Caprioli, RM TI Protein profiling in brain tumors using mass spectrometry: Feasibility of a new technique for the analysis of protein expression SO CLINICAL CANCER RESEARCH LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; BIOLOGICAL TISSUE; CANCER; LOCALIZATION; PROTEOMICS; CELLS AB Purpose: The purpose of this research was to perform a preliminary assessment of protein patterns in primary brain tumors using a direct-tissue mass spectrometric technique to profile and map biomolecules. Experimental Design: We examined 20 prospectively collected, snap-frozen normal brain and brain tumor specimens using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS), and compared peptide and protein expression in primary brain tumor and nontumor brain tissues. Results: MS can be used to identify protein expression patterns in human brain tissue and tumor specimens. The mass spectral patterns can reliably identify glial neoplasms of similar histological grade and differentiate them from tumors of different histological grades as well as from nontumor brain tissues. Initial bioinformatics cluster analysis algorithms classified tumor and nontumor tissues into similar groups comparable with their histological grade. Conclusions: We describe a novel tool for the analysis of protein expression patterns in human glial neoplasms. Initial results demonstrate that MALDI-MS technology can significantly aid in the process of unraveling and understanding the molecular complexities of gliomas. MALDI-MS accurately and reliably identified normal and neoplastic tissues, and could be used to discriminate between tumors of increasing grades. C1 NINDS, Surg Neurol Branch, Unit Tumor Physiol & Surg Therapeut, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Neurosurg, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mass Spect Res Ctr, Nashville, TN 37232 USA. Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. RP Weil, RJ (reprint author), NINDS, Surg Neurol Branch, Unit Tumor Physiol & Surg Therapeut, NIH, Bldg 10,Rm 5D37,10 Ctr Dr,9000 Rockville Pik, Bethesda, MD 20892 USA. EM weilr@ninds.nih.gov FU NCI NIH HHS [CA 86243-01] NR 23 TC 136 Z9 145 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 981 EP 987 DI 10.1158/1078-0432.CCR-0927-3 PG 7 WC Oncology SC Oncology GA 774MF UT WOS:000188982700022 PM 14871976 ER PT J AU Grube, M Rezvani, K Wiestner, A Fujiwara, H Sconocchia, G Melenhorst, JJ Hensel, N Marti, GE Kwak, LW Wilson, W Barrett, JA AF Grube, M Rezvani, K Wiestner, A Fujiwara, H Sconocchia, G Melenhorst, JJ Hensel, N Marti, GE Kwak, LW Wilson, W Barrett, JA TI Autoreactive, cytotoxic T lymphocytes specific for peptides derived from normal B-cell differentiation antigens in healthy individuals and patients with B-cell malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; RECEPTOR TRANSGENIC MICE; CANCER-IMMUNOTHERAPY; DENDRITIC CELLS; EXPRESSION; TOLERANCE; VACCINATION; LYMPHOMA; INDUCTION; THERAPY AB Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-gamma mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8(+) T-cell responses were detected in one to CD19(74-82) in three to CD20(127-135), and three to CD20(188-196). Seven of 27 patients (6 with CLL) had CD8(+) T cells recognizing CD19(74-82). Seven patients responded to CD20(127-135) and three to CD20(188-196). All were CLL patients. CD1974-12-specific CTLs from three patients were expanded over 4 weeks. These cells were HLAA*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. RP Barrett, JA (reprint author), NIH, Hematol Branch, Bldg 10,9000 Rockville Pike,Room 7C 103,, Bethesda, MD 20892 USA. EM barrettj@nih.gov NR 65 TC 12 Z9 12 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 1047 EP 1056 DI 10.1158/1078-0432.CCR-03-0075 PG 10 WC Oncology SC Oncology GA 774MF UT WOS:000188982700030 PM 14871984 ER PT J AU Kudo-Saito, C Schlom, J Hodge, JW AF Kudo-Saito, C Schlom, J Hodge, JW TI Intratumoral vaccination and diversified subcutaneous/intratumoral vaccination with recombinant poxviruses encoding a tumor antigen and multiple costimulatory molecules SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; COLONY-STIMULATING FACTOR; HERPES-SIMPLEX-VIRUS; GENE-THERAPY; VACCINIA VIRUS; IMMUNE-RESPONSES; PROSTATE-CANCER; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; CELL VACCINE AB Purpose: Intratumoral (i.t.) vaccination represents a potential modality for the therapy of tumors. Previous i.t. vaccination studies have focused on the efficacy of i.t. vaccination alone. There are no reports that clearly compared i.t. vaccination with systemic vaccination achieved by s.c., intradermal, or i.m. injection, or combining both modalities of systemic and i.t. vaccination. Here, we compared the antitumor effects induced by a systemic vaccination regimen (s.c.) and i.t. vaccination, and a sequential s.c/i.t. vaccination regimen. In this study, we used a recombinant vaccinia virus containing the transgenes for carcinoembryonic antigen (CEA) and a triad of T-cell costimulatory molecules (B7-1, ICAM-1, and LFA-3; designated rV-CEA/TRICOM) for s.c. priming and a replication defective avipox (fowlpox) virus containing the same four transgenes (designated rF-CEA/TRICOM) for i.t. vaccination or s.c. booster vaccinations. Experimental Design: Vaccination was started on day 8 after s.c. implantation with CEA-positive tumors. We compared the antitumor activity induced by these vaccines when administered via the i.t. route versus the s.c. route. Subsequent therapy studies examined the sequential combination of these routes, s.c. priming with rV-CEA/TRICOM followed by i.t. boosting with rF-CEA/TRICOM. Initial studies were conducted in conventional mice to define optimal vaccine regimens and then in CEA-transgenic mice that expressed CEA as a "self" antigen in a manner similar to that of an advanced colorectal cancer patient. Results: The results demonstrate that the antitumor activity induced by i.t. vaccination is superior to that induced by s.c. vaccination. For more advanced tumors, a s.c. priming vaccination, followed by i.t. boosting vaccinations was superior to either s.c. or i.t. vaccination alone. Both of these phenomena were observed in tumor models where the tumor-associated antigen is a foreign antigen and in a CEA-transgenic tumor model where the tumor-associated antigen is a self-antigen. The cytokine, granulocyte macrophage colony-stimulating factor admixed in vaccines, was shown to be essential in inducing the antitumor activity. Conclusions: These studies demonstrate that the diversified vaccine regimens that consisted of s.c. prime and i.t. boosts with CEA/TRICOM vectors could induce antitumor therapy superior to that seen by either route alone. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 43 TC 32 Z9 33 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2004 VL 10 IS 3 BP 1090 EP 1099 DI 10.1158/1078-0432.CCR-03-0145 PG 10 WC Oncology SC Oncology GA 774MF UT WOS:000188982700035 PM 14871989 ER PT J AU Bakalov, VK Cooley, MM Troendle, J Bondy, CA AF Bakalov, VK Cooley, MM Troendle, J Bondy, CA TI The prevalence of diabetes mellitus in the parents of women with Turner's syndrome SO CLINICAL ENDOCRINOLOGY LA English DT Letter ID GONADAL DYSGENESIS C1 Natl Inst Child Hlth, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Bakalov, VK (reprint author), Natl Inst Child Hlth, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NR 5 TC 4 Z9 4 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD FEB PY 2004 VL 60 IS 2 BP 272 EP 272 DI 10.1046/j.1365-2265.2004.01971.x PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 764VB UT WOS:000188225800019 PM 14725692 ER PT J AU Woolhiser, MR Brockow, K Metcalfe, DD AF Woolhiser, MR Brockow, K Metcalfe, DD TI Activation of human mast cells by aggregated IgG through Fc gamma RI: additive effects of C3a SO CLINICAL IMMUNOLOGY LA English DT Article DE mast cell; Fc receptor; degranulation; cytokine; IgG; C3a; taqman; beta-hexosaminidase ID NECROSIS-FACTOR-ALPHA; HIGH-AFFINITY; RHEUMATOID-ARTHRITIS; SIGNAL-TRANSDUCTION; CROHNS-DISEASE; UP-REGULATION; IFN-GAMMA; RECEPTOR; LINE; EXPRESSION AB Human mast cells (huMC) increase surface expression of FcgammaRI (CD64) in response to IFNgamma. Subsequent receptor aggregation of FcgammaRI using CD64-specific F(ab')(2) or antibody directed against FcgammaRI-bound IgG results in cell activation. Human mast cells may be observed degranulating in inflammation associated with autoimmune disease and where IFNgamma is produced. We sought to determine if human mast cells cultured in IFNgamma would degranulate in response to aggregated IgG, what mediators might be generated (i.e., cytokines and eicosanoids), and whether C3a might enhance such activation. Activation of IFNgamma-treated huMC sensitized with 1 mug/ml aggregated IgG(1) resulted in 15-30% degranulation (beta-hexosaminidase release), which was half-maximal by 7.5 min; no degranulation was observed using heat-generated aggregates of IgG(2), IgG(3), or IgG(4). Activation using aggregated IgG(1) led to PGD(2) and LTC4 generation as well as enhanced IL-3, IL-13, GM-CSF, and TNFalpha production. Preincubation of cells with F(ab')(2) from CD64-specific clone 10.1 reduced aggregated IgG(1)-mediated beta-hexosaminidase release by 38% while degranulation was unaffected by blocking FcgammaRII with F(ab')(2)-specific antibody (clone 7.3). Simultaneous activation of huMC via aggregated IgG and C3a led to additive degranulation. These data support a mechanism by which mast cells may contribute to the inflammatory component in fibrosis, vasculitis, and arthritis. (C) 2003 Elsevier Inc. All rights reserved. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Woolhiser, MR (reprint author), Dow Chem Co USA, 1803 Bldg, Midland, MI 48674 USA. EM mwoolhiser@dow.com NR 42 TC 73 Z9 77 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD FEB PY 2004 VL 110 IS 2 BP 172 EP 180 DI 10.1016/j.clim.2003.11.007 PG 9 WC Immunology SC Immunology GA 803KF UT WOS:000220229300008 PM 15003814 ER PT J AU Jung, HY Sohn, YH Mason, A Considine, E Hallett, M AF Jung, HY Sohn, YH Mason, A Considine, E Hallett, M TI Flumazenil does not affect intracortical motor excitability in humans: a transcranial magnetic stimulation study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE flumazenil; benzodiazepine; gamma-aminobutyric acid; cortical excitability; transcranial magnetic stimulation ID ANTAGONIST RO 15-1788; BENZODIAZEPINE ANTAGONIST; CORTICAL EXCITABILITY; CORTEX; PLASTICITY; PHARMACOKINETICS; VOLUNTEERS; LORAZEPAM AB Objective: The motor cortex may be subject to tonic inhibitory drive. One inhibitory mechanism is supported by activity at benzodiazepine (BZP) receptors. In this study we investigate whether or not the BZP antagonist, flumazenil, increases cortical motor excitability in humans. Methods: Eight healthy subjects received a I mg intravenous (i.v.) loading dose of flumazenil followed by a 0.5 mg i.v. infusion over the next 30 min. Before, during, and I h after flumazenil infusion, we measured cortical motor excitability using transcranial magnetic stimulation (TMS). This included resting motor threshold (rMT), paired-pulse measurements of intracortical inhibition and facilitation (10 and ICF), recruitment curve (RC), and silent period (SP). We also measured F response and compound muscle action potential (CMAP) with peripheral nerve stimulation. The study was carried out using a randomized, double-blind crossover design controlled with a saline infusion. Results: None of the measures of cortical or peripheral excitability were significantly affected by drug administration. Conclusions: Our findings suggest that flumazenil has Do effect on cortical motor excitability in normal humans. Significance: There does not appear to be any tonic activity at benzodiazepine receptors in the normal resting human motor cortex. (C) 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Inha Univ, Coll Med, Dept Rehabil Med, Inchon, South Korea. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov NR 23 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2004 VL 115 IS 2 BP 325 EP 329 DI 10.1016/S1388-2457(03)00335-3 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 774KL UT WOS:000188978600009 PM 14744573 ER PT J AU Sohn, YH Voller, B Dimyan, M Gibson, AS Hanakawa, T Leon-Sarmiento, FE Jung, HY Hallett, M AF Sohn, YH Voller, B Dimyan, M Gibson, AS Hanakawa, T Leon-Sarmiento, FE Jung, HY Hallett, M TI Cortical control of voluntary blinking: a transcranial magnetic stimulation study SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; motor cortex; frontal cortex; facial muscle; blink reflex ID HUMAN MOTOR CORTEX; LOWER BRAIN-STEM; FACIAL NUCLEUS; MUSCLES; CORTICOBULBAR; PROJECTIONS; ACTIVATION; RESPONSES; ORGANIZATION; MOTONEURONS AB Objective: To investigate cortical regions related to voluntary blinking. Methods: Transcranial magnetic stimulation (TMS) was applied to the facial motor cortex (M1) and the midline frontal region (Fz) in 10 healthy subjects with eyes opened and closed. Motor-evoked potentials were recorded front the orbicularis oculi (OOC), orbicularis oris (OOR), abductor digiti minimi and tibialis anterior using surface and needle electromyography electrodes. Facial M waves and blink reflex were measured using supramaximal electrical stimulation of the facial and supraorbital nerves. Results: TMS at Fz elicited 3 waves in OOC with no response in other tested muscles except for the early wave in OOR. Facial M1 stimulation produced only early and late waves. Because of their latencies, shapes, and relationship to coil position and stimulation intensity, early and late waves appeared to be analogous to the facial M wave and R1 component of the blink reflex. The intermediate wave at 6-8 ms latency was elicited in OOC by Fz stimulation with eyes closed. Conclusions: Since its latency matches the central conduction time of other cranial muscles and it has characteristic of muscle activation-related facilitation, the intermediate wave is presumably related to cortical stimulation. This result provides evidence that the cortical center for the upper facial movements, including blinking, is not principally located in the facial M1, but rather in the mesial frontal region. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Neurol, Seoul 120749, South Korea. Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120749, South Korea. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Dimyan, Michael/B-1715-2012; OI Voller, Bernhard/0000-0001-5809-874X; Dimyan, Michael/0000-0002-9715-9741 NR 29 TC 35 Z9 37 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD FEB PY 2004 VL 115 IS 2 BP 341 EP 347 DI 10.1016/j.clinph.2003.10.035 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 774KL UT WOS:000188978600011 PM 14744575 ER PT J AU Lamar, M Swenson, R Kaplan, E Libon, DJ AF Lamar, M Swenson, R Kaplan, E Libon, DJ TI Characterizing alterations in executive functioning across distinct subtypes of cortical and subcortical dementia SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID ISCHEMIC VASCULAR DEMENTIA; VERBAL-LEARNING TEST; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; WORKING-MEMORY; PREFRONTAL CORTEX; DIAGNOSIS; FLUENCY; PATTERNS; DEFICITS AB Differential patterns of executive function deficits (EFD) exist in cortical and subcortical dementia; however, little work exists attempting to integrate these findings into a conceptual framework. The current study aimed to characterize EFD in cortical and subcortical dementia. Patients with Alzheimer's disease (AD; n=65), subcortical ischemic vascular dementia (IVD; n=64), or Parkinson's disease with dementia (dPD; n=21) completed a variety of measures purported to require executive systems. We extracted variables of interest from measures shown in a growing body of literature to be associated with EFD in dementia. These measures included the Boston Revision of the WMS Mental Control subtest, letter fluency, WAIS-R Similarities subtest, CVLT, the Graphical Sequence Test-Dementia version, and Clock Drawing. When submitted to a PCA with varimax rotation, these variables produced a four-component solution (62% of the variance). Component 1 appeared to reflect adequacy of working memory, Component 2 irrelevant or context nonspecific interference, Component 3 reflected response preparation and Component 4 relevant or context-specific interference. Post hoc analyses of z-transformed composite scores revealed that AD differentially affected context-specific interference, IVD and dPD disrupted working memory and response preparation while IVD differentially affected context non-specific interference. EFD in dementia can be divided into specific components that are differentially impaired by cortical and subcortical dementias. Implications for an overall conceptual framework of EFD in dementia are discussed. C1 NIA, Baltimore, MD 21224 USA. Univ N Dakota, Sch Med, Dept Neurosci, Fargo, ND USA. Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. Boston Univ, Med Ctr, Dept Psychiat, Boston, MA USA. Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Sch Osteopath Med, Ctr Aging, Stratford, NJ 08084 USA. Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Lamar, M (reprint author), Columbia Univ, Dept Psychiat, 1051 Riverside Dr,Unit 74, New York, NY 10032 USA. EM m112325@columbia.edu NR 47 TC 21 Z9 21 U1 2 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD FEB PY 2004 VL 18 IS 1 BP 22 EP 31 DI 10.1080/13854040490507127 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 850HT UT WOS:000223602500004 PM 15595355 ER PT J AU Edwards, J Prescilla, RP Fratarelli, DA Haritos, D Aranda, JV AF Edwards, J Prescilla, RP Fratarelli, DA Haritos, D Aranda, JV TI Pharmacokinetics of rofecoxib in children. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 Wayne State Univ, Childrens Hosp Michigan, Detroit, MI 48202 USA. NICHD, Pediat Pharmacol Res Unit Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P73 EP P73 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200271 ER PT J AU Eldadah, BA Pacak, K Eisenhofer, G Holmes, C Kopin, IJ Goldstein, DS AF Eldadah, BA Pacak, K Eisenhofer, G Holmes, C Kopin, IJ Goldstein, DS TI Inhibition of uptake-1 activity in the human heart in a hypernoradrenergic state. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 NINDS, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P54 EP P54 DI 10.1016/j.clpt.2003.11.206 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200201 ER PT J AU Kim, H Picco, C Rowan, J Brahim, J Dionne, R AF Kim, H Picco, C Rowan, J Brahim, J Dionne, R TI The influence of tumor necrosis factor gene polymorphisms on experimental and clinical pain responses in humans. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P70 EP P70 DI 10.1016/j.clpt.2003.11.262 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200257 ER PT J AU Krishnaraju, RK Kim, HS Goldman, DA Dionne, RA AF Krishnaraju, RK Kim, HS Goldman, DA Dionne, RA TI The haplotype structure in the gene encoding the delta-opioid receptor in humans. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P4 EP P4 DI 10.1016/j.clpt.2003.11.015 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200014 ER PT J AU Mager, DE Mascelli, MA Kleiman, NS Fitzgerald, DJ Abernethy, DR AF Mager, DE Mascelli, MA Kleiman, NS Fitzgerald, DJ Abernethy, DR TI Nonlinear binding models suggest that abciximab (AB) pharmacokinetics (PK) and pharmacodynamics (PD) are target-mediated. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 NIA, Baltimore, MD 21224 USA. Centocor Inc, Malvern, PA 19355 USA. Baylor Coll Med, Houston, TX 77030 USA. Royal Coll Surgeons Ireland, Dublin 2, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P88 EP P88 DI 10.1016/j.clpt.2003.11.338 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200331 ER PT J AU Neville, K Parise, RA Blaney, SM Thompson, P Aleksic, A Egorin, MJ Balis, FM McGuffey, L McCully, C Berg, SL AF Neville, K Parise, RA Blaney, SM Thompson, P Aleksic, A Egorin, MJ Balis, FM McGuffey, L McCully, C Berg, SL TI Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to non-human primates. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 Indiana Univ, Indianapolis, IN 46204 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P59 EP P59 DI 10.1016/j.clpt.2003.11.223 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200218 ER PT J AU Picco, CC Lee, Y Chuang, BP Gordon, SM Brahim, JS Dionne, RA AF Picco, CC Lee, Y Chuang, BP Gordon, SM Brahim, JS Dionne, RA TI Effect of a selective COX-2 inhibitor in the development of central sensitization in the oral surgery model. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P4 EP P4 DI 10.1016/j.clpt.2003.11.014 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200013 ER PT J AU Preston, KL Schmittner, J Schroeder, JR Boyd, SJ Moolchan, ET Epstein, DH AF Preston, KL Schmittner, J Schroeder, JR Boyd, SJ Moolchan, ET Epstein, DH TI Differential effects of methadone dose/contingency management combinations on abstinence from heroin and cocaine. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 NIDA, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P21 EP P21 DI 10.1016/j.clpt.2003.11.079 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200077 ER PT J AU Slattum, PW Ramchandani, VA Venitz, J AF Slattum, PW Ramchandani, VA Venitz, J TI Lack of development of acute tolerance (AT) to intravenous (IV) ethanol (ETH) in the elderly. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2004 CL Miami Beach, FL SP Amer Soc Clin Pharmacol Therapeut C1 Virginia Commonwealth Univ, Richmond, VA 23284 USA. NIAAA, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2004 VL 75 IS 2 BP P2 EP P2 DI 10.1016/j.clpt.2003.11.007 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774MA UT WOS:000188982200006 ER PT J AU Korn, EL Freidlin, B George, SL AF Korn, EL Freidlin, B George, SL TI Data monitoring and large apparent treatment effects SO CONTROLLED CLINICAL TRIALS LA English DT Letter C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. EM kome@ctep.nci.nih.gov NR 5 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 2004 VL 25 IS 1 BP 67 EP 69 DI 10.1016/S0197-2456(03)00109-0 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 809KR UT WOS:000220636100005 PM 14980749 ER PT J AU Kalish, LA Buczynski, B Connell, P Gemmel, A Goertz, C Macklin, EA Pian-Smith, M Stevens, S Thompson, J Valaskatgis, P Wayne, PM Zusman, RM AF Kalish, LA Buczynski, B Connell, P Gemmel, A Goertz, C Macklin, EA Pian-Smith, M Stevens, S Thompson, J Valaskatgis, P Wayne, PM Zusman, RM TI Stop Hypertension with the Acupuncture Research Program (SHARP): clinical trial design and screening results SO CONTROLLED CLINICAL TRIALS LA English DT Article DE acupuncture; blood pressure; hypertension; randomized clinical trial; traditional Chinese medicine ID QUALITY-OF-LIFE; BLOOD-PRESSURE; RISK-FACTORS; ARTERIAL-HYPERTENSION; ALTERNATIVE MEDICINE; HEALTH; PLACEBO; POPULATION; THERAPY; EFFICACY AB Hypertension is a major public health problem with serious medical and financial consequences. Barriers to successful conventional pharmacological treatment include side effects, out-of-pocket expenses, patient noncompliance and insufficient dosages. Acupuncture has been studied as an alternative therapy for controlling blood pressure (BP) but previous studies have serious methodological limitations. This paper describes the design of the Stop Hypertension with the Acupuncture Research Program (SHARP) trial, a pilot randomized clinical trial designed to gather preliminary data regarding the efficacy of traditional Chinese medicine (TCM)based acupuncture for control of essential hypertension. The design of the SHARP trial balanced rigorous clinical trial methodology with principles of TCM. Eligible participants had systolic BP (SBP) 140-179 mm Hg and diastolic BP (DBP) 90-109 mm Hg in the absence of antihypertensive therapy. Following screening, participants were randomized to one of three groups: individualized, standardized or control acupuncture. Treatments were designed according to principles of TCM; nonspecific effects associated with the interventions were standardized across the randomized groups. For individualized acupuncture, points were tailored to each participant. Standardized acupuncture used a prespecified set of points. The invasive sham control acupuncture regimen was designed to be non-active. Each participant received a "prescription" for individualized acupuncture from an acupuncturist who was masked to treatment assignment, and was subsequently treated by an independent acupuncturist. Patients and those assessing BP were masked to treatment group. Acupuncture was delivered twice a week for 6 weeks. Follow-up visits were every 2 weeks to week 10 and then at months 4, 6, 9 and 12. The primary endpoint will be change in SBP from baseline to 10 weeks. DBP, BP trajectories over the 12-month follow-up and antihypertensive medication requirements will also be examined. Initial contact was documented for 1442 prospective participants from March 2001 to April 2002; 424 provided informed consent and 192 were ultimately randomized. (C) 2004 Elsevier Inc. All rights reserved. C1 New England Res Inst, Watertown, MA 02472 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Med Serv, Dept Med,Div Hypertens & Vasc Med,Cardiac Unit, Boston, MA USA. Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. Marblehead Holist Hlth Consultants, Marblehead, MA USA. New England Sch Acupuncture, Watertown, MA USA. RP Kalish, LA (reprint author), Childrens Hosp, Clin Res Program, 300 Longwood Ave, Boston, MA 02115 USA. EM leslie.kalish@childrens.har-vard.edu; emacklin@neri.org RI Macklin, Eric/E-2955-2013; OI Macklin, Eric/0000-0003-1618-3502; Goertz, Christine/0000-0002-4700-3669 FU NCCIH NIH HHS [U01 AT00210] NR 84 TC 27 Z9 28 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 2004 VL 25 IS 1 BP 76 EP 103 DI 10.1016/j.cct.2003.08.006 PG 28 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 809KR UT WOS:000220636100010 PM 14980754 ER PT J AU Rush, AJ Fava, M Wisniewski, SR Lavori, PW Trivedi, MH Sackeim, HA Thase, ME Nierenberg, AA Quitkin, FM Kashner, TM Kupfer, DJ Rosenbaum, JF Alpert, J Stewart, JW McGrath, PJ Biggs, MM Shores-Wilson, K Lebowitz, BD Ritz, L Niederehe, G AF Rush, AJ Fava, M Wisniewski, SR Lavori, PW Trivedi, MH Sackeim, HA Thase, ME Nierenberg, AA Quitkin, FM Kashner, TM Kupfer, DJ Rosenbaum, JF Alpert, J Stewart, JW McGrath, PJ Biggs, MM Shores-Wilson, K Lebowitz, BD Ritz, L Niederehe, G CA STAR D Investigators Grp TI Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design SO CONTROLLED CLINICAL TRIALS LA English DT Article DE major depressive disorder; antidepressants; cognitive therapy; randomized clinical trial; multistep multicenter clinical trial; utilization and costs ID MEDICATION ALGORITHM PROJECT; INTERACTIVE VOICE RESPONSE; MAJOR DEPRESSION; RECURRENT DEPRESSION; SYMPTOMATOLOGY IDS; COGNITIVE THERAPY; ECONOMIC BURDEN; RATING SCALE; HEALTH-CARE; DISORDERS AB STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants without sufficient improvement are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessments. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Dept Vet Affairs, Cooperat Studies Program, Palo Alto, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Texas, SW Med Ctr, Dept Vet Affairs, Hlth Serv Res & Dev Serv, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. NIMH, Bethesda, MD 20892 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH-30915, N01-MH-90003] NR 70 TC 480 Z9 488 U1 5 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 2004 VL 25 IS 1 BP 119 EP 142 DI 10.1016/S0197-2456(03)00112-0 PG 24 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 809KR UT WOS:000220636100012 PM 15061154 ER PT J AU Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C AF Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C TI Should we continue to target the platelet-activating factor pathway in septic patients? SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID TUMOR-NECROSIS-FACTOR; PLACEBO-CONTROLLED TRIAL; INTERLEUKIN-1 RECEPTOR ANTAGONIST; INFLAMMATORY RESPONSE SYNDROME; CONTROLLED MULTICENTER TRIAL; FACTOR ANTIBODY-FRAGMENT; PHASE-II TRIAL; DOUBLE-BLIND; SEVERE SEPSIS; MONOCLONAL-ANTIBODY C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Minneci, PC (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 38 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD FEB PY 2004 VL 32 IS 2 BP 585 EP 588 DI 10.1097/01.CCM.0000110730.38696.9C PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 774ME UT WOS:000188982600041 PM 14758184 ER PT J AU Hofstede, G McCrae, RR AF Hofstede, G McCrae, RR TI Personality and culture revisited: Linking traits and dimensions of culture SO CROSS-CULTURAL RESEARCH LA English DT Article DE culture and personality; personality traits; Five-Factor Model; IBM dimensions; value systems; cross-national comparisons ID NATIONAL DIFFERENCES; 5-FACTOR MODEL; PROJECT GLOBE; NEUROTICISM; EXTRAVERSION; PERSPECTIVE; PSYCHOLOGY; VALUES AB "Culture and personality" was a focus of anthropology and psychology in the first half of the 20th century. It was concerned with traditional and preliterate societies and drew many of its constructs from psychoanalysis. In this article, we note that taxonomies of personality traits and cultural values developed independently since 1980 have created new possibilities for exploring the topic. The Five-Factor Model of personality is a universally valid taxonomy of traits. The IBM study (conducted by Hofstede) dimensions of culture represent a well-validated operationalization of differences between cultures as manifested in dominant value systems. In reanalyses of recently reported data, mean personality scores from 33 countries were significantly and substantially correlated with culture dimension scores. We discuss environmental and temperamental explanations for these associations and suggest directions for future research, including replications, experimental simulations, acculturation studies, and research on the interaction of traits and culture in shaping human lives. C1 Inst Res Intercultural Cooperat, Tilburg, Netherlands. NIA, NIH, DHHS, Baltimore, MD 21224 USA. RP Hofstede, G (reprint author), Den Bruyl 15, NL-6881 AN Velp, Netherlands. EM hofstede@bart.nl NR 100 TC 287 Z9 294 U1 31 U2 241 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1069-3971 J9 CROSS-CULT RES JI Cross-Cult. Res. PD FEB PY 2004 VL 38 IS 1 BP 52 EP 88 DI 10.1177/1069397103259443 PG 37 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 763WA UT WOS:000188122400003 ER PT J AU Yarilin, AA Belyakov, IM AF Yarilin, AA Belyakov, IM TI Cytokines in the thymus: Production and biological effects SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID T-CELL DEVELOPMENT; NECROSIS-FACTOR-ALPHA; HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKEMIA INHIBITORY FACTOR; POLYMERASE CHAIN-REACTION; GROWTH-FACTOR-BETA; HUMAN THYMOCYTE PROLIFERATION; MACROPHAGE-DERIVED CHEMOKINE; DOUBLE-POSITIVE THYMOCYTES; RECEPTOR TRANSGENIC MICE AB All types of thymic cells are able to produce cytokines either spontaneously or after stimulation. The main producers of cytokines in the thymus are thymic epithelial cells (TEC) and thymocytes. Thymic cytokines act at short distance and their effects are limited by the internal space of the organ. The spectrum of biological effects of thymic cytokines is determined by the expression of cytokine receptors on the thymic cell surface. Some cytokines produced by the thymic cells of one type are supplied to cells of other types; other cytokines act as autocrine factors. Examples of paracrine thymic cytokines are IL-7 (produced by TEC or stromal fibroblasts induces CD4(-)CD8(-) thymocyte growth and differentiation) and INFgamma (produced by thymocytes, induces TEC activation). An example of an autocrine factor is IL-2, for which the producers and targets are thymocytes. The ability of thymocytes to produce cytokines and express cytokine receptors is gradually reduced as they mature from the stage of CD44(+)CD3(-)CD4(-)CD8(-) precursor cells to the stage of CD3(1o)CD4(+)CD8(+) cortical thymocytes; in the latter stage both these capacities become completely blocked. This change reflects the decrease of cytokine dependence of the respective processes. After the completion of the selection process, the capacity of thymocytes to produce cytokines and respond to their action is restored. Some differences in the function of the cytokine system in thymus and peripheral compartments of the immune system can be noted. 1. Unlike the periphery, where cytokine production and receptor expression are inducible, the synthesis of cytokines and expression of their receptors in the thymus has mainly a "spontaneous" character (or it is induced by cell-cell interactions). 2. Cytokines tightly interact, forming a cytokine network both at the periphery and in the thymus, but the structure of the peripheral and intrathymic cytokine network is different. The latter can be termed as a "minor cytokine network". Some peptide hormone-like factors play a significant role in the intrathymic cytokine network. 3. The principal role of thymic cytokines is to provide constitutive processes (migration and development of thymocytes, regulation of cell number in the cell populations, etc.), but not inducible ones (inflammation, immune response, etc.) as in the periphery. 4. The functions of some cytokines in the thymus can be significantly different from those in the periphery of the immune system. For example, proinflammatory cytokines act in the thymus as factors or cofactors of thymocyte or TEC activation, proliferation or differentiation. The key cytokines of Th1 and Th2 cells - IFNgamma and IL-4 - do not participate in the immune response but mediate the dialogue between thymocyte and TEC and play a role in autoregulating the thymocyte population. The functions of many cytokines in the thymus are not established up to now. Detailed analysis of the "minor cytokine network" and intrathymic cytokine effects will reveal some unknown events of thymus physiology. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Minst Hlth Serv Russia, Inst Immunol, Moscow, Russia. RP Belyakov, IM (reprint author), NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. EM belyakov@mail.nih.gov NR 202 TC 56 Z9 63 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD FEB PY 2004 VL 11 IS 4 BP 447 EP 464 DI 10.2174/0929867043455972 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 780LQ UT WOS:000189382500007 PM 14965226 ER PT J AU Petricoin, EF Liotta, LA AF Petricoin, EF Liotta, LA TI SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID MOLECULAR WEIGHT PROTEINS; PROSTATE-CANCER; IDENTIFICATION; DISCOVERY AB Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity-based processes. Serum proteomic pattern diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. This approach has recently shown tremendous promise in the detection of early-stage cancers. The biomarkers found by SELDI-TOF-based pattern recognition analysis are mostly low molecular weight fragments produced at the specific tumor microenvironment. C1 US FDA, Ctr Biol Evaluat & Res, Off Cell & Gene Teherapies, FDA NCI Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Pathol Lab, FDA NCI Clin Proteom Program,NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Cell & Gene Teherapies, FDA NCI Clin Proteom Program, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 22 TC 228 Z9 255 U1 2 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD FEB PY 2004 VL 15 IS 1 BP 24 EP 30 DI 10.1016/j.copbio.2004.01.005 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 780EC UT WOS:000189358300005 PM 15102462 ER PT J AU Parent, CA AF Parent, CA TI Making all the right moves: chemotaxis in neutrophils and Dictyostelium SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID NUCLEOTIDE EXCHANGE FACTOR; PLECKSTRIN HOMOLOGY DOMAIN; G-BETA-GAMMA; CELL POLARITY; LIVING CELLS; PHOSPHOINOSITIDE 3-KINASE-GAMMA; CHEMOATTRACTANT RECEPTORS; EUKARYOTIC CHEMOTAXIS; SIGNAL-TRANSDUCTION; MEDIATED ACTIVATION AB Neutrophils and Dictyostelium discoideum share the ability to migrate directionally in response to external chemoattractant gradients. The binding of chemoattractants to specific receptors that are coupled to heterotrimeric G proteins leads to a wide range of biochemical responses that become highly localized as cells polarize and migrate by chemotaxis. The signaling mechanisms that lead to the predominant polymerization of Factin at the front of cells for propulsion and to myosin II assembly at the sides to suppress lateral pseudopod formation and at the back for retraction are now beginning to emerge. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Rm 1E24, Bethesda, MD 20892 USA. EM parentc@helix.nih.gov NR 67 TC 125 Z9 132 U1 2 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD FEB PY 2004 VL 16 IS 1 BP 4 EP 13 DI 10.1016/j.ceb.2003.11.008 PG 10 WC Cell Biology SC Cell Biology GA 771DG UT WOS:000188769900002 PM 15037299 ER PT J AU Poloso, NJ Roche, PA AF Poloso, NJ Roche, PA TI Association of MHC class II-peptide complexes with plasma membrane lipid microdomains SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL ACTIVATION; DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE; TETRASPAN MICRODOMAINS; RAFTS; MOLECULES; ANTIGEN; TRANSPORT; DOMAINS; APC AB Activation of CD4(+) T cells requires the interaction of multiple T-cell receptors with MHC class II-peptide complexes on the surface of antigen-presenting cells (APCs). Recent studies have shown that MHC class II complexes are clustered in APC plasma membrane microdomains, thereby providing a mechanism for localized concentration of MHC class II-peptide complexes. The integrity of one type of AIPC membrane microdomain, the lipid raft, is important for antigen presentation to T cells. We propose a model in which the coordinated processes of MHC class II peptide loading and intracellular trafficking enhance T-cell activation by loading specific MHC class II-peptide complexes in discrete lipid raft microdomains. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM paul.roche@nih.gov NR 44 TC 39 Z9 40 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 2004 VL 16 IS 1 BP 103 EP 107 DI 10.1016/j.coi.2003.11.009 PG 5 WC Immunology SC Immunology GA 771AN UT WOS:000188763500016 PM 14734117 ER PT J AU Germain, RN Jenkins, MK AF Germain, RN Jenkins, MK TI In vivo antigen presentation SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CD4 T-CELLS; CLASS-II COMPLEXES; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; LYMPH-NODES; SELF-PEPTIDE; B-CELLS; TISSUE; EXPRESSION; PROTEIN AB Monoclonal antibodies specific for defined peptide-MHC complexes are now being used to physically detect T-cell receptor ligands. These reagents have resulted in the identification of the cells that present antigen in lymphoid and non-lymphoid tissues after various forms of antigen administration. In addition, recent advances in real-time imaging technology have begun to measure the rate and directionality of T-cell movement relative to antigen-presenting cells in lymph nodes, shedding light on the earliest events in T-cell activation in a physiological setting. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. RP Germain, RN (reprint author), NIAID, Immunol Lab, NIH, Bldg 10 Room 11N311,10 Ctr Dr,MSC-1892, Bethesda, MD 20892 USA. EM RGERMAIN@niaid.nih.gov; marcj@mail.ahc.umn.edu RI Jenkins, Marc/G-1063-2012 OI Jenkins, Marc/0000-0001-8009-7655 NR 45 TC 48 Z9 50 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 2004 VL 16 IS 1 BP 120 EP 125 DI 10.1016/j.coi.2003.11.001 PG 6 WC Immunology SC Immunology GA 771AN UT WOS:000188763500019 PM 14734120 ER PT J AU Moayeri, M Leppla, SH AF Moayeri, M Leppla, SH TI The roles of anthrax toxin in pathogenesis SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID LETHAL FACTOR CLEAVES; NECROSIS-FACTOR-ALPHA; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; INHALATIONAL ANTHRAX; BIOTERRORISM EXPOSURE; CELLULAR RECEPTOR; CRYSTAL-STRUCTURE; KINASE-KINASE; EDEMA FACTORS AB Anthrax lethal toxin is a multi-functional virulence factor that has evolved to target multiple host functions to allow for optimal establishment of Bacillus anthracis infection. The toxin appears to play a role in all stages of infection, from germination to the induction of vascular collapse leading to host death. Early in infection, at sublethal doses, it acts to suppress immune cell and cytokine responses, thereby promoting bacterial outgrowth. Later in the disease, lethal levels of toxin induce the cytokine-independent shock-like death associated with anthrax. The understanding of the molecular events induced by anthrax toxin in different target cells at each stage of infection will aid in deciphering the pathogenesis of this bacterium and developing therapies. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, NIH, Bldg 30,Room 307, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov NR 70 TC 184 Z9 191 U1 3 U2 16 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD FEB PY 2004 VL 7 IS 1 BP 19 EP 24 DI 10.1016/j.mib.2003.12.001 PG 6 WC Microbiology SC Microbiology GA 780EF UT WOS:000189358700004 PM 15036135 ER PT J AU Abrams, SI AF Abrams, SI TI Role of anti-CTLA-4 therapies in the treatment of cancer SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE autoimmunity; co-stimulation; CTLA-4 blockade; cytotoxic T-lymphocytes; neoplasia; tumor immunity ID T-CELL RESPONSES; COLONY-STIMULATING FACTOR; CTLA-4 BLOCKADE; ADOPTIVE IMMUNOTHERAPY; ANTIGEN-4 BLOCKADE; ANTITUMOR IMMUNITY; COMBINATION IMMUNOTHERAPY; METASTATIC MELANOMA; TUMOR-IMMUNOTHERAPY; MOUSE MODEL AB Studies in the field of T-cell receptor (TCR)/antigen (Ag) recognition have led to the discovery of a unique receptor/ligand system that, in collaboration with TCR/Ag engagement, underlies the molecular basis of T-cell activation and proliferation. Such a process has been termed co-stimulation, which serves to either upregulate or downregulate T-cell signaling following TCR ligation. As neoplasia represents a pathogenic process whereby a sustained T-cell response may be desirable, intensive efforts to prolong endogenous tumor-induced T-cell activity in vivo have been investigated. One innovative approach has been to block a crucial inhibitory arm of the co-stimulatory pathway using monoclonal antibodies against the CTLA-4 molecule expressed by Ag-primed, activated T-cells. In both preclinical models and clinical settings, such a therapeutic intervention has been found to be effective in promoting antitumor T-cell responses and, in some patients, clinical regression has been concomitant with autoreactivity. Thus, CTLA4 blockade, perhaps in conjunction with other oncological modalities, may comprise important therapeutic paradigms to facilitate long-lasting antineoplastic immunity. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,Room 5B46, Bethesda, MD 20892 USA. EM sa47z@nih.gov NR 45 TC 16 Z9 16 U1 0 U2 0 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD FEB PY 2004 VL 6 IS 1 BP 71 EP 77 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 838TX UT WOS:000222737300009 PM 15011783 ER PT J AU Schellinger, PD Kaste, M Hacke, W AF Schellinger, PD Kaste, M Hacke, W TI An update on thrombolytic therapy for acute stroke SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE diffusion-weighted imaging; perfusion-diffusion mismatch; perfusion-weighted imaging; stroke; thrombolytic therapy; tissue at risk ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; RANDOMIZED CONTROLLED-TRIAL; DIFFUSION-WEIGHTED MRI; HYPERACUTE CEREBRAL-ISCHEMIA; INTRAVENOUS THROMBOLYSIS; INTRACEREBRAL HEMORRHAGE; SYMPTOM ONSET; PERFUSION MRI; STREPTOKINASE AB Purpose of review Stroke is the third leading cause of death after myocardial infarction and cancer, and is the leading cause of permanent disability and disability-adjusted loss of independent life-years in western countries. Thrombolysis is the treatment of choice for acute stroke within 3 h after the onset of symptoms. We present an overview of a diagnostic approach to acute stroke management that allows the individualization of patient management based on pathophysiological reasoning and not rigid time windows established by randomized controlled trials. Recent findings This review concentrates in the first part on giving the reader an integrated knowledge of the current status of thrombolytic therapy in stroke, and in the second part develops a treatment algorithm based on pathophysiological information rendered by a multiparametric stroke magnetic resonance imaging protocol. Summary Thrombolysis is an effective therapy for ischemic stroke, whether performed intravenously within 3 h or intra-arterially within 3-6 h. Meta-analyses have provided evidence of an effect of intravenous thrombolysis beyond the 3 h time window, especially when improved selection criteria such as modern magnetic resonance imaging protocols are applied. Sadly, thrombolysis is still underused. Positive results from studies currently underway may encourage more centers to offer this therapy to an increasing number of stroke patients, and thereby reduce the considerable socioeconomic burden of stroke. C1 Univ Hosp, Dept Neurol, Heidelberg, Germany. NINDS, NIH, Bethesda, MD USA. Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. RP Schellinger, PD (reprint author), Neurol Univ Klin, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM peter_schellinger@med.uni-heidelberg.de RI bashzar, salman/R-5748-2016; OI Kaste, Markku/0000-0001-6557-6412 NR 58 TC 31 Z9 33 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD FEB PY 2004 VL 17 IS 1 BP 69 EP 77 DI 10.1097/01.wco.0000113941.12823.3b PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 780LY UT WOS:000189383200011 PM 15090880 ER PT J AU Rosenzweig, SD Holland, SM AF Rosenzweig, SD Holland, SM TI Congenital defects in the interferon-gamma/interleukin-12 pathway SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE receptors; mutations; pathophysiology; autoimmune ID INTERFERON-GAMMA-RECEPTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CALMETTE-GUERIN INFECTION; SMALL DELETION HOTSPOT; IFN-GAMMA; MYCOBACTERIAL INFECTION; DEFICIENT PATIENTS; MICE; MUTATION; SUSCEPTIBILITY AB Purpose of review The aim of this review is to highlight the most recent and relevant advances in the interferon-gamma/interleukin-12 pathway, a pivotal player of the immune system, and their repercussions on basic and clinical aspects of science. Recent findings Newly described mutations are helping us to dissect the interferon-gamma/interleukin-12 pathway and its role in genetic infectious susceptibility and autoimmunity, and to reevaluate the pathophysiologic mechanisms involved in dominant and recessively inherited mutations. Summary The interferon-gamma/interleukin-12 pathway plays a central role in immune control of both environmental and autochthonous challenges, as reflected in human mutations and animal models. Besides being crucial for mycobacterial control, the interferon-gamma/interleukin-12 pathway is also involved in the pathogenesis of autoimmune disease, as well as tumor development and control. Genotype-phenotype correlations have been established for certain mutants in this pathway, some of which have therapeutic implications. C1 NIAID, Immunopathogenesis Sect, Host Def Lab, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Hosp Nacl Pediat Juan P Garrahan, Dept Pediat, Div Immunol, Buenos Aires, DF, Argentina. RP Holland, SM (reprint author), Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov.email NR 45 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2004 VL 16 IS 1 BP 3 EP 8 DI 10.1097/00008480-200402000-00003 PG 6 WC Pediatrics SC Pediatrics GA 809MP UT WOS:000220641100002 PM 14758107 ER PT J AU Yang, W Van Duyne, GD AF Yang, W Van Duyne, GD TI Protein-nucleic acid interactions - Editorial overview SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Editorial Material C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room B1-03, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov; vanduyne@mail.med.upenn.edu NR 0 TC 27 Z9 29 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2004 VL 14 IS 1 BP 1 EP 3 DI 10.1016/j.sbi.2004.01.007 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 802XX UT WOS:000220197300001 ER PT J AU Baker, D Eaton, WA AF Baker, D Eaton, WA TI Folding and binding - Editorial overview SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Editorial Material C1 Univ Washington, Dept Biochem, Seattle, WA 98195 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Baker, D (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA. EM dabaker@u.washington.edu; eaton@helix.nih.gov NR 0 TC 7 Z9 7 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2004 VL 14 IS 1 BP 67 EP 69 DI 10.1016/j.sbi.2004.01.011 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 802XX UT WOS:000220197300010 ER PT J AU Kubelka, J Hofrichter, J Eaton, WA AF Kubelka, J Hofrichter, J Eaton, WA TI The protein folding 'speed limit' SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID 3-HELIX BUNDLE PROTEIN; MOLECULAR-DYNAMICS SIMULATIONS; INTRAMOLECULAR CONTACT FORMATION; VILLIN HEADPIECE SUBDOMAIN; DIFFUSION-COLLISION MODEL; MONTE-CARLO SIMULATIONS; FREE-ENERGY LANDSCAPE; HELIX-COIL KINETICS; BETA-SHEET; TRP-CAGE AB How fast can a protein possibly fold? This question has stimulated experimentalists to seek fast folding proteins and to engineer them to fold even faster. Proteins folding at or near the speed limit are prime candidates for all-atom molecular dynamics simulations. They may also have no free energy barrier, allowing the direct observation of intermediate structures on the pathways from the unfolded to the folded state. Both experimental and theoretical approaches predict a speed limit of approximately N/100 mus for a generic N-residue single-domain protein, with a proteins folding faster than beta or alphabeta. The predicted limits suggest that most known ultrafast folding proteins can be engineered to fold more than ten times faster. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kubelka, J (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5,Room 104, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov NR 146 TC 535 Z9 545 U1 3 U2 97 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2004 VL 14 IS 1 BP 76 EP 88 DI 10.1016/j.sbi.2004.01.013 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 802XX UT WOS:000220197300012 PM 15102453 ER PT J AU Tycko, R AF Tycko, R TI Progress towards a molecular-level structural understanding of amyloid fibrils SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; SCRAPIE PRION PROTEIN; BETA-SHEET STRUCTURE; ALZHEIMERS-DISEASE; SACCHAROMYCES-CEREVISIAE; SUPRAMOLECULAR STRUCTURE; EXPANDED GLUTAMINE; PEPTIDE FRAGMENT; VIRULENCE FACTOR AB The problem of determining and understanding the molecular structures of amyloid fibrils has attracted considerable attention and effort over the past several years. Although complete, high-resolution structures have not yet been obtained, key features of protein and peptide conformations and supramolecular organization within amyloid fibrils have been elucidated using a variety of novel experimental methods, including magnetic resonance spectroscopies, electron microscopy, X-ray and neutron scattering, and biochemical techniques. The experimental data are beginning to shed light on issues such as the nature of the intermolecular interactions that stabilize amyloid structures, the molecular structural basis for polymorphism in amyloid fibrils, the universality of amyloid structures, and the balance between structural order and disorder within amyloid fibrils. Recent structural data will contribute to an improved understanding of the mechanisms of amyloid formation and to the development of therapeutic agents for amyloid diseases. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertt@niddk.nih.gov NR 63 TC 289 Z9 299 U1 2 U2 27 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 2004 VL 14 IS 1 BP 96 EP 103 DI 10.1016/j.sbi.2003.12.002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 802XX UT WOS:000220197300014 PM 15102455 ER PT J AU Mocellin, S Marincola, F Rossi, CR Nitti, D Lise, M AF Mocellin, S Marincola, F Rossi, CR Nitti, D Lise, M TI The multifaceted relationship between IL-10 and adaptive immunity: putting together the pieces of a puzzle SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE IL-10; adaptive immunity; cytotoxic T lymphocyte ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-CELL RESPONSES; HUMAN DENDRITIC CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ANTIGEN-PRESENTING CELLS; CHRONIC HEPATITIS-C; MHC CLASS-I; HUMAN-IMMUNODEFICIENCY-VIRUS; INTERLEUKIN-10 GENE-TRANSFER; CARDIAC ALLOGRAFT SURVIVAL AB Interleukin-10 (IL-10) is a pleiotropic cytokine that modulates the function of several adaptive immunity-related cells. Although generally considered an immunosuppressive molecule, IL-10 possesses immunostimulatory properties in several in vitro and in vivo models. These very different outcomes are believed to depend upon experimental conditions, the dominant immune effector mediating a given immune response, the timing of IL-10 production/administration, and IL-10 dose and/or location of expression. In the present work, we review the current knowledge regarding IL-10 activity on adaptive immunity related cells, emphasize new insights on IL-10 molecular/cellular targets, and summarize the available data on the relationship between IL-10 and some pathological conditions (e.g. infectious diseases, autoimmunity, allergy, cancer and transplantation) involving adaptive immunity. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Padua, Clin Chirurg 2, Dept Oncol & Surg Sci, I-35128 Padua, Italy. NIH, Dept Transfus Med, Immunogenet Sect, Bethesda, MD USA. RP Mocellin, S (reprint author), Univ Padua, Clin Chirurg 2, Dept Oncol & Surg Sci, Via Giustiniani,2, I-35128 Padua, Italy. EM mocellins@hotmail.com RI Rossi, Carlo Riccardo/A-7685-2010 OI Rossi, Carlo Riccardo/0000-0001-7875-5655 NR 215 TC 143 Z9 149 U1 1 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD FEB PY 2004 VL 15 IS 1 BP 61 EP 76 DI 10.1016/j.cytog.fr.2003.11.001 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 812WT UT WOS:000220870300006 PM 14746814 ER PT J AU Murakami, MS Moody, SA Daar, IO Morrison, DK AF Murakami, MS Moody, SA Daar, IO Morrison, DK TI Morphogenesis during Xenopus gastrulation requires Wee1-mediated inhibition of cell proliferation SO DEVELOPMENT LA English DT Article DE Wee1; cell cycle; gastrulation ID MIDBLASTULA TRANSITION; CYCLE; DROSOPHILA; DEGRADATION; LAEVIS; MITOSIS; EMBRYOS; EMBRYOGENESIS; DIVISION; KINASE AB Major developmental events in early Xenopus embryogenesis coincide with changes in the length and composition of the cell cycle. These changes are mediated in part through the regulation of CyclinB/Cdc2 and they occur at the first mitotic cell cycle, the mid-blastula transition (MBT) and at gastrulation. In this report, we investigate the contribution of maternal Wee1, a kinase inhibitor of CyclinB/Cdc2, to these crucial developmental transitions. By depleting Wee1 protein levels using antisense morpholino oligonucleotides, we show that Wee1 regulates M-phase entry and Cdc2 tyrosine phosphorylation in early gastrula embryos. Moreover, we find that Weel is required for key morphogenetic movements involved in gastrulation, but is not needed for the induction of zygotic transcription. In addition, Weel is positively regulated by tyrosine autophosphorylation in early gastrula embryos and this upregulation of Weel activity is required for normal gastrulation. We also show that overexpression of Cdc25C, a phosphatase that activates the CyclinB/Cdc2 complex, induces gastrulation defects that can be rescued by Weel, providing additional evidence that cell cycle inhibition is crucial for the gastrulation process. Together, these findings further elucidate the developmental function of Weel and demonstrate the importance of cell cycle regulation in vertebrate morphogenesis. C1 NCI, Regulat Cell Growth Lab, Cell Growth Mech Sect, Frederick, MD 21702 USA. NCI, Regulat Cell Growth Lab, Dev Signal Transduct Sect, Frederick, MD 21702 USA. George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. RP Murakami, MS (reprint author), NCI, Regulat Cell Growth Lab, Cell Growth Mech Sect, Frederick, MD 21702 USA. EM monicasmurakami@yahoo.com OI Daar, Ira/0000-0003-2657-526X FU NINDS NIH HHS [NS23158] NR 52 TC 43 Z9 43 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 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 2004 VL 131 IS 3 BP 571 EP 580 DI 10.1242/dev.00971 PG 10 WC Developmental Biology SC Developmental Biology GA 777EF UT WOS:000189162000008 PM 14711880 ER PT J AU Carpenter, MK Rosler, ES Fisk, GJ Brandenberger, R Ares, X Miura, T Lucero, M Rao, MS AF Carpenter, MK Rosler, ES Fisk, GJ Brandenberger, R Ares, X Miura, T Lucero, M Rao, MS TI Properties of four human embryonic stem cell lines maintained in a feeder-free culture system SO DEVELOPMENTAL DYNAMICS LA English DT Article DE embryonic stem cells; human; feeder-free; hES ID NERVOUS-SYSTEM; HEMATOPOIETIC STEM; HUMAN BLASTOCYSTS; DIFFERENTIATION; GROWTH; MAINTENANCE; EXPRESSION AB Several laboratories have begun evaluating human ES (hES) cell lines; however, direct comparisons between different hES cell lines have not been performed. We have characterized the properties of four human cell lines maintained in feeder-free culture conditions. Quantitative assessment of surface markers, microarray analysis of gene expression patterns, expression of SOX-2, UTF-1, Rex-1, OCT3/4, CRIPTO, and telomerase activity demonstrated similar patterns in all hES cell lines examined. Undifferentiated hES cells do not respond to neurotransmitters such as acetylcholine, glutamate, and gamma-aminobutyric acid. In addition, the undifferentiated hES cells possess gap junctions. Although similarities in marker expression were observed, allotyping showed that all four lines have a distinct HLA profile, predicting differences in transplantation responses. These data provide the first detailed comparison of different hES cell lines and demonstrate remarkable similarities among lines maintained in identical culture conditions. C1 Geron Corp, Menlo Pk, CA USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Utah, Dept Physiol, Salt Lake City, UT 84112 USA. RP Carpenter, MK (reprint author), John P Robarts Res Inst, POB 5015,100 Perth Dr, London, ON N6A 5K8, Canada. EM mcarpenter@robarts.ca NR 31 TC 187 Z9 206 U1 1 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 2004 VL 229 IS 2 BP 243 EP 258 DI 10.1002/dvdy.10431 PG 16 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 768HZ UT WOS:000188538700003 PM 14745950 ER PT J AU Rosler, ES Fisk, GJ Ares, X Irving, J Miura, T Rao, MS Carpenter, MK AF Rosler, ES Fisk, GJ Ares, X Irving, J Miura, T Rao, MS Carpenter, MK TI Long-term culture of human embryonic stem cells in feeder-free conditions SO DEVELOPMENTAL DYNAMICS LA English DT Article DE embryonic stem cells; human; karyotype; stability; cell therapy ID TELOMERASE CATALYTIC SUBUNIT; IN-VITRO DIFFERENTIATION; NEURAL PRECURSORS; HUMAN FIBROBLASTS; HUMAN BLASTOCYSTS; LINES; HTERT; NEURONS; INHIBITION; ENRICHMENT AB We have demonstrated previously that human embryonic stem (hES) cells possess a characteristic morphologic, antigenic, and molecular profile that can be used to assess the state of ES cells (Carpenter et al., [2004] Dev Dyn 229:243-258). In this manuscript, we have examined the long-term stability of three hES cell lines in feeder-free culture. We demonstrate that the expression of antigens and transcription factors, telomerase activity, telomere length, and karyotype appear stable for all three hES cell lines after continuous culture for over 1 yr. All three lines retained pluripotent differentiation in vitro and in vivo. Although hES cell lines were remarkably stable over the period of analysis, a detailed quantitative analysis of antigen expression by flow cytometry and gene expression by microarray suggested that cell lines show subtle differences in the expression of small subsets of genes upon long-term culture. C1 Geron Corp, Menlo Pk, CA USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Carpenter, MK (reprint author), John P Robarts Res Inst, POB 5015,100 Perth Dr, London, ON N6A 5K8, Canada. EM mcarpenter@robarts.ca NR 35 TC 242 Z9 261 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 2004 VL 229 IS 2 BP 259 EP 274 DI 10.1002/dvdy.10430 PG 16 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 768HZ UT WOS:000188538700004 PM 14745951 ER PT J AU Fueger, PT Bracy, DP Malabanan, CM Pencek, RR Granner, DK Wasserman, DH AF Fueger, PT Bracy, DP Malabanan, CM Pencek, RR Granner, DK Wasserman, DH TI Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat-fed C57BL/6J mice SO DIABETES LA English DT Article ID HUMAN SKELETAL-MUSCLE; PLASMA-MEMBRANE; LUMPED CONSTANT; TRANSGENIC MICE; POTENTIAL MECHANISM; INDIVIDUAL TISSUES; TRANSPORT ACTIVITY; GLUT4 CONTENT; IN-VIVO; RATS AB The aim of the present study was to determine the specific sites of impairment to muscle glucose uptake (MGU) in the insulin-resistant high-fat-fed, conscious C57BL/6J mouse. Wild type (WT) and hexokinase 11 overexpressing (HKTg) mice were fed either a standard diet or high-fat diet and studied at 4 months of age. A carotid artery and jugular veins had catheters chronically implanted for sampling and infusions, respectively, and mice were allowed to recovery for at least 5 days. Mice were fasted for 5 h and underwent a hyperinsulinemic-euglycemic clamp or saline infusion for 120 min. Separate groups of mice were studied during 30-min sedentary or treadmill exercise periods. A bolus. of 2-deoxy[H-3]glucose was administered 25 min before the end of each study for determination of R-g, an index of tissue-specific glucose uptake. Fasting blood glucose was increased in high-fat compared with standard diet-fed WT (194 +/- 4 vs. 171 +/- 4 mg/dl) but not HKTg 179 +/- 5 vs. 171 +/- 3 mg/dl) mice. High-fat feeding created hyperinsulinemia in both WT and HKTg mice (58 +/- 8 and 77 +/- 15 muU/ml) compared with standard diet-fed mice (91 +/- 2 and 20 +/- 1 muU/ml). R-g was not affected by genotype or diet during either saline infusion or sedentary conditions. HK II overexpression augmented insulin-stimulated R-g in standard diet-fed but not high-fat-fed mice. Exercise-stimulated R-g was impaired by high-fat feeding in WT mice, but this impairment was largely rectified in HKTg mice. In conclusion, high-fat feeding impairs both insulin- and exercise-stimulated MGU, but only exercise-stimulated MGU was corrected by HK II overexpression. C1 Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. RP Fueger, PT (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, 221 Kirkland Hall, Nashville, TN 37232 USA. EM patrick.fueger@vanderbilt.edu FU NIDDK NIH HHS [U24-DK-59637, DK-20593, R01 DK-54902] NR 48 TC 36 Z9 48 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2004 VL 53 IS 2 BP 306 EP 314 DI 10.2337/diabetes.53.2.306 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770PQ UT WOS:000188739600005 PM 14747279 ER PT J AU Steele, C Hagopian, WA Gitelman, S Masharani, U Cavaghan, M Rother, KI Donaldson, D Harlan, DM Bluestone, J Herold, KC AF Steele, C Hagopian, WA Gitelman, S Masharani, U Cavaghan, M Rother, KI Donaldson, D Harlan, DM Bluestone, J Herold, KC TI Insulin secretion in type 1 diabetes SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; BLOOD-GLUCOSE CONTROL; C-PEPTIDE LEVELS; DEPENDENT DIABETICS; CLINICAL REMISSION; NATURAL COURSE; MELLITUS; IDDM; CHILDREN; ONSET AB Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing beta-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of beta-cell function at an average rate of 756 +/- 132 pmol/month to a final value of 28 +/- 8.4% of initial levels after 2 years. There was a significant correlation be tween the total insulin secretory response and control of glucose, measured by RbA(1c) (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate. that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction. Diabetes 53: 426-433, 2004. C1 Columbia Univ, Naomi Berrie Diabet Ctr, Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Dept Med, Div Endocrinol, New York, NY 10032 USA. Pacific NW Res Inst, Seattle, WA USA. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. Indiana Univ, Dept Med, Indianapolis, IN 46204 USA. NIDDKD, Transplant & Autoimmun Branch, Bethesda, MD 20892 USA. Univ Utah, Dept Pediat, Salt Lake City, UT USA. RP Herold, KC (reprint author), Columbia Univ, Naomi Berrie Diabet Ctr, Coll Phys & Surg, 1150 St Nicholas Ave, New York, NY 10032 USA. EM kh318@columbia.edu FU NCRR NIH HHS [M01 RR00645, M01RR01271]; NIAID NIH HHS [U19AI46132]; NIDDK NIH HHS [P60DK20595, DK20595, R01DK57846] NR 43 TC 84 Z9 86 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD FEB PY 2004 VL 53 IS 2 BP 426 EP 433 DI 10.2337/diabetes.53.2.426 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770PQ UT WOS:000188739600020 PM 14747294 ER PT J AU Klein, DJ Friedman, LA Harlan, WR Barton, BA Schreiber, GB Cohen, RM Harlan, LC Morrison, JA AF Klein, DJ Friedman, LA Harlan, WR Barton, BA Schreiber, GB Cohen, RM Harlan, LC Morrison, JA TI Obesity and the development of insulin resistance and impaired fasting glucose in black and white adolescent girls - A longitudinal study SO DIABETES CARE LA English DT Article ID DIABETES-MELLITUS; AFRICAN-AMERICAN; CHILDREN; PREVALENCE; SECRETION; DISEASE; HYPERINSULINEMIA; SENSITIVITY; OVERWEIGHT; TOLERANCE AB Objective-Age at onset of type 2 diabetes has decreased during the past 20 years, especially in black women. Studies of factors associated with insulin resistance and hyperglycemia in preadolescent and adolescent populations are essential to understanding diabetes development. Research Design and Methods-The National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study (NGHS) is a 10-year cohort study of the development of obesity in black and white girls. Two NGHS centers examined the associations of obesity, puberty, and race with fasting insulin, glucose, and homeostasis model assessment of insulin resistance (HOMA-IR; a calculated index of insulin resistance) measures at 9-10 years of age (baseline) and 10 years later. Results-Black girls had greater baseline and year-10 BMI than white girls, with a greater 10-year incidence of obesity. BMI-insulin correlations were positive in both black and white girls at both visits, but insulin remained higher in black girls after controlling for BMI. In black girls, insulin and HOMA-IR were higher in the prepubertal period (before the emergence of racial differences in BMI), increased more during puberty, and decreased less with its completion. Baseline BMI predicted year-10 glucose and the development of impaired fasting glucose (IFG) in black girls. In white girls, the rate of BMI increase during follow-up predicted these outcomes. The 10-year incidence of diabetes in black girls was 1.4%. Conclusions-Black-white differences in insulin resistance are not just a consequence of obesity, but precede the pubertal divergence in BMI. The development of IFG appears to be a function of the rate of increase of BMI in white girls and early obesity in black girls. C1 Childrens Hosp, Med Ctr, Div Cardiol, Cincinnati, OH 45229 USA. Cincinnati Childrens Hosp, Med Ctr, Div Endocrinol & Cardiol, Cincinnati, OH USA. Maryland Med Res Inst, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Univ Cincinnati, Dept Internal Med, Div Endocrinol, Cincinnati, OH USA. NCI, Bethesda, MD 20892 USA. RP Morrison, JA (reprint author), Childrens Hosp, Med Ctr, Div Cardiol, OSB 4,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM john.morrison@cchmc.org OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [HL 48941, HC 55023-5] NR 26 TC 40 Z9 41 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2004 VL 27 IS 2 BP 378 EP 383 DI 10.2337/diacare.27.2.378 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770PU UT WOS:000188739900015 PM 14747217 ER PT J AU Singh, PK Looker, HC Hanson, RL Krakoff, J Bennett, PH Knowler, WC AF Singh, PK Looker, HC Hanson, RL Krakoff, J Bennett, PH Knowler, WC TI Depression, diabetes, and glycemic control in Pima Indians SO DIABETES CARE LA English DT Letter ID COMORBID DEPRESSION; CONTROLLED-TRIAL; PREVALENCE; CARE C1 NIDDK, NIH, Phoenix, AZ 85014 USA. RP Looker, HC (reprint author), NIDDK, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM hlooker@mail.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 9 TC 20 Z9 20 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2004 VL 27 IS 2 BP 618 EP 619 DI 10.2337/diacare.27.2.618-a PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770PU UT WOS:000188739900052 PM 14747253 ER PT J AU Formanack, ML Baier, LJ AF Formanack, ML Baier, LJ TI Variation in the FABP2 promoter affects gene expression: implications for prior association studies SO DIABETOLOGIA LA English DT Article DE intestinal fatty acid binding protein; IFABP; FABP2; insulin resistance; diabetes candidate gene; Pima Indians ID FATTY-ACID-BINDING; POLYMORPHISM; PROTEIN; SUBSTITUTION; CODON-54 AB Aims/hypothesis. An Ala54Thr polymorphism in the FABP2 gene has previously been associated with insulin resistance and lipid oxidation rates in Pima Indians. Ala54Thr functionally alters the protein's ability to bind and transport dietary fatty acids. In the current report, we sought additional functional variation in FABP2 by sequencing putative regulatory regions. Methods. More than 1.2 Kb of the putative promoter of FABP2 was sequenced in 20 Pima subjects. Variations were genotyped in 84 additional Pima Indian subjects to assess haplotype combinations. Functional activities of variant and nonvariant promoters were compared in Caco-2 cells transfected with luciferase reporter constructs. Results. Seven variations were identified in the FABP2 promoter in Pima Indians. Genotypes of these variants were in complete concordance with each other, and were in complete concordance with Ala54Thr. Therefore, only two promoter alleles were observed in Pima Indians, an Ala54-associated promoter and a Thr54-associated promoter. In contrast, genotyping of these variants in Caucasian DNA showed multiple genotypic combinations. In vitro reporter assays indicated that the Thr54-associated promoter in Pima Indians resulted in a threefold reduction in promoter activity as compared to Ala54-associated promoter. Conclusion/interpretation. Two functional variations exist in FABP2-the coding Ala54Thr and the variant promoter. In the Pima Indian population, but not the Caucasian population, these two functional variants are always carried on the same allele. Therefore, some of the in vivo phenotypic associations previously attributed to the Ala54Thr substitution, which alters binding characteristics of the protein, could instead be due to promoter variation, which alters expression levels. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Baier, LJ (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. EM lbaier@phx.niddk.nih.gov NR 9 TC 23 Z9 24 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 2004 VL 47 IS 2 BP 349 EP 351 DI 10.1007/s00125-003-1289-z PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779FX UT WOS:000189285600022 PM 14666368 ER PT J AU Delle Fave, G Jensen, RT AF Delle Fave, G Jensen, RT TI Somatostatin receptors: from basic science to clinical approach - Foreword SO DIGESTIVE AND LIVER DISEASE LA English DT Editorial Material C1 NIDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Delle Fave, G (reprint author), Univ Roma La Sapienza, S Andrea Hosp, Sch Med & Surg 2, Dept Digest & Liver Dis, Via Grottarossa 1035, Rome, Italy. EM gianfranco.dellefave@uniroma1.it NR 0 TC 0 Z9 0 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD FEB PY 2004 VL 36 SU 1 BP S1 EP S1 DI 10.1016/j.dld.2003.11.014 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 806IQ UT WOS:000220428000001 ER PT J AU Gibril, F Jensen, RT AF Gibril, F Jensen, RT TI Diagnostic uses of radiolabelled somatostatin receptor analogues in gastroenteropancreatic endocrine tumours SO DIGESTIVE AND LIVER DISEASE LA English DT Article; Proceedings Paper CT Meeting on Somatostatin Receptors CY OCT, 2001 CL Borgo Monastero, ITALY DE gastroenteropancreatic tumours; somatostatin receptors; somatostatin receptor scintigraphy ID ZOLLINGER-ELLISON-SYNDROME; METASTATIC NEUROENDOCRINE TUMORS; CARCINOID-TUMORS; COMPUTED-TOMOGRAPHY; BONE METASTASES; RADIONUCLIDE THERAPY; NEOPLASIA TYPE-1; LIVER-TRANSPLANTATION; CLINICAL MANAGEMENT; LONG-TERM AB Numerous studies have established that gastroenteropancreatic endocrine tumours (carcinoids and pancreatic endocrine tumours) resemble a number of other tumours in overexpressing somatostatin receptors that can bind octreotide or lanreotide with high affinity (i.e. possess sst(2)/sst(5) receptors). Recent studies report that radiolabelled somatostatin analogues can be used to image these tumours (somatostatin receptor scintigraphy) and may be useful for peptide-directed radionuclide therapy. In this paper the evidence is reviewed that has led to establishing somatostatin receptor scintigraphy as the initial imaging modality of choice in patients with gastroenteropancreatic tumours. This conclusion is based on an understanding of the results with conventional imaging modalities (ultrasound, computed tomographic scan, magnetic resonance imaging, angiography) available prior to somatostatin receptor scintigraphy and the results of studies demonstrating the sensitivity and specificity of somatostatin receptor scintigraphy. Most important in this regard are the results of studies that have assessed the use of somatostatin receptor scintigraphy on clinical management. Each of these areas is reviewed in this paper. (C) 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr MSC-1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 137 TC 59 Z9 61 U1 0 U2 1 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD FEB PY 2004 VL 36 SU 1 BP S106 EP S120 DI 10.1016/j.dld.2003.11.024 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 806IQ UT WOS:000220428000017 PM 15077919 ER PT J AU Yamanaka, R Xanthopoulos, KG AF Yamanaka, R Xanthopoulos, KG TI Development of improved Sindbis virus-based DNA expression vector SO DNA AND CELL BIOLOGY LA English DT Article ID MODIFIED DENDRITIC CELLS; COMPLEMENTARY-DNA; GENE; RNA; INTERLEUKIN-12; ENHANCEMENT; PROMOTER; MODELS AB We have constructed an improved DNA expression vector based on the Sindbis virus. Several DNA-based Sindbis virus vectors were constructed to investigate the efficiency of transgene expression. These vectors, when transfected into mammalian cells, have been used to express heterologous genes. A recombinant genome of Sindbis plasmid DNA, in which the structural genes were replaced by a polylinker cassette to allow for insertion of heterologous genes, was placed under the control of a simian virus (SV 40) promoter with a hepatitis delta virus (HDV) antigenomic ribozyme and a polyadenylation signal. Transfection of mammalian cells with this Sindbis-based plasmid vector, pSin-SV40-HDV-SV4OpA, resulted in transient high-level expression of the beta-galactosidase reporter gene. The expression level of beta-galactosidase from pSin-SV40-HDV-SV4OpA was more than 16-fold higher than that of pSin-Lux originally reported by Herweijer et al. In vivo expression was also detected after injection of plasmid DNA into mouse quadriceps. In vivo expression was transient and undetectable after day 14. Furthermore, we demonstrate that the transfection of cells with this Sindbis virus vector results in apoptotic death on glioma cells. We have demonstrated a high-level expression of the exogenous beta-galactosidase gene from the pSin-SV40-HDV-SV4OpA construct using a Sindbis replication system. C1 Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 9518122, Japan. NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Yamanaka, R (reprint author), Niigata Univ, Brain Res Inst, Dept Neurosurg, Asahimachi Dori 1-757, Niigata 9518122, Japan. EM ryaman@bri.niigata-u.ac.jp NR 15 TC 12 Z9 15 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD FEB PY 2004 VL 23 IS 2 BP 75 EP 80 DI 10.1089/104454904322759885 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 774CL UT WOS:000188962100001 PM 15000747 ER PT J AU Nikolic, D Li, YM Chadwick, LR Grubjesic, S Schwab, P Metz, P van Breemen, RB AF Nikolic, D Li, YM Chadwick, LR Grubjesic, S Schwab, P Metz, P van Breemen, RB TI Metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus), by human liver microsomes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID IN-VITRO BIOTRANSFORMATION; TANDEM MASS-SPECTROMETRY; PRENYLATED FLAVONOIDS; ESTROGENIC ACTIVITY; PRENYLFLAVONOIDS; IDENTIFICATION; BEER; RAT; 17-BETA-ESTRADIOL; XANTHOHUMOL AB The female flowers of hops are used throughout the world as a flavoring agent for beer. Recently, there has been increasing interest in the potential estrogenic properties of hop extracts. Among the possible estrogenic compounds in hops, 8-prenylnaringenin is perhaps most significant due to its high in vitro potency exceeding that of other known phytoestrogens. Since data regarding the pharmacokinetic properties of this compound are lacking, we investigated the in vitro metabolism of 8-prenylnaringenin by human liver microsomes. A total of 12 metabolites were identified, and biotransformation occurred on the prenyl group and the flavanone skeleton. The major site of oxidation was on the terminal methyl groups, and of the two possible isomers, the trans isomer was more abundant. The double bond on the prenyl group was also oxidized to an epoxide that was opened by intramolecular reaction with the neighboring hydroxyl group. On the flavanone skeleton, the major site of oxidation was at 3' position on the B ring. Other metabolites included oxidation at carbon-3 as well as desaturation of the C ring to produce 8-prenylapigenin. An unusual hydroxy quinone product formed by ipso hydroxylation of the B ring of 8-prenylnaringenin was also detected. This product was probably an intermediate for the B ring cleavage product, 8-prenylchromone. C1 Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, NIH,Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. Univ Illinois, Dept Chem, Chicago, IL 60612 USA. Tech Univ Dresden, Inst Organ Chem, D-8027 Dresden, Germany. RP van Breemen, RB (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, NIH,Ctr Bot Dietary Supplements Res, 833 S Wood St, Chicago, IL 60612 USA. EM breemen@uic.edu FU NCCIH NIH HHS [P50AT00155] NR 22 TC 47 Z9 50 U1 2 U2 14 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD FEB 1 PY 2004 VL 32 IS 2 BP 272 EP 279 DI 10.1124/dmd.32.2.272 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767EH UT WOS:000188426900016 PM 14744951 ER PT J AU Harlan, DM AF Harlan, DM TI Gene-altered islets for transplant: Giant leap or small step? SO ENDOCRINOLOGY LA English DT Editorial Material ID HEPATOCYTE GROWTH-FACTOR; GLUCAGON-LIKE PEPTIDE-1; TYPE-1 DIABETES-MELLITUS; BETA-CELL PROLIFERATION; PANCREAS TRANSPLANTATION; EDMONTON PROTOCOL; IN-VITRO; MICE; EXPRESSION; THERAPY C1 NIDDKD, Islet & Autoimmun Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Harlan, DM (reprint author), NIDDKD, Islet & Autoimmun Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM DavidMH@intra.niddk.nih.gov NR 51 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB 1 PY 2004 VL 145 IS 2 BP 463 EP 466 DI 10.1210/en.2003-1392 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 765VE UT WOS:000188304400001 PM 14739150 ER PT J AU Suk, WA Avakian, MD Carpenter, D Groopman, JD Scammell, M Wild, CP AF Suk, WA Avakian, MD Carpenter, D Groopman, JD Scammell, M Wild, CP TI Human exposure monitoring and evaluation in the arctic: The importance of understanding exposures to the development of public health policy SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE Arctic; biomarker; community-based participatory research ID COMMUNITY; ALASKA; ICE; CONTAMINANTS; POLLUTANTS; POPULATION; LESSONS; PEOPLES; MODEL AB Arctic indigenous peoples face significant challenges resulting from the contamination of Arctic air, water, and soil by persistent organic pollutants, heavy metals, and radionuclides. International cooperative efforts among governments and research institutions are under way to collect the information needed by environmental health scientists and public health officials to address environmental contamination in the Arctic. However, the climatic, political, and cultural conditions of the land and its native populations combine to present a unique set of scientific and logistic challenges to addressing this important public health issue. Public health officials have the responsibility to respect the cultural traditions of indigenous communities, while simultaneously designing strategies that will reduce their exposure to environmental contaminants and rates of disease and dysfunction. Researchers can better understand the link between environmental exposures and disease through monitoring programs for both the subsistence diets and health status of the indigenous populations. We suggest that the incorporation of community-based participatory research methods into programs designed to assess biomarkers of contaminant exposure in children and adults may be a valuable addition to ongoing and newly developed research programs. This approach could serve as a model for international environmental health initiatives, because it involves the participation of the local communities and seeks to builds trust between all stakeholders. C1 US Dept HHS, NIEHS, Ctr Risk & Integrated Sci, NIH, Res Triangle Pk, NC 27709 USA. Michael D Baker Inc, Res Triangle Pk, NC USA. SUNY Albany, Sch Publ Hlth, Dept Environm Hlth & Toxicol, Albany, NY USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ Leeds, Sch Med, Epidemiol & Hlth Serv Res, Mol Epidemiol Unit, Leeds LS2 9JT, W Yorkshire, England. RP Suk, WA (reprint author), US Dept HHS, NIEHS, Ctr Risk & Integrated Sci, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM suk@niehs.nih.gov OI Scammell, Madeleine/0000-0003-3836-083X NR 57 TC 14 Z9 14 U1 2 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2004 VL 112 IS 2 BP 113 EP 120 DI 10.1289/ehp.6383 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 776ZQ UT WOS:000189149800024 PM 14757538 ER PT J AU Peterson, KE Salganik, M Campbell, C Rhoads, GG Rubin, J Berger, O Ware, JH Rogan, W AF Peterson, KE Salganik, M Campbell, C Rhoads, GG Rubin, J Berger, O Ware, JH Rogan, W TI Effect of succimer on growth of preschool children with moderate blood lead levels SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood lead levels; chelation; children; clinical trial; growth; succimer ID INDUCED DEPRESSION; CHELATION-THERAPY; PHYSICAL GROWTH; STATURE; HEALTH; NUTRITION; EXPOSURE; TODDLERS; ACID AB Growth deficits associated with lead exposure might be ameliorated by chelation. We examined the effect of succimer on growth in 780 children 12-33 months old who had blood lead levels of 20-44 mug/dL and were randomized to receive up to three 26-day courses of succimer or placebo in a multicenter, double-blind trial. The difference in changes in weight and height between succimer and placebo groups at 1-34 months was calculated by fitting cubic splines. The difference in height change in children on succimer compared with placebo was -0.27 cm [95% confidence interval (95% CI), -0.42 to -0.11] from baseline to 9 months, when 99% of children had completed treatment, and -0.43 cm (95% CI, -0.77 to -0.09) during 34 months of follow-up. Similar differences in weight gain were not statistically significant. Although succimer lowers blood lead in moderately lead-poisoned children, it does not have a beneficial effect on growth and may have an adverse effect. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Peterson, KE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM kpeterso@hsph.harvard.edu RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU NIEHS NIH HHS [N01 ES35360] NR 40 TC 10 Z9 12 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 2004 VL 112 IS 2 BP 233 EP 237 DI 10.1289/ehp.6331 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 776ZQ UT WOS:000189149800040 PM 14754579 ER PT J AU Launer, LJ AF Launer, LJ TI Epidemiologic evidence of oxidative stress in the brain SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID ALZHEIMER-DISEASE; DIETARY-INTAKE; RADICALS; RISK C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. EM launer1@nia.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD FEB PY 2004 VL 19 IS 2 BP 99 EP 100 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 778JY UT WOS:000189239500002 PM 15074563 ER PT J AU Schnur, J Olah, J Szepesi, A Nagy, P Thorgeirsson, SS AF Schnur, J Olah, J Szepesi, A Nagy, P Thorgeirsson, SS TI Thioacetamide-induced hepatic fibrosis in transforming growth factor beta-1 transgenic mice SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE liver; fibrosis; cirrhosis; thioacetamide; TGF-beta 1; MMP-2; MMP-9 ID LIVER FIBROSIS; MATRIX METALLOPROTEINASES; EXPRESSION; RATS; FACTOR-BETA-1; DISEASE; COLLAGENASE; PROGRESSION; INHIBITORS AB Objective Transforming growth factor beta-1 (TGF-beta1) is thought to be one of the most important factors affecting the development of fibrotic processes in the liver. Aim To discover whether endogenously higher TGF-beta1 production influences the progression and reversibility of liver fibrosis in mice. Method We compared thioacetamide-induced liver fibrosis between wild-type and transgenic mice overexpressing active TGF-beta1 in the liver. Hepatic fibrosis was detected on histological sections, and fibrotic areas were measured by means of morphometric analysis. We also performed Northern blot hybridisation and gelatine zymography to improve our understanding of the process. Results The fibrotic process was faster in the transgenic animals, and regression after the withdrawal of the fibrogenic agent was slower. Fibrosis did not disappear completely from the TGF-beta1 overexpressing mice, even at the endpoint of the experiment. Conclusion Since the increased TGF-beta1 production in the liver slowed down the regression of the liver fibrosis, the behaviour of these transgenic mice is more similar to the human situation, where cirrhosis is irreversible. We propose that this transgenic model is more suitable for investigating fibrotic liver diseases than the experiments done previously on wild-type rodents. (C) 2004 Lippincott Williams Wilkins. C1 Semmelweis Univ, Inst Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Nagy, P (reprint author), Semmelweis Univ, Inst Pathol & Expt Canc Res 1, Uloli Ut 26, H-1085 Budapest, Hungary. EM nagy@korb1.sote.hu NR 23 TC 27 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD FEB PY 2004 VL 16 IS 2 BP 127 EP 133 DI 10.1097/01.meg.0000085545.79233.da PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 774LK UT WOS:000188980800002 PM 15075984 ER PT J AU Huusko, P Juo, SHH Gillanders, E Sarantaus, L Kainu, T Vahteristo, P Allinen, M Jones, M Rapakko, K Eerola, H Markey, C Vehmanen, P Gildea, D Freas-Lutz, D Blomqvist, C Leisti, J Blanco, G Puistola, U Trent, J Bailey-Wilson, J Winqvist, R Nevanlinna, H Kallioniemi, OP AF Huusko, P Juo, SHH Gillanders, E Sarantaus, L Kainu, T Vahteristo, P Allinen, M Jones, M Rapakko, K Eerola, H Markey, C Vehmanen, P Gildea, D Freas-Lutz, D Blomqvist, C Leisti, J Blanco, G Puistola, U Trent, J Bailey-Wilson, J Winqvist, R Nevanlinna, H Kallioniemi, OP TI Genome-wide scanning for linkage in Finnish breast cancer families SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE genome-wide linkage; breast cancer; Finland; chromosome 2q ID SUSCEPTIBILITY GENES; BRCA2 MUTATIONS; OVARIAN-CANCER; CHROMOSOME 8P12-P22; LOW PROPORTION; PENETRANCE; ERRORS; LOCUS; HETEROGENEITY; DELETIONS AB Only a proportion of breast cancer families has germline mutations in the BRCA1 or BRCA2 genes, suggesting the presence of additional susceptibility genes. Finding such genes by linkage analysis has turned out to be difficult due to the genetic heterogeneity of the disease, phenocopies and incomplete penetrance of the mutations. Isolated populations may be helpful in reducing the level of genetic heterogeneity and in providing useful starting points for further genetic analyses. Here, we report results from a genome-wide linkage analysis of 14 high-risk breast cancer families from Finland. These families tested negative for BRCA1 and BRCA2 germline mutations and showed no linkage to the 13q21 region, recently proposed as an additional susceptibility locus. Suggestive linkage was seen at marker D2S364 (2q32) with a parametric two-point LOD score of 1.61 (theta = 0), and an LOD score of 2.49 in nonparametric analyses. Additional genotyping of a 40 cM chromosomal region surrounding the region of interest yielded a maximum parametric two-point LOD score of 1.80 ( theta = 0) at D2S2262 and a nonparametric LOD score of 3.11 at an adjacent novel marker 11291M1 in BAC RP11-67G7. A nonparametric multipoint LOD score of 3.20 was seen at 11291M1 under the assumption of dominant inheritance. While not providing proof of linkage considering the small number of families and large number of laboratory and statistical analyses performed, these results warrant further studies of the 2q32 chromosomal region as a candidate breast cancer susceptibility locus. Both linkage and association studies are likely to be useful, particularly in other isolated populations. C1 Univ Helsinki, Cent Hosp, Canc Genet Branch, NHGRI,NIH, Helsinki, Finland. Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, Oulu, Finland. Univ Helsinki, Cent Hosp, Inherited Dis Res Branch, NHGRI,NIH, Helsinki, Finland. Columbia Genome Ctr, New York, NY USA. Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland. Univ Oulu, Oulu Univ Hosp, Dept Obstet & Gynecol, Oulu, Finland. RP Kallioniemi, OP (reprint author), VTT Tech Res Ctr Finland, Med Biotechnol Grp, POB 106, FIN-20521 Espoo, Finland. EM olli.kallioniemi@vtt.fi RI Juo, Suh-Hang/A-1765-2010; Kallioniemi, Olli/H-5111-2011; Juo, Suh-Hang/C-9545-2009; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Bailey-Wilson, Joan/0000-0002-9153-2920; Nevanlinna, Heli/0000-0002-0916-2976 NR 34 TC 26 Z9 27 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD FEB PY 2004 VL 12 IS 2 BP 98 EP 104 DI 10.1038/sj.ejhg.5201091 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 766WC UT WOS:000188397500004 PM 14560309 ER PT J AU Thornton, AM Piccirillo, CA Shevach, EM AF Thornton, AM Piccirillo, CA Shevach, EM TI Activation requirements for the induction of CD4(+)CD25(+) T cell suppressor function SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; tolerance; suppression; anergy; IL-2 receptor; cytokines; costimulation ID INTESTINAL INFLAMMATION; AUTOIMMUNE GASTRITIS; CUTTING EDGE; ANTIGEN 4; RECEPTOR; MICE; TOLERANCE; COLITIS; CD4(+); CTLA-4 AB The in vivo differentiation/survival of CD4(+)CD25(+) T suppressor cells is dependent on IL-2 and CD28-mediated costimulatory signals. To determine the cytokine and costimulatory requirements for CD25(+) T cells in vitro, we established a two-stage culture system where CD25(+) T cells were activated in a primary culture. In the subsequent culture, activated CD4(+)CD25(+) cells were then mixed with responders in order to assess their suppressor function. Pre-culture of CD25(+) T cells with anti-CD3 alone resulted in poor survival and minimal induction of suppressor activity. Pre-culture in the presence of anti-CD3 and IL-2 or IL-4, but not IL-6, IL-7, IL-9, IL-10 or IL-15, resulted in proliferation of the CD25(+) cells and induction of potent suppressor function. Inhibition of the interaction of CD28 or cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with CD80/CD86 in the pre-culture of CD4(+)CD25(+) cells did not prevent the induction of suppressor function. Furthermore, the inhibition of costimulatory signals did not inhibit the ability of fresh CD25(+) T cells to inhibit CD8(+) responders under conditions where activation of the responders was independent of CD80/ CD86. These studies support the view that activation of CD25(+) T cells requires IL-2/IL-4 for their survival/differentiation into effector cells, but is independent of CD28/CTLA-4-mediated costimulation. C1 NIAID, LI, NIH, Bethesda, MD 20892 USA. RP Thornton, AM (reprint author), NIAID, LI, NIH, Bldg 10,Rm 11N315,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM athornton@niaid.nih.gov NR 34 TC 223 Z9 233 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 2004 VL 34 IS 2 BP 366 EP 376 DI 10.1002/eji.200324455 PG 11 WC Immunology SC Immunology GA 774LF UT WOS:000188980400009 PM 14768041 ER PT J AU Shakhov, AN Rybtsov, S Tumanov, AV Shulenin, S Dean, M Kuprash, DV Nedospasov, SA AF Shakhov, AN Rybtsov, S Tumanov, AV Shulenin, S Dean, M Kuprash, DV Nedospasov, SA TI SMUCKLER/TIM4 is a distinct member of TIM family expressed by stromal cells of secondary lymphoid tissues and associated with lymphotoxin signaling SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokines; lymphotoxin; TNF; asthma; mouse ID TUMOR-NECROSIS-FACTOR; DEFICIENT MICE; ABNORMAL-DEVELOPMENT; HUMAN-MELANOMA; GENE FAMILY; T-CELLS; RECEPTOR; BETA; TNF; SURFACE AB Lymphotoxin-alpha (LTalpha) was originally linked to delayed-type hypersensitivity and its production was later attributed to Th1, but not Th2 cells. Studies employing knockout mice demonstrated that LT signaling is essential for the development and functional compartmentalization of lymphoid tissues. Here, using gene expression profiling, we identified a novel gene termed SMUCKLER (spleen, mucin-containing, knockout of lymphotoxin), that is selectively down-regulated in spleens of LTalpha- or LTbeta-deficient mice. The encoded transmembrane protein contains immunoglobulin V and mucin domains and is identical to TIM4, a predicted member of recently identified TIM family (T cell immunoglobulin- and mucin-domaincontaining molecule). Unlike TIM1 and TIM3, which were implicated in T cell-mediated functions, SMUCKLER lacks tyrosine phosphorylation motif in its intracellular domain and is not expressed by bone marrow-derived cells. In situ hybridization of spleen sections demonstrated SMUCKLER expression by stromal cells predominantly in the marginal zone and to a lesser extent throughout the white pulp. Similarly to other TIM genes, SMUCKLER maps to a locus associated with predisposition to asthma both in mice and in humans (11.b1 and 5q33, respectively) and shows coding sequence variations between BALB/c and DBA mice. Therefore, SMUCKLER/TIM4 may be considered as a candidate disease-predisposition gene for asthma. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. NCI, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD 21701 USA. NCI, Canc Res Ctr, Lab Genom Divers, Frederick, MD 21701 USA. RP Kuprash, DV (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. EM kuprash@online.ru RI Dean, Michael/G-8172-2012; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Dean, Michael/0000-0003-2234-0631; Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-12400] NR 34 TC 29 Z9 32 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 2004 VL 34 IS 2 BP 494 EP 503 DI 10.1002/eji.200324590 PG 10 WC Immunology SC Immunology GA 774LF UT WOS:000188980400022 PM 14768054 ER PT J AU Dina, OA Parada, CA Yeh, J Chen, XJ McCarter, GC Levine, JD AF Dina, OA Parada, CA Yeh, J Chen, XJ McCarter, GC Levine, JD TI Integrin signaling in inflammatory and neuropathic pain in the rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE extracellular matrix; inflammation; integrin; pain; second messenger; sensory neuron ID PROTEIN-KINASE-C; EXTRACELLULAR-MATRIX; LAMININ RECEPTOR; PERIPHERAL-NERVE; ATRIAL MYOCYTES; SENSORY NEURONS; CELL-ADHESION; HYPERALGESIA; EPSILON; FIBRONECTIN AB Many painful conditions are associated with alterations in the extracellular matrix (ECM) of affected tissues. While several integrins, the receptors for ECM proteins, are present on sensory neurons that mediate pain, the possible role of these cell adhesion molecules in inflammatory or neuropathic pain has not been explored. We found that the intradermal injection of peptide fragments of domains of laminin and fibronectin important for adhesive signaling selectively inhibited the hyperalgesia caused by prostaglandin E(2) (PGE(2)) and epinephrine (EPI), respectively The block of EPI hyperalgesia was mimicked by other peptides containing the RGD integrin-binding sequence. Monoclonal antibodies (mAbs) against the alpha(1) or alpha(3) integrin subunits, which participate in laminin binding, selectively blocked PGE(2) hyperalgesia, while a mAb against the alpha(5) subunit, which participates in fibronectin binding, blocked only EPI-induced hyperalgesia. A mAb against the beta(1) integrin subunit, common to receptors for both laminin and fibronectin, inhibited hyperalgesia caused by both agents, as did the knockdown of beta(1) integrin expression by intrathecal injection of antisense oligodeoxynucleotides. The laminin peptide, but not the fibronectin peptides, also reversibly abolished the longer lasting inflammatory hyperalgesia induced by carrageenan. Finally, the neuropathic hyperalgesia caused by systemic administration of the cancer chemotherapy agent taxol was reversibly inhibited by antisense knockdown of beta(1) integrin. These results strongly implicate specific integrins in the maintenance of inflammatory and neuropathic hyperalgesia. C1 Univ Calif San Francisco, Dept Med, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, NIH Pain Ctr, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Med, Div Neurosci, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu RI Parada, Carlos Amilcar/C-3974-2012 NR 50 TC 66 Z9 67 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2004 VL 19 IS 3 BP 634 EP 642 DI 10.1111/j.1460-9568.2004.03169.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 775WU UT WOS:000189084300014 PM 14984413 ER PT J AU Brasted, PJ Wise, SP AF Brasted, PJ Wise, SP TI Comparison of learning-related neuronal activity in the dorsal premotor cortex and striatum SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE basal ganglia; conditional motor learning; frontal cortex; stimulus-response learning; visually guided movement ID POSITRON-EMISSION-TOMOGRAPHY; PRIMARY MOTOR CORTEX; SUPPLEMENTARY EYE FIELD; INFEROTEMPORAL-FRONTAL DISCONNECTION; CONDITIONAL OCULOMOTOR ASSOCIATIONS; ARBITRARY VISUOMOTOR ASSOCIATIONS; MONKEYS MACACA-FASCICULARIS; ORBITAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; LINKING BASAL GANGLIA AB Previous studies have reported learning-related changes in neuronal activity during conditional visuomotor learning, also known as arbitrary sensorimotor mapping, conditional visual discrimination, and symbolic or endogenous mapping. Qualitatively similar observations have been reported for the dorsal premotor cortex, the supplementary eye field, the prefrontal cortex, the hippocampus, the striatum and the globus pallidus. The fact that cells in both the dorsal premotor cortex (PMd) and the basal ganglia show changes in activity during associative learning enables a test of the hypothesis that cortex and basal ganglia function in distributed architectures known as cortical-basal ganglionic modules or 'loops'. We reasoned that if these loops represent functional entities, as proposed, then learning-related changes in activity should occur simultaneously in both the cortical and striatal nodes of a loop. The present results confirmed this prediction; as monkeys learned conditional visuomotor associations, neurons in the premotor cortex and associated parts of the putamen changed their rates at approximately the same time. For the largest number of neurons, the evolution in neural activity occurred in close correspondence to the monkeys' learning curves. As a population, however, learning-related changes in activity continued after the monkeys reached an asymptote in performance. C1 NIMH, Sect Neurophysiol, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Sect Neurophysiol, Lab Syst Neurosci, NIH, 49 Convent Dr,MSC 4401,Bldg 49,Room B1EE17, Bethesda, MD 20892 USA. EM stevenwise@mail.nih.gov NR 111 TC 114 Z9 118 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2004 VL 19 IS 3 BP 721 EP 740 DI 10.1111/j.0953-816X.2003.03181.x PG 20 WC Neurosciences SC Neurosciences & Neurology GA 775WU UT WOS:000189084300024 PM 14984423 ER PT J AU Thiruchelvam, MJ Powers, JM Cory-Slechta, DA Richfield, EK AF Thiruchelvam, MJ Powers, JM Cory-Slechta, DA Richfield, EK TI Risk factors for dopaminergic neuron loss in human alpha-synuclein transgenic mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ageing; gender; mouse strain background; paraquat; Parkinson's disease; pesticides; substantia nigra ID PARKINSONS-DISEASE PHENOTYPE; COMBINED PARAQUAT; LEWY NEURITES; WILD-TYPE; MODEL; MANEB; MPTP; SENSITIVITY; ONSET; BRAIN AB Genetic background, pesticide exposure, age, gender, diet and lifestyle are implicated risk factors in Parkinson's disease. We demonstrate dopamine neuron loss and other features of Parkinsonism based on the interaction of several of these human risk factors in transgenic mice expressing human alpha-synuclein. Mice expressing different forms of human alpha-synuclein had progressive declines in locomotor activity and abnormal responses to apomorphine that were modified by transgenic status. Stereological counts of tyrosine hydroxylase-positive neurons significantly declined with age only in the transgenic lines, consistent with a constant or decreasing risk, with the line expressing a double-mutant form of human alpha-synuclein more severely affected than the line expressing wild-type human alpha-synuclein. Treatment with Mn2+-ethylenebisdithiocarbamate and paraquat resulted in significantly greater effects in the double-mutant line than the other lines. Inclusions were not identified in the transgenic lines. Overexpression of human alpha-synuclein had adverse effects on substantia nigra pars compacta dopaminergic neurons that were modified by risk factors interacting in humans, including human alpha-synuclein mutations, ageing, and exposure to pesticides. C1 Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, NIEHS, Environm Hlth Sci Ctr, Rochester, NY 14642 USA. RP Richfield, EK (reprint author), Univ Med & Dent New Jersey, EOHSI, Dept Pathol & Lab Med, 170 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM ekr@eohsi.rutgers.edu FU NIEHS NIH HHS [1R21ES11839, ES01247, ES05017, ES05903] NR 48 TC 112 Z9 115 U1 1 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2004 VL 19 IS 4 BP 845 EP 854 DI 10.1111/j.1460-9568.2004.03139.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 803TE UT WOS:000220252600006 PM 15009131 ER PT J AU Arnegard, ME Kondrashov, AS AF Arnegard, ME Kondrashov, AS TI Sympatric speciation by sexual selection alone is unlikely SO EVOLUTION LA English DT Review DE African cichlids; ecological selection; mate preference; modeling; sympatric speciation ID AFRICAN CICHLID FISHES; FEMALE MATE CHOICE; GUPPY POECILIA-RETICULATA; LAKE MALAWI; MATING PREFERENCES; STABILIZING SELECTION; REPRODUCTIVE SUCCESS; SPECIES RECOGNITION; GENETIC-VARIABILITY; POLYGENIC MODEL AB According to Darwin, sympatric speciation is driven by disruptive, frequency-dependent natural selection caused by competition for diverse resources. Recently, several authors have argued that disruptive sexual selection can also cause sympatric speciation. Here, we use hypergeometric phenotypic and individual-based genotypic models to explore sympatric speciation by sexual selection under a broad range of conditions. If variabilities of preference and display traits are each caused by more than one or two polymorphic loci, sympatric speciation requires rather strong sexual selection when females exert preferences for extreme male phenotypes. Under this kind of mate choice, speciation can occur only if initial distributions of preference and display are close to symmetric. Otherwise, the population rapidly loses variability. Thus, unless allele replacements at very few loci are enough for reproductive isolation, female preferences for extreme male displays are unlikely to drive sympatric speciation. By contrast, similarity-based female preferences that do not cause sexual selection are less destabilizing to the maintenance of genetic variability and may result in sympatric speciation across a broader range of initial conditions. Certain groups Of African cichlids have served as the exclusive motivation for the hypothesis of sympatric speciation by sexual selection. Mate choice in these fishes appears to be driven by female preferences for extreme male phenotypes rather than similarity-based preferences, and the evolution of premating reproductive isolation commonly involves at least several genes. Therefore, differences in female preferences and male display in cichlids and other species of sympatric origin are more likely to have evolved as isolating mechanisms under disruptive natural selection. C1 Cornell Univ, Dept Neurobiol & Behav, Ithaca, NY 14853 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Arnegard, ME (reprint author), Cornell Univ, Dept Neurobiol & Behav, Ithaca, NY 14853 USA. EM mea21@cornell.edu; kondrashov@ncbi.nlm.nih.gov NR 132 TC 87 Z9 89 U1 4 U2 50 PU SOC STUDY EVOLUTION PI LAWRENCE PA 810 E 10TH STREET, LAWRENCE, KS 66044 USA SN 0014-3820 J9 EVOLUTION JI Evolution PD FEB PY 2004 VL 58 IS 2 BP 222 EP 237 DI 10.1111/j.0014-3820.2004.tb01640.x PG 16 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 802WS UT WOS:000220194200002 PM 15068341 ER PT J AU Bossert, JM Shaham, Y AF Bossert, JM Shaham, Y TI Drug onset cues, conditioned withdrawal, and drug relapse: Comment on McDonald and Siegel (2004) SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID HEROIN-SEEKING; HUMAN BRAIN; TOLERANCE; COCAINE; RESPONSES; ADDICTION; STRESS AB Previous research has shown that under certain conditions environmental cues associated with morphine administration induce drug-opposite conditioned effects that mimic symptoms of opiate withdrawal. R. V. McDonald and S. Siegel (2004) extend these observations by demonstrating that acute exposure to a low dose of morphine induces symptoms of opiate withdrawal in rats previously exposed to a high dose of morphine. They hypothesized that early drug onset cues, repeatedly paired with later, larger drug effects, mediate the paradoxical effect of the low drug dose on behavior. They also hypothesized that conditioned withdrawal symptoms induced by the early drug onset cues may mediate the "priming" effect of drugs on relapse and craving. The authors of this comment discuss the degree to which the literature supports this hypothesis. C1 IRP NIDA NIH, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), IRP NIDA NIH, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 NR 24 TC 2 Z9 2 U1 3 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD FEB PY 2004 VL 12 IS 1 BP 15 EP 17 DI 10.1037/1064-1297.12.1.15 PG 3 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 770GB UT WOS:000188713900003 PM 14769093 ER PT J AU Shorts, LH Dancz, CE Shupp, JW Pontzer, CH AF Shorts, LH Dancz, CE Shupp, JW Pontzer, CH TI Characterization of N-terminal interferon tau mutants: P26L affords enhanced activity and lack of toxicity SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE interferon tau; interferon alpha; antiviral; cytotoxicity; antiproliferative ID PREGNANCY RECOGNITION HORMONE; IFN-TAU; CRYSTAL-STRUCTURE; ANTIPROLIFERATIVE ACTIVITIES; ANTIVIRAL ACTIVITIES; ANGSTROM RESOLUTION; HUMAN-CELLS; ALPHA; RECEPTOR; BETA AB Interferon (IFN)-tau is a type I IFN that is responsible for the maternal recognition of pregnancy in ruminants. This protein also has classic IFN-like properties, including antiviral, anti-proliferative, and immunomodulatory functions. Using IFN-tau as a model, we examined the structural basis for the activity of type I IFNs, focusing on amino acids within helix A and the first section of the AB loop, which have been proposed as a site for receptor interaction. Six amino-acid substitutions were made that replaced a residue in ovine IFN-tau1 mod with the corresponding residue in human IFN-alphaA. Receptor binding was enhanced by a P26L mutation and was reduced by a conservative lysine-to-histidine substitution at residue 34. Alterations in the antiviral and antiproliferative activities of the IFN-tau mutants were not always correlated, but both functions were maintained or enhanced relative to the wild-type IFN-tau by the proline-to-leucine mutation at residue 26. In contrast, this mutation did not affect the low in vitro cytotoxicity that is characteristic of ovine IFN-tau1mod. Thus, the IFN-tau P26L mutant may have potential as an improved IFN-based therapeutic. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Pontzer, CH (reprint author), Natl Ctr Complementary & Alernat Med, NIH, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM pontzerc@mail.nih.gov NR 33 TC 5 Z9 6 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD FEB PY 2004 VL 229 IS 2 BP 194 EP 202 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 833FJ UT WOS:000222321600008 PM 14734798 ER PT J AU Koivisto, L Hakkinen, L Matsumoto, K McCulloch, CA Yamada, KM Larjava, H AF Koivisto, L Hakkinen, L Matsumoto, K McCulloch, CA Yamada, KM Larjava, H TI Glycogen synthase kinase-3 regulates cytoskeleton and translocation of Rac1 in long cellular extensions of human keratinocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE lamellipodia; actin; tubulin; Rho GTPases ID DEPENDENT PROTEIN PHOSPHATASE; RHO-ASSOCIATED KINASE; INTERMEDIATE-FILAMENTS; EXTRACELLULAR-MATRIX; ACTIN CYTOSKELETON; EPITHELIAL-CELLS; ARP2/3 COMPLEX; SMOOTH-MUSCLE; CDC42 GTPASES; WOUND REPAIR AB Wound keratinocytes form long cellular extensions that facilitate their migration from the wound edge into provisional matrix. We have previously shown that similar extensions can be induced by a long-term exposure to EGF or rapidly by staurosporine in Cultured cells. This morphological change depends on the activity of glycogen synthase kinase-3 (GSK-3). Here, we have characterized the cytoskeletal changes involved in formation of these extended lamellipodia (E-lam) in human HaCaT keratinocytes. E-lams contained actin filaments, stable microtubules and keratin intermediate filaments. E-lam formation was prevented by cytochalasin D, colchicine and low concentrations of taxol and nocodazole, suggesting that actin and microtubule organization and dynamics are essential for E-lam formation. Staurosporine induced recruitment of filamentous actin (F-actin), cortactin, filamin, Arp2/3 complex, Rac1 GTPase and phospholipase C-gamma1 (PLC-gamma1) to lamellipodia. Treatment of cells with the GSK-3 inhibitors SB-415286 and LiCl2 inhibited E-lam formation and prevented the accumulation of Rac1 and Arp2/3 complex at lamellipodia. The formation of E-lams was dependent on fibronectin-binding integrins and normally regulated Rac1, and expression of either dominant-negative or constitutively active forms of Rac1 prevented E-lam formation. Overexpression of either RhoA or Cdc42 GTPases suppressed E-lam formation. We conclude that extended lamellipodia formation in keratinocytes requires actin and tubulin assembly at the leading edge, and this process is regulated by Rac1 downstream of GSK-3. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3, Canada. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Univ Toronto, Toronto, ON M5S 3E2, Canada. RP Larjava, H (reprint author), Univ British Columbia, Fac Dent, Dept Oral Biol & Med Sci, 2199 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. EM lajava@interchange.ube.ca RI Hakkinen, Lari/B-2228-2016; OI Yamada, Kenneth/0000-0003-1512-6805 NR 69 TC 24 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 1 PY 2004 VL 293 IS 1 BP 68 EP 80 DI 10.1016/j.yexcr.2003.09.026 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 767PZ UT WOS:000188462300007 PM 14729058 ER PT J AU Kjoller, L Engelholm, LH Hoyer-Hansen, M Dano, K Bugge, TH Behrendt, N AF Kjoller, L Engelholm, LH Hoyer-Hansen, M Dano, K Bugge, TH Behrendt, N TI uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE extracellular matrix turnover; plasminogen activation; basement membrane; integrin; endocytosis ID RECEPTOR-ASSOCIATED PROTEIN; PLASMINOGEN-ACTIVATOR RECEPTOR; MANNOSE RECEPTOR; HUMAN FIBROBLASTS; LECTIN RECEPTOR; HUMAN BREAST; PHAGOCYTOSIS; BINDING; CELLS; INTERNALIZATION AB Collagen turnover is crucial for tissue homeostasis and remodeling and pathological processes such as cancer invasion, but the underlying molecular mechanisms are poorly understood. A major pathway appears to be internalization and degradation by fibroblasts. We now show that the endocytic transmembrane glycoprotein urokinase plasminogen activator receptor-associated protein (uPARAP/endo180) directs collagen IV for lysosomal delivery and degradation. In wild-type fibroblasts, fluorescently labeled collagen IV was first internalized into vesicular structures with diffuse fluorescence eventually appearing uniformly within the wild-type cells after longer incubation times. In these cells, some collagen-containing vesicles were identified as lysosomes by staining for LAMP-1. In contrast, collagen IV remained extracellular and associated with fiber-like structures on uPARAP/endo180-deficient fibroblasts. Blocking lysosomal cysteine proteases with the inhibitor E64d resulted in strong accumulation of collagen IV in lysosomes in wild-type cells, but only very weak intracellular fluorescence accumulation in uPARAP/endo180-deficient fibroblasts. We conclude that uPARAP/endo180 is critical for targeted delivery of collagen IV to lysosomes for degradation implicating the receptor in normal and malignant extracellular matrix degradation. A similar localization pattern was observed for collagen V, suggesting that uPARAP/endo180 might be generally involved in collagen degradation. (C) 2003 Elsevier Inc. All rights reserved. C1 Rigshosp, Finsen Lab, DK-2100 Copenhagen O, Denmark. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Danish Canc Soc, Apoptosis Lab, DK-2100 Copenhagen O, Denmark. RP Rigshosp, Finsen Lab, Bldg 7-2,Strandblvd 49, DK-2100 Copenhagen O, Denmark. EM lkjoller@finsenlab.dk OI Engelholm, Lars/0000-0002-6616-1232 NR 26 TC 54 Z9 58 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 1 PY 2004 VL 293 IS 1 BP 106 EP 116 DI 10.1016/j.yexcr.2003.10.008 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 767PZ UT WOS:000188462300010 PM 14729061 ER PT J AU Sosne, G Xu, LH Prach, L Mrock, LK Kleinman, HK Letterio, JJ Hazlett, LD Kurpakus-Wheater, M AF Sosne, G Xu, LH Prach, L Mrock, LK Kleinman, HK Letterio, JJ Hazlett, LD Kurpakus-Wheater, M TI Thymosin beta 4 stimulates laminin-5 production independent of TGF-beta SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE thymosin beta 4; cornea; epithelial cell; cell migration; laminin-5; TGF-beta; cytokines; extracellular matrix ID GROWTH-FACTOR-BETA; CORNEAL EPITHELIAL-CELLS; BASEMENT-MEMBRANE; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1; KERATINOCYTE MOTILITY; GENE-EXPRESSION; TGF-BETA-1; PEPTIDE; MICE AB Thymosin beta 4 (Tbeta(4)) stimulates epithelial cell migration and promotes laminin-5 (LM-5) expression. Using gene expression analysis with human corneal epithelial cells treated with Tbeta(4), we find that both LM-5 gamma2 chain and transforming growth factor beta 1 (TGFbeta-1) are increased by more than 2-fold over untreated cells. These findings were confirmed by RT-PCR and at the protein level. Although TGFbeta-1 increases LM-5 synthesis in a dose-dependent manner, it does not appear to be the mechanism by which Tbeta(4) acts on LM-5 gamma2 chain synthesis based on three independent experiments. In a time-course analysis, Tbeta(4) increases LM-5 gamma2 chain expression at 2 h and peaks at 6 h, while TGFbeta-1 increases LM-5 gamma2 chain expression only at 4 h and peaks at 8 h. When Tbeta(4)-induced LM-5 gamma2 chain expression is blocked with neutralizing antibodies to TGFbeta-1, LM-5 gamma2 chain expression is increased. Finally, in TGFbeta-1 knock-out mice, Tbeta(4) increases LM-5 gamma2 chain expression to levels higher than that observed in wild-type mice treated with Tbeta(4). These findings demonstrate that Tbeta(4) induces both TGFbeta-1 and LM-5 gamma2 chain expression in corneal epithelial cells. Tbeta(4) and TGFbeta-1 increase LM-5 2 gamma2 chain expression by independent pathways. Suppression of TGFbeta-1 further increases LM-5 gamma2 chain expression. (C) 2003 Elsevier Inc. All rights reserved. C1 Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Wayne State Univ, Kresge Eye Inst, Dept Ophthalmol, Detroit, MI 48201 USA. NIDCR, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Sosne, G (reprint author), Wayne State Univ, Sch Med, Dept Anat & Cell Biol, 540 E Canfield,Scott Hall Room 8314, Detroit, MI 48201 USA. EM gsosne@med.wayne.edu FU NEI NIH HHS [K08 EY13412] NR 43 TC 42 Z9 47 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 1 PY 2004 VL 293 IS 1 BP 175 EP 183 DI 10.1016/j.yexcr.2003.09.022 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 767PZ UT WOS:000188462300016 PM 14729067 ER PT J AU Becerra, SP Fariss, RN Wu, YQ Montuenga, LM Wong, P Pfeffer, BA AF Becerra, SP Fariss, RN Wu, YQ Montuenga, LM Wong, P Pfeffer, BA TI Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal pigment epithelium; pigment epithelium-derived factor; secretion; polarization; interphotoreceptor matrix; monkey eye; apical; basal ID ENDOTHELIAL GROWTH-FACTOR; FACTOR PEDF; NEUROTROPHIC ACTIVITY; NONINHIBITORY SERPIN; TISSUE INHIBITOR; FACTOR RECEPTORS; MOTOR-NEURONS; BINDING-SITE; BOVINE EYES; CELLS AB Pigment epithelium-derived factor (PEDF) is an extracellular protein derived from the retinal pigment epithelium (RPE), a tissue formed by polarized cells that release growth and trophic factors in a directional fashion. We have investigated the distribution and directional release of PEDF protein by the monkey RPE. We established primary cultures of monkey RPE cells that expressed the PEDF gene, and that synthesized and secreted the PEDF protein. Northern analysis of RPE cultures and monkey ocular tissues showed that PEDF transcripts were highly expressed in RPE as compared with several other monkey ocular tissues, being even more abundant in cultured cells than they were in the native RPE. The differentiated RPE cells in culture secreted protein that shared the immunological, biochemical and biological characteristics of PEDF. The overall PEDF levels in the RPE conditioned media reached 6.5 mg ml(-) after 8 days in culture (i.e. 1.1 pg of PEDF per RPE cell). RPE cells were cultivated on permeable supports as monolayers forming a barrier between apical and basal compartments. Apical and basal culture media were sampled at three or four-day intervals for 18 cycles, and the PEDF content was quantified. Most of the PEDF protein was significantly higher in the apical than in the basal medium (>4 times) at the initial recovery intervals, to be detected only in the apical medium at the latter intervals. In the native monkey eye, the concentration of soluble PEDF in the interphotoreceptor matrix (144 nM) was 7-fold and 25-fold greater than in vitreous and aqueous, respectively. PEDF was abundant in the interphotoreceptor matrix surrounding rod and cone outer segments, and was detectable at lower levels in the RPE as visualized by confocal microscopy. We concluded that PEDF synthesized by the RPE is secreted preferentially from the apical surface and is distributed apically to the RPE bordering the outer segments of photoreceptors. PEDF can be a useful marker for RPE polarization and differentiation. The polarization of RPE may be an important mechanism to control PEDF secretion and our results offer interesting possibilities on regulation of PEDF. (C) 2004 Elsevier Ltd. All rights reserved. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NCI, DCS, NIH, Bethesda, MD 20892 USA. Univ Navarra, Dept Histol & Pathol, Navarra, Spain. Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada. Bausch & Lomb, Rochester, NY USA. RP Becerra, SP (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 308,6 Ctr Dr MSC 2740, Bethesda, MD 20892 USA. EM becerrap@nei.nih.gov NR 51 TC 57 Z9 60 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 2004 VL 78 IS 2 BP 223 EP 234 DI 10.1016/j.exer.2003.10.013 PG 12 WC Ophthalmology SC Ophthalmology GA 773TQ UT WOS:000188939200007 PM 14729355 ER PT J AU Czapiga, M Kirk, AD Lekstrom-Himes, J AF Czapiga, M Kirk, AD Lekstrom-Himes, J TI Platelets deliver costimulatory signals to antigen-presenting cells: A potential bridge between injury and immune activation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID SOLUBLE CD40 LIGAND; CD40-CD40 LIGAND; DIFFERENTIAL REGULATION; DENDRITIC CELLS; EXPRESSION; MACROPHAGES; TRIGGERS; RELEASE; NONSELF; DANGER AB The danger model of immunity and tolerance holds that antigen-presenting cells (APCs), activated by stress, injury, or necrosis, but not by physiological (apoptotic) cell death, initiate adaptive immune responses. APC activation is fundamentally associated with binding of CD40 to its ligand CD154. Platelets express CD154 upon activation and are thus potential primal danger signals linking the homeostatic response to trauma to activation of the acquired immune system. Previously, we showed that platelets can undergo gradient-driven migration, or chemotaxis, toward supernatants from cells injured by repeated freeze/thaws, UV light, or ischemia/reperfusion. Herein, we demonstrate that platelet-derived CD154 induces immature dendritic cell maturation with upregulation of costimulatory molecules and IL-12p40 production. Overall, these results provide a mechanism for platelet activation of APC facilitating the induction of adaptive immunity in environments of cell injury. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIAID, Host Def Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NIDDKD, Transplantat Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Lekstrom-Himes, J (reprint author), Millennium Pharmacuet Inc, 35 Landsdowne St, Cambridge, MA 02139 USA. EM lekstrom@mpi.com RI Kirk, Allan/B-6905-2012 NR 26 TC 43 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD FEB PY 2004 VL 32 IS 2 BP 135 EP 139 DI 10.1016/j.exphem.2003.11.004 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HJ UT WOS:000220965500002 PM 15102473 ER PT J AU Radosevic, N Winterstein, D Keller, JR Neubauer, H Pfeffer, K Linnekin, D AF Radosevic, N Winterstein, D Keller, JR Neubauer, H Pfeffer, K Linnekin, D TI JAK2 contributes to the intrinsic capacity of primary hematopoietic cells to respond to stem cell factor SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; EPIDERMAL-GROWTH-FACTOR; C-KIT; TYROSINE KINASE; MAST-CELLS; SIGNAL-TRANSDUCTION; SELF-RENEWAL; FETAL LIVER; CYTOKINE RECEPTORS; STAT ACTIVATION AB Objective. Stem cell factor (SCF) is the ligand for the receptor tyrosine kinase (RTK) Kit. The literature contains conflicting reports regarding the capacity of SCF to activate JAK2. Previous work has addressed this controversial issue using biochemical approaches. Here we use a genetic approach to determine the direct role of JAK2 in SCF-mediated growth and differentiation of primary hematopoietic cells. Materials and Methods. Fetal liver cells were isolated from JAK2-deficient murine embryos at day 12 of development. SCF-induced growth and differentiation of this unfractionated population of cells were determined by H-3-thymidine incorporation in bulk cultures, single-cell colony assays, and cytochemistry. In addition, Kit(+) cells were isolated from fetal liver by fluorescence-activated cell sorting (FACS) and assessed for growth using H-3-thymidine and colony assays. Results. SCF-induced growth of unfractionated JAK2-deficient fetal liver cells was reduced by 70% compared to cells from wild-type fetal liver in single-cell assays. This was of particular note because there were three-fold more Kit+ cells in JAK2-deficient fetal liver. Reductions in SCF-induced growth were not observed in bulk cultures of JAK2-deficient fetal liver, suggesting that additional factors cooperate with SCF to overcome the absence of JAK2 in this heterogeneous population of cells. SCF-induced 3H-thymidine incorporation of FACS-purified Kit+ fetal liver deficient for JAK2 was impaired by approximately 50%, whereas colony formation in methylcellulose was reduced 95%. JAK2 also was required for differentiation of this purified population of progenitors into mast cells. Conclusion. JAK2 contributes to the intrinsic capacity of fetal liver hematopoietic progenitor cells to proliferate and differentiate in response to SCF. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NCI, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-8000 Munich, Germany. RP Linnekin, D (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Bldg 567,Room 226, Frederick, MD 21702 USA. EM dlinnekin@mail.ncifcrf.gov RI Neubauer, Hans/C-4467-2016; OI Neubauer, Hans/0000-0002-3467-4105; Pfeffer, Klaus/0000-0002-5652-6330 FU NCI NIH HHS [N01-CO-12400] NR 53 TC 19 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD FEB PY 2004 VL 32 IS 2 BP 149 EP 156 DI 10.1016/j.exphem.2003.11.006 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HJ UT WOS:000220965500004 PM 15102475 ER PT J AU Sellers, SE Tisdale, JF Agricola, BA Donahue, RE Dunbar, CE AF Sellers, SE Tisdale, JF Agricola, BA Donahue, RE Dunbar, CE TI The presence of the carboxy-terminal fragment of fibronectin allows maintenance of non-human primate long-term hematopoietic repopulating cells during extended ex vivo culture and transduction SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-CELLS; MEDIATED GENE-TRANSFER; HIGH-DOSE CHEMOTHERAPY; STEM-CELLS; PROGENITOR CELLS; PERIPHERAL-BLOOD; RETROVIRAL VECTORS; CORD BLOOD; AUTOLOGOUS TRANSPLANTATION; CD34(+) CELLS AB Objective. Ex vivo expansion of primitive hematopoietic cells remains of interest for gene therapy and transplantation. Previous studies reported loss of repopulating activity following culture of cells for more than 4-7 days in the presence of cytokines or stromal cells. In the current study, we investigated whether prolonged culture and transduction in the presence of the carboxy-terminal portion of fibronectin (FN) could maintain or expand retrovirally transduced repopulating hematopoietic stem cells (HSCs). Methods. The impact of culture and transduction on rhesus macaque CD34(+) peripheral blood stem cells (PBSCs) was assessed in the presence of FN and stimulatory cytokines. A competitive repopulation design using up to three retroviral vectors allowed direct comparison of repopulating activity between cells transduced and cultured for 4 days vs 10 days. Results. In the first animal, all cells were cultured and transduced for 10 days, with one vector used on days 0-4 and a second on days 4-10. There was stable long-term marking from both vectors, indicating that cells cycling both early and late could engraft. In three animals, we compared cells that were cryopreserved following a 4-day transduction to cells that were continued in culture for an additional 6 days. Total marking derived from the 10-day expanded cells was significantly higher than marking from the 4-day cultured cells. Conclusions. These results suggest that culture on FN support allows prolonged ex vivo maintenance and even expansion of transduced repopulating stem cells. (C) 2004 International Society for Experimental Hemotology. Published by Elsevier Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 41 TC 12 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD FEB PY 2004 VL 32 IS 2 BP 163 EP 170 DI 10.1016/j.exphem.2003.10.003 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HJ UT WOS:000220965500006 PM 15102477 ER PT J AU Re, F Srinivasan, R Igarashi, T Marincola, F Childs, R AF Re, F Srinivasan, R Igarashi, T Marincola, F Childs, R TI Green fluorescent protein expression in dendritic cells enhances their immunogenicity and elicits specific cytotoxic T-cell responses in humans SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID IN-VITRO; RECOMBINANT ADENOVIRUS; HEMATOPOIETIC-CELLS; IMMUNE-RESPONSE; GENE; IDENTIFICATION; LYMPHOCYTES; EFFICIENT; VACCINES; MARKER AB Objective. Green fluorescent protein (GFP) has been used to monitor and select cells transduced with vectors encoding other transgenes of interest. We investigated the immunogenic nature of GFP in humans and further explored whether this xenoprotein could be used as a functional adjuvant to enhance T-cell immunity to the melanoma tumor antigen MART1. Methods. Peripheral blood lymphocytes from healthy donors were stimulated by autologous dendritic cells expressing GFP, then cloned by limiting dilution and tested for antigen specificity following coculture with GFP-expressing or GFP-negative targets. In a parallel experiment, lymphocytes from HLA A 0201(+) healthy donors were stimulated with four different Melan-A/MART1(27-35) peptide-pulsed stimulators: 1) MART1 peptide-pulsed DCs, 2) MART1 peptide-pulsed DCs loaded with GFP protein, 3) MART1 peptide-pulsed GFP adenovirus-transduced DCs, and 4) MART1 peptide-pulsed null adenovirus-transduced DCs. The percentage of CD3(+)/CD8(+) MART1 peptide-specific T cells was determined by intracellular cytokine staining for gamma-IFN. Results. Multiple CD4(+) and CD8(+) T cell clones were expanded which secreted gamma-IFN and demonstrated high levels of cytotoxicity to GFP-expressing targets as assessed by ELISA and Cr-51 release respectively. We next investigated the impact of GFP expression on DCs used to stimulate cytotoxic T cells specific fora tumor-associated peptide. The percentage of MART1-specific CD8+ T cells that were generated was higher when MART1-pulsed GFP adenovirus-transduced DCs were used as stimulators (28%) compared to MART1-pulsed DCs alone (11%, p = 0.01), MART1-pulsed null adenovirus-transduced DCs (11.7%, p = 0.02), or MART1-pulsed DCs loaded with GFP protein (12.2%). Conclusions. These findings further support GFP's immunogenicity and suggest this xenoprotein might further be used to enhance the expansion of tumor-specific T cells. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 San Raffaele Sci Inst, Milan, Italy. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. RP Re, F (reprint author), Hosp San Raffaele, UTMO, Via Olgettina 60, I-20132 Milan, Italy. EM francesca.re@hsr.it NR 18 TC 22 Z9 22 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD FEB PY 2004 VL 32 IS 2 BP 210 EP 217 DI 10.1016/j.exphem.2003.10.014 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HJ UT WOS:000220965500012 PM 15102483 ER PT J AU Luzzio, FA Figg, WD AF Luzzio, FA Figg, WD TI Thalidomide analogues: derivatives of an orphan drug with diverse biological activity SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE angiogenesis; cachexia; chemotherapy; glutarimide; HIV; immunomodulatory; metabolic activation; phthalimide; prodrug; teratogenicity; TNF-alpha; multiple myeloma; myelodysplastic syndrome ID TNF-ALPHA PRODUCTION; IMMUNODEFICIENCY-VIRUS TYPE-1; MULTIPLE-MYELOMA; INHIBITORY-ACTIVITY; CYTOKINE PRODUCTION; CHIRAL INVERSION; TUMOR-GROWTH; IN-VITRO; T-CELLS; ANGIOGENESIS AB Introduced as a sedative during the late 1950s, the realisation of the potent human embryotoxicity of thalidomide led to its withdrawal from the market in early 1961. Although the drug was discontinued, its teratogenic properties attracted unceasing interest as evidenced by numerous reports over the years. As investigations into its teratogenicity continued, thalidomide was serendipitously found, in separate investigations, to be effective therapy for the symptoms of leprosy (erythema nodosum leprosum). Later, the compound was found to be active against the aphthous ulcers of Behcet's syndrome and effective as a substitute for immunosuppressive therapy for graft-versus-host disease. The relevance of thalidomide in immunosuppressive therapy has also included ailments such as cachexia, HIV wasting and Crohn's disease. Although reports dating from the mid 1990s have disclosed the antiangiogenic activity of thalidomide, its inhibition of TNF-alpha, together with its immunomodulatory properties and therapeutic effectiveness in multiple myeloma, have been fast gaining attention. Consequently, a number of synthetic and biological investigations have targeted analogues with higher potencies in several of the above-mentioned therapeutic areas, as well as having lower undesirable side effects. As a result, a number of interesting compounds of varied structure have been synthesised and tested for their ability to inhibit angiogenesis or act as immunosuppressant, immunomodulatory, anti-inflammatory or anticancer agents. C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. NCI, Pharmacol Sect, Bethesda, MD 20892 USA. RP Luzzio, FA (reprint author), Univ Louisville, Dept Chem, 2320 S Brook St, Louisville, KY 40292 USA. EM faluzz01@athena.louisville.edu; wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 78 TC 7 Z9 7 U1 0 U2 6 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD FEB PY 2004 VL 14 IS 2 BP 215 EP 229 DI 10.1517/eotp.14.2.215.26394 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 774KM UT WOS:000188978700006 ER PT J AU Jayanthi, S Deng, XL Noailles, PAH Ladenheim, B Cadet, JL AF Jayanthi, S Deng, XL Noailles, PAH Ladenheim, B Cadet, JL TI Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades SO FASEB JOURNAL LA English DT Review DE apoptosis-inducing factor; CHOP transcription factor; BiP/GRP78; DNA fragmentation ID DISMUTASE TRANSGENIC MICE; GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; CYTOCHROME-C RELEASE; CELL-DEATH; INDUCED NEUROTOXICITY; DNA FRAGMENTATION; OXIDATIVE STRESS; GENE-EXPRESSION; MOUSE-BRAIN AB Methamphetamine (METH) is an illicit drug that causes neurodegenerative effects in humans. In rodents, METH induces apoptosis of striatal glutamic acid decarboxylase (GAD) -containing neurons. This paper provides evidence that METH-induced cell death occurs consequent to interactions of ER stress and mitochondrial death pathways. Specifically, injections of METH are followed by an almost immediate activation of proteases calpain and caspase-12, events consistent with drug-induced ER stress. Involvement of ER stress was further supported by observations of increases in the expression of GRP78/BiP and CHOP. Participation of the mitochondrial pathway was demonstrated by the transition of AIF, smac/DIABLO, and cytochrome c from mitochondrial into cytoplasmic fractions. These changes occur before the apoptosome-associated pro-caspase-9 cleavage. Effector caspases-3 and -6, but not -7, were cleaved with the initial time of caspase-3 activation occurring before caspase 9 cleavage; this suggests possible earlier cleavage of caspase-3 by caspase-12. These events preceded proteolysis of the caspase substrates DFF-45, lamin A, and PARP in nuclear fractions. These findings indicate that METH causes neuronal apoptosis in part via cross-talks between ER- and mitochondria-generated processes, which cause activation of both caspase-dependent and -independent pathways. C1 NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 109 TC 152 Z9 156 U1 3 U2 15 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 2004 VL 18 IS 2 BP 238 EP 251 DI 10.1096/fj.03-0295com PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806HM UT WOS:000220425000004 PM 14769818 ER PT J AU Fisher, JT Vincent, SG Gomeza, J Yamada, M Wess, J AF Fisher, JT Vincent, SG Gomeza, J Yamada, M Wess, J TI Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M-2 or M-3 muscarinic acetylcholine receptors SO FASEB JOURNAL LA English DT Article DE heart rate; airway smooth muscle; asthma; COPD; vagus nerve; parasympathetic nervous system ID KNOCKOUT MICE; SMOOTH-MUSCLE; HUMAN HEART; MULTIPLE SUBTYPES; MESSENGER-RNAS; RAT-HEART; GENE; ASTHMA; IDENTIFICATION; LOCALIZATION AB The presence of multiple muscarinic acetylcholine receptor (mAChR) subtypes in the heart and lung, combined with the lack of mAChR subtype-selective ligands, have complicated the task of identifying the mAChR subtypes mediating cardiac slowing (bradycardia) and airway narrowing (bronchoconstriction) due to vagal innervation. To determine which of the five mAChRs are responsible for the cholinergic control of heart rate and airway caliber in vivo, we performed experiments on mutant mice lacking the two prime candidates for such control, the M-2 or M-3 mAChR. Here, we report that in vivo, bradycardia caused by vagal stimulation or administration of the muscarinic agonist methacholine (MCh) was abolished in mice lacking functional M-2 mAChRs (M2(-/-) mice). In contrast, heart rate responses remained unchanged in M-3 receptor-deficient mice (M3(-/-) mice). The reduced hypotensive response of M3-/- mice to MCh suggests M-3 mAChRs contribute to peripheral vasodilation. The M2-/- mice showed significantly enhanced in vivo bronchoconstrictor responses to vagal stimulation or MCh administration. In contrast, bronchoconstrictor responses were totally abolished in M3-/- mice. Because altered cardiac or pulmonary vagal tone is involved in a number of pathophysiological conditions, including cardiac arrhythmias, chronic obstructive pulmonary disease and asthma, these results should be of considerable therapeutic relevance. C1 Queens Univ, Dept Physiol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Med, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Pediat, Kingston, ON K7L 3N6, Canada. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Fisher, JT (reprint author), Queens Univ, Dept Physiol, Kingston, ON K7L 3N6, Canada. EM fisherjt@post.queensu.ca RI Fisher, John/E-2568-2012 OI Fisher, John/0000-0001-6185-5940 NR 50 TC 72 Z9 77 U1 0 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2004 VL 18 IS 2 BP 711 EP + DI 10.1096/fj.03-0648fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806HM UT WOS:000220425000015 PM 14977875 ER PT J AU Fedarko, NS Jain, A Karadag, A Fisher, LW AF Fedarko, NS Jain, A Karadag, A Fisher, LW TI Three small integrin-binding ligand N-linked glycoproteins (SIBLINGs) bind and activate specific matrix metalloproteinases SO FASEB JOURNAL LA English DT Article DE bone sialoprotein; osteopontin; dentin matrix protein 1 ID COMPLEMENT-MEDIATED ATTACK; HUMAN BREAST-CANCER; HUMAN LUNG-CANCER; BONE SIALOPROTEIN; OSTEOPONTIN EXPRESSION; PROSTATE-CANCER; THYROID-CANCER; GROWTH; CELLS; MIGRATION AB Matrix metalloproteinases (MMPs) are critical for development, wound healing, and for the progression of cancer. It is generally accepted that MMPs are secreted in a latent form (proMMP) and are activated only upon removal of their inhibitory propeptides. This report shows that three members of the SIBLING (Small, Integrin-Binding LIgand, N-linked Glycoprotein) family can specifically bind (K(d)approximate tonM) and activate three different MMPs. Binding of SIBLING to their corresponding proMMPs is associated with structural changes as indicated by quenching of intrinsic tryptophan fluorescence, increased susceptibility to plasmin cleavage, and decreased inhibition by specific natural and synthetic inhibitors. Activation includes both making the proMMPs enzymatically active and the reactivation of the TIMP (tissue inhibitors of MMP) inhibited MMPs. Bone sialoprotein specifically binds proMMP-2 and active MMP-2, while osteopontin binds proMMP-3 and active MMP-3, and dentin matrix protein-1 binds proMMP-9 and active MMP-9. Both pro and active MMP-SIBLING complexes are disrupted by the abundant serum protein, complement Factor H, thereby probably limiting SIBLING-mediated activation to regions immediately adjacent to sites of secretion in vivo. These data suggest that the SIBLING family offers an alternative method of controlling the activity of at least three MMPs. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr, Baltimore, MD 21224 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fedarko, NS (reprint author), Room 5B-79 JHAAC,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM ndarko@jhmi.edu OI Fedarko, Neal/0000-0001-6055-6279 NR 32 TC 135 Z9 141 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD FEB PY 2004 VL 18 IS 2 BP 734 EP + DI 10.1096/fj.03-0966fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806HM UT WOS:000220425000041 PM 14766790 ER PT J AU Leppert, PC AF Leppert, PC TI The changing face of peer review at the National Institutes of Health SO FERTILITY AND STERILITY LA English DT Article DE National Institutes of Health; reproductive sciences; peer review AB Objective: To discuss the new peer review system at the National Institutes of Health (NIH) and to present the process undertaken to accomplish these changes, with an emphasis on the reproductive sciences. Design: A discussion of the many NIH committees and their composition and reports leading to the changes in peer review affecting the reproductive sciences. Result(s) and Conclusion(s): The Center for Scientific Review (CSR), which reviews grants for all NIH Institutes, will initiate the Cellular, Molecular, and Integrative Reproduction, the Integrative and Clinical Endocrinology and Reproduction, and the Pregnancy and Neonatology study sections in February 2004. The National Institute of Child Health and Human Development (NICHD)'s Division of Scientific Review has the following subcommittees, which started review in July 2003: Pediatrics; Developmental Biology; Biobehavior and Behavior Sciences; Population Science; Obstetrics and Matemal-Fetal Biology; Reproduction, Andrology, and Gynecology; and Function, Integration, and Rehabilitation Science. (C) 2004 by American Society for Reproductive Medicine. C1 Natl Inst Child Hlth & Human Dev, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Leppert, PC (reprint author), Natl Inst Child Hlth & Human Dev, Reprod Sci Branch, Bldg 6100,Room 8B01, Bethesda, MD 20892 USA. EM leppertp@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2004 VL 81 IS 2 BP 279 EP 286 DI 10.1016/j.fertnstert.2003.10.006 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 774GB UT WOS:000188970500010 PM 14967360 ER PT J AU Dikalov, SI Vitek, MP Mason, RP AF Dikalov, SI Vitek, MP Mason, RP TI Cupric-amyloid beta peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE copper; amyloid; ascorbate; hydroxyl radical; ESR; Alzheimer's disease; free radical ID ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; CATALYZED OXIDATION; A-BETA; NEUROTOXICITY; STRESS; PROTEIN; PLAQUES; AGENTS; ZINC AB A growing body of evidence supports an important role for oxidative stress in the pathogenesis of Alzheimer's disease. Recently, a number of papers have shown a synergistic neurotoxicity of amyloid p peptide and cupric ions. We hypothesized that complexes of cupric ions with neurotoxic amyloid peptides (A) can stimulate copper-mediated free radical formation. We found that neurotoxic Abeta (1-42), Abeta (1-40), and Abeta (25-35) stimulated copper-mediated oxidation of ascorbate, whereas nontoxic Abeta (40-1) did not. Formation of ascorbate free radical was significantly increased by A (1-42) in the presence of ceruloplasmin. Once cupric ion is reduced to cuprous ion, it can be oxidized by oxygen to generate superoxide radical or it can react with hydrogen peroxide to form hydroxyl radical. Hydrogen peroxide greatly increased the oxidation of cyclic hydroxylamines and ascorbate by cupric-amyloid peptide complexes, implying redox cycling of copper ions. Using the spin-trapping technique, we have shown that toxic amyloid peptides led to a 4-fold increase in copper-mediated hydroxyl radical formation. We conclude that toxic A peptides do indeed stimulate copper-mediated oxidation of ascorbate and generation of hydroxyl radicals. Therefore, cupric-amyloid p peptide-stimulated free radical generation may be involved in the pathogenesis of Alzheimer's disease. Published by Elsevier Inc. C1 NIEHS, Free Radical Metabolite Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Emory Univ, Div Cardiol, FRIMCORE, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Dept Med, Div Neurol, Durham, NC 27110 USA. RP Mason, RP (reprint author), NIEHS, Free Radical Metabolite Sect, Lab Pharmacol & Chem, NIH, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov NR 30 TC 71 Z9 72 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD FEB 1 PY 2004 VL 36 IS 3 BP 340 EP 347 DI 10.1016/j.freeradbiomed.2003.11.004 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 778TJ UT WOS:000189256600008 PM 15036353 ER PT J AU Siegel, KL Kepple, TM Stanhope, SJ AF Siegel, KL Kepple, TM Stanhope, SJ TI Joint moment control of mechanical energy flow during normal gait SO GAIT & POSTURE LA English DT Article DE power; mechanical energy; moment; gait ID WALKING; ANKLE; PROGRESSION; GENERATION; ABSORPTION; SUPPORT; POWER; SPEED AB The study purpose was to estimate the ability of joint moments to transfer mechanical energy through the leg and trunk during gait. A segmental power analysis of five healthy adult subjects revealed that internal joint extensor moments removed energy from the leg and added energy to the trunk, while flexor moments and gravity produced the opposite effects. The only exception to this pattern was during the push off phase of gait when the ankle plantar flexor moment added energy to both the leg and the trunk. Pairs of joint moments with opposite energetic effects (knee extensor vs gravity, hip flexor vs ankle plantar flexor) worked together to balance energy flows through the segments. This intralimb coordination suggests that moments with contradictory effects are generated simultaneously to control mechanical energy flow within the body during walking. Published by Elsevier B.V. C1 NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Siegel, KL (reprint author), NIH, Phys Disabil Branch, Bldg 10,Rm 6S235,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM karen_siegel@nih.gov RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 16 TC 35 Z9 36 U1 0 U2 16 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD FEB PY 2004 VL 19 IS 1 BP 69 EP 75 DI 10.1016/S0966-6362(03)00010-9 PG 7 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 769KG UT WOS:000188648800008 PM 14741305 ER PT J AU El-Serag, HB Tran, T Everhart, JE AF El-Serag, HB Tran, T Everhart, JE TI Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma SO GASTROENTEROLOGY LA English DT Article ID NONALCOHOLIC FATTY LIVER; OF-VETERANS-AFFAIRS; UNITED-STATES; NATURAL-HISTORY; CANCER RISK; INSULIN-RESISTANCE; MELLITUS; STEATOHEPATITIS; CIRRHOSIS; HEPATITIS AB Background & Aims: An association between diabetes and chronic liver disease has been reported. However, the temporal relationship between these conditions remains unknown. Methods: We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs. We randomly assigned 3 patients without diabetes for every patient with diabetes. We excluded patients with concomitant liver disease. The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease (CNLD) and hepatocellular carcinoma (HCC). Hazard rate ratios (HRR) were determined in Cox proportional hazard survival analysis. Results: The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes. Most were men (98%). Patients with diabetes were older (62 vs. 54 years) than patients without diabetes. The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes (incidence rate: 18.13 vs. 9.55 per 10,000 person-years, respectively, P < 0.0001). Similar results were obtained for HCC (incidence rate: 2.39 vs. 0.87 per 10,000 person-years, respectively, P < 0.0001). Diabetes was associated with an HRR of 1.98 (95% Cl: 1.88 to 2.09, P < 0.0001) of CNLD and an HRR of 2.16 (1.86 to 2.52, P < 0.0001) of hepatocellular carcinoma. Diabetes carried the highest risk among patients with longer than 10 years of follow-up. Conclusions: Among men with diabetes, the risk of CNLD and HCC is doubled. This increase in risk is independent of alcoholic liver disease, viral hepatitis, or demographic features. C1 Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD 20892 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 51 TC 551 Z9 569 U1 1 U2 18 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 2004 VL 126 IS 2 BP 460 EP 468 DI 10.1053/j.gastro.2003.10.065 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 771XJ UT WOS:000188811100013 PM 14762783 ER PT J AU James, SP AF James, SP TI Enhancing endoscopic research SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter C1 NIDDKD, Div Digest Dis & Nutr, Bethesda, MD USA. RP James, SP (reprint author), NIDDKD, Div Digest Dis & Nutr, Bethesda, MD USA. EM sj158p@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2004 VL 59 IS 2 BP 328 EP 328 DI 10.1016/S0016-5107(03)02690-7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 772ZA UT WOS:000188872100036 PM 14989231 ER PT J AU Berg, AH Westerlund, L Olsson, PE AF Berg, AH Westerlund, L Olsson, PE TI Regulation of Arctic char (Salvelinus alpinus) egg shell proteins and vitellogenin during reproduction and in response to 17 beta-estradiol and cortisol SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article DE Arctic char; Salvelinus alpinus; reproductive cycle; 17 beta-estradiol; vitelline envelope proteins; zona pellucida proteins; vitellogenin; estrogen receptor; cortisol ID TROUT ONCORHYNCHUS-MYKISS; VITELLINE ENVELOPE PROTEINS; SALMO-TRUTTA-L; HETEROPNEUSTES-FOSSILIS BLOCH; PITUITARY-INTERRENAL AXIS; RECEPTOR MESSENGER-RNA; FEMALE RAINBOW-TROUT; ZONA-PELLUCIDA GENE; GILTHEAD SEA BREAM; ESTROGEN-RECEPTOR AB Estrogens induce both vitellogenin (Vtg) and egg shell (zona pellucida; ZP) protein synthesis in salmonids. However, while Vtg is strictly under estrogenic control, recent reports suggest that additional mechanisms are involved in ZP protein synthesis. During sexual maturation both estrogen and glucocorticoid levels increase in the circulation of female fish. As glucocorticoids have been shown to interfere with Vtg induction in fish we investigated whether cortisol (F) had similar effects on ZP regulation. In the present study we determined both the natural variation in Vtg and ZP during an annual reproductive cycle in female Arctic char (Salvelinus alpinus), and the effect of co-treatment of juvenile Arctic char with 17beta-estradiol (E2) and F. During sexual maturation the expression of Vtg and ZP correlated to plasma levels of E2 and F. Determination of Vtg and ZP protein levels following co-treatment with E2 and F showed that F antagonized E2 induction of Vtg. However, F was observed to potentiate the expression of ZP protein in the same fish. These results indicate that in Arctic char Vtg and ZP proteins are not regulated by the same mechanisms and suggest that ZP protein expression does not necessarily imply exposure to estrogenic compounds alone, and may thus not be ideally suited as a biomarker of exposure to estrogenic compounds. (C) 2003 Elsevier Inc. All rights reserved. C1 Umea Univ, Dept Biol Mol, SE-90187 Umea, Sweden. NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Univ Orebro, Dept Nat Sci, Unit Mol Biol, SE-70182 Orebro, Sweden. RP Olsson, PE (reprint author), Umea Univ, Dept Biol Mol, SE-90187 Umea, Sweden. EM per-erik.olsson@nat.oru.se OI Olsson, Per-Erik/0000-0001-7336-6335; Vesterlund, Liselotte/0000-0003-3547-9288 NR 63 TC 37 Z9 41 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD FEB PY 2004 VL 135 IS 3 BP 276 EP 285 DI 10.1016/j.ygcen.2003.10.004 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 764QG UT WOS:000188217100003 PM 14723879 ER PT J AU Nupponen, NN Wallen, MJ Ponciano, D Robbins, CM Tammela, TLJ Vessellas, RL Carpten, JD Visakorpi, T AF Nupponen, NN Wallen, MJ Ponciano, D Robbins, CM Tammela, TLJ Vessellas, RL Carpten, JD Visakorpi, T TI Mutational analysis of susceptibility genes RNASEL/HPC1, ELAC2/HPC2, and MSRI in sporadic prostate cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID SCAVENGER RECEPTOR-1 GENE; GERMLINE MUTATIONS; SEQUENCE VARIANTS; CHROMOSOME; HPC2/ELAC2; LOCUS; FAMILIES; ASSOCIATION; EXPRESSION; HEREDITARY AB Three putative prostate cancer-susceptibility genes, RNASEL/HPCI at 1q24, MSRI at 8p22, and ELAC2/HPC2 at 17p11, have recently been identified. Our objective was to investigate somatic mutations in these genes in sporadic prostate cancer. We analyzed 39 clinical prostate cancer specimens, 10 prostate cancer xenografts (LuCaP series), and 4 prostate cancer cell lines (LNCaP, DU145, PC-3, and MPC-3) for genetic changes using denaturing high-performance liquid chromatography and direct sequencing in order to screen the whole coding regions of RNASEL and MSRI , as well as exons 7 and 17 of ELAC2. The known 471delAAAG truncating mutation was found in the RNASEL gene in cell line LNCaP. The only new missense variation in RNASEL, Gly296Val, was found in cell line DU145, but not in any other samples. RNASEL and ELAC2 also showed the common missense polymorphic changes. A previously reported truncating mutation (Arg293X) was found in MSRI in the germ line of one individual. Our results indicate that inactivation of the RNASEL, ELAC2, or MSRI genes by somatic mutation is a rare phenomenon in sporadic prostate cancer. (C) 2003 Wiley-Liss, Inc. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Univ Helsinki, Biomedicum, Dept Med Genet, FIN-00014 Helsinki, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Tampere, Dept Urol, FIN-33014 Tampere, Finland. Univ Washington, Dept Urol, Seattle, WA 98195 USA. RP Visakorpi, T (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. NR 32 TC 18 Z9 19 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD FEB PY 2004 VL 39 IS 2 BP 119 EP 125 DI 10.1002/gcc.10308 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 760TT UT WOS:000187851500003 PM 14695991 ER PT J AU Morris, RW Kaplan, NL AF Morris, RW Kaplan, NL TI Testing for association with a case-parents design in the presence of genotyping errors SO GENETIC EPIDEMIOLOGY LA English DT Article DE SNP; EM algorithm; likelihood ratio test; haplotype ID TRANSMISSION/DISEQUILIBRIUM TEST; MARKERS; TRIADS AB Genotyping errors can create a problem for the analysis of case-parents data because some families will exhibit genotypes that are inconsistent with Mendelian inheritance. The problem with correcting Mendelian inconsistent genotype errors by regenotyping or removing families in which they occur is that the remaining unidentified genotype errors can produce excess type I (false positive) error for some family-based tests for association. We address this problem by developing a likelihood ratio test (LRT) for association in a case-parents design that incorporates nuisance parameters for a general genotype error model. We extend the likelihood approach for a single SNP to include short haplotypes consisting of 2 or 3 SNPs. The extension to haplotypes is based on assumptions of random mating, multiplicative penetrances, and at most a single genotype error per family. For a single SNP, we found, using Monte Carlo simulation, that type I error rate can be controlled for a number of genotype error models at different error rates. Simulation results suggest the same is true for 2 and 3 SNPs. In all cases, power declined with increasing genotyping error rates. In the absence of genotyping errors, power was similar whether nuisance parameters for genotype error were included in the LRT or not. The LRT developed here does not require prior specification of a particular model for genotype errors and it can be readily computed using the EM algorithm. Consequently, this test may be generally useful as a test of association with case-parents data in which Mendelian inconsistent families are observed. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Morris, RW (reprint author), Duke Univ, Med Ctr, Dept Anesthesiol, 279 Hanes House, Durham, NC 27710 USA. EM richard.morris@duke.edu NR 17 TC 22 Z9 22 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD FEB PY 2004 VL 26 IS 2 BP 142 EP 154 DI 10.1002/gepi.10297 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 769JW UT WOS:000188647800008 PM 14748014 ER PT J AU Cherry, JL AF Cherry, JL TI Selection, subdivision and extinction and recolonization SO GENETICS LA English DT Article ID LOCAL EXTINCTION; CHROMOSOMAL REARRANGEMENTS; FIXATION PROBABILITY; POPULATION; DRIFT; COLONIZATION; DOMINANCE; FREQUENT; SIZE; GENE AB In a subdivided population, the interaction between natural selection and stochastic change in allele frequency is affected by the occurrence of local extinction and subsequent recolonization. The relative importance of selection can be diminished by this additional source of stochastic change in allele frequency. Results are presented for subdivided populations with extinction and recolonization where there is more than one founding allele after extinction, where these may tend to come from the same source deme, where the number of founding alleles is variable or the founders make unequal contributions, and where there is dominance for fitness or local frequency dependence. The behavior of a selected allele in a subdivided population is in all these situations approximately the same as that of an allele with different selection parameters in an unstructured population with a different size. The magnitude of the quantity N(e)s(e), which determines fixation probability in the case of genic selection, is always decreased by extinction and recolonization, so that deleterious alleles are more likely to fix and advantageous alleles less likely to do so. The importance of dominance or frequency dependence is also altered by extinction and recolonization. Computer simulations confirm that the theoretical predictions of both fixation probabilities and mean times to fixation are good approximations. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Cherry, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr, Bethesda, MD 20894 USA. EM jcherry@ncbi.nlm.nih.gov NR 19 TC 12 Z9 12 U1 0 U2 8 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD FEB PY 2004 VL 166 IS 2 BP 1105 EP 1114 DI 10.1534/genetics.166.2.1105 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 805UG UT WOS:000220390600038 PM 15020490 ER PT J AU Mitreva, M McCarter, JP Martin, J Dante, M Wylie, T Chiapelli, B Pape, D Clifton, SW Nutman, TB Waterston, RH AF Mitreva, M McCarter, JP Martin, J Dante, M Wylie, T Chiapelli, B Pape, D Clifton, SW Nutman, TB Waterston, RH TI Comparative genomics of gene expression in the parasitic and free-living nematodes Strongyloides stercoralis and Caenorhabditis elegans SO GENOME RESEARCH LA English DT Article ID DAUER LARVA DEVELOPMENT; DOUBLE-STRANDED-RNA; C-ELEGANS; SEQUENCE TAGS; MELOIDOGYNE-INCOGNITA; MICROFILARIAL SHEATH; FILARIAL PARASITES; NECATOR-AMERICANUS; BRUGIA-MALAYI; PROTEIN AB Although developmental timing of gene expression is used to infer potential gene function, Studies have yet to correlate this information between species. We analyzed 10,921 ESTs in 3311 clusters from first- and infective third-stage larva (L1, L3i) of the parasitic nematode Strongyloides stercoralis and compared the results to Caenorhabditis elegans, a species that has an L3i-like dauer stage. In the comparison of S. stercoralis clusters with stage-specific expression to C elegans homologs expressed in either dauer or nondauer stages, matches between S. stercoralis L1 and C elegans nondauer-expressed genes dominated, suggesting conservation in the repertoire of genes expressed during growth in nutrient-rich conditions. For example, S. stercoralis collagen transcripts were abundant in L1 but not L3i, a pattern consistent with C elegans collagens. Although a greater proportion of S. stercoralis L3i than L1 genes have homologs among the C elegans dauer-specific transcripts, we did not uncover evidence of a robust conserved L3i/dauer 'expression signature.' Strikingly, in comparisons of S. stercoralis clusters to C elegans homologs with RNAi knockouts, those with significant L1-specific expression were more than twice as likely as L3i-specific clusters to match genes with phenotypes. We also provide functional classifications of S. stercoralis clusters. C1 Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. Divergence Inc, St Louis, MO 63141 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. EM mmitreva@watson.wustl.edu FU NIAID NIH HHS [AI46593, U01 AI046593] NR 90 TC 74 Z9 79 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 EI 1549-5469 J9 GENOME RES JI Genome Res. PD FEB PY 2004 VL 14 IS 2 BP 209 EP 220 DI 10.1101/gr.1524804 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 771XR UT WOS:000188811800002 PM 14762059 ER PT J AU Leem, SH Kouprina, N Grimwood, J Kim, JH Mullokandov, M Yoon, YH Chae, JY Morgan, J Lucas, S Richardson, P Detter, C Glavina, T Rubin, E Barrett, JC Larionov, V AF Leem, SH Kouprina, N Grimwood, J Kim, JH Mullokandov, M Yoon, YH Chae, JY Morgan, J Lucas, S Richardson, P Detter, C Glavina, T Rubin, E Barrett, JC Larionov, V TI Closing the gaps on human chromosome 19 revealed genes with a high density of repetitive tandemly arrayed elements SO GENOME RESEARCH LA English DT Article ID TRANSFORMATION-ASSOCIATED RECOMBINATION; COMPLEX GENOMES; SEQUENCE; CLONING; YEAST; DNA; REPEATS; ORGANIZATION; CHROMOSOME-2; REGION AB The reported human genome sequence includes about 400 gaps of unknown sequence that were not found in the bacterial artificial chromosome (BAC) and cosmid libraries used for sequencing of the genome. These missing sequences correspond to similar to1% of euchromatic regions of the human genome. Gap filling is a laborious process because it relies on analysis of random clones of numerous genomic BAC or cosmid libraries. In this work we demonstrate that closing the gaps can be accelerated by a selective recombinational capture of missing chromosomal segments in yeast. The use of both methodologies allowed us to close the four remaining gaps on the human chromosome 19. Analysis of the gap sequences revealed that they contain several abnormalities that could result in instability of the sequences in microbe hosts, including large blocks of micro- and minisatellites and a high density of Alu repeats. Sequencing of the gap regions, in both BAC and YAC forms, allowed us to generate a complete sequence of four genes, including the neuronal cell signaling gene SCK1/SLI The SCK1/SLI gene contains a record number of minisatellites, most of which are polymorphic and transmitted through meiosis following a Mendelian inheritance. In conclusion, the use of the alternative recombinational cloning system in yeast may greatly accelerate work on closing the remaining gaps in the human genome (as well as in other complex genomes) to achieve the goal of annotation of all human genes. C1 NCI, Lab Biosyst & Canc, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Dong A Univ, Dept Biol, Pusan 604714, South Korea. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA. RP Larionov, V (reprint author), NCI, Lab Biosyst & Canc, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM larionov@mail.nih.gov NR 27 TC 29 Z9 32 U1 2 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2004 VL 14 IS 2 BP 239 EP 246 DI 10.1101/gr.1929904 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 771XR UT WOS:000188811800005 PM 14718380 ER PT J AU Veeramachaneni, V Makalowski, W Galdzicki, M Sood, R Makalowska, I AF Veeramachaneni, V Makalowski, W Galdzicki, M Sood, R Makalowska, I TI Mammalian overlapping genes: The comparative perspective SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; ANTISENSE TRANSCRIPTS; DNA STRANDS; SEQUENCE; ANNOTATION; REGION; LOCUS AB It is believed that 3.2 billion bp of the human genome harbor similar to35,000 protein-coding genes. On average, one could expect one gene per 300,000 nucleotides (nt). Although the distribution of the genes in the human genome is not random, it is rather surprising that a large number of genes overlap in the mammalian genomes. Thousands of overlapping genes were recently identified in the human and mouse genomes. However, the origin and evolution of overlapping genes are still unknown. We identified 1316 pairs of overlapping genes in humans and mice and studied their evolutionary patterns. It appears that these genes do not demonstrate greater than usual conservation. Studies of the gene structure and overlap pattern showed that only a small fraction of analyzed genes preserved exactly the same pattern in both organisms. C1 Penn State Univ, Dept Biol, State Coll, University Pk, PA 16802 USA. Penn State Univ, Inst Mol Evolutionary Genet, State Coll, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, State Coll, University Pk, PA 16802 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Makalowska, I (reprint author), Penn State Univ, Dept Biol, State Coll, University Pk, PA 16802 USA. EM izabelam@psu.edu RI Galdzicki, Michal/F-5682-2010; Makalowski, Wojciech/I-2843-2016 OI Galdzicki, Michal/0000-0002-8392-8183; NR 25 TC 80 Z9 87 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD FEB PY 2004 VL 14 IS 2 BP 280 EP 286 DI 10.1101/gr.1590904 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 771XR UT WOS:000188811800009 PM 14762064 ER PT J AU Lee, SK Kim, YS Lee, SS Lee, YJ Song, IS Park, SC Kozak, CA Yamada, Y AF Lee, SK Kim, YS Lee, SS Lee, YJ Song, IS Park, SC Kozak, CA Yamada, Y TI Molecular cloning, chromosomal mapping, and characteristic expression in tooth organ of rat and mouse Krox-25 SO GENOMICS LA English DT Article DE Krox-25; rat; mouse; tooth; in situ hybridization; immunohistochemistry ID FINGER TRANSCRIPTION FACTOR; ENAMEL MATRIX; CDNA; AMELOBLASTIN; DIFFERENTIATION; INCISORS; GENES; LOCALIZATION; SEQUENCES; PROTEINS AB A novel member of the Krox family of proteins, designated Krox-25, was identified by screening clones from the cDNA libraries of a rat incisor and mouse embryo cramofacial tissue. Rat and mouse Krox-25 mRNAs are about 2.4 kb long, encoding 225 and 224 amino acids, respectively. Krox-25 consists of five zinc finger motifs homologous to the Drosophila Kruppel segmentation gene and also contains several consensus amino acid sequences for a protein kinase C binding domain. Northern blot analysis revealed an intense expression of Krox-25 mRNA in rat and mouse teeth, although it was expressed weakly in other tissues, including calvaria, brain, lung, thymus, kidney, and submandibular gland of mouse. In situ hybridization showed that Krox-25 mRNA began to be expressed weakly in the early odontogenic mesenchyme and primitive enamel epithelium located at the apical end of the rat incisor, and Krox-25 expression increased in the presecretory ameloblasts and became intense in the secretory ameloblasts. This expression was also similar to the results of immunohistochemistry and Western blot, especially the Krox-25 localization in the nuclei of enamel epithelial cells. These results suggest that Krox-25 plays an important role as a transcription factor for the cytodifferentiation and amelogenesis of enamel epithelium. (C) 2003 Elsevier Inc. All rights reserved. C1 Kangnung Natl Univ, Coll Dent, Dept Oral Pathol, Kangnung 210702, South Korea. Seoul Natl Univ, Coll Med, Dept Biochem, Seoul 110799, South Korea. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIDCR, Mol Biol Sect, CDBRB, NIH, Bethesda, MD 20892 USA. RP Lee, SK (reprint author), Kangnung Natl Univ, Coll Dent, Dept Oral Pathol, Kangnung 210702, South Korea. EM sklee@kangnung.ac.kr NR 38 TC 3 Z9 5 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 FEB PY 2004 VL 83 IS 2 BP 243 EP 253 DI 10.1016/j.ygeno.2003.08.006 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 764MV UT WOS:000188211400006 PM 14706453 ER PT J AU Danis, M Biddle, AK Goold, SD AF Danis, M Biddle, AK Goold, SD TI Enrollees choose priorities for Medicare SO GERONTOLOGIST LA English DT Article DE Medicare; patient participation; insurance benefits; health priorities ID CARE; SERVICES; BENEFIT AB Purpose: The purpose of this study was to demonstrate the feasibility and results of ascertaining Medicare enrollees' priorities for insured medical benefits. Design and Methods: Structured group exercises were conducted with Medicare enrollees from clinical and community settings in central North Carolina. By participating in a decision exercise, CHAT: Choosing Healthplans All Together, individuals and groups chose medical benefits within the constraints of a monthly Medicare + Choice premium. The acceptability of the exercise and the resulting benefit package were assessed. Results: Ten groups (121 individuals) made trade-offs that involved the selection of more tightly managed care in order to add pharmacy, dental, and long-term care benefits. All were willing to forgo experimental therapy; 7 groups gave priority to insuring the uninsured. Participants found the exercise overwhelmingly acceptable and were willing to abide by their groups' choices. Implications: Medicare enrollees are able to come to consensus about financially constrained benefit packages that may be useful in reform of the Medicare program. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Hlth Policy & Adm, Chapel Hill, NC 27515 USA. Univ Michigan, Sch Med, Bioeth Program, Ann Arbor, MI 48109 USA. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM mdanis@nih.gov OI Biddle, Andrea/0000-0003-0273-7439; Goold, Susan Dorr/0000-0002-0258-9774 NR 25 TC 12 Z9 12 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2004 VL 44 IS 1 BP 58 EP 67 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 777EZ UT WOS:000189164000007 PM 14978321 ER PT J AU Farley, J Uyehara, C Hashiro, G Belnap, C Birrer, M Salminen, E AF Farley, J Uyehara, C Hashiro, G Belnap, C Birrer, M Salminen, E TI Cyclooxygenase-2 expression predicts recurrence of cervical dysplasia following loop electrosurgical excision procedure SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cyclooxygenase-2; LEEP; cervical dysplasia ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; LYMPH-NODE METASTASIS; HUMAN BREAST-CANCER; HUMAN-PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; P27(KIP1) EXPRESSION; TRANSFORMATION ZONE; KINASE INHIBITOR; NATURAL-HISTORY AB Objective. To evaluate the expression of Cox-2 protein by immunohistochemistry in cervical dysplasias, and to determine any relationship to clinical factors such as degree or recurrence of dysplasia. Methods. Immunohistochemical expression of p27 and Cox-2 was initially examined in 62 cervical LEEP specimens, which spanned the histologic spectrum from benign to severe dysplasia. Histology and cytology from colposcopic follow-up exams were reviewed for I year after LEEP procedure. Primary outcome variable was recurrent dysplasia, either cytologic or histologic. Statistical analysis utilizing chi-square test for trend and Fisher's Exact tests were performed to determine relative risk of recurrent dysplasia. Results. A total of 62 LEEP specimens were examined by immunohistochemistry (IHC). This included 18 mild, 19 moderate, and 25 severely dysplastic LEEP specimens. The percentage of tumor cells in each specimen that stained for p27 protein or Cox-2 enzyme was documented. A specimen was considered positive for p27 or Cox-2 if 50% or more of the cells in a specimen were stained: 94% of mild, 89% of moderate, and 44% of severe dysplasias stained positive for p27; 50% of mild, 42% of moderate, and 68% of severe dysplasia specimens stained positive for Cox-2. The average intensity of Cox-2 staining increased with severity of dysplasia-1.6 for mild, 1.8 for moderate, and 2.1 for severe dysplasia. There was a significant increase in both Cox-2 and p27 staining when severely dysplastic specimens were compared to mild and moderate dysplasia (P < 0.001). Of the 35 specimens that stained positive for Cox-2 protein, 59% of these specimens had positive Cox-2 staining that extended to the margins of the LEEP resection specimen. The average length of Cox-2 protein staining beyond the histologic dysplasia was 1.64 min. Positive margin status for Cox-2 was a significant independent risk factor for persistent and recurrent dysplasia, RR 1.68 95% CI (1.07 < RR < 2.65), P < 0.027. Conclusion. Cox-2 and p27 protein expression could be involved in squamous cervical cancer carcinogenesis. Cox-2 staining is often found outside the dysplastic lesion and this factor is associated with an increased risk of persistent and recurrent dysplasia following LEEP procedure. Should the histologic margin of LEEP resection approach 2.0 mm, follow-up algorithms for these patients should include intensive surveillance to ensure adequate treatment of disease. Published by Elsevier Inc. C1 Tripler Army Med Ctr, Dept Obstet & Gynecol, Honolulu, HI 96859 USA. Tripler Army Med Ctr, Dept Clin Invest, Honolulu, HI 96859 USA. Tripler Army Med Ctr, Dept Pathol, Honolulu, HI 96859 USA. NCI, Cell & Canc Biol Dept, Med Branch, Div Clin Sci, Rockville, MD 20850 USA. RP Farley, J (reprint author), Tripler Army Med Ctr, Dept Obstet & Gynecol, 1 Jarrett White Rd, Honolulu, HI 96859 USA. EM john.farley@amedd.army.mil NR 47 TC 20 Z9 29 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2004 VL 92 IS 2 BP 596 EP 602 DI 10.1016/j.ygyno.2003.10.052 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 779DX UT WOS:000189281100014 PM 14766253 ER PT J AU Li, SF Miner, K Fannin, R Barrett, JC Davis, BJ AF Li, SF Miner, K Fannin, R Barrett, JC Davis, BJ TI Cyclooxygenase-1 and 2 in normal and malignant human ovarian epithelium SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cyclooxygenase; epithelium; malignant ID GENE-EXPRESSION; BREAST-CANCER; COX-2; ADENOCARCINOMAS; RECEPTOR; MICE AB Objectives. Cyclooxygenase-1 and 2 (COX-1 and COX-2) play important roles in normal physiology and are often dysregulated in neoplastic tissues. The present study determines whether COX-1 and COX-2 are expressed in ovarian cancers and whether the pattern of expression of these enzymes reveals clues to their roles in this cancer. Methods. The expression of COX-1 and COX-2 proteins in 9 normal human ovaries, in 137 cases of ovarian cancers of epithelial origin (83 primary and 54 metastatic), and in 7 ovarian cancer cell lines was examined by immunohistochemistry and western analysis. Results. COX-1 protein was present in 95/137 (69.3%) of the total cancers studied, with 55/83 (66.3%) of the primary cancers and 40/54 (74.1%) of the metastatic cancers positive for protein. COX-2 was present in 97/137 (70.8%) of all cancers studied, with 53/83 (63.9%) of the primary cancers and 44/54 (81.5%) of the metastatic cancers positive for protein. Notably, the quickscores for COX-2-positive staining were significantly higher in metastatic cancers. Moreover, COX-2 immunostaining was frequently found at the advancing margin of tumor invasion or in new metastatic loci. COX-1 protein expression was observed in the ovarian surface epithelial cells, especially that of the inclusion cysts. COX-1 was also detected by western blot in seven of nine ovarian cancer cell lines. However, no COX-2 was detected in either normal epithelium or cancer cell lines. Conclusion. COX-1 and COX-2 were expressed in every type of ovarian epithelial cancer, suggesting that each may contribute to the cancer development or progression. Published by Elsevier Inc. C1 NIEHS, Lab Womens Hlth, Res Triangle Pk, NC 27709 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Davis, BJ (reprint author), NIEHS, Lab Womens Hlth, POB 12233, Res Triangle Pk, NC 27709 USA. EM davis1@niehs.nih.gov NR 17 TC 47 Z9 60 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 2004 VL 92 IS 2 BP 622 EP 627 DI 10.1016/j.ygyno.2003.10.053 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 779DX UT WOS:000189281100017 PM 14766256 ER PT J AU Lehrnbecher, T Fleischhock, G Hanisch, F Deinlein, F Simon, A Bernig, T Chanock, SJ Klingebiel, T AF Lehrnbecher, T Fleischhock, G Hanisch, F Deinlein, F Simon, A Bernig, T Chanock, SJ Klingebiel, T TI Circulating levels and promoter polymorphisms of interleukins-6 and 8 in pediatric cancer patients with fever and neutropenia SO HAEMATOLOGICA LA English DT Letter DE children; febrile neutropenia; chemotherapy; interleukin; polymorphisms ID C-REACTIVE PROTEIN; VIRUS; SERUM; RISK C1 Univ Frankfurt, Dept Pediat Hematol, D-6000 Frankfurt, Germany. Univ Frankfurt, Dept Oncol, D-6000 Frankfurt, Germany. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Lehrnbecher, T (reprint author), Univ Frankfurt, Childrens Hosp 3, Dept Pediat Hematol & Oncol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM thomas_lehrnbecher@yahoo.com NR 10 TC 13 Z9 13 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD FEB PY 2004 VL 89 IS 2 BP 234 EP 236 PG 3 WC Hematology SC Hematology GA 775KT UT WOS:000189040000015 PM 15003900 ER PT J AU Young, WB Oshinsky, ML Shechter, AL Gebeline-Myers, C Bradley, KC Wassermann, EM AF Young, WB Oshinsky, ML Shechter, AL Gebeline-Myers, C Bradley, KC Wassermann, EM TI Consecutive Transcranial magnetic stimulation: Phosphene thresholds in migraineurs and controls SO HEADACHE LA English DT Article DE migraine; transcranial magnetic stimulation; phosphene; aura; hyperexcitability ID OCCIPITAL CORTEX; HYPEREXCITABILITY; EXCITABILITY; POTENTIALS; CORTICES; MOTOR AB Objective.-To characterize the temporal course of transcranial magnetic stimulation-induced phosphene thresholds in subjects with migraine and in controls. Methods.-Eleven subjects with migraine with aura, 10 subjects with migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no history of migraine and without migraine during the study) were studied. Subjects were not on preventive medication. Transcranial magnetic stimulation was performed, and a phosphene threshold was measured 3 times a week over 3 weeks in a manner timed to incorporate the menstrual period in females. A headache calendar was kept during the study. Results.-Mean transcranial magnetic stimulation thresholds were lower for each migraine group compared with controls (P < .001) for each comparison. There was a trend for lower thresholds among subjects with migraine with aura compared with subjects with migraine without aura (P < .10), but not subjects with menstrual migraine. There was consistent lowering of thresholds from the first to the last stimulation in all migraine groups and in the controls. Maximum and minimum thresholds did not predict headache occurrence, nor did the occurrence of headache predict an ensuing maximum or minimum phosphene threshold. Conclusions.-Transcranial magnetic stimulation thresholds are lower in subjects with migraine compared with controls. The reported phosphene threshold is lowered with repeated measurement. Neither high nor low phosphene thresholds predict a subsequent headache, nor do migraines predict a subsequent high or low threshold. C1 Thomas Jefferson Univ Hosp, Dept Neurol, Jefferson Headache Ctr, Philadelphia, PA 19107 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA. RP Young, WB (reprint author), Thomas Jefferson Univ Hosp, Dept Neurol, Jefferson Headache Ctr, Gibbon Bldg,Suite 8130,111 S 11th St, Philadelphia, PA 19107 USA. NR 15 TC 37 Z9 37 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-8748 J9 HEADACHE JI Headache PD FEB PY 2004 VL 44 IS 2 BP 131 EP 135 DI 10.1111/j.1526-4610.2004.04028.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 775ER UT WOS:000189028200003 PM 14756850 ER PT J AU Simons-Morton, BG Hartos, JL Haynie, DL AF Simons-Morton, BG Hartos, JL Haynie, DL TI Prospective analysis of peer and parent influences on minor aggression among early adolescents SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE aggression; youth; early adolescents; school; parenting behavior; peer influences ID MIDDLE SCHOOL STUDENTS; FIGHTING BEHAVIOR; VIOLENCE; YOUTH; DELINQUENCY; MEDIATORS; FAMILY; RISK AB The research examined the influence of parent and school variables on minor aggression among early adolescents. Sixth-grade students (N = 1,081) were interviewed at the beginning of the school year (Time 1) about aggressive behaviors and selected psychosocial variables and at the end of the year (Time 2) about aggressive behaviors. Aggression increased over time and was greater for boys than girls at both time points. In path analyses, Time 1 aggression was directly associated with Time 2 aggression and indirectly associated through affiliation with Time 2 problem-behaving friends. School engagement was associated indirectly with Time 2 aggression through affiliation with problem-behaving friends. Parenting behavior was negatively and directly associated with Time 2 aggression and indirectly through Time 2 affiliation with problem-behaving friends. The findings indicated that selection and previous behavior predicted peer affiliation and parenting and school engagement protected against early adolescent aggression. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, BG (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B13, Bethesda, MD 20892 USA. EM bruce_simons-morton@nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 FU NICHD NIH HHS [N01-HD-4-3207] NR 32 TC 20 Z9 20 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2004 VL 31 IS 1 BP 22 EP 33 DI 10.1177/1090198103258850 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 764ND UT WOS:000188212200002 PM 14768655 ER PT J AU Wang, YL Cui, F Lv, XX Li, CL Xu, XL Deng, CX Wang, DP Sun, YS Hu, GX Lang, ZW Huang, CF Yang, X AF Wang, YL Cui, F Lv, XX Li, CL Xu, XL Deng, CX Wang, DP Sun, YS Hu, GX Lang, ZW Huang, CF Yang, X TI HBs4g and HBx knocked into the p21 locus causes hepatocellular carcinoma in mice SO HEPATOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-BETA; TRANSGENIC MICE; X-PROTEIN; MESSENGER-RNAS; EXPRESSION; LIVER; PATHOGENESIS; TUMOR; PHOSPHORYLATION; PROLIFERATION AB Hepatocellular carcinoma (HCC) affects males in a significantly higher proportion than females and is one of the human cancers etiologically related to viral factors. Many studies provide strong evidence of the direct role that hepatitis B virus (HBV) plays in hepatic carcinogenesis, but the functions of HBV surface antigen (HBsAg) and X protein (HBx) in hepatocarcinogenesis through direct or indirect mechanisms are still being debated. We generated two HBV gene knock-in transgenic mouse lines by homologous recombination. HBsAg and HBx genes were integrated into the mouse p21 locus. Both male and female p21-HBx transgenic mice developed HCC after the age of 18 months; however, male p21-HBsAg transgenic mice began to develop HCC 3 months earlier. The expression of a number of genes related to metabolism and genomic instability largely resembled the molecular changes during the development of HCC in humans. ER-beta (estrogen receptor-beta) was extremely up-regulated only in tumor tissues of male p21-HBsAg mice, providing genetic evidence that HBsAg might be the major risk factor affecting the gender difference in the causes of HCC. In conclusion, these mice might serve as good models for studying the different roles of HBsAg and HBx in early events of HBV-related hepatocarcinogenesis. C1 Inst Biotechnol, Genet Lab Dev & Dis, Beijing 100071, Peoples R China. NIDDKD, Bethesda, MD 20892 USA. Inst Jingfeng Med Lab Anim, Beijing, Peoples R China. Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China. You An Hosp, Beijing, Peoples R China. RP Yang, X (reprint author), Inst Biotechnol, Genet Lab Dev & Dis, 20 Donggajie, Beijing 100071, Peoples R China. EM yangx@nic.bmi.ac.cn RI deng, chuxia/N-6713-2016 NR 32 TC 86 Z9 103 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2004 VL 39 IS 2 BP 318 EP 324 DI 10.1002/hep.20076 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805OM UT WOS:000220375600010 PM 14767984 ER PT J AU Sanchez, A Factor, VM Schroeder, IS Nagy, P Thorgeirsson, SS AF Sanchez, A Factor, VM Schroeder, IS Nagy, P Thorgeirsson, SS TI Activation of NF-kappa B and STAT3 in rat oval cells during 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration SO HEPATOLOGY LA English DT Article ID INDUCED HEPATOCELLULAR-CARCINOMA; STEM-CELLS; GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; CHEMICAL CARCINOGENS; EMBRYONIC LETHALITY; TRANSGENIC MICE; DEFICIENT MICE; KNOCKOUT MICE; ALLYL ALCOHOL AB Proliferation and differentiation of hepatic stem cell progenies (i.e., oval cells) sustain liver regeneration when the replicative and functional capacity of hepatocytes is impaired. The signaling pathways that control stem cell activation remain poorly understood. In this study, we investigated the involvement of nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) in oval cell-mediated liver regeneration induced by 2-acetylaminofluorene/partial hepatectomy (AAF/PH) protocol. Using OV1 as a marker for identification and sorting of oval cells, we established that both NF-kappaB and STAT3 were highly activated in the OV1(+) cell population. Three distinct subpopulations of oval cells were defined as OV1(low), OV1(medium), and OV1(high), based on the intensity of OV1 staining. Quantitative polymerase chain reaction analysis revealed that they represent different stages of oval cell differentiation along hepatocyte lineage. OV1(low) cells displayed the least differentiated phenotype as judged by high expression of c-kit and lack of hepatocytic differentiation markers, whereas OV1(high) cells lost c-kit expression, were more proliferative, and acquired more mature hepatocytic phenotype. Notably, NF-kappaB was activated uniformly in all three subpopulations of oval cells. In contrast, phosphorylation of STAT3 was detected only in OV1(high) cells. In conclusion, transcriptional activity supported by NF-kappaB and STAT3 is required for oval cell activation, expansion, and differentiation. The differential induction of NF-kappaB and STAT3 point to a distinct role for these transcription factors at different stages of hepatic stem cell differentiation. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Inst Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. RP 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 RI Sanchez, Aranzazu/H-7810-2015 OI Sanchez, Aranzazu/0000-0001-9145-6633 NR 50 TC 36 Z9 41 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 2004 VL 39 IS 2 BP 376 EP 385 DI 10.1002/hep.20040 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805OM UT WOS:000220375600016 PM 14767990 ER PT J AU Kim, JW Ye, QH Forgues, M Chen, YD Budhu, A Sime, J Hofseth, LJ Kaul, R Wang, XW AF Kim, JW Ye, QH Forgues, M Chen, YD Budhu, A Sime, J Hofseth, LJ Kaul, R Wang, XW TI Cancer-associated molecular signature in the tissue samples of patients with cirrhosis SO HEPATOLOGY LA English DT Article ID HUMAN HEPATOCELLULAR CARCINOMAS; GENE-EXPRESSION; EP-CAM; RISK-FACTORS; HUMAN LIVER; CARCINOGENESIS; IDENTIFICATION; PATHOGENESIS; MICROARRAY; DIVERSITY AB Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P < .001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P < .001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. Univ Minnesota, Div Pediat Gastroenterol & Nutr, Minneapolis, MN USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov.fax RI Wang, Xin/B-6162-2009 NR 36 TC 75 Z9 76 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2004 VL 39 IS 2 BP 518 EP 527 DI 10.1002/hep.20053 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805OM UT WOS:000220375600032 PM 14768006 ER PT J AU Collins-Schramm, HE Chima, B Morii, T Wah, K Figueroa, Y Criswell, LA Hanson, RL Knowler, WC Silva, G Belmont, JW Seldin, MF AF Collins-Schramm, HE Chima, B Morii, T Wah, K Figueroa, Y Criswell, LA Hanson, RL Knowler, WC Silva, G Belmont, JW Seldin, MF TI Mexican American ancestry-informative markers: Examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians SO HUMAN GENETICS LA English DT Article ID ADMIXTURE LINKAGE DISEQUILIBRIUM; ADMIXED POPULATIONS; GALLBLADDER-DISEASE; FREQUENCIES; PROPORTIONS AB Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with EA and Pima allele frequencies. Markers with large allele frequency differences between EA and one Amerindian tribe showed only small differences between the Amerindian tribes. Examination of structure in individuals demonstrated a clear separation of subjects of European from those of Amerindian ancestry, and similarity between individuals from disparate Amerindian populations. The AIMs demonstrated the variation in ancestral composition of individual Mexican Americans, providing evidence of applicability in admixture mapping and in controlling for structure in association tests. In addition, a high percentage of single-nucleotide polymorphisms (SNPs) selected on the basis of large frequency differences between EA and Asian populations had large allele frequency differences between EA and Amerindians, suggesting an efficient method for greatly expanding AIMs for use in admixture mapping/structure analysis in Mexican Americans. Together, these data provide additional support for the practical application of admixture mapping in the Mexican American population. C1 Univ Calif Davis, Dept Biol Chem, Rowe Program Human Genet, Davis, CA 95616 USA. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. Univ Calif San Francisco, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94143 USA. NIDDKD, NIH, Phoenix, AZ 85014 USA. Obras Sociales Hermano Pedro, Antigua, Guatemala. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Seldin, MF (reprint author), Univ Calif Davis, Dept Biol Chem, Rowe Program Human Genet, 1 Shields Ave, Davis, CA 95616 USA. EM mfseldin@ucdavis.edu RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Belmont, John/0000-0001-7409-3578 FU NICHD NIH HHS [R01-HD39056]; NIDDK NIH HHS [U01-DK57249] NR 29 TC 81 Z9 85 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2004 VL 114 IS 3 BP 263 EP 271 DI 10.1007/s00439-003-1058-6 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 766PN UT WOS:000188384900006 PM 14628215 ER PT J AU Kaminska, A Strelkov, SV Goudeau, B Olive, M Dagvadorj, A Fidzianska, A Simon-Casteras, M Shatunov, A Dalakas, MC Ferrer, I Kwiecinski, H Vicart, P Goldfarb, LG AF Kaminska, A Strelkov, SV Goudeau, B Olive, M Dagvadorj, A Fidzianska, A Simon-Casteras, M Shatunov, A Dalakas, MC Ferrer, I Kwiecinski, H Vicart, P Goldfarb, LG TI Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy SO HUMAN GENETICS LA English DT Article ID DOMINANT DISTAL MYOPATHY; HELICAL COILED COILS; INTERMEDIATE-FILAMENTS; MISSENSE MUTATION; CARDIOMYOPATHY; DISEASE; GENE AB Desmin (DES) mutations have been recognized as a cause of desmin-related myopathy (OMIM 601419), or desminopathy, a disease characterized by progressive limb muscle weakness and accumulation of desmin-reactive granular aggregates in the myofibers. We have studied three families with skeletal or cardioskeletal myopathy caused by small in-frame deletions in the desmin gene. The newly identified in-frame deletions E359_S361del and N366del alter the heptad periodicity within a critical 2B coiled-coil segment. Structural analysis reveals that the E359_S361 deletion introduces a second stutter immediately downstream of the naturally occurring stutter, thus doubling the extent of the local coiled-coil unwinding. The N366del mutation converts the wild-type stutter into a different type of discontinuity, a stammer. A stammer, as opposed to a stutter, is expected to cause an extra overwinding of the coiled-coil. These mutations alter the coiled-coil geometry in specific ways leading to fatal damage to desmin filament assembly. Expression studies in two cell lines confirm the inability of desmin molecules with this changed architecture to polymerize into a functional filamentous network. This study provides insights into molecular pathogenetic mechanisms of desmin mutation-associated skeletal and cardioskeletal myopathy. C1 NINDS, NIH, Bethesda, MD 20892 USA. Polish Acad Sci, Med Res Ctr, Neuromuscular Unit, Warsaw, Poland. Med Univ Warsaw, Dept Neurol, Warsaw, Poland. Biozentrum Basel, ME Muller Inst Struct Biol, CH-4056 Basel, Switzerland. Schemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. Univ Paris 06, CNRS, UMR 7000, Lab Cytosquelette & Dev, F-75013 Paris, France. Ciudad Sanitaria & Univ Bellvitge, Inst Neuropatol, Barcelona, Spain. RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 10,Room 4B37,10 Ctr Dr,MSC 1361, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov RI Shatunov, Aleksey/E-6946-2011; Strelkov, Sergei/G-7425-2014; OI Olive, Montse/0000-0001-5727-0165 NR 25 TC 42 Z9 44 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 2004 VL 114 IS 3 BP 306 EP 313 DI 10.1007/s00439-003-1057-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 766PN UT WOS:000188384900012 PM 14648196 ER PT J AU Schulze, TG Zhang, K Chen, YS Akula, N Sun, FZ McMahon, FJ AF Schulze, TG Zhang, K Chen, YS Akula, N Sun, FZ McMahon, FJ TI Defining haplotype blocks and tag single-nucleotide polymorphisms in the human genome SO HUMAN MOLECULAR GENETICS LA English DT Article ID LINKAGE-DISEQUILIBRIUM; FLUORESCENCE-POLARIZATION; RECOMBINATION HOTSPOT; MAXIMUM-LIKELIHOOD; ASSOCIATION; ALGORITHM; MAP; HUMAN-CHROMOSOME-21; DIVERSITY; SELECTION AB Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about their relative performance in real data or about the impact of allele frequencies and parameter choices on the detection of haplotype blocks and the markers that tag them. Here we present a formal comparison of two major algorithms, a linkage disequilibrium (LD)-based method and a dynamic programming algorithm (DPA), in three chromosomal regions differing in gene content and recombination rate. The two methods produced strikingly different results. DPA identified fewer and larger haplotype blocks as well as a smaller set of tag SNPs than the LD method. For both methods, the results were strongly dependent on the allele frequency. Decreasing the minor allele frequency led to an up to 3.7-fold increase in the number of haplotype blocks and tag SNPs. Definition of haploytpe blocks and tag SNPs was also sensitive to parameter changes, but the results could not be reconciled simply by parameter adjustment. These results show that two major methods for detecting haplotype blocks and tag SNPs can produce different results in the same data and that these results are sensitive to marker allele frequencies and parameter choices. More information is needed to guide the choice of method, marker allele frequencies, and parameters in the development of a haplotype map. C1 Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-68159 Mannheim, Germany. NIMH, Genet Unit, Mood & Anxiety Disorders Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. RP Schulze, TG (reprint author), Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-68159 Mannheim, Germany. EM schulze@zi-mannheim.de RI McMahon, Francis/A-7290-2009; Sun, Fengzhu /G-4373-2010; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X FU NHGRI NIH HHS [P50 HG 002790] NR 38 TC 27 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 1 PY 2004 VL 13 IS 3 BP 335 EP 342 DI 10.1093/hmg/ddh035 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 771PJ UT WOS:000188795000008 PM 14681300 ER PT J AU Khan, SG Metin, A Gozukara, E Inui, H Shahlavi, T Muniz-Medina, V Baker, CC Ueda, T Aiken, JR Schneider, TD Kraemer, KH AF Khan, SG Metin, A Gozukara, E Inui, H Shahlavi, T Muniz-Medina, V Baker, CC Ueda, T Aiken, JR Schneider, TD Kraemer, KH TI Two essential splice lariat branchpoint sequences in one intron in a xeroderma pigmentosum DNA repair gene: mutations result in reduced XPC mRNA levels that correlate with cancer risk SO HUMAN MOLECULAR GENETICS LA English DT Article ID GROUP-C; POLYPYRIMIDINE TRACT; INFORMATION-CONTENT; TRANSCRIPT LEVELS; SITE MUTATIONS; SKIN-CANCER; FAMILIES; DISEASE; DISORDER; DELETION AB The lariat branch point sequence (BPS) is crucial for splicing of human nuclear pre-mRNA yet BPS mutations have infrequently been reported to cause human disease. Using an inverse RT-PCR technique we mapped two BPS to the adenosine residues at positions -4 and -24 in intron 3 of the human XPC DNA repair gene. We identified homozygous mutations in each of these BPS in two newly diagnosed Turkish families with the autosomal recessive disorder xeroderma pigmentosum (XP). Cells from two severely affected children in family A harbor a homozygous point mutation in XPC intron 3 (-9 T to A), located within the downstream BPS. Using a real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) assay, these cells expressed no detectable (<0.1%) normal XPC message. Instead they expressed an XPC mRNA isoform with deletion of exon 4 that has no DNA repair activity in a host cell reactivation (HCR) assay. In contrast, in cells from three mildly affected siblings in family B, the BPS adenosine located at the -24 position in XPC intron 3 is mutated to a G. Real-time QRT-PCR revealed 3-5% of normal XPC message. These cells from family B had a higher level of HCR than cells from the severely affected siblings in family A, who had multiple skin cancers. Mutations identified in two BPS of the XPC intron 3 resulted in alternative splicing that impaired DNA repair function, thus implicating both of these BPS as essential for normal pre-mRNA splicing. However, a small amount of normal XPC mRNA can provide partial protection against skin cancers. C1 NCI, DNA Repair Sect, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Yuzuncu Yil Univ, Dept Dermatol, Van, Turkey. Inonu Univ, Sch Med, Dept Biochem, Malatya, Turkey. NCI, Cellular Oncol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21701 USA. RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Basic Res Lab, Ctr Canc Res, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA. EM kraemerk@nih.gov FU Intramural NIH HHS [Z01 BC004517-31] NR 44 TC 41 Z9 42 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 1 PY 2004 VL 13 IS 3 BP 343 EP 352 DI 10.1093/hmg/ddh026 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 771PJ UT WOS:000188795000009 PM 14662655 ER PT J AU Gramlich, T Kleiner, DE McCullough, AJ Matteoni, CA Boparai, N Younossi, ZM AF Gramlich, T Kleiner, DE McCullough, AJ Matteoni, CA Boparai, N Younossi, ZM TI Pathologic features associated with fibrosis in nonalcoholic fatty liver disease SO HUMAN PATHOLOGY LA English DT Article DE nonalcoholic fatty liver disease; nonalcoholic steatohepatitis ID NATURAL-HISTORY; HEPATIC IRON; STEATOHEPATITIS; STEATOSIS AB Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopatholologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with NASH can progress. This study focuses on the clinical and pathological characteristics of patients with NAFLD associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through our NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2% had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3% of patients, whereas perivenular fibrosis was seen in 17.2%. Ballooning degeneration and Mallory bodies were independently associated with both sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. We conclude that the presence of hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosis of the progressive form of NAFLD or NASH. C1 Inova Fairfax Hosp, Ctr Liver Dis, Dept Med, Falls Church, VA 22042 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NCI, NIH, Bethesda, MD 20892 USA. Metrohlth Med Ctr, Cleveland, OH USA. RP Younossi, ZM (reprint author), Inova Fairfax Hosp, Ctr Liver Dis, Dept Med, 3300 Gallows Rd, Falls Church, VA 22042 USA. OI Kleiner, David/0000-0003-3442-4453 NR 29 TC 72 Z9 75 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2004 VL 35 IS 2 BP 196 EP 199 DI 10.1016/j.humpath.2003.09.018 PG 4 WC Pathology SC Pathology GA 779XP UT WOS:000189327700009 PM 14991537 ER PT J AU Wang, JX Norman, RJ Wilcox, AJ AF Wang, JX Norman, RJ Wilcox, AJ TI Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology SO HUMAN REPRODUCTION LA English DT Article DE assisted reproductive technology; infertility; maternal age; ovarian stimulation; spontaneous abortion ID GAMETE INTRAFALLOPIAN TRANSFER; FERTILIZATION-EMBRYO TRANSFER; INVITRO FERTILIZATION; OVARIAN HYPERSTIMULATION; OOCYTE DONATION; UNITED-STATES; RISK-FACTORS; WOMEN; INFERTILITY; GONADOTROPIN AB BACKGROUND: There has been increasing number of pregnancies following assisted reproductive technology treatment and their survival is understandably a matter of interest. The relative risk of spontaneous abortion in these pregnancies remains unclear. The objectives of this study were to quantify the relative risk in assisted reproductive technology pregnancies in relation to two cohorts of naturally conceived pregnancies and to assess the possible risk factors for spontaneous abortion among assisted reproductive technology pregnancies. METHODS: Three cohorts of pregnancies, 1945 pregnancies conceived following assisted reproductive technology treatment in a tertiary infertility clinic, 549 natural pregnancies in a prospective study of lifestyle and pregnancy (the Ford cohort), and 4265 pregnancies from another cohort (the Treloar cohort), were used in the study. RESULTS: After adjusting for age, the relative risk of spontaneous abortion was 1.20 (95% CI 1.03-1.46) in the assisted reproductive technology cohort in comparison with the Ford cohort. Within the assisted reproductive technology cohort, a history of spontaneous abortion predicted increased risk, while a low level of ovarian stimulation seemed to be related to a reduced risk. CONCLUSIONS: The study showed that the risk of spontaneous abortion was slightly increased in the assisted reproductive technology pregnancies after adjusting for maternal age and previous spontaneous abortion. Within the assisted reproductive technology cohort, several variables, including the level of stimulation, appeared to be linked with the risk of spontaneous abortion. C1 Univ Adelaide, Queen Elizabeth Hosp, Dept Obstet & Gynaecol, Reprod Med Unit, Woodville, SA 5011, Australia. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Wang, JX (reprint author), Univ Adelaide, Queen Elizabeth Hosp, Dept Obstet & Gynaecol, Reprod Med Unit, Woodville, SA 5011, Australia. EM jim.wang@adelaide.edu.au RI Norman, Robert/A-1155-2007; OI Norman, Robert/0000-0002-3118-3896; Wilcox, Allen/0000-0002-3376-1311 NR 46 TC 60 Z9 72 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 2004 VL 19 IS 2 BP 272 EP 277 DI 10.1093/humrep/deh078 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 771RR UT WOS:000188800300009 PM 14747166 ER PT J AU Harsha, DW Sacks, FM Obarzanek, E Svetkey, LP Lin, PH Bray, GA Aickin, M Conlin, PR Miller, ER Appel, LJ AF Harsha, DW Sacks, FM Obarzanek, E Svetkey, LP Lin, PH Bray, GA Aickin, M Conlin, PR Miller, ER Appel, LJ TI Effect of dietary sodium intake on blood lipids - Results from the DASH-Sodium trial SO HYPERTENSION LA English DT Article; Proceedings Paper CT 57th Annual Fall Conference and Scientific Sessions of the American-Heart-Association-Council-for-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Amer Heart Assoc Council High Blood Pressure Res DE diet; sodium; lipids; cholesterol; blood pressure; hypertension ID LEFT-VENTRICULAR MASS; SALT RESTRICTION; INSULIN-RESISTANCE; NATIONAL-HEART; PRESSURE; HYPERTENSION; METAANALYSIS; CHOLESTEROL; REDUCTION; PATTERNS AB We evaluated the effect on serum lipids of sodium intake in 2 diets. Participants were randomly assigned to a typical American control diet or the Dietary Approaches to Stop Hypertension (DASH) diet, each prepared with 3 levels of sodium (targeted at 50, 100, and 150 mmol/d per 2100 kcal). The DASH diet is increased in fruits, vegetables, and low-fat dairy products and is reduced in saturated and total fat. Within assigned diet, participants ate each sodium level for 30 days. The order of sodium intake was random. Participants were 390 adults, age 22 years or older, with blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic. Serum lipids were measured at baseline and at the end of each sodium period. Within each diet, sodium intake did not significantly affect serum total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides. On the control diet, the ratio of total cholesterol-to-HDL cholesterol increased by 2% from 4.53 on higher sodium to 4.63 on lower sodium intake (P=0.04). On the DASH diet, sodium intake did not affect this ratio. There was no dose-response of sodium intake on serum lipids or the cholesterol ratio in either diet. At each sodium level, total cholesterol, LDL cholesterol, and HDL cholesterol were lower on the DASH diet versus the typical American diet. There were no significant interactions between the effects of sodium and the DASH diet on serum lipids. In conclusion, changes in dietary sodium intake over the range of 50 to 150 mmol/d did not affect blood lipid concentrations. C1 Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Duke Hypertens Ctr, Durham, NC USA. Duke Univ, Sch Med, Sarah W Stedman Nutr & Metab Ctr, Durham, NC USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Appel, LJ (reprint author), Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Suite 2-600,2024 E Monument St, Baltimore, MD 21205 USA. EM lappel@jhmi.edu FU NCRR NIH HHS [M01-RR02635, M01-RR00722]; NHLBI NIH HHS [K08 HL03857-01, U01-HL 57173, U01-HL57114, U01-HL57139, U01-HL57156, U01-HL57190] NR 25 TC 46 Z9 46 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 2004 VL 43 IS 2 BP 393 EP 398 DI 10.1161/01.HYP.0000113046.83819.a2 PN 2 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 769VD UT WOS:000188669700018 PM 14707154 ER PT J AU Langenickel, T Buttgereit, J Pagel, I Dietz, R Willenbrock, R Bader, M AF Langenickel, T Buttgereit, J Pagel, I Dietz, R Willenbrock, R Bader, M TI Forced homodimerization by site-directed mutagenesis alters guanylyl cyclase activity of natriuretic peptide receptor B SO HYPERTENSION LA English DT Article; Proceedings Paper CT 57th Annual Fall Conference and Scientific Sessions of the American-Heart-Association-Council-for-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, D.C. SP Amer Heart Assoc Council High Blood Pressure Res DE natriuretic peptides; receptors, natriuretic peptides; cyclic GMP; signal transduction ID SIGNAL-TRANSDUCTION; HORMONE-BINDING; ACTIVATION; DOMAIN; DEPHOSPHORYLATION; DESENSITIZATION; ENDOCRINE; MUTANT; DIMER AB Natriuretic peptides mediate their physiologic effects through activation of membrane-bound, guanylyl cyclase - coupled receptors (NPRs). Receptor dimerization is an important feature of signal transduction. This study was aimed at characterizing structurally important residues of the extracellular ligand-binding domain of NPR-B for receptor dimerization and cGMP generation. Deletion mutagenesis was used to replace cysteine residues at positions 53 (C53S), 417 (C417S), and 426 (C426S) by serine. Receptor expression, dimerization, whole-cell cGMP response, and guanylyl cyclase activity of membrane fractions were determined in stably transfected COS-7 cells. C53S, C417S, and C426S mutants were expressed and found to form disulfide-bridged covalent dimers. In contrast to NPR-B and C53S, C417S and C426S mutants displayed constitutive activity in whole cells ( C417S, 146 +/- 12%, P < 0.01; C426S, 153 +/- 7% of ligand-independent NPR-B cGMP generation, P < 0.01). The cGMP response of C417S and C426S mutants in whole cells was dose dependent and approximate to 4 times lower than that in NPR-B, whereas it was blunted in C53S-transfected cells ( 1 mumol/L CNP, NPR-B 2868 +/- 436%; C53S, 206 +/- 16% of control, P < 0.001 vs NPR-B, C417S, and C426S). Guanylyl cyclase assay in transfected cells confirmed the constitutive activity of C417S and C426S mutants. These data suggest that receptor dimerization by covalent disulfide bridges alters ligand-independent as well as ligand-dependent receptor activity. Localization of the crosslink in relation to the cell membrane is important for configuration of the extracellular domain and the consecutive signal transduction. C1 Max Delbruck Ctr Mol Med, Berlin, Germany. Humboldt Univ, Charite, Franz Volhard Clin, Berlin, Germany. RP Langenickel, T (reprint author), NHLBI, 50 Ctr Dr,Bldg 50-4529, Bethesda, MD 20892 USA. EM langenit@nhlbi.nih.gov; mbader@mdc-berlin.de NR 21 TC 10 Z9 10 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 FEB PY 2004 VL 43 IS 2 BP 460 EP 465 DI 10.1161/01.HYP.0000110907.33263.0b PN 2 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 769VD UT WOS:000188669700027 PM 14691198 ER PT J AU Guo, LY Hu-Li, J Paul, WE AF Guo, LY Hu-Li, J Paul, WE TI Probabilistic regulation of IL-4 production in Th2 cells: Accessibility at the Il4 locus SO IMMUNITY LA English DT Article ID CYTOKINE GENE-EXPRESSION; T-CELLS; COORDINATE REGULATOR; HISTONE ACETYLATION; CHROMATIN-STRUCTURE; LINEAGE COMMITMENT; IMMUNE-SYSTEM; CUTTING EDGE; C-MAF; DIFFERENTIATION AB IL-4 secreting and nonsecreting cells from Th2 cultures have a similar probability of producing IL-4 upon subsequent stimulation, implying that there is stochastic element in IL-4 production by stimulated Th2 cells. Purified IL-4 producers and nonproducers have similar Gata3 and c-maf mRNA expression. 114 gene accessibility, analyzed by restriction enzyme accessibility (REA) at sites in the promoter, in the second intron (DNase I hypersensitivity sites HSII and HSIII) and in CNS-1 in the two populations was also similar. However, upon TCR stimulation, site V-A, which is 5 kB 3' of exon 4, displayed a striking increase in accessibility but REA was 2- to 3-fold greater in producers than nonproducers. Cyclosporin A treatment inhibited VA opening, implying the involvement of NFAT in increased VA accessibility. Induction of VA accessibility is sensitive to cycloheximide, suggesting an additional factor(s) is needed. Thus, opening of V-A is a probabilistic event determining which Th2 cells transcribe II4. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wepaul@nih.gov NR 32 TC 48 Z9 52 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2004 VL 20 IS 2 BP 193 EP 203 DI 10.1016/S1074-7613(04)00025-1 PG 11 WC Immunology SC Immunology GA 821EI UT WOS:000221442400008 PM 14975241 ER PT J AU Wang, LH Yang, XY Zhang, XH Huang, JQ Hou, J Li, J Xiong, H Mihalic, K Zhu, HM Xiao, WH Farrar, WL AF Wang, LH Yang, XY Zhang, XH Huang, JQ Hou, J Li, J Xiong, H Mihalic, K Zhu, HM Xiao, WH Farrar, WL TI Transcriptional inactivation of STAT3 by PPAR gamma suppresses IL-6-responsive multiple myeloma cells SO IMMUNITY LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; HUMAN T-LYMPHOCYTES; ESTROGEN-RECEPTOR; GROWTH-FACTOR; CYTOKINE RECEPTORS; INDUCE APOPTOSIS; IL-2 PRODUCTION; CROSS-TALK; C-MYC; INTERLEUKIN-6 AB Multiple myeloma (MM) remains largely incurable despite conventional and high-dose therapies. Therefore, novel biologically based treatment approaches are urgently required. Here we demonstrate that expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in MM cells and its agonists 15-d-PGJ2 and troglitazone completely abolished IL-6-inducible MM cell proliferation and induced apoptosis through affecting expression of multiple cell cycle or apoptosis genes, whereas PPARgamma antagonist GW9662 and PPARalpha agonist WY14643 did not display this inhibitory effect. These PPARgamma agoinists significantly inhibited DNA binding and transactivation of STAT3 bound to the promoter of target genes in chromatin, but did not affect the expression of IL-6 receptor and phosphorylation of JAK/STAT3, MAPK, and PI3K/Akt. Interestingly, although inactivation of STAT3 by PPAR-y agonists is in a PPARgamma-dependent manner, the molecular mechanism by which two structurally distinct PPARgamma agonists suppress IL-6-activated STAT3 shows the divergent interactions between PPARgamma and STAT3 including direct or SMRT-mediated association. C1 Natl Canc Inst, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. Natl Canc Inst, Cytoking Mol Mech Sect, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. Second Mil Med Univ, Changzheng Hosp, Shanghai 200003, Peoples R China. Second Mil Med Univ, Xinhua Hosp, Shanghai 200003, Peoples R China. RP Wang, LH (reprint author), Natl Canc Inst, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM lhwang@ncifcrf.gov; farrar@ncifcrf.gov RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 FU NCI NIH HHS [N01-CA-12400] NR 59 TC 67 Z9 68 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2004 VL 20 IS 2 BP 205 EP 218 DI 10.1016/S1074-7613(04)00030-5 PG 14 WC Immunology SC Immunology GA 821EI UT WOS:000221442400009 PM 14975242 ER PT J AU Catalfamo, M Karpova, T McNally, J Costes, SV Lockett, SJ Bos, E Peters, PJ Henkart, PA AF Catalfamo, M Karpova, T McNally, J Costes, SV Lockett, SJ Bos, E Peters, PJ Henkart, PA TI Human CD8(+) T cells store RANTES in a unique secretory compartment and release it rapidly after TcR stimulation SO IMMUNITY LA English DT Article ID BETA-CHEMOKINES; LYMPHOCYTES; EFFECTOR; GRANULES; INTERFERON; LEUKOCYTE; PATHWAYS AB The chemokine RANTES is secreted rapidly after activation of human CD8(+) T cells, with a cycloheximide-resistant burst during the first hour. This pattern was observed in purified memory and effector phenotype CD8+ cells from blood as well as in blasts. In contrast, secretion of other chemokines and interferon-gamma by these cells was sensitive to cycloheximide and detectable only after a lag. Immunofluorescence microscopy of CD8(+) memory and effector cells and blasts showed RANTES present in intracellular vesicles that do not significantly colocalize with cytotoxic granule markers or other markers of defined cytoplasmic compartments. Immunoelectron microscopy confirmed that RANTES is stored in small vesicles distinct from the lysosomal secretory granules. RANTES(+) vesicles polarize rapidly in response to TcR engagement and are more rapidly depleted from the cytoplasm. These results show that CD8+ T cells have two distinct TcRregulated secretory compartments characterized by different mobilization kinetics, effector molecules, and biological function. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Microscopy & Image Anal Lab, Frederick, MD 21702 USA. Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. RP Henkart, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM henkartp@mail.nih.gov RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 NR 20 TC 67 Z9 69 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2004 VL 20 IS 2 BP 219 EP 230 DI 10.1016/S1074-7613(04)00027-5 PG 12 WC Immunology SC Immunology GA 821EI UT WOS:000221442400010 PM 14975243 ER PT J AU Kamohara, H Matsuyama, W Shimozato, O Abe, K Galligan, C Hashimoto, SI Matsushima, K Yoshimura, T AF Kamohara, H Matsuyama, W Shimozato, O Abe, K Galligan, C Hashimoto, SI Matsushima, K Yoshimura, T TI Regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in human neutrophils SO IMMUNOLOGY LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; FAS LIGAND; FACTOR-ALPHA; TNF-ALPHA; NK CELLS; T-CELLS; CYTOKINE; GRANULOCYTES; MONOCYTES; INDUCTION AB Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily, which is capable of inducing apoptosis in many cell types, including tumour and virus-infected cells, but rarely in normal cells. Expression of TRAIL mRNA and TRAIL receptors has previously been detected in neutrophils; however, the expression of TRAIL protein and the regulation of TRAIL and TRAIL receptor expression in these cells remain unknown. Here we report, for the first time, that neutrophils constitutively express TRAIL protein on their cell surface and that the TRAIL protein is shed during culture. TNF-alpha is a down-regulator of TRAIL expression, whereas IFN-gamma up-regulates the expression of TRAIL. Neutrophils did not express a detectable level of TRAIL-R1 or -R4, but constitutively expressed a low, but substantial, level of TRAIL-R2 and a high level of TRAIL-R3. Although the level of TRAIL-R2 was not significantly altered during culture under different experimental conditions, approximate to 30% of TNF-alpha-treated cells rapidly lost their high-level TRAIL-R3 expression, whereas the majority of IFN-gamma-treated cells retained a high level of TRAIL-R3 expression. Anti-TRAIL neutralizing antibody significantly inhibited neutrophil apoptosis during cultures in medium alone, or in the presence of TNF-alpha or IFN-gamma. Thus, our study identified human neutrophils as a cellular source of TRAIL and suggests that neutrophil-derived TRAIL may play a role in immune surveillance. Our results also suggest a role for the TRAIL/TRAIL receptor system in neutrophil apoptosis. C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Univ Tokyo, Sch Med, Dept Mol Prevent Med, Tokyo 113, Japan. RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Bldg 559,Rm 9, Frederick, MD 21702 USA. EM yoshimur@mail.ncifcrf.gov NR 33 TC 47 Z9 52 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD FEB PY 2004 VL 111 IS 2 BP 186 EP 194 DI 10.1111/j.1365-2567.2003.01794.x PG 9 WC Immunology SC Immunology GA 766EN UT WOS:000188353900008 PM 15027904 ER PT J AU Kumar, S Jones, TR Oakley, MS Zheng, H Kuppusamy, SP Taye, A Krieg, AM Stowers, AW Kaslow, DC Hoffman, SL AF Kumar, S Jones, TR Oakley, MS Zheng, H Kuppusamy, SP Taye, A Krieg, AM Stowers, AW Kaslow, DC Hoffman, SL TI CpG oligodeoxynucleotide and montanide ISA 51 adjuvant combination enhanced the protective efficacy of a subunit malaria vaccine SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; CARBOXYL-TERMINAL FRAGMENT; PLASMODIUM-FALCIPARUM; AOTUS MONKEYS; INTERFERON-GAMMA; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSE; C-TERMINUS; NK CELLS; IN-VIVO AB Unmethylated CpG dinucleotide motifs present in bacterial genomes or synthetic oligodeoxynucleotides (ODNs) serve as strong immunostimulatory agents in mice, monkeys and humans. We determined the adjuvant effect of murine CpG ODN 1826 on the immunogenicity and protective efficacy of the Saccharomyces cerevisiae-expressed 19-kDa C-terminal region of merozoite surface protein 1 (yMSP1(19)) of the murine malaria parasite Plasmodium yoelli. We found that in C57BL/6 mice, following sporozoite challenge, the degree of protective immunity against malaria induced by yMSP1(19) in a formulation of Montanide ISA 51 (ISA) plus CpG ODN 1826 was similar or superior to that conferred by yMSP1(19) emulsified in complete Freund's adjuvant (CFA/incomplete Freund's adjuvant). In total, among mice immunized with yMSP1(19), 22 of 32 (68.7%) with ISA plus CpG 1826, 0 of 4 (0%) with CFA/incomplete Freund's adjuvant, 0 of 4 (0%) with CpG 1826 mixed with ISA (no yMSP1(19)), and 0 of 11 (0%) with CpG 1826 alone were completely protected against development of erythrocytic stage infection after sporozoite challenge. The adjuvant effect of CpG ODN 1826 was manifested as both significantly improved complete protection from malaria (defined as the absence of detectable erythrocytic form parasites) (P = 0.007, chi square) and reduced parasite burden in infected mice. In vivo depletions of interleukin-12 and gamma interferon cytokines and CD4(+) and CD8(+) T cells in vaccinated mice had no significant effect on immunity. On the other hand, immunoglobulin G (IgG) isotype levels appeared to correlate with protection. Inclusion of CpG ODN 1826 in the yMSP1(19) plus ISA vaccine contributed towards the induction of higher levels of IgG2a and IgG2b (Th1 type) antibodies, suggesting that CpG ODN 1826 caused a shift towards a Th1 type of immune response that could be responsible for the higher degree of protective immunity. Our results indicate that this potent adjuvant formulation should be further evaluated for use in clinical trials of recombinant malarial vaccine candidates. C1 Naval Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Microbiol & Immunol, Baltimore, MD 21205 USA. Coley Pharmaceut Grp, Wellesley, MA 02481 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NIAID, Malaria Vaccine Dev Unit, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), US FDA, Bacterial & Parasit Dis Sect, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, HFM-313,1401 Rockville Pike, Rockville, MD 20852 USA. EM kumarS@cber.fda.gov NR 45 TC 45 Z9 48 U1 0 U2 2 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 FEB PY 2004 VL 72 IS 2 BP 949 EP 957 DI 10.1128/IAI.72.2.949-957.2004 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 771BV UT WOS:000188766400040 PM 14742540 ER PT J AU Mello, K Daly, TM Long, CA Burns, JM Bergman, LW AF Mello, K Daly, TM Long, CA Burns, JM Bergman, LW TI Members of the merozoite surface protein 7 family with similar expression patterns differ in ability to protect against Plasmodium yoelii malaria SO INFECTION AND IMMUNITY LA English DT Article ID FALCIPARUM MEROZOITES; SERINE-PROTEASE; COMPLEX; GENE; RECOMBINANT; PRECURSOR; VACCINES; GLYCOPROTEIN; FRAGMENTS; INFECTION AB Previously, we described the isolation of the Plasmodium yoelii sequence-related molecules P. yoelii MSP-7 (merozoite surface protein 7) and P. yoelii MSRP-2 (MSP-7-related protein 2) by their ability to interact with the amino-terminal end of P. yoeld MSP-1 in a yeast two-hybrid system. One of these molecules was the homologue of Plasmodium falciparum MSP-7, which was biochemically isolated as part of the shed MSP-1 complex. In the present study, with antibodies directed against recombinant proteins, immunoprecipitation analyses of the rodent system demonstrated that both P. yoelii MSP-7 and P. yoelii MSRP-2 could be isolated from parasite lysates and from parasite culture supernatants. Immunofluorescence studies colocalized P. yoelii MSP-7 and P. yoelii MSRP-2 with the amino-terminal portion of MSP-1 and with each other on the surface of schizonts. Immunization with P. yoelii MSRP-2 but not P. yoeld MSP-7 protected mice against a lethal infection with P, yoeld strain 17XL. These results establish that both P. yoelii MSP-7 and P. yoelii MSRP-2 are expressed on the surface of merozoites and released from the parasite and that P. yoeld MSRP-2 may be the target of a protective immune response. C1 Drexel Univ, Coll Med, Dept Microbiol & Immunol, Div Mol Parasitol, Philadelphia, PA 19129 USA. NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD USA. RP Bergman, LW (reprint author), Drexel Univ, Coll Med, Dept Microbiol & Immunol, Div Mol Parasitol, 2900 Queen Ln, Philadelphia, PA 19129 USA. EM Lawrence.Bergman@drexel.edu NR 28 TC 16 Z9 16 U1 0 U2 1 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 FEB PY 2004 VL 72 IS 2 BP 1010 EP 1018 DI 10.1128/IAI.72.2.1010-1018.2004 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 771BV UT WOS:000188766400048 PM 14742548 ER PT J AU Harris, AD Nemoy, L Johnson, JA Martin-Carnahan, A Smith, DL Standiford, H Perencevich, EN AF Harris, AD Nemoy, L Johnson, JA Martin-Carnahan, A Smith, DL Standiford, H Perencevich, EN TI Co-carriage rates of vancomycin-resistant Enterococcus and extended-spectrum beta-lactamase-producing bacteria among a cohort of intensive care unit patients: Implications for an active surveillance program SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID KLEBSIELLA-PNEUMONIAE; RISK-FACTORS; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; EPIDEMIOLOGY; INFECTION; COLONIZATION; TRANSMISSION; OUTBREAK; CULTURES AB OBJECTIVE: To assess the co-colonization rates of extended-spectrum beta-lactamase (ESBL) -producing bacteria and vancomycin-resistant Enterococcus (VRE) obtained on active surveillance cultures. DESIGN: Prospective cohort study. SETTING: Medical and surgical intensive care units (ICUs) of a tertiary-care hospital. PATIENTS: Patients admitted between September 2001 and November 2002 to the medical and surgical ICUs at the University of Maryland Medical System had active surveillance perirectal cultures performed. Samples were concurrently processed for VRE and ESBL-producing bacteria. RESULTS: Of 1,362 patients who had active surveillance cultures on admission, 136 (1096) were colonized with VRE. Among these, 15 (positive predictive value, 11%) were co-colonized with ESBL. Among the 1,226 who were VRE negative, 1,209 were also ESBL negative (negative predictive value, 99%). Among the 1,362 who had active surveillance cultures on admission, 32 (2%) were colonized with ESBL. Among these, 15 (47%) were co-colonized with VRE. Of the 32 patients colonized with ESBL, 10 (31%) had positive clinical cultures for ESBL on the same hospital admission. For these 10 patients, the surveillance cultures were positive an average of 2.7 days earlier than the clinical cultures. CONCLUSIONS: Patients who are colonized with VRE can also be co-colonized with other antibiotic-resistant bacteria such as ESBL-producing bacteria. Our study is the first to measure co-colonization rates of VRE and ESBL-producing bacteria. Isolating VRE-colonized patients would isolate 47% of the ESBI, colonized patients without the need for further testing. Hence, active surveillance for VRE should also theoretically diminish the amount of patient-to-patient transmission of ESBL-producing bacteria. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Div Healthcare Outcomes Res, Baltimore, MD 21201 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Univ Maryland Med Syst, Baltimore, MD USA. Vet Affairs Maryland Health Care Syst, Baltimore, MD USA. NIH, Fogarty Int Ctr, Bethesda, MD USA. RP Harris, AD (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Div Healthcare Outcomes Res, 100 Greene St,Lower Level, Baltimore, MD 21201 USA. RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU NIAID NIH HHS [K23 AI01752-01A1] NR 23 TC 46 Z9 46 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD FEB PY 2004 VL 25 IS 2 BP 105 EP 108 DI 10.1086/502358 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 775CC UT WOS:000189022300005 PM 14994933 ER PT J AU Calvo, E Andersen, J Francischetti, IM deL Capurro, M deBianchi, AG James, AA Ribeiro, JMC Marinotti, O AF Calvo, E Andersen, J Francischetti, IM deL Capurro, M deBianchi, AG James, AA Ribeiro, JMC Marinotti, O TI The transcriptome of adult female Anopheles darlingi salivary glands SO INSECT MOLECULAR BIOLOGY LA English DT Article DE Anopheles darlingi; salivary glands; proteome; transcriptome ID PATHOGENESIS-RELATED PROTEINS; MOSQUITO AEDES-AEGYPTI; MALARIA VECTOR; TRYPANOSOMA-CRUZI; SPOROGONIC DEVELOPMENT; LUTZOMYIA-LONGIPALPIS; RHODNIUS-PROLIXUS; IMMUNE-RESPONSES; CDNA CLONING; IN-VITRO AB Anopheles (Nyssorhynchus) darlingi is an important malaria vector in South and Central America; however, little is known about molecular aspects of its biology. Genomic and proteomic analyses were performed on the salivary gland products of Anopheles darlingi. A total of 593 randomly selected, salivary gland-derived cDNAs were sequenced and assembled based on their similarities into 288 clusters. The putative translated proteins were classified into three categories: (S) secretory products, (H) housekeeping products and (U) products with unknown cell location and function. Ninety-three clusters encode putative secreted proteins and several of them, such as an anophelin, a thrombin inhibitor, apyrases and several new members of the D7 protein family, were identified as molecules involved in haematophagy. Sugar-feeding related enzymes (alpha-glucosidases and alpha-amylase) also were found among the secreted salivary products. Ninety-nine clusters encode housekeeping proteins associated with energy metabolism, protein synthesis, signal transduction and other cellular functions. Ninety-seven clusters encode proteins with no similarity with known proteins. Comparison of the sequence divergence of the S and H categories of proteins of An. darlingi and An. gambiae revealed that the salivary proteins are less conserved than the housekeeping proteins, and therefore are changing at a faster evolutionary rate. Tabular and supplementary material containing the cDNA sequences and annotations are available at http://www.ncbi.nlm.nih.gov/projects/Mosquito/A_darlingi_sialome/. C1 Univ Calif Irvine, Dept Biochem & Mol Biol, Irvine, CA 92697 USA. NIAID, Sect vector Biol, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. Univ Sao Paulo, ICB, Dept Parasitol, Sao Paulo, Brazil. RP Marinotti, O (reprint author), Univ Calif Irvine, Dept Biochem & Mol Biol, 2315 McGaugh Hall, Irvine, CA 92697 USA. EM omarinot@uci.edu RI Capurro, Margareth/F-8679-2012; OI Capurro, Margareth/0000-0002-7480-2116; Marinotti, Osvaldo/0000-0002-7173-7160; Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [AI29746] NR 86 TC 72 Z9 76 U1 0 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD FEB PY 2004 VL 13 IS 1 BP 73 EP 88 DI 10.1111/j.1365-2583.2004.00463.x PG 16 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 764UJ UT WOS:000188224200009 PM 14728669 ER PT J AU Debrabant, A Joshi, MB Pimenta, PFP Dwyer, DM AF Debrabant, A Joshi, MB Pimenta, PFP Dwyer, DM TI Generation of Leishmania donovani axenic amastigotes: their growth and biological characteristics SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Australian-Society-for-Parasitology CY 2003 CL Darwin, AUSTRALIA DE trypanosomatid; leishmaniasis; parasite; culture system; infectivity; virulence ID PROTOZOAN PARASITE LEISHMANIA; SECRETORY ACID-PHOSPHATASES; PROGRAMMED CELL-DEATH; FUNCTIONAL DOMAINS; GENE-EXPRESSION; PROMASTIGOTES; IDENTIFICATION; TRANSPORTER; PROTEIN; FAMILY AB In this report, we describe an in vitro culture system for the generation and propagation of axenic amastigotes from the well characterised 1S-CL2D line of Leishmania donovani. Fine structure analyses of these in vitro-grown amastigotes demonstrated that they possessed morphological features characteristic of L. donovani tissue-derived amastigotes. Further, these axenic amastigotes (LdAxAm) were shown to synthesise and release a secretory acid phosphatase isoform similar to that produced by intracellular amastigotes. Such LdAxAm also expressed surface membrane 3'-nucleotidase enzyme activity similar to that of tissue-derived amastigotes. Moreover, LdAxAm, in contrast to promastigotes, expressed significant levels of the amastigote-specific A2 proteins. In addition, LdAxAm, derived from long term cultures of Ld 1S-CL2D promastigotes, had significant infectivity for both human macrophages in vitro and for hamsters in vivo. Thus, the in vitro culture system described herein provides a useful tool for the generation of large quantities of uniform populations of axenic amastigotes of the L. donovani 1S-CL2D line. The availability of such material should greatly facilitate studies concerning the cell and molecular biology of this parasite developmental stage. (C) 2003 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Fdn Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Med Entomol, Belo Horizonte, MG, Brazil. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. EM ddwyer@niaid.nih.gov NR 44 TC 131 Z9 137 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD FEB PY 2004 VL 34 IS 2 BP 205 EP 217 DI 10.1016/j.ijpara.2003.10.011 PG 13 WC Parasitology SC Parasitology GA 801FU UT WOS:000220082600008 PM 15037106 ER PT J AU Ryu, JK Han, JY Chu, YC Song, SU Lee, KH Yoon, SM Suh, JK Kim, SJ AF Ryu, JK Han, JY Chu, YC Song, SU Lee, KH Yoon, SM Suh, JK Kim, SJ TI Expression of cavernous transforming growth factor-beta(1) and its Type II Receptor in patients with erectile dysfunction SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article DE erectile dysfunction; fibrosis; penis; transforming growth factor ID SMOOTH-MUSCLE FIBERS; FACTOR-BETA; COLLAGEN-SYNTHESIS; GENE-EXPRESSION; IMPOTENT MEN; RISK-FACTORS; ATHEROSCLEROSIS; CELLS; TISSUE; FIBROSIS AB It has been hypothesized that transforming growth factor-beta(1) (TGF-beta(1)) signalling is involved in erectile dysfunction (ED). This study was undertaken to elucidate in detail whether expression of TGF-beta(1) and its type II receptor is clinically related to various causes of ED. Fifty-four patients with ED and 24 potent men were the subjects of this study. After multidisciplinary work-up, the ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n = 33). In every subject, percutaneous cavernous biopsy was performed using a Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres and immunohistochemical staining to evaluate both TGF-beta(1) and its type II receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen fibres were significantly more abundant in men with vasculogenic ED (72.7 +/- 17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0 +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta(1) was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II receptor expression was also significantly increased in vasculogenic ED (3.9 +/- 1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the hyperlipidaemia and the atherosclerosis patients showed significantly more fibrosis than those without the condition (p < 0.05). The abundance of collagen fibres correlated well with both TGF-beta(1) expression (gamma = 0.81; p < 0.001) and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that TGF-beta(1) and its receptor II pathway are involved in cavernous fibrosis and ED in man. Patients with vascular risk factors such as hyperlipidaemia and atherosclerosis are liable to ED by activation of this pathway. C1 Inha Univ, Sch Med, Dept Urol, Inchon, South Korea. Inha Univ, Sch Med, Dept Pathol, Inchon, South Korea. Inha Univ, Sch Med, Clin Res Ctr, Inchon, South Korea. NCI, NIH, Bethesda, MD 20892 USA. RP Suh, JK (reprint author), Inha Univ Hosp, Dept Urol, Inchon 400103, South Korea. EM jksuh@inha.ac.kr NR 28 TC 17 Z9 20 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD FEB PY 2004 VL 27 IS 1 BP 42 EP 49 DI 10.1046/j.0105-6263.2003.00447.x PG 8 WC Andrology SC Endocrinology & Metabolism GA 763LK UT WOS:000188086900008 PM 14718046 ER PT J AU Bodegas, E Martinez, A Ozbun, LL Garayoa, M Letterio, JJ Montuenga, LM Jakowlew, SB AF Bodegas, E Martinez, A Ozbun, LL Garayoa, M Letterio, JJ Montuenga, LM Jakowlew, SB TI Depressed adrenomedullin in the embryonic transforming growth factor-beta 1 null mouse becomes elevated postnatally SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE TGF-beta; adrenomedullin; expression; development; mouse ID EXPRESSION; EMBRYOGENESIS; AUTOCRINE; CELL AB Transforming growth factor-beta (TGF-beta) and adrenomedullin are multifunctional regulatory proteins which are expressed in developing embryonic and adult tissues. Because of their colocalization, TGF-beta1 and adrenomedullin maybe able to coordinately act to influence development and differentiation. In order to learn more about the biology of adrenomedullin in the absence of the effects of TGF-beta1 in vivo, we examined adrenomedullin in the TGF-beta1 null mouse. A generally lower amount of adrenomedullin was detected by immunohistochemical staining analysis in multiple tissues from embryonic TGF-beta1 null mice compared to wildtype animals, including the heart, lung, brain, liver, and kidney, among others. In contrast, immunohistochemical staining for adrenomedullin was more intense in tissues of the postnatal TGF-beta1 null mouse compared to the wildtype mouse. These observations were confirmed by quantitative real time RT-PCR for adrenomedullin in both embryos and postnatal animals, as well as in cultured mouse embryo fibroblasts from TGF-beta1 null and wildtype mice. In addition, when cultured mouse embryo fibroblasts were treated with a neutralizing monoclonal antibody against TGF-beta1, the levels of adrenomedullin expression were statistically reduced compared to untreated cells. Our data show that expression of adrenomedullin is reduced in tissues of the developing embryonic TGF-beta1 null mouse compared to the wildtype mouse, but increases during postnatal development in TGF-beta1 null mice. The elevated expression of adrenomedullin which occurs postnatally in the TGF-beta1 null mouse may be a cause or a consequence of the multifocal wasting syndrome which is characteristic of postnatal TGF-beta1 null mice. C1 NCI, Cell & Canc Biol Branch, Rockville, MD 20850 USA. Univ Navarra, Div Oncol, Ctr Appl Med Res, E-31080 Pamplona, Spain. Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Jakowlew, SB (reprint author), NCI, Cell & Canc Biol Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM jakowles@mail.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 8 TC 6 Z9 7 U1 0 U2 1 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD FEB PY 2004 VL 48 IS 1 BP 67 EP 70 DI 10.1387/ijdb.15005577 PG 4 WC Developmental Biology SC Developmental Biology GA 777DZ UT WOS:000189161400010 PM 15005577 ER PT J AU Zeng, QT Kogan, S Plovnick, RM Crowell, J Lacroix, EM Greenes, RA AF Zeng, QT Kogan, S Plovnick, RM Crowell, J Lacroix, EM Greenes, RA TI Positive attitudes and failed queries: an exploration of the conundrums of consumer health information retrieval SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE information retrieval; Internet; consumer health; interview study; observation study ID INTERNET; WEB AB Several studies have found that consumers report a high level of satisfaction with the Internet as a health information resource. Belied by this positive attitude, however, are other studies reporting that consumers were often unsuccessful in searching for health information. In this paper, we present an interview and observation study in which we asked health consumers to search for health information on the Internet after first stating their search goals. Upon the conclusion of the session they were asked to evaluate their searches. We found that many consumers were unable to find satisfactory information when performing a specific query, while in general the group viewed health information retrieval (HIR) on the Internet in a positive light. We analyzed the observed search sessions to determine what factors accounted for the failure of specific searches and positive attitudes, and also discussed potential informatics solutions. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Decis Syst Grp, Boston, MA 02115 USA. NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Zeng, QT (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Decis Syst Grp, Thorn 309,75 Francis St, Boston, MA 02115 USA. EM qzeng@dsg.bwh.harvard.edu FU NLM NIH HHS [R01 LM 07222] NR 19 TC 42 Z9 42 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD FEB PY 2004 VL 73 IS 1 BP 45 EP 55 DI 10.1016/j.ijmedinf.2003.12.015 PG 11 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 803VV UT WOS:000220259500004 PM 15036078 ER PT J AU Zoico, E Di Francesco, V Guralnik, JM Mazzali, G Bortolani, A Guariento, S Sergi, G Bosello, O Zamboni, M AF Zoico, E Di Francesco, V Guralnik, JM Mazzali, G Bortolani, A Guariento, S Sergi, G Bosello, O Zamboni, M TI Physical disability and muscular strength in relation to obesity and different body composition indexes in a sample of healthy elderly women SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE disability; sarcopenia; sarcopenic obesity; BMI; aging ID SKELETAL-MUSCLE MASS; X-RAY ABSORPTIOMETRY; REPORTED FUNCTIONAL LIMITATION; FAT-FREE MASS; OLDER PERSONS; AGED 70; SARCOPENIA; WEIGHT; MEN; PERFORMANCE AB OBJECTIVES: The aim of the present study was to test the association between muscular strength, functional limitations, body composition measurements and indexes of sarcopenia in a sample of community-dwelling, elderly women at the high end of the functional spectrum. DESIGN: Cross-sectional. SUBJECTS: In all, 167 women aged 67-78 y were selected from the general population in central Verona. A group of 120 premenopausal healthy women aged 20-50 y represented the young reference group. MEASUREMENTS: Body weight, height, body mass index (BMI) and the presence of acute and chronic conditions were evaluated in each subject. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Physical functioning was assessed using a modified version of the Activities of Daily Living Scale. Dominant leg isometric strength was measured with a Spark Handheld Dynamometer. RESULTS: Elderly women with BMI higher than 30 kg/m(2) and in the highest quintile of body fat percent showed a significantly higher prevalence of functional limitation. In our population study, about 40% of sarcopenic elderly women and 50% of elderly women with high body fat and normal muscle mass were functionally limited. The prevalence of functional limitation significantly increased in subjects with class II sarcopenia, defined according to the skeletal muscle mass index (SMI = skeletal muscle mass/body mass x 100). In logistic regression models, after adjusting for age and different chronic health conditions, subjects with BMI higher than 30 kg/m(2), in the highest quintile of body fat, or with high body fat and normal muscle mass or class II sarcopenia according to SMI, had a 3-4 times increased risk of functional limitations. Finally, isometric leg strength was significantly lower in subjects in the lowest quintile of relative muscle mass and in sarcopenic and sarcopenic obese women. CONCLUSIONS: High body fat and high BMI values were associated with a greater probability of functional limitation in a population of elderly women at the high end of the functional spectrum. Among the different indexes of sarcopenia used in this study, only SMI predicted functional impairment and disability. Isometric leg strength was significantly lower in subjects with sarcopenia and sarcopenic obesity. C1 Univ Verona, Div Geriatr Med, I-37100 Verona, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Padua, Div Geriatr Med, Padua, Italy. RP Zamboni, M (reprint author), Univ Verona, Osped Maggiore, Cattedra Geriatria, Piazzale Stefani 1, I-37126 Verona, Italy. EM mzamboni@univr.it OI ZAMBONI, Mauro/0000-0001-6961-9483; ZOICO, Elena/0000-0002-5235-1545 NR 38 TC 156 Z9 159 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD FEB PY 2004 VL 28 IS 2 BP 234 EP 241 DI 10.1038/sj.ijo.0802552 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 765VH UT WOS:000188304700007 PM 14708033 ER PT J AU Miller, KE Dietz, JM AF Miller, KE Dietz, JM TI Fruit yield, not DBH or fruit crown volume, correlates with time spent feeding on fruits by wild Leontopithecus rosalia SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE fruit productivity; DBH; frugivory; crown volume; primate ID FOOD COMPETITION; RANGING PATTERNS; CEBUS-CAPUCINUS; BIRD ABUNDANCE; NATIONAL-PARK; SIZE; MONKEYS; FOREST; PATCH; TREES AB Assessing fruit availability is a critical element in testing hypotheses concerning resource use by frugivores. One method to estimate fruit availability is to measure tree diameter at breast height (DBH) and assume a positive correlation with fruit tree productivity. Our first objective was to test the relationship between DBH and tree productivity. We used as our measures of tree productivity: volume of the fruit bearing region of the tree crown (FBRv) and fruit yield measured as grams of dry fruit matter per fruit bearing region (FBR). Our second objective was to determine if time spent feeding on fruits by golden lion tamarins was correlated with 3 measures of tree productivity within their territories. We define tree productivity within a territory as tree productivity x tree density (fruit tree productivity/ha). We used as our measures of tree productivity/ ha: (1) DBH x tree density, (2) fruit yield x tree density, and (3) FBRv x tree density. We measured DBH and FBRv for 17 fruit species commonly eaten by golden lion tamarins in Poco das Antas Reserve, Brazil. We counted fruits in trees and collected fruits to calculate fruit yield. We used measures of tree densities to calculate tree productivity/ha. We found that DBH correlated with fruit yield. The time tamarins spent feeding did not correlate with DBH (x tree density) or FBRv (x tree density), but it correlated with fruit yield (x tree density). Our results emphasize the importance of recording temporal and spatial measures of fruit productivity that are meaningful to the frugivore studied. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RP Miller, KE (reprint author), NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Room 205,Bldg 112,POB 529, Poolesville, MD 20837 USA. EM bocolobo00@yahoo.com NR 37 TC 5 Z9 9 U1 1 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD FEB PY 2004 VL 25 IS 1 BP 27 EP 39 DI 10.1023/B:IJOP.0000014643.20674.97 PG 13 WC Zoology SC Zoology GA 770TJ UT WOS:000188746700002 ER PT J AU Feril, LB Kondo, T Takaya, K Riesz, P AF Feril, LB Kondo, T Takaya, K Riesz, P TI Enhanced ultrasound-induced apoptosis and cell lysis by a hypotonic medium SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID HYPERTHERMIA-INDUCED APOPTOSIS; INTENSITY FOCUSED ULTRASOUND; FREE-RADICAL FORMATION; SAPHENOUS-VEIN GRAFTS; ECHO CONTRAST AGENT; DISSOLVED-GASES; GENE TRANSFECTION; U937 CELLS; IN-VITRO; CHANNELS AB Purpose: To test the hypothesis that non-lethal hypotonia will enhance ultrasound-induced cell killing in vitro and that the mechanism is mechanical in nature. Materials and methods: Hypotonic RPMI medium (146 mOsm) was used to induce non-lethal osmotic swelling of human myelomonocytic, leukaemia U937 cells. Hypotonia for 10 min was started just before exposure to 1 MHz ultrasound at 0.5 or 1.0 W cm(-2) for 10 min, or 5 min before exposure to 2.0 W cm(-2) for 1 min. Surviving intact cells were then determined by the trypan blue dye exclusion test immediately after treatment. After 6-h incubation of the treated cells, early apoptosis and secondary necrosis were measured using a flow cytometer. Intracellular free calcium ion imaging by Fura-2 fluorescence and Cellular ion scanning using a secondary ion mass spectrometer were also performed. Results: Enhancement of ultrasound-induced cell lysis was observed at all intensities, and most prominently at 2.0 W cm(-2), while apoptosis induction was significantly enhanced at intensities of 0.5 and 1.0 W cm(-2), but not at 2.0 W cm(-2). The enhanced cell lysis is attributed to the increased susceptibility of the cells to mechanical damage. This is consistent with previous reports describing the effects of mechanical stresses on cell membranes. Cellular ion scanning images also suggest that hypotonia has an effect on the membrane damage-and-repair mechanism of the cells. Conclusions: The results Support the hypothesis that non-lethal hypotonia can enhance ultrasound-induced cell killing. These findings also suggest the 'sonomechanical' nature of the effects on the cells. C1 Toyama Med & Pharmaceut Univ, Fac Med, Dept Radiol Sci, Toyama 9300194, Japan. Toyama Med & Pharmaceut Univ, Fac Med, Dept Anat 2, Toyama 9300194, Japan. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Kondo, T (reprint author), Toyama Med & Pharmaceut Univ, Fac Med, Dept Radiol Sci, Toyama 9300194, Japan. EM kondot@ms.toyama-mpu.ac.jp NR 44 TC 39 Z9 44 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD FEB PY 2004 VL 80 IS 2 BP 165 EP 175 DI 10.1080/09553000310001654684 PG 11 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 809UJ UT WOS:000220661300008 PM 15164798 ER PT J AU Coleman, CN AF Coleman, CN TI International Conference on Translational Research ICTR 2003 Conference Summary: Marshalling resources in a complex time SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 2nd International Conference in Translational Research and Preclinical Strategies in Radiation Oncology (ICTR 2003) CY MAR, 2003 CL LUGANO, SWITZERLAND DE oncology; radiation biology; molecular targets; Imaging; biological models; translational research ID TISSUE OXYGEN CONCENTRATION; DNA-DAMAGE; RADIATION-THERAPY; PREDICTIVE ASSAYS; CANCER-TREATMENT; MICE; GENE; P53; RNA; EFFICACY AB The knowledge, tools, and environment for the practice of radiation oncology are changing rapidly. The National Cancer Institute has articulated the need for a balanced portfolio, including the interrelated components of discovery,development, and delivery. Underpinning practice is the emerging knowledge from molecular, cellular, and tumor biology that is the engine of discovery. The use of high-throughput technologies to analyze biochemical and molecular profiles will ultimately enable the individualization of cancer treatment requiring the appropriate integration of radiation with a range of systemic therapies, including chemotherapy, biologic therapy, and immunotherapy. Technological advances in treatment delivery using photons, brachytherapy, particle therapy, radioisotopes, and other forms of energy require an improved ability to localize the tumor and critical subregions and to ensure necessary tissue immobilization and/or real-time target adjustment. Functional imaging is helping to define tumor characteristics and response to treatment. The development of appropriate radiation oncology treatment requires a wide range of expertise, a multimodality approach, and multi-institutional collaboration to provide improved and cost-effective outcome. The delivery of appropriate cancer care to those who need it requires biology and technology but also reaching the underserved populations worldwide. ICTR 2003 demonstrated substantial progress in translational radiation oncology. Faced with financial constraints for research and patient care, the broad field of radiation oncology must continually examine and balance its research and development portfolio and invest in its future leaders to enable it be an important contributor to the future of cancer care. (C) 2004 Elsevier Inc. C1 NCI, Radiat Oncol Sci Program, Canc Res Ctr, Div Canc Treatment & Diagnos, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NIH, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov NR 58 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2004 VL 58 IS 2 BP 307 EP 319 DI 10.1016/j.ijrobp.2003.09.056 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 767QZ UT WOS:000188465300002 PM 14751498 ER PT J AU Citrin, D Scott, T Sproull, M Menard, C Tofilon, PJ Camphausen, K AF Citrin, D Scott, T Sproull, M Menard, C Tofilon, PJ Camphausen, K TI In vivo tumor imaging using a near-infrared-labeled endostatin molecule SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 2nd International Conference in Translational Research and Preclinical Strategies in Radiation Oncology (ICTR 2003) CY MAR, 2003 CL LUGANO, SWITZERLAND DE near-infrared; angiogenesis; endostatin; murine ID ANGIOGENESIS INHIBITOR; PROLIFERATION; RADIOTHERAPY; SUPPRESSION; CARCINOMA; THERAPY AB Purpose: Endostatin is a 20-kD C-terminal fragment of collagen XVIII and is a potent inhibitor of angiogenesis. Imaging technologies that use near-infrared (NIR) fluorescent probes are well suited to the laboratory setting. The goal of this study was to determine whether endostatin labeled with a NIR probe (Cy5.5) could be detected in an animal after intraperitoneal injection and whether it would selectively localize in a tumor. Methods: Endostatin was conjugated to Cy5.5 monofunctional dye and purified from free dye by gel filtration. LLC, a murine tumor, was implanted in C57BL/6 mice. The tumors were allowed to grow to 350 mm(2), at which point the mice were injected with 100 mug/100 muL endostatin-Cy5.5 and imaged at various points under sedation. Imaging was performed using a lightproof box affixed to a fluorescent microscope mounted with a filter in the NIR bandwidth (absorbance maximum 675 run and emission maximum 694 nm). Images were captured by a CCD and desktop computer and stored as 16-bit Tiff files. The mice were also serially imaged for uptake into the tumor and washout from the tumor. Results: After intraperitoneal injection, endostatin-Cy5.5 was quickly absorbed, producing a NIR fluorescent image of the tumors at 24 h that persisted through 7 days. However, the signal peaked at 42 h after injection. Control animals included mice containing green fluorescent protein (GFP) under the control of an actin promotor, which expresses GFP in every cell; tumor-free mice injected with endostatin-Cy5.5; mice with tumors that were not injected with endostatin-Cy5.5; and mice with tumors injected with dye alone. In the four sets of control animals, no NIR photon emissions were detected at 24 hours or 5 days. Only the GFP mouse was detected using the GFP filter. Unlike previous analogous studies with 4-N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO)-Cy5.5 in which the tumor image faded with time, the endostatin-Cy5.5 NIR signal was emitted from the tumor up to 7 days after injection, the last time point examined. Conclusion: The results of this study demonstrated that endostatin covalently bound to Cy5.5 will migrate from a distant intraperitoneal injection site to a tumor. These data indicate that endostatin-Cy5.5 is appropriate for selectively imaging tumors in experimental animals. Furthermore, data suggest that the anti-angiogenic effect of endostatin occurs through a local mechanism of action, within the tumor or tumor vasculature, rather than through a systemic mechanism. (C) 2004 Elsevier Inc. C1 NCI, Imaging & Mol Therapuet Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Imaging & Mol Therapuet Sect, Radiat Oncol Branch, Bldg 10,Rm B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov NR 21 TC 23 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2004 VL 58 IS 2 BP 536 EP 541 DI 10.1016/j.ijrobp.2003.09.068 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 767QZ UT WOS:000188465300029 PM 14751525 ER PT J AU Norman, B Davis, J Piatigorsky, J AF Norman, B Davis, J Piatigorsky, J TI Postnatal gene expression in the normal mouse cornea by SAGE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Review ID ALDEHYDE DEHYDROGENASE-3 GENE; GROWTH-FACTOR RECEPTOR; TRANSCRIPTION FACTOR; STEM-CELLS; SERIAL ANALYSIS; EPITHELIAL-CELLS; TRANSGENIC MICE; OCULAR SURFACE; INTESTINAL EPITHELIUM; PROTEIN SUPERFAMILY AB PURPOSE. To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS. Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS. A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS. In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, 7 Mem Dr,Bldg 7,Room 100A, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov NR 129 TC 48 Z9 48 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2004 VL 45 IS 2 BP 429 EP 440 DI 10.1167/iovs.03-0449 PG 12 WC Ophthalmology SC Ophthalmology GA 771CX UT WOS:000188769000011 PM 14744882 ER PT J AU Nguyen, QD Shah, SM Van Anden, E Sung, JU Vitale, S Campochiaro, PA AF Nguyen, QD Shah, SM Van Anden, E Sung, JU Vitale, S Campochiaro, PA TI Supplemental oxygen improves diabetic macular edema: A pilot study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 106th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 20-23, 2002 CL ORLANDO, FL SP Amer Acad Ophthalmol ID ENDOTHELIAL GROWTH-FACTOR; OPTICAL COHERENCE TOMOGRAPHY; RETINAL NEOVASCULARIZATION; FACTOR VEGF; RETINOPATHY; INHIBITION; EXPRESSION; ISCHEMIA; PRIMATE; MODEL AB PURPOSE. Diabetic macular edema (DME) is the most common cause of moderate visual disability in persons of working age in the United States. The pathogenesis of DME is poorly understood. In this study, the effect of retinal hypoxia in the development and maintenance of DME was investigated. METHODS. Five patients with chronic DME despite at least one focal laser photocoagulation treatment (nine eyes) received 4 L/min of inspired oxygen by nasal cannula for 3 months. Best corrected visual acuity (VA) and retinal thickness, assessed by optical coherence tomography (OCT), were measured at baseline, during 3 months of oxygen treatment, and for 3 months after stopping oxygen. RESULTS. After 3 months of oxygen therapy, nine of nine eyes with DME at baseline showed a reduction in thickness of the center of the macula. Foveal thickness (FTH) above the normal range was reduced by an average of 43.5% (range, 14%-100%), excess foveolar thickness (CEN) was reduced by an average of 42.1% (range, 13%-100%), and excess macular volume was reduced by an average of 54% (range, 35%-100%). Statistical analyses suggested that these changes were unlikely to be due to chance (P = 0.0077 by Wilcoxon signed-rank test). Three eyes showed improvement in VA by at least 2 lines, one by slightly less than 2 lines, and five eyes showed no change. Three months after discontinuation of oxygen, five of the nine eyes showed increased thickening of the macula compared with when oxygen was discontinued . CONCLUSIONS. Supplemental inspired oxygen may decrease macular thickness due to DME, suggesting that retinal hypoxia is involved in the development and maintenance of DME. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Campochiaro, PA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Maumenee 719,600 N Wolfe St, Baltimore, MD 21287 USA. EM pcampo@jhmi.edu FU NEI NIH HHS [EY13552] NR 21 TC 100 Z9 104 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2004 VL 45 IS 2 BP 617 EP 624 DI 10.1167/iovs.03-0557 PG 8 WC Ophthalmology SC Ophthalmology GA 771CX UT WOS:000188769000035 PM 14744906 ER PT J AU Leker, RR AF Leker, RR TI Tissue plasminogen activator for stroke in Israel: The time has finally come SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material DE tissue plasminogen activator; stroke; thrombolysis ID ACUTE ISCHEMIC-STROKE; THROMBOLYTIC THERAPY; INTRAVENOUS TPA; HYPOTHERMIA; MANAGEMENT; ALTEPLASE; COMMUNITY; RISK C1 Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91010 Jerusalem, Israel. Hadassah Univ Hosp, Dept Neurol, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Agnes Ginges Ctr Human Neurogenet, IL-91120 Jerusalem, Israel. RP Leker, RR (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Room 3C12,36 Convent Dr,MSC 4092, Bethesda, MD 20892 USA. EM LekerR@ninds.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISRAEL MED ASSOC J JI Isr. Med. Assoc. J. PD FEB PY 2004 VL 6 IS 2 BP 95 EP 96 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 772JE UT WOS:000188838200008 PM 14986466 ER PT J AU Wilson, CM Gray, G Read, JS Mwatha, A Lala, S Johnson, S Violari, A Sibiya, PM Fleming, TR Koonce, A Vermund, SH McIntyre, J AF Wilson, CM Gray, G Read, JS Mwatha, A Lala, S Johnson, S Violari, A Sibiya, PM Fleming, TR Koonce, A Vermund, SH McIntyre, J TI Tolerance and safety of different concentrations of chlorhexidine for peripartum vaginal and infant washes: HIVNET 025 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE vertical transmission; chlorhexidine; peripartum microbicide washes ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CLINICAL-TRIAL; HIV TRANSMISSION; PERCUTANEOUS-ABSORPTION; VERTICAL TRANSMISSION; POVIDONE-IODINE; CORD CARE; INTERVENTION; INACTIVATION; BACTERIA AB Background: There is a continuing need to evaluate sustainable interventions for prevention of mother-to-child transmission (MTCT) of HIV type 1. We evaluated different concentrations (0.25%, 1%, and 2%) of chlorhexidine (CHX) for perinatal maternal and infant washes to identify the maximum tolerable concentration of CHX for such an intervention. Methods: Women were enrolled during their third trimester at the maternity unit of the Chris Ham Baragwanath Hospital in Soweto, South Africa, and perinatal maternal and infant washes were completed. Subjective maternal symptoms as well as infant examinations were used to assess tolerability of the washes. Results: The 0.25% concentration of CHX was well tolerated by the mothers (n = 29). Ten of 79 women (13%) with 1% CHX washes complained of mild vaginal area burning or itching, and washes were stopped in 5 (6%). Twenty-three of 75 women (31%) in the 2% CHX wash group had subjective complaints, and the washes were stopped in 12 (16%). There were no clinical indications of toxicity of the CHX washes among infants. Conclusion: A 1% solution of CHX appears to be a safe and tolerable concentration of CHX for consideration in an MTCT prevention trial. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Chris Hani Baragwanath Hosp, Perinatal HIV Res Unit, Soweto, South Africa. NICHD, NIH, Bethesda, MD USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Family Hlth Int, Durham, NC USA. RP Wilson, CM (reprint author), Univ Alabama, Dept Med, 845 19th St S,BBRB 206F, Birmingham, AL 35294 USA. EM cwilson@uab.edu OI Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [5 U01 AI46749, N01 AI035173, N01 AI045200, N01-AI-35173-414, N01-AI-35173-418, U01 AI046749, U01 AI046749-01] NR 24 TC 21 Z9 23 U1 0 U2 1 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 FEB 1 PY 2004 VL 35 IS 2 BP 138 EP 143 DI 10.1097/00126334-200402010-00006 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 804VU UT WOS:000220327000006 PM 14722445 ER PT J AU Dabis, F Newell, ML Fowler, MG Read, JS AF Dabis, F Newell, ML Fowler, MG Read, JS CA Ghent IAS Working Grp HIV Women TI Prevention of HIV transmission through breast-feeding: Strengthening the research agenda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article AB Mother-to-child transmission of HIV through breast-feeding is the remaining challenge facing mothers in resource-poor settings with a high HIV prevalence. Nearly all infants in developing countries are initially breast-fed, and most children continue to receive some breast-feeding until at least 6 months of age but frequently into the 2nd year of life, especially in sub-Saharan Africa and Asia. In December 2002, international researchers convened in Ghent, Belgium, to discuss mechanisms for, rates and risk factors of, and approaches to prevention of HIV transmission through breast-feeding. Four papers were compiled bringing together the presentation and discussions during this workshop, while the fourth paper also benefits from presentation made during an earlier workshop on vaccines in the prevention of mother-to-child transmission. These papers summarize the current state of knowledge and highlight the outstanding issues that will need to be addressed in the very near future before research advances can be translated into public health practice. C1 UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. Ghent Working Grp HIV Infect Women & Children, Ghent, Belgium. Univ Bordeaux 2, ISPED, INSERM, U 330, F-33076 Bordeaux, France. Ctr Dis Control, Atlanta, GA 30333 USA. NICHD, PAMA, NIH, Bethesda, MD USA. RP Newell, ML (reprint author), UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. EM m.newell@ich.ucl.ac.uk RI Van de Perre, Philippe/B-9692-2008; OI Van de Perre, Philippe/0000-0002-3912-0427; Newell, Marie-Louise/0000-0002-1074-7699 NR 0 TC 8 Z9 8 U1 0 U2 0 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 FEB 1 PY 2004 VL 35 IS 2 BP 167 EP 168 DI 10.1097/00126334-200402010-00011 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 804VU UT WOS:000220327000011 PM 14722450 ER PT J AU Safrit, JT Ruprecht, R Ferrantelli, F Xu, WD Kitabwalla, M Van Rompay, K Marthas, M Haigwood, N Mascola, JR Luzuriaga, K Jones, SA Mathieson, BJ Newell, ML AF Safrit, JT Ruprecht, R Ferrantelli, F Xu, WD Kitabwalla, M Van Rompay, K Marthas, M Haigwood, N Mascola, JR Luzuriaga, K Jones, SA Mathieson, BJ Newell, ML CA Ghent IAS Working Grp HIV Women TI Immunoprophylaxis to prevent mother-to-child transmission of HIV-1 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE immunoprophylaxis; prevention mother-to-child transmission; neonates; vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; BROADLY NEUTRALIZING ANTIBODIES; NEWBORN RHESUS MACAQUES; VERTICAL TRANSMISSION; NEONATAL MACAQUES; PASSIVE-IMMUNIZATION; PHASE-I; ENVELOPE GLYCOPROTEIN; MATERNAL ANTIBODIES AB Antiretroviral therapy can profoundly reduce the risk of mother-to-child transmission (MTCT) of HIV, but the drugs have a relatively short half-life and should thus be administered throughout breast-feeding to optimally prevent postnatal infection of the infant. The potential toxicities and the development of resistance may limit the long-term efficacy of antiretroviral prophylaxis, and a safe and effective active/passive immunoprophylaxis regimen, begun at birth, and potentially overlapping with interpartum or neonatal chemoprophylaxis, would pose an attractive alternative. This review draws on data presented at the Ghent Workshop on prevention of breast milk transmission and on selected issues from a workshop specifically relating to immunoprophylaxis held in Seattle in October 2002. This purpose of this review is to address the scientific rationale for the development of passive (antibody) and active (vaccine) immunization strategies for prevention of MTCT. Data regarding currently or imminently available passive and active immunoprophylaxis products are reviewed for their potential use in neonatal trials within the coming 1-2 years. C1 UCL, Ctr Paediat Epidemiol & Biostat, Inst Child Hlth, London, England. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. NIAID, Vaccine Res Ctr, Bethesda, MD USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NIAID, Div Aids, Bethesda, MD 20892 USA. US Dept HHS, NIH, Off AIDS Res, Bethesda, MD USA. UCL, Inst Child Hlth, London, England. RP Newell, ML (reprint author), UCL, Ctr Paediat Epidemiol & Biostat, Inst Child Hlth, London, England. EM m.newell@ich.ucl.ac.uk RI Van de Perre, Philippe/B-9692-2008; Ferrantelli, Flavia/J-7794-2016; OI Van de Perre, Philippe/0000-0002-3912-0427; Ferrantelli, Flavia/0000-0002-0768-1078; Newell, Marie-Louise/0000-0002-1074-7699 NR 47 TC 43 Z9 43 U1 0 U2 0 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 FEB 1 PY 2004 VL 35 IS 2 BP 169 EP 177 DI 10.1097/00126334-200402010-00012 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 804VU UT WOS:000220327000012 PM 14722451 ER PT J AU John-Stewart, G Mbori-Ngacha, D Ekpini, R Janoff, EN Nkengasong, J Read, JS Van de Perre, P Newell, ML AF John-Stewart, G Mbori-Ngacha, D Ekpini, R Janoff, EN Nkengasong, J Read, JS Van de Perre, P Newell, ML CA Ghent IAS Working Grp HIV Women TI Breast-feeding and transmission of HIV-1 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE breastfeeding; mother-to-child transmission; postnatal transmission; risk factors; mechanisms ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-CHILD; SHORT-COURSE ZIDOVUDINE; LEUKOCYTE PROTEASE INHIBITOR; VIRAL LOAD; POSTNATAL TRANSMISSION; COTE-DIVOIRE; VERTICAL TRANSMISSION; TYPE-1 TRANSMISSION; RANDOMIZED-TRIAL AB Breast-feeding substantially increases the risk of HIV-1 transmission from mother to child, and although peripartum antiretroviral therapy prophylaxis significantly decreases the risk of mother-to-child transmission around the time of delivery, this approach does not affect breast-feeding transmission. Increased maternal RNA viral load in plasma and breast milk is strongly associated with increased risk of transmission through breast-feeding, as is breast health, and it has been suggested that exclusive breast-feeding could be associated with lower rates of breast-feeding transmission than mixed feeding of both breast- and other milk or feeds. Transmission through breast-feeding can take place at any point during lactation, and the cumulative probability of acquisition of infection increases with duration of breast-feeding. HIV-1 has been detected in breast milk in cell-free and cellular compartments; infant gut mucosal surfaces are the most likely site at which transmission occurs. Innate and acquired immune factors may act most effectively in combination to prevent primary HIV-1 infection by breast milk. C1 UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. Univ Montpellier 1, Montpellier, France. CHU Arnaud de Villeneuve, Lab Bacteriol Virol, Villeneuve, France. NICHD, PAMA Branch, NIH, Bethesda, MD USA. CDCP, Div HIV AIDS Prevent Surveillance & Epidemiol, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. Projet RETRO CI, Abidjan, Cote Ivoire. Univ Minnesota, Vet Affairs Med Ctr, Div Infect Dis, Minneapolis, MN USA. Univ Nairobi, Dept Paediat, Nairobi, Kenya. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Newell, ML (reprint author), UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, Mortimer St, London, England. EM m.newell@ich.ucl.ac.uk RI Van de Perre, Philippe/B-9692-2008; OI Van de Perre, Philippe/0000-0002-3912-0427; Newell, Marie-Louise/0000-0002-1074-7699 FU NIAID NIH HHS [P30 AI027757-12, P30 AI027757]; NICHD NIH HHS [HD-41361, K24 HD054314, N01 HD 43208, R01 HD041361]; NIDCR NIH HHS [DE-72621] NR 53 TC 79 Z9 82 U1 0 U2 3 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 FEB 1 PY 2004 VL 35 IS 2 BP 196 EP 202 DI 10.1097/00126334-200402010-00015 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 804VU UT WOS:000220327000015 PM 14722454 ER PT J AU Arnold, LE Chuang, S Davies, M Abikoff, HB Conners, CK Elliott, GR Greenhill, LL Hechtman, L Hinshaw, SP Hoza, B Jensen, PS Kraemer, HC Langworthy-Lam, KS March, JS Newcorn, JH Pelham, WE Severe, JB Swanson, JM Vitiello, B Wells, KC Wigal, T AF Arnold, LE Chuang, S Davies, M Abikoff, HB Conners, CK Elliott, GR Greenhill, LL Hechtman, L Hinshaw, SP Hoza, B Jensen, PS Kraemer, HC Langworthy-Lam, KS March, JS Newcorn, JH Pelham, WE Severe, JB Swanson, JM Vitiello, B Wells, KC Wigal, T TI Nine months of multicomponent behavioral treatment for ADHD and effectiveness of MTA fading procedures SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE ADHD; treatment; fading; generalization; maintenance ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; MULTIMODAL-TREATMENT; TREATMENT STRATEGIES; TREATMENT RESPONSE; TREATMENT OUTCOMES; CHILDREN; MODERATORS; RELEVANCE; DESIGN AB We examined 9-month data from the 14-month NIMH Multimodal Treatment Study of Children with ADHD (the MTA) as a further check on the relative effect of medication (MedMgt) and behavioral treatment (Beh) for attention-deficit/hyperactivity disorder (ADHD) while Beh was still being delivered at greater intensity than at 14-month endpoint, and conversely as a check on the efficacy of the MTA behavioral generalization/maintenance procedures. Intention-to-treat analysis at 9 months showed essentially the same results as at 14 months, after Beh had been completely faded; MedMgt and the combination (Comb) of medication and Beh were significantly superior to Beh and community care (CC) for ADHD and oppositional-defiant (ODD) symptoms, with mixed results for social skills and internalizing symptoms. All treatment-group differences examined as changes in slopes from 9 to 14 months were nonsignificant (we found general improvement for all groups). Slopes from baseline to 9 months correlated highly (r > .74, p < .0001) with slopes from baseline to 14 months for all groups. The time function from baseline to 14 months showed a significant linear, but not quadratic, trend for the main outcome measure (a composite of parent- and teacher-rated ADHD and ODD symptoms) for all groups. Findings suggest that in contrast to the hypothesized deterioration in the relative benefit of Beh between 9 and 14 months (after completion of fading), the MTA Beh generalization and maintenance procedures implemented through 9 months apparently yielded continuing improvement through 14 months, with preservation of the relative position of Beh compared to other treatment strategies. C1 Ohio State Univ, Columbus, OH 43210 USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. NYU Med Ctr, New York, NY 10016 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. Univ Calif Berkeley, Berkeley, CA 94720 USA. Purdue Univ, Lafayette, IN USA. Stanford Univ, Stanford, CA 94305 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. SUNY Buffalo, Buffalo, NY 14260 USA. NIMH, Rockville, MD 20857 USA. Univ Calif Irvine, Irvine, CA USA. RP Arnold, LE (reprint author), 479 S Galena Rd, Sunbury, OH 43074 USA. OI Jensen, Peter/0000-0003-2387-0650; Newcorn, Jeffrey /0000-0001-8993-9337 FU NIMH NIH HHS [UO1 MH50447, MH50467, U01-MH50453, U01-MH50461, UO1 MH50440, UO1 MH50453, UO1 MH50454, UO1 MH50461, UO1 MH50467] NR 25 TC 19 Z9 19 U1 2 U2 9 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 2004 VL 32 IS 1 BP 39 EP 51 DI 10.1023/B:JACP.0000007579.61289.31 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 752LE UT WOS:000187161300004 PM 14998110 ER PT J AU Lin, H Boesel, KM Prussin, C Foster, B Romero, FA Townley, R Casale, TB AF Lin, H Boesel, KM Prussin, C Foster, B Romero, FA Townley, R Casale, TB TI Omalizumab rapidly decreases nasal allergic response and Fc epsilon RI on basophils SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergic rhinitis; anti-IgE treatment; omalizumab; Fc epsilon RI receptor; basophils ID ANTI-IGE ANTIBODY; HUMANIZED MONOCLONAL-ANTIBODY; ASTHMATIC SUBJECTS; PERIPHERAL-BLOOD; RHINITIS; EXPRESSION; CELLS AB Background: Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. Objective: This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI receptors on basophils. Methods: We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD30 ragweed nasal allergen challenge, patients received either omalizumab, similar to0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD30 dose biweekly. FcepsilonRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. Results: Mean IgE levels decreased by 96% (P < .001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P < .001) and 12.2% at 35 to 42 days (P < .001) for the omalizumab group. There was a median decrease in basophil FcepsilonRI expression of 73% (P < .001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcepsilonRI expression were observed throughout the study in the placebo group. Conclusions: Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor expression on immune effector cells. C1 Creighton Univ, Dept Med, Div Allergy immunol, Omaha, NE 68131 USA. NIAID, NIH, Lab Allerg Dis, Bethesda, MD USA. RP Casale, TB (reprint author), Creighton Univ, Dept Med, Div Allergy immunol, 601 N 30th St, Omaha, NE 68131 USA. RI Casale, Thomas/K-4334-2013 OI Casale, Thomas/0000-0002-3149-7377 NR 15 TC 133 Z9 140 U1 0 U2 2 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 FEB PY 2004 VL 113 IS 2 BP 297 EP 302 DI 10.1016/j.jaci.2003.11.044 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 773EX UT WOS:000188885700018 PM 14767445 ER PT J AU Dokholyan, N Glabe, C Holtzman, D Koudinov, A Lomakin, A Paganini, N Teplow, D Thirumalai, D Tycko, R AF Dokholyan, N Glabe, C Holtzman, D Koudinov, A Lomakin, A Paganini, N Teplow, D Thirumalai, D Tycko, R TI Live discussion: Protein folding and neurodegeneration: Biophysics to the rescue? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Editorial Material ID HIGH-DENSITY-LIPOPROTEIN; AMYLOID-BETA; ALZHEIMERS; MECHANISM; OLIGOMERS C1 Univ N Carolina, Chapel Hill, NC 27514 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Washington Univ, St Louis, MO USA. Russian Acad Med Sci, Moscow, Russia. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Maryland, College Pk, MD 20742 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Dokholyan, N (reprint author), Univ N Carolina, Chapel Hill, NC 27514 USA. RI Dokholyan, Nikolay/B-2238-2009 OI Dokholyan, Nikolay/0000-0002-8225-4025 NR 8 TC 0 Z9 0 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD FEB PY 2004 VL 6 IS 1 BP 99 EP 105 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 862NP UT WOS:000224498000011 ER PT J AU Metter, EJ Talbot, LA Schrager, M Conwit, RA AF Metter, EJ Talbot, LA Schrager, M Conwit, RA TI Arm-cranking muscle power and arm isometric muscle strength are independent predictors of all-cause mortality in men SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE muscle mass; aging; physical activity ID WINGATE ANAEROBIC TEST; AGE-RELATED DECLINE; HEALTHY-MEN; CARDIORESPIRATORY FITNESS; PHYSICAL-ACTIVITIES; PEAK TORQUE; BODY-MASS; WOMEN; PERFORMANCE; OUTPUT AB Poor muscle strength is associated with mortality, presumably due to low muscle mass. Notably, muscle power declines more rapidly than muscle strength with increasing age, which may be related to more complex central nervous system movement control. We examined arm-cranking power against four workloads and isometric strength measured in the upper extremities of 993 men longitudinally tested over a 25-yr period. Muscle mass was estimated by using 24-h creatinine excretion; physical activity was assessed by self-reported questionnaire. Muscle power and strength were modeled by time by using mixed-effects models, which developed regression equations for each individual. The first derivative of these equations estimated rate of change in strength or power at each evaluation. Survival analyses, using the counting method, examined the impact of strength, power, and their rates of change on all-cause mortality while adjusting for age. Arm-cranking power [relative risk (rr) = 0.984 per 100 kg . m . min(-1), P < 0.001] was a stronger predictor of mortality than was arm strength (rr = 0.986 per 10 kg, P = not significant), whereas rate of power change (rr = 0.989 per 100 kg &BULL; min(-1) &BULL; yr(-1)) and rate of arm strength change (rr = 0.888 per 10 kg/yr) were risks independent of the power or strength levels. The impacts of power and strength were partially independent of muscle mass and physical activity. The risk of mortality was similar across the four power workloads (rr = 0.93 - 0.96 per 100 kg &BULL; m &BULL; min(-1)), whereas the lowest load generated less than one-half the power as the higher loads. Arm-cranking power is a risk factor for mortality, independent of muscle strength, physical activity, and muscle mass. The impact is found with loads that do not generate maximal power, suggesting an important role for motor coordination and speed of movement. C1 NIA, Intramural Res Program, Clin Res Branch, ASTRA,Harbor Hosp, Baltimore, MD 21225 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NINDS, Bethesda, MD 20894 USA. RP Metter, EJ (reprint author), NIA, Intramural Res Program, Clin Res Branch, ASTRA,Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. NR 55 TC 47 Z9 49 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB 1 PY 2004 VL 96 IS 2 BP 814 EP 821 DI 10.1152/japplphysiol.00370.2003 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 761EU UT WOS:000187888400056 PM 14555682 ER PT J AU Pezdek, K Morrow, A Blandon-Gitlin, I Goodman, GS Quas, JA Saywitz, KJ Bidrose, S Pipe, ME Rogers, M Brodie, L AF Pezdek, K Morrow, A Blandon-Gitlin, I Goodman, GS Quas, JA Saywitz, KJ Bidrose, S Pipe, ME Rogers, M Brodie, L TI Detecting deception in children: Event familiarity affects criterion-based content analysis ratings SO JOURNAL OF APPLIED PSYCHOLOGY LA English DT Article ID FALSE CHILDHOOD MEMORIES; SEXUAL ABUSE; STATEMENTS; SUGGESTIBILITY; PLAUSIBILITY; CREDIBILITY; TESTIMONY; INTERVIEW; ADULTS AB Statement Validity Assessment (SVA) is a comprehensive credibility assessment system, with the Criterion-Based Content Analysis (CBCA) as a core component. Worldwide, the CBCA is reported to be the most widely used veracity assessment instrument. We tested and confirmed the hypothesis that CBCA scores are affected by event familiarity; descriptions of familiar events are more likely to be judged true than are descriptions of unfamiliar events. CBCA scores were applied to transcripts of 114 children who recalled a routine medical procedure (control) or a traumatic medical procedure that they had experienced one time (relatively unfamiliar) or multiple times (relatively familiar). CBCA scores were higher for children in the relatively familiar than the relatively unfamiliar condition, and CBCA scores were significantly correlated with age. Results raise serious questions regarding the forensic suitability of the CBCA for assessing the veracity of children's accounts. C1 Claremont Grad Sch Univ, Sch Behav & Org, Dept Psychol, Claremont, CA 91711 USA. Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. Univ Calif Irvine, Program Social Ecol, Irvine, CA 92717 USA. Harbor UCLA Med Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Otago, Dept Psychiat, Dunedin, New Zealand. NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. RP Pezdek, K (reprint author), Claremont Grad Sch Univ, Sch Behav & Org, Dept Psychol, 123 E 8th St, Claremont, CA 91711 USA. EM kathy.pezdek@cgu.edu NR 31 TC 22 Z9 25 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-9010 EI 1939-1854 J9 J APPL PSYCHOL JI J. Appl. Psychol. PD FEB PY 2004 VL 89 IS 1 BP 119 EP 126 DI 10.1037/0021-9010.89.1.119 PG 8 WC Psychology, Applied; Management SC Psychology; Business & Economics GA 770NC UT WOS:000188736000009 PM 14769124 ER PT J AU Rzhetsky, A Iossifov, I Koike, T Krauthammer, M Kra, P Morris, M Yu, H Duboue, PA Weng, WB Wilbur, WJ Hatzivassiloglou, V Friedman, C AF Rzhetsky, A Iossifov, I Koike, T Krauthammer, M Kra, P Morris, M Yu, H Duboue, PA Weng, WB Wilbur, WJ Hatzivassiloglou, V Friedman, C TI GeneWays: a system for extracting, analyzing, visualizing, and integrating molecular pathway data SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE text mining; bioinformatics; information extraction; molecular networks; molecular interactions; database; artificial intelligence; knowledge engineering; machine learning ID PROTEIN-PROTEIN INTERACTIONS; NAMES; INFORMATION; ONTOLOGY; ARTICLES; NETWORKS; BIOLOGY; ECOCYC; GENES; TEXT AB The immense growth in the volume of research literature and experimental data in the field of molecular biology calls for efficient automatic methods to capture and store information. In recent years. several groups have worked on specific problems in this area, such as automated selection of articles pertinent to molecular biology. or automated extraction of information using natural-language processing. information visualization. and generation of specialized knowledge bases for molecular biology. GeneWays is an integrated system that combines several such subtasks. It analyzes interactions between molecular Substances, drawing on multiple Sources of information to infer a consensus view of molecular networks. GeneWays is designed as an open platform, allowing researchers to query. review. and critique stored information. (C) 2003 Elsevier Inc. All rights reserved. C1 Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. Columbia Univ, Dept Biomed Informat, New York, NY 10032 USA. Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10032 USA. Columbia Univ, Dept Comp Sci, New York, NY 10032 USA. Hitachi Software Engn Co Ltd, Yokohama, Kanagawa, Japan. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20984 USA. RP Rzhetsky, A (reprint author), Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. EM ar345@columbia.edu RI rzhetsky, andrey/B-6118-2012; OI Rzhetsky, Andrey/0000-0001-6959-7405 FU NIGMS NIH HHS [GM61372] NR 62 TC 149 Z9 157 U1 3 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD FEB PY 2004 VL 37 IS 1 BP 43 EP 53 DI 10.1016/j.jbi.2003.10.001 PG 11 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 813YS UT WOS:000220943000005 PM 15016385 ER PT J AU Jacob, J Louis, JM Richter, BWM Duckett, CS Torchia, DA AF Jacob, J Louis, JM Richter, BWM Duckett, CS Torchia, DA TI Letter to the Editor: The C-terminal domain of Viral IAP associated factor (cVIAF) is a structural homologue of phosducin: Resonance assignments and secondary structure of the C-terminal domain of VIAF SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE apoptosis; cVIAF; IAP; NMR assignments; phosducin ID PROTEIN; IDENTIFICATION; APOPTOSIS; FAMILY C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Jacob, J (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. EM jaison.jacob@vanderbilt.edu NR 10 TC 2 Z9 2 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD FEB PY 2004 VL 28 IS 2 BP 197 EP 198 DI 10.1023/B:JNMR.0000013820.43366.99 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 777KM UT WOS:000189177600013 PM 14755167 ER PT J AU Lukin, JA Kontaxis, G Simplaceanu, V Yuan, Y Bax, A Ho, C AF Lukin, JA Kontaxis, G Simplaceanu, V Yuan, Y Bax, A Ho, C TI Letter to the Editor: Backbone resonance assignments of human adult hemoglobin in the carbonmonoxy form SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE backbone resonance assignments; carbonmonoxy-hemoglobin; NMR ID PROTEINS C1 Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Ho, C (reprint author), Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM cnho@andrew.cmu.edu RI Ho, Chien/O-6112-2016 OI Ho, Chien/0000-0002-4094-9232 FU NCRR NIH HHS [S10RR-11248]; NHLBI NIH HHS [R01HL-24525] NR 10 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD FEB PY 2004 VL 28 IS 2 BP 203 EP 204 DI 10.1023/B:JNMR.0000013816.64039.6f PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 777KM UT WOS:000189177600016 PM 14755170 ER PT J AU Streeten, EA McBride, DJ Lodge, AL Pollin, TI Stinchcomb, DG Agarwala, R Schaffer, AA Shapiro, JR Shuldiner, AR Mitchell, BD AF Streeten, EA McBride, DJ Lodge, AL Pollin, TI Stinchcomb, DG Agarwala, R Schaffer, AA Shapiro, JR Shuldiner, AR Mitchell, BD TI Reduced incidence of hip fracture in the Old Order Amish SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoporosis; Amish; bone mineral density; hip fracture; geographic information systems ID PHYSICAL-ACTIVITY; PROXIMAL FEMUR; US ADULTS; HONG-KONG; BONE; OSTEOPOROSIS; PREVALENCE; URBAN; WOMEN; RATES AB Introduction: Understanding the patterns of fracture risk across populations could reveal insights about bone health and lead to the earlier detection and prevention of osteoporosis. Toward this aim, we compared hip fracture incidence and bone mineral density (BMD) between an Old Order Amish (OOA) community, characterized by a rural and relatively active lifestyle, and non-Amish U.S. whites. Materials and Methods: All hospital admissions for hip fracture among OOA individuals in Lancaster County, PA, were identified between 1995 and 1998 from four area hospitals. Hip fracture incidence was calculated by cross-referencing an available Anabaptist genealogy database with communities located within these hospital service areas and compared with non-Amish whites obtained from National Hospital Discharge data. Additionally, BMD at the hip was compared between 287 Amish subjects and non-Amish whites from the National Health and Nutrition Examination Survey III survey. Results and Conclusions: OOA experienced 42% fewer hip fractures than would be expected had they experienced the same rate of hip fracture as observed in non-Amish whites (p < 0.01) and a higher mean BMD that was significant in women (p < 0.05) but not men. Further evaluation of lifestyle and/or genetic differences between Amish and non-Amish populations may shed insights into etiologic factors influencing hip fracture risk. C1 Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Texas Dept Hlth, Ctr Hlth Stat, Austin, TX 78756 USA. NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, US Dept HHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD USA. Armed Forces Univ, Bethesda, MD USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA. RP Streeten, EA (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Room N3W130,22 S Greene St, Baltimore, MD 21201 USA. EM estreete@medicine.umaryland.edu RI Schaffer, Alejandro/F-2902-2012; OI Mitchell, Braxton/0000-0003-4920-4744 FU NCI NIH HHS [K07-CA67960]; NCRR NIH HHS [M01 RR165001]; NIA NIH HHS [R01-AG18728]; NIAMS NIH HHS [R01-AR46838]; NIDDK NIH HHS [R01-DK54261, K24-DK02673] NR 28 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 2004 VL 19 IS 2 BP 308 EP 313 DI 10.1359/JBMR.0301223 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 767DY UT WOS:000188426000016 PM 14969401 ER PT J AU Giles, TD Chatterjee, K Cohn, JN Colucci, WS Feldman, AM Ferrans, VJ Roberts, R AF Giles, TD Chatterjee, K Cohn, JN Colucci, WS Feldman, AM Ferrans, VJ Roberts, R TI Definition, classification, and staging of the adult cardiomyopathies: A proposal for revision SO JOURNAL OF CARDIAC FAILURE LA English DT Editorial Material ID TASK-FORCE C1 LSUHSC, Cardiovasc Res, New Orleans, LA 70112 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Minnesota, Minneapolis, MN USA. Boston Univ, Med Ctr, Boston, MA USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. NHLBI, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Giles, TD (reprint author), LSUHSC, Cardiovasc Res, Room 331 E,1542 Tulane Ave,Box T3M-3, New Orleans, LA 70112 USA. NR 5 TC 4 Z9 4 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD FEB PY 2004 VL 10 IS 1 BP 6 EP 8 DI 10.1016/S1071-9164(03)00580-3 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 779BL UT WOS:000189275700003 PM 14966768 ER PT J AU Peyster, E Norman, J Domanski, M AF Peyster, E Norman, J Domanski, M TI Prevalence and predictors of heart failure with preserved systolic function: Community hospital admissions of a racially and gender diverse elderly population SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; preserved systolic function; diastolic dysfunction ID EJECTION FRACTION; PROGNOSIS; DYSFUNCTION; AGE AB Background: The reported prevalence of preserved systolic function (PSF) heart failure (HF) varies widely and has not been well-studied in nonwhite patients. To estimate the prevalence of PSF HF resulting in hospital admission, we studied admissions to a large community hospital serving a racially diverse community. Methods: The charts of 300 consecutive patients greater than or equal to65 years old with a primary discharge diagnosis of HF were reviewed. In patients who met the Framingham criteria for HF diagnosis, an assessment of left ventricular function was obtained from review of chart data. Comparison of baseline characteristics and multivariate analysis of potential predictors of PSF HF was undertaken. Results: Of the 300 patients, 247 (82%) met the Framingham criteria for diagnosis of HF. Ninety-seven patients (39%) of these had PSF. Twenty (8%) of the diagnosed HF patients had a diagnosis of severe aortic or mitral valvular disease, 9 of whom had preserved systolic functions. Thus 88 (36%) of the HF patients had PSF HF likely resulting from diastolic dysfunction. On multivariate analysis, age, hypertension at presentation, peripheral edema, normal sinus rhythm and a history of coronary artery bypass grafting or coronary angioplasty were significantly associated with PSF HF rather than HF with reduced systolic function. Left bundle branch block or other intraventricular conduction delay was independently associated with reduced systolic function HF. However, because these findings occurred in patients with and without systolic dysfunction, none were pathognomonic of PSF HF. Conclusion: In this racially diverse, majority nonwhite, cohort of older patients admitted for HF, the Framingham criteria for the diagnosis of HF were met in 82% of the patients. Of these, 39% had PSF HF and 36% had PSF HF in the absence of severe aortic or mitral valve disease, suggesting that diastolic dysfunction was etiologic. Although there was an independent association of PSF HF with a number of clinical characteristics, none of these characteristics was pathognomonic of preserved, versus reduced, systolic function HF. C1 NHLBI, Div Heart & Vasc Dis, Rockledge Ctr 2, Clin Trials Grp, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Domanski, M (reprint author), NHLBI, Div Heart & Vasc Dis, Rockledge Ctr 2, Clin Trials Grp, Room 8146,6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. NR 28 TC 15 Z9 15 U1 2 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD FEB PY 2004 VL 10 IS 1 BP 49 EP 54 DI 10.1016/S1071-9164(03)00579-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 779BL UT WOS:000189275700010 PM 14966775 ER PT J AU Ilias, I Pacak, K AF Ilias, I Pacak, K TI Current approaches and recommended algorithm for the diagnostic localization of pheochromocytoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; OF-THE-ART; METAIODOBENZYLGUANIDINE MIBG SCINTIGRAPHY; PRIMARY HEPATIC PHEOCHROMOCYTOMA; FALSE-POSITIVE DIAGNOSIS; NEURAL CREST TUMORS; MALIGNANT PHEOCHROMOCYTOMA; ADRENAL MASSES; I-131 METAIODOBENZYLGUANIDINE C1 NICHHD, Unit Clin Neuroendocrinol, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Unit Clin Neuroendocrinol, Pediat & Reprod Endocrinol Branch, NIH, Bldg 100,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov NR 214 TC 137 Z9 159 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 FEB 1 PY 2004 VL 89 IS 2 BP 479 EP 491 DI 10.1210/jc.2003-031091 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 771AT UT WOS:000188763900004 PM 14764749 ER PT J AU Chrousos, GP Charmandari, E Kino, T AF Chrousos, GP Charmandari, E Kino, T TI Editorial: Glucocorticoid action networks - An introduction to systems biology SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CLINICAL-IMPLICATIONS; STRESS; NEUROENDOCRINE C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM chrousog@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 12 TC 37 Z9 43 U1 0 U2 5 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 FEB 1 PY 2004 VL 89 IS 2 BP 563 EP 564 DI 10.1210/jc.2003-032026 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 771AT UT WOS:000188763900017 PM 14764762 ER PT J AU Weise, M Mehlinger, SL Drinkard, B Rawson, E Charmandari, E Hiroi, M Eisenhofer, G Yanovski, JA Chrousos, GP Merke, DP AF Weise, M Mehlinger, SL Drinkard, B Rawson, E Charmandari, E Hiroi, M Eisenhofer, G Yanovski, JA Chrousos, GP Merke, DP TI Patients with classic congenital adrenal hyperplasia have decreased epinephrine reserve and defective glucose elevation in response to high-intensity exercise SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; CATECHOLAMINE RESPONSES; METABOLIC-RESPONSES; TREADMILL EXERCISE; PROLONGED EXERCISE; RUNNING RATS; HYPOGLYCEMIA; CHILDREN; ADRENOMEDULLARY; STRESS AB Classic congenital hyperplasia (CAH) is characterized by impaired adrenocortical function with a decrease in cortisol and aldosterone secretion and an increase in androgen secretion. Adrenomedullary function is also compromised due to developmental defects in the formation of the adrenal medulla, leading to decreased production of epinephrine. To examine the response to a natural stressful stimulus in patients with classic CAH, we studied hormonal, metabolic, and cardiorespiratory parameters in response to a standardized high-intensity exercise protocol in nine adolescent patients with CAH and nine healthy controls matched for gender, age, and percent body fat. The same relative workload was applied, based on individual maximal aerobic capacity, and all patients received their usual glucocorticoid and mineralocorticoid replacement. When compared with their normal counterparts, patients with CAH had significantly lower epinephrine levels both at baseline and at peak exercise (P<0.01), whereas norepinephrine levels did not differ. Blood glucose concentrations were similar at baseline, but the normal exercise-induced rise observed in the healthy controls was significantly blunted in the CAH patients (P<0.01). Peak heart rate was also lower in CAH patients than healthy controls (P<0.05). As expected, the normal exercise-induced increase in cortisol was not observed in patients with CAH. No significant differences were found in serum levels of insulin, glucagon, GH, lactate and free fatty acids, blood pressure, or ability to sustain exercise between the two groups. Patients with CAH replaced with glucocorticoids have decreased adrenomedullary reserve and impaired exercise-induced changes in glucose but normal short-term high-intensity exercise performance. Whether the combination of epinephrine and cortisol deficiency poses a risk for hypoglycemia and/or decreased endurance during long-term physical stress has to be determined. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NIH, Ctr Clin, Bldg 10,Room 13S260,10 Ctr Dr MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov RI Charmandari, Evangelia/B-6701-2011; OI Yanovski, Jack/0000-0001-8542-1637 NR 46 TC 36 Z9 39 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB 1 PY 2004 VL 89 IS 2 BP 591 EP 597 DI 10.1210/jc.2003-030634 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 771AT UT WOS:000188763900022 PM 14764767 ER PT J AU Thadhani, R Mutter, WP Wolf, M Levine, RJ Taylor, RN Sukhatme, VP Ecker, J Karumanchi, SA AF Thadhani, R Mutter, WP Wolf, M Levine, RJ Taylor, RN Sukhatme, VP Ecker, J Karumanchi, SA TI First trimester placental growth factor and soluble Fms-like tyrosine kinase 1 and risk for preeclampsia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW-DOSE ASPIRIN; PREGNANCY-INDUCED HYPERTENSION; MATERNAL SERUM LEVELS; INSULIN-RESISTANCE; SUBSEQUENT PREECLAMPSIA; PREVENT PREECLAMPSIA; RANDOMIZED-TRIAL; POTENTIAL ROLE; WOMEN; 2ND-TRIMESTER AB An imbalance of pro- and antiangiogenic factors may lead to preeclampsia (PE). In this prospective nested case-control study, we investigated whether first trimester serum levels of placental growth factor (PlGF), a potent angiogenic factor, and its soluble inhibitor, soluble fms-like tyrosine kinase 1 (sFlt1), distinguished women who developed PE (n = 40) from those who developed gestational hypertension (n = 40), delivered a small for gestational age (SGA) newborn (n = 40), or completed a full term normal pregnancy (n = 80). Compared with controls, serum PlGF levels were lower among women who developed PE (2 +/- 24 pg/ml vs. 63 +/- 145 pg/ml; P < 0.01) or gestational hypertension (27 +/- 19 pg/ml; P = 0.03), or who delivered a SGA newborn (21 +/- 16 pg/ml; P < 0.01). In contrast, serum sFlt1 levels did not markedly differ between the groups: PE, 1048 +/- 657 pg/ml; gestational hypertension, 942 +/- 437 pg/ml; SGA newborns, 1011 +/- 479 pg/ml; and normal controls, 973 +/- 490 pg/ml. Multivariable analysis adjusting for potential confounders and serum sFlt1 levels demonstrated a 3.7-fold (95% confidence interval, 1.2-12.5) increase in risk for PE for every log unit decrease in serum levels of PlGF compared with controls. Analyses for gestational hypertension and SGA were not significant. Examined in tertiles, the risk for PE was increased 28.7-fold (95% confidence interval, 2.3-351.0) in the third (< 12 pg/ml) compared with the first (>39 pg/ml) PlGF tertile. First trimester serum levels of PlGF and sFlt1 may identify women at high risk for PE. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Obstet & Gynecol, Boston, MA 02215 USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. RP Thadhani, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu FU NCRR NIH HHS [RR17376]; NHLBI NIH HHS [HL73469]; NICHD NIH HHS [HD39223]; NIDDK NIH HHS [DK02825, DK64255] NR 55 TC 271 Z9 283 U1 1 U2 10 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 FEB 1 PY 2004 VL 89 IS 2 BP 770 EP 775 DI 10.1210/jc.2003-031244 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 771AT UT WOS:000188763900051 PM 14764795 ER PT J AU Nikolova, V Leimena, C McMahon, AC Tan, JC Chandar, S Jogia, D Kesteven, SH Michalicek, J Otway, R Verheyen, F Rainer, S Stewart, CL Martin, D Feneley, MP Fatkin, D AF Nikolova, V Leimena, C McMahon, AC Tan, JC Chandar, S Jogia, D Kesteven, SH Michalicek, J Otway, R Verheyen, F Rainer, S Stewart, CL Martin, D Feneley, MP Fatkin, D TI Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; HUTCHINSON-GILFORD PROGERIA; FAMILIAL PARTIAL LIPODYSTROPHY; RECRUITABLE STROKE WORK; HEART-FAILURE; GENE-EXPRESSION; LMNA MUTATIONS; CARDIAC MYOCYTES; LACKING DESMIN; ENVELOPE AB Laminopathies are a group of disorders caused by mutations in the LMNA gene that encodes the nuclear lamina proteins, lamin A and lamin C; their pathophysiological basis is unknown. We report that lamin A/C-deficient (Lmna(-/-)) mice develop rapidly progressive dilated cardiomyopathy (DCM) characterized by left ventricular (LV) dilation and reduced systolic contraction. Isolated Lmna(-/-) myocytes show reduced shortening with normal baseline and peak amplitude of Ca2+ transients. Lmna(-/-) LV myocyte nuclei have marked alterations of shape and size with central displacement and fragmentation of heterochromatin; these changes are present but less severe in left atrial nuclei. Electron microscopy of Lmna(-/-) cardiomyocytes shows disorganization and detachment of desmin filaments from the nuclear surface with progressive disruption of the cytoskeletal desmin network. Alterations in nuclear architecture are associated with defective nuclear function evidenced by decreased SREBP1 import, reduced PPARgamma expression, and a lack of hypertrophic gene activation. These findings suggest a model in which the primary pathophysiological mechanism in Lmna(-/-) mice is defective force transmission resulting from disruption of lamin interactions with the muscle-specific desmin network and loss of cytoskeletal tension. Despite severe DCM, defects in nuclear function prevent Lmna(-/-) cardiornyocytes from developing compensatory hypertrophy and accelerate disease progression. C1 Victor Chang Cardiac Res Inst, Mol Cardiol Program, Darlinghurst, NSW 2010, Australia. Victor Chang Cardiac Res Inst, Cardiac Mech Program, Darlinghurst, NSW 2010, Australia. Victor Chang Cardiac Res Inst, Mol Genet Program, Darlinghurst, NSW 2010, Australia. Univ Maastricht, Dept Mol Cell Biol, CARIM, Maastricht, Netherlands. St Vincents Hosp, Div Anat Pathol, Darlinghurst, NSW, Australia. NCI, Frederick Canc Res & Dev Ctr, Lab Canc & Dev Biol, Frederick, MD USA. RP Fatkin, D (reprint author), Victor Chang Cardiac Res Inst, Mol Cardiol Program, Level 6,384 Victoria St, Darlinghurst, NSW 2010, Australia. EM d.fatkin@victorchang.unsw.edu.au RI Kesteven, Scott/I-8008-2015 NR 73 TC 213 Z9 223 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 2004 VL 113 IS 3 BP 357 EP 369 DI 10.1172/JCI200419448 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 770YQ UT WOS:000188759300009 PM 14755333 ER PT J AU Lammerding, J Schulze, PC Takahashi, T Kozlov, S Sullivan, T Kamm, RD Stewart, CL Lee, RT AF Lammerding, J Schulze, PC Takahashi, T Kozlov, S Sullivan, T Kamm, RD Stewart, CL Lee, RT TI Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; HUTCHINSON-GILFORD PROGERIA; A-TYPE LAMIN; PARTIAL LIPODYSTROPHY; STRUCTURAL ORGANIZATION; DILATED CARDIOMYOPATHY; ENDOTHELIAL-CELLS; IN-VIVO; GENE; MUTATIONS AB Mutations in the lamin A/C gene (LMNA) cause a variety of human diseases including Emery-Drei-fuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. The tissue-specific effects of lamin mutations are unclear, in part because the function of lamin A/C is incompletely defined, but the many muscle-specific phenotypes suggest that defective lamin A/C could increase cellular mechanical sensitivity. To investigate the role of lamin A/C in mechanotransduction, we subjected lamin A/C-deficient mouse embryo fibroblasts to mechanical strain and measured nuclear mechanical properties and strain-induced signaling. We found that Lmna(-/-) cells have increased nuclear deformation, defective mechanotransduction, and impaired viability under mechanical strain. NF-kappaB-regulated transcription in response to mechanical or cytokine stimulation was attenuated in Lmna(-/-) cells despite increased transcription factor binding. Lamin A/C deficiency is thus associated with both defective nuclear mechanics and impaired mechanically activated gene transcription. These findings suggest that the tissue-specific effects of lamin A/C mutations observed in the laminopathies may arise from varying degrees of impaired nuclear mechanics and transcriptional activation. C1 MIT, Biol Engn Div, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA USA. NCI, Canc & Dev Biol Lab, Frederick, MD USA. RP Lee, RT (reprint author), Partners Res Facil, Room 280,65 Landsdowne St, Cambridge, MA 02139 USA. EM rlee@rics.bwh.harvard.edu RI Lammerding, Jan/A-9498-2016 OI Lammerding, Jan/0000-0003-4335-8611 NR 39 TC 495 Z9 517 U1 3 U2 54 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 FEB PY 2004 VL 113 IS 3 BP 370 EP 378 DI 10.1172/JCI200419670 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 770YQ UT WOS:000188759300010 PM 14755334 ER PT J AU Cloud, JL Conville, PS Croft, A Harmsen, D Witebsky, FG Carroll, KC AF Cloud, JL Conville, PS Croft, A Harmsen, D Witebsky, FG Carroll, KC TI Evaluation of partial 16S ribosomal DNA sequencing for idefitification of Nocardia species by using the MicroSeq 500 system with an expanded database SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION-ENDONUCLEASE ANALYSIS; RNA GENE; SP-NOV; ASTEROIDES; DIFFERENTIATION; IDENTIFICATION; VETERANA; PATHOGEN; STRAINS; TRANSVALENSIS AB Identification of clinically significant nocardiae to the species level is important in patient diagnosis and treatment. A study was performed to evaluate Nocardia species identification obtained by partial 16S ribosomal DNA (rDNA) sequencing by the MicroSeq 500 system with an expanded database. The expanded portion of the database was developed from partial 5' 16S rDNA sequences derived from 28 reference strains (from the American Type Culture Collection and the Japanese Collection of Microorganisms). The expanded MicroSeq 500 system was compared to (i) conventional identification obtained from a combination of growth characteristics with biochemical and drug susceptibility tests; (ii) molecular techniques involving restriction enzyme analysis (REA) of portions of the 16S rRNA and 65-kDa heat shock protein genes; and (iii) when necessary, sequencing of a 999-bp fragment of the 16S rRNA gene. An unknown isolate was identified as a particular species if the sequence obtained by partial 16S rDNA sequencing by the expanded MicroSeq 500 system was 99.0% similar to that of the reference strain. Ninety-four nocardiae representing 10 separate species were isolated from patient specimens and examined by using the three different methods. Sequencing of partial 16S rDNA by the expanded MicroSeq 500 system resulted in only 72% agreement with conventional methods for species identification and 90% agreement with the alternative molecular methods. Molecular methods for identification of Nocardia species provide more accurate and rapid results than the conventional methods using biochemical and susceptibility testing. With an expanded database, the MicroSeq 500 system for partial 16S rDNA was able to correctly identify the human pathogens N. brasiliensis, N. cyriacigeorgica, N. farcinica, N. nova, N. otitidiscaviarum, and N. veterana. C1 ARUP Inst Clin & Expt Pathol, Salt Lake City, UT 84108 USA. ARUP Labs, Salt Lake City, UT USA. Univ Utah, Dept Pathol, Salt Lake City, UT USA. NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,Dept Hlth & Human Serv, Bethesda, MD USA. Univ Munster, Inst Hyg, D-4400 Munster, Germany. RP Cloud, JL (reprint author), ARUP Inst Clin & Expt Pathol, 500 Chipeta Way, Salt Lake City, UT 84108 USA. EM cloudjl@aruplab.com RI Harmsen, Dag/J-3041-2012 NR 34 TC 78 Z9 83 U1 0 U2 1 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 FEB PY 2004 VL 42 IS 2 BP 578 EP 584 DI 10.1128/JCM.42.2.578-584.2004 PG 7 WC Microbiology SC Microbiology GA 780KC UT WOS:000189379000014 PM 14766819 ER PT J AU Koreen, L Ramaswamy, SV Graviss, EA Naidich, S Musser, JA Kreiswirth, BN AF Koreen, L Ramaswamy, SV Graviss, EA Naidich, S Musser, JA Kreiswirth, BN TI spa Typing method for discriminating among Staphylococcus aureus isolates: Implications for use of a single marker to detect genetic micro- and macrovariation SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; NATURAL-POPULATIONS; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; STRAINS; SEQUENCE; EVOLUTION; DNA; CLONES; IDENTIFICATION AB Strain typing of microbial pathogens has two major aims: (i) to index genetic microvariation for. use in outbreak investigations and (ii) to index genetic macrovariation for use in phylogenetic and population-based analyses. Until now, there has been no clear indication that one genetic marker can efficiently be used for both purposes. Previously, we had shown that DNA sequence analysis of the protein A gene variable repeat region (spa typing) provides a rapid and accurate method to discriminate Staphylococcus aureus outbreak isolates from those deemed epidemiologically unrelated. Here, using the hypothesis that the genetic macrovariation within a low-level recombinogenic species would accurately be characterized by a single-locus marker, we tested whether spa typing could congruently index the extensive genetic variation detected by a whole-genome DNA microarray in a collection of 36 isolates, which was recovered from 10 countries on four continents over a period of four decades, that is representative of the breadth of diversity within S. aureus. Using spa and coa typing, pulsed-field gel electrophoresis (PFGE), and microarray and multilocus enzyme electrophoresis (MLEE) data in molecular epidemiologic and evolutionary analyses, we determined that S. aureus likely has a primarily clonal population structure and that spa typing can singly index genetic variation with 88% direct concordance with the microarray and can correctly assign isolates to phylogenetic lineages. spa typing performed better than MLEE, PFGE, and coa typing in discriminatory power and in the degree of agreement with the microarray at various phylogenetic depths. This study showed that genetic analysis of the repeat region of protein A comprehensively characterizes both micro- and macrovariation in the primarily clonal population structure of S. aureus. C1 Int Ctr Publ Hlth, PHRI TB Ctr, Newark, NJ 07103 USA. Int Ctr Publ Hlth, Publ Hlth Res Inst, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, Grad Sch Biomed Sci, Newark, NJ 07103 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Genom, New York, NY 10013 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Kreiswirth, BN (reprint author), Int Ctr Publ Hlth, PHRI TB Ctr, 225 Warren St, Newark, NJ 07103 USA. EM barry@phri.org NR 37 TC 265 Z9 283 U1 0 U2 7 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 FEB PY 2004 VL 42 IS 2 BP 792 EP 799 DI 10.1128/JCM.42.2.792-799.2004 PG 8 WC Microbiology SC Microbiology GA 780KC UT WOS:000189379000050 PM 14766855 ER PT J AU Sosman, JA Weeraratna, AT Sondak, VK AF Sosman, JA Weeraratna, AT Sondak, VK TI When will melanoma vaccines be proven effective? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ALLOGENEIC-TUMOR VACCINE; SOUTHWEST-ONCOLOGY-GROUP; NODE-NEGATIVE MELANOMA; ADJUVANT IMMUNOTHERAPY; INTERMEDIATE-THICKNESS; METASTATIC MELANOMA; MALIGNANT-MELANOMA; CANCER; EXPRESSION; THERAPY C1 Vanderbilt Univ, Med Ctr, Nashville, TN 37240 USA. NIA, Immunol Lab, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. RP Sosman, JA (reprint author), Vanderbilt Univ, Med Ctr, 221 Kirkland Hall, Nashville, TN 37240 USA. NR 23 TC 12 Z9 14 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2004 VL 22 IS 3 BP 387 EP 389 DI 10.1200/JCO.2004.11.950 PG 3 WC Oncology SC Oncology GA 770PJ UT WOS:000188738900001 PM 14691126 ER PT J AU Chan, LW Moses, MA Goley, E Sproull, M Muanza, T Coleman, CN Figg, WD Albert, PS Menard, C Camphausen, K AF Chan, LW Moses, MA Goley, E Sproull, M Muanza, T Coleman, CN Figg, WD Albert, PS Menard, C Camphausen, K TI Urinary VEGF and MMP levels as predictive markers of 1-year progression-free survival in cancer patients treated with radiation therapy: A longitudinal study of protein kinetics throughout tumor progression and therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROGNOSTIC VALUE; OVARIAN-CANCER; CARCINOMA; MATRIX-METALLOPROTEINASE-9; ANGIOGENESIS; EXPRESSION; ANTIGEN; TARGET; TESTS AB Purpose To determine the predictive value of urinary levels of two angiogenic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMPs), in a longitudinal study to determine their correlation with 1-year progression-free survival in patients with cancer. Patients and Methods VEGF and MMP levels were measured in the urine of 65 cancer patients at first evaluation, during therapy, and at follow-up (n = 242); normalized by creatinine levels; and compared with 16 healthy controls. The correlation of initial levels and trends of VEGF and MMPs with 1-year progression-free survival was assessed using two-sample tests and stepwise logistic regression. Results Urinary VEGF levels at presentation were different between patients with local-regional cancer and normal controls, and between patients with metastatic prostate cancer and local-regional disease (P = .04 and .01, respectively). Similar results were found with MMP measurement (P = .03 and .0001, respectively). Of those patients subsequently treated with radiation, VEGF levels at presentation between patients with no evidence of disease (NED) after radiation and those who had persistent or recurrent disease after radiotherapy were also different (P = .039). The comparison between angiogenic factor levels taken at least 1 month postradiotherapy and the last level taken during treatment was the strongest predictor of patient 1-year progress ion-free survival (P = .004). Similarly, the overall MMP trend was also significantly associated with 1-year progression-free survival, as was the individual MMP-2 trend (P = .004 and .001, respectively). Stepwise logistic regression revealed that the VEGF trend comparing postradiation levels with last level taken during treatment was an independent predictor of progression-free survival (P = .02). Conclusion This small exploratory study suggests that the angiogenic urinary trends of VEGF and MMPs may be useful predictive markers for progression-free survival in cancer patients after the completion of radiotherapy. C1 NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Canc Res Ctr,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, Canc Res Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Vasc Biol Program, Boston, MA USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Canc Res Ctr,NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM Camphauk@mail.nih.gov RI Figg Sr, William/M-2411-2016 NR 31 TC 51 Z9 57 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2004 VL 22 IS 3 BP 499 EP 506 PG 8 WC Oncology SC Oncology GA 770PJ UT WOS:000188738900018 PM 14752073 ER PT J AU McElroy, SL Zarate, CA Cookson, J Suppes, T Huffman, RF Greene, P Ascher, J AF McElroy, SL Zarate, CA Cookson, J Suppes, T Huffman, RF Greene, P Ascher, J TI A 52-week, open-label continuation study of lamotrigine in the treatment of bipolar depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; UNITED-STATES; I DISORDER; ILLNESS; LITHIUM; MONOTHERAPY; EFFICACY; SCALE; MANIA; RISK AB Background: Lamotrigine has demonstrated efficacy for the acute treatment of depression in bipolar I patients in a placebo-controlled, monotherapy study. We describe the results of a 52-week, open-label continuation of that trial. Method: Patients meeting DSM-IV criteria for bipolar I disorder with a current major depressive episode who completed a 7-week, double-blind study of bipolar depression were offered 1 year of open-label lamotrigine therapy (flexible doses of 100-500 mg/day) in a continuation study. To maintain the acute study blind, the first 3 weeks of the continuation study remained blinded while patients previously randomly assigned to placebo were titrated to a lamotrigine dose of 50 mg/day. Patients who had been randomly assigned to lamotrigine continued at their fixed doses. Beginning at week 4, all patients received open-label lamotrigine for up to 49 additional weeks. Concomitant psychotropic medications were permitted during the open-label phase. Effectiveness (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions-Improvement scale) and safety assessments were administered at weeks 4, 12, 24, 36, and 52. The study was conducted from June 1996 to December 1998. Results: Of 135 patients completing the acute study, 124 (92%) entered the continuation study: 77 had received lamotrigine and 47 had received placebo in the acute study. The mean duration of lamotrigine exposure was 10.4 months, with a mean modal dose of 187 mg/day. Sixty-nine patients (56%) completed 1 year of treatment. Significant and sustained improvement from baseline was seen in mean observed MADRS scores (p < .05). The proportion of patients achieving remission (MADRS score less than or equal to 11) by week 4 of the study was 81.4%, and episodes of mania/hypomania occurred less frequently than in the preceding year. Headache was the most common drug-related adverse event. Conclusion: During 1 year of open-label therapy with lamotrigine as adjunctive therapy or monotherapy, bipolar I patients experienced sustained improvement in depressive symptoms without evidence of mood destabilization. C1 Univ Cincinnati, Coll Med, Psychopharmacol Res Program, Cincinnati, OH 45267 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Royal London Hosp, London E1 1BB, England. NIMH, Bethesda, MD 20892 USA. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Psychopharmacol Res Program, 231 Bethesda Ave, Cincinnati, OH 45267 USA. EM susan.mcelroy@uc.edu NR 25 TC 36 Z9 40 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 2004 VL 65 IS 2 BP 204 EP 210 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JH UT WOS:000222190200010 PM 15003074 ER PT J AU Tanofsky-Kraff, M Yanovski, SZ Wilfley, DE Marmarosh, C Morgan, CM Yanovski, JA AF Tanofsky-Kraff, M Yanovski, SZ Wilfley, DE Marmarosh, C Morgan, CM Yanovski, JA TI Eating-disordered behaviors, body fat, and psychopathology in overweight and normal-weight children SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID X-RAY ABSORPTIOMETRY; ELEMENTARY-SCHOOL-CHILDREN; ADOLESCENT GIRLS; RISK-FACTORS; FEMALE ADOLESCENTS; PREADOLESCENT GIRLS; ANOREXIA-NERVOSA; PUBERTAL CHANGES; MASS INDEX; BINGE AB This study examined eating-disordered pathology in relation to psychopathology and adiposity in 162 non-treatment-seeking overweight (OW) and normal weight (NW) children, ages 6-13 years. Participants experienced objective or subjective binge eating (S/OBE; loss-of-control eating), objective overeating (OO), or no episodes (NE). OW children experienced significantly higher eating-disordered cognitions and behaviors than NW children and more behavior problems than NW children: 9.3% endorsed S/OBEs, 20.4% reported OOs, and 70.4% reported NEs. OW children reported S/OBEs more frequently than did NW children (p = .01); but similar percentages endorsed OOs. S/OBE children experienced greater eating-disordered cognitions (ps from < .05 to < .01) and had higher body fat (p < .05) than OOs or NEs. OOs are common in childhood, but S/OBEs are more prevalent in OW children and associated with increased adiposity and eating-disordered cognitions. C1 NICHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. US PHS, Washington, DC 20201 USA. Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. Univ Fed Sao Paulo, Dept Psiquiatria, Sao Paulo, Brazil. 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. NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10N262,MSC 1862, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z-01-HD-04-00641] NR 65 TC 170 Z9 170 U1 1 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 2004 VL 72 IS 1 BP 53 EP 61 DI 10.1037/0022-006X.72.1.53 PG 9 WC Psychology, Clinical SC Psychology GA 768GH UT WOS:000188534900005 PM 14756614 ER PT J AU Wang, J Zhou, J Cheng, CM Kopchick, JJ Bondy, CA AF Wang, J Zhou, J Cheng, CM Kopchick, JJ Bondy, CA TI Evidence supporting dual, IGF-I-independent and IGF-I-dependent, roles for GH in promoting longitudinal bone growth SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID HORMONE INSENSITIVITY; POSTNATAL-GROWTH; MICE; GENE; MOUSE; CHONDROCYTES; SOMATOMEDIN; EXPRESSION; MECHANISMS; PLATE AB The possibility that growth hormone (GH) has effects on long bone growth independent of insulin-like growth factor-I (IGF-I) has long been debated. If this is true, then long bone growth should be more profoundly affected by the absence of GH (since both GH and GH-stimulated IGF-I effects are absent) than by the absence of IGF-I alone (since GH is still present and actually elevated). To test this hypothesis, we compared long bone growth in mice with targeted deletions of Igf1 vs growth hormone receptor (Ghr). Tibial linear growth rate was reduced by approximately 35% in Igf1 null mice and by about 65% in Ghr null mice between postnatal days 20 and 40, a time of peak GH effect during normal longitudinal growth. The 190 null mouse growth plate demonstrated significant enlargement of the germinal zone; chondrocyte proliferation and numbers were normal but chondrocyte hypertrophy was significantly reduced. In contrast, the Ghr null mouse germinal zone was hypoplastic, chondrocyte proliferation and numbers were significantly reduced, and chondrocyte hypertrophy was also reduced. We have previously demonstrated that IGF-II is highly expressed in growth plate germinal and proliferative zones, so we considered the possibility that GH-stimulated IGF-II production might promote germinal zone expansion and maintain normal proliferation in the Igf1 null mouse growth plate. Supporting this view, IGF-II mRNA was increased in the Igf1 null mouse and decreased in the Ghr null mouse growth plate. Thus, in the complete absence of IGF-I but in the presence of elevated GH in the Igf1 null mouse, reduction in chondrocyte hypertrophy appears to be the major defect in longitudinal bone growth. In the complete absence of a GH effect in the Ghr null mouse, however, both chondrocyte generation and hypertrophy are compromised, leading to a compound deficit in long bone growth. These observations support dual roles for GH in promoting longitudinal bone growth: an IGF-I-independent role in growth plate chondrocyte generation and an IGF-I-dependent role in promoting chondrocyte hypertrophy. The question of whether GH has direct effects on chondrocyte generation is still not settled, however, since it now appears that IGF-II may medicate some. of these effects on the growth plate. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM bondyc@exchange.nih.gov NR 21 TC 99 Z9 104 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 FEB PY 2004 VL 180 IS 2 BP 247 EP 255 DI 10.1677/joe.0.1800247 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 778XA UT WOS:000189265600004 PM 14765976 ER PT J AU Dimmock, JR Chamankhah, M Das, U Zello, GA Quail, JW Yang, J Nienaber, KH Sharma, RK Selvakumar, P Balzarini, J De Clercq, E Stables, JP AF Dimmock, JR Chamankhah, M Das, U Zello, GA Quail, JW Yang, J Nienaber, KH Sharma, RK Selvakumar, P Balzarini, J De Clercq, E Stables, JP TI Cytotoxic and topographical properties of 6-arylidene-2-dimethylaminomethylcyclohexanone hydrochlorides and related compounds SO JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY LA English DT Article DE Mannich bases; cytotoxicity; molecular modeling; X-ray crystallography; QSAR; human N-myristoyltransferase; tyrosine kinase ID NATIONAL-CANCER-INSTITUTE; MANNICH-BASES; N-MYRISTOYLTRANSFERASE; DRUG DISCOVERY; STYRYL KETONES; KINASE; SYSTEM; ALPHA; 2-BENZYLIDENECYCLOHEXANONES; TRANSFERASE AB A number of 2-arylidenecyclohexanones (1a-h) were converted into the corresponding Mannich bases (2a-h) and (3a,f). Evaluation against murine L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes revealed the marked cytotoxicity of the Mannich bases and also the fact that almost invariably these compounds were more potent than the precursor enones (1a-h). Further evaluation of most of the Mannich bases towards a panel of nearly 60 human tumour cell lines confirmed their utility as potent cytotoxins. In this assay, the compounds showed growth-inhibiting properties greater than the anticancer alkylator melphalan. QSAR studies revealed that in some cell lines compounds possessing small electron-attracting aryl substituents showed the greatest potencies. Molecular modeling and X-ray crystallography demonstrated that various interatomic distances and torsion angles correlated with cytotoxicity. A representative compound (2a) demonstrated weak inhibiting properties towards human N-myristoyltransferase and stimulated a tyrosine protein kinase. A single dose of 100 mg/kg of most of the compounds did not prove to be lethal in mice. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Dept Chem, Saskatoon, SK S7N 5C9, Canada. Univ Saskatchewan, Coll Med, Dept Biochem, Saskatoon, SK S7N 5E5, Canada. Saskatoon Canc Ctr, Coll Med, Dept Pathol, Saskatoon, SK S7N 4H4, Canada. Saskatoon Canc Ctr, Canc Res Unit, Saskatoon, SK S7N 4H4, Canada. Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. NINDS, NIH, Bethesda, MD 20892 USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. EM dimmock@skyway.usask.ca NR 50 TC 9 Z9 9 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1475-6366 J9 J ENZYM INHIB MED CH JI J. Enzym. Inhib. Med. Chem. PD FEB PY 2004 VL 19 IS 1 BP 1 EP 10 DI 10.1080/14756360310001624975 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 771AW UT WOS:000188764200001 PM 15202487 ER PT J AU Feldman, ED Wu, PC Beresneva, T Helsabeck, C Rodriguez, M Bartlett, DL Libutti, SK Pinpank, JF Alexander, HR AF Feldman, ED Wu, PC Beresneva, T Helsabeck, C Rodriguez, M Bartlett, DL Libutti, SK Pinpank, JF Alexander, HR TI Treatment of patients with unresectable primary hepatic malignancies using hyperthermic isolated hepatic perfusion SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE regional perfusion; hyperthermia; liver neoplasms ID TUMOR-NECROSIS-FACTOR; ISOLATED LIMB PERFUSION; PRIMARY LIVER-CANCER; HEPATOCELLULAR-CARCINOMA; LIPIODOL CHEMOEMBOLIZATION; CHEMOTHERAPY; MELPHALAN; MELANOMA; EXPERIENCE; METASTASES AB Primary hepatocellular carcinoma is one of the most common malignancies worldwide. Isolated hepatic perfusion (IHP) is a regional treatment technique that isolates the organ to allow delivery of high-dose chemotherapy, biological agents, and hyperthermia directly to unresectable cancers confined to the liver. This study presents our experience using IHP with melphalan with or without tumor necrosis factor (TNF) to treat patients with hepatocellular carcinoma or adenocarcinoma of hepatobiliary origin. Nine patients with unresectable primary hepatic malignancies underwent a 60-minute IHP with 1.5 mg/kg melphalan with or without 1.0 mg TNF. Four patients failed one or more previous treatment regimens, and the mean hepatic replacement by tumor was 41% (range 10% to 75%). Patients were monitored for response, toxicity, time to recurrence, and survival. Six (67%) of nine patients experienced greater than 50% regression of tumor by objective radiographic imaging and an additional patient had a 45% reduction in tumor burden. Mean time to progression was 7.7 months for those who responded to treatment. Patients who had a response to therapy had an average overall survival of 16.3 months. IHP can be performed safely and has significant antitumor activity in patients with unresectable primary hepatic malignancies. Hepatic progession continues to be the dominant factor influencing survival in this group of patients. (C) 2004 The Society for Surgery of the Alimentary Tract. C1 NCI, Surg Branch, Surg Metab Sect, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, Surg Metab Sect, NIH, NIH Bldg 10,Room 2B07, Bethesda, MD 20892 USA. EM Richard_Alexander@nih.gov NR 34 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD FEB PY 2004 VL 8 IS 2 BP 200 EP 207 DI 10.1016/j.gassur.2003.11.005 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 800JI UT WOS:000220024200012 PM 15036196 ER PT J AU Shavers, VL Brown, ML Potosky, AL Klabunde, CN Davis, WW Moul, JW Fahey, A AF Shavers, VL Brown, ML Potosky, AL Klabunde, CN Davis, WW Moul, JW Fahey, A TI Race/ethnicity and the receipt of watchful waiting for the initial management of prostate cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE conservative management; ethnicity; health disparities; prostate cancer; race; watchful waiting ID SEER-MEDICARE DATA; RADIATION-THERAPY; TREATMENT OPTIONS; AFRICAN-AMERICAN; UNITED-STATES; ANTIGEN; MEN; CARCINOMA; OUTCOMES; TRENDS AB INTRODUCTION: Several recent studies have noted that African Americans disproportionately receive "watchful waiting" for the initial management of their prostate cancer. To determine whether racial/ethnic differences in the receipt of watchful waiting are explained by differences in clinical presentation and life expectancy at the time of diagnosis, we examined Surveillance, Epidemiology, and End Results (SEER)-Medicare data for men diagnosed with prostate cancer in 1994 to 1996. METHODS: Race/ethnicity, comorbidity, stage, grade, age, and expected lifespan and their association with the receipt of watchful waiting were examined in multivariate logistic regression analyses. Race-stratified logistic regression analyses were also used to examine racial/ethnic variation in the association of clinical and demographic factors with the receipt of watchful waiting among African-American, Hispanic, and non-Hispanic white men. RESULTS: African-American (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.3 to 1.6) and Hispanic men (OR, 1.3; 95% CI, 1.1 to 1.5) were significantly more likely than non-Hispanic white men to receive watchful waiting in a multivariate model adjusted for age, comorbidity, stage, grade, and life expectancy. Advanced stage and grade, lower life expectancy, older age, and high comorbidity indices were also significantly associated with an increase in the odds of receipt of watchful waiting in multivariate analyses. In general, the association between the receipt of watchful waiting and the clinical characteristics (i.e., stage, grade, and age) were similar for the three racial/ethnic groups. In race-stratified logistic regression analyses, life expectancy was associated with an increase in the odds of receiving watchful waiting but results were statistically significant for whites only. There was also a statistically significant increase in the odds of receiving watchful waiting for African-American and white men with high comorbidity indices but not Hispanic men. The odds of receiving watchful waiting were also higher for African-American and Hispanic men who resided in census tracts where a large percentage of residents had not completed high school than for white men who resided in similar census tracts. CONCLUSION: The disproportionate receipt of watchful waiting among African Americans and Hispanics is not completely explained by racial/ethnic variation in clinical characteristics or life expectancy as measured in this study. These data suggest that there are other factors that contribute to racial/ethnic differences in receipt of watchful waiting that warrant investigation. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, HSEB, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, DoD Ctr Prostate Dis Res, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Informat Management Syst, Bethesda, MD USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, HSEB, 6130 Execut Blvd,EPN 4005 MSC 7344, Bethesda, MD 20892 USA. EM shaversv@mail.nih.gov NR 50 TC 85 Z9 87 U1 0 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 2004 VL 19 IS 2 BP 146 EP 155 DI 10.1111/j.1525-1497.2004.30209.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 779KD UT WOS:000189293100006 PM 15009794 ER PT J AU Bella, JN MacCluer, JW Roman, MJ Almasy, L North, KE Best, LG Lee, ET Fabsitz, RR Howard, BV Devereux, RB AF Bella, JN MacCluer, JW Roman, MJ Almasy, L North, KE Best, LG Lee, ET Fabsitz, RR Howard, BV Devereux, RB TI Heritability of left ventricular dimensions and mass in American indians: The Strong Heart Study SO JOURNAL OF HYPERTENSION LA English DT Article DE genetics; epidemiology; echocardiography; left ventricular mass; hypertension; diabetes mellitus ID CORONARY-ARTERY DISEASE; CARDIOVASCULAR RISK; CARDIAC SIZE; HYPERTENSION; ECHOCARDIOGRAPHY; HYPERTROPHY; GEOMETRY; VARIANCE; ADULTS; TWINS AB Objective We sought to determine the heritability of left ventricular dimensions and mass in adult American Indians. Methods Echocardiograms were analysed in 1373 American Indian participants, from 445 families, in the Strong Heart Study (SHS) to determine the heritability of left ventricular dimensions and mass. Heritability calculations were performed using variance component analysis in SOLAR, a computer analysis program. Results The SHS participants analysed in this study included 1305 relative pairs, predominantly (n = 1077) sib-pairs. After simultaneously adjusting for sex, age and centre, the proportion of the residual phenotypic variance due to additive genetic effects or heritability (h(2)) of left ventricular mass was 0.27 (SE = 0.08, P < 0.001). Addition of body weight height, systolic blood pressure, heart rate, medications and diabetes into the polygenic model attenuated the residual h(2) of left ventricular mass to 0.17 (SE = 0.09, P < 0.05). The residual h(2) for left ventricular end-diastolic chamber diameter (LVID), after simultaneously adjusting for sex, age and centre was 0.36 (SE = 0.08, P < 0.001) for the analysed families. The residual h(2) for interventricular septal wall thickness was 0.26 (SE = 0.07), while that of left ventricular posterior wall thickness was 0.19 (SE = 0.08, both P < 0.001). While adjustment for body weight, height, systolic blood pressure, heart rate, medications and diabetes reduced the h(2) of LVID to 0.33 (SE = 0.09, P < 0.001), the h(2) of septal (0.12, SE = 0.10) and posterior wall thickness (0.09, SE = 0.09) were no longer significant after similar adjustment. The residual h(2) for relative wall thickness, a measure of left ventricular geometry, was 0.22 (SE = 0.07, P < 0.001) after adjusting for sex, age and centre, and 0.17 (SE = 0.08, P < 0.05) after additional adjustment for body weight, height, systolic blood pressure, heart rate, medications and diabetes. Conclusions A substantial proportion of the variance of left ventricular dimensions and mass can be explained by heredity, independent of the effects of sex, age, body size, blood pressure, heart rate, medications and diabetes. Identification of genes influencing left ventricular size and geometry may provide mechanistic and therapeutic targets to prevent left ventricular hypertrophy. (C) 2004 Lippincott Williams Wilkins. C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Medstar Res Inst, Washington, DC USA. NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Sch Publ Hlth Serv, Oklahoma City, OK USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA. RP Bella, JN (reprint author), Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Div Cardiol, Box 222,525 E 68th St, New York, NY 10021 USA. EM jonnbella@earthlink.net FU NCRR NIH HHS [M10RR0047-34]; NHLBI NIH HHS [U01-HL41654, U01-HL41642, U01-HL41652] NR 36 TC 48 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 2004 VL 22 IS 2 BP 281 EP 286 DI 10.1097/01.hjh.0000098197.36890.d5 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 805BM UT WOS:000220341800011 PM 15076185 ER PT J AU Fedorova, OV Talan, MI Agalakova, NI Lakatta, EG Bagrov, AY AF Fedorova, OV Talan, MI Agalakova, NI Lakatta, EG Bagrov, AY TI Coordinated shifts in Na/K-ATPase isoforms and their endogenous ligands during cardiac hypertrophy and failure in NaCl-sensitive hypertension SO JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; left ventricular hypertrophy; congestive heart failure; Na/K-ATPase; endogenous digitalis-like inhibitors; marinobufagenin; ouabain ID CONGESTIVE-HEART-FAILURE; ALPHA-SUBUNIT ISOFORMS; SODIUM-PUMP; PROTEIN-LEVELS; MESSENGER-RNA; MARINOBUFAGENIN; OUABAIN; RAT; EXPRESSION; NA,K-ATPASE AB Objectives NaCl loading of Dahl salt-sensitive rats (DS) stimulates marinobufagenin (MBG), an alpha(1) Na/K-ATPase (NKA) isoform ligand. Cardiac function depends on NKA, which is regulated in part by endogenous digitalis-like ligands. Our goal was to study whether changes occur in MBG and endogenous ouabain (EO) production during cardiac remodelling in hypertensive DS, and whether these are associated with changes in myocardial NKA isoforms and sensitivity to MBG and ouabain. Methods Changes in MBG and EO levels, changes in myocardial NKA isoform composition, and sensitivity to endogenous ligands during development of cardiac hypertrophy and the transition to heart failure were studied in DS rats with an 8% NaCl intake. Results The animals developed compensated left ventricular hypertrophy after 4 weeks, which progressed to heart failure at 9-12 weeks. The hypertrophic stage was associated with increased plasma MBG levels (mean +/- SEM of 1.22 +/- 0.22 versus 0.31 +/- 0.03 nmol/l; P < 0.01), increased sensitivity of NKA to MBG, and an increased abundance of a, NKA. Plasma levels of EO did not change, and the sensitivity of NKA to ouabain decreased. The transition to heart failure was accompanied by a decrease in a, NKA, a reduction in plasma MBG, and decreased sensitivity of NKA to MBG. In addition, an increased abundance of ouabain-sensitive alpha(3) NKA, a three-fold rise in plasma EO (1.01 +/- 0.13 versus 0.27 +/- 0.06 nmol/l), and a seven-fold increase in the ouabain sensitivity of NKA compared with controls were observed. Conclusions During cardiac hypertrophy and the transition to heart failure, a shift in endogenous NKA ligands production is linked to a shift in myocardial NKA isoforms. (C) 2004 Lippincott Williams Wilkins. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Fedorova, OV (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM FedorovO@grc.nia.nih.gov NR 39 TC 15 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 2004 VL 22 IS 2 BP 389 EP 397 DI 10.1097/01.hjh.0000098217.37783.60 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 805BM UT WOS:000220341800025 PM 15076199 ER PT J AU Wang, JG Staessen, JA Franklin, SS Boissel, JP Cutler, JA Fagard, R Gueyffier, F AF Wang, JG Staessen, JA Franklin, SS Boissel, JP Cutler, JA Fagard, R Gueyffier, F TI Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome on antihypertensive drug treatment SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 20th ISH Meeting CY FEB 15-19, 2004 CL Soa Paulo, BRAZIL SP ISH C1 Shanghai Med Univ 2, Ruijin Hosp, Shanghai, Peoples R China. Katholieke Univ Leuven, Louvain, Belgium. Univ Lyon 1, F-69365 Lyon, France. NHLBI, NIH, Bethesda, MD 20892 USA. RI Staessen, Jan/A-1065-2011; Gueyffier, Francois/B-8545-2008 OI Staessen, Jan/0000-0002-3026-1637; Gueyffier, Francois/0000-0002-9921-0977 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 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 2004 VL 22 SU 1 BP S14 EP S14 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 835PR UT WOS:000222497400048 ER PT J AU Makrigiannis, AP Rousselle, E Anderson, SK AF Makrigiannis, AP Rousselle, E Anderson, SK TI Independent control of Ly49g alleles: Implications for NK cell repertoire selection and tumor cell killing SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; RECEPTOR REPERTOIRE; GENE-EXPRESSION; MURINE CYTOMEGALOVIRUS; MONOCLONAL-ANTIBODY; MULTIGENE FAMILY; VIRUS-INFECTION; VIRAL-INFECTION; MOUSE STRAINS; C57BL/6 MICE AB A novel murine NK cell-reactive mAb, AT8, was generated. AT8 recognizes Ly49G from 129/J, BALB/c, and related mouse strains, but does not bind to Ly49G(B6). Costaining with AT8 and a Ly49G(B6)-restricted Ab (Cwy-3) provides the first direct evidence that Ly49G protein is expressed from both alleles on a significant proportion of NK cells from four different types of F-1 hybrid mice. The observed level of biallelic Ly49G expression reproducibly followed the product rule in both freshly isolated and cultured NK cells. Surprisingly, the percentage of NK cells expressing both Ly49G alleles could be dramatically increased in vitro and in vivo through IL-2R- and IFN receptor-dependent signaling pathways, respectively. Unexpectedly, Ly49G(B6+) NK cells in an H-2(d), but not H-2(b), background were more likely to lyse Dd+ and Chinese hamster ovary tumor cells than Ly49G(BALB/129+) NK cells. Furthermore, Ly49G(B6+) NK cells also proliferated to a higher degree in response to poly(I:C) than NK cells expressing a non-Ly49G(B6) allele in an H-2(d), but not H-2(b), background. These results suggest that Ly49G(B6) has a lower affinity for H-2D(d) than Ly49G(BALB/129), and the genetic background calibrates the responsiveness of NK cells bearing self-specific Ly49. Other H-2D(d) receptors on the different Ly49G(+) NK cell subsets were unequally coexpressed, possibly explaining the disparate responses of Ly49G(B6+) NK cells in different hybrid mice. These data indicate that the stochastic mono- and biallelic expression of divergent Ly49G alleles increases the range of MHC affinities and the functional potential in the total NK cell population of heterozygous mice. C1 Inst Rech Clin Montreal, Lab Mol Immunol, Montreal, PQ H2W 1R7, Canada. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Makrigiannis, AP (reprint author), Inst Rech Clin Montreal, Lab Mol Immunol, Room 1340,110 Ave Pins Ouest, Montreal, PQ H2W 1R7, Canada. EM makriga@ircm.qc.ca RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-12400] NR 47 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1414 EP 1425 PG 12 WC Immunology SC Immunology GA 766LW UT WOS:000188378700011 PM 14734717 ER PT J AU De Rosa, SC Andrus, JP Perfetto, SP Mantovani, JJ Herzenberg, LA Herzenberg, LA Roederer, M AF De Rosa, SC Andrus, JP Perfetto, SP Mantovani, JJ Herzenberg, LA Herzenberg, LA Roederer, M TI Ontogeny of gamma delta T cells in humans SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FLOW-CYTOMETRY; PERIPHERAL-BLOOD; STEM-CELLS; RECEPTOR; GAMMA/DELTA; LYMPHOCYTES; RECOGNITION; EXPRESSION; INFECTION; THYMUS AB T cell receptors consist either of an a-chain combined with a beta-chain or a gamma-chain combined with a delta-chain. alphabeta T cells constitute the majority of T cells in human blood throughout life. Flow cytometric analyses presented in this study, which focus on the representation of the developmental (naive and memory) subsets of gammadelta T cells, show by function and phenotype that this lineage contains both naive and memory cells. In addition, we show that the representation of naive T cells is higher among alphabeta than gammadelta T cells in adults and that the low frequency of naive gammadelta T cells in adults reflects ontological differences between the two major gammadelta subsets, which are distinguished by expression of Vdelta1 vs Vdelta2 delta-chains. Vdelta1 cells, which mirror alphabeta cells with respect to naive representation, predominate during fetal and early life, but represent the minority of gammadelta cells in healthy adults. In contrast, Vdelta2 cells, which constitute the majority of adult gammadelta cells, show lower frequencies of naive cells than Vdelta1 early in life and show vanishingly small naive frequencies in adults. In essence, nearly all naive Vdelta2 cells disappear from blood by 1 year of life. Importantly, even in children less than 1 year old, most of the nonnaive Vdelta2 cells stain for perforin and produce IFN-gamma after short-term in vitro stimulation. This represents the earliest immunological maturation of any lymphocyte compartment in humans and most likely indicates the importance of these cells in controlling pathology due to common environmental challenges. C1 NIAID, Immunol Technol Sect, Immunol Lab, Vaccine Res Ctr,NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. RP Roederer, M (reprint author), NIAID, Immunol Technol Sect, Immunol Lab, Vaccine Res Ctr,NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov; Roederer@nih.gov RI Roederer, Mario/G-1887-2011 NR 35 TC 89 Z9 90 U1 3 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1637 EP 1645 PG 9 WC Immunology SC Immunology GA 766LW UT WOS:000188378700039 PM 14734745 ER PT J AU Bosco, MC Puppo, M Pastorino, S Mi, ZH Melillo, G Massazza, S Rapisarda, A Varesio, L AF Bosco, MC Puppo, M Pastorino, S Mi, ZH Melillo, G Massazza, S Rapisarda, A Varesio, L TI Hypoxia selectively inhibits monocyte chemoattractant protein-1 production by macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; RNA-BINDING PROTEIN; OXIDE SYNTHASE PROMOTER; NF-KAPPA-B; GROWTH-FACTOR; MESSENGER-RNA; GENE-EXPRESSION; NITRIC-OXIDE; INDUCIBLE FACTOR-1; INTERFERON-GAMMA AB Hypoxia, a local decrease in oxygen tension occurring in inflammatory and tumor lesions, modulates gene expression in macrophages. Because macrophages are important chemokine producers, we investigated the regulatory effects of hypoxia on macrophage-derived chemokines. We demonstrated that hypoxia inhibits the production of the macrophage and T lymphocyte chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1). Exposure of mouse macrophages to low oxygen tension resulted in the down-regulation of constitutive MCP-1 mRNA expression and protein secretion. Hypoxia inhibitory effects were selective for MCP-1 because the chemokines macrophage inflammatory protein-1beta (MIP-1beta), RANTES, IFN-gamma-inducible protein-10, and MIP-2 were not affected, and MIP-1alpha was induced. Hypoxia also inhibited, in a time-dependent fashion, MCP-1 up-regulation by IFN-gamma and LPS. Moreover, the inhibitory action of hypoxia was exerted on human monocytic cells. MCP-1 down-regulation was associated with inhibition of gene transcription and mRNA destabilization, suggesting a dual molecular mechanism of control. Finally, we found that the triptophan catabolite picolinic acid and the iron chelator desferrioxamine, which mimic hypoxia in the induction of gene expression, differentially regulated the expression of MCP-1. This study characterizes a novel property of hypoxia as a selective inhibitor of MCP-1 production induced by different stimuli in macrophages and demonstrates that down-regulation of gene expression by hypoxia can be controlled at both transcriptional and posttranscriptional levels. Inhibition of MCP-1 may represent a negative regulatory mechanism to control macrophage-mediated leukocyte recruitment in pathological tissues. C1 Ist Giannina Gaslini, Mol Biol Lab, I-16147 Genoa, Italy. NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Tumor Hypoxia Lab, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Bosco, MC (reprint author), Ist Giannina Gaslini, Mol Biol Lab, Padiglione 2,Lgo Gerolamo Gaslini 5, I-16147 Genoa, Italy. EM mcbosco1@virgilio.it RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 FU NCI NIH HHS [N01-CO-56000] NR 67 TC 68 Z9 70 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1681 EP 1690 PG 10 WC Immunology SC Immunology GA 766LW UT WOS:000188378700044 PM 14734750 ER PT J AU Llewelyn, M Sriskandan, S Peakman, M Ambrozak, DR Douek, DC Kwok, WW Cohen, J Altmann, DM AF Llewelyn, M Sriskandan, S Peakman, M Ambrozak, DR Douek, DC Kwok, WW Cohen, J Altmann, DM TI HLA class II polymorphisms determine responses to bacterial superantigens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STREPTOCOCCAL PYROGENIC EXOTOXIN; STAPHYLOCOCCAL-ENTEROTOXIN-A; SCARLET FEVER TOXIN; V-BETA-SPECIFICITY; HUMAN T-CELLS; MHC CLASS; STRUCTURAL BASIS; PYOGENES; BINDING; RECOGNITION AB The excessive immunological response triggered by microbial superantigens has been implicated in the etiology of a wide range of human diseases but has been most clearly defined for the staphylococcal and streptococcal toxic shock syndromes. Because MHC class II presentation of superantigens to T cells is not MHC-restricted, the possibility that HLA polymorphisms could influence superantigenicity, and thus clinical susceptibility to the toxicity of individual superantigens, has received little attention. In this study, we demonstrate that binding of streptococcal and staphylococcal superantigens to HLA class II is influenced by allelic differences in class II. For the superantigen streptococcal pyrogenic exotoxin A, class II binding is dependent on DQ alpha-chain polymorphisms such that HLA-DQA1*01 alpha-chains show greater binding than DQA1*03/05 alpha-chains. The functional implications of differential binding on T cell activation were investigated in various experimental systems using human T cells and murine Vbeta8.2 transgenic cells as responders. These studies showed quantitative and qualitative differences resulting from differential HLA-DQ binding. We observed changes in T cell proliferation and cytokine production, and in the Vbeta specific changes in T cell repertoire that have hitherto been regarded as a defining feature of an individual superantigen. Our observations reveal a mechanism for the different outcomes seen following infection by toxigenic bacteria. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Infect Dis, London, England. Guys Kings & St Thomas Sch Med, Dept Immunol, London, England. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Virginia Mason Res Ctr, Seattle, WA 98101 USA. Brighton & Sussex Med Sch, Div Med, Brighton, E Sussex, England. RP Altmann, DM (reprint author), Hammersmith Hosp, Dept Infect Dis, Human Dis Immunogenet Grp, London W12 0NN, England. EM d.altmann@ic.ac.uk RI Llewelyn, Martin/A-7194-2011 OI Llewelyn, Martin/0000-0002-6811-1124 NR 36 TC 51 Z9 54 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1719 EP 1726 PG 8 WC Immunology SC Immunology GA 766LW UT WOS:000188378700048 PM 14734754 ER PT J AU Sadikot, RT Zeng, H Yull, FE Li, B Cheng, DS Kernodle, DS Jansen, ED Contag, CH Segal, BH Holland, SM Blackwell, TS Christman, JW AF Sadikot, RT Zeng, H Yull, FE Li, B Cheng, DS Kernodle, DS Jansen, ED Contag, CH Segal, BH Holland, SM Blackwell, TS Christman, JW TI p47(phox) deficiency impairs NF-kappa B activation and host defense in Pseudomonas pneumonia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NADPH OXIDASE; ANTIOXIDANT TREATMENT; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; REDOX REGULATION; GENE-EXPRESSION; MOUSE MODEL; LIPOPOLYSACCHARIDE; INFLAMMATION; AERUGINOSA AB We examined the role of redox signaling generated by NADPH oxidase in activation of NF-kappaB and host defense against Pseudomonas aeruginosa pneumonia. Using mice with an NF-kappaB-driven luciferase reporter construct (HIV-LTR/luciferase (HLL)), we found that intratracheal administration of P. aeruginosa resulted in a dose-dependent neutrophilic influx and activation of NF-kappaB. To determine the effects of reactive oxygen species generated by the NADPH oxidase system on activation of NF-kappaB, we crossbred mice deficient in p47(phox) with NF-kappaB reporter mice (p47(phox -/-)HLL). These p47(phox-/-)HLL mice were unable to activate NF-kappaB to the same degree as HLL mice with intact NADPH oxidase following P. aeruginosa infection. In addition, lung TNF-alpha levels were significantly lower in p47(phox-/-)HLL mice compared with HLL mice. Bacterial clearance was impaired in p47(phox-/-)HLL mice. In vitro studies using bone marrow-derived macrophages showed that Toll-like receptor 4 was necessary for NF-kappaB activation following treatment with P. aeruginosa. Additional studies with macrophages from p47(phox-/-) mice confirmed that redox signaling was necessary for maximal Toll-like receptor 4-dependent NF-kappaB activation in this model. These data indicate that the NADPH oxidase-dependent respiratory burst stimulated by Pseudomonas infection contributes to host defense by modulating redoxdependent signaling through the NF-kappaB pathway. C1 Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Vet Affairs, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Biomed Engn, Nashville, TN 37232 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP Sadikot, RT (reprint author), Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care, T-1217 Med Ctr N, Nashville, TN 37232 USA. EM ruxana.sadikot@Vanderbilt.edu RI Jansen, E. Duco/B-1894-2013 FU NHLBI NIH HHS [HL66196, HL61419] NR 34 TC 72 Z9 75 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1801 EP 1808 PG 8 WC Immunology SC Immunology GA 766LW UT WOS:000188378700057 PM 14734763 ER PT J AU Partida-Sanchez, S Iribarren, P Moreno-Garcia, ME Gao, XL Murphy, PM Oppenheimer, N Wang, JM Lund, FE AF Partida-Sanchez, S Iribarren, P Moreno-Garcia, ME Gao, XL Murphy, PM Oppenheimer, N Wang, JM Lund, FE TI Chemotaxis and calcium responses of phagocytes to formyl peptide receptor ligands is differentially regulated by cyclic ADP ribose SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; N-FORMYLPEPTIDE RECEPTOR; SIGNAL-TRANSDUCTION; HUMAN MONOCYTES; CHEMOATTRACTANT RECEPTOR; CHEMOKINE RECEPTORS; HUMAN NEUTROPHILS; ESCHERICHIA-COLI; CYCLASE ACTIVITY; CA2+ INFLUX AB Cyclic ADP ribose (cADPR) is a calcium-mobilizing metabolite that regulates intracellular calcium release and extracellular calcium influx. Although the role of cADPR in modulating calcium mobilization has been extensively examined, its potential role in regulating immunologic responses is less well understood. We previously reported that cADPR, produced by the ADP-ribosyl cyclase, CD38, controls calcium influx and chemotaxis of murine neutrophils responding to fMLF, a peptide agonist for two chemoattractant receptor subtypes, formyl peptide receptor and formyl peptide receptor-like 1. In this study, we examine whether cADPR is required for chemotaxis of human monocytes and neutrophils to a diverse array of chemoattractants. We found that a cADPR antagonist and a CD38 substrate analogue inhibited the chemotaxis of human phagocytic cells to a number of formyl peptide receptor-like 1-specific ligands but had no effect on the chemotactic response of these cells to ligands selective for formyl peptide receptor. In addition, we show that the cADPR antagonist blocks the chemotaxis of human monocytes to CXCR4, CCR1, and CCR5 ligands. In all cases, we found that cADPR modulates intracellular free calcium levels in cells activated by chemokines that induce extracellular calcium influx in the apparent absence of significant intracellular calcium release. Thus, cADPR regulates calcium signaling of a discrete subset of chemoattractant receptors expressed by human leukocytes. Since many of the chemoattractant receptors regulated by cADPR bind to ligands that are associated with clinical pathology, cADPR and CD38 represent novel drug targets with potential application in chronic inflammatory and neurodegenerative disease. C1 Trudeau Inst Inc, Saranac Lake, NY 12983 USA. NCI, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. RP Lund, FE (reprint author), Trudeau Inst Inc, 154 Algonquin Ave, Saranac Lake, NY 12983 USA. EM flund@trudeauinstitute.org RI Partida-Sanchez, Santiago/B-7523-2008 OI Partida-Sanchez, Santiago/0000-0003-2996-9440 NR 64 TC 71 Z9 72 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1896 EP 1906 PG 11 WC Immunology SC Immunology GA 766LW UT WOS:000188378700069 PM 14734775 ER PT J AU O'Keefe, CL Plasilova, M Wlodarski, M Risitano, AM Rodriguez, AR Howe, E Young, NS Hsi, E Maciejewski, JP AF O'Keefe, CL Plasilova, M Wlodarski, M Risitano, AM Rodriguez, AR Howe, E Young, NS Hsi, E Maciejewski, JP TI Molecular analysis of TCR clonotypes in LGL: A clonal model for polyclonal responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; T-CELL REPERTOIRE; VERSUS-HOST-DISEASE; V-BETA REPERTOIRE; FLOW-CYTOMETRIC ANALYSIS; FELTYS-SYNDROME; LYMPHOPROLIFERATIVE DISEASE; APLASTIC-ANEMIA; MYELODYSPLASTIC SYNDROMES; RHEUMATOID-ARTHRITIS AB Large granular lymphocytic (LGL) leukemia is a clonal lymphoproliferative disorder of CTL associated with cytopenias resulting from an immune and cytokine attack on hemopoietic progenitor cells. Extreme clonality of CTL expansions seen in LGL leukemia makes it an ideal model to study the role of the T cell repertoire in other less-polarized immune-mediated disorders. Complementarity-determining region 3 (CDR3) of the TCR is a unique Ag-specific region that can serve as a molecular marker, or clonotype, of the disease-specific T cells. We studied the variable portion of the beta-chain spectrum in a cohort of LGL leukemia patients. The CDR3 sequences were determined for the immunodominant clones and used to design clonotype-specific primers. By direct and semi-nested amplification, clonotype amplicons were found to be shared by multiple patients and controls. Analysis of the generated sequences demonstrated that the original clonotypes are rarely encountered in normal control samples; however, high levels of homology were found in both controls and patients. Clonotypes derived from individual LGL patients can be used as tumor markers for the malignant clone. More generally, clonotypic analysis and comparison of the variable portion of the beta-chain CDR3-specific sequences from a large number of patients may lead to better subclassification of not only LGL but also other immune-mediated disorders. C1 Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Hematopathol Sect, Cleveland, OH 44195 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr R40, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM maciejj@cc.ccf.org NR 43 TC 45 Z9 48 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2004 VL 172 IS 3 BP 1960 EP 1969 PG 10 WC Immunology SC Immunology GA 766LW UT WOS:000188378700076 PM 14734782 ER PT J AU Vorberg, I Raines, A Story, B Priola, SA AF Vorberg, I Raines, A Story, B Priola, SA TI Susceptibility of common fibroblast cell lines to transmissible spongiform encephalopathy agents SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE PRION PROTEINS; NEUROBLASTOMA-CELLS; BLOOD-TRANSFUSION; ABNORMAL ISOFORM; STRAIN VARIATION; INFECTION; PRP; KERATINOCYTES; REPLICATION AB The risk of contamination of tissue culture cells with transmissible spongiform encephalopathy (TSE) agents as a result of the use of animal products as medium components has been considered to be low, in part, because only a few brain-derived cell lines have been reported to be susceptible to TSE infection. In the present study, we demonstrate that the common laboratory fibroblast cell lines NIH/3T3 and L929, which express low levels of cellular mouse prion protein, are susceptible to infection with mouse-adapted scrapie. Our results show that the susceptibility of a cell line to TSE infection cannot be predicted on the basis of its tissue origin or its level of expression of the cellular prion protein, and they suggest that any cell line expressing normal host prion protein could have the potential to support propagation of TSE agents. Thus, testing of cells for TSE susceptibility might be necessary for all cell lines that are routinely used in vaccine production and in other medical applications. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Vorberg, I (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM vorberg@lrz.tum.de NR 43 TC 79 Z9 83 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 FEB 1 PY 2004 VL 189 IS 3 BP 431 EP 439 DI 10.1086/381166 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767TC UT WOS:000188467900010 PM 14745700 ER PT J AU Belshe, RB Newman, FK Tsai, TF Karron, RA Reisinger, K Roberton, D Marshall, H Schwartz, R King, J Henderson, FW Rodriguez, W Severs, JM Wright, PF Keyserling, H Weinberg, GA Bromberg, K Loh, R Sly, P McIntyre, P Ziegler, JB Hackell, J Deatly, A Georgiu, A Paschalis, M Wu, SL Tatem, JM Murphy, B Anderson, E AF Belshe, RB Newman, FK Tsai, TF Karron, RA Reisinger, K Roberton, D Marshall, H Schwartz, R King, J Henderson, FW Rodriguez, W Severs, JM Wright, PF Keyserling, H Weinberg, GA Bromberg, K Loh, R Sly, P McIntyre, P Ziegler, JB Hackell, J Deatly, A Georgiu, A Paschalis, M Wu, SL Tatem, JM Murphy, B Anderson, E TI Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFLUENZA VIRUS TYPE-3; WEANLING HAMSTERS; TRIVALENT; INFANTS; EPIDEMIOLOGY; PROTECTION AB A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3) -cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6 - 18 months old; 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature greater than or equal to38 degreesC) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a greater than or equal to4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1: 25 in the vaccine group and <1: 4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial. C1 St Louis Univ, Div Infect Dis & Immunol, St Louis, MO 63103 USA. Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Primary Phys Res, Pittsburgh, PA USA. Vienna Pediat, Vienna, VA USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. Natl Childrens Hosp, Dept Pediat Infect Dis, Washington, DC USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Wyeth Vaccines Res, Pearl River, NY USA. SUNY Hlth Sci Ctr, Vaccine Study Ctr, Brooklyn, NY 11203 USA. Univ Adelaide, Womens & Childrens Hosp, Dept Pediat, Adelaide, SA, Australia. Univ Western Australia, Princess Margaret Hosp Children, Ctr Child Hlth Res, Div Clin Sci, Perth, WA 6009, Australia. Univ Sydney, Sch Publ Hlth, Westmead, NSW 2145, Australia. St Louis Univ, Childrens Hosp Westmead, Discipline Paediat & Child Hlth, Natl Ctr Immunisat Res & Surveillance Vaccine Pre, St Louis, MO USA. Univ New S Wales, Sydney Childrens Hosp, Sydney, NSW, Australia. RP Belshe, RB (reprint author), St Louis Univ, Div Infect Dis & Immunol, 3635 Vista Ave FDT-8N, St Louis, MO 63103 USA. EM belsherb@slu.edu RI Sly, Peter/F-1486-2010; Marshall, Helen/G-3603-2013 OI Sly, Peter/0000-0001-6305-2201; NR 17 TC 36 Z9 36 U1 0 U2 3 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 FEB 1 PY 2004 VL 189 IS 3 BP 462 EP 470 DI 10.1086/381184 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767TC UT WOS:000188467900014 PM 14745704 ER PT J AU Ito, Y Grivel, JC Chen, S Kiselyeva, Y Reichelderfer, P Margolis, L AF Ito, Y Grivel, JC Chen, S Kiselyeva, Y Reichelderfer, P Margolis, L TI CXCR4-tropic HIV-1 suppresses replication of CCR5-tropic HIV-1 in human lymphoid tissue by selective induction of CC-chemokines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DEPLETION; IN-VIVO; PERIPHERAL-BLOOD; MONONUCLEAR-CELLS; INFECTED INDIVIDUALS; COFACTOR UTILIZATION; CEREBROSPINAL-FLUID; GENETIC-DIFFERENCES; GENITAL SECRETIONS AB In infected individuals, human immunodeficiency virus type 1 (HIV-1) exist as a "swarm" of quasi species compartmentalized in tissues where individual viral variants may interact locally. We have used human lymphoid tissue, where the critical events of HIV disease occur, to study local interactions in model HIV-1 binary swarms ex vivo. We infected tissue blocks with binary mixtures consisting either of CCR5-dependent and CXCR4-dependent variants or of 2 dual-tropic HIV-1 variants, of which one is skewed to utilization of CXCR4 and the other of CCR5. HIV-1 variants that use CXCR4 suppress replication of CCR5-dependent HIV-1 variants, whereas CCR5-dependent HIV-1 variants do not affect replication of CXCR4-dependent HIV-1. CC-chemokines that inhibit replication of CCR5-dependent HIV-1 variants were up-regulated by CXCR4-dependent HIV-1, thus possibly contributing to this suppression. Tissue-specific chemokine/cytokine network modulations triggered by individual HIV-1 variants may be an important mechanism of local interactions among HIV-1 quasi species in infected tissue. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), NICHD, NIH, Bldg 10,Rm 9D58,10 Ctr Dr, Bethesda, MD 20892 USA. EM margolis@helix.nih.gov NR 68 TC 11 Z9 11 U1 0 U2 0 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 FEB 1 PY 2004 VL 189 IS 3 BP 506 EP 514 DI 10.1086/381153 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767TC UT WOS:000188467900019 PM 14745709 ER PT J AU Duggal, P Haque, R Roy, S Mondal, D Sack, RB Farr, BM Beaty, TH Petri, WA AF Duggal, P Haque, R Roy, S Mondal, D Sack, RB Farr, BM Beaty, TH Petri, WA TI Influence of human leukocyte antigen class II alleles on susceptibility to Entamoeba histolytica infection in Bangladeshi children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the International Centers for Tropical Disease Research Network CY MAY 13-15, 2003 CL BERTHESDA, MARYLAND ID NONRADIOACTIVE OLIGONUCLEOTIDE PROBES; HEPATITIS-B-VIRUS; HLA; AMEBIASIS; LECTIN; EPIDEMIOLOGY; POLYMORPHISM; ABSCESS; LIVER; DNA AB Background. The association of antibody responses with both innate and acquired immunity to amebiasis indicate that CD4(+) T cells play a role in protection against Entamoeba histolytica infection. To test this hypothesis, we compared the genotype frequencies of human leukocyte antigen (HLA) class II alleles in a cohort of Bangladeshi children intensively monitored for E. histolytica infection for a 3-year period. Methods. Using logistic regression, we calculated the odds of disease by genotype and by haplotype. Results. The DQB1* 0601 heterozygous and homozygous genotypes were found in 55% of E. histolytica negative children but in only 34% of E. histolytica - positive children ( overall odds ratio, 2.39; 95% confidence interval [CI], 1.26 - 4.54). Children who were heterozygous for the DQB1* 0601/DRB1* 1501 haplotype were 10.1 times (95% CI, 2.02 - 50.6) more likely to be both E. histolytica negative and serum anti - lectin immunoglobulin G negative at baseline. Other DQB1 and DRB1 alleles ( DQB1* 0202, DQB1* 0301, and DRB1*0701) were not associated with any of the clinical outcomes related to amebiasis. Conclusion. A potential protective association was observed with the HLA class II allele DQB1* 0601 and the heterozygous haplotype DQB1* 0601/DRB1* 1501. This association may explain why amebiasis does not occur in some children who are exposed to the parasite and implicates HLA class II - restricted immune responses in protection against E. histolytica infection. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Univ Virginia, Dept Med, Charlottesville, VA USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Int Ctr Diarrhoeal Dis Res, Ctr Hlth & Populat Res, Dhaka 1000, Bangladesh. RP Petri, WA (reprint author), Univ Virginia Hlth Syst, Div Infect Dis, POB 801340,Rm 2115,MR4 Bldg, Charlottesville, VA 22908 USA. EM wap3g@virginia.edu FU NIAID NIH HHS [AI-43596] NR 23 TC 37 Z9 38 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2004 VL 189 IS 3 BP 520 EP 526 DI 10.1086/381272 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 767TC UT WOS:000188467900021 PM 14745711 ER PT J AU Hildesheim, J Awwad, RT Fornace, AJ AF Hildesheim, J Awwad, RT Fornace, AJ TI p38 mitogen-activated protein kinase inhibitor protects the epidermis against the acute damaging effects of ultraviolet irradiation by blocking apoptosis and inflammatory responses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE keratinocyte; sunburn cell; inflammation; p38 MAPK; UV ID METHYL METHANESULFONATE; DIFFERENTIAL ACTIVATION; SIGNAL-TRANSDUCTION; HUMAN KERATINOCYTES; GENOTOXIC STRESS; OSMOTIC-STRESS; GROWTH ARREST; UV-RADIATION; P53; CARCINOGENESIS AB The primary function of the epidermis is to provide a protective barrier against numerous environmental insults, including ultraviolet radiation (UVR). UVR, particularly in the UVB spectrum, is a potent carcinogen known to damage DNA directly or through the generation of free radicals. Although in the long term, protective measures such as apoptosis and inflammation may prove beneficial in safeguarding the epidermis against the propagation of potentially tumorigenic cells, after high-dose UV irradiation these biologic events may be acutely detrimental to the architectural and functional integrity of the tissue owing to rampant cell death and inflammatory responses, which can culminate in epidermal erosion and consequently loss of barrier functions. The mitogen-activated protein kinase (MAPK) signaling pathway is known to be activated by UVR and herein we identify p38 MAPK as a key modulator of these physiologic events. Mice treated with the p38 MAPK inhibitor SB202190 are protected against several detrimental effects of acute UV irradiation, namely, sunburn cell/apoptosis, inflammation, and a hyperproliferation response. Based on our results, selectively blocking p38 activation with the SB202190 inhibitor could prove beneficial in treating victims from severe sunburn or exposure to other chemical agents known to trigger the p38 pathway. C1 NCI, Gene Response Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hildesheim, J (reprint author), NCI, Gene Response Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 36 TC 54 Z9 57 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 FEB PY 2004 VL 122 IS 2 BP 497 EP 502 DI 10.1046/j.0022-202X.2004.22229.x PG 6 WC Dermatology SC Dermatology GA 774PF UT WOS:000188991100052 PM 15009736 ER PT J AU He, YY Huang, JL Sik, RH Liu, J Waalkes, MP Chignell, CF AF He, YY Huang, JL Sik, RH Liu, J Waalkes, MP Chignell, CF TI Expression profiling of human keratinocyte response to ultraviolet A: Implications in apoptosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE apoptosis; carcinogenesis; keratinocytes; microarray; ultraviolet A ID RADIATION-INDUCED APOPTOSIS; IONIZING-RADIATION; TUMOR-SUPPRESSOR; C-MYC; DEPENDENT PROTEOLYSIS; DEVELOPING CEREBELLUM; GENOMIC INSTABILITY; GENE-EXPRESSION; GROWTH ARREST; CELL-DEATH AB Ultraviolet A radiation from sunlight is a major human health concern, as it is not absorbed by the ozone layer and can deeply penetrate into the skin causing skin damage. To study the molecular mechanism involved in the ultraviolet A effect, human HaCaT keratinocytes were exposed to ultraviolet A at doses of 10 J per cm(2) and 30 J per cm(2). Ultraviolet A irradiation caused dose- and time-dependent apoptotic cell death, as evidenced by DNA fragmentation, flow cytometry, and the activation of caspase-3. To study the genes altered by ultraviolet A at an apoptosis-inducing dose (30 J per cm(2)), cells were harvested immediately after ultraviolet A treatment (0 h), and 6 h and 24 h after ultraviolet A exposure. Total RNA was extracted for microarray and real-time RT-PCR analysis, and cellular proteins were extracted for western blot analysis. Of the selected critical genes/proteins, the induction of c-Jun, c-myc, and p33(ING1), and the repression of epidermal growth factor receptor, inhibitor of apoptosis protein, and survivin pathways, could be involved in ultraviolet-A-induced apoptosis. On the other hand, the late induction of cyclin D1 and cyclin-dependent kinase 4 was indicative of possible cell cycle recovery in surviving cells. Real-time RT-PCR analysis confirmed these results and a majority of the protein levels paralleled their corresponding RNA levels. In addition, ultraviolet A treatment altered the expression of genes involved in signal transduction, RNA processing, structural proteins, and metabolism in a time-dependent manner. This initial microarray analysis could advance our understanding of cellular responses to ultraviolet A exposure, and provide a platform from which to further study ultraviolet-A-induced apoptosis and carcinogenesis. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Comparat Carcinogenesis Lab, Natl Canc Ctr, NIH, Res Triangle Pk, NC 27709 USA. RP He, YY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM he3@niehs.nih.gov NR 58 TC 20 Z9 20 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 FEB PY 2004 VL 122 IS 2 BP 533 EP 543 DI 10.1046/j.0022-202X.2003.22123.x PG 11 WC Dermatology SC Dermatology GA 774PF UT WOS:000188991100057 PM 15009741 ER PT J AU Jiang, YJ Lu, B Xu, FY Gartshore, J Taylor, WA Halayko, AJ Gonzalez, FJ Takasaki, J Choy, PC Hatch, GM AF Jiang, YJ Lu, B Xu, FY Gartshore, J Taylor, WA Halayko, AJ Gonzalez, FJ Takasaki, J Choy, PC Hatch, GM TI Stimulation of cardiac cardiolipin biosynthesis by PPAR alpha activation SO JOURNAL OF LIPID RESEARCH LA English DT Article DE phospholipid; heart; lipid metabolism; gene expression; gene regulation ID PHOSPHATIDYLGLYCEROLPHOSPHATE SYNTHASE ACTIVITY; RAT-HEART MITOCHONDRIA; LIVER MITOCHONDRIA; PHOSPHOLIPASE A(2); FATTY-ACID; CELLS; EXPRESSION; MONOLYSOCARDIOLIPIN; DERIVATIVES; RECEPTORS AB The role of peroxisome proliferator-activated receptor alpha (PPARalpha)-stimulated phospholipase A(2) (PLA(2)) in cardiac mitochondrial cardiolipin (CL) biosynthesis was examined in both in vivo and in vitro models. Treatment of rat heart H9c2 cells with clofibrate increased the expression and activity of 14 kDa PLA(2) but did not affect the pool size of CL. Clofibrate treatment stimulated de novo CL biosynthesis via an increase in phosphatidylglycerolphosphate (PGP) synthase activity, accounting for the unaltered CL content. Cardiac PLA(2), PGP synthase, and CDP-1,2-diacyl-sn-glycerol synthase (CDS-2) activities and CDS-2 mRNA levels were elevated in mice fed clofibrate for 14 days compared with controls. In PPARalpha-null mice, clofibrate feeding did not alter cardiac PLA(2), PGP synthase activities, or CDS-2 activity and mRNA level, confirming that these enzymes are regulated by PPARalpha activation. In contrast to mouse heart, clofibrate treatment did not affect the activity or mRNA levels of CDS-2 in H9c2 cells, indicating that CDS-2 is regulated differently in rat heart H9c2 cells in vitro and in mouse heart in vivo. These results clearly indicate that cardiac CL de novo biosynthesis is stimulated by PPARalpha activation in responsive rodent models and that CDS-2 is an example of an enzyme that exhibits alternative regulation in vivo and in cultured cell lines. This study is the first to demonstrate that CL de novo biosynthesis is regulated by PPARalpha activation. C1 Univ Manitoba, Fac Med, Ctr Res & Treatment Atherosclerosis, Winnipeg, MB, Canada. Univ Manitoba, Fac Med, Dept Biochem & Med Genet, Winnipeg, MB, Canada. Univ Manitoba, Fac Med, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada. Univ Manitoba, Fac Med, Dept Physiol, Winnipeg, MB, Canada. NCI, NIH, Bethesda, MD 20892 USA. Yamanouchi Pharmaceut Co Ltd, Mol Med Labs, Tokyo, Japan. Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Tokyo, Japan. RP Hatch, GM (reprint author), Univ Manitoba, Fac Med, Ctr Res & Treatment Atherosclerosis, Winnipeg, MB, Canada. EM hatchgm@ms.umanitoba.ca NR 39 TC 23 Z9 24 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 2004 VL 45 IS 2 BP 244 EP 252 DI 10.1194/jlr.M300314-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 776JM UT WOS:000189112900005 PM 14594999 ER PT J AU Kitazume, E Takatsuka, T Sato, N Ito, Y AF Kitazume, E Takatsuka, T Sato, N Ito, Y TI Mutual metal separation system with enrichment using pH-peak focusing countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE mutual metal separation; pH-peak focusing countercurrent chromatography; enrichment; metal ions AB A highly efficient enrichment of metal ions was achieved by pH-peak-focusing high-speed countercurrent chromatography (CCC) that is developed by the variation of the pH-zone refining high-speed CCC. In this method, Ca, Cd, Cu, Mg, Mn, and Zn are chromatographically extracted in a basic organic stationary phase containing ammonia and a complex-forming reagent such as di(2-ethylhexyl) phosphoric acid, by introducing the sample solution into the column rotated at 800-1200 rpm. When the column is eluted with the acidified mobile phase containing hydrochloric acid, metal ions are trapped and concentrated around the sharp pH border formed in between the acidic and the basic zones, moving toward the outlet of the column. Enriched metal ions are finally eluted with the sharp pH-border as a highly concentrated peak into a small amount of eluent. The pH of the border is determined by the kinds of base and acid, and it shows the neutralization point. At this pH, trapped solute is moved towards the outlet of the column, based on its distribution ratio in each phase. The travel of this pH border through the column is determined by the molar ratio between the base in the stationary phase and acid in the mobile phase. By selecting appropriate experimental conditions, such as an acidity of the sample, bore of the column, and volume of the sample, each metal separation was achieved due to a longitudinally pH gradient on both sides of the pH border. Metal ions were concentrated at different positions in the moving pH border. When the pH border was sufficiently wide in the final stage of the elution, each concentrated metal could be separated mutually. The present method can be successfully applied to trace determination of cadmium in tap water, with coexsisting relatively large amounts of magnesium. C1 Iwate Univ, Fac Humanities & Social Sci, Morioka, Iwate 0208550, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kitazume, E (reprint author), Iwate Univ, Fac Humanities & Social Sci, Morioka, Iwate 0208550, Japan. EM kitazume@iwate-u.ac.jp NR 4 TC 0 Z9 0 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PD FEB PY 2004 VL 27 IS 3 BP 437 EP 449 DI 10.1081/JLC-120027616 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 801QQ UT WOS:000220110800004 ER PT J AU Aletras, AH Freidlin, RZ Navon, G Arai, AE AF Aletras, AH Freidlin, RZ Navon, G Arai, AE TI AIR-SPAMM: alternative inversion recovery spatial modulation of magnetization for myocardial tagging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE cardiac; function; SPAMM; DENSE; tagging; heart; MRI; HARP ID MOTION; HEART; ECHOES; MRI AB Alternate inversion recovery spatial modulation of magnetization (AIR-SPAMM) can be used either for doubling the number of tags for a given tagging encoding gradient strength or for improving tagging contrast ratio. AIR-SPAMM requires only a single acquisition and utilizes inversion pulses spaced throughout the gradient recalled echo (GRE) cine acquisition to "lock" the recovering magnetization at a desired level. The theory of AIR-SPAMM is presented along with simulations and results from phantoms. AIR-SPAMM can be used either for imaging systole as demonstrated by initial in vivo results or potentially for imaging the entire cardiac cycle in a slice-interleaved manner. (C) 2003 Elsevier Inc. All rights reserved. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NIH, US Dept Hlth & Human Serv, Ctr Informat Technol, Bethesda, MD USA. Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1D416,MSC 1061, Bethesda, MD 20892 USA. EM Anthony_Aletras@nih.gov OI Aletras, Anthony/0000-0002-3786-3817 NR 16 TC 6 Z9 7 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD FEB PY 2004 VL 166 IS 2 BP 236 EP 245 DI 10.1016/j.jmr.2003.10.021 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 767TU UT WOS:000188469400011 PM 14729035 ER PT J AU Paschal, CB Morris, HD AF Paschal, CB Morris, HD TI k-space in the clinic SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE k-spaces; spatial frequency; trajectory; echo planar imaging; spiral; parallel imaging ID ARTICULAR-CARTILAGE DEFECTS; SERIES RECONSTRUCTION RIGR; ECHO-PLANAR; MOTION ARTIFACTS; CHEMICAL-SHIFT; MR-IMAGES; LUNG PARENCHYMA; LIVER-LESIONS; CONTRAST; FMRI AB Magnetic resonance imaging (MRI) sequences are characterized by both radio frequency (RF) pulses and time-varying gradient magnetic fields. The RF pulses manipulate the alignment of the resonant nuclei and thereby generate a measurable signal. The gradient fields spatially encode the signals so that those arising from one location in an excited slice of tissue may be distinguished from those arising in another location. These signals are collected and mapped into an array called k-space that represents the spatial frequency content of the imaged object. Spatial frequencies indicate how rapidly an image feature changes over a given distance. It is the action of the gradient fields that determines where in the k-space array each data point is located, with the order in which k-space points are acquired being described by the k-space trajectory. How signals are mapped into k-space determines much of the spatial, temporal, and contrast resolution of the resulting images and scan duration. The objective of this article is to provide an understanding of k-space as is needed to better understand basic research in MRI and to make well-informed decisions about clinical protocols. Four major classes of trajectories-echo planar imaging (EPI), standard (non-EPI) rectilinear, radial, and spiral-are explained. Parallel imaging techniques SMASH (simultaneous acquisition of spatial harmonics) and SENSE (sensitivity encoding) are also described. C1 Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Sch Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Engn, Dept Biomed Engn, Nashville, TN 37232 USA. NINDS, NIH Magnet Resonance Facil, Bethesda, MD 20892 USA. RP Paschal, CB (reprint author), Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Sch Med, R-1321 MCN,1161 21st Ave S, Nashville, TN 37232 USA. EM cynthia.paschal@vanderbilt.edu OI Morris, H. Douglas/0000-0002-7942-3748 NR 84 TC 34 Z9 36 U1 2 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD FEB PY 2004 VL 19 IS 2 BP 145 EP 159 DI 10.1002/jmri.10451 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770QJ UT WOS:000188741500001 PM 14745747 ER PT J AU Kim, SYH Millard, RW Nisbet, P Cox, C Caine, ED AF Kim, SYH Millard, RW Nisbet, P Cox, C Caine, ED TI Potential research participants' views regarding researcher and institutional financial conflicts of interest SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID INFORMED CONSENT; CLINICAL-TRIALS; INDUSTRY; INVESTIGATORS; DISCLOSURE; POLICIES; FACULTY; SCIENCE AB Background: Financial conflict of interest in clinical research is an area of active debate. While data exist on the perspectives and roles of academic institutions, investigators, industry sponsors, and scientific journals, little is known about the perspectives of potential research participants. Methods: The authors surveyed potential research participants over the internet, using the Harris Interactive Chronic Illness Database. A potential research participant was defined by: (1) self report of diagnosis by a health care professional and (2) willingness to participate in clinical trials. Email invitations were sent to 20 205 persons with coronary artery disease, breast cancer, or depression; a total of 6363 persons were screened; of these, 86% or 5478 met inclusion criteria and completed the survey. The outcome measures were respondents' ratings on: importance of knowing conflict of interest information, whether its disclosure ought to be required, and its effect on willingness to participate - across seven widely discussed scenarios of financial conflicts of interest (ranging from commercial funding to equity ownership). Results: Majority responded that knowing conflict of interest information was "extremely" or "very" important; a larger majority felt financial conflicts of interest should be disclosed as part of informed consent (64% to 87%). In all seven scenarios, a majority was still willing to participate but in some scenarios a sizable minority would be wary of participation. Respondents were more wary of individual than institutional conflicts of interest. Illness group and sociodemographic factors had modest effects and did not affect the main trends. Conclusions: The prevailing practice of non-disclosure of financial conflicts of interest in clinical research appears contrary to the values of potential research participants. C1 Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. NICHHD, Biometry & Math Stat Branch, Bethesda, MD USA. HarrisInteract Inc, Rochester, NY USA. RP Kim, SYH (reprint author), Univ Rochester, Med Ctr, Dept Psychiat, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM Scott_Kim@urmc.rochester.edu NR 35 TC 58 Z9 58 U1 0 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD FEB 1 PY 2004 VL 30 IS 1 BP 73 EP 79 DI 10.1136/jme.2002.001461 PG 7 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 772TG UT WOS:000188856900016 PM 14872080 ER PT J AU Smucny, DA Allison, DB Ingram, DK Roth, GS Kemnitz, JW Kohama, SG Lane, MA Black, A AF Smucny, DA Allison, DB Ingram, DK Roth, GS Kemnitz, JW Kohama, SG Lane, MA Black, A TI Changes in blood chemistry and hematology variables during aging in captive rhesus macaques (Macaca mulatta). J Med Primatol 30 : 161-173 2001 SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE age effects; monkeys; veterinary care of older primates AB The Primate Aging Database (PAD) is being developed to assist research using nonhuman primate models for various gerontological applications. We provide now an update of an earlier report providing data on hernatological and blood chemistry values for rhesus monkeys across the adult lifespan. These data were collected from several research colonies and have been submitted to rigorous statistical analyses to identify relationships with chronological age. C1 NIA, Lab Expt Gerontol, Ctr Gerontol Res, Behav Neurosci Sect, Baltimore, MD 21224 USA. SW Fdn Biomed Res, SW Natl Primate Res Ctr, San Antonio, TX 78284 USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL USA. Univ Alabama, Dept Biostat, Clin Nutr Res Ctr, Birmingham, AL USA. Univ Wisconsin, Natl Primate Res Ctr, Dept Physiol, Madison, WI USA. Oregon Primate Res Ctr, Beaverton, OR 97006 USA. Merck & Co Inc, Rahway, NJ 07065 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Ctr Gerontol Res, Behav Neurosci Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM IngramD@grc.nia.nih.gov OI Allison, David/0000-0003-3566-9399 NR 1 TC 15 Z9 16 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB PY 2004 VL 33 IS 1 BP 48 EP 54 DI 10.1111/j.1600-0684.2003.00052.x PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 800OI UT WOS:000220037200008 PM 15061733 ER PT J AU Kim, MK Kim, HS Kim, BO Yoo, SY Seong, JH Kim, DK Lee, SE Choe, SJ Park, JC Min, BM Jeong, MJ Kim, DK Shin, YK Kook, JK AF Kim, MK Kim, HS Kim, BO Yoo, SY Seong, JH Kim, DK Lee, SE Choe, SJ Park, JC Min, BM Jeong, MJ Kim, DK Shin, YK Kook, JK TI Multiplex PCR using conserved and species-specific 16S rDNA primers for simultaneous detection of Fusobacterium nucleatum and Actinobacillus actinomycetemcomitans SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Actinobacillus actinomycetemcomitans; Fusobacterium nucleatum; multiplex PCR; 16S rDNA ID POLYMERASE-CHAIN-REACTION; PUTATIVE PERIODONTAL PATHOGENS; DOT-BLOT HYBRIDIZATION; RNA GENE PRIMERS; PORPHYROMONAS-GINGIVALIS; BACTEROIDES-FORSYTHUS; JUVENILE PERIODONTITIS; PREVOTELLA-INTERMEDIA; SUBGINGIVAL PLAQUE; LEUKOTOXIN GENE AB This study was undertaken to develop PCR primers for the simultaneous detection of Fusobacterium nucleatum and Actinobacillus actinomycetemcomitans, using two species-specific reverse primers in combination with a single conserved forward primer. These primers target the variable and conserved regions of the 16S rDNA. The primer specificity was tested against (i) four E nucleatum and three A. actinomycetemcomitans strains and (ii) seven representatives of the different species of oral bacteria. The primer sensitivity was determined by testing serial dilutions of the purified genomic DNA of F nucleatum and A. actinomycetemcomitans. The data indicate that species-specific amplicons could be obtained for all the E nucleation and A. actinomycetemcomitans strains tested, which were not found in the seven other species. The multiplex PCR could detect as little as 4 fg of chromosomal DNA of F nucleatum and A. actinomycetemcomitans simultaneously. These findings suggest that these PCR primers are highly sensitive and are suitable for applications in epidemiological studies, diagnosis, and monitoring F nucleatum and A. actinomycetemcomitans after the treatment of periodontitis. C1 Chosun Univ, Dept Oral Biochem, Coll Dent, Kwangju 501759, South Korea. Chosun Univ, Oral Biol Res Inst, Coll Dent, Kwangju 501759, South Korea. Chosun Univ, BK21, Coll Dent, Kwangju 501759, South Korea. Chonnam Natl Univ, Coll Dent, Dept Dent Pharmacol, Kwangju 500757, South Korea. Seoul Natl Univ, Coll Dent, Dept Oral Microbiol & Immunol, Seoul 110749, South Korea. Seoul Natl Univ, Coll Dent, Dept Oral Biochem, Seoul 110749, South Korea. NHGRI, Div Genome Resources Bank & Reservat, NIH, Seoul 122701, South Korea. RP Kook, JK (reprint author), Chosun Univ, Dept Oral Biochem, Coll Dent, Kwangju 501759, South Korea. EM jkkook@chosun.ac.kr; jkkook@chosun.ac.kr RI Park, Joo Cheol/D-6437-2012; Min, Byung-Moo/F-2854-2012; OI Kook, Joong-Ki/0000-0003-2628-2870 NR 31 TC 8 Z9 9 U1 0 U2 2 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD FEB PY 2004 VL 14 IS 1 BP 110 EP 115 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 778YA UT WOS:000189267900016 ER PT J AU Cheng, RYS Birely, LA Lum, NL Perella, CM Cherry, JM Bhat, NK Kasprzak, KS Powell, DA Alvord, WG Anderson, LM AF Cheng, RYS Birely, LA Lum, NL Perella, CM Cherry, JM Bhat, NK Kasprzak, KS Powell, DA Alvord, WG Anderson, LM TI Expressions of hepatic genes, especially IGF-binding protein-1, correlating with serum corticosterone in microarray analysis SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER; PROMOTER ACTIVITY; PLASMA-INSULIN; CIS-ELEMENTS; RAT; GLUCOCORTICOIDS; DEXAMETHASONE; CELLS; STIMULATION; INHIBITION AB Microarray technology was evaluated for usefulness in assessing relationships between serum corticosterone and hepatic gene expression. Nine pairs of female Swiss mice were chosen to provide a wide range of serum corticosterone ratios; cDNA microarray analysis (similar to8000 genes) was performed on their livers. A statistical method based on calculation of 99% confidence intervals discovered 32 genes which varied significantly among the livers. Five of these ratios correlated significantly with serum corticosterone ratio, including tyrosine aminotransferase, stress-induced protein, pleiotropic regulator I and insulin-like growth factor-binding protein-1; the latter has a potential role in cancer development. Secondly, linear regression of gene expression vs corticosterone ratios was screened for those with r greater than or equal to 0.8 (P < 0.01), yielding 141 genes, including some known to be corticosterone regulated and others of interest as possible glucocorticoid targets. Half of these significant correlations involved data sets where no microarray ratio exceeded +/- 1.5. These results showed that microarray may be used to survey tissues for changes in gene expression related to serum hormones, and that even small changes in expression can be of statistical significance in a study with adequate numbers of replicate samples. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. SAIC Frederick Inc, Frederick, MD USA. Data Management Serv Inc, Frederick, MD USA. RP Cheng, RYS (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538, Frederick, MD 21701 USA. EM rcheng@mail.ncifcrf.gov OI Cheng, Robert/0000-0003-0287-6439 NR 50 TC 9 Z9 12 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD FEB PY 2004 VL 32 IS 1 BP 257 EP 278 DI 10.1677/jme.0.0320257 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 804NM UT WOS:000220305400020 PM 14766007 ER PT J AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ TI A tale of two tumor targets: Topoisomerase I and tubulin. The Wall and Wani contribution to cancer chemotherapy SO JOURNAL OF NATURAL PRODUCTS LA English DT Review ID SORANGIUM-CELLULOSUM; BIOLOGICAL EVALUATION; ANTICANCER ACTIVITY; ANTIMITOTIC AGENTS; NATURAL-PRODUCTS; DIAZONAMIDE-A; DISCODERMOLIDE; ANALOGS; DNA; MICROTUBULES AB The seminal discoveries of camptothecin and Taxol by Wall and Wani are discussed in a manner that demonstrates the influence that these two compounds has had on the further development of natural product, natural product-derived, and (some) synthetic entities as potential drug leads that interact either with tubulin or with topoisomerase I. The major categories of tubulin interactive agents in terms of inhibition and promotion of tubulin polymerization are briefly discussed. Likewise, a brief discussion of topoisomerase I inhibitors is presented. Lists of tubulin interactive agents and topoisomerase I inhibitors in preclinical and clinical development are given in Tables 2 and 3, respectively. This review is not meant to be exhaustive, but does illustrate the profound impact that these two plant-derived agents have had on cancer chemotherapy. C1 NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cragg, GM (reprint author), NCI, POB B, Ft Detrick, MD 21702 USA. EM craggg@mail.nih.gov NR 53 TC 147 Z9 151 U1 1 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 2004 VL 67 IS 2 BP 232 EP 244 DI 10.1021/np030420c PG 13 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 800IZ UT WOS:000220023300021 PM 14987065 ER PT J AU Harish, CP Kesavapani, S Zheng, Y AF Harish, CP Kesavapani, S Zheng, Y TI Signal transduction and topographic regulation of neuronal cytoskeletal protein SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 6th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY FEB 04-07, 2004 CL Hong Kong, PEOPLES R CHINA SP Asian-Pacific Soc Neurochem DE cytoskeleton; neurodegeneration; phosphorylation; proteins; regulation/deregulation C1 NIH, LNC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 SU 1 BP 8 EP 8 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 775UH UT WOS:000189078700019 ER PT J AU Zhu, JPQ Xu, W Cadet, JL Angulo, JA AF Zhu, JPQ Xu, W Cadet, JL Angulo, JA TI Methamphetamine-induced postsynaptic cell death precedes dopaminergic terminal damage SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 6th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY FEB 04-07, 2004 CL Hong Kong, PEOPLES R CHINA SP Asian-Pacific Soc Neurochem DE drugs of abuse; neurotoxicity C1 CUNY Hunter Coll, New York, NY 10021 USA. NIDA, Mol Neuropsychiat Sect, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 SU 1 BP 69 EP 69 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 775UH UT WOS:000189078700218 ER PT J AU Shine, HD Grider, MH Mamounas, LA Baumgartner, BJ Le, W AF Shine, HD Grider, MH Mamounas, LA Baumgartner, BJ Le, W TI In situ expression of BDNF or NT-3 promotes local regeneration of lesioned serotonergic axons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 6th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY FEB 04-07, 2004 CL Hong Kong, PEOPLES R CHINA SP Asian-Pacific Soc Neurochem DE BDNF; neurotrophin; NT-3; regeneration; serotonergic C1 Baylor Coll Med, Houston, TX 77030 USA. NINDS, Bethesda, MD 20892 USA. Valley Community Coll, Athens, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 SU 1 BP 75 EP 75 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 775UH UT WOS:000189078700233 ER PT J AU Kesavapany, S Amin, N Zheng, Y Jaffe, H Nijhara, R Gutkind, S Takahashi, S Kulkarni, A Grant, P Pant, HC AF Kesavapany, S Amin, N Zheng, Y Jaffe, H Nijhara, R Gutkind, S Takahashi, S Kulkarni, A Grant, P Pant, HC TI p35/Cdk5 phosphorylates RasGRF2 regulating RasGRF2-mediated Rac signaling and ERK1/2 activity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 6th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY FEB 04-07, 2004 CL Hong Kong, PEOPLES R CHINA SP Asian-Pacific Soc Neurochem DE cell surface-cell membrane; cytoskeleton; signal transduction C1 NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 SU 1 BP 81 EP 81 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 775UH UT WOS:000189078700253 ER PT J AU Koshimizu, H Lu, B Suzuki, S Hara, T Kojima, M AF Koshimizu, H Lu, B Suzuki, S Hara, T Kojima, M TI Decreased trophic effects of BDNF SNPs variants to CNS neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 6th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY FEB 04-07, 2004 CL Hong Kong, PEOPLES R CHINA SP Asian-Pacific Soc Neurochem DE amino acids; cell death and survival; diseases and mo; neurotransmitters; peptides; proteins; trophic factors and cytokines C1 Natl Inst AIST, Ikeda, Osaka, Japan. NICHD, NIH, Bethesda, MD USA. RI Koshimizu, Hisatsugu/G-5536-2010; Lu, Bai/A-4018-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 SU 1 BP 90 EP 90 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 775UH UT WOS:000189078700285 ER PT J AU Suzuki, S Numakawa, T Koshimizu, H Hatanaka, H Lu, B Kojima, M AF Suzuki, S Numakawa, T Koshimizu, H Hatanaka, H Lu, B Kojima, M TI Lipid rafts mediate BDNF/TRKB signaling in CNS neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 6th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry CY FEB 04-07, 2004 CL Hong Kong, PEOPLES R CHINA SP Asian-Pacific Soc Neurochem DE exocytosis; lipids; receptors; signal transduction; trophic factors C1 AIST Kansai, Div Life Sci Technol, Osaka, Japan. Osaka Univ, Inst Prot Res, Suita, Osaka 565, Japan. Natl Inst Neurosci, NCNP, Tokyo, Japan. NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD USA. RI Koshimizu, Hisatsugu/G-5536-2010; Lu, Bai/A-4018-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 SU 1 BP 90 EP 90 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 775UH UT WOS:000189078700284 ER PT J AU Canals, M Burgueno, J Marcellino, D Cabello, N Canela, EI Mallol, J Agnati, L Ferre, S Bouvier, M Fuxe, K Ciruela, F Lluis, C Franco, R AF Canals, M Burgueno, J Marcellino, D Cabello, N Canela, EI Mallol, J Agnati, L Ferre, S Bouvier, M Fuxe, K Ciruela, F Lluis, C Franco, R TI Homodimerization of adenosine A(2A) receptors: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 7TM receptors; dopamine receptors; G protein-coupled receptors; heteromerization; homomerization; receptor-receptor interactions ID PROTEIN-PROTEIN INTERACTIONS; DOPAMINE-D-2 RECEPTORS; TRANSFER BRET; LIVING CELLS; LIVE CELLS; OLIGOMERIZATION; AGONIST; DIMERIZATION; MODULATION; COMPLEXES AB The results presented in this paper show that adenosine A(2A) receptor (A(2A)R) form homodimers and that homodimers but not monomers are the functional species at the cell surface. Fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) techniques have been used to demonstrate in transfected HEK293 cells homodimerization of A(2A)R, which are heptaspanning membrane receptors with enriched expression in striatum. The existence of homodimers at the cell surface was demonstrated by time-resolved FRET. Although agonist activation of the receptor leads to the formation of receptor clusters, it did not affect the degree of A(2A)R-A(2A)R dimerization. Both monomers and dimers were detected by immunoblotting in cell extracts. However, cell surface biotinylation of proteins has made evident that more than 90% of the cell surface receptor is in its dimeric form. Thus, it seems that homodimers are the functional form of the receptor present on the plasma membrane. A deletion mutant version of the A(2A) receptor, lacking its C-terminal domain, was also able to form both monomeric and dimeric species when cell extracts from transfected cells were analyzed by immunoblotting. This suggests that the C-terminal tail does not participate in the dimerization. This is relevant as the C-terminal tail of A(2A)R is involved in heteromers formed by A(2A)R and dopamine D2 receptors. BRET ratios corresponding to A(2A)R-A(2A)R homodimers were higher than those encountered for heterodimers formed by A(2A)R and dopamine D2 receptors. As A(2A)R and dopamine D2 receptors do indeed interact, these results indicate that A(2A)R homodimers are the functional species at the cell surface and that they coexist with A(2A)R/D2 receptor heterodimers. C1 Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Univ Modena & Reggio Emilia, Dept Biomed Sci, Modena, Italy. Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, Stockholm, Sweden. RP Franco, R (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, Marti Franques 1, E-08028 Barcelona, Spain. EM rfranco@ub.edu RI Canela, Enric I./M-8726-2013; Bouvier, Michel/H-2758-2014; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; OI Canela, Enric I./0000-0003-4992-7440; Bouvier, Michel/0000-0003-1128-0100; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Marcellino, Daniel/0000-0002-4618-7267; Canals, Meritxell/0000-0002-7942-5006 NR 29 TC 99 Z9 100 U1 4 U2 14 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 IS 3 BP 726 EP 734 DI 10.1046/j.1471-4159.2003.02200.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 763YQ UT WOS:000188128400022 PM 14720222 ER PT J AU Wang, TG Qin, L Liu, B Liu, YX Wilson, B Eling, TE Langenbach, R Taniura, S Hong, JS AF Wang, TG Qin, L Liu, B Liu, YX Wilson, B Eling, TE Langenbach, R Taniura, S Hong, JS TI Role of reactive oxygen species in LPS-induced production of prostaglandin E-2 in microglia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cyclooxygenase-2; lipopolysaccharide; microglia; NADPH oxidase; prostaglandin E-2; reactive oxygen species ID ALZHEIMERS-DISEASE BRAINS; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B/; NITRIC-OXIDE; CYCLOOXYGENASE-2 EXPRESSION; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; INDUCIBLE CYCLOOXYGENASE; OXIDATIVE STRESS; SUBSTANTIA-NIGRA AB We determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin E-2 (PGE(2)) in lipopolysaccharide (LPS)-activated microglia. LPS treatment increased intracellular ROS in rat microglia dose-dependently. Pre-treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge intracellular ROS, significantly attenuated LPS-induced release in PGE(2). Diphenylene iodonium (DPI), a non-specific NADPH oxidase inhibitor, decreased LPS-induced PGE(2) production. In addition, microglia from NADPH oxidase-deficient mice produced less PGE(2) than those from wild-type mice following LPS treatment. Furthermore, LPS-stimulated expression of COX-2 (determined by RT-PCR analysis of COX-2 mRNA and western blot for its protein) was significantly reduced bypre-treatment with SOD/catalase or SOD/catalase mimetics. SOD/catalase mimetics were more potent than SOD/catalase in reducing COX-2 expression and PGE(2) production. As a comparison, scavenging ROS had no effect on LPS-induced nitric oxide production in microglia. These results suggest that ROS play a regulatory role in the expression of COX-2 and the subsequent production of PGE(2) during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX-2 expression and PGE(2) production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation-mediated neurodegenerative diseases. C1 NIEHS, Neuropharm Sect, Lab Pharm & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Neuropharm Sect, Lab Pharm & Chem, NIH, POB 12233,MDF1-01, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov RI liu, Bin/A-7695-2009 NR 57 TC 139 Z9 147 U1 1 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2004 VL 88 IS 4 BP 939 EP 947 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 774UK UT WOS:000189003500018 PM 14756815 ER PT J AU Khalsa, JH Royal, W AF Khalsa, JH Royal, W TI Do drugs of abuse impact on HIV disease? SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 9th Conference of the Society-of-NeuroImmune-Pharmacology CY OCT 02-06, 2002 CL CLEARWATER BEACH, FLORIDA SP SNIP, Univ So Florida DE HIV/AIDS; drug abuse; disease progression ID AIDS; DEMENTIA; USERS; VIRUS AB Drug abuse, certain lifestyles, access and adherence to drug abuse treatment, and medical consequences of drug abuse remain as important factors that impact on HIV disease among AIDS patients worldwide. Most in vitro and in vivo studies show a significant impact on HIV disease. Epidemiological studies in the past have failed to support these observations. However, new and limited evidence shows that drug abuse may accelerate HIV disease in humans. Research is needed to design new or refine known techniques that more closely mimic natural conditions of HIV disease, and perform additional assessments of basic laboratory, clinical, and epidemiological data to determine whether drug abuse significantly impacts on HIV disease. (C) 2003 Elsevier B.V. All rights reserved. C1 NIDA, CAMCODA, NIH, Bethesda, MD 20892 USA. Morehouse Sch Med, Neurosci Inst, Atlanta, GA 30310 USA. RP Khalsa, JH (reprint author), NIDA, CAMCODA, NIH, 6001 Execut Blvd,Room 5198,MSC 9593, Bethesda, MD 20892 USA. EM jk98@nih.gov; wroyal@msm.edu NR 12 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 2004 VL 147 IS 1-2 BP 6 EP 8 DI 10.1016/j.jneuroim.2003.10.007 PG 3 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 772GQ UT WOS:000188834000004 PM 14741417 ER PT J AU Wang, TG Liu, B Qin, LY Wilson, B Hong, JS AF Wang, TG Liu, B Qin, LY Wilson, B Hong, JS TI Protective effect of the SOD/catalase mimetic MnTMPyP on inflammation-mediated dopaminergic neurodegeneration in mesencephalic neuronal-glial cultures SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 9th Conference of the Society-of-NeuroImmune-Pharmacology CY OCT 02-06, 2002 CL CLEARWATER BEACH, FLORIDA SP SNIP, Univ So Florida DE MnTMPyP; lipopolysaccharide; microglia; reactive oxygen species; dopamine; prostaglandin E-2 ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; MICROGLIA; ACTIVATION; BRAIN; EXPRESSION; MECHANISMS; INJURY; DAMAGE; CELLS AB Reactive oxygen species (ROS) produced by activated microglia are deleterious to neurons. In this study, we studied the effect of Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a superoxide dismutase/catalase mimetic, on the lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons in rat mesencephalic neuroglia cultures. MnTMPyP exhibited a significantly protective effect against LPS (5 ng/ml)-induced neurotoxicity as determined by [3 H]dopamine uptake and immunocytochemical analysis. MnTMPyP significantly attenuated LPS-induced production of superoxide free radical and prostaglandin E-2 (PGE(2)) in microglia. These results indicate that MnTMPyP may potentially be used for the treatment of inflammation-related degenerative neurological disorders. (C) 2003 Elsevier B.V. All rights reserved. C1 NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, Lab Pharmacol & Chem, Neuropharmacol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov RI liu, Bin/A-7695-2009 NR 24 TC 33 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 2004 VL 147 IS 1-2 BP 68 EP 72 DI 10.1016/j.neuroim.2003.10.040 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 772GQ UT WOS:000188834000017 PM 14741430 ER PT J AU Dagvadorj, A Olive, M Urtizberea, JA Halle, M Shatunov, A Bonnemann, C Park, KY Goebel, HH Ferrer, I Vicart, P Dalakas, MC Goldfarb, LG AF Dagvadorj, A Olive, M Urtizberea, JA Halle, M Shatunov, A Bonnemann, C Park, KY Goebel, HH Ferrer, I Vicart, P Dalakas, MC Goldfarb, LG TI A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin SO JOURNAL OF NEUROLOGY LA English DT Article DE cardiomyopathy; skeletal myopathy; desmin gene; de novo mutation ID DOMINANT DISTAL MYOPATHY; INTERMEDIATE-FILAMENTS; MISSENSE MUTATION; GENE CAUSES; CARDIOMYOPATHY; ORIGIN; MOTIF; 2B AB Desminopathy is a familial or sporadic cardiac and skeletal muscular dystrophy associated with mutations in desmin. We have previously characterized a de novo desmin R406W mutation in a patient of European origin with early onset muscle weakness in the lower extremities and atrioventricular conduction block requiring a permanent pacemaker. The disease relentlessly progressed resulting in severe incapacity within 5 years after onset. We have now identified three other patients with early onset rapidly progressive cardiac and skeletal myopathy caused by this same desmin R406W mutation. The mutation was present in each studied patient, but not in their parents or other unaffected family members, indicating that the mutation in all four cases was generated de novo. The patients' mutation-carrying chromosomes showed no similarity, suggesting that the R406W mutation has occurred independently. These observations strongly confirm that the de novo R406W desmin mutation is the genetic basis for early-onset cardiac and skeletal myopathy in patients with sporadic disease and indicate that desmin position 406 is a hot spot for spontaneous mutations. The high pathogenic potential of this mutation can be explained by its location in the highly conserved YRKLLEGEE motif at the C-terminal end of the 2B helix that has a critical role in the process of desmin filament assembly. C1 NINDS, NIH, Bethesda, MD 20892 USA. Ciutat Sanitaria & Univ Bellvitge, Hosp Llobregat, Inst Neuropatol, Barcelona, Spain. Hop Ray Poincare, F-92380 Garches, France. Univ Gottingen, Med Klin, D-37075 Gottingen, Germany. Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. Univ Mainz, Med Ctr, Dept Neuropathol, D-55131 Mainz, Germany. Univ Paris 06, CNRS, UMR 7000, Lab Cytosquelette & Dev, F-75013 Paris, France. RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 10,Room 4B37,10 Ctr Dr,MSC 1361, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov RI Shatunov, Aleksey/E-6946-2011; OI Olive, Montse/0000-0001-5727-0165 NR 23 TC 29 Z9 32 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD FEB PY 2004 VL 251 IS 2 BP 143 EP 149 DI 10.1007/s00415-004-0289-3 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 777KL UT WOS:000189177500003 PM 14991347 ER PT J AU Kawagoe, R Takikawa, Y Hikosaka, O AF Kawagoe, R Takikawa, Y Hikosaka, O TI Reward-predicting activity of dopamine and caudate neurons - A possible mechanism of motivational control of saccadic eye movement SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NIGRA PARS RETICULATA; PRIMATE SUBSTANTIA-NIGRA; MEDIUM SPINY NEURONS; OCULOMOTOR FUNCTIONS; BASAL GANGLIA; CORTICOSTRIATAL PROJECTIONS; FUNCTIONAL-PROPERTIES; RECEPTOR ACTIVATION; AUDITORY RESPONSES; STRIATAL NEURONS AB Recent studies have suggested that the basal ganglia are related to motivational control of behavior. To study how motivational signals modulate motor signals in the basal ganglia, we examined activity of midbrain dopamine (DA) neurons and caudate (CD) projection neurons while monkeys were performing a one-direction-rewarded version (1DR) of memory-guided saccade task. The cue stimulus indicated the goal position for an upcoming saccade and the presence or absence of reward after the trial. Among four monkeys we studied, three were sensitive to reward such that saccade velocity was significantly higher in the rewarded trials than in the nonrewarded trials; one monkey was insensitive to reward. In the reward-sensitive monkeys, both DA and CD neurons responded differentially to reward-indicating and no-reward-indicating cues. Thus DA neurons responded with excitation to a reward-indicating cue and with inhibition to a no-reward-indicating cue. A group of CD neurons responded to the cue in their response fields (mostly contralateral) and the cue response was usually enhanced when it indicated reward. In the reward-insensitive monkey, DA neurons showed no response to the cue, while the cue responses of CD neurons were not modulated by reward. Many CD neurons in the reward-sensitive monkeys, but not the reward-insensitive monkey, showed precue activity. These results suggest that DA neurons, with their connection to CD neurons, modulate the spatially selective signals in CD neurons in the reward-predicting manner and CD neurons in turn modulate saccade parameters with their polysynaptic connections to the oculomotor brain stem. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Dept Physiol, Tokyo 1138421, Japan. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr,Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov NR 52 TC 89 Z9 93 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB 1 PY 2004 VL 91 IS 2 BP 1013 EP 1024 DI 10.1152/jn.00721.2003 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 770TH UT WOS:000188746600037 PM 14523067 ER PT J AU Iuliano, BA Pluta, RM Jung, C Oldfield, EH AF Iuliano, BA Pluta, RM Jung, C Oldfield, EH TI Endothelial dysfunction in a primate model of cerebral vasospasm SO JOURNAL OF NEUROSURGERY LA English DT Article DE vasospasm; subarachnoid hemorrhage; nitric oxide; endothelial dysfunction; Macaca fascicularis ID NITRIC-OXIDE SYNTHASE; EXPERIMENTAL SUBARACHNOID HEMORRHAGE; CANINE BASILAR ARTERY; L-ARGININE; DEPENDENT RELAXATION; SIGNAL-TRANSDUCTION; GUANYLATE-CYCLASE; RELAXING FACTOR; BLOOD-FLOW; MECHANISMS AB Object. Although abnormalities in the control of endothelial vasomotility have been reported in both experimental and clinical studies, the mechanism of the endothelial dysfunction that occurs following subarachnoid hemorrhage (SAH) remains unclear. Because of the absence of previous in vivo studies of endothelial function in cerebral vessels in response to SAH or cerebral vasospasm, the authors investigated endothelium-dependent responses in an established primate model of vasospasm after SAH. Endothelial function was assessed by examining vascular responses to intracarotid injections of various drugs known to act via the endothelium. Drugs that have a rapid total body clearance were selected so that their pharmacological effects would be limited to the cerebral circulation after an intracarotid infusion. Methods. Seventeen adult male cynomolgus monkeys were used. Cerebrovascular endothelium-dependent responses were examined in control animals and in animals with SAH 7, 14, and 21 days after placement of a subarachnoid clot around the right middle cerebral artery. Cortical cerebral blood flow (CBF) and cerebrovascular resistance (CVR) were recorded continuously during 5-minute intracarotid infusions of 5% dextrose vehicle, acetylcholine, histamine, bradykinin, or Calcimycin. In control animals the intracarotid infusion of acetylcholine produced a significant (7.8 +/- 9.5%) increase in CBF and a 9.3 +/- 8.7% reduction in CVR in comparison with a control infusion of dextrose vehicle. The responses to acetylcholine disappeared in animals 7 days post-SAH, specifically in the subset of animals in which arteriography confirmed the presence of vasospasm. Infusion of Calcimycin produced no significant changes in CBF or CVR in control animals, but resulted in a significant reduction in CBF and increase in CVR in animals 7 days after SAH and in animals with vasospasm. An infusion of histamine or bradykinin had no significant effect on CBF or CVR. Conclusions. An intracarotid infusion of acetylcholine, but not one of histamine, bradykinin, or Calcimycin, produced a measurable physiological response in the normal primate cerebrovasculature. Cerebral vasospasm that occurred after SAH produced a pathophysiological effect similar to the endothelial denudation shown in the in vitro experiments of Furchgott and Zawadzki, in which acetylcholine constricted the vessels via activation of receptors on smooth-muscle cells. Changes in vascular responses to acetylcholine and Calcimycin in animals with vasospasm, compared with control animals, provide evidence that endothelial dysfunction plays a key role in the development and/or sustenance of vasospasm after SAH. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Neurol Surg, Rochester, MN USA. Univ Frankfurt, Dept Neurosurg, D-6000 Frankfurt, Germany. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM oldfielde@ninds.nih.gov NR 73 TC 38 Z9 42 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2004 VL 100 IS 2 BP 287 EP 294 DI 10.3171/jns.2004.100.2.0287 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 768TT UT WOS:000188551700016 PM 15086237 ER PT J AU Reinwald, S Li, Y Moriguchi, T Salem, N Watkins, BA AF Reinwald, S Li, Y Moriguchi, T Salem, N Watkins, BA TI Repletion with (n-3) fatty acids reverses bone structural deficits in (n-3)-deficient rats SO JOURNAL OF NUTRITION LA English DT Article DE (n-3) fatty acids; rats; bone; mechanical properties; bone modeling ID MECHANICAL-PROPERTIES; DIETARY LIPIDS; EICOSAPENTAENOIC ACID; MINERAL CONTENT; CELL-FUNCTION; LONG-TERM; GROWTH; TISSUES; ALTERS; TIBIA AB (n-3) PUFA deficiency and repletion effects on bone mechanical properties have not been examined. The primary research aim was to evaluate whether changes in the fatty acid composition of bone tissue compartments previously reported to influence bone formation rates would affect bone modeling and mechanical properties. In this investigation, three groups of rats were studied, second generation (n-3)-deficient, (n-3)-repleted, and a control (n-3)-adequate. The (n-3)-adequate diet contained a-linolenic acid [LNA, 18:3(n-3), 2.6% of total fatty acids) and docosahexaenoic acid [DHA, 22:6(n-3),1.3% of total fatty acids]. Fatty acid composition of the hindlimb tissues (bone and muscle) of chronically (n-3)-deficient rats revealed a marked increase in (n-6) PUFA [20:4(n-6), 22:4(n-6), and 22:5(n-6)] and a corresponding decrease in (n-3) PUFA [1 8:3(n-3), 20:5(n-3), 22:5(n-3) and 22:6(n-3)]. Measurement of bone mechanical properties (energy to peak load) of tibiae showed that (n-3) deficiency diminished structural integrity. Rats repleted with (n-3) fatty acids demonstrated accelerated bone modeling (cross-sectional geometry) and an improved second moment in tibiae compared with control (n-3)-adequate rats after 28 d of dietary treatment. This study showed that repletion with dietary (n-3) fatty acids restored the ratio of (n-6)/(n-3) PUFA in bone compartments and reversed compromised bone modeling in (n-3)- deficient rats. C1 Purdue Univ, Lipid Chem & Mol Biol Lab, Ctr Enhancing Foods Protect Hlth, W Lafayette, IN 47907 USA. NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. RP Watkins, BA (reprint author), Purdue Univ, Lipid Chem & Mol Biol Lab, Ctr Enhancing Foods Protect Hlth, W Lafayette, IN 47907 USA. EM baw@purdue.edu NR 32 TC 47 Z9 48 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2004 VL 134 IS 2 BP 388 EP 394 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 770DN UT WOS:000188708100015 PM 14747677 ER PT J AU Mai, V Katki, HA Harmsen, H Gallaher, D Schatzkin, A Baer, DJ Clevidence, B AF Mai, V Katki, HA Harmsen, H Gallaher, D Schatzkin, A Baer, DJ Clevidence, B TI Effects of a controlled diet and black tea drinking on the fecal microflora composition and the fecal bile acid profile of human volunteers in a double-blinded Randomized feeding study SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA DE fecal microflora; black tea; human; FISH; DGGE; diet ID 16S RIBOSOMAL-RNA; IN-SITU HYBRIDIZATION; HUMAN FECES; OLIGONUCLEOTIDE PROBES; INTESTINAL MICROFLORA; UNITED-STATES; BACTERIA; MICROBIOTA; SAMPLES; FLORA AB Although diet has been clearly associated with human health many potential mechanisms remain undefined. For instance, although the intestinal bacterial microflora has long been postulated to contribute to human health, little is known about the effects of diet on the bacterial microflora composition and the specific contributions of the microflora, to human health. Thus, we analyzed 1) changes in the fecal microflora composition by fluorescent in-situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) and 2) changes in the fecal bile acid profile, in a crossover feeding study that investigated the effects of black tea drinking on blood lipids in hypercholesterolemic volunteers. DGGE analysis shows that each study subject harbors a specific bacterial profile that exhibits little change over time. Change from a "free" living diet to the controlled study diet or to black tea drinking did not significantly change these bacterial profiles. FISH analysis revealed that even though black tea did not affect the specific bacterial groups that were analyzed, it did decrease the amounts of bacteria that were detected by the universal bacterial probe, but not by any of the specific probes. We did not detect any consistent effects of either diet or black tea drinking on the levels and proportions of fecal bile acids. Our results indicate that tea drinking affects some microflora components. Larger studies with well defined end points that control for the observed variation are needed to improve our understanding of the effects of diet on intestinal microflora. and fecal bile acid profile. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Groningen, Dept Med Microbiol, Groningen, Netherlands. Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN 55108 USA. USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP Mai, V (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. EM vmai@epi.umaryland.edu RI Katki, Hormuzd/B-4003-2015; OI Gallaher, Daniel/0000-0002-5969-4938 NR 31 TC 31 Z9 35 U1 2 U2 10 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2004 VL 134 IS 2 BP 473 EP 478 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 770DN UT WOS:000188708100029 PM 14747691 ER PT J AU Wendler, D Forster, H AF Wendler, D Forster, H TI Why we need legal standards for pediatric research SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID CHILDREN; EXPERIMENTATION C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 17 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2004 VL 144 IS 2 BP 150 EP 153 DI 10.1016/j.jpeds.2003.10.033 PG 4 WC Pediatrics SC Pediatrics GA 773LT UT WOS:000188925800005 PM 14760251 ER PT J AU Gafni, RI Baron, J AF Gafni, RI Baron, J TI Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy X-ray absorptiometry (DEXA) SO JOURNAL OF PEDIATRICS LA English DT Article ID BONE-MINERAL DENSITY; HEALTHY-CHILDREN; BODY-COMPOSITION; PUBERTY; DENSITOMETRY; MASS; DISCREPANCIES; DETERMINANTS; ADOLESCENTS; OSTEOPENIA AB Objective Dual-energy x-ray absorptiometry (DEXA) is increasingly used to evaluate children for osteoporosis. However, the interpretation of pediatric DEXA is complicated by growth and development. Because most DEXA scans are performed on adults, we hypothesized that physicians who interpret DEXA may not be aware of these pediatric issues, potentially leading to misdiagnosis. Study design Children (n = 34, aged 4-17 years) diagnosed with low bone mineral density (BMD) based on a DEXA scan were referred for possible inclusion in a childhood osteoporosis protocol. The referral DEXA scans were analyzed for accuracy. Results Thirty (88%) of the scans had at least one error in interpretation. The most frequent error (62%) was use of T-score (SD score compared with young adults) to diagnose osteoporosis, which is inappropriate for children. Other errors included use of a reference database that does not consider gender or ethnic differences (21%), incorrect bone map (21%), inattention to short stature (15%), and other measurement or statistical error (12%). After correcting for these errors, 53% had normal BMD, whereas only 26% retained the diagnosis of low BMD. The remaining 21% could not be given a definitive diagnosis. Conclusion In children, the diagnosis of osteoporosis is often due to misinterpretation of a DEXA scan. C1 NICHHD, Unit Growth & Dev, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gafni, RI (reprint author), NICHHD, Unit Growth & Dev, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM gafnir@mail.nih.gov NR 27 TC 114 Z9 120 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 2004 VL 144 IS 2 BP 253 EP 257 DI 10.1016/j.jpeds.2003.08.054 PG 5 WC Pediatrics SC Pediatrics GA 773LT UT WOS:000188925800025 PM 14760271 ER PT J AU Song, J Knepper, MA Hu, XQ Verbalis, JG Ecelbarger, CA AF Song, J Knepper, MA Hu, XQ Verbalis, JG Ecelbarger, CA TI Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NITRIC-OXIDE; PULMONARY-EDEMA; RECEPTOR-GAMMA; FATTY RATS; THIAZOLIDINEDIONES; KIDNEY; ALDOSTERONE; HYPERTENSION; TROGLITAZONE; PROTEIN AB Synthetic agonists of the peroxisomal proliferator-activated receptor subtype gamma(PPAR-gamma) are highly beneficial in the treatment of type II diabetes. However, they are also associated with fluid retention and edema, potentially serious side effects of unknown origin. These studies were designed to test the hypothesis that rosiglitazone (RGZ, PPAR-gamma agonist) may activate sodium- and water-reabsorptive processes in the kidney, possibly in response to a drop in mean arterial blood pressure (MAP), as well as directly through PPAR-gamma. Targeted proteomics of the major renal sodium and water transporters and channel proteins was used to identify potentially regulated sites of renal sodium and water reabsorption. RGZ (47 or 94 mg/kg diet) was fed to male, Sprague-Dawley rats (similar to270 g) for 3 days. MAP, measured by radiotelemetry, was decreased significantly in rats fed either level of RGZ, relative to control rats. Delta MAP from baseline was -3.2+/-1.2 mm Hg in rats fed high-dose RGZ versus +3.4+/-0.8 for rats fed control diet. RGZ did not affect feed or water intake, but rats treated with high-dose RGZ had decreased urine volume (by 22%), sodium excretion (44%), kidney weight (9%), and creatinine clearance (35%). RGZ increased whole kidney protein abundance of the alpha-1 subunit of Na-K-ATPase, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the sodium hydrogen exchanger (NHE3), the aquaporins 2 and 3, and endothelial nitric-oxide synthase. We conclude that both increases in renal tubule transporter abundance and a decrease in glomerular filtration rate likely contribute to the RGZ-induced sodium retention. C1 Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20057 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Ecelbarger, CA (reprint author), Georgetown Univ, Dept Med, Div Endocrinol & Metab, Box 571412, Washington, DC 20057 USA. EM ecelbarc@georgetown.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [R01 HL074142]; NIDDK NIH HHS [K01 DK02672, R01 DK38094] NR 38 TC 96 Z9 99 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 FEB 1 PY 2004 VL 308 IS 2 BP 426 EP 433 DI 10.1124/jpet.103.058008 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767TB UT WOS:000188467800004 PM 14593089 ER PT J AU Li, Q Ma, L Innis, RB Seneca, N Ichise, M Huang, H Laruelle, M Murphy, DL AF Li, Q Ma, L Innis, RB Seneca, N Ichise, M Huang, H Laruelle, M Murphy, DL TI Pharmacological and genetic characterization of two selective serotonin transporter ligands: 2-[2-(dimethylaminomethylphenylthio)]-5-fluoromethylphenylamine (AFM) and 3-amino-4-[2-(dimethylaminomethylphenylthio)]benzonitrile (DASB) SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; BINDING-SITES; HIGH-AFFINITY; RAT-BRAIN; IN-VITRO; ANTIDEPRESSANT DRUG; RECOGNITION SITES; D-FENFLURAMINE; RELEASE; VIVO AB The expression and function of the serotonin transporter (SERT) is important in the regulation of mood and emotion. Determination of SERT alterations in physiological and pathological states is essential for understanding the role of SERT in mood regulation, and in the etiology and therapy of psychiatric disorders. Two SERT ligands, AFM ([H-3]2-[2-(dimethylaminomethylphenylthio)]-5-fluoromethylphenylamine) and DASB ([H-3] 3-amino-4-[2-(dimethylaminomethylphenylthio)] benzonitrile), have recently been developed for positron emission tomography (PET) imaging. The aim of the present study was to determine the selectivity of these compounds for SERT. Autoradiography of AFM or DASB binding was compared in the brains of mice with genetically normal, diminished, or absent SERT. In addition, the pharmacodynamic profile of [H-3] AFM was examined in the mouse brain. The distribution of [H-3] AFM and [H-3] DASB binding in the normal brains was consistent with that of previously studied serotonin reuptake inhibitors. Both ligands had negligible binding in the brain of SERT knockout mice, and binding was reduced approximately 50% in heterozygote SERT mice. The K-d of [H-3] AFM binding in the cortex and midbrain was 1.6 and 1.0 nM, respectively. Competition studies showed that [H-3] AFM has very low affinity for norepinephrine and dopamine transporters as well as 5-HT receptors, including 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptors. In addition, fenfluramine showed a low capability to compete with [H-3] AFM. The present results suggest that both AFM and DASB are highly selective SERT ligands potentially suitable for use in human PET studies of SERT. C1 Univ Texas, Med Branch, Dept Psychiat & Behav Sci, Galveston, TX 77555 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Psychiat, New York, NY USA. RP Li, Q (reprint author), Univ Texas, Med Branch, Dept Psychiat & Behav Sci, 5-220 Mary Moody No Paval,301 Univ Blvd, Galveston, TX 77555 USA. EM qili@utmb.edu NR 36 TC 11 Z9 12 U1 2 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 FEB 1 PY 2004 VL 308 IS 2 BP 481 EP 486 DI 10.1124/jpet.103.058636 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767TB UT WOS:000188467800012 PM 14610240 ER PT J AU Chen, YP Ferguson, SS Negishi, M Goldstein, JA AF Chen, YP Ferguson, SS Negishi, M Goldstein, JA TI Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; ORPHAN NUCLEAR RECEPTOR; ST JOHNS WORT; DISTAL ENHANCER MODULE; HUMAN HEPATOCYTES; DRUG-METABOLISM; TRANSCRIPTIONAL REGULATION; CYTOCHROME P4502C9; CYP3A4 EXPRESSION; GENES AB Human CYP2C9 is important in the metabolism of numerous clinically used drugs such as the anticoagulant warfarin, the anticonvulsant phenytoin, antidiabetic drugs such as tolbutamide and glipizide, the hypertensive agent losartan, and numerous nonsteroidal anti-inflammatory drugs. Several studies have reported that certain drugs such as rifampicin and phenobarbital induce CYP2C9, but the molecular basis for this induction remains unknown. In the present study, we demonstrate that the human pregnane X receptor (hPXR) mediates induction of CYP2C9 by the prototype drugs rifampicin, hyperforin (found in St. John's Wart), and phenobarbital. Deletion and mutagenesis studies with luciferase reporter constructs showed that a functional PXR-responsive element located -1839/-1824 base pairs upstream from the translation start site was the primary binding site mediating the rifampicin induction of CYP2C9. This site was previously described as a constitutive androstane receptor-responsive element (CAR-RE). Mutational analysis of 3- and 12-kilobase CYP2C9 promoter fragments indicated that this proximal binding site was essential for rifampicin inducibility, although a cooperative effect could be attributed to a second CAR-RE located at -2899/-2883. In summary, we have demonstrated rifampicin induction of CYP2C9 promoter constructs that is consistent with the magnitude of induction of CYP2C9 protein and mRNA reported in vivo and in primary human hepatocytes, and we have identified the cis-element essential for this response. This is the first report to demonstrate that the nuclear receptor PXR mediates induction of CYP2C9 with rifampicin, phenobarbital, and hyperforin. C1 NIEHS, Lab Pharmacol & Chem, Human Metab Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, Human Metab Sect, Pharmacogenet Sect, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, Human Metab Sect, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012 NR 36 TC 131 Z9 139 U1 0 U2 12 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB 1 PY 2004 VL 308 IS 2 BP 495 EP 501 DI 10.1124/jpet.103.058818 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767TB UT WOS:000188467800014 PM 14600250 ER PT J AU Rhodes, MC Seidler, FJ Abdel-Rahman, A Tate, CA Nyska, A Rincavage, HL Slotkin, TA AF Rhodes, MC Seidler, FJ Abdel-Rahman, A Tate, CA Nyska, A Rincavage, HL Slotkin, TA TI Terbutaline is a developmental neurotoxicant: Effects on neuroproteins and morphology in cerebellum, hippocampus, and somatosensory cortex SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BETA-ADRENERGIC STIMULATION; RAT-BRAIN; CELLS; APOPTOSIS; RECEPTORS; EXPOSURE; PROTEINS; DRUGS; ISOPROTERENOL; EXPRESSION AB beta(2)-Adrenoceptor agonists, especially terbutaline, are widely used to arrest preterm labor, but they also cross the placenta to stimulate fetal beta-adrenoceptors that control neural cell differentiation. We evaluated the effects of terbutaline administration in neonatal rats, a stage of neurodevelopment corresponding to human fetal development. Terbutaline administered on postnatal days PN2 to 5 elicited neurochemical changes indicative of neuronal injury and reactive gliosis: immediate increases in glial fibrillary acidic protein and subsequent induction of the 68-kDa neurofilament protein. Quantitative morphological evaluations carried out on PN30 indicated structural abnormalities in the cerebellum, hippocampus, and somatosensory cortex. In the cerebellum, PN2 to 5 terbutaline treatment reduced the number of Purkinje cells and elicited thinning of the granular and molecular layers. The hippocampal CA3 region also displayed thinning, along with marked gliosis, effects that were restricted to females. In the somatosensory cortex, terbutaline evoked a reduction in the proportion of pyramidal cells and an increase in smaller, nonpyramidal cells; again, females were affected more than males. Although abnormalities were obtained with later terbutaline treatment (PN11 to 14), in general the effects were smaller than those seen with PN2 to 5 exposure. Our results indicate that terbutaline is a neurotoxicant that elicits biochemical alterations and structural damage in the immature brain during a critical period. These effects point to a causal relationship between fetal terbutaline exposure and the higher incidence of cognitive and neuropsychiatric disorders reported for the offspring of women receiving terbutaline therapy for preterm labor. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813 DUMC, Durham, NC 27710 USA. EM t.slotkin@duke.edu FU NICHD NIH HHS [HD09713]; NIEHS NIH HHS [ES07031] NR 44 TC 41 Z9 41 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB 1 PY 2004 VL 308 IS 2 BP 529 EP 537 DI 10.1124/jpet.103.060095 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767TB UT WOS:000188467800018 PM 14610225 ER PT J AU Thompson, CM Wojno, H Greiner, E May, EL Rice, KC Selley, DE AF Thompson, CM Wojno, H Greiner, E May, EL Rice, KC Selley, DE TI Activation of G-proteins by morphine and codeine congeners: Insights to the relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INDUCED ANALGESIA; RAT THALAMUS; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); BINDING; OXYCODONE; DIHYDROCODEINE; AGONIST; MICE; HYDROCODONE; MODULATION AB Phenotypic differences in analgesic sensitivity to codeine (3-methoxymorphine) results from polymorphisms in cytochrome P450-2D6, which catalyzes O-demethylation of codeine to morphine. However, O-demethylation reportedly is not required for analgesic activity of the 7,8-saturated codeine congeners dihydrocodeine, hydrocodone, and oxycodone. This study determined the potency and efficacy of these compounds and their demethylated derivatives to stimulate mu- and delta-opioid receptor-mediated G-protein activation using agonist-stimulated guanosine 5'-O-(3-[S-35]thio) triphosphate ([S-35] GTPgammaS) binding. Results showed that 7,8-saturated codeine congeners were more efficacious than codeine in activating mu-receptors, but only dihydrocodeine was more efficacious at delta-receptors. Hydrocodone and oxycodone were similar to10-fold more potent than codeine and dihydrocodeine at either receptor. Morphine-like compounds with a 3-hydroxy group were similar to30- to 100-fold more potent than their 3-methoxy analogs at the mu-receptor, and these compounds generally exhibited greater efficacy ( e. g., morphine produced 2-fold greater maximal stimulation than codeine). Removal of the N-methyl group did not affect efficacy or potency of codeine congeners to activate mu-receptors, whereas this modification generally increased efficacy but decreased potency of morphine congeners. At the delta receptor, morphine congeners showed greater potency and structure-dependent differences in efficacy compared with codeine congeners, whereas removal of the N-methyl group had effects similar to those observed at the mu-receptor. These results demonstrate that 7,8-saturated codeine congeners are more efficacious than codeine, which may explain their lack of requirement for 3-O-demethylation in vivo. Nonetheless, because all 7,8-saturated codeine congeners were significantly less potent than their morphine derivatives, further research is needed to understand the relationship between metabolism and in vivo activity of these compounds. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Inst Drug & Alcohol Studies, Richmond, VA 23298 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Box 980524,1112 E Clay St, Richmond, VA 23298 USA. EM deselley@hsc.vcu.edu FU NIDA NIH HHS [DA-01647, DA-05274, DA-07027, DA-10770] NR 41 TC 43 Z9 44 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB 1 PY 2004 VL 308 IS 2 BP 547 EP 554 DI 10.1124/jpet.103.058602 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 767TB UT WOS:000188467800020 PM 14600248 ER PT J AU Boheler, KR AF Boheler, KR TI Functional markers and the 'homogeneity' of human mesenchymal stem cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID IN-VITRO C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21113 USA. RP Boheler, KR (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21113 USA. EM bohelerk@grc.nia.nih.gov NR 7 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 1 PY 2004 VL 554 IS 3 BP 592 EP 592 DI 10.1113/jphysiol.2003.0572224 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 772FC UT WOS:000188829800002 PM 14634205 ER PT J AU McCrae, RR AF McCrae, RR TI Human nature and culture: A trait perspective SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the Association-for-Research-in-Personality CY FEB, 2003 CL LOS ANGELES, CALIFORNIA SP Assoc Res Personal ID PERSONALITY-TRAITS AB The relation of the individual to society has always been a central concern of personality psychologists. Building on recent empirical and conceptual advances in trait psychology, I propose a new approach to personality and culture. The fact that trait structure, age and gender differences, and cross-observer agreement are all universal supports the view that traits are biologically based characteristics of the human species. After discussing ethical and scientific issues, I provide preliminary data consistent with the view that aggregate levels of traits may lead to features of cultures, such as Individualism/Collectivism. I discuss alternative interpretations and future directions for research and conclude that the trait perspective holds exceptional promise for understanding human nature and culture. Published by Elsevier Inc. C1 NIA, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Dept Hlth & Human Serv, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jeffm@lpc.grc.nia.nih.gov NR 38 TC 44 Z9 46 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 J9 J RES PERS JI J. Res. Pers. PD FEB PY 2004 VL 38 IS 1 BP 3 EP 14 DI 10.1016/j.jrp.2003.09.009 PG 12 WC Psychology, Social SC Psychology GA 769BV UT WOS:000188607300002 ER PT J AU Zametkin, AJ Zoon, CK Klein, HW Munson, S AF Zametkin, AJ Zoon, CK Klein, HW Munson, S TI Psychiatric aspects of child and adolescent obesity: A review of the past 10 years SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE obesity; child; ethics; treatment; psychiatry ID BODY-MASS INDEX; 3-FACTOR EATING QUESTIONNAIRE; FAMILY-BASED TREATMENT; WEIGHT-GAIN; SELF-ESTEEM; PEDIATRIC OBESITY; OVERWEIGHT CHILDREN; YOUNG ADULTHOOD; FOLLOW-UP; PSYCHOLOGICAL-PROBLEMS AB Objective: To review the past 10 years of published research on psychiatric aspects of child and adolescent obesity and highlight information mental health professionals need for preventing obesity in youths and diagnosing and treating it. Method: Researchers performed computerized and manual searches of the literature and summarized the most relevant articles. Results: The growing epidemic of child and adolescent obesity deserves attention for its immediate mental health and long-term medical complications. Mental health professionals working with obese youths should be aware of recent advances in neuroscience, genetics, and etiologies associated with obesity. Those who assess and treat obese youth should view obesity as a chronic disease. Currently, no approved pharmacological or surgical approaches exist to treat childhood obesity. Conclusions: Health care providers should focus on modest weight-loss goals that correlate with significant health benefits. The most effective treatments include substantial parental involvement. Mental health professionals should help obese children build self-esteem to help them lead full lives regardless of weight. C1 NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. RP Zametkin, AJ (reprint author), NIH, Bldg 10,Room 3N210, Bethesda, MD 20892 USA. EM zametkin@mail.nih.gov NR 138 TC 139 Z9 144 U1 4 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 2004 VL 43 IS 2 BP 134 EP 150 DI 10.1097/01.chi.0000100427.25002.06 PG 17 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 765NH UT WOS:000188289500008 PM 14726719 ER PT J AU Weening, JJ D'Agati, VD Schwartz, MM Seshan, SV Alpers, CE Appel, GB Balow, JE Bruijn, JA Cook, T Ferrario, F Fogo, AB Ginzler, EM Hebert, L Hill, G Hill, P Jennette, JC Kong, NC Lesavre, P Lockshin, M Looi, LM Makino, H Moura, LA Nagata, M AF Weening, JJ D'Agati, VD Schwartz, MM Seshan, SV Alpers, CE Appel, GB Balow, JE Bruijn, JA Cook, T Ferrario, F Fogo, AB Ginzler, EM Hebert, L Hill, G Hill, P Jennette, JC Kong, NC Lesavre, P Lockshin, M Looi, LM Makino, H Moura, LA Nagata, M CA Int Soc Nephrology Renal Pathology TI The classification of glomerulonephritis in systemic lupus erythematosus revisited SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CLINICAL COURSE; NEPHRITIS; MANAGEMENT; FORMS AB The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; H, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving &GE;50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class W and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification. C1 Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1006 AZ Amsterdam, Netherlands. Columbia Univ, Coll Phys & Surg, New York, NY USA. Rush Med Coll, Chicago, IL 60612 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. Imperial Coll Sch Med, London, England. San Carlo Borromeo Hosp, Milan, Italy. Vanderbilt Univ, Nashville, TN USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Ohio State Univ, Columbus, OH 43210 USA. Georges Pompidou European Hosp, Paris, France. St Vincents Hosp, Fitzroy, Vic 3065, Australia. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Kebangsaan Malaysia, Kuala Lumpur, Malaysia. Hop Necker Enfants Malad, Paris, France. Univ Malaya, Sch Med, Kuala Lumpur, Malaysia. Okayama Univ, Grad Sch Med & Dent, Okayama, Japan. Univ Fed Sao Paulo, Sao Paulo, Brazil. Univ Tsukuba, Tsukuba, Ibaraki 305, Japan. RP Weening, JJ (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Pathol, POB 22660, NL-1006 AZ Amsterdam, Netherlands. EM j.j.weening@amc.uva.nl RI Looi, Lai Meng/A-3382-2009; OI Looi, Lai Meng/0000-0001-8325-0117; Kong, Norella Chiew-Tong/0000-0001-5165-5216 NR 23 TC 682 Z9 758 U1 4 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2004 VL 15 IS 2 BP 241 EP 250 DI 10.1097/01.ASN.0000108969.21691.5D PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 769AQ UT WOS:000188604600001 PM 14747370 ER PT J AU Eis, V Luckow, B Vielhauer, V Siveke, JT Linde, Y Segerer, S de Lema, GP Cohen, CD Kretzler, M Mack, M Horuk, R Murphy, PM Gao, JL Hudkins, KL Alpers, CE Grone, HJ Schlondorff, D Anders, HJ AF Eis, V Luckow, B Vielhauer, V Siveke, JT Linde, Y Segerer, S de Lema, GP Cohen, CD Kretzler, M Mack, M Horuk, R Murphy, PM Gao, JL Hudkins, KL Alpers, CE Grone, HJ Schlondorff, D Anders, HJ TI Chemokine receptor CCR1 but not CCR5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; INTERSTITIAL FIBROSIS; TRANSPLANT REJECTION; HOST-DEFENSE; MICE LACKING; EXPRESSION; ANTAGONIST; GLOMERULONEPHRITIS; INFILTRATION; NEPHROPATHY AB As chemokine receptor CCR1 and CCR5 expression on circulating leukocytes is thought to contribute to leukocyte recruitment during renal fibrosis, the authors examined the effects of unilateral ureteral obstruction (UUO) in mice deficient for CCR1 or CCR5. Analysis of UUO kidneys from CCR1-deficient mice revealed a reduction of interstitial macrophages and lymphocytes (35% and 55%, respectively) compared with wild-type controls. CCR1-deficient mice had reduced CCR5 mRNA levels in UUO kidneys, which correlated with a reduction of CCR5+ T cell infiltrate as determined by flow cytometry. Interstitial fibroblasts, renal TGF-beta1 mRNA expression, interstitial volume, and collagen I deposits were all significantly reduced in CCR1-deficient mice. In contrast, renal leukocytes and fibrosis were unaffected in CCR5-deficient mice with UUO. However, if treated with the CCR1 antagonist BX471, CCR5-deficient mice showed a similar reduction of renal leukocytes and fibrosis as CCR1-deficient mice. To determine the underlying mechanism labeled macrophages and T cells isolated from either wild-type, CCR1-deficient, or CCR5-deficient mice were injected into wild-type mice with UUO. Three hours later, renal cell recruitment was reduced for CCR1-deficient cells or cells pretreated with BX471 compared with CCR5-deficient or wild-type cells. Thus, CCR1 but not CCR5 is required for leukocyte recruitment and fibrosis after UUO in mice. Therefore, CCR1 is a promising target for therapeutic intervention in leukocyte-mediated fibrotic tissue injury, e.g. progressive renal fibrosis. C1 Univ Munich, Med Policlin, Nephrol Ctr, Munich, Germany. Berlex Biosci, Dept Immunol, Richmond, CA USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. German Canc Res Ctr, Dept Cellular & Mol Pathol, D-6900 Heidelberg, Germany. RP Anders, HJ (reprint author), Med Poliklin LMU, Pettenkoferstr 8A, D-80336 Munich, Germany. EM hjanders@med.uni-muenchen.de NR 32 TC 85 Z9 86 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 2004 VL 15 IS 2 BP 337 EP 347 DI 10.1097/01.ASN.0000111246.87175.32 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 769AQ UT WOS:000188604600011 PM 14747380 ER PT J AU Wang, HY Parry, S Macones, G Sammel, M Kuivaniemi, H Tromp, G Romero, R Strauss, JF AF Wang, HY Parry, S Macones, G Sammel, M Kuivaniemi, H Tromp, G Romero, R Strauss, JF TI Identification of functionally significant polymorphisms in the MMP-8 promoter, allele frequencies, and relationship to proterm premature rupture of the fetal membranes (PPROM). SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NICHD, Hutzel Hosp, Perinatol Res Branch, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 3 BP 70A EP 70A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500004 ER PT J AU Kim, GJ Kim, M Kim, YM Chaiworapongsa, T Bujould, E Espinoza, J Gomez, R Romero, R AF Kim, GJ Kim, M Kim, YM Chaiworapongsa, T Bujould, E Espinoza, J Gomez, R Romero, R TI Vascular endothelial growth factor receptor-1 is highly expressed in interstital trophoblast, but reduced in endovascular trophoblast. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, DHHS, NIH, Perinatol Res Branch, Detroit, MI USA. Wayne State Univ, Detroit, MI 48202 USA. Sotero del Rio Hosp, Santiago, Chile. NR 1 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 83 BP 97A EP 97A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500083 ER PT J AU Parker, J Sinaii, N Segars, J Godoy, H Winkel, C Stratton, P AF Parker, J Sinaii, N Segars, J Godoy, H Winkel, C Stratton, P TI Radical laparoscopic excision of endometriosis: What is the risk of formation of adhesions? SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, Pediat & Reprod Endocrine Branch, Bethesda, MD USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 211 BP 142A EP 142A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500210 ER PT J AU Potlog-Nahari, C Stratton, P Koziol, DE Reynolds, JC Hearns-Stokes, RM Nieman, LK AF Potlog-Nahari, C Stratton, P Koziol, DE Reynolds, JC Hearns-Stokes, RM Nieman, LK TI Does endometriosis influence bone mineral density? SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHHD, Pediat Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nucl Med, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 215 BP 144A EP 144A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500214 ER PT J AU Klebanoff, M Andrews, W AF Klebanoff, M Andrews, W CA Longitudinal Vaginal Flora Study G TI The longitudinal study of vaginal flora: A randomized trial of douching and bacterial vaginosis. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, NIH, DESPR, Bethesda, MD USA. Univ Alabama, Birmingham, AL USA. 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 260 BP 159A EP 159A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500259 ER PT J AU Stratton, P Tamari, M Turner, M AF Stratton, P Tamari, M Turner, M TI Vulvar and vaginal graft versus host disease in women after hematopoietic stem cell transplantation. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 268 BP 162A EP 162A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500267 ER PT J AU Hartmann, KE Herring, AH Savitz, DA Baird, DD AF Hartmann, KE Herring, AH Savitz, DA Baird, DD TI Uterine fibroids and spontaneous abortion: A prospective study. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 351 BP 191A EP 191A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500349 ER PT J AU McDaniel, K Mayers, C Venere, M Driggers, P Westphal, H Gorivodsky, M Segars, J AF McDaniel, K Mayers, C Venere, M Driggers, P Westphal, H Gorivodsky, M Segars, J TI Brx, a cytoplasmic protein capable of augmenting estrogen action, is essential for murine development. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NIH, Lab Mammalian Genes & Dev, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 375 BP 199A EP 199A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500373 ER PT J AU Hendler, I AF Hendler, I TI The preterm prediction study: Impact of maternal obesity on spontaneous preterm birth. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, Maternal Fetal Med Units Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 383 BP 202A EP 202A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500381 ER PT J AU Nuthalapaty, FS AF Nuthalapaty, FS TI The preterm prediction study: Quantitative fetal fibronectin levels and the risk for peripartum infectious morbidity. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, MFMU Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 387 BP 203A EP 203A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500385 ER PT J AU Ramsey, PS Parker, CR AF Ramsey, PS Parker, CR TI Are midtrimester maternal serum levels of endocrine markers associated with the subsequent development of spontaneous preterm birth (SPB)? SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, Maternal Fetal Units Network, NIH, Bethesda, MD USA. Univ Alabama, Birmingham, AL 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 390 BP 204A EP 204A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500388 ER PT J AU Bukowski, R Hankins, GD Malone, FD Porter, TF Nyberg, DA Comstock, CH Saade, GR Eddleman, K Gross, S Dugoff, L Hobbins, JC Craigo, SD Timor, IE Carr, SR Wolfe, HM Tibbetts, N Hanson, JW D'Alton, ME AF Bukowski, R Hankins, GD Malone, FD Porter, TF Nyberg, DA Comstock, CH Saade, GR Eddleman, K Gross, S Dugoff, L Hobbins, JC Craigo, SD Timor, IE Carr, SR Wolfe, HM Tibbetts, N Hanson, JW D'Alton, ME TI Early pregnancy origins of spontaneous preterm delivery. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Texas, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77550 USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY 10027 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. Swedish Med Ctr, Dept Obstet & Gynecol, Seattle, WA USA. William Beaumont Army Med Ctr, Dept Obstet & Gynecol, Royal Oak, MI USA. Mt Sinai Med Ctr, Dept Obstet & Gynecol, New York, NY 10029 USA. Montefiore Med Ctr, Dept Obstet & Gynecol, Bronx, NY 10467 USA. Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA. Tufts Univ, Dept Obstet & Gynecol, Boston, MA 02111 USA. NYU Med Ctr, Dept Obstet & Gynecol, New York, NY 10016 USA. Brown Univ, Women & Infants Hosp, Dept Obstet & Gynecol, Providence, RI USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. DM Stat, Medford, MA USA. NICHHD, Bethesda, MD 20892 USA. RI Malone, Fergal/D-6233-2012 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 397 BP 206A EP 207A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500395 ER PT J AU Yost, NP AF Yost, NP TI The influence of coitus in women at risk for recurrent preterm delivery. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, MFMU Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 396 BP 206A EP 206A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500394 ER PT J AU Armant, DR Kilburn, BA Duniec-Dmuchkowski, ZM Romero, R Leach, RE AF Armant, DR Kilburn, BA Duniec-Dmuchkowski, ZM Romero, R Leach, RE TI EGF receptor transactivation in hypoxic human cytotrophoblasts is regulated by metalloproteinase-induced cleavage of transmembrane heparin-binding EGF-like growth factor to its secreted form. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Wayne State Univ, Sch Med, Dept Obstet, CS Mott Ctr Human Growth & Dev, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Dept Gynecol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48202 USA. NICHHD, Perinatol Res 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 423 BP 214A EP 215A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500421 ER PT J AU Pridjian, G Durst, J Vu, H Ianosi-Irimie, M Pridjian, C Bagrov, A Fedorova, O Puschett, JB AF Pridjian, G Durst, J Vu, H Ianosi-Irimie, M Pridjian, C Bagrov, A Fedorova, O Puschett, JB TI Neutralization of marinobufagenin normalizes blood pressure in a rat model of preeclampsia. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NIA, NIH, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 556 BP 260A EP 261A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500553 ER PT J AU Parker, CR Ramsey, P AF Parker, CR Ramsey, P TI Racial differences in midtrimester maternal markers of the feto-placental unit. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Alabama, Birmingham, AL USA. 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 588 BP 271A EP 271A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500585 ER PT J AU Kishida, T Kostetskii, I Radice, GL Dwyer, NK Blanchette-Mackie, EJ Strauss, JF AF Kishida, T Kostetskii, I Radice, GL Dwyer, NK Blanchette-Mackie, EJ Strauss, JF TI The role of the MLN64 start domain in sterol metabolism: Normal steroidogenesis but altered intracellular neutral lipid storage in MLN64-deificient mice. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. NIDDK, Lipid Cell Biol Sect, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 605 BP 277A EP 277A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500602 ER PT J AU Abrahams, VM Kim, YM Straszewski-Chavez, SL Romero, R Mor, G AF Abrahams, VM Kim, YM Straszewski-Chavez, SL Romero, R Mor, G TI Efficient clearance of apoptotic cells by macrophages at the maternal-fetal interface is critical for successful pregnancy. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA. NICHHD, Perinatol Res Branch, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 616 BP 281A EP 281A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500613 ER PT J AU Liu, ZT Kilburn, BA Leach, RE Romero, R Paria, BC Armant, DR AF Liu, ZT Kilburn, BA Leach, RE Romero, R Paria, BC Armant, DR TI Histamine enhances cytotrophoblast invasion by inducing intracellular calcium transients through the histamine type-1 receptor. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHHD, Intramural Div, Perinatol Res Branch, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Div Reprod & Dev Biol, Dept Pediat, Nashville, TN 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 640 BP 290A EP 290A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500637 ER PT J AU Poggi, SH Park, JJ Wood, L Abebe, DT Spong, CY AF Poggi, SH Park, JJ Wood, L Abebe, DT Spong, CY TI Mediation of alcohol-induced learning impairment in fetal alcohol syndrome adult offspring. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. NICHHD, Dev Neurobiol Lab, Sect Dev & Mol Pharmacol, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 655 BP 295A EP 295A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500652 ER PT J AU Varner, M AF Varner, M TI The association of inflammatory cytokine and Toll-like receptor gene polymorphisms with spontaneous preterm birth. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Alabama, Birmingham, AL USA. NICHD, Maternal Fetal Med Units Network, Bethesda, MD 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 699 BP 310A EP 310A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500696 ER PT J AU Abrahams, VM Straszewski-Chavez, SL Bole-Aldo, P Romero, R Mor, G AF Abrahams, VM Straszewski-Chavez, SL Bole-Aldo, P Romero, R Mor, G TI Trophoblast apoptosis is induced through Toll-like receptor 2, but not Toll-like receptor 4: A novel mechanism for first trimester pregnancy failure. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06510 USA. NICHHD, Perinatol Res Branch, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 722 BP 318A EP 319A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500719 ER PT J AU Goepfert, AR AF Goepfert, AR TI Differences in inflammatory cytokine genes and bacterial vaginosis (BV) in pregnancy. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Alabama, Birmingham, AL USA. NICHHD, Maternal Fetal Med Units Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 723 BP 319A EP 319A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500720 ER PT J AU Mitchell, MD Sato, TA Chang, MC Romero, RJ Chaiworapongsa, T Helliwell, RJA AF Mitchell, MD Sato, TA Chang, MC Romero, RJ Chaiworapongsa, T Helliwell, RJA TI Identification of 9 alpha,11 beta-prostaglandin F-2 in human amniotic fluid and characterization of its production by human gestational tissues. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Auckland, Liggins Inst, Auckland 1, New Zealand. NICHD, Perinatal Res Branch, Detroit, MI USA. RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 759 BP 330A EP 331A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500756 ER PT J AU Harper, MA AF Harper, MA TI The risk of repeat preterm delivery following preterm delivery of a singleton versus a multifetal gestation. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, MFMU Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 788 BP 340A EP 340A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500785 ER PT J AU Hartmann, KE Herring, AH Savitz, DA Baird, DD AF Hartmann, KE Herring, AH Savitz, DA Baird, DD TI Predictors of the presence of uterine fibroids in the first trimester of pregnanacy: A prospective cohort study. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 789 BP 340A EP 341A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500786 ER PT J AU Hartmann, KE Herring, AH Savitz, DA Baird, DD AF Hartmann, KE Herring, AH Savitz, DA Baird, DD TI Defining the proportion of pregnant women with uterine fibroids in a non-clinical prospective cohort. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 790 BP 341A EP 341A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500787 ER PT J AU Varner, M AF Varner, M TI The MFMU cesarean registry: VBAC with a twin gestation. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD Maternal Fetal Med Units Network, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 800 BP 344A EP 344A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500797 ER PT J AU Bianco, K Romero, R Zhou, Y Maymon, E Fisher, S AF Bianco, K Romero, R Zhou, Y Maymon, E Fisher, S TI Cytotrophoblast expression of L-selectin as a barometer of inflammation in preterm delivery with and without preeclampsia. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Yale Univ, New Haven, CT 06520 USA. NICHHD, Perinatol Res Branch, Detroit, MI USA. Univ Calif San Francisco, San Francisco, CA 94143 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 806 BP 346A EP 346A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500803 ER PT J AU McGovern, PG Myers, ER Silva, S Coutifaris, C Carson, SA Legro, RS Schlaff, WD Carr, BR Steinkampf, MP Giudice, LC Leppert, PC Diamond, MP AF McGovern, PG Myers, ER Silva, S Coutifaris, C Carson, SA Legro, RS Schlaff, WD Carr, BR Steinkampf, MP Giudice, LC Leppert, PC Diamond, MP TI Absence of secretory endometrium after false positive home urine luteinizing hormone testing. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. Penn State Univ, Hershey, PA USA. Univ Colorado, Denver, CO 80202 USA. Univ Alabama, Birmingham, AL USA. Stanford Univ, Palo Alto, CA 94304 USA. NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI 48202 USA. Univ Texas, SW Med Ctr, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 895 BP 378A EP 378A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500892 ER PT J AU Stratton, P Leondires, M Sinaii, N Premkumar, A Nieman, L AF Stratton, P Leondires, M Sinaii, N Premkumar, A Nieman, L TI Pelvic pain: Persistence of dysmenorrhea and non-menstrual pain after optimal endometriosis surgery may indicate adenomyosis. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Ctr Adv Reprod Med, Norwalk, CT USA. NICHHD, Pediat & Reprod Endocrinol 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 898 BP 379A EP 379A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500895 ER PT J AU Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R AF Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R TI Gender differences in vascular responses to an antigen challenge and histamine in guinea pigs. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHD, Perinatol Res Branch, NIH, Detroit, MI 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 902 BP 380A EP 380A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500899 ER PT J AU Parker, JD Wu, TJ Segars, JH Catherino, WH AF Parker, JD Wu, TJ Segars, JH Catherino, WH TI GnRH expression in uterine leiomyomata. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 956 BP 397A EP 397A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500952 ER PT J AU Baird, DD Newbold, R AF Baird, DD Newbold, R TI Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NIEHS, NIH, Mol Toxicol Lab, Res Triangle Pk, NC 27709 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 957 BP 398A EP 398A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500953 ER PT J AU Catherino, WH Morris, S Armstrong, AY Leppert, PC Segars, JH AF Catherino, WH Morris, S Armstrong, AY Leppert, PC Segars, JH TI Molecular dissection of hereditary leiomyomatosis. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 963 BP 400A EP 400A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500959 ER PT J AU Hanauske-Abel, HM Cracchiolo, BM Park, MH Wolff, EC Clement, PMJ Heller, DS AF Hanauske-Abel, HM Cracchiolo, BM Park, MH Wolff, EC Clement, PMJ Heller, DS TI The mature, hypusine-containing form of eukaryotic translation initiation factor 5A (EIF5A) in normal ovaries and in ovarian cancer: Anatomical evidence for a potential biomarker. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. NR 1 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 975 BP 404A EP 404A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500971 ER PT J AU Shankar, S Clair, T Stracke, M Auersperg, N Fishman, DA AF Shankar, S Clair, T Stracke, M Auersperg, N Fishman, DA TI Role of autotaxin (ATX) in epithelial ovarian cancer (EOC). SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Investigat C1 Northwestern Univ, Chicago, IL 60611 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC V5Z 1M9, Canada. 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2004 VL 11 IS 2 SU S MA 993 BP 409A EP 409A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 802SZ UT WOS:000220184500989 ER PT J AU Nguyen, DM Chen, GA Reddy, R Tsai, W Schrump, WD Cole, G Schrump, DS AF Nguyen, DM Chen, GA Reddy, R Tsai, W Schrump, WD Cole, G Schrump, DS TI Potentiation of paclitaxel cytotoxicity in lung and esophageal cancer cells by pharmacologic inhibition of the phosphoinositide 3-kinase/protein kinase B (Akt)-mediated signaling pathway SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-07, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID NF-KAPPA-B; CELLULAR-SURVIVAL; INDUCED APOPTOSIS; BREAST-CANCER; IN-VIVO; PHOSPHORYLATION; AKT; ACTIVATION; SUBUNIT; ALPHA AB Background: Constitutive activation of the phosphoinositide 3-kinase/protein kinase B survival signal transduction pathway influences the intrinsic chemoresistance of cancer cells. This study evaluates the effect of LY294002, a pharmacologic inhibitor of phosphoinositide 3-kinase, on the sensitivity of lung and esophageal cancer cells to paclitaxel (Taxol) in vitro. Materials and Methods: Cell viability and apoptosis of cancer cells treated with paclitaxel + LY294002 combinations were quantitated by methyl-thiazol-diphenyltetrazolium and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling-based ApoBrdU assays, respectively. The effect of LY294002-mediated phosphoinositide 3-kinase inhibition on protein kinase B (Akt) activation and nuclear factor-kappaB signaling was determined. by Western blot analysis. Nuclear factor-kappaB transcription activity in cultured cancer cells either at baseline or after treatments with LY294002 or BAY11-0782 (a pharmacologic inhibitor of nuclear factor-kappaB) was determined by the nuclear factor-kappaB-Luciferase reporter system. Results: A 4- to more than 20-fold reduction of paclitaxel IC50 values was observed in cancer cells treated with paclitaxel + LY294002 combinations. This was paralleled with synergistic induction of apoptosis. LY294002 treatment caused a significant dose-dependent inhibition of protein kinase B (Akt) activation and suppression of nuclear factor-kappaB transcriptional activity that was accompanied by elevation of IkappaB the intrinsic inhibitor of nuclear factor-kappaB, and concomitant reduction of nuclear factor-kappaB-regulated antiapoptotic proteins cIAP1, cIAP2, and BclXL. Direct inhibition of nuclear factor-kappaB activity by BAY11-0782 also resulted in profound enhancement of paclitaxel sensitivity and paclitaxel-mediated induction of apoptosis in lung and esophageal cancer cells. Conclusion: LY294002-mediated inhibition of the phosphoinositide 3-kinase/protein kinase B-dependent survival pathway with secondary suppression of nuclear factor-kappaB transcriptional activity was associated with enhancement of paclitaxel cytotoxicity in lung and esophageal cancer cells. Direct inhibition of nuclear factor-kappaB by BAY11-0782 also sensitized these cancer cells to paclitaxel, indicating that nuclear factor-kappaB may be the crucial intermediary step connecting phosphomositide 3-kinase/protein kinase B (Akt) to the intrinsic susceptibility of cancer cells to chemotherapeutic agents. C1 NCI, Sect Thorac Oncol, Surg Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), NCI, Sect Thorac Oncol, Surg Branch, Canc Res Ctr,NIH, Room 2B07,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM Dao_Nguyen@nih.gov NR 21 TC 42 Z9 46 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 2004 VL 127 IS 2 BP 365 EP 375 DI 10.1016/j.jtcvs.2003.09.033 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 772PY UT WOS:000188851500011 PM 14762343 ER PT J AU Pritchard, WF Wray-Cahen, D Karanian, JW Hilbert, S Wood, BJ AF Pritchard, WF Wray-Cahen, D Karanian, JW Hilbert, S Wood, BJ TI Radiofrequency cauterization with biopsy introducer needle SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS LIVER-BIOPSY; FIBRIN SEALANT; TRACT IMPLANTATION; CANINE MODEL; EMBOLIZATION; HEMATOMAS AB PURPOSE: The principal risks of needle biopsy are hemorrhage and implantation of tumor cells in the needle tract. This study compared hemorrhage after liver and kidney biopsy with and without radiofrequency (RF) ablation of the needle tract. MATERIALS AND METHODS: Biopsies of liver and kidney were performed in swine through introducer needles modified to allow RF ablation with the distal 2 cm of the needle. After each biopsy, randomization determined whether the site was to undergo RF ablation during withdrawal of the introducer needle. Temperature was measured with a thermistor stylet near the needle tip, with a target temperature of 70 degrees C-100 degrees C with RF ablation. Blood loss was measured as grams of blood absorbed in gauze at the puncture site for 2 minutes after needle withdrawal. Selected specimens were cut for gross examination. RESULTS: RF ablation reduced bleeding compared with absence of RF ablation in liver and kidney (P <.01), with mean blood loss reduced 63% and 97%, respectively. Mean amounts of blood loss (+/- SD) in the liver in the RF and no-RF groups were 2.03 g +/- 4.03 (CI, 0.53-3.54 g) and 5.50 g +/- 5.58 (CI, 3.33-7.66 g), respectively. Mean amounts of blood loss in the kidney in the RF and no-RF groups were 0.26 g +/- 0.32 (CI, -0.01 to 0.53 g) and 8.79 g +/- 7.72 (CI, 2.34-15.24 g), respectively. With RF ablation, thermal coagulation of the tissue surrounding the needle tract was observed. CONCLUSION: RF ablation of needle biopsy tracts reduced hemorrhage after biopsy in the liver and kidney and may reduce complications of hemorrhage as well as implantation of tumor cells in the tract. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Special Procedures Div, Bethesda, MD 20892 USA. RP Pritchard, WF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. EM wfp@cdrh.fda.gov FU Intramural NIH HHS [Z99 CL999999] NR 17 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD FEB PY 2004 VL 15 IS 2 BP 183 EP 187 DI 10.1097/01.RVI.000019398.74740.69 PN 1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 919EF UT WOS:000228600400011 PM 14963187 ER PT J AU Brenchley, JM Hill, BJ Ambrozak, DR Price, DA Guenaga, FJ Casazza, JP Kuruppu, J Yazdani, J Migueles, SA Connors, M Roederer, M Douek, DC Koup, RA AF Brenchley, JM Hill, BJ Ambrozak, DR Price, DA Guenaga, FJ Casazza, JP Kuruppu, J Yazdani, J Migueles, SA Connors, M Roederer, M Douek, DC Koup, RA TI T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: Implications for HIV pathogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) LYMPHOCYTES; TYPE-1 INFECTION; PERIPHERAL-BLOOD; BETA-CHEMOKINES; CD4; NAIVE; REPLICATION; EXPRESSION; ACTIVATION; DEPLETION AB Identification of T-cell subsets that are infected in vivo is essential to understanding the pathogenesis of human immunodeficiency virus (HIV) disease; however, this goal has been beset with technical challenges. Here, we used polychromatic flow cytometry to sort multiple T-cell subsets to 99.8% purity, followed by quantitative PCR to quantify HIV gag DNA directly ex vivo. We show that resting memory CD4(+) T cells are the predominantly infected cells but that terminally differentiated memory CD4(+) T cells contain 10-fold fewer copies of HIV DNA. Memory CD8(+) T cells can also be infected upon upregulation of CD4; however, this is infrequent and HIV-specific CD8(+) T cells are not infected preferentially. Naive CD4(+) T-cell infection is rare and principally confined to those peripheral T cells that have proliferated. Furthermore, the virus is essentially absent from naive CD8(+) T cells, suggesting that the thymus is not a major source of HIV-infected T cells in the periphery. These data illuminate the underlying mechanisms that distort T-cell homeostasis in HIV infection. C1 NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. RP Koup, RA (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bldg 40 3504,40 Convent Dr, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov RI Roederer, Mario/G-1887-2011; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 55 TC 222 Z9 231 U1 3 U2 13 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 FEB PY 2004 VL 78 IS 3 BP 1160 EP 1168 DI 10.1128/JVI.78.3.1160-1168.2004 PG 9 WC Virology SC Virology GA 764KK UT WOS:000188205900011 PM 14722271 ER PT J AU Oshima, M Muriaux, D Mirro, J Dryden, NK Yeager, M Rein, A AF Oshima, M Muriaux, D Mirro, J Dryden, NK Yeager, M Rein, A TI Effects of blocking individual maturation cleavages in murine leukemia virus Gag SO JOURNAL OF VIROLOGY LA English DT Article ID ACID-CHAPERONE ACTIVITY; HIV-1 CAPSID PROTEIN; NUCLEOCAPSID PROTEINS; RETROVIRUS PARTICLES; VIRION PRODUCTION; GENE-PRODUCTS; TRANSFER-RNA; GENOMIC RNA; VIRAL-RNA; TYPE-1 AB A single protein, termed Gag, is responsible for retrovirus particle assembly. After the assembled virion is released from the cell, Gag is cleaved at several sites by the viral protease (PR). The cleavages catalyzed by PR bring about a wide variety of physical changes in the particle, collectively termed maturation, and convert the particle into an infectious virion. In murine leukemia virus (MLV) maturation, Gag is cleaved at three sites, resulting in formation of the matrix (MA), p12, capsid (CA), and nucleocapsid (NC) proteins. We introduced mutations into MLV that inhibited cleavage at individual sites in Gag. All mutants had lost the intensely staining ring characteristic of immature particles; thus, no single cleavage event is required for this feature of maturation. Mutant virions in which MA was not cleaved from p12 were still infectious, with a specific infectivity only similar to10-fold below that of the wild type. Particles in which p12 and CA could not be separated from each other were noninfectious and lacked a well-delineated core despite the presence of dense material in their interiors. In both of these mutants, the dimeric viral RNA had undergone the stabilization normally associated with maturation, suggesting that this change may depend upon the separation of CA from NC. Alteration of the C-terminal end of CA blocked CA-NC cleavage but also reduced the efficiency of particle formation and, in some cases, severely disrupted the ability of Gag to assemble into regular structures. This observation, highlights the critical role of this region of Gag in assembly. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. NCI, Image Analysis Lab, SAIC, Ft Detrick, MD 21702 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, POB B, Ft Detrick, MD 21702 USA. EM rein@ncifcrf.gov NR 52 TC 28 Z9 29 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 FEB PY 2004 VL 78 IS 3 BP 1411 EP 1420 DI 10.1128/JVI.78.3.1411-1420.2004 PG 10 WC Virology SC Virology GA 764KK UT WOS:000188205900036 PM 14722296 ER PT J AU Ono, A Freed, EO AF Ono, A Freed, EO TI Cell-type-dependent targeting of human immunodeficiency virus type 1 assembly to the plasma membrane and the multivesicular body SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; MATRIX PROTEIN; INTRACELLULAR-TRANSPORT; MONONUCLEAR PHAGOCYTES; ENDOCYTIC COMPARTMENTS; PARTICLE-PRODUCTION; PRIMARY MACROPHAGES; GAG PROTEINS; LATE DOMAIN; HIV-1 AB The human immunodeficiency virus type 1 (HIV-1) assembly-and-release pathway begins with the targeting of the Gag precursor to the site of virus assembly. The molecular mechanism by which Gag is targeted to the appropriate subcellular location remains poorly understood. Based on the analysis of mutant Gag proteins, we and others have previously demonstrated that a highly basic patch in the matrix (MA) domain of Gag is a major determinant of Gag transport to the plasma membrane. In this study, we determined that in HeLa and T cells, the MA mutant Gag proteins that are defective in plasma membrane targeting form virus particles in a CD63-positive compartment, defined as the late endosome or multivesicular body (MVB). Interestingly, we find that in primary human macrophages, both wild-type (WT) and MA mutant Gag proteins are targeted specifically to the MVB. Despite the fact that particle assembly in macrophages occurs at an intracellular site rather than at the plasma membrane, we observe that WT Gag expressed in this cell type is released as extracellular virions with high efficiency. These results demonstrate that Gag targeting to and assembly in the MVB are physiologically important steps in HIV-1 virus particle production in macrophages and that particle release in this cell type may follow an exosomal pathway. To determine whether Gag targeting to the MVB is the result of an interaction between the late domain in p6(Gag) and the MVB sorting machinery (e.g., TSG101), we examined the targeting and assembly of Gag mutants lacking p6. Significantly, the MVB localization of Gag was still observed in the absence of p6, suggesting that an interaction between Gag and TSG101 is not required for Gag targeting to the MVB. These data are consistent with a model for Gag targeting that postulates two different cellular binding partners for Gag, one on the plasma membrane and the other in the MVB. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Ono, A (reprint author), NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, NIH, Bldg 535,Rm 124, Frederick, MD 21702 USA. EM aono@ncifcrf.gov OI Ono, Akira/0000-0001-7841-851X NR 63 TC 197 Z9 205 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 FEB PY 2004 VL 78 IS 3 BP 1552 EP 1563 DI 10.1128/JVI.78.3.1552-1563.2004 PG 12 WC Virology SC Virology GA 764KK UT WOS:000188205900049 PM 14722309 ER PT J AU Newman, JT Riggs, JM Surman, SR McAuliffe, JM Mulaikal, TA Collins, PL Murphy, BR Skiadopoulos, MH AF Newman, JT Riggs, JM Surman, SR McAuliffe, JM Mulaikal, TA Collins, PL Murphy, BR Skiadopoulos, MH TI Generation of recombinant human parainfluenza virus Type 1 vaccine candidates by importation of temperature-sensitive and attenuating mutations from heterologous paramyxoviruses SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; ACUTE OTITIS-MEDIA; SENDAI-VIRUS; REVERSE GENETICS; MUCOSAL IMMUNIZATION; HEALTHY INFANTS; RHESUS-MONKEYS; YOUNG-CHILDREN; MEASLES-VIRUS; V-PROTEIN AB Human parainfluenza virus type 1 (HPIV1) is a significant cause of respiratory tract disease in infants and young children for which a vaccine is needed. In the present study, we sought to attenuate HPIV1 by the importation of one or more known attenuating point mutations from heterologous paramyxoviruses into homologous sites in HPIV1. The introduced mutations were derived from three attenuated paramyxoviruses: (i) HPIV3cp45, a live-attenuated HPIV3 vaccine candidate containing multiple attenuating mutations; (ii) the respiratory syncytial virus cpts530 with an attenuating mutation in the L polymerase protein; and (iii) a murine PIV1 (MPIV1) attenuated by a mutation in the accessory C protein. Recombinant HPIV1 (rHPIV1) mutants bearing a single imported mutation in C, any of three different mutations in L, or a pair of mutations in F exhibited a 100-fold or greater reduction in replication in the upper or lower respiratory tract of hamsters. Both temperature-sensitive (is) (mutations in the L and F proteins) and non-ts (the mutation in the C protein) attenuating mutations were identified. rHPfV1 mutants containing a combination of mutations in L were generated that were more attenuated than viruses bearing the individual mutations, showing that the systematic accretion of mutations can yield progressive increases in attenuation. Hamsters immunized with rHPIV1 mutants bearing one or two mutations developed neutralizing antibodies and were resistant to challenge with wild-type HPIV1. Thus, importation of attenuating mutations from heterologous viruses is an effective means for rapidly identifying mutations that attenuate HPIV1 and for generating live-attenuated HPIV1 vaccine candidates. C1 NIAID, Res Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Skiadopoulos, MH (reprint author), NIH, Bldg 50,Room 6511,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM mskiadopoulos@niaid.nih.gov NR 54 TC 36 Z9 36 U1 1 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 FEB PY 2004 VL 78 IS 4 BP 2017 EP 2028 DI 10.1128/JVI.78.4.2017-2028.2004 PG 12 WC Virology SC Virology GA 769RE UT WOS:000188662900041 PM 14747566 ER PT J AU McAuliffe, JM Surman, SR Newman, JT Riggs, JM Collins, PL Murphy, BR Skiadopoulos, MH AF McAuliffe, JM Surman, SR Newman, JT Riggs, JM Collins, PL Murphy, BR Skiadopoulos, MH TI Codon substitution mutations at two positions in the L polymerase protein of human parainfluenza virus type 1 yield viruses with a spectrum of attenuation in vivo and increased phenotypic stability in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; TEMPERATURE-SENSITIVE MUTATIONS; ACUTE OTITIS-MEDIA; VACCINE CANDIDATE; REVERSE GENETICS; HEALTHY INFANTS; SINDBIS VIRUS; LIVE; RECOMBINANT; REPLICATION AB The Y942H and L992F temperature-sensitive (ts) and attenuating amino acid substitution mutations, previously identified in the L polymerase of the HPIV3cp45 vaccine candidate, were introduced into homologous positions of the L polymerase of recombinant human parainfluenza virus type 1 (rHPIV1). In rHPIV1, the Y942H mutation specified the ts phenotype in vitro and the attenuation (att) phenotype in hamsters, whereas the L992F mutation specified neither phenotype. Each of these codon mutations was generated by a single nucleotide substitution and therefore had the potential to readily revert to a codon specifying the wild-type amino acid residue. We introduced alternative amino acid assignments at codon 942 or 992 as a strategy to increase genetic stability and to generate mutants that exhibit a range of attenuation. Twenty-three recombinants with codon substitutions at position 942 or 992 of the L protein were viable. One highly ts and att mutant, the Y942A virus, which had a difference of three nucleotides from the codon encoding a wild-type tyrosine, also possessed a high level of genetic and phenotypic stability upon serial passage in vitro at restrictive temperatures compared to that of the parent Y942H virus, which possessed a single nucleotide substitution. We obtained mutants with substitutions at position 992 that, in contrast to the L992F virus, possessed the ts and att phenotypes. These findings identify the use of alternative codon substitution mutations as a method that can be used to generate candidate vaccine viruses with increased genetic stability and/or a modified level of attenuation. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Skiadopoulos, MH (reprint author), NIH, Bldg 50,Room 6511,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM mskiadopoulos@niaid.nih.gov NR 35 TC 28 Z9 29 U1 1 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 FEB PY 2004 VL 78 IS 4 BP 2029 EP 2036 DI 10.1128/JVI.78.4.2029.2036.2004 PG 8 WC Virology SC Virology GA 769RE UT WOS:000188662900042 PM 14747567 ER PT J AU Reyes, RA Canfield, DR Esser, U Adamson, LA Brown, CR Cheng-Mayer, C Gardner, MB Harouse, JM Luciw, PA AF Reyes, RA Canfield, DR Esser, U Adamson, LA Brown, CR Cheng-Mayer, C Gardner, MB Harouse, JM Luciw, PA TI Induction of simian AIDS in infant rhesus Macaques infected with CCR5- or CXCR4-utilizing Simian-human immunodeficiency viruses is associated with distinct lesions of the thymus SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL DEPLETION; IN-VIVO; MOLECULAR CLONES; TYPE-1 INFECTION; CCR5; CXCR4; HIV-1; PATHOGENESIS; REPLICATION; EXPRESSION AB Newborn rhesus macaques were infected with two chimeric simian-human immunodeficiency virus (SHIV) strains which contain unique human immunodeficiency virus type 1 (HIV-1) env genes and exhibit distinct phenotypes. Infection with either the CCR5-specific SHIVSF162P3 or the CXCR4-utilizing SHIVSF33A resulted in clinical manifestations consistent with simian AIDS. Most prominent in this study was the detection of severe thymic involution in all SHIVSF33A-infected infants, which is very similar to HIV-1-induced thymic dysfunction in children who exhibit a rapid pattern of disease progression. In contrast, SHIVSF162P3 induced only a minor disruption in thymic morphology. Consistent with the distribution of the coreceptors CXCR4 and CCR5 within the thymus, the expression of SHIVSF162P3 was restricted to the thymic medulla, whereas SHIVSF33A was preferentially detected in the cortex. This dichotomy of tissue tropism is similar to the differential tropism of HIV-1 isolates observed in the reconstituted human thymus in SCID-hu mice. Accordingly, our results show that the SHIV-monkey model can be used for the molecular dissection of cell and tissue tropisms controlled by the HIV-1 env gene and for the analysis of mechanisms of viral immunopathogenesis in AIDS. Furthermore, these findings could help explain the rapid progression of disease observed in some HIV-1-infected children. C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Univ Calif Davis, Dept Med Pathol, Davis, CA 95616 USA. NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. Rockefeller Univ, Aaron Diamond Res Ctr, New York, NY 10016 USA. RP Luciw, PA (reprint author), Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. EM paluciw@ucdavis.edu FU NCRR NIH HHS [P51 RR000169, RR-00169] NR 39 TC 16 Z9 16 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 FEB PY 2004 VL 78 IS 4 BP 2121 EP 2130 DI 10.1128/JVI.78.4.2121.2130.2004 PG 10 WC Virology SC Virology GA 769RE UT WOS:000188662900052 PM 14747577 ER PT J AU Race, RE Raymond, GJ AF Race, RE Raymond, GJ TI Inactivation of transmissible spongiform encephalopathy (Prion) agents by environ LpH SO JOURNAL OF VIROLOGY LA English DT Article ID SCRAPIE AGENT AB Agents causing transmissible spongiform encephalopathy (TSE) diseases are resistant to inactivation by several conventional decontamination methods. Using an animal bioassay, we compared the TSE agent disinfectant efficacy of a commercially available product referred to alternatively as LpH-SE, LpH-AG, or LpH-st to that of a similarly named but differently formulated product, Environ LpH, which was found to be an effective TSE agent disinfectant in a previous study. Here, we found LpH-SE to be at least 10(4)-fold to 10(5)-fold less effective than Environ LpH. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT USA. RP Race, RE (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT USA. EM rrace@niaid.nih.gov NR 6 TC 28 Z9 28 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 FEB PY 2004 VL 78 IS 4 BP 2164 EP 2165 DI 10.1128/JVI.78.4.2164-2165.2004 PG 2 WC Virology SC Virology GA 769RE UT WOS:000188662900058 PM 14747583 ER PT J AU Daniel, C Wiede, J Krutzsch, HC Ribeiro, SMF Roberts, DD Murphy-Ullrich, JE Hugo, C AF Daniel, C Wiede, J Krutzsch, HC Ribeiro, SMF Roberts, DD Murphy-Ullrich, JE Hugo, C TI Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in the rat in vivo SO KIDNEY INTERNATIONAL LA English DT Article DE TGF-beta activation; thrombospondin-1; glomerulonephritis; extracellular matrix ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; MESANGIAL CELLS; EXPERIMENTAL GLOMERULONEPHRITIS; ENDOTHELIAL-CELLS; IGA NEPHROPATHY; GENE; EXPRESSION; FIBROSIS; KIDNEY AB Background. Transforming growth factor-beta (TGF-beta), a profibrotic cytokine involved in many scarring processes, has to be activated extracellularly before it can bind to its receptors. Thrombospondin 1 (TSP1), a multifunctional matricellular glycoprotein, has been identified as an activator of TGF-beta in in vitro systems and during mouse postnatal development in vivo. TSP1 is expressed de novo in many inflammatory disease processes, including glomerular disease. Methods. In this study we investigated whether peptides specifically interfering with the activation process of TGF-beta by TSP1 may be able to block activation of TGF-beta in an in vivo model of mesangial proliferative glomerulonephritis. Results. Continuous intravenous infusion of blocking peptide by minipumps significantly reduced expression of active TGF-beta in glomeruli on day 7 of disease as indicated by immunohistochemistry, bioassay, and activation of the TGF-beta signal transduction pathway, while total TGF-beta expression was unchanged. Inhibition of glomerular TGF-beta activation was accompanied by a decrease of glomerular extracellular matrix accumulation and proteinuria, but was without effect on mesangial cell proliferation or influx of monocytes/macrophages. Conclusion. TSP1 is a major endogenous activator of TGF-beta in experimental inflammatory glomerular disease. Drugs interfering with the activation of TGF-beta by locally produced TSP1 may be considered as a future specific treatment of scarring kidney disease. C1 Univ Erlangen Nurnberg, Div Nephrol, D-91054 Erlangen, Germany. NCI, Biochem Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Div Mol & Cellular Pathol, Birmingham, AL 35294 USA. RP Hugo, C (reprint author), Univ Erlangen Nurnberg, Div Nephrol, Loschgestr 8, D-91054 Erlangen, Germany. EM Christian.Hugo@rzmail.uni-erlangen.de RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NHLBI NIH HHS [HL50061]; NIDDK NIH HHS [DK64624] NR 43 TC 85 Z9 102 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2004 VL 65 IS 2 BP 459 EP 468 DI 10.1111/j.1523-1755.2004.00395.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 761QM UT WOS:000187919500011 PM 14717916 ER PT J AU Weening, JJ D'Agati, VD Schwartz, MM Seshan, SV Alpers, CE Appel, GB Balow, JE Bruijn, JA Cook, T Ferrario, F Fogo, AB Ginzler, EM Hebert, L Hill, G Hill, P Jennette, JC Kong, NC Lesavre, P Lockshin, M Looi, LM Makino, H Moura, LA Nagata, M AF Weening, JJ D'Agati, VD Schwartz, MM Seshan, SV Alpers, CE Appel, GB Balow, JE Bruijn, JA Cook, T Ferrario, F Fogo, AB Ginzler, EM Hebert, L Hill, G Hill, P Jennette, JC Kong, NC Lesavre, P Lockshin, M Looi, LM Makino, H Moura, LA Nagata, M CA Int Soc Nephrology Renal Soc Working Grp Classificati TI The classification of glomerulonephritis in systemic lupus erythematosus revisited SO KIDNEY INTERNATIONAL LA English DT Article DE lupus erythematosus; classification; glomerulonephritis ID CLINICAL COURSE; NEPHRITIS; MANAGEMENT; FORMS AB The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving < 50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis(i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification. C1 Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1006 AZ Amsterdam, Netherlands. Columbia Univ, Coll Phys & Surg, New York, NY USA. Rush Med Coll, Chicago, IL 60612 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. Imperial Coll Med Sch, London, England. San Carlo Borromeo Hosp, Milan, Italy. Vanderbilt Univ, Nashville, TN USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Ohio State Univ, Columbus, OH 43210 USA. Georges Pompidou European Hosp, Paris, France. St Vincents Hosp, Fitzroy, Vic 3065, Australia. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Kebangsaan Malaysia, Kuala Lumpur, Malaysia. Hop Necker Enfants Malad, Paris, France. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Malaya, Sch Med, Kuala Lumpur, Malaysia. Okayama Univ, Grad Sch Med & Dent, Okayama, Japan. Univ Fed Sao Paulo, Sao Paulo, Brazil. Univ Tsukuba, Ibaraki, Japan. RP Weening, JJ (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Pathol, POB 22660, NL-1006 AZ Amsterdam, Netherlands. EM j.j.weening@amc.uva.nl RI Looi, Lai Meng/A-3382-2009; OI Looi, Lai Meng/0000-0001-8325-0117; Kong, Norella Chiew-Tong/0000-0001-5165-5216 NR 23 TC 482 Z9 584 U1 2 U2 29 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2004 VL 65 IS 2 BP 521 EP 530 DI 10.1111/j.1523-1755.2004.00443.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 761QM UT WOS:000187919500017 PM 14717922 ER PT J AU Abbott, KC Glanton, CW Trespalacios, FC Oliver, DK Ortiz, MI Agodoa, LY Cruess, DF Kimmel, PL AF Abbott, KC Glanton, CW Trespalacios, FC Oliver, DK Ortiz, MI Agodoa, LY Cruess, DF Kimmel, PL TI Body mass index, dialysis modality, and survival: Analysis of the United States Renal Data System Dialysis Morbidity and Mortality Wave II Study SO KIDNEY INTERNATIONAL LA English DT Article DE obesity; body mass index; peritoneal dialysis; hemodialysis; survival; mortality ID SHORT-TERM SURVIVAL; HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS; MAINTENANCE HEMODIALYSIS; PATIENT CHARACTERISTICS; DISEASE PATIENTS; RISK-FACTORS; OBESITY; IMPACT; DEATH AB Background. The impact of obesity on survival in end-stage renal disease (ESRD) patients as related to dialysis modality (i.e., a direct comparison of hemodialysis with peritoneal dialysis) has not been assessed adjusting for differences in medication use, follow-up 2 years, or accounting for changes in dialysis modality. Methods. We performed a retrospective cohort study of the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Wave II Study (DMMS) patients who started dialysis in 1996, and were followed until October 31 2001. Cox regression analysis was used to model adjusted hazard ratios (AHR) for mortality for categories of body mass index (BMI), both as quartiles and as greater than or equal to30 kg/m(2) vs. lower. Because such a large proportion of peritoneal dialysis patients changed to hemodialysis during the study period (45.5%), a sensitivity analysis was performed calculating survival time both censoring and not censoring on the date of change from peritoneal dialysis to hemodialysis. Results. There were 1675 hemodialysis and 1662 peritoneal dialysis patients. Among hemodialysis patients, 5-year survival for patients with BMI greater than or equal to30 kg/m(2) was 39.8% vs. 32.3% for lower BMI (P < 0.01 by log-rank test). Among peritoneal dialysis patients, 5-year survival for patients with BMI 30 kg/m(2) was 38.7% vs. 40.4% for lower BMI (P > 0.05 by log-rank test). In adjusted analysis, BMI greater than or equal to30 kg/m(2) was associated with improved survival in hemodialysis patients (AHR 0.89; 95% CI 0.81, 0.99; P = 0.042) but not peritoneal dialysis patients (AHR = 0.99; 95% CI, 0.86, 1.15; P = 0.89). Results were not different on censoring of change from peritoneal dialysis to hemodialysis. Conclusion. We conclude that any survival advantage associated with obesity among chronic dialysis patients is significantly less likely for peritoneal dialysis patients, compared to hemodialysis patients. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Wilford Hall USAF Med Ctr, Serv Nephrol, Lackland AFB, TX 78236 USA. Madigan Army Med Ctr, Serv Nephrol, Ft Lewis, WA USA. NIDDK, NIH, Bethesda, MD USA. George Washington Hosp Ctr, Serv Nephrol, Washington, DC USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 42 TC 159 Z9 167 U1 0 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 2004 VL 65 IS 2 BP 597 EP 605 DI 10.1111/j.1523-1755.2004.00385.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 761QM UT WOS:000187919500025 PM 14717930 ER PT J AU Zha, HB Raffeld, M Charboneau, L Pittaluga, S Kwak, LW Petricoin, E Liotta, LA Jaffe, ES AF Zha, HB Raffeld, M Charboneau, L Pittaluga, S Kwak, LW Petricoin, E Liotta, LA Jaffe, ES TI Similarities of prosurvival signals in Bcl-2-positive and Bcl-2-negative follicular lymphomas identified by reverse phase protein microarray SO LABORATORY INVESTIGATION LA English DT Article DE apoptosis; follicular lymphoma; Bcl-2; protein microarray; proteomics ID LASER CAPTURE MICRODISSECTION; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; NF-KAPPA-B; BCL-2 FAMILY; CHROMOSOMAL-ABNORMALITIES; TRANSCRIPTION FACTOR; UP-REGULATION; EXPRESSION; SURVIVAL AB Overexpression of Bcl-2 protein has been known to play a role in the pathogenesis of follicular lymphoma (FL). However, 10-15% of FLs are negative for Bcl-2 by immunohistochemistry, raising the possibility that another gene product(s) may provide prosurvival signal(s). We used reverse phase protein microarray to analyze lysates of follicle center cells isolated by laser capture microdissection from: Bcl-2+ FL, Bcl-2- FL and reactive follicular hyperplasia (FH) (nine cases each group). TUNEL assay confirmed similar and reduced levels of apoptosis in Bcl-2+ FL and Bcl-2- FL, indicating the likelihood of Bcl-2-independent inhibition of apoptosis. Arrays were quantitatively analyzed with antibodies to proteins involved in the apoptotic pathway. As expected, Bcl-2 levels were up to eight-fold higher in Bcl-2+ FL than in FH and Bcl-2- FL. However, there was no difference in levels of Mcl-1 and survivin among these three groups. Bcl-X-L showed a trend for increased expression in Bcl-2- FL as compared with Bcl-2+ FL, although the differences did not reach statistical significance (P>0.1). The increase in Bcl-X-L may provide an alternative antiapoptotic signal in FL negative for Ill protein. Interestingly, Bax expression was higher in FL (Bcl-2+ or -) than in FH (P=0.001). Notably, phospho-Akt (Ser-473) was increased in FL (Bcl-2+ or -) (P<0.03) with increased phospho-Bad (Ser-136), as compared with levels in FH. The activation of the Akt/Bad pathway provides further evidence of prosurvival signals in FL, independent of Bcl-2 alone. These data suggest that nodal FL represents a single disease with a final common biochemical pathway. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2N202,MSC-1500, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov NR 66 TC 63 Z9 68 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 FEB PY 2004 VL 84 IS 2 BP 235 EP 244 DI 10.1038/labinvest.3700051 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 840BW UT WOS:000222833000013 PM 14767488 ER PT J AU Johnson, T Gitiban, N Mertz, S Durbin, R Durbin, J AF Johnson, T Gitiban, N Mertz, S Durbin, R Durbin, J TI The severity of respiratory syncytial virus lung disease is determined by the interaction of host and viral factors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Pediatric-Pathology CY MAR 06-07, 2004 CL Vancouver, CANADA SP Soc Pediat Pathol C1 NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Columbus Childrens Res Inst, Columbus, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2004 VL 84 IS 2 MA 17 BP 271 EP 271 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 840BW UT WOS:000222833000034 ER PT J AU Theodore, WH Fisher, RS AF Theodore, WH Fisher, RS TI Brain stimulation for epilepsy SO LANCET NEUROLOGY LA English DT Review ID VAGUS-NERVE-STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; CENTROMEDIAN THALAMIC NUCLEUS; MEDICALLY INTRACTABLE SEIZURES; CHRONIC ELECTRICAL-STIMULATION; HIGH-FREQUENCY STIMULATION; MOTOR CORTEX EXCITABILITY; TEMPORAL-LOBE EPILEPSY; LONG-TERM; REFRACTORY EPILEPSY AB Neural stimulation is a promising new technology for the treatment of medically-intractable seizures. Vagus-nerve stimulation (VNS) is licensed in several countries as an adjunctive therapy. VNS is as effective as antiepileptic drug therapy, and serious complications are rare. Transcranial magnetic stimulation is simple, non-invasive, and widely used in neurophysiology. Therapeutic results in a few studies are equivocal at best. Deep brain stimulation, although experimental, has been applied to the cerebellum, caudate nucleus, centromedian thalamus, anterior thalamus, subthalamus, hippocampus, and neocortical seizure foci. Preliminary results are encouraging, but not conclusive. Electrode implantation in the brain for indications other than seizures has been associated with a 5% risk for intracranial haemorrhage and 5% for infection. A controlled study of anterior thalamic stimulation in patients with intractable partial and secondarily generalised seizures has been started. Future investigations are likely to study extrathalamic sites of stimulation, and effects of stimulation contingent upon detection of or prediction of EEG patterns of epileptiform activity. C1 NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Stanford Univ, Epilepsy Ctr, Stanford, CA 94305 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 108 TC 231 Z9 238 U1 3 U2 39 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD FEB PY 2004 VL 3 IS 2 BP 111 EP 118 DI 10.1016/S1474-4422(03)00664-1 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 772AQ UT WOS:000188818500021 PM 14747003 ER PT J AU Popescu, NC AF Popescu, NC TI Fragile sites and cancer genes on the short arm of chromosome 8 SO LANCET ONCOLOGY LA English DT Letter ID COMMON C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD FEB PY 2004 VL 5 IS 2 BP 77 EP 77 DI 10.1016/S1470-2045(04)01377-4 PG 1 WC Oncology SC Oncology GA 771ZU UT WOS:000188816600013 PM 14761808 ER PT J AU Dancey, J Shepherd, FA Gralla, RJ Kim, YS AF Dancey, J Shepherd, FA Gralla, RJ Kim, YS TI Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial SO LUNG CANCER LA English DT Article DE docetaxel; non-small-cell lung cancer; quality of life; best supportive care ID ONCOLOGY-GROUP EXPERIENCE; CLINICAL-TRIALS; EUROPEAN-ORGANIZATION; SYMPTOM RELIEF; MITOMYCIN-C; CISPLATIN; PACLITAXEL; SURVIVAL; DEXAMETHASONE; VINBLASTINE AB Purpose and methods: Docetaxel second-line chemotherapy for non-small-cell lung cancer (NSCLC) has previously been shown to improve survival significantly compared with best supportive care (BSC). This multicenter phase III trial prospectively investigated quality of life QOL) in NSCLC patients treated with either second-line docetaxel or BSC. Patients with stage IIIB/IV NSCLC, performance status less than or equal to2, and adequate biochemistry and hematology were eligible if they had received greater than or equal to1 platinum-based chemotherapy regimens. Patients were randomized to docetaxel 100 mg/m(2) (n = 49) or, after protocol amendment, to docetaxel 75 mg/m(2) (n = 55), or to BSC (n = 100), with Lung Cancer Symptom Scale (LCSS) and/or QLQ-C30 (with LC13 module) assessment every 3 weeks. Results: Longitudinal analysis including all available assessments over time showed statistically significant differences in patient-rated pain scores in favor of docetaxel overall (P = 0.005) or docetaxel 100 mg/m(2) (P = 0.003) compared to BSC. Trends in favor of docetaxel were noted on observer-rated scales for fatigue and pain for all docetaxel patients, and for total LCSS score, appetite and fatigue with docetaxel 100 mg/m(2). Changes from baseline to the last available assessment (end point) showed significantly (P < 0.05) less deterioration in LCSS pain score in patients with docetaxel. (75 and 100 mg/m(2) combined) than with BSC. An improved mean pain score with docetaxel 100 mg/m(2) was contrasted with a deterioration in mean pain score with BSC (P < 0.01). There was also significantly less deterioration in the global QOL today score with docetaxel 100 mg/m(2) (P < 0.01). Similar trends were recorded with QLQ-C30 assessments. Conclusions: Second-tine docetaxel therapy for advanced NSCLC significantly improves survival with a trend towards less deterioration in QOL compared with BSC. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Toronto, ON, Canada. Scott Taylor Chair Lung Canc Res, Toronto, ON, Canada. New York Lung Canc Alliance, New York, NY USA. RP Dancey, J (reprint author), NCI, DCTD, CTEP, Invest Drug Branch, 6130 Execut Blvd,EPN 7131, Bethesda, MD 20892 USA. EM danceyj@ctep.nci.nih.gov NR 46 TC 102 Z9 108 U1 1 U2 10 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 FEB PY 2004 VL 43 IS 2 BP 183 EP 194 DI 10.1016/j.lungcan.2003.09.001 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 772HH UT WOS:000188836200008 PM 14739039 ER PT J AU Gaede, HC Gawrisch, K AF Gaede, HC Gawrisch, K TI Multi-dimensional pulsed field gradient magic angle spinning NMR experiments on membranes SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; gradients; pulsed field gradient; magic angle spinning; lipid membranes; liposomes; ibuprofen ID OVERHAUSER ENHANCEMENT SPECTROSCOPY; DIFFUSION MEASUREMENTS; HIGH-RESOLUTION; BIOLOGICAL-MEMBRANES; ETHANOL DISTRIBUTION; CROSS-RELAXATION; STIMULATED ECHO; LIPID BILAYERS; MODEL MEMBRANE; MAS-NMR AB The benefits of gradient techniques in the study of lipid membranes are demonstrated on a sample of 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC) liposomes embedded with ibuprofen. Most techniques from gradient NMR spectroscopy on solution samples are directly applicable to membrane samples subjected to magic angle spinning (MAS). Gradient-enhanced homo- and heteronuclear chemical shift correlation techniques were used to make resonance assignments. Gradient NOESY experiments provide insight into the location and dynamics of lipids, ibuprofen and water. Application of gradients not only reduces experiment time but also the t(1) noise in the multi-dimensional spectra. Diffusion measurements with pulsed field gradients characterize lateral movements of lipid and drug molecules in membranes. The theoretical framework for data analysis of MAS diffusion experiments on randomly oriented multilamellar liposomes is presented. Published in 2004 by John Wiley Sons, Ltd. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr, Rockville, MD 20852 USA. EM gawrisch@helix.nih.gov RI Gaede, Holly/B-7392-2015 OI Gaede, Holly/0000-0003-4444-4394 NR 36 TC 31 Z9 33 U1 2 U2 10 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD FEB PY 2004 VL 42 IS 2 BP 115 EP 122 DI 10.1002/mrc.1329 PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 770TR UT WOS:000188747400005 PM 14745790 ER PT J AU Brummer, ME Moratal-Perez, D Hong, CY Pettigrew, RI Millet-Roig, J Dixon, WT AF Brummer, ME Moratal-Perez, D Hong, CY Pettigrew, RI Millet-Roig, J Dixon, WT TI Noquist: Reduced field-of-view imaging by direct Fourier inversion SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; image reconstruction; reduced field of view; cardiac imaging; Fast cine imaging ID TEMPORAL RESOLUTION; SCAN TIME; MRI; REDUCTION AB A novel technique called "Noquist" is introduced for the acceleration of dynamic cardiac magnetic resonance imaging (CMRI). With the use of this technique, a more sparsely sampled dynamic image sequence is reconstructed correctly, without Nyquist foldover artifact. Unlike most other reduced field-of-view (rFOV) methods, Noquist does not rely on data substitution or temporal interpolation to reconstruct the dynamic image sequence. The proposed method reduces acquisition time in dynamic MRI scans by eliminating the data redundancy associated with static regions in the dynamic scene. A reduction of imaging time is achieved by a fraction asymptotically equal to the static fraction of the FOV, by omitting acquisition of an appropriate subset of phase-encoding views from a conventional equidistant Cartesian acquisition grid. The theory behind this method is presented along with sample reconstructions from real and simulated data. Noquist is compared with conventional cine imaging by retrospective selection of a reduced. data set from a full-grid conventional image sequence. in addition, a comparison is presented, using real and simulated data, of our technique with an existing rFOV technique that uses temporal interpolation. The experimental results confirm the theory, and demonstrate that Noquist reduces scan time for cine MRI while fully preserving both spatial and temporal resolution, but at the cost of a reduced signal-to-noise ratio (SNR). (C) 2004 Wiley-Liss, Inc. C1 Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Univ Politecn Valencia, E-46071 Valencia, Spain. Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. NIH, Bethesda, MD 20892 USA. GE Co, Global Res, Niskayuna, NY USA. RP Brummer, ME (reprint author), Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. EM mbrumme@emory.edu RI Moratal, David/D-1853-2010 OI Moratal, David/0000-0002-2825-3646 FU NHLBI NIH HHS [HL58147]; NLM NIH HHS [LM06486] NR 25 TC 26 Z9 26 U1 1 U2 4 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 FEB PY 2004 VL 51 IS 2 BP 331 EP 342 DI 10.1002/mrm.10694 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770JC UT WOS:000188718600016 PM 14755659 ER PT J AU Reijnders, K English, SJ Krishna, MC Cook, JA Sowers, AL Mitchell, JB Zhang, YT AF Reijnders, K English, SJ Krishna, MC Cook, JA Sowers, AL Mitchell, JB Zhang, YT TI Influence of body temperature on the BOLD effect in murine SCC tumors SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE tumor oxygenation; carbogen; BOLD MRI; hypothermia; Eppendorf ID BLOOD-FLOW; RAT-TUMORS; OXYGENATION; MICE; HYPOTHERMIA; PERFUSION AB Changes in the blood oxygen level dependent (BOLD) enhancements in tumors (squamous cell carcinoma, (SCCVII)) implanted in mice maintained at core temperatures of 30degreesC or 37degreesC were measured using MRI and compared to tumor oxygen levels obtained using an oxygen-sensitive Eppendorf electrode. Tumors were implanted in a hindleg of the mice intramuscularly. Tumor-bearing mice were imaged by BOLD MRI, while first breathing air and then carbogen (95% O-2, 5% CO2) for 15-min intervals at a core temperature of 30degreesC. After an equilibration period, the identical regimen was conducted with the same animal maintained at 37degreesC. This procedure was repeated with additional mice starting at 37degreesC followed by imaging at 30degreesC. Likewise, oxygen electrode measurements of the tumor were determined at core temperatures of 30degreesC and 37degreesC. The Eppendorf measurements showed that tumors in animals maintained at 30degreesC were significantly more hypoxic than at 37degreesC. MRI studies demonstrated stronger BOLD enhancement at 30degreesC than at 37degreesC, suggesting significant changes in hypoxia and/or blood flow in tumors at these temperatures. The findings of the study stress the importance of maintaining normal core temperature when assessing tumor oxygen status using functional imaging modalities or oxygen-sensitive electrodes. Published 2004 Wiley-Liss, lnc.dagger C1 NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Groningen Hosp, Dept Surg, Groningen, Netherlands. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 19 TC 14 Z9 16 U1 0 U2 0 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 FEB PY 2004 VL 51 IS 2 BP 389 EP 393 DI 10.1002/mrm.10695 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770JC UT WOS:000188718600022 PM 14755665 ER PT J AU Kellman, P Dyke, CK Aletras, AH McVeigh, ER Arai, AE AF Kellman, P Dyke, CK Aletras, AH McVeigh, ER Arai, AE TI Artifact suppression in imaging of myocardial infarction using B-1-weighted phased-array combined phase-sensitive inversion recovery SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; artifact; delayed hyperenhancement; heart; myocardial infarction; phased array; cerebrospinal fluid (CSF); phase-sensitive ID MRI AB Regions of the body with long T-1, such as cerebrospinal fluid (CSF), may create ghost artifacts on gadolinium-hyperenhanced images of myocardial infarction when inversion recovery (IR) sequences are used with a segmented acquisition. Oscillations in the transient approach to steady state for regions with long T-1 may cause ghosts, with the number of ghosts being equal to the number of segments. B-1-weighted phased-array combining provides an inherent degree of ghost artifact suppression because the ghost artifact is weighted less than the desired signal intensity by the coil sensitivity profiles. Example images are shown that illustrate the suppression of CSF ghost artifacts by the use of B-1-weighted phased-array combining of multiple receiver coils. Published 2004 Wiley-Liss, Inc.dagger C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, 10 Ctr Dr,MSC-1061,Bldg 10,Rm B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [Z01 HL004608-08] NR 9 TC 14 Z9 14 U1 0 U2 1 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 FEB PY 2004 VL 51 IS 2 BP 408 EP 412 DI 10.1002/mrm.10689 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 770JC UT WOS:000188718600026 PM 14755669 ER PT J AU Dyer, KD Nitto, T Moreau, JM McDevitt, AL Rosenberg, HF AF Dyer, KD Nitto, T Moreau, JM McDevitt, AL Rosenberg, HF TI Identification of a purine-rich intronic enhancer element in the mouse eosinophil-associated ribonuclease 2 (mEar 2) gene SO MAMMALIAN GENOME LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; RNASE-A SUPERFAMILY; ANTIVIRAL ACTIVITY; MOLECULAR-CLONING; NEUROTOXIN RNS2; RAPID EVOLUTION; PROTEIN GENE; FAMILY; TRANSCRIPTION; EXPRESSION AB The Mus musculus eosinophil-associated ribonuclease (mEar) gene cluster includes multiple distinct coding sequences that are highly divergent orthologs of the human eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3). We present a transcriptional analysis of the gene encoding mEar 2, the only member of this cluster with a well-defined expression profile. In this work, we demonstrate that the presence of non-coding exon 1 and the intron in tandem with a 361-bp 5'promoter of mEar 2 results in enhanced reporter gene expression, as much as 6- to 10-fold over the activity observed with the 5' promoter alone. We have identified a conserved purine-rich element in the intron of the mEar 2 gene that is necessary for maximum transcription and that interacts specifically with NFAT-binding proteins in nuclear extracts derived from the mouse LA4 epithelial cell line. Similar intronic enhancers have been described as regulating transcription of the human EDN gene, suggesting an overall conservation of an important regulatory strategy. C1 NIAID, Eosinophil Pathophysiol Sect, LHD, NIH, Bethesda, MD 20892 USA. RP Dyer, KD (reprint author), 10 Ctr Dr,MSC 1886,Bldg 10,Room 11N104, Bethesda, MD 20892 USA. EM kdyer@niaid.nih.gov NR 33 TC 5 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 2004 VL 15 IS 2 BP 126 EP 134 DI 10.1007/s00335-003-2304-x PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 766ZY UT WOS:000188414700006 PM 15058383 ER PT J AU Dawson, H Collins, G Pyle, R Deep-Dixit, V Taub, DD AF Dawson, H Collins, G Pyle, R Deep-Dixit, V Taub, DD TI The immunoregulatory effects of homocysteine and its intermediates on T-lymphocyte function SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT International Conference on Immunology and Aging CY JUN, 2002 CL WASHINGTON, DC DE aging; lymphocytes; immunodeficiency; homocysteine; folate; apoptosis; th1; cardiovascular disease ID INDUCED APOPTOSIS; FOLIC-ACID; HYPERSENSITIVITY; INHIBITION; HYDROLASE AB Elevated levels of homocysteine (Hcy) have been identified as independent risk identifiers for cardiovascular disease, cerebrovascular disease as well as for all-cause mortality. Despite the potential importance of these observations, a definitive pathological role for Hcy or its various metabolites in any of these conditions has not been established. Particularly deficient is a description of the effects of elevated levels of homocysteine on immune function. Folic acid and vitamin B12 deficiency have been independently associated with decreased immune function, the apoptosis of bone marrow hematopoietic progenitor cells and the appearance of leukocytes with hypomethylated DNA in the peripheral circulation. A specific role for Hcy or its metabolites in these processes has not been described. We have examined the effects of Hcy and its various derivatives on T cell activation, differentiation and cell viability. Our results have demonstrated that Hcy is a potent concentration-dependent T cell activator promoting cellular activation and differentiation as well as potentiating activation-induced cell death (AICD) and cellular apoptosis. Overall, Hcy appears to exert diverse effects on immune function in the circulation and within the tissue microenvironment possibly contributing to age-related immune dysfunction and disease pathology. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Gerontol Res Ctr, Clin Immunol Sect, Lab Immunol,NIH, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Gerontol Res Ctr, Clin Immunol Sect, Lab Immunol,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM taubd@grc.nia.nih.gov RI Dawson, Harry/H-8242-2013 NR 9 TC 31 Z9 38 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD FEB PY 2004 VL 125 IS 2 SI SI BP 107 EP 110 DI 10.1016/j.mad.2003.11.013 PG 4 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 778DH UT WOS:000189223500005 PM 15037011 ER PT J AU Philp, D Goldstein, AL Kleinman, HK AF Philp, D Goldstein, AL Kleinman, HK TI Thymosin beta(4) promotes angiogenesis, wound healing, and hair follicle development SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT International Conference on Immunology and Aging CY JUN, 2002 CL WASHINGTON, DC ID ENDOTHELIAL-CELLS; AGED MICE; IN-VIVO; REPAIR AB New blood vessel formation is important in many physiological process, including development, wound repair, and tumor growth. In aged animals, angiogenesis is reduced resulting in poor wound healing. We have identified a novel small molecule, thymosin beta(4), that promotes angiogenesis and wound repair in both normal and aged rodents. It also promotes hair growth in normal and aged rodents. It acts by increasing angiogenesis and cell migration and is currently in clinical trials for wound repair. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NIDCR, CRBRB, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. RP Kleinman, HK (reprint author), NIDCR, CRBRB, Cell Biol Sect, NIH, 30-433, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov NR 11 TC 80 Z9 92 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD FEB PY 2004 VL 125 IS 2 SI SI BP 113 EP 115 DI 10.1016/j.mad.2003.11.005 PG 3 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 778DH UT WOS:000189223500007 PM 15037013 ER PT J AU Roilides, E Walsh, T AF Roilides, E Walsh, T TI Recombinant cytokines in augmentation and immunomodulation of host defenses against Candida spp. SO MEDICAL MYCOLOGY LA English DT Review DE cytokines; Candida spp.; candidiasis; immunomodulation; host defenses ID COLONY-STIMULATING FACTOR; BONE-MARROW-TRANSPLANTATION; TUMOR-NECROSIS-FACTOR; ACUTE MYELOID-LEUKEMIA; HUMAN POLYMORPHONUCLEAR NEUTROPHILS; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; HUMAN MONOCYTE FUNCTION; HIGH-DOSE CHEMOTHERAPY AB Invasive candidiasis is one of the leading causes of morbidity and mortality in immunocompromised and critically ill patients. Clinical and experimental observations have demonstrated that phagocytic immunity is central in the outcome of deeply invasive candidiasis. Quantitative and qualitative modulation of anticandidal host defenses by the use of cytokines as an adjunct to antifungal drug therapy against Candida infections has been supported by extensive in vitro and in vivo preclinical data. Modulation of Th1/Th2 balance and use of combinations of antifungal agents together with cytokines also have shown promising preclinical results. However, clinical studies of the prevention or of adjunctive therapy in combination with antifungal agents are limited and do not allow specific recommendations for their cost effective use in patients. Thus, there is an urgent need of well-structured, randomized clinical trials to determine the safety, efficacy, optimal dose, duration and timing for different combinations of immunotherapy and antifungal agents in high-risk patients. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, Thessaloniki 54642, Greece. RP Walsh, T (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 120 TC 21 Z9 22 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD FEB PY 2004 VL 42 IS 1 BP 1 EP 13 DI 10.1080/13693780310001631341 PG 13 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 772NE UT WOS:000188847500001 PM 14982109 ER PT J AU Mahabir, S Frenkel, K Brady, MS Coit, D Leibes, L Karkoszka, J Berwick, M AF Mahabir, S Frenkel, K Brady, MS Coit, D Leibes, L Karkoszka, J Berwick, M TI Randomized, placebo-controlled pilot trial of the effects of alpha-tocopherol supplementation on levels of autoantibodies against 5-hydroxymethyl-2-deoxyuridine in melanoma patients SO MELANOMA RESEARCH LA English DT Article DE vitamin E; alpha-tocopherol; 5-hydroxymethyl-2-deoxyuridine; anti-HMdU antibodies; supplementation ID INDUCED CHROMOSOMAL DAMAGE; VITAMIN-E; GAMMA-TOCOPHEROL; MALIGNANT-MELANOMA; BETA-CAROTENE; DNA-DAMAGE; CIGARETTE SMOKERS; CANCER-RISK; PLASMA; SERUM AB We conducted a randomized, placebo-controlled pilot trial to assess whether supplementation of 1000 mg/day alpha-tocopherol for 3 months offered protection against DNA base damage in melanoma outpatients (n=46). Plasma autoantibodies (aAbs) against 5-hydroxymethyl-2-deoxyuridine (HMdU) were measured as an immune marker of DNA base damage. After 3 months of supplementation (final level), plasma levels of alpha-tocopherol increased significantly (P<0.0005) in the α-tocopherol compared with the placebo treatment group. Supplementation with at-tocopherol also resulted in a significant (P=0.04) decrease in plasma γ-tocopherol levels among males. Overall, we did not find any significant differences in the plasma anti-HMdU aAb levels between the two treatment groups. However, when the patients were stratified by the clinical characteristics of the melanoma, we found that α-tocopherol supplementation resulted in a borderline significant (P=0.06) 48% decrease in plasma anti-HMdU aAb levels in patients with less aggressive melanomas (Breslow thickness &LE;1 mm) only. Within-group analysis showed that women had significantly (P<0.05) higher baseline levels of anti-HMdU aAbs compared with men in each treatment group. However, the final levels of anti-HMdU aAbs were significantly (P<0.05) higher in women in the α-tocopherol supplemented group only. Although reliable conclusions cannot be drawn from this pilot study, which is limited by the small sample size, the results suggest that short-term α-tocopherol supplementation may offer some protection against less aggressive melanomas. Further studies using much larger sample sizes are required to confirm this finding. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. NYU, Kaplan Canc Ctr, New York, NY USA. NYU, Dept Environm Med, New York, NY USA. RP Mahabir, S (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Suite 705, Bethesda, MD 20892 USA. EM mahabirs@mail.nih.gov RI Mahabir, Somdat/A-9788-2008; Berwick, Marianne/E-9608-2010 FU NCI NIH HHS [R0-3 CA 58581]; NIA NIH HHS [R01 AG14587] NR 48 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD FEB PY 2004 VL 14 IS 1 BP 49 EP 56 DI 10.1097/01.cmr.0000113342.53882.3d PG 8 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 809WY UT WOS:000220668000007 PM 15091194 ER PT J AU Johnson, T Gitiban, N Mertz, S Durbin, R Durbin, J AF Johnson, T Gitiban, N Mertz, S Durbin, R Durbin, J TI The severity of respiratory syncytial virus lung disease is determined by the interaction of host and viral factors. SO MODERN PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Pediatric-Pathology CY MAR 06-07, 2004 CL Vancouver, CANADA SP Soc Pediat Pathol C1 NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Columbus Childrens Res Inst, Columbus, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 2004 VL 17 IS 2 MA 17 BP 269 EP 269 PG 1 WC Pathology SC Pathology GA 856DZ UT WOS:000224027200036 ER PT J AU Kang, H Cui, KR Zhao, KJ AF Kang, H Cui, KR Zhao, KJ TI BRG1 controls the activity of the retinoblastoma protein via regulation of p21(CIP1/WAF1/SDI) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE ARREST; CHROMATIN REMODELING ENZYMES; SUSCEPTIBILITY GENE-PRODUCT; SWI-SNF COMPLEX; HISTONE DEACETYLASE; HUMAN FIBROBLASTS; FUNCTIONAL INTERACTIONS; REPLICATIVE SENESCENCE; REPRESS TRANSCRIPTION; PRB PHOSPHORYLATION AB The ubiquitous mammalian chromatin-remodeling SWI/SNF-like BAF complexes play critical roles in tumorigenesis. It was suggested that the direct interaction of BRG1 with the retinoblastoma protein pRB is required for regulation of cell cycle progression by pRB. We present evidence that the BRG1-containing complexes regulate the expression of the cdk inhibitor p21(CIP1/WAF1/SDI). Furthermore, we show that the physical interaction between BRG1 and pRB is not required for induction of cell growth arrest and transcriptional repression of E2F target genes by pRB. Instead, BRG1 activates pRB by inducing its hypophosphorylation through up-regulation of the cdk inhibitor p21. The hypophosphorylation of pRB is reinforced by down-regulation of critical components, including cdk2, cyclin E, and cyclin D, in the pRB regulatory network. We demonstrate that up-regulation of p21 by BRG1 is necessary to induce formation of flat cells, growth arrest, and finally, cell senescence. Our results suggest that the BRG1-containing complexes control cellular proliferation and senescence by modulating the pRB pathway via multiple mechanisms. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhao, KJ (reprint author), Bldg 10,Room 7N311,9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov NR 74 TC 84 Z9 89 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 FEB PY 2004 VL 24 IS 3 BP 1188 EP 1199 DI 10.1128/MCB.24.3.1188-1199.2004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MW UT WOS:000188211500022 PM 14729964 ER PT J AU Brodsky, MH Weinert, BT Tsang, G Rong, YS McGinnis, NM Golic, KG Rio, DC Rubin, GM AF Brodsky, MH Weinert, BT Tsang, G Rong, YS McGinnis, NM Golic, KG Rio, DC Rubin, GM TI Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR; ATAXIA-TELANGIECTASIA; P53-DEPENDENT APOPTOSIS; CYCLE CHECKPOINT; MIDBLASTULA TRANSITION; P53-MEDIATED APOPTOSIS; MEIOTIC CHECKPOINT; FUNCTIONAL HOMOLOG; RESPONSE ELEMENT AB We have used genetic and microarray analysis to determine how ionizing radiation (IR) induces p53-dependent transcription and apoptosis in Drosophila melanogaster. IR induces MNK/Chk2-dependent phosphorylation of p53 without changing p53 protein levels, indicating that p53 activity can be regulated without an Mdm2-like activity. In a genome-wide analysis of IR-induced transcription in wild-type and mutant embryos, all IR-induced increases in transcript levels required both p53 and the Drosophila Chk2 homolog MNK. Proapoptotic targets of p53 include hid, reaper, sickle, and the tumor necrosis factor family member Eiger. Overexpression of Eiger is sufficient to induce apoptosis, but mutations in Eiger do not block IR-induced apoptosis. Animals heterozygous for deletions that span the reaper, sickle, and hid genes exhibited reduced IR-dependent apoptosis, indicating that this gene complex is haploinsufficient for induction of apoptosis. Among the genes in this region, hid plays a central, dosage-sensitive role in IR-induced apoptosis. p53 and MNK/Chk2 also regulate DNA repair genes, including two components of the nonhomologous end-joining repair pathway, Ku70 and Ku80. Our results indicate that MNK/Chk2-dependent modification of Drosophila p53 activates a global transcriptional response to DNA damage that induces error-prone DNA repair as well as intrinsic and extrinsic apoptosis pathways. C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT USA. Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. NCI, Mol Cell Biol Lab, Bethesda, MD 20892 USA. RP Brodsky, MH (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, 623 LRB, Worcester, MA 01605 USA. EM michael.brodsky@umassmed.edu RI rong, yikang/G-6179-2011; OI Weinert, Brian/0000-0002-1335-9915; Rubin, Gerald/0000-0001-8762-8703 FU NIGMS NIH HHS [R01 GM065604] NR 80 TC 185 Z9 191 U1 0 U2 8 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 FEB PY 2004 VL 24 IS 3 BP 1219 EP 1231 DI 10.1128/MCB.24.3.1219-1231.2004 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MW UT WOS:000188211500025 PM 14729967 ER PT J AU Cheng, JC Weisenberger, DJ Gonzales, FA Liang, GN Xu, GL Hu, YG Marquez, VE Jones, PA AF Cheng, JC Weisenberger, DJ Gonzales, FA Liang, GN Xu, GL Hu, YG Marquez, VE Jones, PA TI Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MESSENGER-RNA EXPRESSION; DNA METHYLATION; MYELODYSPLASTIC SYNDROMES; CYTIDINE DEAMINASE; CPG ISLANDS; 5-AZA-2'-DEOXYCYTIDINE; METHYLTRANSFERASES; GENE; INHIBITORS; 5-AZACYTIDINE AB During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Recently, we reported that zebularine [1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. Here we show that continuous application of zebularine to T24 cells induces and maintains p16 gene expression and sustains demethylation of the 5' region for over 40 days, preventing remethylation. In addition, continuous zebularine treatment effectively and globally demethylated various hypermethylated regions, especially CpG-poor regions. The drug caused a complete depletion of extractable DNA methyltransferase I (DNMT1) and partial depletion of DNMT3a and DNMT3b3. Last, sequential treatment with 5-aza-2'-deoxycytidine followed by zebularine hindered the remethylation of the p16 5' region and gene resilencing, suggesting the possible combination use of both drugs as a potential anticancer regimen. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Mol Biol, Keck Sch Med, Los Angeles, CA 90089 USA. Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. Natl Canc Inst, Canc Res Ctr, Med Chem Lab, Frederick, MD USA. RP Jones, PA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr & Hosp, 1441 Eastlake Ave,Room 8302L,Mail Stop 83, Los Angeles, CA 90089 USA. EM jones_p@ccnt.hsc.usc.edu OI Liang, Gangning/0000-0001-8664-922X FU NCI NIH HHS [T32 CA009659, 1R01 CA 82422, 1R01 CA 83867, R01 CA082422, R01 CA083867, T32 CA09659] NR 44 TC 148 Z9 160 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 FEB PY 2004 VL 24 IS 3 BP 1270 EP 1278 DI 10.1128/MCB.24.3.1270-1278.2004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MW UT WOS:000188211500029 PM 14729971 ER PT J AU Shimizu, M Takeshita, A Tsukamoto, T Gonzalez, FJ Osumi, T AF Shimizu, M Takeshita, A Tsukamoto, T Gonzalez, FJ Osumi, T TI Tissue-selective, bidirectional regulation of PEX11 alpha- and perilipin genes through a common peroxisome proliferator response element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACYL-COA OXIDASE; ACTIVATED RECEPTOR-ALPHA; CHICKEN BETA-GLOBIN; PPAR-ALPHA; MEMBRANE-PROTEIN; SACCHAROMYCES-CEREVISIAE; TARGETED DISRUPTION; HORMONE RECEPTORS; CDNA CLONING; EXPRESSION AB Most cis-acting regulatory elements have generally been assumed to activate a single nearby gene. However, many genes are clustered together, raising the possibility that they are regulated through a common element. We show here that a single peroxisome proliferator response element (PPRE), located between the mouse PEX11alpha and perilipin genes, confers on both genes activation by peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma. A functional PPRE 8.4 kb downstream of the promoter of PEX11a, a PPARalpha target gene, was identified by a gene transfection study. This PPRE was positioned 1.9 kb upstream of the perilipin gene and also functioned with the perilipin promoter. In addition, this PPRE, when combined with the natural promoters of the PEX11alpha and perilipin genes, conferred subtype-selective activation by PPARalpha and PPARgamma2. The PPRE sequence specifically bound to the heterodimer of RXRalpha and PPARalpha or PPARgamma2, as assessed by electrophoretic gel mobility shift assays. Furthermore, tissue-selective binding of PPARalpha and PPARgamma to the PPRE was demonstrated in hepatocytes and adipocytes, respectively, by chromatin immuno-precipitation assay. Hence, the expression of these genes is induced through the same PPRE in the liver and adipose tissue, where the two PPAR subtypes are specifically expressed. C1 Himeji Inst Technol, Grad Sch Sci, Dept Life Sci, Kamigori, Hyogo 6781297, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Osumi, T (reprint author), Himeji Inst Technol, Grad Sch Sci, Dept Life Sci, Kamigori, Hyogo 6781297, Japan. EM osumi@sci.himeji-tech.ac.jp NR 77 TC 45 Z9 51 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 FEB PY 2004 VL 24 IS 3 BP 1313 EP 1323 DI 10.1128/MCB.24.3.1313-1323.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MW UT WOS:000188211500033 PM 14729975 ER PT J AU Hough, RB Piatigorsky, J AF Hough, RB Piatigorsky, J TI Preferential transcription of rabbit Aldh1a1 in the cornea: Implication of hypoxia-related pathways SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID XENOBIOTIC RESPONSE ELEMENT; 3 ALDEHYDE DEHYDROGENASE; LENS EPITHELIAL-CELLS; PAS DOMAIN PROTEIN-1; HYDROCARBON RECEPTOR; DNA-BINDING; GENE-EXPRESSION; AH RECEPTOR; INDUCIBLE GENE; GENOMIC DNA AB Here we examine the molecular basis for the known preferential expression of rabbit aldehyde dehydrogenase class I (ALDH1A1) in the cornea. The rabbit Aldh1a1 promoter-firefly luciferase reporter transgene (-3519 to +43) was expressed preferentially in corneal cells in transfection tests and in transgenic mice, with an expression pattern resembling that of rabbit Aldh1a1. The 5' flanking region of the rabbit Aldh1a1 gene resembled that in the human gene (60.2%) more closely than that in the mouse (46%) or rat (51.5%) genes. We detected three xenobiotic response elements (XREs) and one E-box consensus sequence in the rabbit Aldh1a1 upstream region; these elements are prevalent in other highly expressed corneal genes and can mediate stimulation by dioxin and repression by CoCl2 which simulates hypoxia. The rabbit Aldh1a1 promoter was stimulated fourfold by dioxin in human hepatoma cells and repressed threefold by CoCl2 treatment in rabbit corneal stromal and epithelial cells. Cotransfection, mutagenesis, and gel retardation experiments implicated the hypoxia-inducible factor 3alpha/aryl hydrocarbon nuclear translocator heterodimer for Aldh1a1 promoter activation via the XREs and stimulated by retinoic acid protein 13 for promoter repression via the E-box. These experiments suggest that XREs, E-boxes, and PAS domain/basic helix-loop-helix transcription factors (bHLH-PAS) contribute to preferential rabbit Aldh1a1 promoter activity in the cornea, implicating hypoxia-related pathways. C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, 6 Ctr Dr,Room 201, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov NR 80 TC 13 Z9 14 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 FEB PY 2004 VL 24 IS 3 BP 1324 EP 1340 DI 10.1128/MCB.24.3.1324-1340.2004 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MW UT WOS:000188211500034 PM 14729976 ER PT J AU Strasser, V Fasching, D Hauser, C Mayer, H Bock, HH Hiesberger, T Herz, J Weeber, EJ Sweatt, JD Pramatarova, A Howell, B Schneider, WJ Nimpf, J AF Strasser, V Fasching, D Hauser, C Mayer, H Bock, HH Hiesberger, T Herz, J Weeber, EJ Sweatt, JD Pramatarova, A Howell, B Schneider, WJ Nimpf, J TI Receptor clustering is involved in reelin signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; BRAIN-DEVELOPMENT; LAMINAR ORGANIZATION; NEURONAL MIGRATION; CORTICAL-NEURONS; VLDL RECEPTOR; MOUSE-BRAIN; DISABLED 1; PROTEIN; BINDING AB The Reelin signaling cascade plays a crucial role in the correct positioning of neurons during embryonic brain development. Reelin binding to apolipoprotein E receptor 2 (ApoER2) and very-low-density-lipoprotein receptor (VLDLR) leads to phosphorylation of disabled I (Dab1), an adaptor protein which associates with the intracellular domains of both receptors. Coreceptors for Reelin have been postulated to be necessary for Dahl phosphorylation. We show that bivalent agents specifically binding to ApoER2 or VLDLR are sufficient to mimic the Reelin signal. These agents induce Dab1 phosphorylation, activate members of the Src family of nonreceptor tyrosine kinases, modulate protein kinase B/Akt phosphorylation, and increase long-term potentiation in hippocampal slices. Induced dimerization of Dab1 in HEK293 cells leads to its phosphorylation even in the absence of Reelin receptors. The mechanism for and the sites of these phosphorylations are identical to those effected by Reelin in primary neurons. These results suggest that binding of Reelin, which exists as a homodimer in vivo, to ApoER2 and VLDLR induces clustering of ApoER2 and VLDLR. As a consequence, Dahl becomes dimerized or oligomerized on the cytosolic side of the plasma membrane, constituting the active substrate for the kinase; this process seems to be sufficient to transmit the signal and does not appear to require any coreceptor. C1 Bioctr, Div Mol Genet, Dept Biochem Med, A-1030 Vienna, Austria. Univ Vienna, Dept Biochem Med, Max F Perutz Labs, Univ Dept Vienna Bioctr, A-1030 Vienna, Austria. Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75230 USA. Baylor Coll Med, Div Neurosci, Houston, TX USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Nimpf, J (reprint author), Bioctr, Div Mol Genet, Dept Biochem Med, Dr Bohrgasse 9-2, A-1030 Vienna, Austria. EM Johannes.Nimpf@univie.ac.at RI Weeber, Edwin/A-5396-2012; OI Howell, Brian/0000-0002-0204-0773; Sweatt, J. David/0000-0003-3567-485X FU NHLBI NIH HHS [R37 HL063762] NR 38 TC 123 Z9 131 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 FEB PY 2004 VL 24 IS 3 BP 1378 EP 1386 DI 10.1128/MCD.24.3.1378-1386.2004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764MW UT WOS:000188211500038 PM 14729980 ER PT J AU Duh, FM Fivash, M Moody, M Lung, ML Guo, X Stanbridge, E Dean, M Voevoda, M Hu, LF Kashuba, V Zabarovsky, ER Qian, CN Godbole, S Teh, BT Lerman, MI AF Duh, FM Fivash, M Moody, M Lung, ML Guo, X Stanbridge, E Dean, M Voevoda, M Hu, LF Kashuba, V Zabarovsky, ER Qian, CN Godbole, S Teh, BT Lerman, MI TI Characterization of a new SNP c767A/T (Arg222Trp) in the candidate TSG FUS2 on human chromosome 3p21.3: prevalence in Asian populations and analysis of association with nasopharyngeal cancer SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE nasopharyngeal carcinoma; single nucleotide polymorphism; FUS2; genetic association ID HIGH-FREQUENCY; CARCINOMA; DELETION AB The FUS2 gene, encoding a novel cytoplasmic acetyltransferase, resides in the tumor suppressor gene region on human chromosome 3p21.3 and is considered a promising candidate tumor suppressor gene. We have identified a new single nucleotide polymorphism (SNP), c767A/T, in the coding region of the gene. The polymorphism leads to a non-conservative amino acid change (R222W) located between the acetyltransferase (GNAT) and the proline-rich domains of the protein. We have analyzed 254 subjects included in 14 sub-populations. The occurrence of the SNP varies with the ethnicity of the population, suggesting that this SNP could be a valuable biomarker for population genetics. It is most prevalent in various Asian populations (T allele frequency > 0.54), followed by the Canadian polar Inuit (T allele frequency = 0.3), African American (T allele frequency = 0.17), and Caucasian population (T allele frequency = 0.1). Since nasopharyngeal carcinoma (NPC) is frequent in Southern China, Taiwan, Borneo and polar Canada, we further tested for the possible association of the FUS2 SNP with this form of endemic cancer. Our analysis, albeit limited, suggests no likely association between NPC and the FUS2 gene polymorphism. Further large-scale case-control studies are necessary and warranted to prove the strength of this contention. (C) 2003 Elsevier Ltd. All rights reserved. C1 NCI, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv Inc, Ft Detrick, MD 21702 USA. NCI, Canc Res Ctr, Immunobiol Lab, Ft Detrick, MD 21702 USA. Hong Kong Univ Sci & Technol, Dept Biol, Hong Kong, Hong Kong, Peoples R China. Sun Yat Sen Univ, Ctr Canc, Guangzhou 510060, Peoples R China. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92695 USA. NCI, Canc Res Ctr, Lab Genom Divers, Frederick, MD 21702 USA. Russian Acad Sci, Inst Cytol & Genet, Siberian Branch, Novosibirsk 630090, Russia. Russian Acad Med Sci, Inst Internal Med, Siberian Branch, Novosibirsk 630090, Russia. Karolinska Inst, Ctr Microbiol & Tumor Biol, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden. Queen Elizabeth Hosp, Dept Ear Nose & Throat, Sabah 88586, Malaysia. Van Andel Res Inst, Canc Genet Lab, Grand Rapids, MI 49503 USA. RP Duh, FM (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. EM duh@ncifcrf.gov RI Zabarovsky, Eugene/A-6645-2010; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 18 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD FEB PY 2004 VL 18 IS 1 BP 39 EP 44 DI 10.1016/j.mcp.2003.09.002 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 802KB UT WOS:000220161300005 PM 15036368 ER PT J AU Sharma, S Otterlei, M Sommers, JA Driscoll, HC Dianov, GL Kao, HI Bambara, RA Brosh, RM AF Sharma, S Otterlei, M Sommers, JA Driscoll, HC Dianov, GL Kao, HI Bambara, RA Brosh, RM TI WRN helicase and FEN-1 form a complex upon replication arrest and together process branch-migrating DNA structures associated with the replication fork SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID WERNER-SYNDROME PROTEIN; HUMAN FLAP ENDONUCLEASE-1; SYNDROME GENE-PRODUCT; BASE EXCISION-REPAIR; SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; HOLLIDAY JUNCTIONS; RECQ HELICASES; S-PHASE AB Werner Syndrome is a premature aging disorder characterized by genomic instability, elevated recombination, and replication defects. It has been hypothesized that defective processing of certain replication fork structures by WRN may contribute to genomic instability. Fluorescence resonance energy transfer (FRET) analyses show that WRN and Flap Endonuclease-1 (FEN-1) form a complex in vivo that colocalizes in foci associated with arrested replication forks. WRN effectively stimulates FEN-1 cleavage of branch-migrating double-flap structures that are the physiological substrates of FEN-1 during replication. Biochemical analyses demonstrate that WRN helicase unwinds the chicken-foot HJ intermediate associated with a regressed replication fork and stimulates FEN-1 to cleave the unwound product in a structure-dependent manner. These results provide evidence for an interaction between WRN and FEN-1 in vivo and suggest that these proteins function together to process DNA structures associated with the replication fork. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Norwegian Univ Sci & Technol, Inst Canc Res & Mol Med, N-7005 Trondheim, Norway. MRC, Radiat & Genome Stabil Unit, Harwell OX11 ORD, Oxon, England. Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. Univ Hyderabad, Sch Life Sci, Dept Biochem, Hyderabad 500046, Andhra Pradesh, India. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 FU NIGMS NIH HHS [R01 GM024441, GM24441] NR 64 TC 89 Z9 91 U1 0 U2 1 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 FEB PY 2004 VL 15 IS 2 BP 734 EP 750 DI 10.1091/mbc.E03-08-0567 PG 17 WC Cell Biology SC Cell Biology GA 770JF UT WOS:000188718900032 PM 14657243 ER PT J AU Wang, QMJ Lu, GW Schlapkohl, WA Goerke, A Larsson, C Mischak, H Blumberg, PM Mushinski, JF AF Wang, QMJ Lu, GW Schlapkohl, WA Goerke, A Larsson, C Mischak, H Blumberg, PM Mushinski, JF TI The V5 domain of protein kinase C plays a critical role in determining the isoform-specific localization, translocation, and biological function of protein kinase C-delta and -epsilon SO MOLECULAR CANCER RESEARCH LA English DT Article ID BETA-II; CATALYTIC DOMAIN; PHORBOL ESTER; PKC-DELTA; SUBCELLULAR-LOCALIZATION; REGULATORY DOMAINS; NIH 3T3-CELLS; CELLS; APOPTOSIS; CHIMERAS AB The catalytic domain of overexpressed protein kinase C (PKC)-delta mediates phorbol 12-myristate 13-acetate (PMA)-induced differentiation or apoptosis in appropriate model cell lines. To define the portions of the catalytic domain that are critical for these isozyme-specific functions, we constructed reciprocal chimeras, PKC-delta/epsilonV5 and -epsilon/deltaV5, by swapping the V5 domains of PKC-delta and -epsilon. PKC-delta/epsilonV5 failed to mediate PMA-induced differentiation of 32D cells, showing the essential nature of the V5 domain for PKC-delta's functionality. The other chimera, PKC-epsilon/deltaV5, endowed inactive PKC-epsilon with nearly all PKC-delta's apoptotic ability, confirming the importance of PKC-delta in this function. Green fluorescent protein (GFP)-tagged PKC-deltaV5 and -epsilon/deltaV5 in A7r5 cells showed substantial basal nuclear localization, while GFP-tagged PKC-epsilon and -delta/epsilonV5 showed significantly less, indicating that the V5 region of PKC-delta contains determinants critical to its nuclear distribution. PKC-epsilon/deltaV5-GFP showed much slower kinetics of translocation to membranes in response to PMA than parental PKC-epsilon, implicating the PKC-epsilonV5 domain in membrane targeting. Thus, the V5 domain is critical in several of the isozyme-specific functions of PKC-delta and -epsilon. C1 NCI, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. NCI, Genet Lab, Bethesda, MD 20892 USA. Hannover Med Sch, Nephrol Abt, D-3000 Hannover, Germany. Lund Univ, Dept Lab Med, Div Mol Med, Malmo, Sweden. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA USA. RP Mushinski, JF (reprint author), NIH, Bldg 37,Room 3134C,37 Convent Dr,MSC-4256, Bethesda, MD 20892 USA. EM jm8p@nih.gov RI Mischak, Harald/E-8685-2011; Wang, Qiming/B-6064-2012 NR 39 TC 27 Z9 27 U1 0 U2 2 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 FEB PY 2004 VL 2 IS 2 BP 129 EP 140 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 779RG UT WOS:000189313800007 PM 14985469 ER PT J AU Jansen, AP Camalier, CE Stark, C Colburn, NH AF Jansen, AP Camalier, CE Stark, C Colburn, NH TI Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TUMOR-CELL-LINES; GENE-EXPRESSION; TRANSFORMATION SUPPRESSOR; TOPOISOMERASE INHIBITORS; AP-1 TRANSACTIVATION; ANSAMYCINS CAUSES; BCR-ABL; PDCD4; GELDANAMYCIN; PROTEIN AB Programmed cell death 4 (Pdcd4), originally identified as an inhibitor of murine cellular transformation, inhibits protein synthesis by directly interacting with eukaryotic initiation factor 4A (eIF4A) of the translation initiation complex. The relevance of Pdcd4 to a broad range of human cancers derived from multiple tissue sites is unknown. Protein expression patterns from the National Cancer Institute drug-screening panel of 60 human cancer cells (NC160) were analyzed by Western blot methods and revealed frequent reduction of Pdcd4 protein levels in renal-, lung-, and glia-derived tumors. Greater than mean Pdcd4 protein levels correlated with the antitumor activity of geldanamycin and tamoxifen. Stable expression of antisense PDCD4 significantly reduced the sensitivity of MCF-7 breast cancer cells to geldanamycin and to tamoxifen. Sensitivity to geldanamycin significantly increased in UO-31 renal cancer cells expressing sense PDCD4 cDNA. Increased geldanamycin sensitivity was accompanied by enhanced cell cycle arrest and apoptosis. One primary mode of inactivation of Pdcd4 in human cancers appears to involve down-regulated expression, and this down-regulation causes a decreased sensitivity to geldanamycin cytotoxicity. Thus, up-regulating Pdcd4 expression may be promising for geldanamycin-based combination therapy. C1 NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. RP Jansen, AP (reprint author), NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Bldg 567,Room 187, Frederick, MD 21702 USA. EM ajansen@ncifcrf.gov NR 44 TC 97 Z9 107 U1 1 U2 1 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 FEB PY 2004 VL 3 IS 2 BP 103 EP 110 PG 8 WC Oncology SC Oncology GA 778ME UT WOS:000189244700001 PM 14985450 ER PT J AU Bani, MR Nicoletti, MI Alkharouf, NW Ghilardi, C Petersen, D Erba, E Sausville, EA Liu, ET Giavazzi, R AF Bani, MR Nicoletti, MI Alkharouf, NW Ghilardi, C Petersen, D Erba, E Sausville, EA Liu, ET Giavazzi, R TI Gene expression correlating with response to paclitaxel in ovarian carcinoma xenografts SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID POTENT ANTITUMOR-ACTIVITY; BETA-TUBULIN ISOTYPES; CANCER CELL-LINES; HISTONE DEACETYLASE; ANTICANCER DRUGS; NUDE-MICE; CONFERS RESISTANCE; HUMAN-TUMORS; CDC2 KINASE; PROTEIN AB We have investigated gene expression profiles of human ovarian carcinomas in vivo during Taxol(R) (paclitaxel) treatment and observed a difference in expression. Nude mice bearing 1A9 or 1A9PTX22 xenografts were given 60 mg/kg of paclitaxel. Therapeutic efficacy was achieved for 1A9, while 1A9PTX22 did not respond. Tumor tissues harvested 4 and 24 h after treatment were evaluated by cDNA microarray against untreated tumors. Paclitaxel caused the modulation of more genes in 1A9 than in 1A9PTX22 tumors, in accordance to their therapeutic response. Most gene expression alterations were detected 24 h after paclitaxel administration and affected genes involved in various biological functions including cell cycle regulation and cell proliferation (CDC2, CDKN1A, PLAB, and TOP2A), apoptosis (BNIP3 and PIG8), signal transduction and transcriptional regulation (ARF1, ATF2, FOS, GNA11, HDAC3, MADH2, SLUG, and SPRY4), fatty acid biosynthesis and sterol metabolism (FDPS, IDI1, LIPA, and SC5D), and IFN-mediated signaling (G1P3, IFI16, IFI27, IFITM1, and ISG15). The modulation of two representative genes, CDKN1A and TOP2A, was validated by Northern analyses on a panel of seven ovarian carcinoma xenograft models undergoing treatment with paclitaxel. We found that the changes in expression level of these genes was strictly associated with the responsiveness to paclitaxel. Our study shows the feasibility of obtaining gene expression profiles of xenografted tumor models as a result of drug exposure. This in turn might provide insights related to the drugs' action in vivo that will anticipate the response to treatment manifested by tumors and could be the basis for novel approaches to molecular pharmacodynamics. C1 Mario Negri Inst Pharmacol Res, I-24125 Bergamo, Italy. Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy. Natl Univ Singapore, Genome Inst Singapore, Singapore 117548, Singapore. NCI, Dev Therapeut Program, Rockville, MD USA. NCI, Ctr Adv Technol, Gaithersburg, MD USA. RP Giavazzi, R (reprint author), Mario Negri Inst Pharmacol Res, Via Gavazzeni 11, I-24125 Bergamo, Italy. EM giavazzi@marionegri.it RI Liu, Edison/C-4141-2008 NR 61 TC 49 Z9 51 U1 1 U2 7 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 FEB PY 2004 VL 3 IS 2 BP 111 EP 121 PG 11 WC Oncology SC Oncology GA 778ME UT WOS:000189244700002 PM 14985451 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI Specifically targeted killing of interleukin-13 (IL-13) receptor-expressing breast cancer by IL-13 fusion cytotoxin in animal model of human disease SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; ALPHA-2 CHAIN; (IL)-13 BINDING; TUMOR IMMUNOSURVEILLANCE; ANTITUMOR-ACTIVITY; SYSTEMIC DELIVERY; MALIGNANT GLIOMA AB Interleukin-13 receptor (IL-13R) alpha2 chain binds IL-13 with high affinity and can internalize after binding to ligand. We have exploited this property of IL-13Ralpha2 chain by receptortargeted breast cancer therapy. Previous studies have demonstrated that in vivo intraturnoral (i.t.) gene transfer of this chain followed by IL-13 cytotoxin [comprised of IL-13 and Pseudomonas exotoxin (IL13-PE38QQR)] therapy causes regression of established human tumors in xenografted models. Breast carcinoma cells do not express IL-13Ralpha2 chain and are resistant to the antitumor effect of IL-13 cytotoxin. To determine whether IL-13Ralpha2 chain can render sensitivity of breast cancer to IL-13 cytotoxin, we injected IL-13Ralpha2 plasmid in s.c. established tumors by i.t. route, followed by systemic or i.t. IL-13 cytotoxin administration. This combination approach showed profound antitumor activity against human breast tumors in xenografted immunodeficient mice. Interestingly, there was dominant infiltration of inflammatory cells in regressing tumors, which were identified to be macrophages producing nitric oxide (NO) and natural killer cells. The partial role of inducible nitric oxide synthase (iNOS)-positive macrophages was confirmed by in vivo macrophage depletion experiments. Serum chemistry, hematology, and organ histology from treated mice did not show any remarkable toxicity resulting from the combination therapy. Taken together, local gene transfer of IL-13Ralpha2 followed by receptor-targeted IL-13 cytotoxin therapy may be applied safely and effectively to the treatment of localized breast cancer. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 50 TC 16 Z9 19 U1 0 U2 1 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 FEB PY 2004 VL 3 IS 2 BP 137 EP 147 PG 11 WC Oncology SC Oncology GA 778ME UT WOS:000189244700005 PM 14985454 ER PT J AU Gruvberger-Saal, SK Eden, P Ringner, M Baldetorp, B Chebil, G Borg, A Ferno, M Peterson, C Meltzer, PS AF Gruvberger-Saal, SK Eden, P Ringner, M Baldetorp, B Chebil, G Borg, A Ferno, M Peterson, C Meltzer, PS TI Predicting continuous values of prognostic markers in breast cancer from microarray gene expression profiles SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ESTROGEN-RECEPTOR STATUS; PATTERNS; TUMORS; CARCINOMAS; GROWTH; CELLS AB The prognostic and treatment-predictive markers currently in use for breast cancer are commonly based on the protein levels of individual genes (e.g., steroid receptors) or aspects of the tumor phenotype, such as histological grade and percentage of cells in the DNA synthesis phase of the cell cycle. Microarrays have previously been used to classify binary classes in breast cancer such as estrogen receptor (ER)-alpha status. To test whether the properties and specific values of conventional prognostic markers are encoded within tumor gene expression profiles, we have analyzed 48 well-characterized primary tumors from lymph node-negative breast cancer patients using 6728-element cDNA microarrays. In the present study, we used artificial neural networks trained with tumor gene expression data to predict the ER protein values on a continuous scale. Furthermore, we determined a gene expression profile-directed threshold for ER protein level to redefine the cutoff between ER-positive and ER-negative classes that may be more biologically relevant. With a similar approach, we studied the prediction of other prognostic parameters such as percentage cells in the S phase of the cell cycle (SPF), histological grade, DNA ploidy status, and progesterone receptor status. Interestingly, there was a consistent reciprocal relationship in expression levels of the genes important for both ER and SPF prediction. This and similar studies may be used to increase our understanding of the biology underlying these markers as well as to improve the currently available prognostic markers for breast cancer. C1 NHGRI, Mol Genet Sect, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Helsingborg Hosp, Dept Pathol, Helsingborg, Sweden. Lund Univ, Dept Theoret Phys, Complex Syst Div, S-22362 Lund, Sweden. Lund Univ, Dept Oncol, S-22362 Lund, Sweden. RP Meltzer, PS (reprint author), NHGRI, Mol Genet Sect, Canc Genet Branch, NIH, MSC 8000,Room 5139,50 South Dr, Bethesda, MD 20892 USA. EM pmeltzer@nhgri.nih.gov RI Ringner, Markus/G-3641-2011 OI Ringner, Markus/0000-0001-5469-8940 NR 30 TC 24 Z9 28 U1 0 U2 1 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 FEB PY 2004 VL 3 IS 2 BP 161 EP 168 PG 8 WC Oncology SC Oncology GA 778ME UT WOS:000189244700007 PM 14985456 ER PT J AU Tao, LH Wang, W Kramer, PM Lubet, RA Steele, VE Pereira, MA AF Tao, LH Wang, W Kramer, PM Lubet, RA Steele, VE Pereira, MA TI Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE biomarkers; chemoprevention; colon tumors; DNA hypomethylation ID FAMILIAL ADENOMATOUS POLYPOSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; AZOXYMETHANE-INDUCED TUMORS; ABERRANT CRYPT FOCI; CYCLOOXYGENASE-2 INHIBITOR; COLORECTAL-CANCER; ASPIRIN USE; RAT COLON; C-MYC; METHYLATION AB Surrogate end-point biomarkers are being developed as indicators of the efficacy of chemopreventive agents. These biomarkers are molecular and biological end-points that can be modulated by chemopreventive agents in accordance with their efficacy to prevent cancer. DNA hypomethylation is a common alteration found in colon tumors that has the potential of being modulated by chemopreventive agents and thus being useful as a surrogate end-point biomarker. Agents that were either effective or ineffective in preventing colon cancer were evaluated for the ability to modulate DNA hypomethylation in azoxymethane-induced colon tumors in male F344 rats. DNA methylation was determined by Dot Blot Analysis using a mouse monoclonal anti-5-methylcytosine antibody. Colon tumors had a 70% reduction in DNA methylation relative to normal colonic mucosa. DNA methylation in the tumors was increased by 7 days of treatment with agents that have been shown to prevent colon cancer (calcium chloride, alpha-diflouromethylornithine [DFMO], piroxicam, and sulindac), whereas agents shown not to prevent colon cancer in rats (low dose aspirin, 2-carboxyphenyl retinamide [2-CPR], quercetin, 9-cis retinoic acid, and rutin) did not increase DNA methylation. The results suggest that the ability to reverse the DNA hypomethylation in colon tumors could be useful as a surrogate m end-point biomarker for chemoprevention of colon cancer. (C) 2004 Wiley-Liss, Inc. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Chemoprevent, Bethesda, MD USA. RP Tao, LH (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Dept Internal Med, 300 W 10th Ave,1148 CHRI, Columbus, OH 43210 USA. FU NCI NIH HHS [N01-CN-05123, N01-CN-75102] NR 29 TC 15 Z9 16 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2004 VL 39 IS 2 BP 79 EP 84 DI 10.1002/mc.2003 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 771TM UT WOS:000188802200001 PM 14750212 ER PT J AU Langlais, P Dong, LLQ Ramos, FJ Hu, DR Li, YH Quon, MJ Liu, F AF Langlais, P Dong, LLQ Ramos, FJ Hu, DR Li, YH Quon, MJ Liu, F TI Negative regulation of insulin-stimulated mitogen-activated protein kinase signaling by Grb10 SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; RAT ADIPOSE-CELLS; RECEPTOR-BINDING-PROTEIN; SRC HOMOLOGY-2 DOMAIN; PLECKSTRIN HOMOLOGY; STRUCTURAL BASIS; ADAPTER PROTEIN; MAMMALIAN-CELLS; SH2 DOMAINS; EXPRESSION AB Grb10 is a Pleckstrin homology and Src homology 2 (SH2) domain-containing protein that binds to the tyrosine-phosphorylated insulin receptor in response to insulin stimulation. Loss of Grb10 function in mice results in fetal and placental overgrowth; however, the molecular mechanism remains unknown. In the present study, we show that overexpression of Grb10 in Chinese hamster ovary cells expressing the insulin receptor or in 3T3-L1 adipocytes reduced insulin-stimulated phosphorylation of MAPK. Overexpression of Grb10 in rat primary adipocytes also inhibited insulin-stimulated phosphorylation of the MAPK downstream substrate Elk1. To determine the mechanism by which Grb10 inhibited insulin-stimulated MAPK signaling, we examined whether Grb10 affects the phosphorylation of MAPK upstream signaling components. We found that overexpression of Grb10 inhibited the insulin-stimulated phosphorylation of Shc, a positive regulator of the MAPK signaling pathway. The inhibitory effect was diminished when the SH2 domain of Grb10 was deleted. The negative role of Grb10 in insulin signaling was established by suppression of endogenous Grb10 by RNA interference in HeLa cells overexpressing the insulin receptor, which enhanced insulin-stimulated phosphorylation of MAPK, Shc, and Akt. Taken together, our findings suggest that Grb10 functions as a negative regulator in the insulin-stimulated MAPK signaling pathway. In addition, the inhibitory effect of Grb10 on the MAPK pathway is most likely due to a direct block of insulin-stimulated Shc tyrosine phosphorylation. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Liu, F (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM liuf@uthscsa.edu RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU NIDDK NIH HHS [R01 DK52933] NR 32 TC 36 Z9 39 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB 1 PY 2004 VL 18 IS 2 BP 350 EP 358 DI 10.1210/me.2003-0117 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 767EC UT WOS:000188426400008 PM 14615605 ER PT J AU Kostic, TS Andric, SA Stojilkovic, SS AF Kostic, TS Andric, SA Stojilkovic, SS TI Receptor-controlled phosphorylation of alpha(1) soluble guanylyl cyclase enhances nitric oxide-dependent cyclic guanosine 5 '-monophosphate production in pituitary cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HORMONE-RELEASING-HORMONE; HUMAN GHRH RECEPTOR; MOLECULAR-CLONING; PROTEIN-KINASE; RAT LUNG; SYNTHASE; EXPRESSION; SUBUNIT; ACTIVATION; INHIBITION AB It is generally accepted that G protein-coupled receptors stimulate soluble guanylyl cyclase (sGC)mediated cGMP production indirectly, by increasing nitric oxide (NO) synthase activity in a calcium- and kinase-dependent manner. Here we show that normal and GH(3) immortalized pituitary cells expressed alpha(1)beta(1)-sGC heterodimer. Activation of adenylyl cyclase by GHRH, pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal peptide, and forskolin increased NO and cGMP levels, and basal and stimulated cGMP production was abolished by inhibition of NO synthase activity. However, activators of adenylyl cyclase were found to enhance this NO-dependent cGMP production even when NO was held constant at basal levels. Receptor-activated cGMP production was mimicked by expression of a constitutive active protein kinase A and was accompanied with phosphorylation of native and recombinant alpha(1)-sGC subunit. Addition of a protein kinase A inhibitor, overexpression of a dominant negative mutant of regulatory protein kinase A subunit, and substitution of Ser(107)-Ser(108) N-terminal residues of alpha(1)-subunit with alanine abolished adenylyl cyclase-dependent cGMP production without affecting basal and NO donor-stimulated cGMP production. These results indicate that phosphorylation of alpha(1)-subunit by protein kinase A enlarges the NO-dependent sGC activity, most likely by stabilizing the NO/alpha(1)beta(1) complex. This is the major pathway by which adenylyl cyclase-coupled receptors stimulate cGMP production. C1 NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov NR 46 TC 22 Z9 22 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB 1 PY 2004 VL 18 IS 2 BP 458 EP 470 DI 10.1210/me.2003-0015 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 767EC UT WOS:000188426400017 PM 14630997 ER PT J AU Nino-Vasquez, JJ Allicotti, G Borras, E Wilson, DB Valmori, D Simon, R Martin, R Pinilla, C AF Nino-Vasquez, JJ Allicotti, G Borras, E Wilson, DB Valmori, D Simon, R Martin, R Pinilla, C TI A powerful combination: the use of positional scanning libraries and biometrical analysis to identify cross-reactive T cell epitopes SO MOLECULAR IMMUNOLOGY LA English DT Article DE T cells; TCR degeneracy; epitopes; molecular mimicry; PS-SCL-based biometrical analysis ID RANDOM PEPTIDE LIBRARIES; MHC CLASS-I; MYELIN BASIC-PROTEIN; MOLECULAR MIMICRY; ANTIGEN RECOGNITION; SEQUENCE HOMOLOGY; LYMPHOCYTE CLONE; VIRAL PEPTIDES; SINGLE TCR; LIGANDS AB Studies on the elucidation of the specificity of the T cell receptor (TCR) at the antigen and peptide level have contributed to the current understanding of T cell cross-reactivity. Historically, most studies of T cell specificity and degeneracy have relied on the determination of the effects on T cell recognition of amino acid changes at individual positions or MHC binding residues, and thus they have been limited to a small set of possible ligands. Synthetic combinatorial libraries (SCLs), and in particular positional scanning synthetic combinatorial libraries (PS-SCLs) represent collections of millions to trillions of peptides which allow the unbiased elucidation of T cell ligands that stimulate clones of both known and unknown specificity. PS-SCLs have been used successfully to study T cell recognition and to identify and optimize T cell clone (TCC) epitopes in infectious diseases, autoimmune disorders and tumor antigens. PS-SCL-based biometrical analysis represents a further refinement in the analysis of the data derived from the screening of a library with a TCC. It combines this data with information derived from protein sequence databases to identify natural peptide ligands. PS-SCL-based biometrical analysis provides a method for the determination of new microbial antigen and autoantigen sequences based solely on functional data rather than sequence homology or motifs, making the method ideally suited for the prediction and identification of both native and cross-reactive epitopes by virtue of its ability to integrate the examination of trillions of peptides in a systematic manner with all of the protein sequences in a given database. We review here the application of PS-SCLs and biometrical analysis to identify cross-reactive T cell epitopes, as well as the current efforts to refine this strategy. (C) 2003 Elsevier Ltd. All rights reserved. C1 Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. Univ Lausanne Hosp, Lausanne Branch, Ludwig Inst Canc Res, Lausanne, Switzerland. NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Mixture Sci Inc, San Diego, CA 92121 USA. RP Pinilla, C (reprint author), Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. EM cpinilla@tpims.org RI Valmori, Danila/K-2439-2015 NR 64 TC 39 Z9 40 U1 0 U2 1 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 FEB PY 2004 VL 40 IS 14-15 BP 1063 EP 1074 DI 10.1016/j.molimm.2003.11.005 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 800BB UT WOS:000220002800013 PM 15036911 ER PT J AU Quandt, JS Borras, E Prat, E Gelderblom, H Houghten, RA Kashani, A Pinilla, C Stuerzebecher, CS Martin, R AF Quandt, JS Borras, E Prat, E Gelderblom, H Houghten, RA Kashani, A Pinilla, C Stuerzebecher, CS Martin, R TI Peptidic complex mixtures as therapeutic agents in CNS autoimmunity SO MOLECULAR IMMUNOLOGY LA English DT Article DE experimental autoimmune encephalomyelitis; multiple sclerosis; copolymers; peptides ID MYELIN BASIC-PROTEIN; T-CELL RECOGNITION; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; INDIVIDUAL AMINO-ACIDS; CENTRAL-NERVOUS-SYSTEM; GLATIRAMER ACETATE; COPOLYMER 1; BYSTANDER SUPPRESSION; CROSS-REACTIVITY AB Limited success with antigen-specific immunotherapies has led to the identification of novel approaches which consider the degeneracy of the T cell response, i.e. their ability to respond to multiple antigenic peptides. Random complex mixtures of polypeptides such as glatiramer acetate (GA) were among; the first to be applied as immunodulators that take into account T cell degeneracy. While the mechanisms of action are not completely understood, the immunogenicity of GA, its strong major histocompatability complex (MHC) binding, immune deviation and bystander suppression all appear to be important. In the present study we have designed peptidic complex mixtures (CM) of varied lengths and compositions to test their potential as immunomodulating agents. CM were synthesized that had defined lengths and contained aa corresponding to binding motifs of MHC class II molecules relevant in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), specifically HLA-DRB1*1501 and HLA-DRB5*0101, which are related to MS, and H2-IA(s) associated with EAE in SJL mice. Additional CM were designed based on specificity profiles derived from positional scanning synthetic combinatorial library (PS-SCL) testing of a GA-specific T cell clone (TCC). Several mixtures were strongly stimulatory for peripheral blood mononuclear cells (PBMC) from MS patients and healthy donors suggesting a high degree of cross-reactivity with other peptide antigens. A subset of these mixtures exhibited cross-reactivity to myelin antigens and prophylactic efficacy in reducing the severity of EAE. Based on these observations we envision mixture-based peptidic compounds can be developed not only for immunotherapeutic purposes in autoimmune diseases and cancer, but also in vaccine development. (C) 2003 Published by Elsevier Ltd. C1 NINDS, NIH, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. Mixture Sci Inc, San Diego, CA 92121 USA. Schering AG, SBU Therapeut, Berlin, Germany. RP Martin, R (reprint author), NINDS, NIH, Bldg 10,Room 5B16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. EM martinr@ninds.nih.gov NR 54 TC 7 Z9 7 U1 0 U2 1 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 FEB PY 2004 VL 40 IS 14-15 BP 1075 EP 1087 DI 10.1016/j.molimm.2003.11.006 PG 13 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 800BB UT WOS:000220002800014 ER PT J AU Grizot, S Buchanan, SK AF Grizot, S Buchanan, SK TI Structure of the OmpA-like domain of RmpM from Neisseria meningitidis SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; CELL-ENVELOPE; PEPTIDOGLYCAN; LIPOPROTEIN; SEQUENCE; PAL; INTEGRITY; SURFACE; MODELS AB RmpM is a putative peptidoglycan binding protein from Neisseria meningitidis that has been shown to interact with integral outer membrane proteins such as porins and TonB-dependent transporters. Here we report the 1.9 Angstrom crystal structure of the C-terminal domain of RmpM. The 150-residue domain adopts a betaalphabetaalphabetabeta fold, as first identified in Bacillus subtilis chorismate mutase. The C-terminal RmpM domain is homologous to the periplasmic, C-terminal domain of Escherichia coli OmpA; these domains are thought to be responsible for non-covalent interactions with peptidoglycan. From the structure of the OmpA-like domain of RmpM, we suggest a putative peptidoglycan binding site and identify residues that may be essential for binding. Both the crystal structure and solution experiments indicate that RmpM may exist as a dimer. This would promote more efficient peptidoglycan binding, by allowing RmpM to interact simultaneously with two glycan chains through its C-terminal, OmpA-like binding domain, while its (structurally uncharacterized) N-terminal domain could stabilize oligomers of porins and TonB-dependent transporters in the outer membrane. C1 NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDKD, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov NR 35 TC 91 Z9 91 U1 0 U2 6 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 FEB PY 2004 VL 51 IS 4 BP 1027 EP 1037 DI 10.1046/j.1365-2958.2003.03903.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 771CQ UT WOS:000188768300011 PM 14763978 ER PT J AU Toth, A Blumberg, PM Chen, ZL Kozikowski, AP AF Toth, A Blumberg, PM Chen, ZL Kozikowski, AP TI Design of a high-affinity competitive antagonist of the vanilloid receptor selective for the calcium entry-linked receptor population SO MOLECULAR PHARMACOLOGY LA English DT Article ID ROOT GANGLION NEURONS; PROTEIN-KINASE-C; ACTIVATED ION-CHANNEL; CAPSAICIN RECEPTOR; ANALGESIC AGENTS; AGONIST ACTIVITY; DIRECT PHOSPHORYLATION; NEUROPATHIC PAIN; VR1; ANALOGS AB We describe the synthesis and characterization of N-(4-chlorobenzyl) -N'-(4-hydroxy-3-iodo-5-methoxybenzyl) thiourea (IBTU), a novel antagonist of the vanilloid receptor 1 (TRPV1 or VR1). IBTU competitively inhibited Ca-45(2+) uptake into CHO cells heterologously expressing rat TRPV1, whether induced by capsaicin or resiniferatoxin (K-i = 99 +/- 23 and 93 +/- 34 nM, respectively). IBTU was thus somewhat more potent (5-fold) than capsazepine. In contrast to its antagonism of vanilloid-induced calcium uptake, IBTU (30 muM) inhibited [H-3] resiniferatoxin binding to TRPV1 by less than 10%. We hypothesize that these dramatically distinct potencies reflect different fractions of TRPV1 in this system: namely, a minor plasma membrane fraction controlling Ca-45(2+) uptake, and the predominant intracellular fraction that dominates the [H-3] resiniferatoxin binding measurements. Intracellular Ca2+ imaging supports this explanation. IBTU antagonized the elevation in intracellular Ca2+ in response to 50 nM capsaicin with an IC50 of 106 +/- 35 nM. Likewise, 600 nM IBTU was able to antagonize the elevation in intracellular Ca2+ in response to 100 pM resiniferatoxin in the presence of normal (1.8 mM) extracellular Ca2+, where the increase in intracellular calcium reflects calcium influx. In contrast, in the absence of extracellular Ca2+, where in this system resiniferatoxin induces a modest increase in calcium from intracellular stores, IBTU was unable to block the response to resiniferatoxin, although the TRPV1 antagonist 5-iodoresiniferatoxin was able to do so. In summary, IBTU is a novel, potent TRPV1 antagonist with marked selectivity between subpopulations of TRPV1 and may permit the function of these distinct pools to be explored and potentially exploited. C1 NCI, Mol Mech Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Med Chem & Pharmacol, Chicago, IL USA. RP Blumberg, PM (reprint author), NCI, Mol Mech Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Rm 4048,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 NR 46 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB 1 PY 2004 VL 65 IS 2 BP 282 EP 291 DI 10.1124/mol.65.2.282 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 766DH UT WOS:000188329800003 PM 14742669 ER PT J AU Knox, SS Wilk, JB Zhang, Y Weidner, G Ellison, RC AF Knox, SS Wilk, JB Zhang, Y Weidner, G Ellison, RC TI A genome scan for hostility: the national heart, lung, and blood institute family heart study SO MOLECULAR PSYCHIATRY LA English DT Letter ID LINKAGE ANALYSIS; BEHAVIORS; SEROTONIN; VARIANCE; DISEASE; TWINS C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Knox, SS (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Bldg 10, Bethesda, MD 20892 USA. EM knoxs@nhlbi.nih.gov OI Ellison, Robert Curtis/0000-0002-0582-7467; Zhang, Yuqing/0000-0001-7954-1149 NR 16 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD FEB PY 2004 VL 9 IS 2 BP 124 EP 126 DI 10.1038/sj.mp.4001447 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 774GN UT WOS:000188971600003 PM 14610523 ER PT J AU Dejneka, NS Surace, EM Aleman, TS Cideciyan, AV Lyubarsky, A Savchenko, A Redmond, TM Tang, WX Wei, ZY Rex, TS Glover, E Maguire, AM Pugh, EN Jacobson, SG Bennett, J AF Dejneka, NS Surace, EM Aleman, TS Cideciyan, AV Lyubarsky, A Savchenko, A Redmond, TM Tang, WX Wei, ZY Rex, TS Glover, E Maguire, AM Pugh, EN Jacobson, SG Bennett, J TI In utero gene therapy rescues vision in a murine model of congenital blindness SO MOLECULAR THERAPY LA English DT Article DE adeno-associated virus; retinal degeneration; retina; mouse model; gene therapy; neurodegeneration; in utero therapy; viral gene transfer; genetic disease; phototransduction ID CHILDHOOD BLINDNESS; FACTOR-IX; RPE65; VECTORS; AMAUROSIS; MUTATIONS; DELIVERY; EXPRESSION; RETINA; EPITHELIUM AB The congenital retinal blindness known as Leber congenital amaurosis (LCA) can be caused by mutations in the RPE65 gene. RPE65 plays a critical role in the visual cycle that produces the photosensitive pigment rhodopsin. Recent evidence from human studies of LCA indicates that earlier rather than later intervention may be more likely to restore vision. We determined the impact of in utero delivery of the human RPE65 cDNA to retinal pigment epithelium cells in a murine model of LCA, the Rpe65(-/-) mouse, using a serotype 2 adeno-associated virus packaged within an AAV1 capsid (AAV2/1). Delivery of AAV2/1-CMV-hRPE65 to fetuses (embryonic day 14) resulted in efficient transduction of retinal pigment epithelium, restoration of visual function, and measurable rhodopsin. The results demonstrate AAV-mediated correction of the deficit and suggest that in utero retinal gene delivery may be a useful approach for treating a variety of blinding congenital retinal diseases. C1 Univ Penn, FM Kirby Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Ophthalmol, Scheie Eye Inst, Philadelphia, PA 19104 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bennett, J (reprint author), Univ Penn, FM Kirby Ctr, 51 N 39th St, Philadelphia, PA 19104 USA. EM jebennet@mail.med.upenn.edu RI Cideciyan, Artur/A-1075-2007; OI Cideciyan, Artur/0000-0002-2018-0905; Surace, Enrico Maria/0000-0002-2975-942X; Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [F32-EY07065, EY02660, EY12156, EY13203, EY13385, R01 EY002660, R01 EY10820, U10EY013729]; NIDDK NIH HHS [5-P30-DK-47747-10] NR 31 TC 126 Z9 128 U1 0 U2 7 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 FEB PY 2004 VL 9 IS 2 BP 182 EP 188 DI 10.1016/j.ymthe.2003.11.013 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 774BY UT WOS:000188960900008 PM 14759802 ER PT J AU Bruno, MK Ravina, B Garraux, G Hallett, M Ptacek, L Singleton, A Johnson, J Singleton, A Hanson, M Considine, E Gwinn-Hardy, K AF Bruno, MK Ravina, B Garraux, G Hallett, M Ptacek, L Singleton, A Johnson, J Singleton, A Hanson, M Considine, E Gwinn-Hardy, K TI Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; familial; exercise-induced dystonia; parkin ID FOOT DYSTONIA; DIAGNOSIS; GAIT AB Paroxysmal exercise-induced dystonia can occur with Parkinson's disease (PD), and in rare cases, this can also be the presenting symptom. We report on 2 second cousins (no known consanguinity) who presented with paroxysmal exercise-induced dystonia who later developed clinical features of PD. Although autosomal recessive inheritance was suggested, and the dystonic features further suggest parkin as a possible cause, ssequencing for parkin mutations was negative and this family may represent a genetic variant of PD. Further genotype-phenotype studies in this and similar families may give clues to pre-symptomatic symptoms in PD and may reflect a particular phenotype of interest for genetics studies in the future. (C) 2004 Movement Disorder Society C1 NINDS, Parkinsons Unit, Div Neurogenet, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Howard Hughes Med Inst, Dept Neurol, San Francisco, CA 94143 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Bruno, MK (reprint author), Bldg 10,Room 5N226,9000 Rockville Pike,10 Ctr Dr,, Bethesda, MD 20892 USA. EM brunom@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009; Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; Garraux, Gaetan/G-9050-2011; OI Gwinn, Katrina/0000-0002-8277-651X FU PHS HHS [43533] NR 16 TC 8 Z9 8 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB PY 2004 VL 19 IS 2 BP 228 EP 230 DI 10.1002/mds.10626 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 777DR UT WOS:000189160700018 PM 14978684 ER PT J AU Evidente, VGH Cooper, C Gwinn-Hardy, K AF Evidente, VGH Cooper, C Gwinn-Hardy, K TI Limb cooling and focal dystonia SO MOVEMENT DISORDERS LA English DT Letter ID TEMPERATURE; MUSCLE C1 Mayo Clin, Dept Neurol, Scottsdale, AZ USA. Mayo Clin, Occupat Therapy Sect, Scottsdale, AZ USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Evidente, VGH (reprint author), Mayo Clin, Dept Neurol, Scottsdale, AZ USA. RI Gwinn, Katrina/C-2508-2009; OI Gwinn, Katrina/0000-0002-8277-651X NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD FEB PY 2004 VL 19 IS 2 BP 238 EP 238 DI 10.1002/mds.10673 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 777DR UT WOS:000189160700021 PM 14978687 ER PT J AU Faulkner, DJ Newman, DJ Cragg, GM AF Faulkner, DJ Newman, DJ Cragg, GM TI Investigations of the marine flora and fauna of the Islands of Palau SO NATURAL PRODUCT REPORTS LA English DT Review ID BEE VENOM PHOSPHOLIPASE-A2; CYANOBACTERIUM SYMPLOCA-SP; AUSTRALIAN SOFT CORALS; SPONGE LUFFARIELLA SP; TUNICATE LISSOCLINUM-PATELLA; ASCIDIAN DIDEMNUM SP; NATURAL-PRODUCTS; ANTINEOPLASTIC AGENTS; THEONELLA-SWINHOEI; AXINYSSA-APLYSINOIDES AB The Islands of Palau have proven to be an excellent source of bioactive marine natural products primarily as a result of the systematic studies from the late 1970s by the research groups of Scheuer at the University of Hawaii, Faulkner at the Scripps Oceanographic Institution/University of California at San Diego, and Paul at the University of Guam. Their efforts were materially aided by the excellent facilities provided by the Government of Palau and for the last 10 years, those of the NCI's shallow water collection contractor, the Coral Reef Research Foundation. This review covers the structures and biological activities where noted, of the multitudinous marine-derived natural products isolated from the marine flora and fauna of this nation and demonstrates the enormous variety of novel structures elaborated by these organisms. C1 NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, POB B, Frederick, MD 21702 USA. EM dn22a@nih.gov NR 155 TC 17 Z9 19 U1 2 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 J9 NAT PROD REP JI Nat. Prod. Rep. PD FEB PY 2004 VL 21 IS 1 BP 50 EP 76 DI 10.1039/b300664f PG 27 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 803TP UT WOS:000220253700004 ER PT J AU Powers, MA Dasso, M AF Powers, MA Dasso, M TI Nuclear transport erupts on the slopes of Mount Etna SO NATURE CELL BIOLOGY LA English DT Editorial Material ID PORE COMPLEX; EXPORT; MECHANISM; CELLS; RCC1; RAN AB Nuclear pore complexes (NPCs) mediate the active transport of large substrates and allow the passive diffusion of small molecules into the nucleus of eukaryotic cells. The EMBO Workshop on the Mechanisms of Nuclear Transport focused on NPCs and on the soluble nucleocytoplasmic transport machinery. This meeting, organized by Valerie Doye (Institut Curie, Paris) and Ed Hurt ( University of Heidelberg), was held within view of Mount Etna at Taormina, Sicily ( November 1 - 5, 2003). Presentations emphasized the dynamic properties of the nuclear trafficking machinery, and demonstrated the continuity of nuclear transport with processes in the nucleus and cytoplasm. C1 Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA. NICHD, NIH, LGRD, Bethesda, MD 20892 USA. RP Powers, MA (reprint author), Emory Univ, Sch Med, Dept Cell Biol, 455 whitehead Bldg,615 Michael St, Atlanta, GA 30322 USA. EM mpowers@cellbio.emory.edu; mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 NR 26 TC 10 Z9 11 U1 0 U2 0 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 FEB PY 2004 VL 6 IS 2 BP 82 EP 86 DI 10.1038/ncb0204-82 PG 5 WC Cell Biology SC Cell Biology GA 769UN UT WOS:000188668300002 PM 14755266 ER PT J AU Sedelnikova, OA Horikawa, I Zimonjic, DB Popescu, NC Bonner, WM Barrett, JC AF Sedelnikova, OA Horikawa, I Zimonjic, DB Popescu, NC Bonner, WM Barrett, JC TI Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks SO NATURE CELL BIOLOGY LA English DT Article ID IN-VIVO; CELLULAR SENESCENCE; HISTONE H2AX; DAMAGE; GAMMA-H2AX; TELOMERASE; MOUSE; FOCI AB Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear(1,2). Here we show that gamma-H2AX foci (gamma-foci), which reveal DNA double-strand breaks (DSBs)(3,4), accumulate in senescing human cell cultures and in ageing mice. They colocalize with DSB repair factors, but not significantly with telomeres. These cryptogenic gamma-foci remain after repair of radiation-induced gamma-foci, suggesting that they may represent DNA lesions with unrepairable DSBs. Thus, we conclude that accumulation of unrepairable DSBs may have a causal role in mammalian ageing. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM bonnerw@mail.nih.gov NR 15 TC 390 Z9 404 U1 0 U2 24 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 FEB PY 2004 VL 6 IS 2 BP 168 EP + DI 10.1038/ncb1095 PG 4 WC Cell Biology SC Cell Biology GA 769UN UT WOS:000188668300017 PM 14755273 ER PT J AU Muppidi, JR Siegel, RM AF Muppidi, JR Siegel, RM TI Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death SO NATURE IMMUNOLOGY LA English DT Article ID KAPPA-B ACTIVATION; SIGNALING COMPLEX; LYMPHOCYTE APOPTOSIS; IN-VIVO; BCL-2; MICRODOMAINS; MECHANISM; RESPONSES; PATHWAYS; LIVE AB Clonotypic elimination of activated T cells through Fas-Fas ligand (CD95-CD95L) interactions is one mechanism of peripheral self-tolerance. T cell receptor (TCR) stimuli trigger FasL synthesis but also sensitize activated T cells to Fas-mediated apoptosis through an unknown mechanism. Here we show that TCR restimulation of activated human CD4(+) T cells resulted in Fas translocation into lipid raft microdomains before binding FasL, rendering these cells sensitive to apoptosis after stimulation with bivalent antibody or FasL. Disruption of lipid rafts reduced sensitivity to Fas-mediated apoptosis after TCR restimulation. Thus, the redistribution of Fas and other tumor necrosis factor family receptors into and out of lipid rafts may dynamically regulate the efficiency and outcomes of signaling by these receptors. C1 NIAMSD, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAMSD, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU NIEHS NIH HHS [5T32 ES 007079] NR 34 TC 152 Z9 162 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 FEB PY 2004 VL 5 IS 2 BP 182 EP 189 DI 10.1038/ni1024 PG 8 WC Immunology SC Immunology GA 768DB UT WOS:000188512000014 PM 14745445 ER PT J AU Nabel, GJ AF Nabel, GJ TI Genetic, cellular and immune approaches to disease therapy: past and future SO NATURE MEDICINE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC LYMPHOCYTIC-LEUKEMIA; T-CELL; RHEUMATOID-ARTHRITIS; DNA VACCINES; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; VIRUS-INFECTION; STEM-CELLS; FACTOR-IX AB Advances in immunology and molecular genetics have accelerated our understanding of the genetic and cellular basis of many diseases. At the same time, remarkable progress in recombinant DNA technology has enabled the development of molecular and cellular treatments for infectious diseases, inherited disorders and cancer. This Perspective is intended to give a sample of the progress over the past ten years in cellular, genetic and immune therapy of disease. During this time, monoclonal antibody technology and cellular transplantation have begun to come of age in biomedicine. Innovations in gene delivery have not only catalyzed the nascent field of human gene therapy, but may also ultimately impact human health by advancing recombinant vaccine technology. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 69 TC 54 Z9 54 U1 6 U2 12 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 FEB PY 2004 VL 10 IS 2 BP 135 EP 141 DI 10.1038/nm990 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 770JN UT WOS:000188719600030 PM 14760423 ER PT J AU Willett, CG Boucher, Y di Tomaso, E Duda, DG Munn, LL Tong, RT Chung, DC Sahani, DV Kalva, SP Kozin, SV Mino, M Cohen, KS Scadden, DT Hartford, AC Fischman, AJ Clark, JW Ryan, DP Zhu, AX Blaszkowsky, LS Chen, HX Shellito, PC Lauwers, GY Jain, RK AF Willett, CG Boucher, Y di Tomaso, E Duda, DG Munn, LL Tong, RT Chung, DC Sahani, DV Kalva, SP Kozin, SV Mino, M Cohen, KS Scadden, DT Hartford, AC Fischman, AJ Clark, JW Ryan, DP Zhu, AX Blaszkowsky, LS Chen, HX Shellito, PC Lauwers, GY Jain, RK TI Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS; THERAPY; CELLS AB The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, AIDS Res Ctr Expt Hematol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NCI, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [P01 CA080124-089001, P01 CA080124, P01 CA080124-01A10002, P01 CA080124-01A19001, P01 CA080124-01A1S10002, P01 CA080124-01A1S19001, P01 CA080124-020002, P01 CA080124-029001, P01 CA080124-030002, P01 CA080124-039001, P01 CA080124-040002, P01 CA080124-049001, P01 CA080124-050002, P01 CA080124-059001, P01 CA080124-06A20006, P01 CA080124-06A29001, P01 CA080124-070006, P01 CA080124-079001, P01 CA080124-080006, P01 CA80124, R21 CA099237, R21 CA099237-02] NR 15 TC 1251 Z9 1329 U1 8 U2 75 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 FEB PY 2004 VL 10 IS 2 BP 145 EP 147 DI 10.1038/nm988 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 770JN UT WOS:000188719600032 PM 14745444 ER PT J AU Inoue, H Ogawa, W Ozaki, M Haga, S Matsumoto, M Furukawa, K Hashimoto, N Kido, Y Mori, T Sakaue, H Teshigawara, K Jin, SY Iguchi, H Hiramatsu, R LeRoith, D Takeda, K Akira, S Kasuga, M AF Inoue, H Ogawa, W Ozaki, M Haga, S Matsumoto, M Furukawa, K Hashimoto, N Kido, Y Mori, T Sakaue, H Teshigawara, K Jin, SY Iguchi, H Hiramatsu, R LeRoith, D Takeda, K Akira, S Kasuga, M TI Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo SO NATURE MEDICINE LA English DT Article ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; INSULIN SENSITIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-INTOLERANCE; COACTIVATOR PGC-1; RAT HEPATOCYTES; TRANSGENIC MICE; INTERLEUKIN-6; EXPRESSION; LIVER AB The transcription factor, signal transducer and activator of transcription-3 (STAT-3) contributes to various physiological processes. Here we show that mice with liver-specific deficiency in STAT-3, achieved using the Cre-loxP system, show insulin resistance associated with increased hepatic expression of gluconeogenic genes. Restoration of hepatic STAT-3 expression in these mice, using adenovirus-mediated gene transfer, corrected the metabolic abnormalities and the alterations in hepatic expression of gluconeogenic genes. Overexpression of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression independently of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), an upstream regulator of gluconeogenic genes. Liver-specific expression of a constitutively active form of STAT-3, achieved by infection with an adenovirus vector, markedly reduced blood glucose, plasma insulin concentrations and hepatic gluconeogenic gene expression in diabetic mice. Hepatic STAT-3 signaling is thus essential for normal glucose homeostasis and may provide new therapeutic targets for diabetes mellitus. C1 Kobe Univ, Grad Sch Med, Div Diabet & Digest & Kidney Dis, Dept Clin Mol Med, Kobe, Hyogo 6500017, Japan. Natl Res Inst Child Hlth & Dev, Dept Onnovat Surg, Bioengn Lab, Tokyo 1548567, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Food & Hlth Sci, Okayama 7008558, Japan. Sumitomo Pharmaceut Co Ltd, Genom Sci Labs, Takarazuka, Hyogo 6650051, Japan. NIDDKD, Sect Mol & Cellular Physiol, Diabet Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka 5650871, Japan. RP Kasuga, M (reprint author), Kobe Univ, Grad Sch Med, Div Diabet & Digest & Kidney Dis, Dept Clin Mol Med, Kobe, Hyogo 6500017, Japan. EM kasuga@med.kobe-u.ac.jp RI Akira, Shizuo/C-3134-2009; Takeda, Kiyoshi/C-9331-2009 NR 37 TC 202 Z9 205 U1 1 U2 15 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 FEB PY 2004 VL 10 IS 2 BP 168 EP 174 DI 10.1038/nm980 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 770JN UT WOS:000188719600036 PM 14716305 ER PT J AU Yu, YL Khan, J Khanna, C Helman, L Meltzer, PS Merlino, G AF Yu, YL Khan, J Khanna, C Helman, L Meltzer, PS Merlino, G TI Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators SO NATURE MEDICINE LA English DT Article ID GENE-EXPRESSION; ERM PROTEINS; CELL-ADHESION; VERTEBRATE MUSCLE; CDNA MICROARRAYS; TUMOR-SUPPRESSOR; RHO-GTPASES; MODEL; RHABDOMYOSARCOMA; PHOSPHORYLATION AB Patients presenting with metastatic rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, have a very poor clinical prognosis. This is due, in large part, to our rudimentary knowledge of the molecular events that dictate metastatic potential. We used cDNA microarray analysis of RMS cell lines, derived from Ink4a/Arf-deficient mice transgenic for hepatocyte growth factor/scatter factor (HGF/SF), to identify a set of genes whose expression was significantly different between highly and poorly metastatic cells. Subsequent in vivo functional studies revealed that the actin filament-plasma membrane linker ezrin (encoded by Vil2) and the homeodomain-containing transcription factor Six-1 (sine oculis-related homeobox-1 homolog) had essential roles in determining the metastatic fate of RMS cells. VIL2 and SIX1 expression was enhanced in human RMS tissue, significantly correlating with clinical stage. The identification of ezrin and Six-1 as critical regulators of metastasis in RMS provides new mechanistic and therapeutic insights into this pediatric cancer. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 45 TC 334 Z9 423 U1 0 U2 8 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 FEB PY 2004 VL 10 IS 2 BP 175 EP 181 DI 10.1038/nm966 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 770JN UT WOS:000188719600037 PM 14704789 ER PT J AU Khanna, C Wan, XL Bose, S Cassaday, R Olomu, O Mendoza, A Yeung, C Gorlick, R Hewitt, SM Helman, LJ AF Khanna, C Wan, XL Bose, S Cassaday, R Olomu, O Mendoza, A Yeung, C Gorlick, R Hewitt, SM Helman, LJ TI The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis SO NATURE MEDICINE LA English DT Article ID CANCER METASTASIS; PLASMA-MEMBRANE; CELLS; INEFFICIENCY; APOPTOSIS; SURVIVAL; PATHWAY; BINDING; MERLIN; TUMORS AB Metastatic cancers, once established, are the primary cause of mortality associated with cancer. Previously, we used a genomic approach to identify metastasis-associated genes in cancer 1. From this genomic data, we selected ezrin for further study based on its role in physically and functionally connecting the actin cytoskeleton to the cell membrane 2. In a mouse model of osteosarcoma, a highly metastatic pediatric cancer, we found ezrin to be necessary for metastasis. By imaging metastatic cells in the lungs of mice, we showed that ezrin expression provided an early survival advantage for cancer cells that reached the lung. AKT and MAPK phosphorylation and activity were reduced when ezrin protein was suppressed. Ezrin-mediated early metastatic survival was partially dependent on activation of MAPK, but not AKT. To define the relevance of ezrin in the biology of metastasis, beyond the founding mouse model, we examined ezrin expression in dogs that naturally developed osteosarcoma. High ezrin expression in dog tumors was associated with early development of metastases. Consistent with this data, we found a significant association between high ezrin expression and poor outcome in pediatric osteosarcoma patients. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tissue Array Project Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Khanna, C (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 NR 27 TC 448 Z9 547 U1 7 U2 46 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 FEB PY 2004 VL 10 IS 2 BP 182 EP 186 DI 10.1038/nm982 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 770JN UT WOS:000188719600038 PM 14704791 ER PT J AU Nicot, C Dundr, M Johnson, JM Fullen, JR Alonzo, N Fukumoto, R Princler, GL Derse, D Misteli, T Franchini, G AF Nicot, C Dundr, M Johnson, JM Fullen, JR Alonzo, N Fukumoto, R Princler, GL Derse, D Misteli, T Franchini, G TI HTLV-1-encoded p30(II) is a post-transcriptional negative regulator of viral replication SO NATURE MEDICINE LA English DT Article ID VIRUS TYPE-I; HTLV-I; LYMPHOTROPIC VIRUS; GENE-EXPRESSION; PX; PROTEINS; CELLS; TAX; REV; RNA AB Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) persists despite a vigorous virus-specific host immune response, and causes adult T-cell leukemia and lymphoma in approximately 2% of infected individuals. Here we report that HTLV-1 has evolved a genetic function to restrict its own replication by a novel post-transcriptional mechanism. The HTLV-1-encoded p30(II) is a nuclear-resident protein that binds to, and retains in the nucleus, the doubly spliced mRNA encoding the Tax and Rex proteins. Because Tex and Rex are positive regulators of viral gene expression(1,2), their inhibition by p30(II) reduces virion production. p30(II) inhibits virus expression by reducing Tax and Rex protein expression. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 30 TC 119 Z9 127 U1 0 U2 0 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 FEB PY 2004 VL 10 IS 2 BP 197 EP 201 DI 10.1038/nm984 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 770JN UT WOS:000188719600041 PM 14730358 ER PT J AU Richmond, B Wiener, M AF Richmond, B Wiener, M TI Recruitment order: a powerful neural ensemble code SO NATURE NEUROSCIENCE LA English DT Editorial Material ID CORTEX C1 NIMH, NIH, Bethesda, MD 20892 USA. Merck Res Labs, Dept Appl Math & Comp Sci, Rahway, NJ 07065 USA. RP Richmond, B (reprint author), NIMH, NIH, Bldg 49,Rm 1B 80,49 Convent Dr, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov NR 11 TC 1 Z9 2 U1 0 U2 1 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 FEB PY 2004 VL 7 IS 2 BP 97 EP 98 DI 10.1038/nn0204-97 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 767TJ UT WOS:000188468500002 PM 14747828 ER PT J AU Umar, A Risinger, JI Hawk, ET Barrett, JC AF Umar, A Risinger, JI Hawk, ET Barrett, JC TI Guidelines - Testing guidelines for hereditary non-polyposis colorectal cancer SO NATURE REVIEWS CANCER LA English DT Editorial Material ID MICROSATELLITE INSTABILITY; COLON-CANCER; GERMLINE MUTATIONS; CELL-LINES; GENE; CARCINOMA; HOMOLOG; ENDOMETRIAL; POLYPOSIS; DIAGNOSIS AB Hereditary non-polyposis colorectal cancer is almost always associated with microsatellite instability, so what is the best way to identify the disorder at an early-stage, and what should the next step be in preventing the development of colorectal cancer? Different clinical and molecular diagnostic guidelines have recently been proposed in the context of recent scientific advances, but how are these criteria interpreted and modified across the world? C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Umar, A (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM Asad.Umar@nih.gov NR 40 TC 101 Z9 105 U1 1 U2 3 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 FEB PY 2004 VL 4 IS 2 BP 153 EP 158 DI 10.1038/nrc1278 PG 7 WC Oncology SC Oncology GA 768ZF UT WOS:000188600800016 PM 14964310 ER PT J AU Alayash, AI AF Alayash, AI TI Oxygen therapeutics: Can we tame haemoglobin? SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; TRAUMATIC HEMORRHAGIC-SHOCK; MYOGLOBIN REDOX CYCLE; NITRIC-OXIDE; BLOOD SUBSTITUTE; HYDROGEN-PEROXIDE; HEME DEGRADATION; POLYOXYETHYLENE CONJUGATE; RECOMBINANT HEMOGLOBIN AB Chemically modified or genetically engineered haemoglobins (Hbs) developed as oxygen therapeutics (often termed 'blood substitutes') are designed to correct oxygen deficit due to ischaemia in a variety of clinical settings. These modifications are intended to stabilize Hb outside its natural environment - red blood cells - in a functional tetrameric and/or polymeric form. Uncontrolled haem-mediated oxidative reactions of cell-free Hb and its reactions with various oxidant/antioxidant and cell signalling systems have emerged as an important pathway of toxicity. Current protective strategies designed to produce safe Hb-based products are focused on controlling or suppressing the 'radical' nature of Hb while retaining its oxygen-carrying function. C1 US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 8800 Rockville Pike,NIH Bldg 29,Room 112, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 85 TC 176 Z9 183 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD FEB PY 2004 VL 3 IS 2 BP 152 EP 159 DI 10.1038/nrd1307 PG 8 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 768ZP UT WOS:000188601800013 PM 15043006 ER PT J AU Taylor, GA Feng, CG Sher, A AF Taylor, GA Feng, CG Sher, A TI P47 GTPases: Regulators of immunity to intracellular pathogens SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HUMAN MXA PROTEIN; INDUCIBLY EXPRESSED GTPASE; NITRIC-OXIDE SYNTHASE; INTERFERON-GAMMA; IFN-GAMMA; TOXOPLASMA-GONDII; ENDOPLASMIC-RETICULUM; BINDING PROTEIN; MURINE CYTOMEGALOVIRUS; LISTERIA-MONOCYTOGENES AB Activation of the innate immune system by interferon-gamma (IFN-gamma) is crucial for host resistance to infection. IFN-gamma induces the expression of a wide range of mediators that undermine the ability of pathogens to survive in host cells, including a newly discovered family of 47-kDa GTPases. Elimination of different p47 GTPases in mice by gene targeting severely cripples IFN-gamma-regulated defence against Toxoplasma gondii, Listeria monocytogenes, Mycobacterium spp. and other pathogens. In this article, we review our understanding of the role of p47 GTPases in resistance to intracellular infection and discuss the present evidence concerning their mode of action. C1 Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Immunol, Div Geriatr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Vet Adm Med Ctr, Durham, NC 27705 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Taylor, GA (reprint author), Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. EM gregory.taylor@duke.edu FU NIAID NIH HHS [R01 AI057831] NR 77 TC 178 Z9 190 U1 2 U2 5 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 FEB PY 2004 VL 4 IS 2 BP 100 EP 109 DI 10.1038/nri1270 PG 10 WC Immunology SC Immunology GA 768ZU UT WOS:000188602200012 PM 15040583 ER PT J AU Dimitrov, DS AF Dimitrov, DS TI Virus entry: Molecular mechanisms and biomedical applications SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID RESPIRATORY SYNCYTIAL VIRUS; SEMLIKI-FOREST-VIRUS; FUSION-INACTIVE CONFORMATION; VESICULAR STOMATITIS-VIRUS; VIRAL MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; LOW-PH; RECEPTOR-BINDING; ENVELOPE GLYCOPROTEIN; HIV-1 ENTRY AB Viruses have evolved to enter cells from all three domains of life - Bacteria, Archaea and Eukaryotes. Of more than 3,600 known viruses, hundreds can infect human cells and most of those are associated with disease. To gain access to the cell interior, animal viruses attach to host-cell receptors. Advances in our understanding of how viral entry proteins interact with their host-cell receptors and undergo conformational changes that lead to entry offer unprecedented opportunities for the development of novel therapeutics and vaccines. C1 NCI, Human Immunovirol & Computat Biol Grp, Lab Expt & Computat Biol, Ctr Canc Res, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Human Immunovirol & Computat Biol Grp, Lab Expt & Computat Biol, Ctr Canc Res, Bldg 469,Room 246,Miller Dr, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov NR 111 TC 203 Z9 212 U1 16 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD FEB PY 2004 VL 2 IS 2 BP 109 EP 122 DI 10.1038/nrmicro817 PG 14 WC Microbiology SC Microbiology GA 806KB UT WOS:000220431700014 PM 15043007 ER PT J AU Oz, M Zakharova, I Dinc, M Shippenberg, T AF Oz, M Zakharova, I Dinc, M Shippenberg, T TI Cocaine inhibits cromakalim-activated K+ currents in follicle-enclosed Xenopus oocytes SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE cocaine; cromakalim; K-ATP channels; Xenopus oocyte ID VASCULAR SMOOTH-MUSCLE; SENSITIVE POTASSIUM CHANNELS; CEREBRAL ARTERIOLES; RAT CARDIOMYOCYTES; LAEVIS OOCYTES; MECHANISM; RECEPTOR; DISPOSITION; BLOCKADE; OPENERS AB The effect of cocaine on K+ currents activated by the K-ATP channel opener cromakalim was investigated in follicular cells of Xenopus oocytes. The results indicate that cocaine in the concentration range of 3-500 muM reversibly inhibits cromakalim-induced K+ currents. The IC50 value for cocaine was 96 muM. Inhibition of the cromakalim-activated K+ current by cocaine was noncompetitive and voltage independent. Pretreatment with the Ca2+ chelator BAPTA did not modify the cocaine-induced inhibition of cromakalim-induced K+ currents, suggesting that Ca2+-activated second messenger pathways are not involved in the actions of cocaine. Outward K+ currents activated by the application of 8-Br-cAMP or forskolin were also inhibited by cocaine. The EC50 and slope values for the activation of K+ currents by cromakalim were 184+/-19 muM and 1.14 in the absence of cocaine as compared to 191+/-23 muM and 1.03 in the presence of cocaine (300 muM). Cocaine also blocked K+ currents mediated through C-terminally deleted form of Kir6.2 (KirDeltaC26) in the absence of sulfonylurea receptor with an IC50 value of 87 muM, suggesting that cocaine interacts directly with the channel forming Kir6.2 subunit. Radioligand binding studies indicated that cocaine (100 muM) did not affect the binding characteristics of the K-ATP ligand, [H-3]glibenclamide. These results demonstrate that cromakalim-activated K+ currents in follicular cells of Xenopus oocytes are modulated by cocaine. C1 Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. Integrat Neurosci Sect, Baltimore, MD 21224 USA. Oncol Hosp, Dept Pulm Dis, TR-06947 Ankara, Turkey. RP Oz, M (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 47 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD FEB PY 2004 VL 369 IS 2 BP 252 EP 259 DI 10.1007/s00210-003-0838-9 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 772HK UT WOS:000188836400016 PM 14652711 ER PT J AU Zoia, C Cogliati, T Tagliabue, E Cavaletti, G Sala, G Galimberti, G Rivolta, I Rossi, V Frattola, L Ferrarese, C AF Zoia, C Cogliati, T Tagliabue, E Cavaletti, G Sala, G Galimberti, G Rivolta, I Rossi, V Frattola, L Ferrarese, C TI Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE human peripheral marker; EAAT2; EAAT3; molecular characterization; excitotoxicity; glutamate uptake ID AMYOTROPHIC-LATERAL-SCLEROSIS; CULTURED HUMAN FIBROBLASTS; CELL-SURFACE EXPRESSION; PRECURSOR PROTEIN FORMS; AMINO-ACID TRANSPORTER; PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASE; NONNEURONAL TISSUES; MOTOR CORTEX; RAT-BRAIN AB Platelets release glutamate upon activation and are an important clearance system of the amino acid from blood, through high-affinity glutamate uptake, similar to that described in brain synaptosomes. Since platelet glutamate uptake is decreased in neurodegenerative disorders, we performed a morphological and molecular characterization of platelet glutamate transporters. The three major brain glutamate transporters EAAT1, EAAT2 and EAAT3 are expressed in platelets, with similar molecular weight, although at lower density than brain. A Na+-dependent-high-affinity glutamate uptake was competitively inhibited by known inhibitors but not by dihydrokainic acid, suggesting platelet EAAT2 does not play a major role in glutamate uptake at physiological conditions. We observed decreased glutamate uptake V-max, without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction compared to age-matched controls, which could explain the decrease of platelet uptake previously described. Platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neuropsychiatric disorders. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Milano Bicocca, Neurobiol Lab, Dept Neurosci & Biomed Technol, I-20052 Monza, MI, Italy. NCI, Med Branch, NIH, Bethesda, MD 20088 USA. S Maugeri Fdn, I-27100 Pavia, Italy. Univ Milano Bicocca, Dept Pediat, I-20052 Monza, MI, Italy. E medea Sci Inst, I-23842 Bosisio Parini, LC, Italy. RP Ferrarese, C (reprint author), Univ Milano Bicocca, San Gerardo Hosp, Neurobiol Lab, Dept Neurosci & Biomed Technol, Via Donizetti 106, I-20052 Monza, MI, Italy. EM carlo.ferrarese@unimib.it OI Sala, Gessica/0000-0003-3573-7523 NR 57 TC 54 Z9 56 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 FEB PY 2004 VL 25 IS 2 BP 149 EP 157 DI 10.1016/S0197-4580(03)00085-X PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 772LU UT WOS:000188844200002 PM 14749132 ER PT J AU Matochik, JA Chefer, SI Lane, MA Roth, GS Mattison, JA London, ED Ingram, DK AF Matochik, JA Chefer, SI Lane, MA Roth, GS Mattison, JA London, ED Ingram, DK TI Age-related decline in striatal volume in rhesus monkeys: assessment of long-term calorie restriction SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; calorie restriction; caudate nucleus; magnetic resonance imaging; putamen; striatum; volumetric ID DIETARY RESTRICTION; NONHUMAN-PRIMATES; OXIDATIVE STRESS; BRAIN; MRI; RECEPTORS; DISEASE; NUCLEI; ATLAS; SIZE AB Using magnetic resonance imaging (MRI), we measured striatal volume in 22 male rhesus monkeys undergoing calorie restriction (CR) for 11-13 years and 38 monkeys who were fed ad libitum (CON). CR delays the onset of many age-related processes, and this study tested whether it would alter the age-related decline in striatal volume. The CON and CR groups were sub-divided into middle age (less than 24 years old) and old age groups. Contrary to expectation, volumes of the putamen (not the caudate nucleus) were larger bilaterally in the CON than in the CR group both at middle age and senescence. Regression analysis (region volume versus age) indicated bilateral age-related declines in putamen and caudate nucleus volumes in the old CON monkeys, but only for the putamen in the old CR monkeys. Because tests for slopes found no differences between the groups, the data do not establish an effect of CR. Further study, involving sequential imaging, is warranted in order to clarify the possible effects of CR on age-related changes in striatal volume. (C) 2003 Elsevier Science Inc. All rights reserved. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Matochik, JA (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jmatochi@intra.nida.nih.gov NR 41 TC 15 Z9 18 U1 0 U2 3 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 FEB PY 2004 VL 25 IS 2 BP 193 EP 200 DI 10.1016/S0197-4580(03)00092-7 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 772LU UT WOS:000188844200007 PM 14749137 ER PT J AU Alexander, GE Chen, K Rice, HJ Reiman, EM Pietrini, P Lewis, DJ Porath, M Krasuski, JS Teichberg, D Teipel, SJ Hampel, H Rapoport, SI Schapiro, MB Grafman, J AF Alexander, GE Chen, K Rice, HJ Reiman, EM Pietrini, P Lewis, DJ Porath, M Krasuski, JS Teichberg, D Teipel, SJ Hampel, H Rapoport, SI Schapiro, MB Grafman, J TI Regional gray matter atrophy in frontotemporal dementia evaluated by voxel-based MRI morphometry SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 2nd Meeting of the Alzheimers Imaging Consortium CY JUL 20, 2002 CL STOCKHOLM, SWEDEN C1 Arizona State Univ, Tempe, AZ 85287 USA. Good Samaritan Reg Med Ctr, Phoenix, AZ USA. Univ Pisa, I-56100 Pisa, Italy. NIA, NIH, Bethesda, MD 20892 USA. Univ Munich, D-80539 Munich, Germany. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NINDS, NIH, Bethesda, MD 20892 USA. Arizona Alzheimers Res Ctr, Phoenix, AZ 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2004 VL 25 IS 2 MA 6 BP 244 EP 244 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 772LU UT WOS:000188844200018 ER PT J AU Lamar, M Yousem, DM Resnick, SM AF Lamar, M Yousem, DM Resnick, SM TI Orbital frontal aging: Evidence for early detection of cognitive changes using fMRI SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 2nd Meeting of the Alzheimers Imaging Consortium CY JUL 20, 2002 CL STOCKHOLM, SWEDEN C1 NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2004 VL 25 IS 2 MA 27 BP 254 EP 254 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 772LU UT WOS:000188844200039 ER PT J AU Resnick, SM Pham, DL Davatzikos, C Kraut, MA AF Resnick, SM Pham, DL Davatzikos, C Kraut, MA TI Sex differences in regional cerebral blood flow: Clinical implications for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 2nd Meeting of the Alzheimers Imaging Consortium CY JUL 20, 2002 CL STOCKHOLM, SWEDEN C1 NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bethesda, MD USA. NR 0 TC 5 Z9 5 U1 1 U2 1 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 FEB PY 2004 VL 25 IS 2 MA 47 BP 263 EP 263 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 772LU UT WOS:000188844200059 ER PT J AU Teipel, SJ Alexander, GE Pogarell, O Moller, HJ Schapiro, MB Rapoport, SJ Hampel, H AF Teipel, SJ Alexander, GE Pogarell, O Moller, HJ Schapiro, MB Rapoport, SJ Hampel, H TI In vivo mapping of neocortical neuronal degeneration in Alzheimer's disease - Studies of the corpus callosum with MRI, EEG and PET SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 2nd Meeting of the Alzheimers Imaging Consortium CY JUL 20, 2002 CL STOCKHOLM, SWEDEN ID WHITE-MATTER PATHOLOGY; ATROPHY; INDICATOR C1 Univ Munich, Dept Psychiat, Dementia & Neuroimaging Sect, D-8000 Munich, Germany. Univ Munich, Electrophysiol Sect, D-80539 Munich, Germany. Arizona State Univ, MRI Morphol Core, Arizona Alzheimers Dis Res Ctr, Tempe, AZ 85287 USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. Childrens Hosp, Med Ctr, Dept Pediat Neurol, Cincinnati, OH 45229 USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 7 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2004 VL 25 IS 2 MA 50 BP 264 EP 265 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 772LU UT WOS:000188844200062 ER PT J AU Wang, VN Chia, LG Ni, DR Cheng, JR Ho, YP Cheng, FC Hong, JS AF Wang, VN Chia, LG Ni, DR Cheng, JR Ho, YP Cheng, FC Hong, JS TI Effects of the combined treatment of naloxone and indomethacin on catecholamines and behavior after intranigral lipopolysaccharide injection SO NEUROCHEMICAL RESEARCH LA English DT Article DE naloxone; indomethacin; lipopolysaccharide; Parkinson's disease; catecholamines; behavior ID IDIOPATHIC PARKINSONS-DISEASE; LOCOMOTOR-ACTIVITY; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; C57BL/6 MICE; RATS; BRAIN; MICROGLIA; DAMAGE AB The present study examined effects of the combined administration of naloxone (NX) and indomethacin (IM) on nigrostriatal catecholamines and locomotor activity after intranigral lipopolysaccharide (LPS) injection in Sprague-Dawley rats. NX plus IM was given 3 days after LPS injection; it significantly (P < .05) reversed LPS inflammation on nigrostriatal dopamine (DA) and nigral serotonin (5-HT) and nigral homovanillic acid (HVA)/DA ratio and nigrostriatal 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio. It also tended to ameliorate the locomotor hyperactivity. However, NX plus IM given 30 min before LPS could not satisfactorily protect against LPS's damage both biochemically and behaviorally. These results reveal that NX plus IM may protect against LPS on DA, 5-HT, and motor function after LPS injection but not before. Thus it suggests that the combined treatment of NX and IM gives a potent therapy, but not prevention, of LPS-induced inflammation and also protect nigrostriatal dopaminergic and serotoninergic systems against LPS in rats. C1 Cardinal Tien Hosp, Neurol Sect, Hsintien 231, Taipei Hsien, Taiwan. Taichung Vet Gen Hosp, Neurol Sect, Taichung 407, Taiwan. Taichung Vet Gen Hosp, Dept Med Res, Taichung 407, Taiwan. Fu Jen Catholic Univ, Sch Med, Taipei 242, Taiwan. Natl Def Med Ctr, Grad Inst Med Sci, Taipei 114, Taiwan. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chia, LG (reprint author), Cardinal Tien Hosp, Neurol Sect, 362 Chung Cheng Rd, Hsintien 231, Taipei Hsien, Taiwan. EM lieganchia@hotmail.com NR 33 TC 10 Z9 11 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 2004 VL 29 IS 2 BP 341 EP 346 DI 10.1023/B:NERE.0000013736.80749.4b PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 769CZ UT WOS:000188610000002 PM 15002729 ER PT J AU Nitschke, JB Nelson, EE Rusch, BD Fox, AS Oakes, TR Davidson, RJ AF Nitschke, JB Nelson, EE Rusch, BD Fox, AS Oakes, TR Davidson, RJ TI Orbitofrontal cortex tracks positive mood in mothers viewing pictures of their newborn infants SO NEUROIMAGE LA English DT Article DE orbitofrontal cortex; positive emotion; infants; fMRI ID HUMAN BRAIN; NEURAL RESPONSES; NUCLEUS-ACCUMBENS; EMOTIONAL VALENCE; MONETARY REWARD; FUNCTIONAL MRI; LEFT AMYGDALA; ACTIVATION; COCAINE; ASYMMETRY AB Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Dept Psychiat, Waisman Ctr, WM Keck Lab Funct Brain Imaging & Behav, Madison, WI 53705 USA. Univ Wisconsin, Dept Psychol, Waisman Ctr, Lab Affect Neurosci, Madison, WI 53705 USA. NIMH, Sect Dev Affect Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Nitschke, JB (reprint author), Univ Wisconsin, Dept Psychiat, Waisman Ctr, WM Keck Lab Funct Brain Imaging & Behav, Room T-229,1500 Highland Ave, Madison, WI 53705 USA. EM jnitschke@wisc.edu RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU NIMH NIH HHS [K05-MH00875, K08-MH63984, MH40747, MH43454, P50-MH52354, T32-MH18931] NR 79 TC 171 Z9 177 U1 14 U2 25 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 2004 VL 21 IS 2 BP 583 EP 592 DI 10.1016/j.neuroimaging.2003.10.005 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 778QM UT WOS:000189252300010 PM 14980560 ER PT J AU Groschel, K Hauser, TK Luft, A Patronas, N Dichgans, J Litvan, I Schulz, JB AF Groschel, K Hauser, TK Luft, A Patronas, N Dichgans, J Litvan, I Schulz, JB TI Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration SO NEUROIMAGE LA English DT Article DE progressive supranuclear palsy; corticobasal degeneration; volumetric MRI ID MULTIPLE SYSTEM ATROPHY; RICHARDSON-OLSZEWSKI-SYNDROME; CLINICAL DIAGNOSTIC-CRITERIA; MRI-BASED VOLUMETRY; GANGLIONIC DEGENERATION; PARKINSONIAN DISORDERS; INTRACRANIAL VOLUME; BASAL GANGLIA; DISEASE; DEMENTIA AB Because there are no biological markers for the clinical diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), we established a mathematical model based on three-dimensional magnetic resonance (MR) imaging to differentiate between these parkinsonian disorders. Using MR imaging-based volumetry we studied the pattern of atrophic changes in patients with probable, possible or definite PSP (n = 33) or CBD (n = 18). Patients were compared with 22 controls with similar age. To establish a mathematical model that would allow for differentiation of PSP, CBD and controls we performed a discriminant analysis. We found a significant reduction in average brain, brainstem, midbrain and frontal gray matter volumes in patients with PSP, whereas patients with CBD showed atrophy of parietal cortex and corpus callosum. With the exception of reduced midbrain volumes in PSP, the measured volumes of anatomical structures showed an extensive overlap with the normal range on an individual basis. Using only post mortem confirmed cases of PSP (n = 8) and CBD (n = 7) as well as all controls, the volumes of midbrain, parietal white matter, temporal gray matter, brainstem, frontal white matter and pons were identified to separate best between groups and were used to construct a model with two canonical variables. This model allowed to correctly predict the diagnosis in 95% of controls as well as in 76% of all PSP and 83% of all CBD patients. Similar results were obtained only when patients with a possible and probable diagnosis of PSP and CBD, who were not involved in the development of the discriminant analysis, were classified. 3D-MR imaging-based volumetry may help to differentiate PSP from CBD ante mortem. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Tubingen, Dept Gen Neurol, Neurodegenerat Lab, Tubingen, Germany. Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany. NIH, Bethesda, MD 20892 USA. Univ Louisville, Sch Med, Dept Neurol, Louisville, KY 40292 USA. RP Schulz, JB (reprint author), Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM joerg.b.schulz@uni-tuebingen.de RI Schulz, Jorg/D-9786-2012; OI Schulz, Jorg/0000-0002-8903-0593; Groschel, Klaus/0000-0002-0244-6116; Litvan, Irene/0000-0002-3485-3445 NR 44 TC 70 Z9 70 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB PY 2004 VL 21 IS 2 BP 714 EP 724 DI 10.1016/j.neuroimage.2003.09.070 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 778QM UT WOS:000189252300024 PM 14980574 ER PT J AU Serkov, SV Pronin, IN Bykova, OV Maslova, OI Arutyunov, NV Muravina, TI Kornienko, VN Fadeeva, LM Marks, H Bonnemann, C Schiffmann, R van der Knaap, MS AF Serkov, SV Pronin, IN Bykova, OV Maslova, OI Arutyunov, NV Muravina, TI Kornienko, VN Fadeeva, LM Marks, H Bonnemann, C Schiffmann, R van der Knaap, MS TI Five patients with a recently described novel leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate SO NEUROPEDIATRICS LA English DT Article DE leukoencephalopathy; inherited; brainstem tracts; spinal tracts; lactate ID VANISHING WHITE-MATTER; INITIATION-FACTOR EIF2B; SCORING METHOD; MR; DISEASE; LEUKODYSTROPHY; CHILDREN; HYPOMYELINATION; DISORDERS; SUBUNITS AB Recently, a novel leukoencephalopathy syndrome was described in eight patients with a distinct pattern of MRI abnormalities. Here we describe the clinical, laboratory, and MRI findings in five new, unrelated patients. The clinical picture was homogeneous with onset in childhood, a slowly progressive course, variable mental deficits, signs of pyramidal and cerebellar dysfunction and sometimes dorsal column dysfunction. In two patients, a minor head trauma was followed by neurological deterioration and fever. No underlying metabolic defect was found. In two patients serum lactate was elevated, but no evidence of a mitochondrial defect was found. MRI showed variably extensive, diffuse, or spotty cerebral white matter abnormalities and a selective involvement of particular brainstem tracts. The tracts involved included the pyramidal tracts, sensory tracts, superior and inferior cerebellar peduncles, and intraparenchymal trajectories of the trigeminal nerve. In four patients spinal MRI was performed and revealed involvement of tracts over the entire length depicted. Single voxel proton MRS in three patients revealed increased lactate within the abnormal white matter. The uniform and highly characteristic MRI findings, in combination with the similarities in clinical and MRS findings, provide evidence for a distinct nosological entity. C1 Free Univ Amsterdam, Ctr Med, Dept Child Neurol, NL-1081 HV Amsterdam, Netherlands. Russian Acad Med Sci, Dept Neuroimaging, Burdenko Neurosurg Inst, Moscow, Russia. Ctr Child Hlth, Dept Psychoneurol, Moscow, Russia. Russian Acad Med Sci, Inst Neurol, Moscow, Russia. Childrens Hosp Philadelphia, Dept Child Neurol, Philadelphia, PA 19104 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP van der Knaap, MS (reprint author), Free Univ Amsterdam, Ctr Med, Dept Child Neurol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM ms.vanderknapp@vumc.nl NR 20 TC 23 Z9 25 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD FEB PY 2004 VL 35 IS 1 BP 1 EP 5 DI 10.1055/s-2003-43548 PG 5 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 803XM UT WOS:000220263800001 PM 15002045 ER PT J AU Patel, SA Warren, BA Rhoderick, JF Bridges, RJ AF Patel, SA Warren, BA Rhoderick, JF Bridges, RJ TI Differentiation of substrate and non-substrate inhibitors of transport system x(c)(-): an obligate exchanger of L-glutamate and L-cystine SO NEUROPHARMACOLOGY LA English DT Article DE excitatory amino acids; uptake; glutathione; quisqualate; S-4-carboxyphenylglycine; xCT ID AMINO-ACID-TRANSPORT; GLIOMA-CELLS; OXIDATIVE STRESS; HIGH-AFFINITY; PRIMARY CULTURE; GLIAL-CELLS; GLUTATHIONE; EXPRESSION; ASTROCYTES; BINDING AB In addition to the we 11-characterized sodium-dependent excitatory amino acid transporters (EAATs) present in the mammalian CNS, a chloride-dependent, sodium-independent transporter has also been identified that is capable of mediating the uptake of L-alutamate. Named system x(c)(-), this transporter is an obligate exchanger that normally couples the export of intracellular L-glutamate with the import of extracellular L-cystine. Two cell lines that express high levels of system x(c)(-) are used to delineate the pharmacology of the transporter and demonstrate that it is distinct from both the EAATs and EAA ionotropic receptors. Potent competitive inhibitors of system x(c)(-) include: L-homocysteate, ibotenate, L-serine-O-sulphate, (RS)-4-bromohomoibotenate, quisqualate, and (S)-4-carboxyphenyl-lycine. A fluorescent-based assay that allows system x-mediated exchange of L-glutamate and L-cystine to be C C followed in real time is used to assess substrate activity. Interestingly, those compounds that proved to be the most potent competitive inhibitors (e.g. L-quisqualate and 4-S-CPG) also proved to be the least active as substrates, suggesting that distinct structural features may control binding and translocation. Lastly, the finding that a number of system x, inhibitors are also commonly used as probes of excitotoxic pathology (e.g., L-quisqualate, ibotenate and L-homocysteate) raises some interesting questions regarding the mechanisms through which these analogues produce CNS damage. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. RP Bridges, RJ (reprint author), Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. EM bridgesr@selway.umt.edu FU NCRR NIH HHS [RR15583]; NINDS NIH HHS [NS30570] NR 46 TC 88 Z9 90 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD FEB PY 2004 VL 46 IS 2 BP 273 EP 284 DI 10.1016/j.neuropharm.2003.08.006 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 776FR UT WOS:000189106400013 PM 14680765 ER PT J AU Mead, AN Crombag, HS Rocha, BA AF Mead, AN Crombag, HS Rocha, BA TI Sensitization of psychomotor stimulation and conditioned reward in mice: Differential modulation by contextual learning SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE amphetamine; conditioning; reinforcer; locomotor activity; cues; drug addiction ID MEDIAL PREFRONTAL CORTEX; PAVLOVIAN APPROACH BEHAVIOR; D-AMPHETAMINE; NUCLEUS-ACCUMBENS; INTRAVENOUS COCAINE; INTRAACCUMBENS AMPHETAMINE; CROSS-SENSITIZATION; DOPAMINE-RECEPTORS; LOCOMOTOR-ACTIVITY; AMYGDALA AB Incentive motivation theory ascribes a critical role to reward-associated stimuli in the generation and maintenance of goal-directed behavior. Repeated psychomotor stimulant treatment, in addition to producing sensitization to the psychomotor-activating effects, can enhance the incentive salience of reward-associated cues and increase their ability to influence behavior. In the present study, we sought to investigate this incentive sensitization effect further by developing a model of conditioned reinforcement (CR) in the mouse and investigating the effects of a sensitizing treatment regimen of amphetamine on CR. Furthermore, we assessed the role of contextual stimuli in amphetamine-induced potentiation of CR. We found that mice responded selectively on a lever resulting in the presentation of a cue previously associated with 30% condensed milk solution, indicating that the cue had attained rewarding properties. Prior treatment with amphetamine (4 x 0.5 mg/kg i.p.) resulted in psychomotor sensitization and enhanced subsequent responding for the CR. Furthermore, this enhancement of responding for the cue occurred independent of the drug-paired context, whereas the sensitized locomotor response was only observed when mice were tested in the same environment as that in which they had received previous amphetamine. These results demonstrate that the CR paradigm previously developed in the rat can be successfully adapted for use in the mouse, and suggest that behavioral sensitization to amphetamine increases the rewarding properties (incentive salience) of reward-paired cues, independent of the drug-paired context. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD USA. RP Mead, AN (reprint author), Univ Sussex, Sch Biol Sci, Expt Psychol Lab, Brighton BN1 9QG, E Sussex, England. EM andym@biols.susx.ac.uk; hcrombag@umich.edu NR 59 TC 18 Z9 18 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 FEB PY 2004 VL 29 IS 2 BP 249 EP 258 DI 10.1038/sj.npp.1300294 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 771DD UT WOS:000188769600004 PM 12942147 ER PT J AU Marenco, S Carson, RE Berman, KF Herscovitch, P Weinberger, DR AF Marenco, S Carson, RE Berman, KF Herscovitch, P Weinberger, DR TI Nicotine-induced dopamine release in primates measured with [C-11]raclopride PET SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE nicotine; dopamine release; primates; anesthesia; schizophrenia ID POSITRON-EMISSION-TOMOGRAPHY; RAT PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; IN-VIVO BINDING; C-11 RACLOPRIDE; SYNAPTIC-TRANSMISSION; ACETYLCHOLINE-RECEPTORS; CONTINUOUS-INFUSION; CIGARETTE-SMOKING; HUMAN-BRAIN AB Nicotine-induced dopamine (DA) release constitutes a pharmacological probe of the DA system that has potential use in patients with schizophrenia, who have abnormally elevated DA release after amphetamine administration and possibly abnormalities in nicotinic signaling, We performed positron emission tomography studies in five rhesus monkeys that received i.v. nicotine doses ranging from 0.01 to 0.06 mg/kg. [C-11]raclopride was administered with either a bolus plus constant infusion or with paired bolus injections. The dynamics of D-2-binding potential (BP) after nicotine administration were studied and compared to amphetamine. Nicotine caused a significant albeit small reduction (5%, p < 0.03) in,BP, regardless of methodology of tracer administration. This effect disappeared 2.5 h after nicotine administration. Amphetamine caused much larger and prolonged displacement of [C-11]raclopride as compared to nicotine. There was no correlation between changes in BP and nicotine dose or plasma level. Regional differences in the nicotine effect within the basal ganglia were not found. Our data are consistent with the increase in DA detected with microdialysis in animals after acute nicotine administration. however, a larger effect size would be desirable to attempt studies comparing human smokers with and without schizophrenia. C1 NIMH, Clin Brain Disorders Branch, IRP, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD USA. RP Marenco, S (reprint author), NIMH, Clin Brain Disorders Branch, IRP, 10 Ctr Dr,Room 4S235, Bethesda, MD 20892 USA. EM marencos@intra.nimh.nih.gov RI Marenco, Stefano/A-2409-2008; Carson, Richard/H-3250-2011 OI Marenco, Stefano/0000-0002-2488-2365; Carson, Richard/0000-0002-9338-7966 NR 66 TC 43 Z9 44 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2004 VL 29 IS 2 BP 259 EP 268 DI 10.1038/sj.npp.1300287 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 771DD UT WOS:000188769600005 PM 14666115 ER PT J AU Cohen, JE Fields, RD AF Cohen, JE Fields, RD TI Extracellular calcium depletion in synaptic transmission SO NEUROSCIENTIST LA English DT Article DE cadherin; calcium-sensitive receptor CaMKII; extracellular calcium; long-term potentiation; synaptic plasticity ID METABOTROPIC GLUTAMATE RECEPTORS; CELL-ADHESION MOLECULES; LONG-TERM POTENTIATION; PROTEIN-KINASE-II; SENSING RECEPTOR; PRIMARY HYPERPARATHYROIDISM; CADHERIN FAMILY; CA2+ DEPLETION; CLONING; ACTIVATION AB Regulation of Ca2+ homeostasis in the extracellular space plays an important role in neuronal function. Several modeling studies and recent measurements have demonstrated that modest action potential or synaptic activity can result in a significant reduction in extracellular calcium ([Ca](o)(2+)). Changes in [Ca](o)(2+) can regulate intracellular signaling enzymes, such as Ca2+/calmodulin-dependent protein kinase II, and influence neuronal function at synaptic and nonsynaptic sites. The change in [Ca](o)(2+) can affect several types of ion channels and neurotransmitter receptors and activate a Ca2+-sensitive receptor in neuronal membranes. Depletion of [Ca](o)(2+) may function as an activity-dependent extracellular messenger that regulates nervous system function during development, learning, and disease. C1 NICHD, NIH, Sect Nervous Syst Dev & Plast, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, NIH, Sect Nervous Syst Dev & Plast, Bldg 49,Room 5A79,49 Convent Dr, Bethesda, MD 20892 USA. EM fields@helix.nih.gov NR 38 TC 25 Z9 25 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD FEB PY 2004 VL 10 IS 1 BP 12 EP 17 DI 10.1177/1073858403259440 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 764YC UT WOS:000188233400009 PM 14987443 ER PT J AU Baptista, MJ Cookson, MR Miller, DW AF Baptista, MJ Cookson, MR Miller, DW TI Parkin and alpha-synuclein: Opponent actions in the pathogenesis of Parkinson's disease SO NEUROSCIENTIST LA English DT Review DE Lewy bodies; mitochondria; parkin; proteasome; synapses; synuclein ID UBIQUITIN-PROTEASOME SYSTEM; CENTRAL-NERVOUS-SYSTEM; A-BETA COMPONENT; PRECURSOR PROTEIN; DROSOPHILA MODEL; SEPTIN CDCREL-1; HUMAN BRAIN; CELL-DEATH; DOPAMINE; EXPRESSION AB Dominant mutations in the gene for alpha-synuclein, a small presynaptic protein, can cause Parkinson's disease. Although there is still substantial debate about the precise mechanisms, alpha-synuclein is toxic to vulnerable neurons, probably as a result of its tendency to aggregate. Opposing this is another gene product that, when mutated, causes a recessive form of parkinsonism, parkin. Parkin has been recently shown to protect cells against alpha-synuclein toxicity. However, the precise details of the mechanism are unclear. This review will discuss the concept that there are multiple neuronal functions that are targeted by mutant alpha-synuclein, and in many cases, there is evidence that parkin can protect cells against damage to the same systems. The authors will also discuss ways in which to test some of these ideas, by using newly identified genes such as DJ-1 that cause similar phenotypes. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10,Room 6C103,MSC1589,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Cookson@mail.nih.gov NR 61 TC 10 Z9 15 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD FEB PY 2004 VL 10 IS 1 BP 63 EP 72 DI 10.1177/1073858403260392 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 764YC UT WOS:000188233400015 PM 14987449 ER PT J AU Lee, EM Malson, JL Moolchan, ET Pickworth, WB AF Lee, EM Malson, JL Moolchan, ET Pickworth, WB TI Quantitative comparisons between a nicotine delivery device (Eclipse) and conventional cigarette smoking SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SMOKERS AB In 1997, R. J. Reynolds introduced Eclipse, a nicotine delivery device (NDD) purported to deliver lower levels of smoke than conventional cigarettes. This NDD uses a carbon fuel element to vaporize the nicotine in the rod; the user then inhales the nicotine vapor. In the present study, the effects of this NDD on smoking topography; substance delivery factors; and physiological, subjective, and biochemical markers of smoking were compared with commercial cigarettes (referred to as Own Brand). All smoking occurred ad lib with the cigarette or NDD hand-held (conventional) or held in a topography mouthpiece. A total of 10 adults (seven males) smoked on five occasions: NDD conventional, NDD topography, Own Brand conventional, Own Brand topography (twice). Sessions were separated by at least 24 hr. Measures were taken before and 2, 5, 10, 15, 30, and 60 min after smoking. The NDD took longer to smoke (366s vs. 292s), required more puffs (14.8 vs. 10.8), and caused a larger increase in exhaled carbon monoxide (CO; 7.3ppm vs. 4.2 ppm) than Own Brand. However, venous plasma nicotine boost was significantly larger 2 min after smoking Own Brand as compared with the NDD (16.4 ng/ml vs. 10.7 ng/ml). Puff volume (90.7 ml vs. 63.0 ml) and puff velocity (81.6 ml/s vs. 58.2 ml/s) were greater after the NDD than Own Brand, whereas inter-puff interval and puff duration were similar. Subjects rated the NDD as less satisfying (5.2 vs. 9.8), less rewarding (9.5 vs. 14.3), and more aversive (5.0 vs. 3.1) than their own brand. The results of this study indicate that this NDD exposes the user to significant quantities of nicotine, CO, and possibly other harmful components of tobacco smoke. The findings further validate the use of a topography device as an effective instrument to quantify smoke exposure. C1 NIDA, Intramural Res Program, Clin Pharmacol Branch, Baltimore, MD 21224 USA. RP Pickworth, WB (reprint author), NIDA, Intramural Res Program, Clin Pharmacol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wpickwo@intra.nida.nih.gov FU NCI NIH HHS [5-P50-CA84718] NR 29 TC 23 Z9 23 U1 10 U2 17 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2004 VL 6 IS 1 BP 95 EP 102 DI 10.1080/14622200310001656911 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 805JW UT WOS:000220363600012 PM 14982693 ER PT J AU Clark, PI Gardiner, PS Djordjevic, MV Leischow, SJ Robinson, RG AF Clark, PI Gardiner, PS Djordjevic, MV Leischow, SJ Robinson, RG TI Menthol cigarettes: Setting the research agenda SO NICOTINE & TOBACCO RESEARCH LA English DT Editorial Material ID LUNG-CANCER RISK; SMOKE EXPOSURE; WHITE SMOKERS C1 Battelle Ctr Publ Hlth Res & Evaluat, Baltimore, MD 21209 USA. Univ Calif, Off President, Tobacco Related Dis Res Program, Oakland, CA USA. NCI, Tobacco Control Res Branch, NIH, Rockville, MD USA. US PHS, Ctr Dis Control & Prevent, Off Smoking & Hlth, Atlanta, GA USA. RP Clark, PI (reprint author), Battelle Ctr Publ Hlth Res & Evaluat, 6115 Falls Rd,Suite 200, Baltimore, MD 21209 USA. EM clarkp@battelle.org NR 37 TC 20 Z9 21 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2004 VL 6 SU 1 BP S5 EP S9 DI 10.1080/14622200310001649441 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 806IK UT WOS:000220427400002 PM 14982704 ER PT J AU Henningfield, JE Djordjevic, MV AF Henningfield, JE Djordjevic, MV TI Menthol cigarettes: Research needs and challenges SO NICOTINE & TOBACCO RESEARCH LA English DT Article; Proceedings Paper CT 1st Conference on Menthol Cigarettes CY MAR 21-22, 2002 CL ATLANTA, GEORGIA ID NICOTINE C1 Pinney Associates Inc, Bethesda, MD 20814 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Behav Sci, Baltimore, MD 21205 USA. NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA. RP Henningfield, JE (reprint author), Pinney Associates Inc, 4800 Montgomery Lane,Suite 1000, Bethesda, MD 20814 USA. EM jhenning@pinneyassociates.com NR 25 TC 10 Z9 10 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2004 VL 6 SU 1 BP S11 EP S16 DI 10.1080/14622200310001649450 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 806IK UT WOS:000220427400003 PM 14982705 ER PT J AU Moolchan, ET AF Moolchan, ET TI Adolescent menthol smokers: Will they be a harder target for cessation? SO NICOTINE & TOBACCO RESEARCH LA English DT Article; Proceedings Paper CT 1st Conference on Menthol Cigarettes CY MAR 21-22, 2002 CL ATLANTA, GEORGIA ID SMOKING; CIGARETTES; EXPOSURE AB Menthol smoking may influence the development of tobacco addiction and related health consequences, yet limited data on menthol smoking by youth are available. We assessed usual brand menthol preference by Baltimore-area teenage smokers applying to a smoking cessation study between September 1999 and December 2002. Of a biethnic (Black and White) sample of 593 youths (mean age=15.5+/-1.4 years, 51% female, 45% African American), the overwhelming majority (93%) were menthol smokers. Menthol preference rates were highest among African American girls and lowest among White boys. Overall, a statistically significant association was found between ethnicity and menthol preference, chi(2) (df = 1) = 19.4, p < .001. This association also was observed separately for girls, chi(2) (df = 1) = 9.21, p = .0024, and for boys, chi(2) (df = 1) = 9.59, p = .0020. Menthol smoking did not vary with age in either ethnic group. These findings of overwhelming menthol preference in a treatment-seeking sample of adolescents warrant further research on the developmental trajectory, cessation, and health-related impact of menthol smoking by youth. C1 NIDA, Teen Tobaco Addict Treatment Res Clin, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobaco Addict Treatment Res Clin, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 20 TC 12 Z9 13 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2004 VL 6 SU 1 BP S93 EP S95 DI 10.1080/14622203310001649522 PG 3 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 806IK UT WOS:000220427400010 PM 14982712 ER PT J AU Toyama, H Ichise, M Liow, JS Vines, DC Seneca, NM Modell, KJ Seidel, J Green, MV Innis, RB AF Toyama, H Ichise, M Liow, JS Vines, DC Seneca, NM Modell, KJ Seidel, J Green, MV Innis, RB TI Evaluation of anesthesia effects on [F-18]FDG uptake in mouse brain and heart using small animal PET SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Japanese-Society-of-Nuclear-Medicine CY NOV 04-06, 2002 CL Kobe, JAPAN SP Japanese Soc Nucl Med DE small animal PET; mouse; [F-18]FDG; anesthesia; brain; heart ID CEREBRAL GLUCOSE-UTILIZATION; BLOOD-FLOW; ISOFLURANE ANESTHESIA; RAT-BRAIN; METABOLISM; KETAMINE; TOMOGRAPHY; DIAZEPAM; XYLAZINE AB This study evaluates effects of anesthesia on F-18-FDG (FDG) uptake in mouse brain and heart to establish the basic conditions of small animal PET imaging. Prior to FDG injection, 12 mice were anesthetized with isoflurane gas; 11 mice were anesthetized with an intraperitoneal injection of a ketamine/xylazine mixture; and 11 mice were awake. In isoflurane and ketamine/xylazine conditions, FDG brain uptake (%ID/g) was significantly lower than in controls. Conversely, in the isoflurane condition, %ID/g in heart was significantly higher than in controls, whereas heart uptake in ketamine/xylazine mice was significantly lower. Results suggest that anesthesia impedes FDG uptake in mouse brain and affects FDG uptake in heart; however, the effects in the brain and heart differ depending on the type of anesthesia used. (C) 2004 Elsevier Inc. All rights reserved. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RP Toyama, H (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM htoyama@fujita-hu.ac.jp NR 28 TC 74 Z9 78 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 2004 VL 31 IS 2 BP 251 EP 256 DI 10.1016/S0969-8051(03)00124-0 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 804FR UT WOS:000220285100013 PM 15013491 ER PT J AU Park, LS Szajek, LP Wong, KJ Plascjak, PS Garmestani, K Googins, S Eckelman, WC Carrasquillo, JA Paik, CH AF Park, LS Szajek, LP Wong, KJ Plascjak, PS Garmestani, K Googins, S Eckelman, WC Carrasquillo, JA Paik, CH TI Semi-automated (86)Y purification using a three-column system SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE (86)Y purification; Sr-Spec resin; RE-Spec resin; Aminex A5 resin; semi-automation ID POSITRON-EMISSION-TOMOGRAPHY; BIODISTRIBUTION; Y-90; PET AB The separation of (86)Y from (86)Sr was optimized by a semi-automated purification system involving the passage of the target sample through three sequential columns. The target material was dissolved in 4 N HNO(3) and loaded onto a Sr-selective (Sr-Spec) column to retain the (86)Sr. The yttrium was eluted with 4 N HNO(3) onto the second Y-selective (RE-Spec) column with quantitative retention. The RE-Spec column was eluted with a stepwise decreasing concentration of HNO(3) to wash out potential metallic impurities to a waste container. The eluate was then pumped onto an Aminex A5 column with 0.1 N HCl and finally with 3 N HCl to collect the radioyttrium in 0.6-0.8 mL with a >80% recovery. This method enabled us to decontaminate Sr by 250,000 times and label 30 mug of DOTA-Biotin with a >95% yield. (C) 2004 Elsevier Inc. All rights reserved. C1 Dept Nucl Med, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, PET Dept, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Radiat Safety Branch, Bethesda, MD 20892 USA. RP Paik, CH (reprint author), Dept Nucl Med, Bethesda, MD 20892 USA. EM cpaik@mail.cc.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 12 TC 24 Z9 24 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD FEB PY 2004 VL 31 IS 2 BP 297 EP 301 DI 10.1016/S0969-8051(03)00141-0 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 804FR UT WOS:000220285100019 PM 15013497 ER PT J AU Marino-Ramirez, L Spouge, JL Kanga, GC Landsman, D AF Marino-Ramirez, L Spouge, JL Kanga, GC Landsman, D TI Statistical analysis of over-represented words in human promoter sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CPG-ISLANDS; TRANSCRIPTION FACTORS; REGULATORY ELEMENTS; BINDING SITES; DNA-SEQUENCES; HUMAN GENOME; START SITES; IDENTIFICATION; FREQUENCIES; DISCOVERY AB The identification and characterization of regulatory sequence elements in the proximal promoter region of a gene can be facilitated by knowing the precise location of the transcriptional start site (TSS). Using known TSSs from over 5700 different human full-length cDNAs, this study extracted a set of 4737 distinct putative promoter regions (PPRs) from the human genome. Each PPR consisted of nucleotides from -2000 to +1000 bp, relative to the corresponding TSS. Since many regulatory regions contain short, highly conserved strings of less than 10 nucleotides, we counted eight-letter words within the PPRs, using z-scores and other related statistics to evaluate their over- and under-representation. Several over-represented eight-letter words have known biological functions described in the eukaryotic transcription factor database TRANSFAC; however, many did not. Besides calculating a P-value with the standard normal approximation associated with z-scores, we used two extra statistical controls to evaluate the significance of over-represented words. These controls have important implications for evaluating over- and under-represented words with z-scores. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Landsman, D (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,MSC 6075, Bethesda, MD 20894 USA. EM landsman@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 31 TC 74 Z9 82 U1 0 U2 2 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 FEB PY 2004 VL 32 IS 3 BP 949 EP 958 DI 10.1093/nar/gkh246 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807GQ UT WOS:000220490400009 PM 14963262 ER PT J AU Constantinesco, F Forterre, P Koonin, EV Aravind, L Elie, C AF Constantinesco, F Forterre, P Koonin, EV Aravind, L Elie, C TI A bipolar DNA helicase gene, herA, clusters with rad50, mre11 and nurA genes in thermophilic archaea SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; BACTERIAL CONJUGATION; PYROCOCCUS-FURIOSUS; REPAIR PROTEINS; ATP HYDROLYSIS; RECBCD ENZYME; P-LOOP; RECOMBINATION; YEAST; MECHANISM AB We showed previously that rad50 and mre11 genes of thermophilic archaea are organized in an operon-like structure with a third gene (nurA) encoding a 5' to 3' exonuclease. Here, we show that the rad50, mre11 and nurA genes from the hyperthermo philic archaeon Sulfolobus acidocaldarius are co-transcribed with a fourth gene encoding a DNA helicase. This enzyme (HerA) is the prototype of a new class of DNA helicases able to utilize either 3' or 5' single-stranded DNA extensions for loading and subsequent DNA duplex unwinding. To our knowledge, DNA helicases capable of translocating along the DNA in both directions have not been identified previously. Sequence analysis of HerA shows that it is a member of the TrwB, FtsK and VirB4/VirD4 families of the PilT class NTPases. HerA homologs are found in all thermophilic archaeal species and, in all cases except one, the rad50, mre11, nurA and herA genes are grouped together. These results suggest that the archaeal Rad50-Mre11 complex might act in association with a 5' to 3' exonuclease (NurA) and a bipolar DNA helicase (HerA) indicating a probable involvement in the initiation step of homologous recombination. C1 Univ Paris 11, CNRS, UMR 8621, Inst Genet & Microbiol, F-91405 Orsay, France. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Elie, C (reprint author), Univ Paris 11, CNRS, UMR 8621, Inst Genet & Microbiol, Batiment 409, F-91405 Orsay, France. EM elie@igmors.u-psud.fr NR 40 TC 61 Z9 64 U1 2 U2 3 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 FEB PY 2004 VL 32 IS 4 BP 1439 EP 1447 DI 10.1093/nar/gkh283 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802RD UT WOS:000220179700029 PM 14990749 ER PT J AU Dash, C Rausch, JW Le Grice, SFJ AF Dash, C Rausch, JW Le Grice, SFJ TI Using pyrrolo-deoxycytosine to probe RNA/DNA hybrids containing the human immunodeficiency virus type-1 3 ' polypurine tract SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; STRAND DNA-SYNTHESIS; T7 RNA-POLYMERASE; POLYPURINE TRACT; CLEAVAGE SPECIFICITY; MUTATIONAL ANALYSIS; RIBONUCLEASE-H; PRIMER GRIP; HELIX CLAMP; INITIATION AB Recent structural analyses indicate that localized regions of abnormal base pairing exist within RNA/DNA hybrids containing the HIV-1 polypurine tract (PPT) and that these distortions may play a role in PPT function. To examine this directly, we have introduced pyrrolo-deoxycytosine (pdC), a fluorescent, environmentally sensitive analog of deoxycytosine (dC), into the DNA strand of PPT-containing hybrids. Steady-state fluorescence analysis of these hybrids reveals that the DNA base 11 nt from the PPT-U3 junction is unpaired even in the absence of reverse transcriptase (RT). Unstable base pairing is also observed within the (rG:dC)(6) tract in the downstream portion of the duplex, suggesting that HIV-1 RT may recognize multiple pre-existing distortions during PPT selection. HIV-1 RT hydrolyzes pdC-containing hybrids primarily at the PPT-U3 junction, indicating that the analog does not induce a gross structural deformation of the duplex. However, aberrant cleavage is frequently observed 3 bp from the site of pdC substitution, most likely reflecting a specific interaction between the analog and amino acid residues within the RNase H primer grip. pdC substitution within the template strand of a DNA duplex does not appear to significantly affect RT-catalyzed DNA synthesis. Implications of these findings on the use of pdC to examine nucleic acid structure are discussed. C1 NCI, Resistance Mech Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, Resistance Mech Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov NR 30 TC 55 Z9 56 U1 0 U2 4 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 FEB PY 2004 VL 32 IS 4 BP 1539 EP 1547 DI 10.1093/nar/gkh307 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802RD UT WOS:000220179700039 PM 15004241 ER PT J AU Xiao, Y Barker, PE AF Xiao, Y Barker, PE TI Semiconductor nanocrystal probes for human metaphase chromosomes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID QUANTUM DOTS; CDSE NANOCRYSTALS; IN-VIVO; DNA AB To improve signal stability and quantitation, an optically stable, novel class of fluorophore for hybridization analysis of human metaphase chromosomes is demonstrated. Detection of hybridization sites in situ was based on fluorescence from streptavidin-linked inorganic crystals of cadmium selenide [(CdSe)ZnS]. Fluorescence of nanocrystal fluorophores was significantly brighter and more photostable than organic fluorophores Texas Red and fluorescein. Thus, semiconductor nanocrystal fluorophores offer a more stable and quantitative mode of fluorescence in situ hybridization (FISH) for research and clinical applications. C1 NIST, NCI, Biomarkers Validat Lab, DNA Technol Grp,Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP Barker, PE (reprint author), NIST, NCI, Biomarkers Validat Lab, DNA Technol Grp,Chem Sci & Technol Lab, 100 Bur Dr,Mail Stop 831, Gaithersburg, MD 20899 USA. EM peter.barker@nist.gov NR 20 TC 113 Z9 120 U1 1 U2 19 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 FEB PY 2004 VL 32 IS 3 AR e28 DI 10.1093/nar/gnh024 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807GQ UT WOS:000220490400045 PM 14960711 ER PT J AU Ahmad, A Momenan, R Van Gelderen, P Moriguchi, T Greiner, RS Salem, N AF Ahmad, A Momenan, R Van Gelderen, P Moriguchi, T Greiner, RS Salem, N TI Gray and white matter brain volume in aged rats raised on n-3 fatty acid deficient diets SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE docosahexaenoic acid; n-3 deficiency; brain volume; white matter; gray matter; MRI ID GENERALIZED PEROXISOMAL DISORDERS; DOCOSAHEXAENOIC ACID; ETHYL-ESTER; MECHANISMS; ACCRETION; REQUIREMENTS; HIPPOCAMPUS; DECREASE; CORTEX; SIZE AB Omega-3 or n-3 fatty acids, especially docosahexaenoic acid, are important structural lipids in the brain. Their deficiency leads to a number of sensory cognitive and behavioral effects. In previous studies, we showed that n-3 deficiency led to a decrease in the neuronal size of a number of brain regions in young rats. In particular, the neuronal size in the hippocampus CA1-CA3 layers decreased with a slight increase in the volumes of these layers. Therefore, we asked whether fatty acid deficiency could affect rat brain morphology in older animals. To address this question, we carried out gross morphological analysis using Magnetic Resonance Imaging on the gray and white matter volumes of brains in older rats (>15 months) that were raised on n-3 deficient diets for three generations. We did not detect any differences in the total or regional gray and white matter volumes of brains of old rats maintained on a n-3 deficient or supplemented diet. C1 NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, Rockville, MD 20852 USA. NIAAA, Div Intramural Clin & Biol Res, Clin Studies Lab, Bethesda, MD USA. NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, Rockville, MD 20852 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, Rockville, MD 20852 USA. EM nsalem@niaaa.nih.gov RI Wilkinson, Stuart/C-2802-2013 NR 37 TC 5 Z9 5 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1028-415X J9 NUTR NEUROSCI JI Nutr. Neurosci. PD FEB PY 2004 VL 7 IS 1 BP 13 EP 20 DI 10.1080/1028415042000202009 PG 8 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA 809UK UT WOS:000220661400002 PM 15085554 ER PT J AU Wright, TC Schiffman, M Solomon, D Cox, JT Garcia, F Goldie, S Hatch, K Noller, KL Roach, N Runowicz, C Saslow, D AF Wright, TC Schiffman, M Solomon, D Cox, JT Garcia, F Goldie, S Hatch, K Noller, KL Roach, N Runowicz, C Saslow, D TI Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID CANCER; WOMEN; INFECTION; NEOPLASIA; ABNORMALITIES; PROVINCE; MEXICO; RISK AB Human papillomavirus (HPV) DNA testing was recently approved by the Food and Drug Administration for use as an adjunct to cytology for cervical cancer screening. To help provide guidance to clinicians and patients when using HPV DNA testing as an adjunct to cervical cytology for screening, a workshop was cosponsored by the National Institutes of Health-National Cancer Institute, American Society of Colposcopy and Cervical Pathology (ASCCP), and American Cancer Society. Consensus was reached based on a literature review, expert opinion, and unpublished results from large ongoing screening studies. ne conclusions of the workshop were that FIPV DNA testing may be added to cervical cytology for screening in women aged 30 years or more. Women whose results are negative by both HPV DNA testing and cytology should not be rescreened before 3 years. Women whose results are negative by cytology, but are high-risk HPV DNA positive, are at a relatively low risk of having high-grade cervical neoplasia, and colposcopy should not be performed routinely in this setting. Instead, HPV DNA testing along with cervical cytology should be repeated in these women at 6 to 12 months. If test results of either are abnormal, colposcopy should then be performed. This guidance should assist clinician in utilizing HPV DNA testing in an effective manner, while minimizing unnecessary evaluations and treatments. (C) 2004 by The American College of Obstetricians and Gynecologists. C1 Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Santa Barbara, Student Hlth Serv, Santa Barbara, CA 93106 USA. Univ Arizona, Arizona Canc Ctr, Dept Obstet & Gynecol, Tucson, AZ USA. Harvard Univ, Ctr Risk Anal, Sch Publ Hlth, Boston, MA 02115 USA. Tufts Univ, Dept Obstet & Gynecol, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Marti Nelson Canc Fdn, Hood River, OR USA. Univ Connecticut, Sch Med, Farmington, CT USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Wright, TC (reprint author), Room 16-404,P&S Bldg,630 W 168th St, New York, NY 10032 USA. EM tcw1@columbia.edu NR 20 TC 288 Z9 310 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2004 VL 103 IS 2 BP 304 EP 309 DI 10.1097/01.AOG.0000109426.82624.f8 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 875IL UT WOS:000225413600015 PM 14754700 ER PT J AU Bai, P Mabley, JG Liaudet, L Virag, L Szabo, C Pacher, P AF Bai, P Mabley, JG Liaudet, L Virag, L Szabo, C Pacher, P TI Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity SO ONCOLOGY REPORTS LA English DT Article DE doxorubicin; cardiac; peroxynitrite; matrix metalloproteinase; heart failure; oxidative stress ID HEART; PEROXYNITRITE; CARDIOMYOPATHY; ADRIAMYCIN; DYSFUNCTION; CONTRIBUTES; INHIBITORS; DRUGS AB Matrix metalloproteinase (MMP) activation contributes to the development of various pathophysiological conditions, including dilated cardiomyopathy, congestive heart failure, and reperfusion injury. Increased oxidative and nitrosative stress have been implicated in the activation of MMPs and also in the cardiotoxicity of doxorubicin (DOX), a commonly used antitumor agent. Thus, we hypothesized that MMP activation occurs in DOX-induced cardiotoxicity. Male Balb/c mice received a single injection of DOX (25 mg/ kcy i.p.) and were sacrificed 12 h, 1, 2, 3 and 4 days later. Hearts and aortae were harvested for MMP zymography. DOX induced time-dependent activation of MMPs both in the heart and in the aortic tissue with an earlier onset in the latter. These results demonstrate that MMP activation is an early event in DOX-induced cardiotoxicity and raises the possibility that MMP inhibitors may influence the outcome of this severe complication. C1 NIAAA, NIH, DICBR, Lab Physiol Studies,Sect Neuroendocrinol, Rockville, MD 20852 USA. Inotek Pharmaceut Corp, Cummings Ctr 100, Beverly, MA 01915 USA. Univ Debrecen, Dept Med Chem, H-4026 Debrecen, Hungary. Univ Hosp, Dept Internal Med, Lausanne, Switzerland. Semmelweis Univ, Sch Med, Inst Human Physiol, Budapest, Hungary. Semmelweis Univ, Sch Med, Inst Pharmacol, Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, NIH, DICBR, Lab Physiol Studies,Sect Neuroendocrinol, 12420 Parklawn Dr,Room 445, Rockville, MD 20852 USA. EM ppacher@lycos.com RI Virag, Laszlo/E-6124-2010; Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU NCI NIH HHS [R43 CA 097559, R43 CA 95807]; NHLBI NIH HHS [R01 HL 59266] NR 20 TC 48 Z9 57 U1 0 U2 5 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 FEB PY 2004 VL 11 IS 2 BP 505 EP 508 PG 4 WC Oncology SC Oncology GA 764YE UT WOS:000188233600040 PM 14719091 ER PT J AU Sutton, JF Stacey, M Kearns, WG Rieg, TS Young, NS Liu, JM AF Sutton, JF Stacey, M Kearns, WG Rieg, TS Young, NS Liu, JM TI Increased risk for aplastic anemia and myelodysplastic syndrome in individuals lacking glutathione S-transferase genes SO PEDIATRIC BLOOD & CANCER LA English DT Article DE aplastic anemia; chromosomal abnormality; genotype; glutathione S-transferase; myelodysplastic syndrome ID ACUTE MYELOID-LEUKEMIA; GSTT1; GSTM1; GENOTYPE; CANCER; DEFECT; THETA; SUSCEPTIBILITY; FREQUENCIES; PREVALENCE AB Background. Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are marrow failure states that may be associated with chromosomal instability. An absence of the glutathione S-transferase (GST) enzyme may genetically predispose individuals to AA or MDS. Procedure and Results. To test this hypothesis, we determined the GSTM1 and GSTT1 genotypes in a total of 196 patients using multiplex PCR. The GSTT1 null genotype was found to he overrepresented in Caucasian, Asian, and Hispanic patients with either AA or MDS. We confirmed a difference in the expected frequency of the GSTM1 null genotype in Caucasian MDS patients. The double no I I GSTM1/ GSTT1 genotype was also overrepresented in Caucasian AA and MDS patients. In our population, 26% of AA patients and 40% of MDS patients had a chromosomal abnormality identified by karyotype or FISH analyses for chromosomes 7 and 8. Patients with AA and the GSTT1 null genotype had an increased frequency of chromosomal abnormalities (P = 0.003). Conclusion. There seems to be an increased risk for AA and MDS in individuals lacking GSTT1 or both GSTM1/GSTT1. Published 2003 Wiley-Liss, Inc(dagger). C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. USN, Med Ctr Portsmouth, Portsmouth, VA USA. Eastern Virginia Med Sch, Ctr Pediat Res, Norfolk, VA 23501 USA. RP Liu, JM (reprint author), CUNY, Mt Sinai Med Ctr, Div Hematol Oncol, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. EM Johnson.Liu@mssm.edu OI Stacey, Michael/0000-0002-3807-6233 NR 20 TC 14 Z9 19 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2004 VL 42 IS 2 BP 122 EP 126 DI 10.1002/pbc.10479 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 906YV UT WOS:000227682000002 PM 14752874 ER PT J AU Zeng, XC Wang, SX Zhu, Y Zhu, SY Li, WX AF Zeng, XC Wang, SX Zhu, Y Zhu, SY Li, WX TI Identification and functional characterization of novel scorpion venom peptides with no disulfide bridge from Buthus martensii Karsch SO PEPTIDES LA English DT Article DE amphipathic; antibacterial; acidic peptides; venom peptides; molecular evolution ID BRADYKININ-POTENTIATING PEPTIDE; ANTIMICROBIAL PEPTIDES; MOLECULAR-CLONING; TEMPORIN-L; CDNA; PRECURSOR; CHANNELS; PURIFICATION; TOXINS AB The scorpion venom peptides with no disulfide bridge are rarely identified and poorly characterized so far. Here, we report the identification and characterization of four novel disulfide-bridge-free venom peptides (BmKa1, BmKa2, BmKb1 and BmKn2) from Buthus martensii Kasch. BmKa1 and BmKa2 are very acidic and hydrophilic, showing no any similarity to other proteins, whereas BmKb1 and BmKn2 both are basic, alpha-helical peptide with an amidated C-terminus, showing a little homology with other peptides. Functional tests with synthetic peptide showed that BmKn2 has strong antimicrobial activity against both Gram-positive and Gram-negative bacteria, whereas BmKb1 has weak activity in inhibiting the growth of these bacteria. (C) 2004 Elsevier Inc. All rights reserved. C1 Wuhan Univ, Coll Life Sci, Inst Virol, Dept Biotechnol, Wuhan 430072, Peoples R China. RP Zeng, XC (reprint author), NHLBI, Cell Biol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM zengx@nhlbi.nih.gov; wxli@whu.edu.cn NR 28 TC 68 Z9 75 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD FEB PY 2004 VL 25 IS 2 BP 143 EP 150 DI 10.1016/j.peptides.2003.12.003 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 813YT UT WOS:000220943100001 PM 15062994 ER PT J AU Weiss, A Egan, V Figueredo, AJ AF Weiss, A Egan, V Figueredo, AJ TI Sensational interests as a form of intrasexual competition SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE mating effort; sensational interests; intrasexual competition; individual differences ID MENTALLY DISORDERED OFFENDERS; REPRODUCTIVE STRATEGY; EVOLUTIONARY; PERSONALITY; SEEKING AB Sensational interests, i.e. a curiosity for the violent and macabre, are reputedly common in mentally disordered offenders. However, ostensibly well-adjusted individuals are also interested in these topics. We tested the hypothesis that individual differences in sensational interests may partially reflect intrasexual competition for status and have an underlying evolutionary function. Several predictions derive from this hypothesis. First, age and sex should be directly related to individual differences in mating effort (the degree that an individual devotes resources to finding and guarding sexual partners). Second, mating effort should directly influence sensational interests. Third, there should also be direct effects of age and sex on sensational interests. To test these predictions we collected data on 969 university undergraduates using the Revised Version of the Sensational Interests Questionnaire (SIQ-R) and the Mating effort Scale (MES). A structural equations model revealed that a single factor accounted for the majority of the variance of the three SIQ-R subscales, Paranormal, Militarism, and Criminal Identity. This model also included direct effects of age and sex on the MES and two SIQ-R subscales and direct effects of the MES on the SIQ-R. Model fit statistics indicated that this model was a good fit to the data. We conclude that, even in a non-clinical sample, an affinity for sensational interests might serve a form of intrasexual competition. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Glasgow Caledonian Univ, Dept Psychol, Glasgow G4 0BA, Lanark, Scotland. RP Weiss, A (reprint author), NIA, Lab Personal & Cognit, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM weissal@grc.nia.nih.gov RI Egan, Vincent /H-2975-2012; OI Egan, Vincent/0000-0003-0878-2556 NR 26 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD FEB PY 2004 VL 36 IS 3 BP 563 EP 573 DI 10.1016/S0191-8869(03)00115-6 PG 11 WC Psychology, Social SC Psychology GA 770LW UT WOS:000188733100006 ER PT J AU McCrae, RR Costa, PT AF McCrae, RR Costa, PT TI A contemplated revision of the NEO Five-Factor Inventory SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE item analysis; scale development; factor analysis; Five-Factor Model; adolescents ID PI-R; PERSONALITY; VALIDATION; SAMPLE; INSTRUMENTS; OBSERVERS; MODEL; TRAIT; FFI AB Previous item factor analyses and readability analyses suggested that 14 of the 60 items in the NEO Five-Factor Inventory might usefully be replaced. New analyses in high school (N = 1959) and adult (N = 1492) samples led to the selection of new items from the remaining pool of Revised NEO Personality Inventory items. The resulting scales showed modest improvements in reliability and factor structure, and equivalent validity. These new scales should be appropriate for most respondents age 14 and up. However, continued use of the current instrument is also reasonable for most applications. Published by Elsevier Ltd. C1 US Dept HHS, NIA, NIH, Baltimore, MD USA. RP McCrae, RR (reprint author), Gerontol Res Ctr, Personal Stress Coping Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jeffm@lpc.grc.nia.nih.gov OI Costa, Paul/0000-0003-4375-1712 NR 21 TC 243 Z9 253 U1 10 U2 102 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD FEB PY 2004 VL 36 IS 3 BP 587 EP 596 DI 10.1016/S0191-8869(03)00118-1 PG 10 WC Psychology, Social SC Psychology GA 770LW UT WOS:000188733100008 ER PT J AU Eiden, LE Schafer, MKH Weihe, E Schutz, B AF Eiden, LE Schafer, MKH Weihe, E Schutz, B TI The vesicular amine transporter family (SLC18): amine/proton antiporters required for vesicular accumulation and regulated exocytotic secretion of monoamines and acetylcholine SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE cholinergic; adrenergic/noradrenergic; serotoninergic; histaminergic; autonomic nervous system; peripheral and central nervous system (PNS; CNS); neuroendocrine; mast cell; adrenal medulla; basophil cells; dendritic (Langerhans) cells; endocrine tumor; pancreatic beta cell (insulin cell) platelet/thrombocyte ID CHOLINERGIC GENE LOCUS; NEUROTRANSMITTER TRANSPORTERS; FUNCTIONAL IDENTIFICATION; SUBSTRATE RECOGNITION; MULTIDRUG TRANSPORTER; ENDOCRINE-CELLS; EXPRESSION; AMPHETAMINE; VMAT2; RESISTANCE AB The vesicular amine transporters (VATs) are expressed as integral proteins of the lipid bilayer membrane of secretory vesicles in neuronal and endocrine cells. Their function is to allow the transport of acetylcholine (by the vesicular acetylcholine transporter VAChT; SLC18A3) and biogenic amines (by the vesicular monoamine transporters VMAT1 and VMAT2; SLC18A1 and SLC18A2) into secretory vesicles, which then discharge them into the extracellular space by exocytosis. Transport of positively charged amines by members of the SLC18 family in all cases utilizes an electrochemical gradient across the vesicular membrane established by proton pumping into the vesicle via a vacuolar ATPase; the amine is accumulated in the vesicle at the expense of the proton gradient, at a ratio of one translocated amine per two translocated protons. The members of the SLC18 family have become important histochemical markers for chemical coding in neuroendocrine tissues and cells. The structural basis of their remarkable ability to transport positively charged amines against a very large concentration gradient, as well as potential disease association with impaired transporter function and expression, are under intense investigation. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, D-35033 Marburg, Germany. Univ Bonn, Mol Neurobiol Lab, Clin Psychiat & Psychotherapy, D-53127 Bonn, Germany. RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 36,Room 2A-11,9000 Rockeville Pike, Bethesda, MD 20892 USA. EM eiden@codon.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 46 TC 83 Z9 86 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD FEB PY 2004 VL 447 IS 5 BP 636 EP 640 DI 10.1007/s00424-003-1100-5 PG 5 WC Physiology SC Physiology GA 772HV UT WOS:000188837300019 PM 12827358 ER PT J AU Sokolov, BP Schindler, CW Cadet, JL AF Sokolov, BP Schindler, CW Cadet, JL TI Chronic methamphetamine increases fighting in mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE substance abuse; behavior; aggressiveness; social interaction; psychostimulant; methamphetamine; amphetamine ID AGGRESSIVE-BEHAVIOR; EVOKED AGGRESSION; AMPHETAMINE ABUSE; SOCIAL-BEHAVIOR; SEROTONIN; BRAIN; RAT; DYSFUNCTION; MDMA AB A propensity for violent behaviors to develop in chronic methamphetamine (METH) abusers has been noted. The idea that increased aggressiveness might result from chronic METH administration was tested in mice after chronic (long-term intermittent, 8 weeks) or single exposures to the drug. A single injection of METH (6 mg/kg) did not augment fighting. In contrast, chronic METH administration significantly increased the number of animals that initiated bite attacks. This regimen also shortened the latency before the first attack. Latency before the first attack was shorter at 20 h after the METH injection than at 15 min after injection. Locomotor activity was not different at 20 h after METH injection, indicating that increased fighting was not secondary to METH-induced hyperactivity. METH-induced increases in fighting were not related to the duration of persistent sniffing after the initial encounter with an intruder since the duration of this behavior was significantly increased at 15 min after METH but not at 20 h post drug. These results indicate that repeated injections of METH can increase fighting behaviors and also alter social interactions in mice. Thus, intermittent administration of METH might be useful as a pharmacological model to study the biochemical and molecular bases of aggressiveness. (C) 2003 Elsevier Inc. All rights reserved. C1 DHHS, Mol Neuropsychiat Branch, NIDA, NIH, Baltimore, MD 21224 USA. DHHS, Natl Inst Drug Abuse, Behav Neurosci Branch, Preclin Pharmacol Sect,NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), DHHS, Mol Neuropsychiat Branch, NIDA, NIH, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 32 TC 20 Z9 21 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 FEB PY 2004 VL 77 IS 2 BP 319 EP 326 DI 10.1016/j.pbb.2003.11.006 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 770LX UT WOS:000188733200016 PM 14751460 ER PT J AU Bianconi, G Laureti, P Yu, YK Zhang, YC AF Bianconi, G Laureti, P Yu, YK Zhang, YC TI Ecology of active and passive players and their impact on information selection SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article DE Internet; information; ranking ID RANDOM NETWORKS AB Is visitors' attendance a fair indicator of a web site's quality? Internet sub-domains are usually characterized by power-law distributions of visits, thus suggesting a rich-get-richer process. If this is the case, the number of visits is not a relevant measure of quality. If, on the other hand, there are active players, i.e., visitors who can tell the value of the information available, better sites start getting richer after a crossover time. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Fribourg, Inst Phys Theor, CH-1700 Fribourg, Switzerland. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Florida Atlantic Univ, Dept Phys, Boca Raton, FL 33431 USA. RP Bianconi, G (reprint author), Univ Fribourg, Inst Phys Theor, CH-1700 Fribourg, Switzerland. EM ginestra.bianconi@unifr.ch NR 11 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD FEB 1 PY 2004 VL 332 BP 519 EP 532 DI 10.1016/j.physa.2003.10.005 PG 14 WC Physics, Multidisciplinary SC Physics GA 763LC UT WOS:000188086200037 ER PT J AU Malley, JD AF Malley, JD TI All quantum observables in a hidden-variable model must commute simultaneously SO PHYSICAL REVIEW A LA English DT Article ID PROBABILITY; MECHANICS; THEOREMS AB Under a standard set of assumptions for a hidden-variable model for quantum events we show that all observables must commute simultaneously. This seems to be an ultimate statement about the inapplicability of the usual hidden-variable model for quantum events. And, despite Bell's complaint that a key condition of von Neumann's was quite unrealistic, we show that these conditions, under which von Neumann produced the first no-go proof, are entirely equivalent to those introduced by Bell and Kochen and Specker. As these conditions are also equivalent to those under which the Bell-Clauster-Horne inequalities are derived, we see that the experimental violations of the inequalities demonstrate only that quantum observables do not commute. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Malley, JD (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. OI Malley, James/0000-0002-9895-7454 NR 16 TC 17 Z9 17 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD FEB PY 2004 VL 69 IS 2 AR 022118 DI 10.1103/PhysRevA.69.022118 PG 3 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA 780MZ UT WOS:000189386300027 ER EF